Objective To analyze the clinical and laboratory characteristics of the ischemic stroke in patients with non-valvular atrial fibrillation (AF), and to provide evidence for the prevention of ischemic stroke. Methods A total of 198 patients with ischemic stroke were chosen and divided into two groups:with AF (71 patients)/and without AF (127 patients) groups. Clinical data and biochemical markers were collected and compared in two groups. CHADS2 and CHA2DS2-VASc score systems were used to determine the risk levels in patients with AF. Finally, related risk factors of ischemic stroke with AF were determined and analyzed. Results The values of age, length of hospital stay, the hypertention history, heart rate and plasma homocysteine (Hcy) were significantly higher in the with-AF group than those in the without-AF group ( P <0.05). The levels of total cholesterol (TC), triglyceride (TG) and very low density lipoprotein cholesterol (VLDL-C) were sig?nificantly lower in the with-AF group than those of the without-AF group (P<0.05). CHA2DS2-VASc scores reached to the moderate-to-high risk level in the with-AF group. Multiple-factor logistic regression analysis showed that age and heart rate were the independent risk factors of the ischemic stroke in patients with non-valvular AF. ROC analysis indicated that age (AUC=0.761, cut-off point=72.50 years old) and heart rate (AUC=0.612, cut-off point=76.50 bit/min) had predictive and di?agnostic value for the ischemic stroke in patients with non-valvular AF. The age of these patients had the best sensitivity (70.4%) and specifity (71.1%), and the cut-off point of which was 72.50 years old. Conclusion The characteristics of isch?emic stroke in patients with non-valvular AF includes older age, faster heart rate, higher CHA2DS2-VASc scores and higher Hcy level.

Objective:To summarize the midterm to long-term outcomes and experiences of endovascular treatment (ET) of spontaneous isolated superior mesenteric artery dissection (SISMAD).Methods:The clinical data of 31 SISMAD patients from Jan 2011 to Dec 2019 treated with ET was retrospectively analyzed.Results:Successful ET was achieved in 29 patients with a technical success rate of 93.5%. A total of 36 self-expandable bare stents were planted in 28 patients and plain old balloon angioplastry (POBA) was performed in 1 patient. Abdominal pain disappeared within 24 hours in 89.3% of the patients after stenting. The rate of perioperative complication was 3.2%. There was no SMA dissection rupture bleeding, nor perioperative death occurred. The mean follow-up time was 53.5 (range, 6 to 110) months. There was no dissecting aneurysm formation, no SMA rupture and bleeding, and no stent rupture during the follow-up. The post ET 1-year, 3-year, and 5-year free from reintervention rate were 100%, 100%, and 91.7%, respectively.Conclusions:ET for SISMAD is safe and effective with satisfactory perioperative and midterm to long-term outcomes.

Hemagglutinin and neuraminidase, two important glycoproteins on the surface of influenza virus, play a considerable role in the entry and release stage of the viral life cycle, respectively. With in-depth investigation of influenza virus glycoproteins and the continuous innovation of drug discovery strategies, a new generation of glycoproteins inhibitors have been continuously discovered. From the point of view of medicinal chemistry, this review summarizes the current advances in seeking small-molecule inhibitors targeting influenza virus glycoproteins, hoping to provide valuable guidance for future development of novel antiviral drugs.

