OBJECTIVETo study the inhibitory effect and mechanism of Ganoderma lipsiense extract (GLE) on the growth of triple-negative breast cancer (TNBC) cell line MDA-MB-231-HM in a mouse model.

METHODSThe mouse model of TNBC was established by subcutaneous injection of 1.5 x 10(6) of MDA-MB-231-HM cells into BALB/c-nu mouse. Twenty successfully modeled mice were divided into the GLE group and the negative control group according to random digit table, 10 in each group. GLE (0.2 mL 100 mg/mL) was peritoneally injected to mice in the GLE group, while equal dose of normal saline was peritoneally injected to mice in the negative control group. The medication was administered once per 3 days and discontinued after 45 days. The CD34 expression was detected using immunohistochemical assay for counting microvessels. Meanwhile, expressions of thrombospondin 1 (TSP-1) and cyclin D1 were detected using immunohistochemical assay.

RESULTSThe average weight was obviously lower in the GLE group than in the negative control group [(0.33 ± 0.16) g vs (0.68 ± 0.37)g, P < 0.05]. The tumor inhibition rate was 51.4% in the GLE group. The volume of transplanted tumor was obviously lesser in the GLE group than in the negative control group (P < 0.05). Results of immunohistochemical staining showed, the microvessel density (MVD) under every field was (20.7 ± 2.1), TSP-1 positive cell count was (66.2 ± 9.2), cyclin D1 positive cell count was (33.8 ± 16.4) in the GLE group, and they were 34.0 ± 2.0, 24.0 ± 6.6, and 168.2 ± 32.6, respectively in the negative control group. There was statistical difference in all indices between the two groups (P < 0.05).

CONCLUSIONGLE could inhibit malignant proliferation of tumor cells by suppressing angiogenesis of blood vessels in tumor tissues and regulating cell cycles, thereby inhibiting TNBC.

Animals ; Biological Products ; pharmacology ; Cell Line, Tumor ; Cyclin D1 ; metabolism ; Disease Models, Animal ; Ganoderma ; chemistry ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microvessels ; Neoplasm Transplantation ; Neovascularization, Pathologic ; prevention & control ; Random Allocation ; Thrombospondin 1 ; metabolism ; Triple Negative Breast Neoplasms ; drug therapy

Objective • To investigate the signalling pathways mediated by synaptic cell adhesion molecules (sCAMs) in the process of human prenatal synapse formation. Methods • The single-cell RNA-sequencing dataset of prenatal human prefrontal cortex was downloaded from GEO (Gene Expression Omnibus) database. The gene expression dynamics was modelled with pseudotime ordering approach and the protein-protein interaction (PPI) network was constructed by utilizing gene co-expression analysis and PPI database. The interacting molecules and associated pathways of sCAMs were explored. Results • The gene expression dynamics of early synapse formation in excitatory neurons can be modelled with linear trajectory. PPI network analysis identified the interacting molecules of neurexins, neuroligins, and LAR-type receptor-type protein tyrosine phosphatases (LAR-type RPTPs). Guanine nucleotide exchange factor 9 (ARHGEF9) interacted with neurexins and neuroligins, while cell division cycle 42 (CDC42) was the hub of the network. Amyloid precursor protein (APP) interacted with neuroligins and leucine-rich repeat transmembrane neuronal protein 3 (LRRTM3), which is a ligand of neurexins. Finally, mitogen-activated protein kinase 8 (MAPK8), dual specificity phosphatase 4 (DUSP4), and CDC42, which participate MAPK signalling pathways, were involved in the PPI network of protein tyrosine phosphatase receptor type D (PTPRD, a member of LAR-type RPTPs) and its ligands leucine rich repeat and fibronectin type III domain containing 1 (LRFN1), LRFN2, and LRFN5. Conclusion • Interacting proteins and associated pathways of neurexins, neuroligins, and LAR-type RPTPs can be predicted with bioinformatics methods, which may provide insights in experimental studies.

