Association between autonomic dysfunction with motor and non-motor symptoms in patients with Parkinson's disease.

To investigate the association between autonomic dysfunction (AutD) and motor as well as non-motor symptoms (NMS) in patients with Parkinson's disease (PD). Fifty-three PD patients were divided into two groups based on the number of domains affected by AutD: a multi-domain AutD group (AutD-M) and a single-domain AutD group (AutD-S), as evaluated using the Scale for Outcomes in Parkinson's disease-Autonomic (SCOPA-AUT), which assesses autonomic symptoms, one of the NMS. A comprehensive comparison was conducted between the two groups, including clinical measures such as clinical scales, quantitative evaluations of motor function and exercise capacity. Spearman correlation analysis was employed to investigate the relationship between AutD severity and PD symptoms. Additionally, we performed multiple linear regression model analysis to determine whether associations between SCOPA-AUT scores and clinical assessments remained significant after adjusting for Hoehn and Yahr stage, sex, and age. PD patients in the AutD-M group exhibited significantly more severe NMS and motor symptoms compared to those in the AutD-S group. In correlation analysis, SCOPA-AUT scores showed significant correlations with multiple clinical symptoms, such as most of the NMS, 10-MWT and CPET parameters. Furthermore, regression analysis also revealed that more pronounced fatigue, anxiety, depressive symptoms, worse walking speed and impaired exercise capacity were associated with higher SCOPA-AUT scores. The presence of AutD is correlated with emotional disturbances, decreased exercise endurance, and impaired gait function in patients with PD. Early management of AutD may prove beneficial in alleviating some NMS and motor symptoms in PD.

Resilience, coping style, and COVID-19 stress: effects on the quality of life in frontline health care workers.

The aims of the study were to assess the contribution of resilience, coping style, and COVID-19 stress on the quality of life (QOL) in frontline health care workers (HCWs). The study was a cross-sectional surveyperformed among 309 HCWs in a tertiaryhospital during the outbreak of COVID-19 in China. Data were collected through an anonymous, self-rated questionnaire, including demographic data, a 10-item COVID-19 stress questionnaire, Generic QOL Inventory-74, Connor-Davidson Resilience Scale, and the Simplified Coping Style Questionnaire. Hierarchical regression was used to analyse the relationship between the study variables and the QOL. Among the 309 participants, resilience and active coping were positively correlated with the QOL (P<0.001), whereas, working in confirmed case wards, COVID-19 stress, and passive coping were negatively correlated with the QOL (P<0.001). Resilience and the active coping were negatively correlated with COVID-19 stress (P<0.001). Resilience, coping style,and COVID-19 stressaccounted for 32%, 13%, and 8% of the variance in predicting the Global QOL, respectively. In conclusion, working in confirmed COVID-19 case wards and COVID-19 stress impaired the QOL in HCWs. Psychological intervention to improve the resilience and coping style, and reduce COVID-19 stress are important in improving the QOL and mental health of HCWs.

ASK1 Enhances Angiotensin II-Induced Liver Fibrosis In Vitro by Mediating Endoplasmic Reticulum Stress-Dependent Exosomes.

BACKGROUND: Apoptosis signal-regulating kinase 1 (ASK1) has been reported to induce fibrotic signaling in the setting of oxidative stress. However, the role of ASK1 and its mechanism of action in angiotensin II- (Ang II-) induced liver fibrosis remain largely unknown. METHODS: Human hepatic LX-2 stellate cells were treated with Ang II alone or cotreated with Ang II plus an ASK1 inhibitor (GS-4997) or siRNA-targeting ASK1. Immunofluorescent staining, real-time PCR, and western blotting were used to determine the expressionof α-SMA, Col I, and Col III expression. Cell viability was assessed by the CCK-8 assay. The concentrations of IL-1ß, IL-18, and TNF-α in conditioned medium were determined by ELISA. The levels of intracellular ROS in LX-2 cells were analyzed using a ROS assay kit. Exosome size was determined by electron microscopy. RESULTS: Ang II markedly increased the expression of extracellular matrix (ECM) proteins (α-SMA, Col I, and Col III) and proinflammatory cytokines (IL-1ß, IL-18, and TNF-α). Ang II also increased the expression of endoplasmic reticulum stress (ERS) markers (GRP78, p-PERK, and CHOP) and p-ASK1. Results also showed that pretreatment with GS-4997 or siRNA could abolish all the abovementioned effects on LX-2 cells. Furthermore, we found that exosome release caused by ASK1-mediated ERS was involved in the activation of LX-2 cells by Ang II. The activation of LX-2 cells could be blocked by treating the exosomes with annexin. CONCLUSIONS: In summary, we found that ASK1 mediates Ang II-activated ERS in HSCs and the subsequent activation of HSCs, suggesting a promising strategy for treating liver fibrosis.

