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Objective:To determine the effect of miR-122-5p on microglia polarization, apoptosis and inflammation after traumatic brain injury (TBI).Methods:A mouse model and an in vitro TBI model were established. Astrocytes were stimulated to synthesize and release exosomes by brain extracts. microRNA microarray analysis was used to analyze the significantly altered microRNAs. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was applied to detect the expression of miR-122-5p in the in vivo and in vitro TBI model. TUNEL, immunofluorescence, and Western blot were performed to detect the effects of miR-122-5p inhibitors on microglia apoptosis, microglia M1/M2 phenotype transformation and the activation of NLRP3 inflammasome pathway and the phosphorylation of NF-κB after TBI.Results:The results of microRNA microarray analysis showed that 83 miRNAs were downregulated significantly (altered more than 2 folds, P < 0.05), among which miR-122-5p was significantly down-regulated ( P < 0.01). Expression of miR-122-5p was significantly decreased in the in vivo and in vitro TBI model [(1.00±0.00) vs. (0.41±0.15), P < 0.001; (1.00±0.00) vs. (0.34±0.07), P < 0.001]. TUNEL and immunofluorescence showed that miR-122-5p inhibitor significantly alleviated microglia apoptosis[(8.03±1.30) vs. (3.17±0.34), P < 0.001] and promoted microglia M1→M2 phenotype transformation ,M1 phenotype polarization was reduced [(56.96±13.70) vs. (34.70±3.47), P =0.002] and M2 phenotype polarization was increased [(30.46±3.67) vs. (40.74±2.49), P =0.005]. Western blot showed that NLRP3 inflammasome activation was inhibited and NF-κB phosphorylation was decreased when miR-122-5p was downregulated[(0.77±0.10) vs. (0.51±0.11), P =0.02; (0.73±0.08) vs. (0.50±0.07), P =0.003]. Conclusions:miR-122-5p is downregulated in microglia and exosomes secreted by astrocytes after TBI. miR-122-5p inhibitor can attenuate the microglia inflammatory response after TBI by inhibiting the activation of NLRP3 inflammasome pathway and the phosphorylation of NF-κB, promoting the microglia M1→M2 phenotypic transformation and reducing microglia apoptosis, thereby reducing the microglia inflammatory injury after TBI.
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BackgroundThe novel coronavirus (CoV) severe acute respiratory syndrome (SARS)-CoV-2 outbreak started at the end of 2019 in Wuhan, China, and spread over 100 countries. SARS-CoV-2 uses the membrane protein Angiotensin I converting enzyme 2(ACE2) as a cell entry receptor. Indeed, it was reported that the balance of Renin-Angiotensin System (RAS), regulated by both ACE and ACE2, was altered in COVID-19 patients. It is controversial, however, whether commonly used anti-hypertensive drugs Angiotensin I converting enzyme inhibitor (ACEI) and Angiotensin II receptor blocker (ARB) shall be continued in the confirmed COVID-19 patients. This study was designed to investigate any difference in disease severity between COVID-19 patients with hypertension comorbidity. The included COVID-19 patients used ACEI, ARB, calcium channel blockers (CCB), beta blockers (BB), or thiazide to treat preexisting hypertension prior to the hospital were compared to patients who did not take any of those drugs. MethodsIn this multicentre retrospective study, clinical data of 511 COVID-19 patients were analyzed. Patients were categorized into six sub-groups of hypertension comorbidity based on treatment using one of anti-hypertension drugs (ACEI, ARB, CCB, BB, thiazide), or none. A meta-analysis was performed to evaluate the use of ACEI and ARB associated with pneumonia using published studies. FindingsAmong the elderly (age>65) COVID-19 patients with hypertension comorbidity, the risk of COVID-19-S (severe disease) was significantly decreased in patients who took ARB drugs prior to hospitalization compared to patients who took no drugs (OR=0{middle dot}343, 95% CI 0{middle dot}128-0{middle dot}916, p=0{middle dot}025). The meta-analysis showed that ARB use has positive effects associated with morbidity and mortality of pneumonia. InterpretationElderly (age>65) COVID-19 patients with hypertension comorbidity who are taking ARB anti-hypertension drugs may be less likely to develop severe lung disease compared to patients who take no anti-hypertension