Increased levels of circulating oxidized mitochondrial DNA contribute to chronic inflammation in metabolic syndrome, and MitoQ-based antioxidant therapy alleviates this DNA-induced inflammation.

Here, the aim was to investigate the role of circulating oxidized mitochondrial DNA (ox-mtDNA) in metabolic syndrome (MetS)-associated chronic inflammation and evaluate the effect of Mito-Quinone (MitoQ)-based antioxidant therapy on inflammation. A total of 112 MetS patients and 111 healthy control individuals (HCs) were recruited. Peripheral blood was collected, and mononuclear cells (PBMCs) were separated. In a preclinical study, MitoQ, a mitochondrial-targeted antioxidant, was administered to Sprague-Dawley (SD) rats fed a high-fat diet (HFD). In vitro, H2O2- or MitoQ-treated HUVECs served as the oxidative or antioxidative cell models to detect the cell-free ox-mtDNA level. Plasma or cell-free ox-mtDNA levels were measured by qPCR. Additionally, THP-1 cells were incubated with plasma cell-free DNA (cfDNA) from MetS patients and HCs or cell-free ox-mtDNA to detect TLR9-NF-κB pathway activation. Plasma ox-mtDNA levels and TLR9 expression levels in PBMCs were increased in MetS patients. In vivo, HFD-fed rats showed elevated plasma ox-mtDNA and TLR9 expression levels in cardiac-residing immune cells, but MitoQ administration attenuated these increases. In vitro, a significant lower level of cell-free ox-mtDNA was detected in MitoQ-treated cells, compared with H2O2-treated cells. Coincubation of plasma cfDNA from MetS patients or cell-free ox-mtDNA and THP-1 cells increased TLR9-NF-κB p65 expression, and promoted IL-1ß, IL-6 and IL-8 secretion in THP-1 cells. In conclusion, increased circulating ox-mtDNA contributes to chronic inflammation in MetS by activating the TLR9-NF-κB pathway. MitoQ-based antioxidant therapy effectively alleviates inflammation by reducing ox-mtDNA release.

Androgen receptor contributes to microglial/macrophage activation in rats with intracranial hemorrhage by mediating the JMJD3/Botch/Notch1 axis.

Intracerebral hemorrhage (ICH) is a leading medical problem and has no effective treatment approach up until now. The transcription factor androgen receptor (AR) has been indicated in the cerebrovascular function recently. However, its participation in ICH remains unclear. The present study aims to expound the regulation of AR in microglia/macrophage phenotypes and the secondary brain injury in a rat model with ICH, and to discuss the involved pathway. Following the induction of ICH in rats, we found that ICH led to increased mNSS score, enhanced microglial activity, and promoted levels of inflammatory factors and apoptosis of brain cells. Using microarray analysis, AR was found to be significantly overexpressed in ICH rat brain tissues. AR repressed the transcription of Jumonji d3 (JMJD3, histone 3 demethylase). JMJD3 inhibited the methylation of Botch and promoted the activity of Notch1. JMJD3 hampered microglial activity and ameliorated secondary brain injury in rats, whereas upregulation of AR or downregulation of Botch reversed the protective effects of JMJD3. In conclusion, we found that AR promoted microglial activation and secondary brain injury via transcriptionally repressing JMJD3 and mediating the subsequent Botch/Notch1 pathway, which may provide novel insights into therapeutic options for the treatment of ICH.

The abnormal distribution of NK cell subsets before HAART treatment may be related to the level of immune reconstitution in HIV patient.

BACKGROUND: HIV infection leads to the damage of NK cells, which is closely associated with the disease's progression, but whether it affects immune reconstitution after Highly Active Antiretroviral Therapy (HAART) is not clear. METHODS: From March 9 to October 31, 2017, a total of 75 confirmed cases with HIV in Wenzhou were collected and analyzed. NK cell subsets were measured and compared among three groups: the control group, the group whose CD4+ T cell counts <200/µL (named as low-CD4 group) and the group whose CD4+ T cell counts ≥200/µL (named as high-CD4 group). The lymphocytic subsets were dynamically monitored in patients with HIV after HAART. RESULTS: Patients in low-CD4 group have lower proportion of CD3-CD56dimCD16+ NK cell subset, but have higher proportion of CD3-CD56-CD16+ NK cell subsets, which were compared with patients in high-CD4 group (All P values <0.01). There is a positive correlation between the proportion of CD3-CD56-CD16+ NK cell subset and CD4+ T cell counts (r = 0.628, p < 0.001). Patients in the low-CD4 group have higher expression of PD-1 and PS on NK cells than patients in the high-CD4 group (All P values < 0.05). The odds ratio of the proportion of the CD3-CD56-CD16+ NK cell subset before treatment for HAART efficacy was 0.826 (p < 0.001). CONCLUSIONS: There are abnormalities in the proportion and function of NK cell subsets in HIV patients, which are associated with disease progression. The proportion of the CD3-CD56-CD16+ NK cell subset before treatment is related with HAART efficacy.

