[Effect analysis of treating intracranial wide-neck bifurcation aneurysms through Woven EndoBridge].

Objective: To explore the clinical effect of Woven EndoBridge (WEB) in the treatment of wide-neck bifurcation aneurysms. Methods: The clinical and imaging data of 11 patients with intracranial wide-neck bifurcation aneurysms treated by WEB alone at Department of Neurosurgery of the Northern Theater General Hospital from September 2017 to May 2018, were retrospectively analyzed. The patients were 7 males and 4 females, aged (54±11) years (ranged from 31 to 66 years). The aneurysms of 5 patients were located in the anterior communicating artery, 3 in the top of the basilar artery, and 3 in the bifurcation of the middle cerebral artery. The intraoperative and postoperative conditions of the patients were recorded, and the degree of aneurysm embolization was evaluated by WEB embolization aneurysm occlusion scale (WOS). Results: The intraoperative WEB release of all the 11 patients was good, with 3 cases of WOS grade A, 1 of grade B and 7 of grade C, with no intraoperative acute complications occurring. The imaging follow-up was not carried out in 1 patient due to economic reason, and the clinical follow-up was good until 3 years after the operation; 10 patients were followed up by imaging for 6 months to 3 years, and no postoperative complications occurred in the target treatment area. Among the 2 patients with WOS grade A and 1 patient with grade B during operation, according to the postoperative follow-up, all were WOS grade A; among the 7 patients with WOS grade C during operation, 4 were still of grade C and 3 were of grade D according to the follow-up. Among the 3 patients with WOS grade D, 1 patient received secondary embolization due to poor recurrence morphology, unstable hemodynamics and high possibility of rupture of aneurysm, stent assisted coil embolization was adopted, with good immediate effect; the other 2 cases had recurrent aneurysms, but the aneurysms had good morphology and stable hemodynamics, therefore, clinical follow-up was continued and no secondary surgery was performed. No complications occurred in all these 11 patients. Conclusions: The operation of treating unruptured intracranial wide-neck bifurcation aneurysms with WEB device alone is simple, and there is no need for anticoagulation and antiplatelet treatment before and after the operation, the clinical effect is being good. WEB device provides a new treatment option for intracranial wide-neck bifurcation aneurysms.

MiR-127-3p inhibits proliferation of ovarian cancer in rats through down-regulating MAPK4.

OBJECTIVE: To reveal the anti-tumor effect of micro ribonucleic acid (miR)-127-3p on epithelial ovarian cancer (EOC). PATIENTS AND METHODS: The expression of miR-127-3p in 7 kinds of EOC cell lines and 10 cases of clinical samples of EOC patients was detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). OVCAR-3 and Caov-3 cell lines were transfected with lentiviruses to overexpress endogenous miR-127-3p. Then, the anti-tumor effect of miR-127-3p on EOC cells was explored through the in vitro cell proliferation assay, bufalin sensitivity assay, wound healing assay, and invasion assay. In addition, whether the mitogen-activated protein kinase 4 (MAPK4) gene is a downstream target of miR-127-3p in EOC was verified via Dual-Luciferase reporter assay and qRT-PCR. The involvement of MAPK4 in regulating phenotypes of OVCAR-3 and Caov-3 cells was finally explored. RESULTS: MiR-127-3p was downregulated in both EOC cell lines and EOC tissues (p<0.05). After lentivirus-mediated overexpression of miR-127-3p, in vitro proliferation and invasion of EOC cells were inhibited, and the sensitivity to bufalin was enhanced (p<0.05). MiR-127-3p directly regulated MAPK4 gene in EOC. Moreover, the upregulation of MAPK4 inhibited the anti-tumor effect of miR-127-3p on EOC, manifested as the remarkably enhanced cell proliferation and migration (p<0.05), and the weakened sensitivity to bufalin (p<0.01). CONCLUSIONS: MiR-127-3p exerts an inhibitory effect on EOC cells via regulating MAPK4 level.

[Esophageal motility and reflux characteristics in gastroesophageal reflux disease patients with or without extra-esophageal symptoms].