MicroRNAs are involved in the self-renewal and differentiation of cancer stem cells.

MicroRNAs (miRNAs) are small non-coding RNA molecules, whose primary function is to regulate gene expression at the post-transcriptional/translational levels. MiRNAs play crucial roles in normal biological processes and are commonly dys-regulated in human diseases. Stem cells are regarded as the "mother" cells of all types of differentiated cells that comprise tissues and organs of the body. A novel hypothesis proposes that tumors are composed of heterogeneous cells derived from cancer stem cells, which have self-renewal and differentiation capabilities similar to those of normal stem cells. Cancer stem cells have been isolated and characterized from various tumors. Given recent studies supporting the critical regulatory roles of miRNAs in the self-renewal and differentiation of cancer stem cells, better understanding the functions of miRNAs will provide invaluable insights into the prevention of tumorigenesis and tumor progression. In this review, we will summarize the research progress in the study of miRNAs involved in the self-renewal and differentiation of cancer stem cells.

Elevated serum YKL-40 level predicts poor prognosis in hepatocellular carcinoma after surgery.

BACKGROUND: YKL-40 is a member of the mammalian chitinase-like proteins. Elevated serum YKL-40 levels in patients with gastrointestinal cancer at time of diagnosis are associated with poor prognosis. The aim of this study is to evaluate the prognostic value of serum YKL-40 before surgery and during follow-up in hepatocellular carcinoma (HCC) patients receiving curative resection. METHODS: Serum YKL-40 levels were determined by enzyme-linked immunosorbent assay. Overall and recurrence-free survival (RFS) curves were constructed using the Kaplan-Meier method and compared by the log-rank test. A Cox proportional-hazards regression model was performed to identify independent prognostic factors. Median follow-up time was 35 months. RESULTS: Baseline serum YKL-40 was elevated in 56% of patients with HCC receiving curative resection. Patients with elevated serum YKL-40 had significantly shorter overall and RFS than patients with normal serum YKL-40 (P = 0.003 and P = 0.001, respectively). Multivariate Cox regression analyses indicated that baseline serum YKL-40 was an independent prognostic variable for overall and RFS [hazard ratio (HR) = 1.968, 95% confidence interval (CI): 1.093-3.543, P = 0.024; HR = 1.891, 95% CI: 1.106-3.232, P = 0.020; respectively]. After curative resection, high serum YKL-40 (log-transformed continuous variable) within 6 months predicted significantly poorer overall survival (HR = 3.003, 95% CI: 1.323-6.817, P = 0.009). CONCLUSIONS: This study indicated that serum YKL-40 was an independent prognostic factor for overall and RFS in HCC patients receiving curative resection. Serial monitoring of serum YKL-40 after curative resection may provide prognostic information.

Hazardous alcohol consumption and aging synergistically increase the risk of death in patients with severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high case fatality rate (CFR). Alcohol consumption which impairs host immunity and contributes to tissue damage in a variety of organs may be a predisposing factor of fatal outcome in SFTS. We aimed to determine the role of alcohol consumption on the fatal outcome of SFTS. Patients with laboratory-diagnosed SFTS who were admitted to the Jinan Infectious Disease Hospital, Jinan, China, between January 2011 and November 2018 were evaluated. Demographic, clinical, and laboratory data were recorded. Alcohol consumption was evaluated. The association between a fatal outcome and each demographic, clinical, and laboratory variable with alcohol consumption was assessed. A total of 694 patients with SFTS were identified during the study period. The overall CFR was 20.9 % (95 % CI: 17.9 %-23.9 %). The CFR in non/light drinkers (0-98 g/week) and moderate/heavy drinkers (>98 g/week) was 18.3 % and 35.6 %, respectively (P < 0.001). In age>60 years patients, the overall CFR in moderate/heavy drinker groups were as high as 53.4 % (95 % CI:40.2 %-66.7 %). Comparing to the age≤60y and non/light drinkers, age>60y and moderate/heavy drinkers was associated with increased risk of death with an odds ratio (95 % CI) of 9.9 (5.1-19.1). The interaction between age>60 and alcohol consumption was a significant determinant for death in both genders (F=10.18, P = 0.001). The clinical manifestation, laboratory parameters, and organ injury were significantly extensive and severe in moderate and heavy drinkers. In conclusion, hazardous alcohol consumption and aging synergistically increase the risk of death in patients with SFTS. In SFTS endemic areas, it is important for older individuals to minimize the exposure risks and abstain from alcohol.

Prodromal fever indicates a high risk of liver failure in acute hepatitis B.