drugs. FundingNational Natural Science Foundation of China, Chinese Academy of Medical Sciences Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for articles published up to March 15, 2020 using keywords "2019-nCoV", "SARS-CoV-2", "novel coronavirus", and COVID-19 AND "ARB", and "angiotensin II receptor blocker" for papers published in both English and Chinese. We found three papers: one from our group, published in Science China Life Science that demonstrated an elevated Angiotensin II level in blood samples from COVID-19 patients; another a perspective article in Chinese recommending ACEI and ARBs as potential remedies for SARS-CoV-2 infections; the third a retrospective study in Chinese identifying no significant difference between ACEI/ARB associated with outcomes in 112 COVID-19 patients with CVD comorbidity. The International society of Hypertension stated on March 16th, 2020: "there are no clinical data in human to show that ACE-inhibitors or ARBs either improve or worsen susceptibility to COVID-19 infection nor do they affect the outcomes of those infected". Added value of this studyWe retrospectively reviewed different types of anti-hypertensive drugs taken by COVID-19 patients with hypertension comorbidity prior to entering the hospital. We discovered that ARB hypertensive drugs were associated with a decreased risk of severe disease in elderly (age>65) COVID-19 patients (OR=0{middle dot}343, 95% CI 0{middle dot}128-0{middle dot}916, p=0{middle dot}025), the first evidence of ARBs association to COVID-19 infections in human. We conducted a meta-analysis in the literature and found that ARB has positive effects associated with morbidity and mortality of pneumonia. Implications of all the available evidenceARB drugs are widely used in the population with hypertension. Treatments with ACEI and ARBs should be continuous according to medical guidelines. RCT trials of ARB associated with morbidity and mortality of SARS-CoV-2 infection are recommended in the future.
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Objective To study in the correlation of the laboratory markers of coagulation,fibrinolysis and thrombosis in patients with sepsis and SOFA score,the procalcitonin (PCT) concentration and seven-day survival rate.Methods From February 2017 to March 2018,119 patients with sepsis admitted in ICU and another 119 patients with non-sepsis undergoing selective surgery were enrolled as control in this study.APTT (activated partial thromboplastin time),PT-INR (prothrombin time-international normalized ratio),FIB (fibrinogen),AT-Ⅲ (antithrombin Ⅲ),D-Dimer,FDP (fibrinogen degradation products),sTM (soluble thrombomodulin),TAT (thrombin antithrombin complex),PIC (plasmin-a2 plasminogen inhibitor complex) and t-PAI-C (tissue plasminogen activator and its inhibitor complex),were simultaneously monitored at admission.The correlation between the given laboratory markers mentioned and SOFA score,the PCT concentration and seven-day survival rate were analyzed with the Spearman correlation analysis.Results (① In the patients with sepsis,a positive correlation between SOFA score and sTM,t-PAI-C,TAT respectively was found,and a negative correlation between SOFA score and PLT (platelet count) was observed,and no correlation between SOFA score and PIC was noticed.(②) A positive correlation between PCT and sTM,t-PAI-C respectively was significant,a negative correlation between PCT and PLT was marked,and no correlation between PCT and AT-Ⅲ,TAT,PIC respectively was found.(③) A negative correlation between seven-day survival rate and sTM,t-PAI-C and TAT respectively was obvious,a positive correlation between seven-day survival rate and AT-Ⅲ,PLT respectively was occurred,and no correlation between seven-day survival rate and PIC was determined.Conclusions Soluble thrombomodulin (sTM),thrombin-antithrombin (TAT),antithrombin Ⅲ (AT-Ⅲ) and tissue plasminogen activator inhibitor complex (t-PAI-c) were good clinical monitoring indicators of coagulation disorder in patients with sepsis,which were the representative of the endothelial cell damage with highly activated coagulation,relatively insufficient anti-coagulation function and poor fibrin degradation ability.These were good adjuvants to PLT,INR and APTT for core diagnostic criteria of coagulation disorder in sepsis.