Objective: To investigate esophageal motility and reflux characteristics in gastroesophageal reflux disease (GERD) with and without extra-esophageal symptoms by high-resolution manometry and 24 h esophageal multichannel intraluminal impedance combined pH (MII-pH) monitoring. Methods: From February 2016 to June 2017, GERD patients with and without extra-esophageal symptoms were enrolled in this prospective controlled study. Esophageal HRM and 24 h MII-pH monitoring were performed. The differences in esophageal motility and reflux parameters were further analyzed between 30 GERD patients with extra-esophageal symptoms and 30 simple GERD patients. Results: The GERD symptom scores didn't show statistical difference between two groups. The GERD symptom scores didn't show statistical difference between two groups. The relaxation pressure of lower esophageal sphincter(LES), the integrated relaxation pressure, and the recovery time of upper esophageal sphincter(UES) of GERD patients with extra-esophageal symptoms were all lower than those of patients without extra-esophageal symptoms [(15±7) vs (21±11)mmHg, (8±3) vs (10±5)mmHg, (388±168) vs (492±170)ms, 1 mmHg=0.133 kPa], and the differences were statistically significant(all P<0.05). The main classification of esophageal motility type of GERD patients with extra-esophageal symptoms was mild esophageal motility disorders (27%, 8/30), and the occurrence of ineffective esophageal motivation was 20% (6/30), which were similar with simple GERD patients. The proximal reflux percentages of weak acid reflux and nonacid reflux, abnormal nonacid reflux in GERD patients with extra-esophageal symptoms were significantly higher than those in simple GERD patients [84.6% (73.2%, 100.0%) vs 75.0% (60.0%, 87.65%), P=0.048; 90.0% (45.8%, 100.0%) vs 0(0, 100.0%), P=0.017; 46.7% vs 3.3%, P=0.03]. Conclusions: The pathogenesis of GERD with extra-esophageal symptoms may be different from typical GERD. Increase of proximal esophageal reflux and abnormal nonacid reflux may all participate in the mechanisms of GERD with extra-esophageal symptoms.

[Analysis of clinical data, esophageal motility and reflux characteristics in patients with non-erosive reflux disease(NERD) and reflux esophagitis(RE)].

Objective: To compare the clinical data, esophageal motility and reflux characteristic in patients with non-erosive reflux disease (NERD) and reflux esophagitis (RE). Methods: A total of 167 patients of NERD were enrolled in the study[60 males, 107 females, mean age(44.1±13.4) years old], and 151 patients of RE were enrolled [74 males, 77 females, mean age(46.5±9.9) years old]. All patients were surveyed by questionnaires to investigate the clinical data. All patients accepted the esophageal highresolution manometry and 24 hours pH+ impedance monitoring to investigate the esophageal motility and reflux characteristic. Results: The proportion of female patients in group NERD was significantly higher than that in group RE(60/107 vs 74/77, P=0.049). The reflux symptom scores and the proportion of reflux in group NERD were significantly lower than those in group RE[(4.5±2.4) vs (5.6±2.1), 44.91% vs 64.24%, P<0.05). The Demeester score of group NERD was significantly lower than that of group RE[12.54(1.60, 10.80) vs 17.31(3.40, 16.64), P=0.044]. The proportion of Demeester scores positive patients in group NERD was significantly lower than that in group RE(15.1% vs 23.8%, P=0.018). The number of acid reflux in group NERD was significantly lower than that in group RE[17.49(3.00, 22.22) vs 21.69(4.00, 30.00), P=0.042]. Conclusions: There are more female patients in group NERD. The reflux symptoms of the group NERD are less serious than those of group RE.RE patients have more acid reflux events. There is no significant difference in the esophageal motility between the two groups.

Impaired vagal activity to meal in patients with functional dyspepsia and delayed gastric emptying.

Objective This study was performed to investigate impaired vagal activity to meal in patients with functional dyspepsia (FD) with delayed gastric emptying (GE). Methods Eighty-five patients were studied. GE parameters, including those in the overall and proximal stomach, were measured by GE functional tests at the Department of Nuclear Medicine. Autonomic nervous function was tested by spectral analysis of heart rate variability (HRV). The vagal activity and sympathetic activity were analyzed by recording the power in the high-frequency component (HF), low-frequency component (LF), and LF/HF ratio. Results Overall and proximal GE were delayed in 47.2% and 50.9% of the patients, respectively. Spectral analysis of HRV showed that the HF in patients with delayed proximal GE was significantly lower and that the LF/HF ratio was significantly higher than those in patients with normal proximal GE after a meal. Conclusion Delayed proximal GE might be caused by disrupted sympathovagal balance as a result of decreased vagal activity after a meal. Improvement in vagal activity may constitute an effective treatment method for patients with FD.