Objective To establish a mini-pool nucleic acid testing (NAT) assay using multiplex RT-nested PCR for the detection of HIV RNA, and apply it in screening for acute HIV infection among MSM. Methods Frozen EDTA plasma samples collected between Oct. 2008 and Mar. 2009 from 3 HIV infectors during window-period, a total of 30 HIV chronically infected individuals and 97 healthy subjects were used to develop the NAT assay. Plasma samples from 10 cases were pooled into one tube and centrifuged at high speed for the collection of viruses. HIV RNA was extracted. Two pairs of primers were designed according to two conserved regions of HIV RNA ( HXB2 nt 5783-nt 6228 and nt 1235-nt 2012).Multiplex RT-PCR and nested PCR were performed. Individual NAT-reactive samples were confirmed by commercially available NAT assays. The sensitivity and performance efficacy were also evaluated. The assay was then applied to 1 005 plasma specimens from MSM with negative or uncertain HIV antibody test results.These were collected in the same period as the other samples. Results ( 1 ) Two fragments of HIV were amplified successfully with the low detection limit of 162 copies/ml plasma; (2) Results of the mini-pool HIV NAT validation with samples from 3 HIV infectors during window-period were consistent with the expected values; (3) All 30 plasma samples from MSM with positive HIV antibody, which were tested by multiplex RT nested PCR, were found to be HIV RNA positive; (4) One out of 1 005 plasma samples was found to be HIV RNA positive, for this case acute infection was followed-up and sero-conversion was found. Conclusion Mini-pool NAT has good sensitivity, and may be applied to screening HIV RNA among MSM during window-period.

BACKGROUNDAccumulating evidence indicates a potential role of adventitial vasa vasorum (VV) dysfunction in the pathophysiology of restenosis. However, characterization of VV vascularization in restenotic arteries with primary lesions is still missing. In this study, we quantitatively evaluated the response of adventitial VV to vascular injury resulting from balloon angioplasty in diseased arteries.

METHODSPrimary atherosclerotic-like lesions were induced by the placement of an absorbable thread surrounding the carotid artery of New Zealand rabbits. Four weeks following double-injury induced that was induced by secondary balloon dilation, three-dimensional patterns of adventitial VV were reconstructed; the number, density, and endothelial surface of VV were quantified using micro-computed tomography. Histology and immunohistochemistry were performed in order to examine the development of intimal hyperplasia.

RESULTSResults from our study suggest that double injured arteries have a greater number of VV, increased luminal surface, and an elevation in the intima/media ratio (I/M), along with an accumulation of macrophages and smooth muscle cells in the intima, as compared to sham or single injury arteries. I/M and the number of VV were positively correlated (R2 = 0.82, P < 0.001).

CONCLUSIONSExtensive adventitial VV neovascularization occurs in injured arteries after balloon angioplasty, which is associated with intimal hyperplasia. Quantitative assessment of adventitial VV response may provide insight into the basic biological process of postangioplasty restenosis.

Angioplasty, Balloon, Coronary ; Animals ; Male ; Neovascularization, Pathologic ; diagnosis ; Rabbits ; Vasa Vasorum ; physiology ; X-Ray Microtomography

The present study investigated the material basis of Urtica fissa for the inhibition of benign prostatic hyperplasia(BPH). The active fractions were screened, and the extracts of dichloromethane and ethyl acetate exhibited significantly inhibitory activities against 5α-reductase in vitro and BPH in model rats. The chemical constituents in the active fractions were systematically investigated, and 28 compounds were obtained, which were identified as lobechine methyl ester(1), dibutyl-O-phthalate(2), 1-monolinolein(3), epipinoresinol(4), 5-hydroxy-3,4-dimethyl-5-pentanyl-2(5H)-furanone(5), E-7,9-diene-11-methenyl palmitic acid(6), evofolin B(7), ficusal(8), threo-2,3-bis-(4-hydroxy-3-methoxyphenyl)-3-ethoxypropan-1-ol(9), α-viniferin(10),(9R,7E)-9-hydroxy-5,7-mengatigmadien-4-one-9-O-β-D-glucopyranoside(11), indole-3-carboxaldehyde(12), p-hydroxy ethyl cinnamate(13), benzyl alcohol-O-β-D-glucoside(14), L-methionine(15), 4-methoxyaniline(16), 6-aminopurine(17), 8'-acetyl oilvil(18), 4-methoxyl-8'-acetyl oilvil(19), vanillic acid(20), β-hydroxypropiovanillone(21), 7-hydroxy-6-methoxycoumarin(22), p-hydroxybenzaldehyde(23), pinoresinol(24), erythro-1,2-bis-(4-hydroxy-3-methoxyphenyl)-1,3-propanediol(25), urticol(26), urticol-7-O-β-D-glucopyranoside(27), and lobechine(28). Compounds 1-17 were isolated from U. fissa for the first time. Meanwhile, compound 1 was a new natural product. Compounds 10, 11, 19, 21, and 27 exhibited significant inhibitory effects on 5α-reductase.
Animals ; Plant Extracts/pharmacology* ; Prostatic Hyperplasia/drug therapy* ; Rats ; Urticaceae/chemistry*

