Exosomal microRNAs as diagnostic biomarkers and therapeutic applications in neurodegenerative diseases.

Originating from slow irreversible and progressive loss and dysfunction of neurons and synapses in the nervous system, neurodegenerative diseases (NDDs) affect millions of people worldwide. Common NDDs include Parkinson's disease, Alzheimer's disease multiple sclerosis, Huntington's disease, and amyotrophic lateral sclerosis. Currently, no sensitive biomarkers are available to monitor the progression and treatment response of NDDs or to predict their prognosis. Exosomes (EXOs) are small bilipid layer-enclosed extracellular vesicles containing numerous biomolecules, including proteins, nucleic acids, and lipids. Recent evidence indicates that EXOs are pathogenic participants in the spread of neurodegenerative diseases, contributing to disease progression and spread. EXOs are also important tools for diagnosis and treatment. Recently, studies have proposed exosomal microRNAs (miRNAs) as the targets for therapies or biomarkers of NDDs. In this review, we outline the latest research on the roles of exosomal miRNAs in NDDs and their applications as potential diagnostic and therapeutic biomarkers, targets, and drugs for NDDs.

Epidemiological investigation and intergenerational clinical characteristics of 24 COVID-19 patients associated with supermarket cluster

ObjectiveTo analyze the epidemiological and intergenerational clinical characteristics of COVID-19 patients associated with cluster, so as to understand the rules of the patients associated with cluster of this outbreak and provide help for the prevention and control of COVID-19. MethodsAll close contacts of the patient were screened since the first supermarket employee with COVID-19 was identified. A retrospective analysis was made on the epidemiological and clinical characteristics of the confirmed cases admitted to the designated hospitals for centralized treatment. The patients were divided into two groups according to the first generation (supermarket employees, group A) and the second or third generation (family members or friends of supermarket employees, group B), and the similarities and differences between the two groups were compared. ResultsA total of 24 COVID-19 patients were diagnosed, with an average age of 48 {+/-}1.73 years. The mean duration from onset to release form quarantine was 21.04{+/-} 6.77 days, and the onset time was concentrated in 5-11 days after the first patient was diagnosed. Among all the patients, 23 patients were moderate, among which 7 patients (29.17%) were asymptomatic. Symptoms of symptomatic patients were cough (75.00%), low fever (62.50%), shortness of breath (41.67%), sore throat (25.00%), gastrointestinal symptoms (25.00%), fatigue (20.83%), etc. Biochemical examination on admission showed that the white blood cell count < 4.0x109/L (29.17%) and the lymphocyte count <1.1x109/L (58.33%). The lymphocyte count of 50.00% of the patients was [≤] 0.6 x 109/L. On admission, chest CT showed pneumonia (100%) with bilateral infiltration (75.00%). Treatment: antiviral drug (100%), Chinese medicine (100%), common oxygen therapy (45.83%). There were 11 cases in group A (first generation, 11 cases) and 13 cases in group B (second generation, 11 cases; third generation, 2 cases). In group B, there were more males, from onset to admission later, more patients had underlying diseases, and more patients were treated with albumin (P<0.05). However, there was no statistical difference between the two groups in other clinical indicators, including the duration from onset to release form quarantine(P>0.05). There was no improvement in granulocyte count in all patients, as well as in groups A and B, between admission and release from quarantine(P>0.05). ConclusionThe clinical characteristics of COVID-19 patients associated with cluster were similar to those of other COVID-19 patients, but there were some special features. The severity of the disease was similar and there was intergenerational spread. There was no difference in clinical characteristics between generations. Asymptomatic infections occurred in a proportion of patients and could cause spread.