Comparative study: efficacy of closed-looptarget controlled infusion of cisatracurium and other administration methods for spinal surgery of elderly patients.

OBJECTIVE: To observe the efficacy of traditional administration, continuous pump injection, and closed-loop target controlled infusion of cisatracurium to determine the optimal method of drug administration, and to establish the individualized and rational administration of muscle relaxants in elderly patients. PATIENTS AND METHODS: A total of 150 patients who underwent spinal surgery under tracheal intubation general anesthesia in our hospital from August 2013 to April 2015 were selected. All patients were administered with general anesthesia and randomly divided into three groups: group A (n = 50) was treated under closed-loop target controlled infusion (CLTCI), group B (n = 50) was treated under muscle relaxation monitoring, and group C (n = 50) was treated under continuous pump injection. Hemodynamic changes and blood oxygen saturation of the three groups were observed, and the muscle relaxation recovery, dosage, and bleeding of the three groups were compared. RESULTS: MAP and HR of group A were significantly lower than those of group B and group C (p < 0.05). There were no cases of insufficient muscle relaxation in group A, five cases in group C, and 14 cases in group B, and the differences between any two groups were statistically significant (p < 0.05). Regarding muscle relaxation recovery, the time (T¬¬1) of recovery from 10%-25% and 25%-75%, and the time from drug withdrawal to recovery to TOFr from 0.7-0.9 of group A were the shortest, followed by group C and group B. The differences between any two groups were statistically significant (p < 0.05). The total dosage of cisatracurium of group A was the least, followed by group C and group B, and differences between any two groups were statistically significant (p < 0.05). Moreover, the bleeding volume of group A (235.2 ± 141.3 ml) was smaller than in group B (353.1 ± 173.8 ml) and group C (316.5 ± 155.2 ml), and differences between the three groups were statistically significant (p < 0.05). CONCLUSIONS: For spinal surgery of elderly patients, closed-loop target controlled infusion of cisatracurium was superior to continuous infusion and intravenous injection. The time of muscle relaxation recovery was shortened, the dosage of cisatracurium was reduced, and the number of cases of insufficient muscle relaxation was reduced.

Decreased TIM-3 mRNA expression in peripheral blood mononuclear cells from nephropathy patients.

Increasing evidence shows that TIM-1 and TIM-3 in-fluence chronic autoimmune diseases, and their expression levels in immune cells from nephritic patients are still unknown. Real-time transcription-polymerase chain reaction analysis was used to deter-mine expression levels of TIM-1 and TIM-3 mRNA in peripheral blood mononuclear cells (PBMCs) from 36 patients with minimal change glo-merulopathy (MCG), 65 patients with lupus nephritis (LN), 78 patients with IgA nephropathy (IgAN), 55 patients with membranous nephropa-thy (MN), 22 patients with crescentic glomerulonephritis (CGN), 26 patients with anaphylactoid purpura nephritis (APN), and 63 healthy controls. TIM-3 mRNA expression significantly decreased in PBMCs from nephritic patients (LN, P < 0.0001; MCG, P < 0.0001; MN, P = 0.0031; CGN, P = 0.0464; IgAN, P = 0.0002; APN, P = 0.0392) com-pared with healthy controls. In contrast, there was no significant differ-ence in TIM-1 mRNA expression between the patients and the healthy controls. Our results suggest that insufficient expression of TIM-3 mRNA may be involved in the pathogenesis of nephropathy.

Downregulation of TIM-3 mRNA expression in peripheral blood mononuclear cells from patients with systemic lupus erythematosus

The T-cell immunoglobulin and mucin domain (TIM) family is associated with autoimmune diseases, but its expression level in the immune cells of systemic lupus erythematosus (SLE) patients is not known. The aim of this study was to investigate whether the expression of TIM-3 mRNA is associated with pathogenesis of SLE. Quantitative real-time reverse transcription-polymerase chain reaction analysis (qRT-PCR) was used to determine TIM-1, TIM-3, and TIM-4 mRNA expression in peripheral blood mononuclear cells (PBMCs) from 132 patients with SLE and 62 healthy controls. The PBMC surface protein expression of TIMs in PBMCs from 20 SLE patients and 15 healthy controls was assayed by flow cytometry. Only TIM-3 mRNA expression decreased significantly in SLE patients compared with healthy controls (P<0.001). No significant differences in TIM family protein expression were observed in leukocytes from SLE patients and healthy controls (P>0.05). SLE patients with lupus nephritis (LN) had a significantly lower expression of TIM-3 mRNA than those without LN (P=0.001). There was no significant difference in the expression of TIM-3 mRNA within different classes of LN (P>0.05). Correlation of TIM-3 mRNA expression with serum IgA was highly significant (r=0.425, P=0.004), but was weakly correlated with total serum protein (rs=0.283, P=0.049) and serum albumin (rs=0.297, P=0.047). TIM-3 mRNA expression was weakly correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; rs=-0.272, P=0.032). Our results suggest that below-normal expression of TIM-3 mRNA in PBMC may be involved in the pathogenesis of SLE.

