To investigate the function and regulation mechanism of ATP-binding cassette, subfamily G, member 2 (ABCG2) in retinoblastoma cancer stem cells (RCSCs), a long-term culture of RCSCs from WERI-Rb1 cell line was successfully established based on the high expression level of ABCG2 on the surface of RCSCs. To further explore the molecular mechanism of ABCG2 on RCSCs, a microRNA that specifically targets ABCG2 was predicted. Subsequently, miR-3163 was selected and confirmed as the ABCG2-regulating microRNA. Overexpression of miR-3163 led to a significant decrease in ABCG2 expression. Additionally, ABCG2 loss-of-function induced anti-proliferation and apoptosis-promoting functions in RCSCs, and multidrug resistance to cisplatin, carboplatin, vincristine, doxorubicin, and etoposide was greatly improved in these cells. Our data suggest that miR-3163 has a significant impact on ABCG2 expression and can influence proliferation, apoptosis, and drug resistance in RCSCs. This work may provide new therapeutic targets for retinoblastoma.
3' Untranslated Regions ; ATP Binding Cassette Transporter, Sub-Family G, Member 2/antagonists & inhibitors/genetics/*metabolism ; Antagomirs/metabolism ; Antineoplastic Agents/toxicity ; Apoptosis/drug effects ; Base Sequence ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Resistance, Neoplasm/drug effects ; Gene Silencing ; Humans ; MicroRNAs/antagonists & inhibitors/genetics/*metabolism ; Neoplasm Proteins/antagonists & inhibitors/genetics/*metabolism ; Neoplastic Stem Cells/*metabolism ; Retinoblastoma/metabolism/pathology ; Sequence Alignment ; Transfection

Objective:To investigate the influence of Jinshuibao tablet on immune function, therapeutic efficacy and safety in treatment of advanced lung squamous cell carcinoma patients treated by chemotherapy.Methods:The clinical data of 124 patients with stage Ⅳ lung squamous cell carcinoma who were admitted to Shanxi Provincial Cancer Hospital from January 2015 to December 2017 were retrospectively analyzed, including 60 patients treated by Jinshuibao tablet combined with chemotherapy (the observation group) and 64 patients treated by chemotherapy alone (the control group). The changes of immune function, therapeutic effect, and side effects were compared between the two groups.Results:The percentage of CD4 + cells after treatment [(33.4±8.9)% vs. (45.5±11.8)%, t = 2.71, P < 0.05] and CD4 +/CD8 + (0.9±0.3 vs. 1.5±0.4, t = 3.31, P < 0.05) in the observation group was increased compared with that before treatment, CD8 + cells was decreased compared with that before treatment [(30.9±8.6)% vs. (21.1±8.1)%, t = 2.42, P < 0.05], interferon-γ (IFN-γ) [(7.7±2.8)% vs. (14.1±2.4)%, t = 2.74, P < 0.05] and interleukin-2 (IL-2) [(8.8±3.2)% vs. (12.7±1.6)%, t = 2.96, P < 0.05] was increased compared with that before treatment. The percentage of CD3 + cells [(57.9±8.2)% vs. (45.2±10.8)%, t = 2.70, P < 0.05], CD4 + cells [(32.9±9.0)% vs. (22.8±9.6)%, t = 3.19, P < 0.05], NK cells [(14.9±3.1)% vs. (9.3±1.4)%, t = 2.97, P < 0.05] in the control group was decreased compared with that before treatment. Tumor necrosis factor α (TNF-α) was decreased compared with that before treatment [(6.8±1.4)% vs. (4.3±0.5)%, t = 3.23, P < 0.05]. There was a statistically significant difference in the level of T-cell subsets of both groups after treatment (all P <0.05); and the level of CD3 +, CD4 +, CD4 +/CD8 +, NK cells in the observation group was higher than that in the control group; CD8 + cell in the observation group was lower than that in the control group. There was no statistical difference in the level of IFN-γ, IL-2, TNF-α of both groups before treatment (all P > 0.05); the level of IFN-γ, IL-2, TNF-α in the observation group was higher than that in the control group after treatment, and the difference was statistically significant of both groups (all P < 0.05). The total effective rate of the observation group was higher than that in the control group, and the difference was statistically significant [31.3% (20/64) vs. 48.3% (29/60), χ 2 = 4.538, P = 0.033]; and the disease control rate in the observation group was higher than that in the control [56.3% (36/64) vs. 71.7% (43/60), χ 2 = 5.276, P = 0.022]. There was no significant difference between the two groups in adverse reactions of chemotherapy (all P > 0.05). Conclusion:Jinshuibao tablet combined with chemotherapy can improve the immune function and the efficacy of chemotherapy for patients with advanced lung squamous cell carcinoma.

