[Acupuncture mediated miR-34c-5p regulates the autophagy of hippocampal neurons in rats with cerebral ischemia/reperfusion injury].

OBJECTIVE: To observe the effect of acupuncture on the expression of miR-34c-5p, autophagy-related proteins and apoptosis rate in hippocampus of rats with cerebral ischemia/reperfusion injury (CI/RI), so as to explore its mechanism in regulating autophagy in hippocampal neurons in CI/RI rats. METHODS: SD rats were randomly divided into sham operation, model, medication and acupuncture groups, with 20 rats in each group. The rat model of CI/RI was established by occlusion of the middle cerebral artery. In the acupuncture group, "Dazhui" (GV14), "Baihui" (GV20) and "Shuigou" (GV26) were punctured with filiform needles and stimulated manually once every 15 min, for 30 min. The rats of the medication group were intraperito-neally injected with edaravone (5 mg/kg). The treatment was conducted once every 12 h for a total of 7 times. The neurological de-ficit score of all the rats were evaluated according to Garcia's methods, and TTC staining was employed to assess the cerebral ischemic area (percentage of cerebral infarct area, CIA). Transmission electron microscopy (TEM) was used to observe the ultrastructural changes of hippocampal neurons. The expression of hippocampal miR-34c-5p was measured by real-time PCR, and the protein expressions of hippocampal LC3B, Beclin1 and p62 were measured by Western blot. The apoptosis rate of ischemic brain tissue was observed by TUNEL staining. RESULTS: Compared with the sham operation group, the neurological deficit score, the expressions of miR-34c-5p, Beclin1, p62 and LC3B-Ⅱ/LC3B-Ⅰ were significantly decreased (P<0.01, P<0.05), and the CIA and the apoptosis rate significantly increased (P<0.01) in the model group. Compared with the model group, the neurological deficit scores, the expressions of miR-34c-5p, Beclin1, p62 and LC3B-Ⅱ/LC3B-Ⅰ were significantly increased (P<0.01, P<0.05), and the CIA and the apoptosis rate significantly decreased (P<0.01) in the medication and acupuncture groups. Compared with the medication group, the expression of miR-34c-5p was significantly increased (P<0.01). The results of electron microscope showed that the neurons in the acupuncture and medication groups were less damaged than those in the model group, the cells showed mild edema, and the structures were relatively complete. Some normal organelles could be seen, and autophagy bodies, autophagy lysosomes and their encapsulated organelles could still be observed. CONCLUSION: Acupuncture can improve the neurological deficit and reduce the area of cerebral infarction in CI/RI rats, which is closely with its effect in promoting hippocampal neuronal autophagy and anti-apoptosis via up-regulating the expression of miR-34c-5p.

Prognostic value of albumin-red cell distribution width score in patients with severe community-acquired pneumonia.

BACKGROUND: It has been recently reported that albumin (ALB) and red cell distribution width (RDW) are correlated with the prognosis of community-acquired pneumonia, while their role in severe communityacquired pneumonia (sCAP) is unknown. This study aimed to investigate the correlation between the ALBRDW score and 90-day mortality of sCAP patients. METHODS: A total of 179 sCAP patients admitted to our hospital between January 1, 2014 and June 30, 2019 were enrolled in this study. Data of patient characteristics and laboratory data were obtained and CURB-65 was calculated. The ALB-RDW score was calculated based on serum ALB and RDW. Receiver operating characteristic (ROC) curve and the value of area under the curve (AUC) were used to evaluate the association between ALB-RDW score and 90-day mortality of sCAP patients. RESULTS: Compared with survivors, age, white blood cell counts, neutrophil counts, RDW, D-dimer, serum creatinine, lactic dehydrogenase, CURB-65 score, ALB-RDW high score ratio, invasive ventilation and septic shock were higher in non-survivors, while ALB and hemoglobin (HB) were lower. Multivariate logistic regression analysis identified that high age, serum creatinine, ALB-RDW score and invasive ventilation were the independent risk factors of 90-day mortality (P<0.05). Moreover, the AUC of ALB-RDW score was 0.742 [95% confidence interval (CI): 0.667-0.817], which was superior to CURB-65 score 0.725 (95% CI: 0.651-0.798). The AUC increased to 0.798 (95% CI: 0.733-0.862) when combined with CURB-65 score. CONCLUSIONS: High age, serum creatinine, ALB-RDW score and invasive ventilation were the independent risk factors of 90-day mortality of sCAP patients. In addition, the correlation between ALB-RDW and 90-day mortality was even stronger when combined with CURB-65 score.

