AIM:To investigate the impact of Bruton tyrosine kinase(BTK)on Alzheimer disease(AD)-like pathology through the NIMA(never in mitosis gene A)-related kinase 7(NEK7)-nucleotide-binding oligomerization do-main-like receptor protein 3(NLRP3)pathway.METHODS:5xFAD and wild-type(WT)mice aged 2,4 and 6 months were utilized to assess the expression of BTK,NEK7 and NLRP3 proteins in the hippocampus and cortex via Western blot and immunofluorescence.Co-immunofluorescence was conducted to identify the interaction between NEK7 and NLRP3 in the brains of 4-month-old mice.Three-month-old mice were divided into a control group and an ibrutinib treatment group,receiving intraperitoneal injections of ibrutinib(10 mg/kg)or solvent for 14 d,and were then subjected to behavioral as-sessments including learning and memory tests using the Morris water maze and Y-maze.Wild-type mice were induced with an AD model by intracerebroventricular injection of Aβ42.Morris water maze tests were performed after 14 d to eva-luate learning and memory,followed by measurement of BTK protein levels in the brain via Western blot.BV2 microglial cells were treated with ibrutinib,followed by LPS or Aβ42 stimulation.Western blot analysis was conducted to measure the protein levels of NEK7,NLRP3,BTK and p-BTK(Y223),while immunofluorescence was used to assess the protein expression of ASC,caspase-1,NEK7 and NLRP3.RESULTS:The levels of BTK,NEK7 and NLRP3 in the brains of 5×FAD mice were significantly elevated compared to WT mice,with observed interaction between NEK7 and NLRP3 in the 5xFAD mouse brains.Ibrutinib treatment significantly improved learning and memory functions in mice compared to the AD group.In BV2 cells,pre-treatment with ibrutinib effectively suppressed the NLRP3 inflammasome pathway and NEK7 proteins in response to Aβ42 stimulation.CONCLUSION:BTK plays a regulatory role in AD-like pathology through the NEK7-NLRP3 pathway both in vivo and in vitro.

Objective:To evaluate the efficacy of postoperative radiotherapy (PRT) for dermatofibrosarcoma protuberans (DFSP).Methods:A systematic review and meta-analysis of articles published before February 23, 2019 were conducted. A total of 655 studies were retrieved consisting of 195 DFSP patients. Among them, 50 cases were assigned into the PRT group and 145 cases in the surgery alone (SA) group. The recurrence rate was statistically compared between two group.Results:Meta-analysis showed that the recurrence rate in the PRT group was significantly lower than that in the SA group (8% vs. 24.1%, OR=0.28, P=0.010). The recurrence rate of patients with positive margins in the PRT group was significantly lower compared with that in the SA group (8% vs. 61.5%, P=0.002). The recurrence rate of patients with negative margins in the PRT group had a decreasing trend than that in the SA group (6% vs. 21.6%, P=0.205). Conclusions:The recurrence rate of surgery combined with PRT is lower than that of SA. The recurrence rate of patients with positive margins is higher than that of those with negative margins. For patients with positive margins, PRT can decrease the recurrence rate. The recurrence rate trends to decline in patients with negative margins after receiving PRT.

OBJECTIVES: Idiopathic intracranial hypertension (IIH) is a syndrome that excludes secondary causes such as intracranial space-occupying lesion, hydrocephalus, cerebrovascular disease, and hypoxic ischemic encephalopathy. If not be treated promptly and effectively, IIH can cause severe, permanent vision disability and intractable, disabling headache. This study aims to explore the clinical and image features for IIH, to help clinicians to understand this disease, increase the diagnose rate, and improve the outcomes of patients. METHODS: We retrospectively analyzed 15 cases of IIH that were admitted to Xiangya Hospital, Central South University, during January 2015 to September 2020. The diagnosis of IIH was based on the updated modified Dandy criteria. We analyzed clinical data of patients and did statistical analysis, including age, gender, height, weight, medical history, physical examination, auxiliary examination, treatment and outcome. RESULTS: There were 10 females and 5 males. Female patients were 22 to 42 years old with median age of 39.5. Male patients were 27 to 52 years old with the median age of 44.0. The BMI was 24.14-34.17 (28.71±2.97) kg/m CONCLUSIONS IIH primarily affects women of childbearing age who are overweight. The major hazard of IIH is the severe and permanent visual loss. Typical image signs have high specificity in IIH diagnosis. Prompt diagnosis and effective treatment are significantly important to improve the outcomes of patients.
Adult ; Anemia, Iron-Deficiency ; Female ; Humans ; Intracranial Hypertension ; Male ; Middle Aged ; Pseudotumor Cerebri/diagnostic imaging* ; Retrospective Studies ; Ventriculoperitoneal Shunt ; Young Adult

