Objective To investigate the expression and clinical significance of thyroid transcription factor-1(TTF-1)and chromogranin A(CgA)in small cell lung cancer(SCLC). Methods The expressions of TTF-1 and CgA protein in 68 cases of SCLC tissues and 20 cases of normal lung tissues were examined by immunohistochemistry method,and their correlations with clinical features of SCLC were analyzed. Results The positive rates of TTF-1 and CgA protein in SCLC were 88. 2%(60 / 68)and 70. 6%(48 / 68),respec-tively,and they were higher than those in normal lung tissue[10. 0%(2 / 20)and 5. 0%(1 / 20);χ2 = 45. 442, P = 0. 000;χ2 = 26. 941,P = 0. 000]. The expression of TTF-1 protein was not related to the patients' age,sex and tumor size,while closely related to smoking index(χ2 = 4. 131,P = 0. 042),lymph node metastasis(χ2 =5. 488,P = 0. 019)and clinical stage(χ2 = 6. 011,P = 0. 014). The expression of CgA protein was not related to the patients' age,sex,tumor size and smoking index,while closely related to lymph node metastasis(χ2 =9. 895,P = 0. 002)and clinical stage(χ2 = 4. 145,P = 0. 042). Conclusion TTF-1 and CgA protein are highly expressed in SCLC,especially in the patients with lymph node metastasis and extensive disease.

OBJECTIVE: To observe the influence of arecoline (Ar) on human sperm motility in vitro. METHODS: 50 cases of normal human male sperm which had been screened were incubated in different concentration of Ar solution (10 ?g?mL-1,50 ?g?mL-1,100 ?g?mL-1),taking the optimized sperm as control group. After the incubation lasting 0.5,1,2 h, computer assisting sperm analysis system (CASA) was used to analyze the Mot, (a+b) PM,VCL and VSL of sperm. RESULTS: The Mot of sperm incubated in 10 ?g?mL-1 Ar solution for 1 h was significantly different from that of control group(P

OBJECTIVETo explore the preoperative diagnostic value of ¹⁸F-fluorodexyglucose positron emission tomography combined with contrast enhanced computed tomography (¹⁸F-FDG PET-ceCT) in patients with colorectal cancer liver metastasis.

METHODSClinical and imaging data of 58 patients with suspicious colorectal cancer liver metastasis between April 2010 and March 2013 were retrospectively evaluated. All the patients underwent ¹⁸F-FDG PET-ceCT. On the basis of definitive diagnosis, the sensitivity, specificity, accuracy and consistency of routine PET-CT, ceCT and ¹⁸F-FDG PET-ceCT were calculated.

RESULTSA total of 147 suspicious lesions of colorectal cancer liver metastasis were found in 58 patients. Finally, 125 lesions were confinmed as malignant, of which 58 (46.4%) lesions were less than 1.0 cm. The other 22 lesions were confinmed as benign, of which 17 (77.3%) lesions were less than 1.0 cm. The diagnostic accuracy of routine PET-CT, ceCT and ¹⁸F-FDG PET-ceCT in colorectal cancer liver metastasis for the lesions more than 1.0 cm was 100%, 93.1%, 100% respectively, and the consistency with final diagnosis was perfect, moderate, and perfect respectively (Kappa value 01.00, 0.408, 1.00). For the lesions less than 1.0 cm, the accuracy was 42.7%, 78.7%, 94.7% respectively, and the consistency with definitive diagnosis was insignificance, fair, and almost perfect respectively (Kappa value -0.005, 0.305, 0.848). The area under curve(AUC) was 0.525 (95% CI: 0.407-0.462) for routine PET-CT, 0.651(95% CI:0.532-0.757) for ceCT, and 0.924 (95% CI:0.839-0.972) for ¹⁸F-FDG PET-ceCT respectively. The AUC of ¹⁸F-FDG PET-ceCT was significantly larger than that of routine PET-CT (Z=5.559, P<0.05) or ceCT (Z=4.183, P<0.05).

