Itch is an unpleasant sensation that urges people and animals to scratch. Neuroimaging studies on itch have yielded extensive correlations with diverse cortical and subcortical regions, including the insular lobe. However, the role and functional specificity of the insular cortex (IC) and its subdivisions in itch mediation remains unclear. Here, we demonstrated by immunohistochemistry and fiber photometry tests, that neurons in both the anterior insular cortex (AIC) and the posterior insular cortex (PIC) are activated during acute itch processes. Pharmacogenetic experiments revealed that nonselective inhibition of global AIC neurons, or selective inhibition of the activity of glutaminergic neurons in the AIC, reduced the scratching behaviors induced by intradermal injection of 5-hydroxytryptamine (5-HT), but not those induced by compound 48/80. However, both nonselective inhibition of global PIC neurons and selective inhibition of glutaminergic neurons in the PIC failed to affect the itching-scratching behaviors induced by either 5-HT or compound 48/80. In addition, pharmacogenetic inhibition of AIC glutaminergic neurons effectively blocked itch-associated conditioned place aversion behavior, and inhibition of AIC glutaminergic neurons projecting to the prelimbic cortex significantly suppressed 5-HT-evoked scratching. These findings provide preliminary evidence that the AIC is involved, at least partially via aversive emotion mediation, in the regulation of 5-HT-, but not compound 48/80-induced itch.
Humans ; Animals ; Serotonin ; Insular Cortex ; Pruritus/chemically induced* ; Cerebral Cortex/physiology* ; Neurons

Objective: To investigate the efficacy and safety of left bundle branch pacing(LBBP) in patients after transcatheter aortic valve implantation (TAVI). Methods: This is a retrospective study. A total of 35 patients underwent TAVI and received pacemaker implantation from January 2018 to December 2020 in Beijing Fuwai Hospital were enrolled. Patients were divided into LBBP group (n=12) and right ventricular apex pacing (RVAP) group (n=23) according to the pacing position. The success rate of operation in LBBP group was calculated, and the occurrence of complications were observed, and the parameters of pacemaker were measured on the 3rd day and 1, 3 and 6 months after operation. The N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiographic and ECG indexes were compared between the two groups on the 3rd day and 1, 3, and 6 months after pacemaker implantation. Result: A total of 35 patients were included, The age was (76.4±7.7) years, including 19 males (54.3%). The procedure time ((86.58±17.10)min vs. (68.74±9.18)min, P<0.001) and fluoroscopy duration ((20.08±4.44)min vs. (17.00±2.26)min, P<0.001) were significantly longer in LBBP group compared with RVAP group. The operation success rate of LBBP group was 11/12. There was no serious operation related complications such as pneumothorax, hemothorax, electrode dislocation, infection, and lower limb bleeding. The patients were followed up for 7.43 (5.21, 9.84) months. The programmed parameters of pacemaker were in the ideal range and stable during follow-up. At 3 and 6 months after operation, the left ventricular ejection fraction in LBBP group was higher than that in RVAP Group (at 3 months: (60.75±2.89)% vs. (57.35±3.33)%, P=0.004; at 6 months: (63.17±3.33)% vs. (56.17±3.97)%, P<0.001), NT-proBNP values was lower in LBBP group than that in RVAP Group (at 3 months: 822 (607, 1 150)ng/L vs. 1 052 (902, 1 536)ng/L, P=0.006; at 6 months: 440 (330,679)ng/L vs. 783 (588, 1 023)ng/L, P=0.001). At 1, 3 and 6 months after operation, the QRS duration was shorter in LBBP group than that in RVAP group (1 month: 99 (97, 107)ms vs. 126(124, 130)ms, P<0.001; 3 months: 98(96, 105)ms vs. 129(128, 133)ms, P<0.001; 6 months: 96(94, 104)ms vs. 130(128, 132)ms, P<0.001). Conclusions: For patients with permanent pacemaker indications after TAVI, LBBP is feasible, safe and reliable. It could improve the cardiac function in the short term, the long-term effect of LBBP needs to be further observed.
Aged ; Aged, 80 and over ; Bundle of His ; Cardiac Pacing, Artificial/methods* ; Electrocardiography/methods* ; Fluoroscopy ; Humans ; Male ; Retrospective Studies ; Stroke Volume ; Transcatheter Aortic Valve Replacement/adverse effects* ; Treatment Outcome ; Ventricular Function, Left

BACKGROUNDRisk factors that contribute to younger patients with lung cancer are still relatively unknown. The aim of this study was to compare the clinical characteristics, histological types, stages at diagnosis, treatment modalities and survival rates between young and old patients with lung cancer.