In the clinical settings, disseminated intravascular coagulation (DIC) and complications such as hemorrhage are commonly seen in acute promyelocytic leukemia patients, whereas thrombosis is rarely reported. We reported a case here that the patient presented with cerebral infarction as the first manifestation. During the admission, the patient encountered differentiation syndrome, pulmonary embolism, pulmonary hemorrhage, and myocardial ischemia, as well as bleeding and thrombosis complications. Hence the patient was diagnosed as DIC. After the treatment of blood transfusion instead of anticoagulation, his condition was stable and the remission was completely achieved. The treatment experience provides guides for other patients with similar complications of simultaneous bleeding and thrombosis.
Blood Coagulation ; Cerebral Infarction ; Disseminated Intravascular Coagulation ; etiology ; Humans ; Leukemia, Promyelocytic, Acute ; complications ; Thrombosis

Objective: To investigate the effect of interleukin-8 (IL-8) on survival and apoptosis of hypoxic human umbilical vein endothelial cells (HUVECs) with its mechanisms.
Methods: Hypoxic HUVECs were induced by CoCl2. HUVECs were cultured with different concentrations of CoCl2 or IL-8 and the survival rates of HUVECs were examined. Normal or hypoxic HUVECs were incubated with IL-8 or simultaneously incubated with anti-IL-8 or Akt inhibitor LY294002 for 48h. The HUVECs survival rate was detected by MTT method, apoptosis rate was measured by Annexin V-FITC/PI method, the protein expressions of Caspase-3, phosphorylated Akt (pAkt) and GSK-3βser9 (pGSK-3βser9) were evaluated by Western blot analysis.
Results: By 12 h incubation with low concentration of CoCl2 (50, 100 μmol/L), HUVECs proliferation were improved, P<0.01; while by 24h and 48 h incubation with high concentration of CoCl2 (200, 400 μmol/L) HUVECs survival were decreased. By 48h and 72h incubation with IL-8 at (10, 50, 100 ng/ml), the hypoxia induced cell apoptosis was decreased and the survival was increased,P<0.01. IL-8 at 10 ng/ml may obviously inhibit the normal and hypoxic HUVECs apoptosis, down-regulate caspase-3 and up-regulate pAkt and pGSK-3βser9 expressions in HUVECs,P<0.01, while the above effects could be reversed by LY294002 and anti-IL-8,P<0.01.
Conclusion: IL-8 could down-regulate caspase-3 and up-regulate pAkt and pGSK-3βser9 expressions in HUVECs and therefore, inhibit the apoptosis and improve the survival of hypoxic HUVECs.

Five patients after prosthetic tricuspid valve, who received pacemaker implantation via coronary sinus during Oct, 2011 and Jul, 2014, were enrolled. Pacemakers were implanted via coronary vein in 5 patients without complications. The stimulation thresholds keep stable and symptoms (such as short breath and fatigue) were disappeared during the follow-up. For patients after tricuspid valve replacement, implantation of pacemaker via coronary sinus provides a safe and invasive approach and avoids opening the chest again.
Cardiac Surgical Procedures ; Coronary Sinus ; Heart Valve Prosthesis Implantation ; Humans ; Pacemaker, Artificial ; Tricuspid Valve

To obtain the P8 protein of Rice gall dwarf virus (RGDV) with biological activity, its outer coat protein gene S8 was expressed in Spodoptera frugiperda (Sf9) insect cells using the baculovirus expression system. The S8 gene was subcloned into the pFastBacTM1 vector, to produce the recombinant baculovirus transfer vector pFB-S8. After transformation, pFB-S8 was introduced into the competent cells (E. coli DH10Bac) containing a shuttle vector, Bacmid, generating the recombinant bacmid rbpFB-S8. After being infected by recombinant baculovirus rvpFB-S8 at different multiplicities of infection, Sf9 cells were collected at different times and analyzed by SDS-PAGE, Western blotting and immunofluorescence microscopy. The expression level of the P8 protein was highest between 48-72 h after transfection of Sf9 cells. Immunofluorescence microscopy showed that P8 protein of RGDV formed punctate structures in the cytoplasm of Sf9 cells.

OBJECTIVETo observe the therapeutic effect of calming the liver and restraining the Yang formula in treating patients with mild or moderate degree of essential hypertension (syndrome of hyperactivity of liver-Yang), and to explore its mechanism in lowering blood pressure.

