Background and purpose:New treatment strategies should be explored for non-small cell lung cancer (NSCLC) patients after the failure of the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). To compare the efficacy and toxicities of chemotherapy in combination with EGFR-TKI or single chemotherapy in advanced NSCLC patients with EGFR-TKI resistence. Methods:In this study, 18 patients were enrolled. Eight patients were treated by chemotherapy combined with EGFR-TKI (CE group);10 patients were treated by single chemotherapy (E group), 21 days for one cycle. All patients received at least 2 cycles of treatment. Results:All 18 patients had been evaluated. The CE group was similar to the E group in objective response rate (ORR:25%vs 10%, P=0.832). The CE group was higher than the E group in disease control rate (DCR:87.5%vs 30%, P=0.046). The median PFS was longer in CE group (3.5 months vs 2.4 months, P=0.05). The CE group was higher than the E group in rash (75%vs 10%, P<0.05). The grade 3-4 toxicities did not have significantly differences between the two groups (P>0.05). Conclusion:Though there was no significant difference in ORR between the 2 groups (P>0.05), the CE group was superior to the E group in DCR and PFS. Patients with retreatment of advanced NSCLC after the failure of EGFR-TKI can be controlled by continued EGFR-TKI and chemotherapy.

Background and purpose: Capecitabine, which is widely used in the first-line treatment of advanced breast cancer, was known little in the maintenance treatment of advanced breast cancer. The present study aimed to explore the efficacy and safety of capecitabine in the maintenance treatment of advanced breast cancer. Methods: A total of 62 advanced breast cancer patients confirmed by histopathology and/or cytology, who had been evaluated as CR/PR/SD after first-line treatment, were divided into two groups. Thirty-one of them received capecitabine orally as maintenance treatment, while the others were followed up without any treatment. The clinical response was evaluated every two cycles. Results:The median time to progression (TTP) of the capecitabine group was 12 (2-24) months, which was signiifcantly higher than the control group. In the subgroup analysis, similar results were detected in the premenopausal group, hormone receptor positive group, HER-2 positive group, metastasis group, no capecitabine used history group. Among the capecitabine group,the overall response rate (CR+PR) was 19.4%, and the disease control rate (CR+PR+SD) was 74.2%. The most common adverse effects were hand-foot syndrome, hematologic toxicity and gastrointestinal reaction, all of which could be tolerated. The overall score of the capecitabine group evaluated by the Chinese vesion of the FACT-B was signiifcantly higher than the control group. Conclusion:Capecitabine can effectively and tolerably prolong survival time and improve the quality of life of patients in the maintenance treatment of advanced breast cancer.

Objective:To investigate the effect of sodium butytate (different concentrations) on the growth and proliferation of rat liver oval cell line WB-F344, and to discuss the conditions and rules for sodium butyrate-inducd WB-F344 cells differentiation into biliary lineage in vitro. Methods: WB-F344 cells were treated with sodium butyrate (0.75, 2.25, 3.75, 4.5 mmol/L) and the cell growth and morphological changes were observed; routinely cultured WB-F344 cells were taken as control. The changes of CK19 protein expression were examined immunohistochemically after WB-F244 cells were treated with 3.75% sodium butyrate; and the expression of phenotypic markers, such as ?-glutamyltransferase (GGT) ,?4-integrin, CK19, AFP and ALB at mRNA level were determined by RT-PCR. Untreated WB-F344 cells were used as blank control. Results: We found that sodium butyrate inhibited the growth of WB-F344 cells. The optical densities were significantly decreased in 3.75 and 4.5 mmol/L groups compared with that in control group(P

Background and purpose:In the process of gastric cancer development, cytothesis and apoptosis, and endoplasmic reticulum stress (ERS) are very important pathological processes. Glucose regulated protein 78 (GRP78) and phosphorylated form of extracellular signal-regulated protein kinase (pERK) play important roles in it. This study aimed to investigate the expression of GRP78 and pERK in gastric adenocarcinoma, chronic atrophic gastritis and superficial gastritis, and the role of GRP78 and pERK in the development of gastric adenocarcinoma. Methods:Gastric adenocarcinoma, chronic atrophic gastritis and superifcial gastritis tissues in 60 cases respectively were employed in the study. We chose 25 fresh tissue samples from each group, and the level of GRP78 and pERK mRNA in different tissues were detected by RT-PCR assay. The expressions of GRP78 and pERK in different parafifn samples were detected using immunohistochemistry assay. In addition, the relationships between GRP78 and pERK expression and age, gender, differentiation, invasion, disease stage, and lymphoid node metastasis were analyzed. Results: The expression level of GRP78 and pERK mRNA in gastric adenocarcinoma(1.26±0.18, 2.35±0.36) were significantly higher than chronic atrophic gastritis (0.89±0.25, 1.18±0.25) and superficial gastritis (0.29±0.09, 0.68±0.10, P<0.01). The positive ratio of GRP78 expression in gastric adenocarcinoma, chronic atrophic gastritis and superficial gastritis were 78.3%, 46.6%, 6.7%. The positive ratios of pERK expression were 88.3%, 43.3%, 5.0%, respectively. The GRP78 and pERK expression in different tissues were signiifcantly different (P<0.01). GRP78 and pERK expression were positively correlated with differentiation, disease stage and lymph node metastasis. There was a positive correlation between the gene and protein expression of GRP78 and pERK with a Pearson correlation value of 0.307 and 0.368, respectively. Both univariate and multivariate analysis revealed that GRP78 was related to the prognosis of gastric adenocarcinoma. Conclusion:GRP78 and pERK may play an important role in the transition of normal gastric cells to malignant cells. The expression of these two genes enhances tumor progression. Overexpression of GRP78 and pERK is significantly correlated with poor prognosis in patients with gastric adenocarcinoma. The determination of the expression of GRP78 and pERK might be helpful for the prevention, early diagnosis of gastric carcinoma. Particularly, GRP78 is valuable for the judgement of prognosis, and might be a new target for the treatment of gastric adenocarcinoma.