OBJECTIVES: The role of prodromal fever in the clinical course of acute hepatitis B virus (HBV) infection is still largely unclear. This study was conducted to investigate the factors associated with prodromal fever and its role in the development of acute liver failure (ALF) in patients with acute hepatitis B (AHB). METHODS: Inpatients with AHB diagnosed between January 2006 and December 2010 were evaluated and followed. Clinical manifestations, results of laboratory tests, and outcomes were compared between patients with and without prodromal fever. The diagnosis of AHB was based on the discrete onset of symptoms, jaundice, abnormal liver function tests, the detection of high-titer IgM antibody to hepatitis B core antigen (anti-HBc), and a compatible clinical history. RESULTS: A total of 618 AHB inpatients were identified during the study period, of whom 102 (16.5%) had prodromal fever and 41 (6.6%) developed ALF. Prodromal fever indicated more severe liver injury and was independently associated with hepatitis B e antigen (HBeAg) negativity. The occurrence of ALF was more common in febrile patients than in non-febrile patients (18.6% vs. 4.3%, p<0.001). Multivariate logistic regression showed prodromal fever and temperature >38.0°C to be independently associated with the risk of ALF, with an odds ratio (95% confidence interval) of 3.5 (1.4-8.6) and 7.1 (2.6-19.7), respectively. CONCLUSIONS: AHB patients with prodromal fever, which is associated with a lack of HBeAg due to HBV mutation, are at high risk of ALF. Febrile patients with AHB should be managed with particular care.

Associations between thyroid autoantibody status and abnormal pregnancy outcomes in euthyroid women.

We investigated whether thyroid autoantibody status influences pregnancy outcomes in euthyroid women, by comparing abnormal pregnancy outcome rates between those who tested positive for thyroid autoantibodies (Ab+) and those who tested autoantibody-negative (Ab-). Euthyroid pregnant women (n=7,641) underwent tests for serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). The subjects were divided into 4 groups according to thyroid antibody status: TPOAb-/TgAb- (92.9%); TPOAb+/TgAb- (3.2%); TPOAb-/TgAb+ (2.0%); and TPOAb+/TgAb+ (1.9%). The incidence rates of the following abnormal pregnancy outcomes were compared among the 4 groups and analyzed by Fisher's exact test: gestational diabetes, gestational hypertension, placenta previa, placental abruption, premature rupture of fetal membrane (PROM), intrauterine growth restriction, fetal distress, fetal anomalies, stillbirth, preterm birth, and low birth weight. Among the 4 groups, there were no significant differences in age, gestational age, or in the incidence rates of abnormal pregnancy outcomes, except for PROM and low birth weight. The highest incidence rates for PROM and low birth weight were in the TPOAb-/TgAb+ and TPOAb+/TgAb+ subjects, respectively. TgAb positivity and TPOAb positivity were associated with PROM and low birth weight, respectively. Underlying factors that govern the association between thyroid autoantibodies and PROM and low birth weight require further investigation.

Effects of subclinical hypothyroidism on maternal and perinatal outcomes during pregnancy: a single-center cohort study of a Chinese population.

OBJECTIVE: Adverse maternal outcomes and perinatal complications are closely associated with overt maternal hypothyroidism, but whether these complications occur in women with subclinical hypothyroidism (SCH) during pregnancy remains controversial. The aim of this study was to evaluate the effects of SCH on maternal and perinatal outcomes during pregnancy. METHODS: A prospective study of data from 8012 pregnant women (371 women with SCH, 7641 euthyroid women) was performed. Maternal serum samples were collected in different trimesters to examine thyroid hormone concentrations. SCH was defined as a thyroid stimulating hormone concentration exceeding the trimester-specific reference value with a normal free thyroxine concentration. The occurrence of maternal outcomes, including gestational hypertension (GH), gestational diabetes mellitus, placenta previa, placental abruption, prelabor rupture of membranes (PROM), and premature delivery; and perinatal outcomes, including intrauterine growth restriction (IUGR), fetal distress, low birth weight (LBW; live birth weight ≤ 2500 g), stillbirth, and malformation, was recorded. Logistic regression with adjustment for confounding demographic and medical factors was used to determine the risks of adverse outcomes in patients with SCH. RESULTS: Compared with euthyroid status, SCH was associated with higher rates of GH (1.819% vs. 3.504%, P = 0.020; χ2 = 7.345; odds ratio (OR), 2.243; 95% confidence interval (CI), 1.251-4.024), PROM (4.973% vs. 8.625%, P = 0.002; χ2 = 72.102; adjusted OR, 6.014; 95% CI, 3.975-9.099), IUGR (1.008% vs. 2.965%, <0.001; χ2 = 13.272; adjusted OR, 3.336; 95% CI, 1.745-6.377), and LBW (1.885% vs. 4.582%, P<0.001; χ2 = 13.558; adjusted OR, 2.919; 95% CI, 1.650-5.163). CONCLUSIONS: The results of this study indicate that pregnant women with SCH had increased risks of GH and PROM, and their fetuses and infants had increased risks of IUGR and LBW. Thus, routine maternal thyroid function testing is necessary to improve maternal and perinatal outcomes.