Objective:To investigate the expression of programmed death ligand 1 (PD-L1) in rectal cancer tissues and the correlation of PD-L1 expression with clinicopathological characteristics and overall survival of patients.Methods:The clinical data of 200 newly treated rectal cancer patients in Shanxi Provincial Cancer Hospital from January 2014 to December 2015 were retrospectively analyzed. The expression of PD-L1 in rectal cancer tissues was detected by immunohistochemistry. The correlations of PD-L1 expression with gender, age, tumor T stage, lymph node metastasis, tumor differentiation, histological type, tumor TNM stage, neutrophil-to-lymphocyte ratio (NLR) and overall survival of patients were analyzed.Results:The positive expression rate of PD-L1 was 24% (48/200). The positive expression rate of PD-L1 was high in patients with lymph node metastasis and high NLR (≥ 3.5) (both P < 0.05). The 5-year overall survival rate in PD-L1-positive group was 42%, and the PD-L1-negative group was 59%, and the difference between the two groups was statistically significant ( P < 0.05). The results of multivariate analysis showed that lymph node metastasis ( HR = 3.456, 95% CI 2.148-5.556, P < 0.01), NLR ≥ 3.5 ( HR = 1.871, 95% CI 1.169-2.996, P = 0.009), and PD-L1-positive expression ( HR = 2.187, 95% CI 1.373-3.484, P = 0.001) were independent adverse influencing factors for the overall survival of rectal cancer patients. Conclusion:PD-L1 is highly expressed in rectal cancer tissues, and the positive expression of PD-L1 is associated with poor overall survival of patients.

Objective To observe the effects of"Sleep Recipe"on the behavior,brain tissue and central neurotransmitters of insomnia rats.Methods The male rats with SD were randomly divided into control group,model group,sleep formula group,and eszolam group,with 10 rats in each group,and the insomnia model was constructed by intraperitoneal injection of P-chlorphenylalanine(PCPA).After successful modeling,the control group and the model group were given saline gavage,and the medylom group and eszolam group were given drug gavage.The insomnia-like behavior of rats in each group was evaluated by pentobarbital sodium correction experiment and open field experiment,Hematoxlin and eosin(HE)staining observed the pathological changes of rat cerebral cortex,hippocampus,and hypothalamic tissue,and Enzyme-linked mmunosorbent assay(ELISA)was used to determine the expression levels of Gamma-aminobutyric acid(GABA),5-hydroxytryptamine(5-HT).Results The sleep latency of rats in the model group was significantly elongated(P<0.01),while the sleep time was less(P<0.01),and the mental state and fur color were poor,significantly decreased in body weight(P<0.01).Compared with the model group,the sleep latency was significantly shortened(P<0.01),the sleep duration was significantly prolonged(P<0.01),and the body mass was significantly increased(P<0.05,P<0.01);In the open field experiment,the total activity distance of rats in the model group increased,the average speed and central region residence time decreased(P<0.05),the total activity distance of rats in the Sleep Formula group and Eszolam group decreased significantly(P<0.05),the average speed increased and the central region residence time increased(P<0.05).HE results showed that the number of neurons,morphological structure and arrangement of neurons,such as cerebral cortex,hippocampus and hypothalamus in the model group,were damaged to varying degrees,and the sleep formula group and estazolam group were significantly improved.ELISA results showed that the expression of 5-HT and GABA in the cerebral cortex and hypothalamus of rats in the model group was significantly reduced(P<0.01,P<0.05),and the expression of GABA in hippocampal tissues was also significantly reduced(P<0.01).The protein expression levels of cerebral cortical GABA,hypothalamic GABA and 5-HT in the Sleep Formula group were significantly increased(P<0.01).Conclusion Sleep Formula can improve the mental state,restore normal body weight,improve sleep efficiency,and reduce anxiety and tension in insomnia rats.The mechanism may be related to increasing the content of 5-HT and GABA,and inhibiting the spread and conduction of hypothalamic and brainstem pro-awakening nuclei.