Predictive role of monocyte-to-lymphocyte ratio in patients with Klebsiella pneumonia infection: A single-center experience.

The aim of the study is to explore whether monocyte-to-lymphocyte ratio (MLR) provides predictive value of the severity in patients with Klebsiella pneumonia infection (KPI).Patients in a tertiary medical center with Klebsiella pneumonia infection from 2014 to 2017 were recruited in this study. Patients with Klebsiella pneumonia infection were stratified into two groups based on the National Early Warning Score (NEWS). MLR was calculated by dividing monocytes count by lymphocytes count obtained from routine blood examination. The area under the curve (AUC) values was determined using the receiver-operating characteristic (ROC) curve. The correlation between the variables was tested with Pearson or Spearman correlation analysis. Ordinal logistic regression analysis was used to assess the relationship between MLR and the severity of Klebsiella pneumonia infection.One hundred fifty-two patients were finally enrolled for analysis. Among those, 43 (28.29%) cases had severe KPI. MLR was found to be an independent risk factor of the serious Klebsiella pneumonia infection (OR: 23.74, 95% CI: 5.41-104.11, P < .001). Besides, MLR was positively correlated with NEWS score (r = 0.57, P < .001). In the receiver-operating characteristic (ROC) curve analysis, MLR, with an optimal cut-off value of 0.665, predicted the severe coronary lesion with a sensitivity of 79.4% and specificity of 84.4%.MLR was an independent predictor of the severe Klebsiella pneumonia infection. Compared with neutrophil-to-lymphocyte ratio (NLR), MLR has a better performance to evaluate the severity of Klebsiella pneumonia infection.

Low FT3 is a valuable predictor of severe acute pancreatitis in the emergency department.

OBJECTIVE: To investigate the relationship between serum levels of thyroid hormones and disease severity at the early stage of acute pancreatitis (AP). METHODS: Cohort data from 172 patients with AP attending the Emergency Department of our hospital from 2012 to 2017 were retrospectively reviewed and analyzed. Patients were categorized into mild (MAP), moderately severe (MSAP) and severe AP (SAP) groups based on the disease severity. The MSAP and SAP groups were combined into a non-MAP group for analysis. The predictive values of C-reactive protein (CRP) levels, Ranson score, APACHE II score and serum thyroid hormone levels were analyzed. RESULTS: In total, 76 (44.2%), 85 (49.4%) and 11 (6.4%) patients were included in the MAP, MSAP and SAP groups, respectively. The free triiodothyronine (FT3) levels were significantly lower in the combined non-MAP group than in the MAP group. The tetraiodothyronine (T4) levels were significantly lower in the SAP group than in the MAP and MSAP groups (P = 0.002). Logistic regression analysis revealed that a low FT3 level was an independent risk factor for the incidence of non-MAP (P = 0.004). The area under the receiver operating characteristic curve and sensitivity of FT3 were 0.729 and 88.2%, respectively, which were higher than those of CRP, Ranson and APACHE II scores. CONCLUSION: Monitoring FT3 levels in the early stage of AP is helpful for evaluating disease severity and predicting the incidence of non-MAP, making it a useful tool for guiding AP treatment.

Hypertriglyceridemic acute pancreatitis in emergency department: Typical clinical features and genetic variants.

