The purpose of the present study was to explore whether substance P (SP) modulates the response mediated by GABAA receptors. Experiments were carried out on cultured hippocampal pyramidal neurons of rats. GABA-activated inward currents were recorded using the whole-cell-patch-clamp techique. The majority of the neurons examined (66/92, 72%) were sensitive to both GABA and SP. When the neurons were treated with SP prior to application of GABA, the GABA-activated current (IGABA) was inhibited markedly, which was concentration-dependent and could be blocked by spantide, an NK1 receptor antagonist. With 10－8, 10－7, 10－6 and 10－5 mol/L SP, IGABA was inhibited by 18%, 24.8%, 25.9% and 28% respectively. Intracellular application of H7, a potent inhibitor of PKC, abolished inhibition of IGABA by SP, suggesting that the inhibition of IGABA by SP may be a result of intracellular phosphorylation of the GABAA receptor.

Objective To evaluate the efficacy of argon surper-cryosurgery system (ASSS) in the treatment of huge hepatic multi-nidus carcinoma at advanced stage in cases of which conventional surgery is impossible. Methods Twenty-two patients with huge hepatic multi-nidus carcinoma at advanced stage, incurable with conventional surgery, were treated by ASSS in combination with entire or reduced-size excision. In terms of combined treatment, 1 patient received reduced-size operation and portal vein chemotherapeutic pump, 2 with entire excision and portal vein chemotherapeutic pump, 1 with entire excision and liver artery chemotherapeutic pump, 3 with only liver artery chemotherapeutic pump, and 6 with portal vein chemotherapeutic pump. Nine patients were simply treated by ASSS. Results The surgical procedures went smoothly in all cases and the complications, such as bleeding at the puncture aperturae, thorax effusion, bile leakage and liver cataphora, were successfully managed. The follow-up study was performed and all patients surived with the longest survival of 11 months up till now. Conclusions ASSS offers a new treatment method for huge hepatic multi-nidus carcinoma at advanced stage, but the indications must be carefully observed, and the surgical skills and prevention of complication are of great importance.

Objective To evaluate the efficacy of argon surper-cryosurgery system (ASSS) in the treatment of huge hepatic multi-nidus carcinoma at advanced stage in cases of which conventional surgery is impossible. Methods Twenty-two patients with huge hepatic multi-nidus carcinoma at advanced stage, incurable with conventional surgery, were treated by ASSS in combination with entire or reduced-size excision. In terms of combined treatment, 1 patient received reduced-size operation and portal vein chemotherapeutic pump, 2 with entire excision and portal vein chemotherapeutic pump, 1 with entire excision and liver artery chemotherapeutic pump, 3 with only liver artery chemotherapeutic pump, and 6 with portal vein chemotherapeutic pump. Nine patients were simply treated by ASSS. Results The surgical procedures went smoothly in all cases and the complications, such as bleeding at the puncture aperturae, thorax effusion, bile leakage and liver cataphora, were successfully managed. The follow-up study was performed and all patients surived with the longest survival of 11 months up till now. Conclusions ASSS offers a new treatment method for huge hepatic multi-nidus carcinoma at advanced stage, but the indications must be carefully observed, and the surgical skills and prevention of complication are of great importance.

OBJECTIVETo explore the effect of ITF2357, a novel histone deacetylase (HDAC) inhibitor, on the growth, differentiation and apoptosis of acute myeloid leukemic (AML) cells and its mechanism.

METHODSAML cell lines kasumi-1 cells as a model for AML1-ETO positive, and THP1 cells for AML1-ETO negative, the leukemic cells proliferation was analyzed by MTT assay, expression of myeloid-specific differentiation antigen and cell cycle by flow cytometry, cell apoptosis by annexin V staining and flow cytometry. AML1-ETO, acetyl-histone, and caspase protein was analyzed by Western blot.

RESULTS0.5 µmol/L ITF2357 treatment significantly inhibited kasumi-1 cells proliferation, with the 48 h half inhibitory concentration (IC(50)) of 0.1 µmol/L. The initial inhibitory concentration of THP1 cell line was 5 µmol/L. ITF 2357 induced apoptosis of kasumi-1 cells in a time- and dose-dependent manner. A dose-dependent increase in early apoptosis occurred at 24 hours treatment and in late apoptosis at 48 hours treatment by ITF2357. Early apoptosis cells increased from (1.44 ± 1.52)% to (24.51 ± 5.79)%. Late apoptosis cells increased from (2.37 ± 2.8)% to (63.66 ± 1.56)%. ITF2357 induced AML1-ETO degradation by caspase-dependent pathway. 0.25 µmol/L ITF2357 induced a time- and dose-dependent increase in expression of myeloid cell surface protein CD13 and CD15. 5 µmol/L ITF2357 blocked the cells at G(0)/G(1) phase, G(0)/G(1) cells increased from (39.69 ± 6.56)% to (79.2 ± 6.51)% and s-phase cells declined from (60.12 ± 3.29)% to (18.97 ± 6.62)%. Kasumi-1 cells incubated with 0.5 µmol/L of ITF2357, AML1-ETO protein began to decrease at 24 hours and could hardly be detected at 96 hours. ITF2357 induced AML1/ETO degradation through a caspase-dependent mechanism. At the same time, acetylated H3 and H4 increased.