Objective:To investigate the heterogeneity of epitopes recognized by anti-GBM autoantibodies in sera from a large cohort of Chinese patients with anti-GBM disease and its clinical significance.Methods: The present study included 108 patients with anti-GBM disease who were diagnosed in our hospital, between Jan 1991 and May 2009, with complete clinical and renal pathological data. Sera or plasma exchange of the patients were used to incubate with cryostat section of normal human renal tissue for indirect immunofluorescence (IIF) assay. The cryostat sections of normal renal tissue were pre-treated by 6 mol/L urea to unmask cryptic epitopes, and untreated cryostat sections were used to detect natural exposed epitopes. The sera were diluted from 1:2 to 1:512 to determine titers of anti-GBM autoantibodies Patients with anti-GBM autoantibodies against cryptic or exposed epitopes were further stratified;their clinical and pathological associations were analyzed. Results: Sera from all the 108 patients could recognize cryptic epitopes on normal renal tissue ( urea treated section). IIF showed IgG linear staining along GBM. However, sera from 56/108 patients (group A) could also recognize exposed epitopes on normal renal tissue (untreated section) ; sera from the rest 52/108 patients (group B) could not recognize exposed epitopes. In urea treated condition, the average titer of anti-GBM autoantibodies from sera of patients in group A was significantly higher than that in group B (P＜0.01) , ANCA-positive patients in group A were significant less than that in group B (P＜0.01) . There was no significant difference between the two groups in regard to other clinical data (including serum creatinine) and renal histopathologic data. Conclusion: Anti-GBM autoantibodies from some patients with anti-GBM disease could recognize natural exposed epitopes, however, their anti-GBM titer for cryptic epitopes was higher than that of those recognizing cryptic epitopes only and the prevalence of serum ANCA was significantly less.

Objective To explore the activation and function of Janus protein-tyrosine kinase (JAK)/ signal transducer and activator of transcription (STAT1) signal transduction pathway in kidney,lung and brain of MRL/lpr mice.Methods MRL/lpr mice with systemic lupus erythematosus (SLE) were studied at the age of 12 weeks up.Non-SLE MRL/lpr mice were used as controls.We used phosphospecific antibodies to detect STAT1 activation in kidney,lung and brain by immunohistochemistry and Western blots.Gene expression of the STAT induced feedback inhibitors of cytokine signaling 1 (SOCS-1) was investigated by SYBR green I real-time reverse transcriptase polymerase chain reaction (PCR).Results Phosphorylation of STAT1 protein was markedly activated in these three organs,although renal and pulmonary STAT1 activation were much more evidently activated.SOCS-1 gene expression increased in all three organs,while renal SOCS-1 gene expres- sion increased less than lung and brain.Conclusion The activation of JAK/STATI signal transduction path- way may be pathogenic in the organ involvement and progression of SLE.The pathogenesis of lupus nephritis may also be associated with the down-regulation of SOCS-1 feedback inhibition.

Hepatitis B virus infection is a serious threat to human life and health. The approved anti-HBV drugs including interferons and nucleos(t)ide analogues have serious adverse effect, rebound phenomena after drug withdrawal, and drug resistance. And the cccDNA cannot be completely eliminated by both of them, which is the reason why a complete cure for hepatitis B cannot be achieved. Therefore, developing anti-HBV drugs directly targeting protein or nucleic acid of HBV remains a current public health priority. Based on the analysis of representative literature from the last decade, this article reviews recent developments in small molecule inhibitors directly targeting HBV from a medicinal chemistry perspective.

OBJECTIVE: To study the morphological characteristics of femurs of adult human and 11 kinds of adult animals from cattle, horses, pigs, goats, sheep, dogs, cats, rabbits, geese, ducks, chickens, and to establish an effective species identification method among various species. METHODS: The 4 cm mid-diaphyseal segment of the femur from adult human (older than 20 years old) at autopsy was obtained. Addi-tionally, the 4 cm ones from 11 kinds of adult animals were obtained. After decalcification, all femurs were made into slices, and then were observed by optical microscope. The 25 indexes were selected and analyzed by step discriminant analysis according to differences between human and mammal, human and poultry, and human and 11 kinds of animals. RESULTS: The histological structure of bone mineral density of middle part of femur had obvious characteristics among the species. And the morphology and number of osteon showed the trend of obvious biological evolution. There were 11 indexes with significant differences between human and 11 kinds of animals to establish some mathematical models to discriminate all species. The correct discrimination rate was 96.3% between human and mammal. The correct discrimination rate was up to 100% between human and poultry, and was 89.4% among human, mammal and poultry. CONCLUSION The mathematical models have good correct discrimination rate among human and the other animals, which could be applied in the practical species identification cases.
Adult ; Animals ; Autopsy ; Bone Density ; Cadaver ; Cats ; Cattle ; Chickens ; Discriminant Analysis ; Dogs ; Femur/ultrastructure* ; Forensic Anthropology ; Haversian System/ultrastructure* ; Horses ; Humans ; Sheep ; Species Specificity ; Swine