METHODThe 348 patients with EH of stage I , II were randomly divided into two groups, the 174 patients in the treated group were treated with the calming the liver and restraining the Yang formula, and the 174 patients in the control group were treated with amlodipine. The treatment course for them all was 12 weeks. The related clincial symptoms score and quality of life score estimated before and after treatment at 4th week, 8th week and 12th week were observed. Before and after treatment, the ambulatory blood pressure (AMBP), heart rate, blood lipid, serum livels of high-sensitivity C-reactive protein (Hs-CRP), Angiotensin-II (Ang II) and calcitonin gene-related peptide (CGRP) were measured respectively in 40 patients of the treared group and 40 patients of the control group.

RESULTAfter treatment, the treatment in the treated group showed an effect better than that in the control group in terms of nigh-time blood pressure reducing rate (P < 0.05). The reducing blood pressure variability and total effective rate in the treated group were no significant than that in the control group. In respect of reducing symptomatic scores on dizzy, soreness and weakness of the waist and knees, disturbed and dry and bitter of mouth, ameliorating quality of life score, decreasing the levels of heart rate, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol(HDL-C) in the treated group were showing marked improvement as compared with that in the control group (P < 0.05 or P < 0.1). The improvement in the level of Ang II , Hs-CRP and CGRP before treatment in two groups were more significant than that after treatment (P < 0.05). However There were no difference in after treatment between the treated group and the control group.

CONCLUSIONThe calming the liver and restraining the Yang formula shows favorable efficacy in lowering blood pressure on the patients with mild or moderate degree of essential hypertension. It can reduce the clincial symptoms, improve the quality of life, regulate blood lipid metabolism. Its mechanism may be related to the functional relieving inflammatory reaction and inhibition the activity of renin-angiotensin-aldosterone system (RAAS).

Adult ; Aged ; Amlodipine ; therapeutic use ; Antihypertensive Agents ; therapeutic use ; Anxiety ; chemically induced ; physiopathology ; Blood Pressure ; drug effects ; Cholesterol ; metabolism ; Cholesterol, HDL ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Heart Rate ; drug effects ; Humans ; Hypertension ; drug therapy ; physiopathology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy ; Triglycerides ; metabolism

OBJECTIVE: To determine the relationship between the number,phenotype and functional status of dendritic cells (DCs) and coronary collateral circulation (CCC) in coronary heart disease (CHD). METHODS: Forty patients with severe coronary stenosis were recruited and divided into a CCC formation group (Group A, n=22) and a non-CCC formation group (Group B, n=18). Density gradient centrifugation was applied to separate the mononuclear cells (MNCs) from coronary artery blood samples, and MNCs were cultured and proliferated in vitro. The morphology of DCs was observed under converted microscope. The number of harvested cells and DCs was counted by hematocytometer. Flow cytometry was applied to investigate the phenotype and the mean fluorescence intensity (MFI). Mixed lymphocyte reaction was used to test the function of DCs to stimulate the proliferation of T lymphocytes. Stimulation index (SI) was calculated and compared. RESULTS: (1) After in vitro proliferation, DCs were cultured successfully from the mononuclear cells from coronary artery blood samples and the morphology of DCs was not different in the 2 groups. (2) The number of mononuclear cells (MNC no) was (3.95+/-1.41)*10(6), in the CCC group and (2.76+/-0.92)*10(6) in the non-CCC group. The MNC number was significantly increased in the CCC group (P=0.003). (3) The number of DCs was (1.54+/-0.96)*10(6) in the CCC group, and (0.99+/-0.46)*10(6) in the non-CCC group (P=0.033). (4)There was no statistical significance in the percent of CD1a+, CD1a+CD80+, CD1a+CD83+, CD1a+CD86+ cells, and MFI in the 2 groups (P>0.05). (5) SI was 4.96+/-2.30 in the CCC group, whereas 2.66+/-1.04 in the non-CCC group. The SI in the CCC group increased significantly(P=0.0003). CONCLUSION In CHD patients with severe coronary stenosis, patients with CCC formation have higher number of DCs and stronger potential of T lymphocyte stimulation.
Aged ; Cells, Cultured ; Collateral Circulation ; immunology ; physiology ; Coronary Circulation ; immunology ; physiology ; Coronary Disease ; blood ; immunology ; physiopathology ; Coronary Stenosis ; blood ; immunology ; physiopathology ; Dendritic Cells ; immunology ; Female ; Humans ; Male ; Middle Aged ; T-Lymphocytes ; cytology ; immunology