OBJECTIVE To evaluate the infection of central venous catheterization in tumor patients with chemotherapy and analyze its risk factors and the role of nursing intervention. METHODS The prospective overall monitoring method was used,including catheterization,maintenance,observation and monitoring. RESULTS Of 446 cases with chemotherapy,the infection rate was 2.24% (10 cases). The infection mainly correlated with age,catheterization time,chemotherapy duration,venous nutrition,complication and hormone. CONCLUSIONS The infection of central venous catheterization is inevitable due to multiple risk factors. The measures to prevent and reduce hospital infection are holding the key steps of central venous catheterization,executing the management system of sterilization,keeping tract smooth,cutting down time of central venous catheterization and strengthening nursing education about central venous catheterization.

OBJECTIVETo discuss the influence of Suoquan capsule (SQJN) on the detrusor of D-galactose mimetic rats, and to explore the mechanism of reducing urine.

METHODInvestigate the enzymes (ATPase, SDH, SOD, MDA, Na+ -K+ -ATPase, Ca2+ - Mg2+ -ATPase) which influence the production and excretion of urine and the reactivity of urinary detrusor strips to different concentrations of ISO and ATP.

RESULTCompared with the model group, the activity of SOD, Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase and SDH increased significantly in aging rats after administrating SQJN (P < 0.01); the complaisance and elasticity of bladder also increased (P < 0.05). The frequency of spontaneous contraction and the MDA decreased significantly (P < 0.05-0.01). The decreased relaxation response to ISO and increased contractile response to ATP were also changed after administrating SQJN.

CONCLUSIONSQJN can regulate the metabolism of fluid through recovering the normal physiologic function of the detrusor of bladder.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Galactose ; adverse effects ; Humans ; Male ; Muscle Contraction ; Muscle, Smooth ; physiology ; Rats ; Urinary Bladder ; drug effects ; metabolism ; physiopathology ; Urinary Incontinence, Urge ; chemically induced ; drug therapy ; metabolism ; physiopathology ; Urination ; drug effects

OBJECTIVETo investigate the effect and mechanism of B16F10-ESAT-6-gpi/IL-21 tumor cell vaccine on pulmonary metastasis in mouse model of melanoma.

METHODSTwelve 8-week old female C57BL/6 mice were used in this study. The mice were injected with wild-type B16F10 cells through tail vein after immunization with B16F10-ESAT-6-gpi/IL-21 tumor cell vaccine, and the pulmonary metastasis was observed. The CD4(+) and CD8(+) T cells were isolated by magnetic activated cell sorting, and then used for the detection of CFSE/7-AAD cytotoxicity by flow cytometry. Serum from the mice immunized with tumor-cell vaccine was used to detect IFN-γ expression by ELISA. The expression of TGF-β2, ZEB1, E-cadherin, and N-cadherin of tumor tissues was detected by RT-PCR and immunofluorescence, respectively.

RESULTSThe mice vaccinated with B16F10-ESAT-6-gpi/IL-21 had significantly fewer nodules in the lung and lower lung weight [(285.8 ± 19.01) mg vs. (406.3 ± 27.12) mg], with lower levels of TGF-β2, ZEB1 and N-cadherin proteins but higher level of E-cadherin protein within the tumor tissue, as compared with the control mice. Meanwhile, the immunized mice had significantly increased CD8(+) T cell killing activity [(42.62 ± 3.465)% vs. (22.29 ± 1.804)%] and IFN-γ expression level [(55.200 ± 7.173) pg/ml vs. (6.435 ± 1.339) pg/ml] over the control mice.

CONCLUSIONSThe B16F10-ESAT-6-gpi/IL-21 vaccine can inhibit the metastasis of melanoma in the lung in vaccinated melanoma-bearing mice. This inhibitory effect is associated with CD8(+) T cell immune response and a higher level of IFN-γ, which may influence on the mesenchymal-epithelial transition of tumor cells.

Animals ; CD8-Positive T-Lymphocytes ; immunology ; Cadherins ; metabolism ; Cancer Vaccines ; immunology ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Female ; Homeodomain Proteins ; metabolism ; Humans ; Interferon-gamma ; metabolism ; Interleukins ; immunology ; Lung ; pathology ; Lung Neoplasms ; metabolism ; secondary ; Melanoma ; metabolism ; pathology ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Organ Size ; Transcription Factors ; metabolism ; Transforming Growth Factor beta2 ; metabolism ; Zinc Finger E-box-Binding Homeobox 1

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia