Tacrolimus is a novel immunosuppressant used in the treatment of a variety of autoimmune diseases.More and more studies have shown that tacrolimus has a certain therapeutic effect on myasthenia gravis (MG).This article reviews the mechanism,clinical researches,adverse reactions,dosage and clinical evaluation of tacrolimus in the treatment of MG.

Objective To evaluate the value of fecal high mobility group box-1 (HMGB 1 ) in early diagnosis and prediction of the severity of neonatal necrotizing enterocolitis (NEC). Methods From July 2013 to June 2015 , the neonates who had distention, vomit, or gross blood in stool and were suspected of NEC were recruited as NEC group while hospitalized children without abdominal distension, vomiting, bloody diarrhea, or other gastrointestinal symptoms were recruited as the control group. Stool samples were collected on day 1 , 3 , 5 and 7 after admission. The level of HMGB 1 was measured by enzyme linked immunosorbent assay (ELISA). Results In the end, there were 46 cases in NEC group and 15 cases in control group. In NEC group, 29 cases were conifrmed of stageⅠof NEC by abdominal radiograph within 24 h after hospitalized, all of them were deteriorated to stageⅡphase in 4 days, and 10 cases were deteriorated to stageⅢ. Seventeen cases were conifrmed of stageⅡby abdominal radiograph within 24 h after hospitalized, 7 cases were deteriorated to stageⅢ. In 17 stageⅢcases, 11 cases received surgical treatment and 6 cases gave up. Eight cases survived and 3 died after surgery. The levels of HMGB 1 in NEC group on day 1 , 3 , 5 and 7 after hospitalized were higher than those in control group (P

Acupuncture Points ; Acupuncture Therapy ; Adult ; Aged ; Blood Pressure ; Female ; Humans ; Hypertension ; physiopathology ; therapy ; Male ; Middle Aged ; Treatment Outcome

Objective To study the effects of diagnostic ultrasound combined with microbubble contrast agent on augmentation thrombolysis in vivo and to discuss the synergism and mechanism of combination of urokinase. Methods Thirty-two rabbits of femoral vein thrombus were divided into four groups: simple urokinase group, ultrasound and contrast microbubble group, ultrasound and contrast microbubble combined with urokinase group, control group. Then according to the best parameter combination which was definited in previous experiment, the experiments combination of urokinase were performed. Color Doppler was used to evaluate the recanalization of different group in 15 rain,30 min and 60 min. Results After the treatment of 15 rain and 30 min,the recanalization rate in ultrasound and contrast microbubble combined with urokinase group improved significantly compared with other groups (P<0.05);after 60 min, the recanalization grade of ultrasound and contrast microbubble and urokinase group was evidently better than other two group. The result of immunohistochemistry showed that disaggregation of clot and fibrous in this group at 60 min was better than the results at 15 min, 30 min. Conclusions Diagnostic ultrasound with microbubble contrast agent showed superior effects of thrombolysis and the synergism of combination of urokinase in vivo.

Objective To investigated the role of antithrombin Ⅲ (AT-Ⅲ) levels in the early diagnosis of disseminated intravascular coagulation (DIC) in patients with sepsis and the predictive effect of AT-Ⅲ on the development of DIC.Methods A retrospective study was conducted. Patients admitted to intensive care unit (ICU) of the First Affiliated Hospital of China Medical University from January to December in 2015 were enrolled. The patients were divided into sepsis group and non-sepsis group according to the diagnostic criteria of sepsis. In addition, sepsis patients were divided into 3 subgroups according to the international society on thrombosis and haemostasis (ISTH) scores on the first day: overt DIC (ISTH ≥ 5), non-overt DIC (ISTH 1-4) and none DIC group (ISTH = 0). Blood routine test, prothrombin time (PT), fibrinogen (Fib), D-dimer, fibrin degradation products (FDP), acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) scores, sequential organ failure assessment (SOFA) scores and ISTH scores were recorded on the first ICU day. AT-Ⅲ was recorded during 7 days. The differences were compared among these 3 groups. Correlations of AT-Ⅲ with various parameters were calculated by using Pearson correlation analysis in sepsis group and overt DIC group. Receiver operating characteristic (ROC) curves for diagnosis of DIC with AT-Ⅲ, AT-Ⅲ+PT were drawn to evaluate the diagnostic efficiency. The AT-Ⅲ levels of DIC patients were compared between early-onset DIC and late-onset DIC during their ICU stay. The change of AT-Ⅲ levels with time and prognosis in patients with early-onset DIC was compared between groups.Results Totally 445 patients were recruited, with 138 patients in sepsis group, and 307 in non-sepsis group. There were 20 patents diagnosed with overt DIC on the first ICU day, 115 patients non-overt DIC and 3 patients of none DIC. Twenty-five sepsis patients were diagnosed overt DIC during the ICU days. AT-Ⅲ level in sepsis patients on the first ICU day were lower than that in non-sepsis patients [(55.29±13.92)% vs. (76.54±12.31)%,P < 0.01]. Patients with overt DIC had a lower AT-Ⅲ level than non-overt DIC or none DIC patients [(43.85±13.00)% vs. (56.95±13.03)%, (68.00±16.52)%, bothP < 0.05]. It was shown by Pearson correlation analysis that AT-Ⅲ level of sepsis patients on the first ICU day was negatively correlated to ISTH score and PT (r value were -0.467, -0.654, bothP < 0.01). AT-Ⅲ level of overt DIC patient on the first ICU day was negatively correlated with PT (r = -0.675,P = 0.001). It was shown by ROC curve that area under ROC curve (AUC) of AT-Ⅲ combined with PT for diagnosis overt DIC in sepsis patients was higher than that of AT-Ⅲ or PT alone (0.843 vs. 0.763, 0.834), the sensitivity 90.0%, specificity 73.7%. The cut-off value for overt DIC diagnosis in sepsis patients of AT-Ⅲ level alone was 48.5%, sensitivity was 78.0%, specificity was 70.0%. On the first ICU day, AT-Ⅲ level was risen when ISTH score improved in patients with sepsis. There was similar change of AT-Ⅲ level between patients with early-onset DIC and late-onset DIC. AT-Ⅲ level increased with DIC improvement.Conclusion AT-Ⅲ level can be used for diagnosing sepsis-associated overt DIC independently or with a combination of PT. When ISTH score improved, AT-Ⅲ level was risen in patients with sepsis associated DIC.

Adenoviridae ; genetics ; Cell Line ; Genetic Vectors ; Humans ; Nitric Oxide Synthase Type III ; genetics ; Virus Replication

Aim To further research into the antithrombotic mechanism of scorpion venom active peptides (SVAP). Methods Human umbilical vein endothelial cells (HUVEC) were cultured with enzyme digestive method. After the cultured HUVC was incubated in conditioned media for 1 hour, the effects of SVAP on the concentration of 6-Keto-PGF 1? and NO of HUVEC were determined with radioactive-immunolygic and nitrate reduction enzyme method respectively. Results As compared with control, SVAP in the doses of 1,5,10, 20 mg?L -1 had the distinctive increase of 54%, 68%,72%,79% of the concentration of 6-Keto-PGF 1? and SVAP in the doses of 10, 20 mg?L -1 had the significantly increased of 27%, 46% of the concentration of NO. Regression anylysis showed that the release levels of PGI 2 and NO in HUVEC induced by SVAP was of positive correlation. Conclusion Antithrombotic mechanism of SVAP is related to the increase of PGI 2 and NO released from HUVEC and synergistic and mediating action between NO and PGI 2.

Endoplasmic reticulum (ER), a multifunctional organelle in eukaryotic cells, is responsible for protein synthesis and intracellular signal transduction, which dominates cell function, survival, and apoptosis. Disequilibrium of ER homeostasis may induce ER stress, which closely intertwines with tumor occurrence and progress. A few clinical-used drugs (such as anthraquinones and oxaliplatin) can mediate the immunogenic cell death of tumor cells through excessive ER stress, and sequentially stimulate anti-tumor immune responses as well as long-term immune memory. However, these drugs often exhibit poor targeting ability and extremely low ER accumulation in tumor cells, limiting their clinical efficacy. Therefore, the researches of ER-targeted delivery of these drugs will significantly benefit the efficient and precise anti-tumor immunotherapy. In this review, we introduce the relationship between ER and tumor immunity, and summarize the ER targeting strategies for anti-tumor immunotherapy in recent years. Furthermore, we discuss the problems of existing ER targeting strategies and look into its broad prospects of application.