Clinical significance of combined detection of peripheral miR-182 and IL-17 in the early diagnosis of patients with eclampsia complicated with cerebral infarction in ICU / 中华危重病急救医学

Objective To observe the effect of peripheral blood microRNA-182 (miR-182) combined with interleukin-17 (IL-17) in the early diagnosis of cerebral infarction (CI) in patients with eclampsia. Methods A prospective non-randomized controlled study was conducted. The patients with eclampsia admitted to intensive care unit (ICU) of Liaocheng People's Hospital from January 1st, 2013 to September 30th 2016 were enrolled. Cerebral imaging was conducted in 7 days after admission to make a definite diagnosis of the occurrence of CI, excluding patients with cerebral hemorrhage. Patients were divided into CI group and non-CI group. Twenty healthy women of childbearing age were selected as control group. Peripheral venous blood of all patients with eclampsia at 1 day after admission, the expression of miR-182 was detected by real-time fluorescence quantitative polymerase chain reaction (PCR), regulatory T cells (Treg) and T helper 17 cells (Th17) ratio was detected by flow cytometry, and the level of plasma IL-17 was detected by enzyme linked immunosorbent assay (ELISA). Pearson method was used to analyze the correlation between the indexes. The receiver operating characteristic curve (ROC) was used to analyze the diagnostic value of each index for CI in patients with eclampsia. Results In the 30 patients with eclampsia, there were 13 cases of CI, including 10 case of cerebral venous thrombosis (CVT) and 3 cases of arterial thrombus; 17 cases of non-CI, including 15 cases of reversible posterior leukoencephalopathy syndrome (RPLS) and 2 cases without obvious abnormalities. Compared with control group, the levels of miR-182, Th17% and IL-17 in non-CI group and CI group were significantly higher, and the Treg% was significantly lower. The levels of parameters mentioned above were further increased in CI group than those in non-CI group [miR-182 (2-ΔΔCt): 2.35±0.79 vs. 1.75±0.56, Th17%: (5.16±1.89)% vs. (3.93±1.92)%, IL-17 (ng/L):37.45±6.20 vs. 26.65±5.13, all P < 0.05]. Pearson correlation analysis showed that miR-182 was positively correlated with Th17% and IL-17 (r1 = 0.761, r2 = 0.842, both P < 0.01). ROC curves showed that when the cut-off value of miR-182 was 2.88, the diagnosis sensitivity of preeclampsia CI was 84.6%, the specificity was 82.4%, and area under the ROC curve (AUC) was 0.816 [95%CI confidence interval (95%CI) = 0.641-0.992]; when cut-off value of IL-17 was 34.44 ng/L, diagnosis of preeclampsia CI the sensitivity was 71.5%, the specificity was 85.3%, and AUC was 0.773 (95%CI = 0.602-0.945); when miR-182 was combined with IL-17, the diagnosis sensitivity was 92.3%, specificity was 83.6%, and AUC was 0.896 (95%CI = 0.759-1.032). Conclusions To some extent the expression of miR-182 and IL-17 in peripheral blood can predict the occurrence of CI in early stage. When the two are used together, the predictive value is better.

Detection of vitamin D in sera of patients with atopic dermatitis and its clinical significance / 中华皮肤科杂志