Downregulation of TIM-3 mRNA expression in peripheral blood mononuclear cells from patients with systemic lupus erythematosus.

The T-cell immunoglobulin and mucin domain (TIM) family is associated with autoimmune diseases, but its expression level in the immune cells of systemic lupus erythematosus (SLE) patients is not known. The aim of this study was to investigate whether the expression of TIM-3 mRNA is associated with pathogenesis of SLE. Quantitative real-time reverse transcription-polymerase chain reaction analysis (qRT-PCR) was used to determine TIM-1, TIM-3, and TIM-4 mRNA expression in peripheral blood mononuclear cells (PBMCs) from 132 patients with SLE and 62 healthy controls. The PBMC surface protein expression of TIMs in PBMCs from 20 SLE patients and 15 healthy controls was assayed by flow cytometry. Only TIM-3 mRNA expression decreased significantly in SLE patients compared with healthy controls (P<0.001). No significant differences in TIM family protein expression were observed in leukocytes from SLE patients and healthy controls (P>0.05). SLE patients with lupus nephritis (LN) had a significantly lower expression of TIM-3 mRNA than those without LN (P=0.001). There was no significant difference in the expression of TIM-3 mRNA within different classes of LN (P>0.05). Correlation of TIM-3 mRNA expression with serum IgA was highly significant (r=0.425, P=0.004), but was weakly correlated with total serum protein (rs=0.283, P=0.049) and serum albumin (rs=0.297, P=0.047). TIM-3 mRNA expression was weakly correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; rs=-0.272, P=0.032). Our results suggest that below-normal expression of TIM-3 mRNA in PBMC may be involved in the pathogenesis of SLE.

Inhibitory effects of curcumin on gastric cancer cells: a proteomic study of molecular targets.

Curcumin, a natural anticancer agent, has been shown to inhibit cell growth in a number of tumor cell lines and animal models. We examined the inhibition of curcumin on cell viability and its induction of apoptosis using different gastric cancer cell lines (BGC-823, MKN-45 and SCG-7901). 3-(4,5-dimethyl-thiazol-2-yl)-2-5-diphenyltetrazolium-bromide (MTT) assay showed that curcumin inhibited cell growth in a dose- (1, 5, 10 and 30 µM) and time- (24, 48, 72 and 96 h) dependent manner; analysis of Annexin V binding showed that curcumin induced apoptosis at the dose of 10 and 30 µM when the cells were treated for 24 and 48 h. As cancers are caused by dysregulation of various proteins, we investigated target proteins associated with curcumin by two-dimensional gel electrophoresis (2-DE) and MALDI-TOF-TOF mass spectrometer. BGC-823 cells were treated with 30 µM curcumin for 24 h and total protein was extracted for the 2-DE. In the first dimension of the 2-DE, protein samples (800 µg) were applied to immobilized pH gradient (IPG) strips (24 cm, pH 3-10, NL) and the isoelectric focusing (IEF) was performed using a step-wise voltage ramp; the second dimension was performed using 12.5% SDS-PAGE gel at 1 W constant power per gel. In total, 75 proteins showed significant changes over 1.5-fold in curcumin-treated cells compared to control cells (Student's t-test, p<0.05). Among them, 33 proteins were upregulated and 42 proteins downregulated by curcumin as determined by spot densitometry. 52 proteins with significant mascot scores were identified and implicated in cancer development and progression. Their biological function included cell proliferation, cycle and apoptosis (20%), metabolism (16%), nucleic acid processing (15%), cytoskeleton organization and movement (11%), signal transduction (11%), protein folding, proteolysis and translation (20%), and immune response (2%). Furthermore, protein-protein interacting analysis demonstrated the interaction networks affected by curcumin in gastric cancer cells. These data provide some clues for explaining the anticancer mechanisms of curcumin and explore more potent molecular targets of the drug expected to be helpful for the development of new drugs.