Objective: To improve the knowledge and experience of ibrutinib combined with CAR-T cells in the treatment of high-risk chronic lymphoblastic leukemia (CLL) patients or small lymphocytic lymphoma (SLL) with TP53 gene aberration. Methods: One case of del (17p) CLL patients with BCL-2 inhibitor resistance was treated with ibrutinib combined with CAR-T cells, successfully bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and the relative literatures were reviewed. Results: The patient was a young female with superficial lymph node enlarging at the beginning of the onset. Lymph node biopsy was confirmed as small lymphocytic lymphoma (SLL) without del (17p) . The disease progressed rapidly to CLL/SLL with del (17p) and bone marrow hematopoietic failure 2 years later. Firstly, the patient was treated with BCL-2 inhibitor (Venetoclax) , and the enlarged lymph nodes shrank significantly 2 months later. After 3 months, the disease progressed rapidly. The spleen was enlarged to 16 cm below the ribs, the neck lymph nodes was rapidly enlarged, and the superior vena cava syndrome appeared, which were mainly attributed to venetoclax resistance; so BTK inhibitor (ibrutinib) was used continuously after venetoclax discontinuation. Partial remission (PR) was achieved without lymphocytosis after 2 months, then ibrutinib was combined with CAR-T cells targeting CD19 antigen. Grade 1 of cytokine release syndrome (CRS) appeared after CAR-T cells infusion, and the complete remission (CR) was achieved after 1 month both in bone marrow and peripheral blood, with minimal residual disease (MRD) negative, then bridging allo-HSCT after 2 months of combined therapy. Conclusion: CLL/SLL patients with TP53 aberration have poor prognosis because of rapid progression, drug resistance, etc. Ibrutinib combined with CAR-T cell therapy can quickly achieved complete remission.
Adenine/analogs & derivatives* ; Female ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/therapy* ; Piperidines ; Proto-Oncogene Proteins c-bcl-2 ; Pyrazoles/therapeutic use* ; Pyrimidines/therapeutic use* ; Recoverin ; T-Lymphocytes

OBJECTIVETo discuss the technique details of subintimal arterial flossing with antegrade-retrograde intervention (SAFARI) to improve technical success in the treatment of chronic total occlusions (CTO) diseases in lower extremity when there is failure to reenter the distal true lumen.

METHODSBetween May 2009 and Aug 2010, 15 patients underwent endovascular recanalization with SAFARI technique. There were 8 male and 7 female patients with a mean age of 74.9 years. There were 3 patients with severe claudication (Rutherford category 3) and 12 patients with critical limb ischemia (Rutherford category 4 to 6). The clinical and follow-up data of these patients were analyzed retrospectively.

RESULTSFourteen patients were treated with SAFARI technique successfully. The technique success rates were 93.3%. The mean ankle brachial index increased from 0.39 to 0.83.Symptoms were relieved in 86.6% patients, Ulcer were healed in 93.3%patients.

CONCLUSIONSSAFARI technique is a safe and effective method in treating CTO diseases, when it is failure to renter the distal true lumen with subintimal angioplasty technique.

Aged ; Aged, 80 and over ; Angioplasty, Balloon ; methods ; Arterial Occlusive Diseases ; surgery ; Female ; Follow-Up Studies ; Humans ; Lower Extremity ; blood supply ; Male ; Middle Aged ; Retrospective Studies

OBJECTIVERight ventricular apical pacing may induce cardiac desynchronize and deteriorate left ventricular systolic performance. We hypothesized that right ventricular outflow tract (RVOT) pacing could produce better mechanical synchrony and left ventricular contraction.

METHODSWe enrolled nine patients without structural heart disease who underwent electrophysiological studies. The pacing sites (right apex, low septum, free wall and septum of RVOT of the right ventricle) were defined with fluoroscopy and ECG. The atrioventricular sequential pacing was applied every 5 minutes in a random order at a rate of 120 bpm. Tissue Doppler imaging was carried out with GE VIVID 7 for off-line analysis at each pacing site. The global systolic contraction amplitude (GSCA) was calculated as the average shortening amplitude of all 16 segments of left ventricle.

RESULTSThe GSCA during pacing was 5.76 mm +/- 0.66 mm at free wall of RVOT and 5.66 mm +/- 1.00 mm at septum of RVOT, respectively. The GSCA at both sites was significantly higher than that at apical pacing 4.82 mm +/- 0.94 mm (P < 0.05) or low septum pacing 4.82 mm +/- 1.06 mm (P < 0.05). Moreover, segmental displacement analysis showed that the longitudinal displacement of lateral, posterior, and inferior walls significantly decreased at apical pacing compared with RVOT pacing, although no difference could be demonstrated in anterior and septum walls. Accordingly, the curve of the myocardial displacement at apical or low septum pacing was M-shaped, and had a negative wave at the end of the diastole in lateral, posterior, and inferior walls. The tissue velocity during isovolumic contraction period was also higher than systolic tissue velocity in these walls. The phenomenon could seldom be seen at RVOT pacing.

CONCLUSIONRVOT pacing in patients without structural heart disease is associated with more favorable immediate myocardial contraction and mechanical synchrony compared with right apical pacing or low septum pacing.

Adult ; Cardiac Pacing, Artificial ; methods ; Female ; Heart Ventricles ; diagnostic imaging ; physiopathology ; Humans ; Male ; Middle Aged ; Myocardial Contraction ; physiology ; Ultrasonography, Doppler ; Ventricular Function, Left

BACKGROUNDEndovascular recanalization (EVR) is becoming the primary therapy for patients with central venous (brachiocephalic, subclavian, and superior vena cava) occlusion (CVO) caused by benign etiology. In this study, we retrospectively analyzed our experience in using EVR to treat benign CVO in 10 patients between April 2005 and September 2010.

METHODSThe mean age of the patients was 65.3 years, 2/10 cases were female, and the origin of cause of CVO in 7/10 cases was the hemodialysis access in the upper extremity. The patients were treated with primary stent placement and evaluated with immediate technical success rate and post-interventional patency rate after the procedure.

RESULTSEight patients were treated successfully with stent placement and experienced symptomatic relief immediately. No technical complications were observed during EVR treatment. Patients were followed up by ultrasonography and venography. Median follow-up was 13 months. Three patients required secondary procedures to maintain patency.

CONCLUSIONSEVR is an effective and safe treatment in patients with benign CVO. It provides immediate symptom relief and maintains a continuous access for hemodialysis.

Adult ; Aged ; Aged, 80 and over ; Brachiocephalic Veins ; pathology ; Endovascular Procedures ; methods ; Female ; Humans ; Male ; Middle Aged ; Subclavian Vein ; pathology ; Vascular Diseases ; therapy ; Vena Cava, Superior ; pathology

BACKGROUNDCentral venous stenosis and obstruction (CVD) is a serious and prevalent challenge to both resolve the venous hypertension symptoms and maintain the pantency of the ipsilateral hemodialysis access in hemodialysis patients. This study aimed to summarize our experience of the endovascular management of the central venous stenosis or obstruction in hemodialysis patients.

METHODSTwenty-four haemodialysis cases of central vein stenosis or obstruction with ipsilateral functional vascular access in our hospital between July 2006 and February 2012 were treated by interventional therapy and the data were analyzed retrospectively.

RESULTSEighteen males and six females with mean age of (66.4 ± 13.8) years and manifesting with arm swelling and venous hypertension were enrolled; 62.5% of them had a history of catheterization. Venography showed stenotic lesion in 10 cases including eight cases of brachiocephalic vein stenosis and two cases of subclavian vein stenosis and 14 cases of obstruction lesions including seven cases of short brachiocephalic obstruction and seven cases of long segment obstruction. Interventional therapy was performed and the technique success rate was 83.3%. Percutaneous transluminal angioplasty (PTA) was performed in nine cases and stent was performed in 11 cases firstly. The symptoms of venous hypertension were resolved after intervention in all the cases. There was no major complication and death perioperatively. During follow-up, reintervention was done, the primary patency rates were (88.9 ± 10.5)%, (64.8 ± 10.5)% and (48.6 ± 18.7)% at 3 months, 6 months and 1 year after treatment in the PTA group; (90.0 ± 9.5)% and (77.1 ± 14.4)% at 6 months and 1 year after treatment in the stent group, respectively. The secondary patency rates were (48.6 ± 18.7)% in the PTA group and (83.3 ± 15.2)% in the stent group 1 year after treatment, respectively. There was no significant difference between the two groups (primary patency, P = 0.20; secondary patency, P = 0.10).

CONCLUSIONSThe endovascular intervention is a safe and effective method for CVD in short term; enhanced follow-up and repeated interventions are required to maintain patency for long term. The prevention is most important. Avoiding and minimizing the placement of the central venous catheter may be the key point for the prevention.

Adult ; Aged ; Aged, 80 and over ; Angioplasty, Balloon ; methods ; Catheterization, Central Venous ; Constriction, Pathologic ; Female ; Humans ; Male ; Middle Aged ; Renal Dialysis ; Retrospective Studies ; Stents ; Treatment Outcome ; Venous Thrombosis ; therapy ; Young Adult