OBJECTIVE: To investigate the clinical characteristics of patients with hypertriglyceridemic acute pancreatitis (HTGAP), and the molecular foundation contributing to hypertriglyceridemia in such patients. METHODS: Clinical data from 329 patients with acute pancreatitis (AP) were analyzed. The patients were divided into the HTGAP group, with fasting serum triglyceride (TG) levels ≥500 mg/dL (5.65 mmol/L), and the non-HTGAP (NHTGAP) group. Targeted next-generation sequencing was applied to 11 HTGAP patients to identify the genetic mutations associated with hypertriglyceridemia, including apolipoprotein A-V (APOA5), APOC2, APOC3 and APOE, BLK, LPL, GPIHBP1 and LMF1. RESULTS: Patients in the HTGAP group, compared with those in the NHTGAP group, had a higher mortality rate (7.5% vs 0.7%, P = 0.001), more commonly seen severe AP (17.5% vs 5.2%, P = 0.004) as well as a higher recurrence rate (32.4% vs 19.9%, P = 0.070). DNA sequencing showed that two patients carried the same compound of p.G185C and p.V153M heterozygous mutations located in the APOA5 gene. Two patients carried a homozygous variation of p.C14F, in the GPIHBP1 gene. One patient had a homozygous variation of p.R176C in the APOE gene. And a rare heterozygous LMF1 gene mutation of p.P562R was detected in two patients. CONCLUSIONS: HTGAP was significantly severe than NHTGAP, with a high recurrence rate. Genetic information may be useful in the clinical setting for the investigation of the pathogenesis of HTGAP and its interventions.

Comparison of three scoring systems in predicting clinical outcomes in patients with acute upper gastrointestinal bleeding: a prospective observational study.

OBJECTIVE: To compare the performances of the Glasgow-Blatchford score (GBS), modified GBS (mGBS) and AIMS65 in predicting clinical outcomes in patients with acute upper gastrointestinal bleeding (AUGIB). METHODS: This study enrolled 320 consecutive patients with AUGIB. Patients at high and low risks of developing adverse clinical outcomes (rebleeding, the need of clinical intervention and death) were categorized according to the GBS, mGBS and AIMS65 scoring systems. The outcome of the patients were the occurrences of adverse clinical outcomes. The areas under the receiver operating characteristics curve (AUROC) of three scoring systems were compared. RESULTS: Irrespective of the systems used, the high-risk groups showed higher rates of rebleeding, intervention and death compared with the low-risk groups (P < 0.05). For the prediction of rebleeding, AIMS65 (AUROC 0.735, 95% CI 0.667-0.802) performed significantly better than GBS (AUROC 0.672, 95% CI 0.597-0.747; P < 0.01) and mGBS (AUROC 0.677, 95% CI 0.602-0.753; P < 0.01). For the prediction of interventions, there was no significant difference among the three systems (GBS: AUROC 0.769, 95% CI 0.668-0.870; mGBS: AUROC 0.745, 95% CI 0.643-0.847; AIMS65: AUROC 0.746, 95% CI 0.640-0.851). For the prediction of in-hospital mortality, there was no significant difference among the three systems (GBS: AUROC 0.796, 95% CI 0.694-0.898; mGBS: AUROC 0.803, 95% CI 0.703-0.904; AIMS65: AUROC 0.786, 95% CI 0.670-0.903). CONCLUSIONS: The three scoring systems are reliable and accurate in predicting the rates of rebleeding, surgery and mortality in AUGIB. However, AIMS65 outperforms GBS and mGBS in predicting rebleeding.

[PTEN impedes EMT during chick embryo gastrulation].

PTEN has been considered as one of the important anti-oncogenes, which possesses very wide biological activities. Endogenous PTEN genes begin to express in epiblast during chick embryo gastrulation, and then the expression extends to neural plate and mesoderm. This suggests that PTEN might be involved in cell migration, proliferation, and differentiation during early embryo development. In this study, we employed in vivo approach to explore if endogenous PTEN participates in EMT (Epithelial-mesenchymal transition) in early chick embryo. PTEN was initially detected to highly express in primitive streak during chick gastrulation, in which EMT occurs, and subsequently mesoderm structure such as somites etc. Then, overexpression of both Wt PTEN-GFP and Wt PTEN-GFP positive transplantation of primitive streak resulted in cell accumulation in primitive streak in the development hereafter, indicating that EMT was blocked in both of our assays, either whole embryo transfection of Wt PTEN-GFP or transplantation of Wt PTEN-GFP primary streak tissue. Finally down-regulation of PTEN gene in one side using PTEN siRNA led to reduce the more number of mesoderm cells in PTNE siRNA side than normal side, which suggests that PTEN gene is probably involved in regulating EMT process in development of early embryonic gastrulation.

Anti-alpha-internexin autoantibody from neuropsychiatric lupus induce cognitive damage via inhibiting axonal elongation and promote neuron apoptosis.

BACKGROUND: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a major complication for lupus patients, which often leads to cognitive disturbances and memory loss and contributes to a significant patient morbidity and mortality. The presence of anti-neuronal autoantibodies (aAbs) has been identified; as examples, anti-NMDA receptors and anti-Ribsomal P aAbs have been linked to certain pathophysiological features of NPSLE. METHODS AND FINDINGS: In the current study, we used a proteomic approach to identify an intermediate neurofilament alpha-internexin (INA) as a pathogenetically relevant autoantigen in NPSLE. The significance of this finding was then validated in an expanded of a cohort of NPSLE patients (n = 67) and controls (n = 270) by demonstrating that high titers of anti-INA aAb was found in both the serum and cerebrospinal fluid (CSF) of approximately 50% NPSLE. Subsequently, a murine model was developed by INA immunization that resulted in pronounced cognitive dysfunction that mimicked features of NPSLE. Histopathology in affected animals displayed cortical and hippocampal neuron apoptosis. In vitro studies further demonstrated that anti-INA Ab mediated neuronal damage via inhibiting axonal elongation and eventually driving the cells to apoptosis. CONCLUSIONS: Taken together, this study identified a novel anti-neurofilament aAb in NPSLE, and established a hitherto undescribed mechanism of aAb-mediated neuron damage that could have relevance to the pathophysiology of NPSLE.

[Expression of caspase-3 in rat kidney with renal tubular damage induced by lipopolysaccharide and hypoxia].

OBJECTIVE: To observe the expression of caspase-3 in the kidney of a rat model of renal tubular damage induced by endotoxin and hypoxia and explore the mechanism of renal tubular damage. METHODS: Ten rats were anesthetized with artificial ventilation and received 2 mg/kg lipopolysaccharide (LPS) injection through the penile vein. The FiO2 was reduced 90 min later from 21% to 5%, and the ventilation was withdrawn after another 90 min. Immediately after ventilation withdrawal, the kidney of the rats were obtained for immunocytochemistry and HE staining. RESULTS: HE staining showed obvious hyperemia in most of the glomeruli, mild swelling of the endothelial and mesangial cells, severe swelling and turbidity in the proximal tubular epithelial cells without obvious changes in most of the distal proximal tubules. A small portion of the interstitial epithelial cells showed swelling and turbidity, and the entire renal interstitium appeared hyperemic but without inflammatory cell infiltration. Immunocytochemistry detected the presence of caspase-3 in the cytoplasm, and most of the distal renal tubule cells were positive for caspase-3, while only occasional cells showed caspase-3 positivity in the proximal tubular epithelial cells. Most of the proximal tubular epithelial and glomerulus cells were negative for caspase-3. CONCLUSIONS: Endotoxin and hypoxia can induce renal damage, particularly in the proximal renal tubule cells, and the distal tubular epithelial cells sustain relatively light damage. Caspase-3 is strongly expressed in the distal renal tubular cells, suggesting that in renal tubular damage induced by endotoxin and hypoxia, cell degeneration, necrosis and apoptosis coexist in the tubular epithelial cells; degeneration and necrosis occur primarily in the proximal tubular epithelial cells, while apoptosis is obvious in the distal renal cells.

Adult clinically amyopathic dermatomyositis with rapid progressive interstitial lung disease: a retrospective cohort study.