Expression of interleukin-17 associated with disease progression and liver fibrosis with hepatitis B virus infection: IL-17 in HBV infection.

BACKGROUND/OBJECTIVES: As a proinflammatory cytokine, interleukin-17 (IL-17) contributes to the inflammation of many autoimmune diseases. We examined IL-17 levels in serum and tissues from patients with chronic hepatitis B virus infection (HBV), and especially evaluated the role of IL-17 in the pathogenesis and progression of liver fibrosis. MATERIALS AND METHODS: Whole venous blood was obtained from four patient groups: chronic hepatitis B (CHB, n = 47), liver cirrhosis (LC, n = 49), primary hepatocellular carcinoma (PHC, n = 44), chronic liver failure (CLF, n = 33), and a normal control group (n = 20). HBsAg was positive in all patients. Liver biopsy samples were acquired from asymptomatic HBsAg carriers (ASC, n = 35), CHB (n = 57), and LC (n = 31) patients. We performed ELISA to measure IL-17 levels in serum samples, and used reverse RT-PCR to measure IL-17 mRNA levels in peripheral blood mononuclear cells (PBMC). IL-17 protein expression was detected in liver biopsy tissues by immunohistochemistry. RESULTS: Compared to normal controls, serum IL-17 protein and mRNA levels were significantly higher in the four infection groups. LC patients exhibited the highest serum IL-17 and PBMC mRNA levels. No significant differences were found between the other three groups. High levels of IL-17 were also observed in tissues from CHB and LC patients, compared to ASC. IL-17 expression was mainly located in the portal area and was positively correlated with inflammation grade and fibrosis stage. CONCLUSIONS: IL-17 expression was found to be increased with increasing degrees of liver fibrosis. This suggests that IL-17 may not only induce the inflammation, but also contribute to disease progression and chronicity. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5306959258322482.

[Expression of interleukin-17 in hepatitis B related liver fibrosis].

AIM: To explore the role of interleukin-17 (IL-17) in the pathogenesis and progress of chronic hepatitis B virus (HBV) related liver diseases, especially in hepatitis B related liver fibrosis. METHODS: Whole vein blood was obtained from the patients with chronic hepatitis B (CHB) (n=36), liver cirrhosis (LC) (n=42) including child-pugh A (n=15), child-pugh B (n=12), child-pugh C (n=15), primary hepatitis carcinoma (PHC) (n=34), chronic severe hepatitis (n=30) and normal control (n=20).The level of serum IL-17 and the expression of IL-17 mRNA in peripheral blood mononuclear cell (PBMC) were analysed by ELISA and RT-PCR respectively. Serum IL-17 and liver fibrosis index (C-IV, LN, HA) concentration of LC classified by child-pugh scores were detected by ELISA. RESULTS: The level of serum IL-17 and the expression of IL-17 mRNA in PBMC in four HBV infectious groups were higher than that in control group ( P<0.01). The level of serum IL-17 and the expression of IL-17 mRNA in PBMC in LC group was higher than that in other groups ( P<0.01). The level of serum IL-17 and liver fibrosis index in child-pugh C group in LC patients were higher than that in Child-pugh B group and that in child-pugh B group were higher than that in child-pugh A group (P<0.01). The level of serum IL-17 in LC group positively correlated to child-pugh score and liver fibrosis index (C-IV, LN, HA) (r=0.582, 0.568, 0.682, 0.764, P<0.01). CONCLUSION: IL-17 is obviously increased in HBV related liver diseases, especially in hepatitis B related liver cirrhosis, indicating that IL-17 may play a part in the development of HBV related liver diseases, especially the pathophysiology of hepatitis B related liver fibrosis.

[Gene chip analysis of mutation of HBV-DNA open reading frame].

OBJECTIVE: To detect the mutation of HBV-DNA open reading frame (ORF), provide evidences for clinical diagnosis and treatment. METHODS: By using gene chip technique, HBV-DNA was amplified by PCR, incorporated with fluorescence, hybridized with oligonucleotide to detect the gene sequence of DNA by computer analysis and observe the natural mutation of HBV-DNA ORF. RESULTS: The mutations of HBV-DNA ORF existed widespread. The rates of mutation on Pre-C 1896, PreC 1814, BCP 1762, BCP 1764, P 528, P 552MI, P 552MV were 23.5%, 3.9%, 55.9%, 53.9%,39.2%, 38.2%, 10.8%, respectively. CONCLUSION: The gene chip technique possesses extremely high sensitivity and reliability,it is one of the effective methods to detect gene mutation. The mutation of HBV-DNA has important influence on the stability and progress of the disease, and on the judgement of prognosis.