CONCLUSIONLow-dose HDAC inhibitor ITF2357 can effectively inhibit the AML cells proliferation, especially for AML1-ETO positive AML cells. It inhibits Kasumi-1 cells proliferation degradation of AML1-ETO protein expression, blocks the cells at G(0)/G(1) phase, and induces apoptosis and differentiation of the cells.

Acetylation ; Apoptosis ; drug effects ; Cell Differentiation ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Histone Deacetylase Inhibitors ; pharmacology ; Histones ; metabolism ; Humans ; Hydroxamic Acids ; pharmacology ; Oncogene Proteins, Fusion ; metabolism

OBJECTIVETo investigate whether CYC116 can potentiate matrine-dependent growth inhibition and apoptosis in multiple myeloma (MM) cells.

METHODSThe dose response relationship of matrine to dexamethasone-resistant and dexamethasone-sensitive MM cells was first established. Myeloma RPMI8226 cells were treated with matrine alone or combined with CYC116 for 24 h. Cell proliferation was measured using an MTT assay and apoptosis induction was evaluated by flow cytometry. Activation of the caspase pathway and expression of apoptosis regulator proteins were detected by Western blotting.

RESULTSMatrine significantly induced growth arrest and apoptosis in both drug-resistant and drug-sensitive MM cells. Treatment with the combination of matrine and CYC116 had a stronger cytotoxic effect on MM cells than did single drug treatments. Enhanced apoptosis observed following the combined treatment of matrine and CYC116 was associated with higher levels of activation of caspase-9, caspase-3, and poly adenosine diphosphate ribose polymerase (PARP) and down-regulation of the anti-apoptotic proteins Bcl-2 and Mcl-1 and the signaling proteins p-Akt and nuclear factor κB (NF-κB).

CONCLUSIONCYC116 enhances the growth inhibitory and apoptotic effects of matrine on MM cells.

Alkaloids ; pharmacology ; Apoptosis ; drug effects ; Cell Division ; drug effects ; Cell Line, Tumor ; Humans ; Multiple Myeloma ; pathology ; Pyrimidines ; pharmacology ; Quinolizines ; pharmacology ; Thiazoles ; pharmacology

This study was purpose to evaluate a new method and instrument for detecting platelet aggregation function, establish the reference intervals for PL-11 platelet analyzer, and evaluate its clinical application. The evaluation was based on the guidelines of Clinical and Laboratory Standards Institute (CLSI or NCCLS) and Clinical Laboratory Improvement Amendment 88. Intravenous blood samples anticoagulated with sodium citrate were detected by PL-11 platelet analyzer. The reference intervals were defined after statistic analysis. The clinical diagnostic significance of the PL-11 platelet analyzer was evaluated by testing the change rate of platelet maximum aggregation rate (MAR) of acute cerebral infarction (ACI) patients in the department of Neurology who took clopidogrel 7 d before and after. The result showed that all the parameters meet the standard of CLIA'88. The platelet MAR of 247 healthy volunteers which was induced by PLR-06, PLR-07, PLR-09 and PLR-10, was detected by the PL-11 platelet analyzer, respectively. The MAR is 58.8 ± 10.1 (%), 61.2 ± 11.8 (%), 51 ± 10.2 (%), 53.1 ± 9.2 (%), respectively. The MAR of ACI patients is significantly lower than that after taking clopidogrel. It is concluded that the PL-11 platelet analyzer is an ideal platelet function detector for early warning and diagnosis of thromboembolic disease, which is worthy to be extended and applied.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation ; Platelet Function Tests ; instrumentation ; methods ; Young Adult

Objective To explore the value of hippocampus hydrogen proton magnetic resonance spectrum analyzes (1 H-MRS) for the diagnosis of temporal lobe epilepsy (TLE) in children.Methods Singa HDe GE company to attain the 1.5T magnetic resonance imaging apparatus was used to analyze the conditions of 30 cases of children with TLE and the other 30 healthy controls received brain MRI and 1H-MRS check.The hippocampal N acetyl aspartate (NAA),creatine (Cr),and the choline (Cho) concentration were observed; NAA/(Cho + Cr),the ratio of NAA/Cr and NAA/Cho were analyzed.The analysis of biochemical components in the hippocampus was performed on the affected sides and the healthy sides of TLE group and the sides of the healthy control group,respectively.Results Hippocampus were anormal by combining MRI and MRS in 28 cases.Levels of NAA/(Cho + Cr),NAA/Cho,and NAA/Cr in the trouble sides of the TLE group had the remarkable statistical significance compared with the normal sides,and the healthy control group (all P ＜ 0.05),but there was no remarkable statistic significance between the normal sides and the healthy control group (all P ＞ 0.05).Nineteen cases had been confirmed by surgery,and postoperative pathological changes:brain surface were wavy,cortex were uneven;there were giant neurons,immature neurons,and scattered across the deformity of neurons in the cortex.A small amount of ectopic neurons can be seen in white matter.Conclusions In the TLE children,the reduction of NAA/(Cho + Cr) value of the side hippocampus may help diagnose the hipppcampal sclerosis earlier,and can provide significant evidence for the diagnosis and treatment of TLE in children.