Objective To measure the serum levels of vitamin D,total immunoglobulin E (tIgE),interleukin-4 (IL-4) and IL-6 in patients with atopic dermatitis (AD),to evaluate the association between vitamin D and severity of AD,and to investigate the role of vitamin D in inflammatory and immunoregulatory processes during the occurrence of AD.Methods Peripheral blood samples were collected from 37 patients with AD (AD group) and 30 healthy controls (control group).The serum levels of vitamin D,tIgE,and IL-6 were measured by chemiluminescent sandwich enzyme immunoassay,and those of IL-4 by enzyme-linked immunosorbent assay.The severity of AD was assessed by the SCORing atopic dermatitis (SCORAD) score.The t test or Mann-Whitney U test was performed to assess the differences in vitamin D,tIgE,IL-4 and IL-6 levels between the AD group and control group,chi-square test to compare the proportion of patients with vitamin D deficiency,insufficiency and sufficiency,and Pearson's correlation analysis or Spearman's correlation analysis to evaluate the correlations between the SCORAD score and serum levels of vitamin D,tIgE,IL-4 and IL-6.Results Compared with the control group,the AD group showed significantly decreased serum levels of vitamin D (24.77 ± 9.29 vs.28.98 ± 6.87 μg/L,t =2.015,P =0.048),but significantly increased serum levels of tIgE (137.68 [37.59-414.53] vs.45.16 [14.56-112.12] IU/ml,Z =-3.399,P =0.001),IL-4 (8.86 ± 4.83 vs.4.78 ± 3.07 ng/L,t =4.147,P ＜ 0.001) and IL-6 (6.53 [3.99-15.30] vs.4.58[2.85-8.17] ng/L,Z =-2.173,P =0.030).Among patients with AD,the SCORAD score was negatively correlated with serum levels of vitamin D (r =-0.505,P =0.001),positively correlated with those of tIgE (r =0.531,P =0.001) and IL-4 (r =0.519,P =0.001),but uncorrelated with those of IL-6 (r =-0.139,P =0.411).There were significant differences in the proportion of patients with vitamin D deficiency,insufficiency and sufficiency between the AD group and control group (x2 =8.762,P =0.013).AD patients with vitamin D deficiency showed significantly increased serum levels of tIgE (2846.87 [319.02-7300.00] IU/ml) and IL-4 ([16.37-2.05] ng/L) compared with those with vitamin D insufficiency (110.07 [26.20-501.48] IU/ml,P =0.045;[8.28 ± 4.48] ng/L,P =0.011) and those with vitamin D sufficiency (123.93 [91.61-273.68] IU/ml,P =0.024;[8.00 ± 4.63] ng/L,P =0.041).In addition,serum levels of IL-6 were also higher in patients with vitamin D deficiency than in those with vitamin D sufficiency (15.10 [8.49-30.72] vs.6.22 [4.47-9.47] ng/L,P =0.011].Conclusions Vitamin D deficiency or insufficiency exists in patients with AD.Vitamin D deficiency is correlated with high serum levels of tIgE,IL-4 and IL-6,and the severity of AD is closely correlated with increased serum levels of tIgE and IL-6 as well as decreased serum levels of vitamin D.

The significance of the monocyte human leukocyte antigen-DR level in the assessment of the severity of acute pancreatitis / 中华危重病急救医学

Objective To investigate the clinical value of the peripheral blood monocyte human leukocyte antigen-DR (mHLA-DR) for assessment of degree of severity and the diagnosis of acute pancreatitis (AP). Methods A case-control study was conducted. Eighty-six AP patients admitted to Shandong Liaocheng People's Hospital from June 2014 to May 2015 were enrolled. Patients were classified into four groups [mild (n = 33), moderate (n = 25), severe (n = 16), critical (n = 12)] according to the disease classification. Eighty healthy persons subjected to physical examination center of our hospital at the same time were served as controls. Acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) scores in patients were estimated. Flow cytometry was used to measure the expression of the peripheral blood mHLA-DR, and the Pearson method was used to analyze the relationship between the level of mHLA-DR and the APACHE Ⅱ score. The receiver-operating characteristic curve (ROC) was plotted, and then the clinical value of the peripheral blood mHLA-DR was analyzed for the diagnostic value in AP patients. Results The expression of the mHLA-DR in patients with AP was significantly lower than that of healthy control group [(63.7±18.6)% vs. (86.4±8.3)%, t = 5.319, P < 0.001]. The expression levels of the mHLA-DR in mild group, moderate group, severe group, and critical group were (79.6±6.5)%, (66.4±9.4)%, (49.9±8.1)%, (32.5±12.0)%, respectively, and the APACHE Ⅱ score were 4.67±1.99, 5.88±2.05, 9.06±2.62, 12.33±3.96, respectively. Pair wise comparisons were statistically significant (all P < 0.05). The HLA-DR expression level in the peripheral blood of patients with AP was negatively correlated with the APACHE Ⅱ score (r = -0.695, P < 0.001). The area under the ROC curve (AUC) of mHLA-DR expression in peripheral blood for AP was 0.894 [95% confidence interval (95%CI) = 0.847-0.941, P < 0.001], and the cut-off point was 84.40%, with the sensitivity of 75.0%, the specificity of 90.7%, and the accuracy rate of 83.1%. The AUC of mHLA-DR expression for mild AP was 0.938 (95%CI = 0.889-0.987, P < 0.001), and the cut-off point was 72.70%, with the sensitivity of 87.9%, the specificity of 88.7%, and the accuracy rate of 88.4%. The AUC of mHLA-DR expression for severe and critical AP was 0.943 (95%CI = 0.881-1.005, P < 0.001), and the cut-off point was 57.85%, with the sensitivity of 84.0%, the specificity of 96.4%, and the accuracy rate of 90.6%. Conclusions The expression levels of the peripheral blood mHLA-DR in AP patients can reflect the degree of disease, and contribute to the diagnosis of AP. The value of mHLA-DR may be used as a new biological indicator in the diagnosis and assessment for the severity of AP.

