This research explored the synergistic effects and the potential mechanisms of RCE-4 and various nonsteroidal anti-inflammatory drugs (NSAIDs) on the proliferation of cervical cancer Ca Ski cells. The MTT assay and CalcuSyn V2.0 software were used to detect cell proliferation and calculate the combination index (CI); the expression levels of various proteins were analyzed using Western blot assay; mitochondrial membrane potential (MMP) was assessed using JC-1 staining; acridine orange/ethidium bromide (AO/EB) double-fluorescence staining was used to detect the apoptosis of Ca Ski cells; a co-immunoprecipitation (Co-IP) assay was used to analyze the relative content of Bcl-2-Beclin 1 complex in Ca Ski cells. The results demonstrate that the combination of RCE-4 and NSAIDs increases the inhibition of Ca Ski cells compared to the single-RCE-4 group, and celecoxib provided the best synergistic effect among the four NSAIDs tested, with a CI of 0.32. The combination of RCE-4 and celecoxib significantly down-regulated the expression of cyclooxygenase-2 (COX-2) and nuclear transcription factor-κB (NF-κB), and promoted the expression of non-steroidal anti-inflammatory drugs activity gene-1 (NAG-1). In addition, autophagy induced by RCE-4 was markedly inhibited in combination with celecoxib, which was associated with down-regulation of the expression of microtubule-associated protein 3 (LC3)-II, Beclin 1, p62 and autophagy-related gene (ATG) 3/4B/5/7/14. RCE-4-induced apoptosis was significantly enhanced by altering the depolarization of mitochondrial membrane potential and the expression of B cell lymphoma-2 (Bcl-2), B cell lymphoma-xl (Bcl-xl), Bcl-2 associated X protein (Bax), Bcl-2/Bcl-xl-associated death promoter (Bad) and cleaved cysteinyl aspartate specific proteinase (cleaved-caspase) 3/7/9. Furthermore, the formation of the Bcl-2-Beclin 1 complex was significantly inhibited in Ca Ski cells treated with RCE-4 in combination with celecoxib. Taken together, this research shows that the combination of RCE-4 and celecoxib has a significant synergistic effect on the proliferation of Ca Ski cells by promoting apoptosis, inhibiting autophagy and disturbing the formation of the Bcl-2-Beclin 1 complex, which may be a novel strategy to increase the sensitivity of anti-cervical cancer drugs.

Aneurysm ; complications ; therapy ; Cardiac Catheterization ; instrumentation ; Child ; Heart Septal Defects, Ventricular ; complications ; therapy ; Humans ; Septal Occluder Device

Acute Disease ; Bone Neoplasms ; diagnosis ; secondary ; Carcinoma, Squamous Cell ; classification ; diagnosis ; Humans ; Hypercalcemia ; complications ; Lung Neoplasms ; complications ; diagnosis ; Male ; Middle Aged ; Myocardial Infarction ; diagnosis ; etiology

AIMTo study the effect of genistein (GEN) on contractility of isolated right ventricular muscles in guinea pig and its mechanisms.

METHODSIsolated guinea pig ventricular muscles were suspended in organ baths containing K-H solution.After an equilibration period, the effect of GEN on contraction of myocardium was observed.

RESULTSGEN and isoprenaline hydrochloride had the positive inotropic effects on contractity of myocardium. Meanwhile, the effect of GEN (1-100 micromol x L(-1)) was in dose-dependent manner. Propranolol (1 micromol x L(-1)) and verapamil hydrochloride (0.5 micromol x L(-1)) attenuated the positive inotropic effect of isoprenaline hydrochloride (1 micromol x L(-1)), but did not change the effect of GEN (50 micromol x L(-1)). Further more, the enhancement of the contraction induced by elevation of extracellular Ca2+ concentration in ventricular muscles had no change after pretreatment with GEN (1.10 micromol x L(-1)). In addition,the positive inotropic effect of GEN was inhibited partially by tamoxifen (1 micromol x L(-1)) and SQ22536 (1 micromol x L(-1)), also, could be attenuated by bpV (1 micromol x L(-1)).

CONCLUSIONGEN has the positive inotropic effect on guinea pig ventricular muscles, which is not related to the activation of beta adrenoceptor, Ca2+ channel on cell membrane,but may involve in cAMP of intracellular signal transduction and tyrosine kinase pathway.

Animals ; Cardiotonic Agents ; pharmacology ; Cyclic AMP ; metabolism ; Genistein ; pharmacology ; Guinea Pigs ; Heart Ventricles ; drug effects ; In Vitro Techniques ; Male ; Myocardial Contraction ; drug effects ; Protein-Tyrosine Kinases ; metabolism

OBJECTIVETo study the role of hypoxia-inducible factor 1 alpha (HIF1alpha) on knee cartilage degeneration,and to explore the effects and mechanisms of Chinese herbal compound Yiqi Huayu prescription on HIF-1alpha gene knockout mice on knee cartilage degeneration.