Laboratory indicators in COVID-19 and other pneumonias: Analysis for differential diagnosis and comparison of dynamic changes during 400-day follow-up.

BACKGROUND: COVID-19 is spreading rapidly all over the world, the patients' symptoms can be easily confused with other pneumonia types. Therefore, it is valuable to seek a laboratory differential diagnostic protocol of COVID-19 and other pneumonia types on admission, and to compare the dynamic changes in laboratory indicators during follow-up. METHODS: A total of 143 COVID-19, 143 bacterial pneumonia and 145 conventional viral pneumonia patients were included. The model group consisted of 140 COVID-19, 80 bacterial pneumonia and 60 conventional viral pneumonia patients, who were age and sex matched. We established a differential diagnostic model based on the laboratory results of the model group on admission via a nomogram, which was validated in an external validation group. We also compared the 400-day dynamic changes of the laboratory indicators among groups. RESULTS: LASSO regression and multivariate logistic regression showed that eosinophils (Eos), total protein (TP), prealbumin (PA), potassium (K), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDLC) could differentiate COVID-19 from other pneumonia types. The C-index of the nomogram model was 0.922. Applying the nomogram to the external validation group showed an area under the curve (AUC) of 0.902. The 400-day change trends of the laboratory indexes varied among subgroups divided by sex, age, oxygenation index (OI), and pathogen. CONCLUSION: The laboratory model was highly accurate at providing a new method to identify COVID-19 in pneumonia patients. The 400-day dynamic changes in laboratory indicators revealed that the recovery time of COVID-19 patients was not longer than that of other pneumonia types.

COVID-19 May Increase the Risk of Insulin Resistance in Adult Patients Without Diabetes: A 6-Month Prospective Study.

OBJECTIVE: During the coronavirus disease 2019 (COVID-19) pandemic, exploring insulin resistance and beta-cell activity is important for understanding COVID-19‒associated new-onset diabetes. We assessed insulin sensitivity and fasting insulin secretion in patients with COVID-19 without diabetes on admission and at 3 and 6 months after discharge. METHODS: This 6-month prospective study assessed data from the records of 64 patients without diabetes diagnosed with COVID-19 at Wenzhou Central Hospital, China. Each patient was followed up at 3 and 6 months after discharge. Repeated measures analysis of variance was used to investigate differences in multiple measurements of the same variable at different times. Linear regression analysis was performed to analyze the contributor for changes in the triglyceride-glucose (TyG) index. RESULTS: Fasting C-peptide levels in patients at baseline were lower than the normal range. Compared with the baseline results, patients had significantly elevated fasting C-peptide levels (0.35 ± 0.24 vs 2.36 ± 0.98 vs 2.52 ± 1.11 µg/L; P < .001), homeostasis model assessment for beta-cell function (0.42, interquartile range [IQR] 0.36-0.62 vs 2.54, IQR 1.95-3.42 vs 2.90, IQR 2.02-4.23; P < .001), and TyG indices (8.57 ± 0.47 vs 8.73 ± 0.60 vs 8.82 ± 0.62; P = .006) and decreased fasting glucose levels (5.84 ± 1.21 vs 4.95 ± 0.76 vs 5.40 ± 0.68 mmol/L; P = .003) at the 3- and 6-month follow-up. Male gender, age, interferon-alfa treatment during hospitalization, and changes in total cholesterol and high-density lipoprotein levels were significantly associated with changes in the TyG index. CONCLUSION: Our study provided the first evidence that COVID-19 may increase the risk of insulin resistance in patients without diabetes.

Clinical features and viral RNA shedding of imported and local cases with COVID-19 in Wenzhou, China.