METHODSThe study was designed as a retrospective review of all lung cancer patients admitted to the Third Affiliated Hospital of Harbin Medical University from 1998 to 2008. Survival analyses using univariate and multivariate approaches were performed to compare the survival rates between different age groups and to discover potential prognostic factors.

RESULTSThis research included 3320 patients with primary lung cancer, of whom 626 (18.8%) were 45 years old or younger at the time of diagnosis. The percentage of smokers and the male to female ratios between the young and old patient groups were 51.27% vs. 70.6% (P < 0.001) and 1.99 vs. 2.13 (P = 0.4801), respectively. The young patient group had a higher incidence of adenocarcinoma and fewer surgeries. The 1-year, 3-year and 5-year survival rates in the young patient group were generally lower than those of the old patient group, with significant differences (P = 0.0232). The clinical stage of the tumor was a prognostic factor for both non-small cell lung cancer patients (P < 0.0001) and small cell lung cancer patients (P = 0.0002). Symptoms, diagnostic method, histology, smoking, treatment modality and body mass index were shown to have significant relationships with the survival of lung cancer patients (P < 0.05).

CONCLUSIONSPatients with lung cancer who are younger than 45 years old might have a significantly poorer prognosis than that of older patients. Symptoms, diagnosis method, histology, smoking, treatment modality and body mass index can be independent prognostic factors for lung cancer.

Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Female ; Humans ; Lung Neoplasms ; epidemiology ; Male ; Middle Aged ; Retrospective Studies ; Smoking ; Survival Rate ; Young Adult

OBJECTIVETo evaluate the effect and adverse effects of arsenic trioxide (As2O3) in the treatment of primary hepatocarcinoma patients, and conduct the pharmacokinetics study.

METHODSA total of one hundred and eleven advanced primary hepatocarcinoma patients in five centers were treated with As2O3 injection 7 - 8 mg/m(2) i.v. qd for 14 days and was repeated after 7 - 14 days. Evaluation of the clinical response and adverse effects was conducted after two cycles of treatment. The patient who had reached partial PR and SD was treated continuously until disease progression or intolerance.

RESULTSAmong the 102 patients evaluable for clinical efficacy analysis, there were 7 PR, 71 SD and 24 PD, the response rate was 6.9% and the clinical benefit rate was 76.5%. The quality of life was improved in 22.5% of patients. The pain relief rate was 71.7%, time to progress (TTP) was 97 days, and the median survival time (MST) was 195 days. The major adverse effects were reversible WHO I-II grade gastrointestinal reactions and bone marrow suppression. The results of pharmacokinetic study showed that the distribution and elimination characteristics in vivo was found to be a two-compartment model. The plasma elimination half-life was (23.94 ± 18.39) h.

CONCLUSIONSAs2O3 is effective in the management of primary hepatocarcinoma, with a significant analgesic effect. To some extent, it can extend TTP and MST in advanced liver cancer patients, while the treatment is well tolerated in the majority of patients.

Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; adverse effects ; pharmacokinetics ; therapeutic use ; Arsenicals ; administration & dosage ; adverse effects ; pharmacokinetics ; therapeutic use ; Carcinoma, Hepatocellular ; blood ; drug therapy ; pathology ; Disease Progression ; Female ; Follow-Up Studies ; Half-Life ; Humans ; Injections ; Leukopenia ; chemically induced ; Liver Neoplasms ; blood ; drug therapy ; pathology ; Lung Neoplasms ; drug therapy ; secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Staging ; Oxides ; administration & dosage ; adverse effects ; pharmacokinetics ; therapeutic use ; Quality of Life ; Remission Induction ; Survival Rate ; Vomiting ; chemically induced

OBJECTIVETo study the effect of resveratrol bovine serum albumin nanoparticles on SKOV3 cell line and its mechanisms.