Interleukin-10 receptor expression and signalling were down-regulated in CD4⁺ T cells of lupus nephritis patients.

Studies have indicated that interleukin (IL)-10 has a pathogenic role in systemic lupus erythematosus (SLE); however, a protective effect of IL-10 in SLE was also observed. Because the exact mechanism of IL-10 signalling in the pathogenesis of SLE is unclear, this study sought to assess the expression and signalling of interleukin-10 receptor (IL-10R) in peripheral leucocytes from patients with SLE. We used flow cytometry to examine the expression of IL-10R1 on different peripheral leucocytes from 28 SLE patients, of whom 14 had lupus nephritis (LN) and 14 were healthy controls. We also examined the effects of IL-10 on phosphorylation of signal transducer and activator of transcription (STAT)-3 and STAT-1 in peripheral blood mononuclear cells (PBMCs) obtained from 13 SLE patients and seven healthy controls. Plasma cytokines were detected by flow cytometric bead array (CBA) techniques. Although IL-10R1 expression levels on each peripheral leucocyte subset from 28 SLE patients and 14 healthy controls were similar, the expression levels on CD4(+) T cells from LN patients were significantly lower than on CD4(+) T cells from controls and SLE patients without nephritis (P < 0·01). IL-10R1 expression levels on CD4(+) and CD8(+) T cells were correlated negatively with the SLE disease activity index (P < 0·01). Additionally, the phosphorylation of STAT-3 was delayed and reduced in PBMCs from LN patients and active SLE patients. Plasma IL-10 levels were significantly higher in LN patients than controls. IL-10R1 expression on CD4(+) T cells and signalling in PBMCs were down-regulated in LN patients, indicating that IL-10 and its receptor may have a special role in LN pathogenesis.

Synergic CSE1L/CAS, TNFR-1, and p53 apoptotic pathways in combined interferon-gamma/adriamycin-induced apoptosis of Hep G2 hepatoma cells.

Many cancers are chemotherapy-resistant. Chemotherapy combined with immunotherapy offers a potential avenue for the treatment of chemotherapy-resistant cancers. In this study, we investigated the apoptotic pathways induced by combined interferon-gamma/adriamycin treatment in Hep G2 cells. Our data showed that Hep G2 cells treated with combined interferon-gamma/adriamycin enhanced cell apoptosis in comparison with that of cells treated with adriamycin. Interferon-y increased TNFR-1, CSE1L/CAS (cellular apoptosis susceptibility protein), Bax, and Bad levels. Adriamycin increased p53 and Bax, but not TNFR- 1 and CAS levels. Interferon-y did not increase p53 accumulation; nevertheless it enhanced adriamycin-induced p53 accumulation. Overexpression of IRF-1 augmented the combined interferon-gamma/adriamycin-induced p53 accumulation. Interferon-gamma co-treatment increased the stability of p53 protein induced by adriamycin. Our data suggest that TNF-gamma may greatly enhance the combined interferon-gamma/chemotherapeutic drug-induced apoptosis of cancers. Our findings also indicate that CAS, TN-FR-1, p53, Bax, and Bad may be the targets for the interferon-y-based chemo-immunotherapy of the chemotherapy-resistant cancers.

The use of low-molecular-weight components from adult cattle serum in culture of hybridoma cells in vitro.

Adequate amounts (3.5-14%) of low-molecular weight fractions from adult cattle serum (LMW-CS) passed through an /Amicon PM30 filter (mol. wt. exclusion = 30000), 20 microM ethanolamine (E), 10 mg/l transferrin (T), 10 mg/l insulin (I), and 40 nM sodium selenite (S), used as the substitutes for fetal calf serum (FCS), were added to the basic medium, RPMI1640 or a 1:1 mixture (by volume) of IMDM (Iscove's Modified Dufbecco's Medium) and Ham's F12, to compose the experimental "serum-free" medium. Maximum density of hybridoma cells cultured in such medium can reach and sometimes exceed that in FCS-containing medium. For the growth of hybridoma cells, 4% LMW-CS in the medium was found to be able to meet the basic requirement; ethanolamine was the primary growth-supporting factor among the 4 essential supplements of T, I, E, and S; and a significant synergistic action on the cell growth was found between LMW-CS and TIES.