The aim of the study was to investigate the characteristics of adult clinically amyopathic dermatomyositis (CADM) with rapid progressive interstitial lung disease (ILD). Hospitalized patients with dermatomyositis (DM) and polymyositis (PM) between 1998 and 2005 in the Shanghai Renji Hospital were retrospectively studied. One hundred and forty-five patients were classified into CADM, classic DM or PM according to the modified Sontheimer's definition or Bohan-Peter's classification criteria. They were further stratified based on the presence or absence of clinical ILD. The Kaplan-Meier survival analysis and COX regression were performed. The predictive factors for ILD and other clinical properties of CADM-ILD were explored. The presence of clinical ILD was a significant risk factor for the poor outcome of DM/PM (OR = 4.237, CI 95%: 1.239-14.49, p = 0.021). Other risk factors are the presence of rashes and elevated urea nitrogen. Patients with DM/PM complicated by ILD had different clinical courses. Patients with CADM-ILD showed a rapidly progressive pattern with 6-month survival rate of 40.8%. The DM-ILD manifested a progressive pattern with a 5-year survival rate of 54%, while PM-ILD was chronic with 5- and 10-year survival rate of 72.4% and 60.3%, respectively. Better preserved muscle strength, elevated erythrocyte sedimentation rate, and hypoalbuminemia may herald ILD in DM/PM. Patients with CADM-ILD who later died had lower PO(2), higher lactate dehydrogenase, and prominent arthritis/arthralgia compared with those who survived. The presence of antinuclear antibody seems to be protective. Rapid progressive CADM-ILD is refractory to conventional treatment. ILD is a common complication in over 40% of our hospitalized DM/PM cohort and is also a prominent prognostic indicator. CADM is a special phenotype of DM/PM. CADM-ILD, which is usually rapidly progressive and fatal, requires further investigation.

[Clinical significance of neuro-reactive autoantibodies in neuro-psychiatric systemic lupus erythematosus].

OBJECTIVE: To investigate the clinical significance of specific/non-specific neuro-reactive autoantibodies in the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Samples of serum and cerebrospinal fluid (CSF) were collected from 25 NPSLE patients, 11 patients with SLE complicated with central nervous system (CNS) infection (control group 1), and 10 SLE patients without CNS infection (non-NPSLE, control group 2)) were detected, Indirect immunofluorescence technique was used to detect the anti-nuclear antibody (ANA) based on the slides with human epithelium cell of laryngocarcinoma of the line Hep-2 or on the slides with cerebellum and peripheral nerve of monkey, he type of immunofluorescence were assayed. RESULTS: The percentages of ANA positive serum of the NPSLE, SLE control 1, and SLE control 2 groups were 92% (23/25), 100% (11/11), and 100% (10/10) respectively without significant differences between any 2 groups (all P > 0.05). The percentage of ANA positive CSF of the NPSLE was 60% (15/25), significantly higher than that of the SLE control group 1 (27%, 3/11, P < 0.01). There was no significant correlation between the titer of serum ANA and the titer of CSF ANA (P > 0.05). The positive rate of neuro-reactive autoantibodies was 40% (10/25), significantly higher than those of the 2 control groups (both 0, both P > 0.001). CONCLUSION: (1) The ANA positivity in the CSF of the NPSLE group is associated with the disease activity and CNS involvement, the higher the titer of autoantibodies the severe the clinical manifestations. (2) The neuro-reactive autoantibodies in the serum may associate with NPSLE with still unknown mechanism.

[The changes of estrogen receptor (ER) and progesterone receptor (PR) mRNAs in endometrium with endometriosis].

AIM: To explore the expression of ER and PR mRNAs in endometrium with endometriosis. METHODS: The rat model of endometriosis was established, and the expression of ER, PR mRNAs in the endometrium was examined by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The expression of ER and PR mRNAs in ectopic endometrium was significantly lower than that in eutopic and normal endometrium (P < 0.01). But no difference was observed between eutopic and normal endometrium (P > 0.05). Ratio of ER/PR mRNA in ectopic endometrium was larger than that in eutopic and in normal endometrium (P < 0.01). CONCLUSION: The result illuminates that the increased ER plays a vital role in the onset of endometriosis.