METHODSThe morphological changes of the cells exposed to the nanoparticles were observed by apoptotic body/cell nucleus DNA staining under inverted microscope and fluorescence microscope, and the pathway of cell death was determined by phosphatidylserine translocation. Western blotting was performed to detect the activation of cyto.c, caspase-3 and caspase-9.

RESULTSDNA ladder was detected with gel electrophoresis and the cell death was partially inhibited by the pan-caspase inhibitor Z-VAD-FMK. Gel electrophoresis displayed both DNA ladder and smear in RES-BSANP exposed groups, while DNA ladder disappeared in Z-VAD-FMK group and only the smear was left. Cyto.c in the cytoplasm was released at 2 h, while the expression of caspase-9 protein reached the peak level at 4 h and caspase-3 expression was obvious enhanced at 8 h. At 4 h, caspase-9 expression in the cells exposed to 100 µmol/L RES-BSANP was decreased significantly as compared to the cells treated with 50 µmol/L RES-BSANP (P>0.05).

CONCLUSIONRES-BSANP can induce the necrosis and apoptosis of SKOV3 cells via either caspase-dependent or caspase-independent pathways.

Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Caspase 9 ; metabolism ; Cell Death ; drug effects ; Cell Line, Tumor ; Cytochromes c ; metabolism ; Female ; Humans ; Nanoparticles ; Ovarian Neoplasms ; pathology ; Stilbenes ; administration & dosage ; pharmacology

OBJECTIVETo search for genes related to cisplatin (DDP) sensitivity in small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) cell lines.

METHODSThe sensitivity of 4 SCLC lines and 6 NSCLC lines to DDP was evaluated by MTT assay. The expression of 1291 genes related to DDP-sensitivity in the 10 cell lines was measured by cDNA macroarray and the relationship between genes and DDP-sensitivity was analyzed.

RESULTS20 genes were negatively related to DDP-sensitivity in the SCLC and NSCLC cell lines, including Metallothionein, Cathepsin B, TIMP1, TNF-R1, TGF beta-induced 68 000, Cathepsin L, Galectin-1, Annexin 11, PAI-1, IGFBP4, UPAR, Jagged, CD13, alpha 1 A-AR, EphA2 (Eck), APC, RhoC, Fibromodulin, GATA-6 and HSC 70, while only procoagula and MDM2 were positively related to DDP-sensitivity in the SCLC and NSCLC cell lines. 10 genes were negatively related to DDP-sensitivity in the SCLC cell lines, including VHL, MMP-7, Elongin A, GSK-3 beta, SLC, Galectin-3, integrin beta 5, moesin, IKK beta, and ETV 1, while only AT2 was positively related to DDP-sensitivity in the SCLC cell lines. 10 genes were negatively related to DDP-sensitivity in the NSCLC cell lines, including Clusterin, FG FR-2, Thrombospondin 1, HSP 32, Lactate dehydrogenase A, P300, Thymosin beta l0, CD81, C/EBP gamma, Rak, while only CaMKK and TPA were positively related to DDP-sensitivity in the NSCLC cell lines.

CONCLUSIONThere were 45 genes related to DDP-sensitivity in 10 lung cancer cell lines. There were 22 co-expressed genes in both SCLC and NSCLC cell lines, and only 11 and 12 genes expressed in the SCLC and NSCLC cell lines, respectively.

Antineoplastic Agents ; pharmacology ; Carcinoma, Non-Small-Cell Lung ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cisplatin ; pharmacology ; Drug Resistance, Neoplasm ; Gene Expression Profiling ; methods ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms ; genetics ; metabolism ; pathology ; Oligonucleotide Array Sequence Analysis ; methods ; Small Cell Lung Carcinoma ; genetics ; metabolism ; pathology

OBJECTIVEThe aim of this study was to investigate the expression of connexin (Cx) and the function of gap junction intercellular communication (GJIC) in the carcinogenesis, progression and metastasis of gastric cancers.

METHODSImmunohistochemistry was used to detect the expression of Cx32 and Cx43 proteins in tissue samples. Indirect immunofluorescence assay was used to investigate the expression of Cx32 and Cx43 proteins in several gastric cancer lines of various differentiation grades. The expression of Cx43 in samples of gastric cancer tissue, adjacent normal tissue and in the gastric cancer cell lines of various differentiation grades was detected by Western blot. Scrape-loading dye transfer (SLDT) technique was used to detect the function of gap junction intercellular communication (GJIC) in the various cell lines.