OBJECTIVETo investigate the serum levels of sCD44v6 and sE-cadherin (sE-cad) in patients with esophageal squamous cell carcinoma.

METHODSThe serum samples were collected from 65 cases of esophageal squamous cell carcinoma, 32 cases of erosive esophagitis and 35 healthy subjects. Serum sCD44v6 and sE-cad levels were measured by enzyme linked immunosorbent assay (ELISA).

RESULTSThe mean levels of serum sCD44v6 and sE-cad in esophageal squamous cell carcinoma patients were significantly higher than those of erosive esophagitis patients and normal controls (both P<0.05). There was no significant difference in serum sCD44v6 and sE-cad levels between erosive esophagitis patients normal controls (P=0.566 and P=0.708, respectively). Serum sCD44v6 and sE-cad levels of esophageal cancer patients were not correlated with their clinicopathological features. Serum sCD44v6 level is not correlated with sE-cad level in squamous cell carcinoma patients(P=0.651).

CONCLUSIONSerum sCD44v6 and sE-cad might be a potential marker for screening of esophageal squamous cell carcinoma.

Adult ; Aged ; Aged, 80 and over ; Cadherins ; blood ; Carcinoma, Squamous Cell ; blood ; pathology ; Case-Control Studies ; Esophageal Neoplasms ; blood ; pathology ; Female ; Humans ; Hyaluronan Receptors ; blood ; Male ; Middle Aged

Background: Thymoma is an uncommon tumor without a widely accepted standard care to date. We aimed to investigate the clinicopathologic variables of patients with thymoma and identify possible predictors of survival and recurrence after initial resection. Methods: We retrospectively selected 307 patients with thymoma who underwent complete resection at the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China) between January 2003 and December 2014. The associations of patients' clinical characteristics with prognosis were estimated using Cox regression and Kaplan–Meier survival analyses. Results: During follow-up (median, 86 months; range, 24–160 months), the 5- and 10-year disease-free survival (DFS) rates were 84.0% and 73.0%, respectively, and the 5- and 10-year overall survival (OS) rates were 91.0% and 74.0%, respectively. Masaoka stage (P < 0.001), World Health Organization (WHO) histological classification (P < 0.001), and postoperative radiotherapy after initial resection (P = 0.006) were associated with recurrence (52/307, 16.9%). Multivariate analysis revealed that, after initial resection, WHO histological classification and Masaoka stage were independent predictors of DFS and OS. The pleura (25/52, 48.0%) were the most common site of recurrence, and locoregional recurrence (41/52, 79.0%) was the most common recurrence pattern. The recurrence pattern was an independent predictor of post-recurrence survival. Patients with recurrent thymoma who underwent repeated resec-tion had increased post-recurrence survival rates compared with those who underwent therapies other than surgery (P = 0.017). Conclusions: Masaoka stage and WHO histological classification were independent prognostic factors of thymoma after initial complete resection. The recurrence pattern was an independent predictor of post-recurrence survival. Locoregional recurrence and repeated resection of the recurrent tumor were associated with favorable prognosis.

Objective: To investigate the effects of cycle-dependent kinase ( CDK) inhibitor SNS-032 on apoptosis in human acute myeloid leukemia ( AML) HL-60 cells and its molecular mechanisms .Methods:Cultured AML HL-60 cells were treated with various concentrations of SNS-032 .Cell apoptosis was determined with flow cytometry;cell viability was measured by MTT assay; the profiles of microRNA expression of HL-60 cells were analyzed by microRNA microarray;the protein expressions of JAK 2/STAT3 pathway were detected by Western blotting .Results:Apoptosis of AML HL-60 cells was induced by SNS-032; the rate of apoptosis was (5.9 ±1.7)%, (12.1 ± 3.1)% and (59.4 ±3.6)% when HL-60 cells were treated with 0,100 and 200 nmol/L SNS-032.MicroRNA microarray analysis revealed that the levels of miR-30a, miR-183, miR-20b, miR-26b, miR-20a, miR-589, miR-107, miR-181a, miR-106a, miR-17 and miR-378 c were down-regulated by SNS-032 , whereas the levels of miR-320a and miR-H7* were up-regulated.Western blotting showed that SNS-032 strongly inhibited phosphorylation of STAT 3 and protein expression of JAK 2, C-MYC and MCL-1.Conclusion:CDK inhibitor SNS-032 can induce apoptosis of AML HL-60 cells, which is associated with the inhibition of MCL-1,C-MYC and JAK2/STAT3, and down-regulation of miR-17-92 family .