ABSTRACT: Wenzhou had the highest number of confirmed novel coronavirus 2019 (COVID-19) cases outside the Hubei province. The aim of this study was to identify the difference in clinical features and viral RNA shedding between the imported and local COVID-19 cases in Wenzhou.All patients with confirmed COVID-19 admitted to Wenzhou Sixth People's Hospital, Wenzhou Central Hospital Medical Group, from January 17 to February 11, 2020, were enrolled in this study. Data was analyzed and compared for the imported and local cases with regard to epidemiological, demographic, clinical, radiological features, and laboratory findings. Outcomes for the enrolled participants were followed up until May 7, 2020.Of the 136 cases, 50 were imported from Wuhan. The median age was 45 years and 73 (53.7%) were men. The most common symptoms at onset were fever (104 [76.5%]) and cough (85[62.5%]). Pleural effusion was more common among imported cases compared to local cases. The white blood cell count, neutrophil count, lymphocyte count and platelet count of the imported cases were significantly lower than those of the local cases, while the prothrombin time was significantly longer than that of the local cases. Severe and critically ill patients accounted for 15.4% and 2.9%, respectively. The median duration of SARS-CoV-2 RNA shedding from symptom onset was 26 days (IQR 17-32.3 days) and there were no significant differences in duration of viral RNA shedding between the two groups.The study findings suggest that imported cases from Wuhan were more likely to be severe compared to the local cases in Wenzhou. However, there was no difference between imported and local cases on the viral shedding among the COVID patients.

Declined serum high density lipoprotein cholesterol is associated with the severity of COVID-19 infection.

BACKGROUND: COVID-19 infection is epidemic worldwide. We describe the serum lipid profile of the patients with COVID-19 infection. METHODS: In this retrospective study, we collected the first clinical laboratory data of 114 patients on admission, and 80 healthy controls. Meanwhile, we monitored the serum lipid profile, COVID-19 nucleic acid and chest CT scan of a severe patient from the early stage of infection to the recovery period for a total of 80 days. RESULTS: Compared with the healthy controls, the patients had sharply decreased concentrations of total cholesterol, HDL-cholesterol and LDL-cholesterol (P < 0.001). Among the patients, HDL-cholesterol concentration in severe groups was significantly lower than the common groups [1.01 (0.88-1.20) vs 1.21 (1.02-1.48) mmol/l, P < 0.001]. The lipid profile of a severe patient showed that serum cholesterol concentration significantly decreased in the early stage and returned to be normal in the recovery period. Moreover, the change of HDL-cholesterol in this patient was consistent with the results of nucleic acid tests and chest CT scans. In correlation analysis, HDL-cholesterol concentration was negatively correlated with C-reactive protein (CRP, r = -0.396, P < 0.001) and positively correlated with lymphocytes (r = 0.336, P < 0.001). The area under curve (AUC) in receiver operating characteristic (ROC) of HDL-cholesterol was 0.732 (P < 0.001), and, the adjusted odd ratio (OR) of HDL-cholesterol was 0.023 (95% CI 0.002-0.227). CONCLUSIONS: Decreased serum HDL-cholesterol is associated with the severity of COVID-19 infection.

Abnormalities of peripheral blood system in patients with COVID-19 in Wenzhou, China.

BACKGROUND: In December 2019, coronavirus disease 2019 (COVID-19) was first found in Wuhan, China and soon was reported all around the world. METHODS: All confirmed cases with COVID-19 in Wenzhou from January 19 to February 20, 2020, were collected and analyzed. Of the 116 patients with COVID-19, 27 were diagnosed as severe cases. Among severe cases, 9 were treated in ICU. The data of blood routine examination were analyzed and compared among common patients (as common group), severe patients admitted to intensive care unit (as severe ICU group) and severe patients not admitted to ICU (as severe non-ICU group). The blood routine examination results were dynamically observed in the above groups after admission. RESULTS: Patients with COVID-19 have lower counts of leucocytes, lymphocytes, eosinophils, platelets, and hemoglobin, but have higher neutrophil-lymphocyte ratio (NLR) and monocyte-lymphocyte ratio (MLR), which were compared with controls (P < 0.001). In severe ICU group, patients have the lowest count of lymphocytes, but the highest neutrophil count and NLR among the above three groups (all P values < 0.05); NLR and MLR indicators were combined for diagnostic efficacy analysis of severe COVID-19, and its area under the curve reached 0.925. The odds ratio of the delay in days to the start of the increase of eosinophil count for predicting the outcome of patients with severe COVID-19 was 2.291 after age adjusted. CONCLUSIONS: Patients with COVID-19 have abnormal peripheral blood routine examination results. Dynamic surveillance of peripheral blood system especially eosinophils is helpful in the prediction of severe COVID-19 cases.