CONCLUSION(18)F-FDG PET-ceCT can improve the diagnostic accuracy for smaller lesions of colorectal cancer liver metastasis.

Colorectal Neoplasms ; Contrast Media ; Fluorodeoxyglucose F18 ; Humans ; Liver Neoplasms ; Multimodal Imaging ; Positron-Emission Tomography ; Retrospective Studies ; Tomography, X-Ray Computed

OBJECTIVETo observe the effect of activation of Notch1 signaling pathway by Notch intracellular domain (NICD) plasmid transfection on pancreatic cancer cell proliferation and explore the underlying mechanism.

METHODSThe transfection rates were observed under microscope with fluorescence stimulation, and mRNA expression levels of Hes1 were detected by real-time PCR. Cell proliferation changes were evaluated by CCK-8 after NICD and control plasmid transfection in pancreatic cancer cells. Caspase 3 activity was examined using a caspase 3 detection kit.

RESULTSThe transfection rates of NICD plasmid were up to 80% by fluorescence stimulation observation. Hes1 expression was significantly increased after NICD plasmid transfection, suggesting the activation of Notch1 signaling pathway. NICD plasmid transfection significantly promoted cancer cell proliferation compared to control plasmid transfeciton. The activities of caspase 3 were obviously decreased after NICD plasmid transfection in 3 pancreatic cancer cell lines.

CONCLUSIONActivation of Notch1 signaling pathway by NICD plasmid transfection can promote the proliferation of pancreatic cancer cells by inhibiting the apoptosis pathway.

Apoptosis ; Basic Helix-Loop-Helix Transcription Factors ; metabolism ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Homeodomain Proteins ; metabolism ; Humans ; Pancreatic Neoplasms ; metabolism ; pathology ; Plasmids ; Receptor, Notch1 ; genetics ; metabolism ; Signal Transduction ; Transcription Factor HES-1 ; Transfection

Chronic heart failure （CHF） is a clinical syndrome resulting from damage to the myocardium， leading to changes in the function or structure of the heart and causing reduced pumping and/or filling capacity. Its pathogenesis is complex， potentially involving myocardial fibrosis， apoptosis and autophagy of cardiomyocytes， inflammatory responses， oxidative stress， and myocardial remodeling. Our team believes that the fundamental pathogenesis of CHF is heart-Qi deficiency， with the disease location in the heart， which is closely related to other organs. Due to heart-Qi deficiency， blood circulation weakens， leading to blood stasis， which in turn generates water-dampness and phlegm turbidity that accumulate over time and become toxic. The interaction between water stasis， Qi stagnation， blood stasis， and phlegm toxicity further weakens the body， creating a vicious cycle （deficiency， stasis， water retention， and toxicity） that is difficult to resolve. Under physiological conditions， the nuclear factor-κB （NF-κB） signaling pathway functions normally， maintaining vital activities and immune responses. However， in pathological states， the NF-κB signaling pathway becomes imbalanced， triggering inflammatory responses and other issues. Research has shown that traditional Chinese medicine （TCM） can regulate the NF-κB signaling pathway through multiple pathways， targets， and effects， effectively improving the progression of CHF. As a result， this has become a research hotspot for the prevention and treatment of the disease. Guided by TCM theory， this research group reviewed the literature to summarize the activation pathways of the NF-κB pathway and its interactions with other pathways. Additionally， the group summarized the research progress on the regulation of the NF-κB pathway in the treatment of CHF using Chinese medicines， their active ingredients， Chinese medicine compounds， and Chinese patent medicines. This study is expected to clarify the mechanisms and targets by which TCM treats CHF by regulating the NF-κB pathway， thereby guiding clinical treatment and drug development for CHF.

Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). This targeted liposome is prepared through a mature preparation process, and indoleamine-2,3-dioxygenase (IDO) inhibitor NLG919 was encapsulated into it. Moreover, mediated by the enhanced permeability and retention effect (EPR effect) and AUNP-12, NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues. At the same time, the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12, thus realizing the precise block of PD-1 signal pathway, and restoring the activity of T cells. The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.

As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.