Clinical Significance of Arterial Stiffness and Thickness Biomarkers in Type 2 Diabetes Mellitus: An Up-To-Date Meta-Analysis.

BACKGROUND: Type 2 Diabetes mellitus (T2DM) is associated with increased risk of cardiovascular disease (CVD). Previous studies explored the association of T2DM with arterial stiffness and thickness biomarkers including the augmentation index (AIX), aortic pulse wave velocity (aPWV), brachial-ankle PWV (baPWV), carotid intima-media wall thickness (IMT) as well as blood pressure (BP), low density lipoprotein cholesterol (LDL-C); however the conclusions are either inconsistent or incomprehensive. MATERIAL AND METHODS: The average differences of each included trial were expressed as the standardized mean difference (SMD) with 95% confidence interval (CI). Analyses of carotid IMT, aPWV, baPWV and AIX Systolic BP (SBP), diastolic BP (DBP), LDL-C and HDL-C were independently performed. Furthermore, subgroup analyses by ethnicity (Caucasian or Asian) were conducted. Begg's and Egger's tests were performed for potential publication biases detection. RESULTS: A total of 14 case-control eligible studies with 1222 T2DM patients and 1094 control subjects were included. In the overall analysis, significant associations were observed between the carotid IMT, aPWV, baPWV, LDL-C, HDL-C, SBP, and DBP with T2DM (IMT: p=1.1*10-12; aPWV: p=1.1*10-7; baPWV: p=1.8*10-33; LDL-C: p=3.1*10-8; HDL-C: p=6.1*10-18; SBP: p=3.9*10-21; DBP: p=4.8*10-5). No association was detected for AIX (p=0.09). Subgroup analyses indicated that aPWV, baPWV, SBP, LDL-C, and HDL-C were associated with T2DM in both white and Asian populations (p<0.05). The significant associations of IMT, AIX and DBP with T2DM were only observed in the Asian subgroup. CONCLUSIONS: Carotid IMT, aPWV, baPWV, as well as LDL-C, HDL-C, SBP, and DBP but not AIX were useful noninvasive early markers for T2DM vascular dysfunction detection.

Expression and clinicopathologic significance of Golgi phosphoprotein 3 in ovarian serous cystadenocarcinoma / 肿瘤研究与临床

Objective To investigate the expression of Golgi phosphoprotein 3 (GOLPH3) at protein and mRNA levels in serous epitheial ovarian carcinoma and its significance.Methods The expression of GOLPH3 at protein and mRNA levels were evaluaed by Western blot and Real time RT-PCR,respectively,in 42 cases of serous epithelium ovarian carcinoma,14 cases of benign serous ovarian tumors and 7 cases of normal ovarian epithelium tissues.Results GOLPH3 mRNA was significantly higher from 2.97 to 7.04 fold in ovarian serous cystadenocarcinoma tissues compared with ovarian serous carcinoma tissues (P ＜ 0.05).There was no positive expression of GOLPH3 protein in normal ovarian epithelium tissues.GOLPH3 protein positive expression rate was higher in ovarian serous cystadenocarcinoma (73.81 ％) than that in ovarian serous carcinoma (35.71％) (P ＜ 0.01).GOLPH3 protein was correlated with the pathologic differentiation (P =0.019),the FIGO stage (P =0.042),and lymphatic metastasis (P =0.000),but was not associated with age (P =0,881).The positive rate and overexpression of GOLPH3 in poor differentiated grade group were higher than that in well and middle differentiated grade group (P ＜ 0.05).Conclusions GOLPH3 may play an important role on the development of ovarian serous cystadenocarcinoma,and may be a potential target of gene therapy.