A Predictive Model for the Identification of Cardiac Effusions Misclassified by Light's Criteria.

OBJECTIVES: The application of Light's criteria misidentifies approximately 30% of transudates as exudates, particularly in patients on diuretics with cardiac effusions. The purpose of this study was to establish a predictive model to effectively identify cardiac effusions misclassified by Light's criteria. METHODS: We retrospectively studied 675 consecutive patients with pleural effusion diagnosed by Light's criteria as exudates, of which 43 were heart failure patients. A multivariate logistic model was developed to predict cardiac effusions. The performance of the predictive model was assessed by receiver operating characteristic (ROC) curves, as well as by examining the calibration. RESULTS: It was found that protein gradient of >23 g/L, pleural fluid lactate dehydrogenase (PF-LDH) levels, ratio of pleural fluid LDH to serum LDH level (P/S LDH), pleural fluid adenosine deaminase (PF-ADA) levels, and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels had a significant impact on the identification of cardiac effusions, and those were simultaneously analyzed by multivariate regression analysis. The area under the curve (AUC) value of the model was 0.953. The model also had higher discriminatory properties than protein gradients (AUC, 0.760) and NT-pro-BNP (AUC, 0.906), all at a P value of <.01. CONCLUSION: In cases of suspected cardiac effusion, or where clinicians cannot identify the cause of an exudative effusion, this model may assist in the correct identification of exudative effusions as cardiac effusions.

Diagnosing malignant pleural effusion using clinical and analytical parameters.

BACKGROUND: Malignant pleural effusion (MPE) is common and diagnosis is often problematic. A cancer ratio (serum lactate dehydrogenases: pleural adenosine deaminase ratio) has been proposed for diagnosing MPE. However, the usefulness of this "cancer ratio" and the clinical-radiological criteria for diagnosing MPE has not been clearly determined to date. The aim of this study was to assess the performance of those parameters in the diagnosis of MPE. METHODS: We analyzed 240 patients including 120 with MPE and 120 with non-MPE (93 tuberculous and 27 parapneumonic). Patients were divided into two groups: MPE and non-MPE (eg, tuberculous and parapneumonic). We constructed two predictive models to assess the probability of MPE: (a) clinical-radiological data only and (b) a combination of clinical-radiological data, the cancer ratio, and the carcinoembryonic antigen (CEA). The performances of the predictive models were assessed using receiver operating characteristic (ROC) curves and by examining the calibration. RESULTS: The area under the ROC curves for model 1 and model 2 were excellent, 0.936 and 0.998, respectively. The overall diagnostic accuracies for model 1 and model 2 were 87.5% and 98.8%, respectively. CONCLUSION: The results confirm that both models achieved a high diagnostic accuracy for MPE; however, model 2 was superior with the addition of its simplicity of use in daily practice. This model should be applied to determine which patients with a pleural effusion of unknown origin would not benefit from further invasive procedures.

RAD51 Gene 135G/C polymorphism and ovarian cancer risk: a meta-analysis.

Previous studies suggest that the RAD51 gene 135G/C polymorphism could be potentially associated with the risk of ovarian cancer. However, results from observational studies are conflicting rather than conclusive. We performed a meta-analysis of the literature aiming to clarify the relationship between the polymorphism of RAD51 gene 135G/C polymorphism and the risk of ovarian cancer. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. We identified five eligible articles, 2336 ovarian cancer cases and 3548 controls. Meta-analysis results showed no significant association between 135G/C polymorphism in the RAD51 gene and ovarian cancer risk (GG vs CC: OR=0.42, 95% CI 0.16-1.06; GC vs CC: OR=0.37, 95% CI 0.12-1.16; Dominant model: OR=0.38, 95% CI 0.13-1.06; Recessive model: OR=1.20, 95% CI 0.91-1.58). No publication bias was found in the present study. This meta-analysis suggests that the RAD51 gene 135G/C polymorphism was not associated with risk of ovarian cancer. Further large and well-designed studies are needed to confirm this conclusion.