Fatigue is a common complication of type 2 diabetes mellitus (T2DM). We examined the relationship between T2DM fatigue and the skeletal muscle 5-hydroxytryptamine (5-HT) system. In animal experiments, a T2DM model was established in mice by feeding a high-fat diet with intraperitoneal injection of streptozotocin. The mice were treated with the 5-HT_2A receptor antagonist sarpogrelate hydrochloride (SH) and the 5-HT synthesis inhibitor carbidopa (CDP) (separately and in combination). In cell culture experiments, C2C12 cells were stimulated with D-glucose, palmitic acid or 5-HT. 5-HT_2AR, 5-HT synthesis and 5-HT degradation were inhibited by SH, CDP, or monoamine oxidase A (MAO-A) inhibitor. The animal experiments were in accordance with the regulations of the Animal Ethics Committee of China Pharmaceutical University. The results showed that 5-HT_2AR, 5-HT synthase and MAO-A were expressed in mouse skeletal muscle and C2C12 cells. The expression of these proteins was significantly up-regulated in T2DM mice or when C2C12 cells were exposed to palmitic acid and D-glucose; palmitic acid was a stronger stimulant of their expression than D-glucose. Rotating rod experiments and biochemical index tests have shown that T2DM fatigue is associated with an increase in skeletal muscle 5-HT_2AR, 5-HT synthesis and 5-HT degradation. 5-HT_2AR mediates the expression of MAO-A and the synthesis of 5-HT, which indirectly regulates the degradation of 5-HT. MAO-A regulates cell inflammation, mitochondrial ROS production and membrane potential depolarization by mediating 5-HT degradation. MAO-A also inhibits the expression of peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1), carnitine palmitoyltransferase-1 (CPT1) and ATP synthase-6 (ATP6), thus inhibiting mitochondrial functions such as fatty acid β oxidation and ATP synthesis. SH and CDP can effectively treat T2DM fatigue, and can also reduce blood glucose and blood lipid, and the combination of SH and CDP has a clear synergistic effect.

Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

Objective To investigate the value of 18F-FDG/99Tcm-MIBI SPECT myocardial imaging for the detection of myocardial viability and prognosis in patients with AMI. Methods 18F-FDG/99Tcm-MIBI SPECT myocardial imaging was performed in 98 consecutive patients [man 87, women 11; average age (58 ±11)y] with AMI. The myocardium was scored individually for nine segments: mildly decreased uptake = 1,significantly decreased uptake = 2, and no uptake = 3. Perfusion defect but preserved 18 F-FDG uptake was defined as perfusion-metabolism mismatch, indicating jeopardized but viable myocardium. Perfusion defect and decreased 18 F-FDG uptake were defined as match, indicating myocardial necrosis. Echocardiogram was performed before and after treatment for evaluating the LVEF. All patients were followed after treatment.The rate of cardiac events was calculated and compared between patients with medication and revascularization. Paired t test, Chi-square test and log-rank test were used for statistical analysis. Results In the group with viable myocardium, 27 patients received revascularization and 10 received medication. In the group with infarcted myocardium, 26 patients received medication and 35 received revascularization. Patients underwent revascularization and with medication had no significant difference in improvement of LVEF between both groups (viable myocardium group: χ2 = 0.509, P > 0. 05; infarcted myocardium group: χ2 =0.035, P > 0.05). In viable myocardium group, cardiac event rate was significantly higher in patients with medication than in those who had undergone revascularization (50.0% vs 14.8%, χ2 =4.91, P<0.05).In the infarcted myocardium group, cardiac event rate was also significantly higher in patients with medication (30.7% vs5.7% ,χ2 =6.83, P<0.05). Conclusions 18F-FDG/ -MIBI SPECT myocardial imaging may well be of value but limited for the detection of myocardial viability and prediction of improvement in cardiac function as well as prognosis. However, more prospective data are needed for final evaluation.