Objective:To investigate the correlation between white matter hyperintensities (WMHs) and stroke etiology classification in patients with acute isolated penetrating artery territory infarction.Methods:Patients with first-ever acute isolated penetrating artery territory infarction admitted to the Department of Neurology, the Affiliated Hospital of Xuzhou Medical University from January 2017 to May 2020 were enrolled retrospectively. According to the Chinese Ischemic Stroke Subclassification (CISS) system, they were divided into large artery atherosclerosis (LAA) and perforating artery disease (PAD). According to the distribution of infarcts, they were divided into lenticulostriate artery (LSA) territory infarction and paramedian pontine artery (PPA) territory infarction. The demographics, vascular risk factors, baseline clinical data, WMHs location, and Fazekas Scale scores were documented. Multivariate logistic regression analysis was used to identify the independent influencing factors of stroke etiology classification. Results:A total of 440 patients with acute isolated penetrating artery territory infarction were enrolled, including 120 (27.3%) in the LAA group, and 320 (72.7%) in the PAD group; 213 (48.4%) with LSA territory infarction, and 227 (51.6%) with PPA territory infarction. The proportion of patients with total Fazekas score 3-6 and periventricular WMHs (PWMHs) score 2-3 in the PAD group was significantly higher than those in the LAA group (all P<0.05). In patients with LSA territory infarction, the proportion of the patients with hypertension, WMHs total Fazekas score 3-6 and PWMHs score 2-3 in PAD subgroup was significantly higher than those in the LAA subgroup, while the proportion of the patients with hyperlipidemia was significantly lower than that in LAA subgroup (all P<0.05). In patients with PPA territory infarction, the levels of low-density lipoprotein cholesterol and homocysteine in the PAD subgroup were significantly lower than those in the LAA subgroup. Multivariate logistic regression analysis showed that PWMHs score 2-3 was an independent correlation factor of PAD (odds ratio [ OR] 2.220, 95% confidence interval [ CI] 1.085-4.541; P=0.029). In patients with LSA territory infarction, hyperlipidemia was independently correlated with LAA ( OR 0.432, 95% CI 0.192-0.972; P=0.042), and PWMHs score 2-3 was independently correlated with PAD ( OR 3.846, 95% CI 1.193-12.397; P=0.024). In patients with PPA territory infarction, higher low-density lipoprotein cholesterol ( OR 0.660, 95% CI 0.494-0.883; P=0.005), homocysteine ( OR 0.958, 95% CI 0.930-0.987; P=0.005) and C-reactive protein ( OR 0.987, 95% CI 0.977-0.997; P=0.008) were independently correlated with LAA. Conclusions:WMHs are common in patients with acute isolated perforating territory infarction caused by LAA and PAD, and more severe PWMHs suggest that PAD is more likely to be the cause of the acute isolated perforating territory infarction, especially in patients with LSA territory infarction.

OBJECTIVETo observe the effect of shikonin on the proliferation of human keratinocytes induced by IL-17 and secretion of chemokines, in order to discuss the mechanism of Shikonin in the treatment of psoriasis.

METHODIn vitro cultured HaCaT cells were stimulated by IL-17A (200 μg x L(-1)) and mixed with different concentrations (2, 1 mg x L(-1)) of shikonin for 24 hours. The cell proliferation was detected by CCK-8 assay. Cell secretion inflammatory factor interleukin-23 (IL-23) was detected by ELISA. The expressions of intracellular chemokines CXCL1, CXCL2, CCL20 and 6-defensin 4 (DEFB4) were detected by Real-time PCR.

RESULTShikonin (2,1 mg x L(-1)) could distinctly inhibit HaCaT cell proliferation induced by IL-17A, with statistical difference (P < 0.01). Each shikonin group showed decreases in the secretion of IL-23 and inhibition in expressions of intracellular CXCL1, CXCL2, CCL20 and DEFB4.

CONCLUSIONShikonin could inhibit HaCaT cells proliferation induced by IL-17 and secretion of relevant cytokines and recruit leukocytes by inhibiting chemokines, so as to show the effect in treating psoriasis.

Cell Line ; Cell Proliferation ; drug effects ; Chemokines ; genetics ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Interleukin-17 ; genetics ; metabolism ; Keratinocytes ; cytology ; drug effects ; metabolism ; Naphthoquinones ; pharmacology