Whether autologous bone marrow mesenchymal stem cell transplantation is safe, feasible, and effective to the treatment of intracerebral hemorrhage: A 32-case analysis / 中国组织工程研究

BACKGROUND: Previous animal studies demonstrated that bone marrow mesenchymal stem cells could differentiate into nerve cells under a certain condition; however, the clinical application for treating nervous system disease has been less reported. OBJECTIVE: To observe a short-term effect of autologous bone marrow mesenchymal stem cell transplantation on treating cerebral hemorrhage.METHODS: A total of 32 patients with cerebral hemorrhage who were selected from the Department of Neurosurgery, Liaocheng Brain Hospital between November 2007 and January 2009 were considered as a treatment group. According to general data and the amount of hematoma, they were treated by drilling drainage or hematoma evacuation. Drainage tubes were detained into hematoma cavity, and 3.5 mL autologous bone marrow mesenchymal stem cell suspension was injected through drainage tube. A total of 40 additional patients who did not treated with stem cell transplantation were considered as a control group. Neurologic impairment (NIHSS) and activities of daily living (Barthel index) were performed before and 6 months after transplantation; meanwhile, the brain MRI, serum biochemical and tumor marker were evaluated to detect security of stem cell transplantation. RESULTS AND CONCLUSION: The NIHSS score and Barthel index in the treatment group were similar to those in the control group before transplantation. Compared with control group, NIHSS scores were significantly decreased in the treatment group (P < 0.01), but Barthel index was significantly increased 6 months after transplantation (P < 0.01). Compared with before transplantation, NIHSS score were significantly decreased (P < 0.01), but Barthel index was significantly increased in the treatment group 6 months after transplantation (P < 0.01). Two patients in the treatment group had febrile, which was recovered after treatment. The following-up 6 months after transplantation demonstrated that brain MRI and biochemical indicators were normal except an increasing of CA-153 caused by lung cancer in one patient. The autologous bone marrow mesenchymal stem cell transplantation for treatment of cerebral hemorrhage is safe and effective in a short-term period; however the long-term effect still needs to be further studied.

Observation on the effect of autologous bone marrow stem cells transplantation in treatment of early spinal cord injury / 中国医师杂志

Objective To investigate the recent efficacy and safety of autologous bone marrow stem cells transplantation in treatment of early spinal cord injury. Methods 51 cases of early spinal cord injury admitted to Liaocheng People Hospital from 2007.11 to 2009.8 were enrolled in this study. In transplantation group, 24 patients were treated by subarachnoid space injection with autologous bone marrow stem cell transplantation. The patients who were not transplanted in the same period of hospitalization were selected as control group. Motor and sensory function ( AISA score) was assessed at 1, 3, 6 months before and after transplantation in two groups patients. And blood routine, clotting mechanisms, biochemical items andtunor markers were determined in followed up. Results After one month of transplantation, two groups ofpatients had recovered in motor and sensory function to some degree. After three months of transplantation,there was significant different between transplantation group and control group in sensory function recovery (P < 0. 05 ). After 6 months of transplantation, there were significant different between transplant group and control group in motor and sensory function recovery (P<0.05). Blood examination results did not show markedly abnormal in followed -up patientsConclusion The safety and recent effect of autologous bone marrow stem cells transplantation in treatment of early spinal cord injury were satisfied, but the long - term effect was still unclear.