RESULTSIn the normal gastric mucosa the expression rates of both Cx32 and Cx43 were 100%. In gastric cancers, the expression rates of Cx32 andCx43 were 49.5% (55/111) and 39.6% (44/111), respectively. There was a significant difference between their expression in normal and cancer tissues (P < 0.05). Age of the patients was not significantly correlated with the expression level of Cx32 and Cx43 (P > 0.05). Cx43 expression was significantly associated with the TMN stage, histological type, depth of infiltration and distant metastasis (P < 0.05), but Cx32 expression was not significantly correlated with depth of infiltration ( P > 0.05). In the cancer cell lines, a positive expression of Cx32 and Cx43 was detected in transfected human stomach mucosal cell line (CES-1) and human well differentiated stomach cancer cell line (N87), but negative in the poorly differentiated stomach cancer cell line (BGC-823) at all. Both Cx32 and Cx43 expression rates were 100% in the cell line GES-1. Cx32 expression rate was 49.0% and Cx43 expression rate was 55.0% in the cell line N87. But in the poorly differentiated cancer cell line BGC-823 both Cx32 and Cx43 expression was negative. GJIC function detection showed: GES-1 showed well GIJC function but no GIJC function in the cell lines N87 and BGC-823. The intensity of fluorescence was gradually decreasing from GES-1 cells to N87 cells and almost no fluorescence in BGC-823 cells. Western blotting showed that Cx43 expression in normal tissue was higher than that in gastric cancer tissue, and in the cell lines GES-1, N87 and BGC-823, the bands seemed decreasing progressively. There was very low expression in BGC-823 cells.

CONCLUSIONThe decreasing expression of connexin Cx32 and Cx43 is obviously correlated with the occurrence, development and metastatic potential of stomach cancers.

Adenocarcinoma ; metabolism ; pathology ; Adult ; Aged ; Cell Communication ; physiology ; Cell Line, Tumor ; Connexin 43 ; metabolism ; Connexins ; metabolism ; Down-Regulation ; Female ; Gap Junctions ; physiology ; Gastric Mucosa ; metabolism ; Humans ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Staging ; Stomach Neoplasms ; metabolism ; pathology

OBJECTIVETo investigate the anti-tumor effect and the mechanism of down-regulation of HER - 2 by cabamazepine in SKBR - 3 cells , a breast cancer cell line with HER - 2 over - expression.

METHODSWestern blotting was performed to evaluate the Her-2 expression level. The mRNA level of HER-2 was detected by RT-PCR. Immunoprecipitation was applied to detect the chaperon function and acetylation level of HSP90. The viability of cells was tested by MTT assay.

RESULTSCabamazepine treatment down-regulated HER-2 expression. Only HER-2 protein level decrease was observed with 10 micromol/L cabamazepine treatment, but both protein and mRNA expressions were inhibited by 100 micromol/L cabamazepine. Cabamazepine treatment could induce a higher acetylation level of HSP90 and destroy its chaperon function. Cabamazepine exerted synergism with Herceptin in promoting HER-2 protein degradation and synergism or potentiation with Herceptin or 17-AAG in inhibition of proliferation.

CONCLUSIONCabamazepine can reduce the expression of HER-2 and show a synergistic effect with Herceptin or 17-AAG. There may be potential benefits of carbamazepine for cancer therapy in future. HER-2;

Acetylation ; drug effects ; Antibodies, Monoclonal ; pharmacology ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; pharmacology ; Benzoquinones ; pharmacology ; Blotting, Western ; Breast Neoplasms ; metabolism ; pathology ; Carbamazepine ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Down-Regulation ; drug effects ; Drug Synergism ; Female ; Gene Expression Regulation, Neoplastic ; drug effects ; HSP90 Heat-Shock Proteins ; antagonists & inhibitors ; genetics ; metabolism ; Histone Deacetylase Inhibitors ; Humans ; Lactams, Macrocyclic ; pharmacology ; RNA, Messenger ; genetics ; metabolism ; Receptor, ErbB-2 ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Trastuzumab

OBJECTIVETo analyze the drug-sensitivity-related genes to anti-tumor drugs navalbine (NVB) and docetaxel (Doc) in four SCLC and six NSCLC cell lines.