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Objective To analysis of multiple myeloma (MM) and non-MM patients with the same clinical manifestations but significant differences in laboratory findings at the first visit to the Emergency Medicine Department suggesting that patient should be rule out the possibilities of suffering from MM by the attending physicians engaging in a specialty other than hematology as soon as possible to avoid misdiagnosis of MM.Methods Retrospective analysis of clinical features of MM cases from February 2013 to December 2016.Patients with renal dysfunction (serum creatinine ≥ 177 mmol/L),infection,bone pain and anemia were divided into four groups.The non-MM patients with the same clinical symptoms were enrolled as control group.SPSS22.0 and Medcalce 15.10 software were used for analyzing the distinct difference and diagnostic validity of routine laboratory tests in patients with MM and non-MM.Results ①The patients with serum creatinine≥ 177 mmol/L,and unexplained renal insufficiency with blood Ca2+ ＞ 2.39mmol/L,ALB ≤ 30.31 g/L and Hb≤84 g/L should be investigated the possibility of MM.②The patient with poor response to the conventional treatment and unexplained infection with IgM ＜0.42 g/L and ALB≤32.7 g/L or ESR ＞ 82 mm/h and Hb ＜ 100 g/L should be investigated the possibility of MM.③The male patients with the first symptom in bone and joint pain associated with bone damage with urinary protein and blood,and the emergence of Ca2+ ＞ 2.39 mmol/L,ALB ＜ 37.5 g/L,Hb ＜ 104 g/L and TT ＞ 19.8 s were suggested to detect MM.④The poor respose to conventional treatment,unexplained anemia (Hb≤90 g/L),IgM ＜ 0.51 g/L,ALB ＜ 34.1 g/L and GLB ＞ 46.4 g/L suggested to detect MM.Conclusions On the basis of symptoms such as renal insufficiency,infection,bone pain,anemia,routine blood laboratory findings of high calcium,low IgM,low albumin,and high globulin,it was recommended that bone marrow biopsy be made to detect MM.
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Objective To investigate risk factors of the prognosis of patients with severe fever with thrombocytopenia syndrome (SFTS).Methods From May 2012 to July 2014,17 cases of severe fever with thrombocytopenia syndrome in Renmin Hospital of Wuhan University were treated.Clinical data including history of epidemiology,clinical manifestations,complications,physical examination and laboratory test results on admission and the third day after admission were retrospectively analyzed and compared with the death group and recovery group by application of Spearman correlation analysis.Results Elderly male patients with neuropsychiatric symptoms,or abnormal liver function,or abnormal blood clotting function had higher risk of the poor prognosis.In SFTS patients,AST,ALT was significantly increased,AST 539 U/L (229.73,545.4) U/L (r =0.597,P =0.015) was a risk factor affecting prognosis.Elevated blood ammonia indicated serious liver dysfunction and neurological dysfunction which were manifested as irritability,delirium,and trembling limbs.In SFTS patients,platelets were significantly decreased accompanied with mouth ulcers / bleeding gums,gastrointestinal bleeding.PLT 24.88 × 10 9/L-1 (12.75,35.00) ×10 9/L-1 (r=0.557,P=0.005) or APTT 86.06 s (66.88,114.18) (r=0.798,P=0.001) or D-dimmer 9.79 mg / L (4.09,16.51) mg/L (r =0.597,P =0.015) are risk factors affecting poor prognosis.Conclusions On the third days after admission,AST,WBC,PLT,APTT,Ddimmer are risk factors for prognosis of patients with severe fever with thrombocytopenia syndrome infected by a novel bunyavirus.
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Objective To investigate the diagnostic and predict vaIue of procalcitonin (PCT) in ICU patients with sepsis and the correlation between PCT concentration and positive results of bacterial culture.Methods A total of 278 patients with sepsis were admitted into emergency ICU,general ICU and respiratory ICU from October 2011 to September 2012.Of them,193 patients had definite microbial infection evidence.Serum PCT levels among groups of different pathogens were compared.The analysis of correlation between the PCT concentration of the first assay was got after admission and short-term prognosis was evaluated.The correlation between PCT level and positive results of bacterial culture was also evaluated.Results Spearman correlation analysis showed that serum PCT levels of bacterial infections in patients with sepsis were significantly higher than those of the non-bacterial infections in patients with sepsis (P =0.001).And there was a positive correlation between the PCT concentration of the first specimen after admission and 7-day in-hospital mortality in patients with sepsis due to bacterial infections (r =0.277,P =0.004).The patients with PCT levels greater than 2 ng/ml had high vulnerability to bacterial infection Conclusions The PCT concentration of the first assay after admission was positively correlated to 7-day mortality in ICU patients with sepsis due to bacterial infections.The serum PCT concentration indicated the severity of host response to the bacterial infection.And etiological evidence directly showed pathogenic factors.Both of PCT and etiological evidence related to bacterial infection,reflected different aspects of bacterial infection.
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Objective To evaluate the diagnostic and predict value of procalcitonin (PCT) levels in patients diagnosis of sepsis with immune system defect in the intensive care unit (ICU).Methods This is a retrospective analysis.We enrolled 278 patients diagnosis of sepsis in Emergency ICU,general ICU and Respiratory ICU in Renmin Hospital of Wuhan University from October 2011 to September 2012.Among them,122 patients have normal immune function and 156 patients have auto-immune system diseases or/and requiring corticosteroids or chemotherapy.According to the APACHE Ⅱ score,patients were divided into low-risk group,middle-risk group and high-risk group,and their PCT levels were compared.Logistic regression analysis of the multiple factors was used to screen independent risk factors for predicting 7 days' mortality.The predictive ability was also evaluated and compared between the first time of PCT concentration after admission and dynamic change of PCT within the first week with area under receiver operator's characteristic curve (ROC curve,AUC).Result The results of Spearman correlation analysis showed that there was a significant positive correlation between the patients' PCT concentration and APACHE Ⅱ score (r =0.979,P ＜ 0.05).And there was a positive correlation between the first PCT concentration after admission and 7 days' mortality in-hospital (r =0.826,P ＜ 0.05).Multiple factors logistic regression analysis indicated that both the first time PCT concentration after admission and APACHE Ⅱ score of patients were independent risk factors for predicting 7 days' mortality (PCT OR =1.77,95％ CI =1.28-3.83,P =0.0023).The warning value of 7 days' mortality for patients with normal immune function was PCT≥7.18 ng/ml and for those with abnormal immune function was PCT ≥ 3.52 ng/ml.Compared to dynamic monitoring of PCT,there was no significant difference in sensitivity but specificity is less than the dynamic monitoring of PCT.Conclusions The diagnostic and predict value of procalcitonin (PCT) levels were not affected by the immuno-suppressive therapy.The first time PCT concentration after admission was an independent risk factor for predict of 7 days' mortality in ICU patients with sepsis.The PCT warning value of the sepsis patients with abnormal immune function was much lower compared to those with normal immune function.
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Objective To evaluate the therapeutic effects of autolngous bone marrow mesenchymal stem cells transplantation in the early phase of acute renal ischemia-reperfusion(I/R)injury in rabbits and their impact on tubular epithelial cell apoptosis.Method Bone marrow mesenchymal stem cells(MSCs)were isolated and cultured in vitro.Thirty rabbits were divided randomly into transplanted group,control group and sham-operated group,10 in each group.Rabbits of transplanted group were induced acute renal I/R injury by clamping bilateral renal arteries for 90 minutes,then transplanted MSCs labeled with BrdU immediately after the resumption of circulation in kidney.The rabbits of control group were induced acute renal I/R injury and then infused with saline instead.The sharn operated rabbits were transplanted autologous MSCs labeled with BrdU after sham operation.Fortyeight hours after transplantation,all rabbits were sacrificed.Renal functional and structural damage were evaluated.MSCs derived BrdU positive cells were determined by immunostalning.Tubular epithelial cell apoptosis was arialyzed by usign TUNEL.The SPSS version 11.3 Software was used for statistical analysis.ANOVA were used to ana lyze the data of renal function and tubular epithelial cell apoptesis.Data of renal structure darnage were analyzed by using the nonparametric Kruskal-Wallis test.Results Compared with control group,the renal functional and struc tural darnage were significantly ameliorated(24 h,BUN:F=7.483,Ser:F:15.091;48 h,BUN:F:17.741.Scr:F=61.865;P<0.05),tubular epithelial cell apoptods Wsa reduced significantly in transplanted group(F=135.495,P<0.01).MSCs derived BrdU positive cell were detected in the renal tissues of transplanted rabbits.Conelusiu Autologous bone marrow mesenchymal stern cells transplantation is curative for acute renal I/R injury in rabbits.Bone marrow MSCs might ameliorate renal I/R injury by reducing tubular epithelial cell apoptosis.