METHODSThe sensitivity of 4 SCLC lines and 6 NSCLC lines to NVB and to Doc was determined with MTT test. The expression of 1291 anti-tumor drug sensitivity-related genes in the 10 cell lines was assayed by cDNA macroarray technique, and cluster analysis was performed to find the relationship between the results obtained by the above mentioned two measurements.

RESULTS(1) The anti-tumor effect of NVB on the 10 cell lines was apparently better than that of Doc. (2) The drug sensitivity-related genes in these 10 cell lines showed a more close positive correlation with Doc than that with NVB, whereas more genes showed negative correlation with NVB than that with Doc. But in 6 NSCLC cell lines, more genes showed the same positive or negative correlation with the two drugs. (3) 51 genes in the 10 cell lines showed correlation with Doc or NVB. 13 of them had negative correlation with Doc, 11 of them showed positive correlation. 24 of them showed negative correlation with NVB, 3 of them showed positive correlation. 67 genes in 6 NSCLC cell lines showed a correlation with sensitivity to Doc or NVB, among them 34 had negative correlation with Doc, 4 had positive correlation. 25 genes had negative correlation with NVB, 4 had positive correlation. (4) Rab 1, Rab 3, Rho B, Rho C, Rac 1, Rac 2, Gho GDI beta, CD44, integrin alpha5, integrin alpha6, integrin beta5, vinculin showed to be cytoskeleton-related genes differently expressing in SCLC or NSCLC cell lines.

CONCLUSIONThere is obvious difference in the drug sensitivity-related genes to NVB or Doc between SCLC and NSCLC cell lines.

Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Cluster Analysis ; Cytoskeletal Proteins ; metabolism ; Cytoskeleton ; genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Integrin alpha5 ; metabolism ; Lung Neoplasms ; genetics ; metabolism ; pathology ; Oligonucleotide Array Sequence Analysis ; Taxoids ; pharmacology ; Vinblastine ; analogs & derivatives ; pharmacology ; rab1 GTP-Binding Proteins ; metabolism ; rac1 GTP-Binding Protein ; metabolism

OBJECTIVETo evaluate the efficacy and adverse effects of transdermal fentanyl in management of patients with cancer pain.

METHODSA total of 4492 patients (aged 3-90) with cancer pain were enrolled in this multicenter study. The mean age was 58.5 (3 approximately 90) years old. All patients received transdermal fentanyl. The patients were asked to record the attacks of pain, quality of life, and any side effects of the treatment.

RESULTSBaseline mean pain intensity was 7.37. On days 1, 3, 6, 9, 15, and 30, the mean scores of pain were decreased to 4.04, 2.98, 2.52, 2.19, 1.85 and 1.61, respectively (P < 0.01). The effective rate was 96.8%. The mean doses of fentanyl were 32.37 microg/h (25-200 microg/h) on the initial day, 42.57 microg/h and 49.57 microg/h (25-225 microg/h) on days 15 and 30. The quality of life was significantly improved after treatment (P < 0.01). The common side effects were constipation (9.8%), nausea (13.6%), dizziness (6.5%), vomiting (3.9%), sedation (2.0%) and respiratory depression (0.2%). The incidence of constipation was related to age, and the incidence of vomiting and difficulty of urination was related to gender. The majority (84.5%) of patients preferred continuation of the treatment with transdermal fentanyl.

CONCLUSIONTransdermal fentanyl for the patients with cancer pain is effective, safe, convenient and can improve the quality of life. Transdermal fentanyl can be recommended as one of first-line drugs for the treatment of patients with moderate to severe cancer pain.

Administration, Cutaneous ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Analgesics, Opioid ; administration & dosage ; adverse effects ; Child ; Child, Preschool ; Digestive System Neoplasms ; complications ; Female ; Fentanyl ; administration & dosage ; adverse effects ; Humans ; Lung Neoplasms ; complications ; Male ; Middle Aged ; Pain Measurement ; Pain, Intractable ; drug therapy ; etiology ; Quality of Life