METHODSThe 4-month and 6-month HIF-1alpha gene knock out mice were obtained by interbreeding, and divided into HIF-1alpha +/+ 4-month mice group,HIF-1alpha -/- 4-month mice group,HIF-1alpha +/+ 6-month mice group and HIF-1alpha -/- 6-month mice group, 3 mice in each group. And then the 2-month-old HIF-1alpha gene knock out mice were randomly divided into Yiqi Huayu prescription group and physiological saline group. There were 6 mice in each group. After 2 months' drug administration, the knee joint of mice was collected, and the Mankin score were evaluated; Safranine-fast green staining, HE Staining, and immunohistochemistry analysis for VEGF, Col X, Col II, MMP-13 and Sox-9 were performed erespectively.

RESULTS(1) Compared to the results in the HIF-1alpha+/+ mice groups, the HIF-1alpha-/- mice developed aging related cartilage loss and bony tissue appearance, cartilage defects increased,and cells reduced. In HIF-1alpha-/-4-month mice and 6-month mice group, the expresion of Col II and Sox9 decreased, and the expression of Col X, MMP-13 and VEGF increased. (2) Compared to the physiological saline group, the ossification and defect of knee joint cartilage reduced of mice in the Yiqi Huayu prescription group, the cartilage cell distribution was more uniform, and the total number of cells increased. The expression of type II collagen and Sox9 protein increased, expression of Col X, MMP-13 and VEGF protein decreased of mice in the Yiqi Huayu prescription group.

CONCLUSIONThe knee cartilage degenerates in the HIF-1alpha cKO mice, and the degeneration increased with age adding. The Yiqi Huayu prescription can delay the degeneration of knee cartilage of HIF-1alpha cKO mice.

Animals ; Cartilage Diseases ; drug therapy ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; deficiency ; genetics ; Joint Diseases ; drug therapy ; genetics ; metabolism ; Knee Joint ; metabolism ; physiopathology ; Male ; Mice ; Mice, Knockout

Objective To compare diagnostic value of ~(18)F-fluoredeoxyglucose (FDG) PET/CT with contrast-enhanced CT in detecting primary hepatic carcinoma and postoperative recurrence.Methods Twenty-five cases of primary hepatic carcinoma or postoperative recurrent tumor underwent whole-body ~(18)F-FDG PET/CT and contrast-enhanced CT within one week's interval.They were retrospectively reviewed and the difierences between these two modalities were investigated.Results Of these 25 cases,there were 13 cases with primary hepatocellular carcinoma.1 case with intrahepatic cholangiocarcinoma and 11 cases with postoperative recurrence.The sensitivity of 18 F-FDG PET/CT and contrast-enhanced CT in diagnosing primary hepatic carcinoma was 78.6%(11/14) and 92.9%(13/14),and sensitivity in diagnosing postoperative recurrent was 100.0%(11/11) and 63.6%(7/11) respectively.Conclusion Contrast-enhanced CT may have a slight advantage over PET/CT in detecting primary hepatic carcinoma,but ~(18)F-FDG PET/CT combined with contrast-enhanced CT has even greater accuracy.Meanwhile,~(18)F-FDG PET/CT has better diagnostic accuracy in detection of postoperative recurrent tumor.

Objective To evaluate the feasibility and safety in the treatment of liver cancer located under the diaphragm with cool-tip radiofrequency ablation(RFA)percutaneously under CT guidance.Methods 20 patients with total 25 lesions were treated by CT-guided RFA with cool-tip electrode involving the induced necroses.The postoperative efficacy was evaluated by enhanced CT or MRI.Results 72% lesions were completely necrotized(18/25),28% lesions were majorly necrotized(7/25).No severe complications occurred. Conclusion CT-RFA with cool-tip electrode is effective and safe in treating liver cancer located under the diaphragm.

The study was to observe the effect of rhG-CSF (lishengsu) in treating leukopenia caused by radiotherapy and chemotherapy in patients with breast cancer. 100 cases of breast cancer received modified radical mastectomy were randomized into two groups with the same treatment of one cycle chemotherapy using the protocol of CAF at two weeks after the operations and then radiotherapy. The patients in treated group received rhG-CSF 75 micro g per day s.c. for 5 - 7 days constantly, and additional 3 - 5 days according to leukopenia during radiotherapy. The patients in control group did not receive rhG-CSF during the chemo- and radio-therapy. The results shows that nadir of WBC and neutrophil counts in the treated group was higher than that in control significantly. In conclusion, effect of lishengsu on leucopenia in process of chemotherapy and radiotherapy shows definite therapeutic effect, the side effects are not remarkable.
Adult ; Breast Neoplasms ; therapy ; Combined Modality Therapy ; Female ; Granulocyte Colony-Stimulating Factor ; adverse effects ; therapeutic use ; Humans ; Leukopenia ; drug therapy ; Middle Aged ; Recombinant Proteins

OBJECTIVETo compare the epidemiological and clinical features of lower respiratory tract infection (LRTI) caused by influenza virus A (IVA) and influenza virus B (IVB) in children.

METHODSThe clinical data of 366 children with LRTI caused by influenza virus (IV), who were hospitalized in Yuying Children′s Hospital of Wenzhou Medical University between 2010 and 2014, were analyzed retrospectively, and there were 272 cases caused by IVA and 94 cases caused by IVB.

RESULTSIV was mainly prevalent from December to March of the next year, with the predominance of IVA. There were small peaks of IVA prevalence in July or September every other year, and IVB was prevalent from December to March of the next year every other year. The children with LRTI caused by IVA alone had a significantly higher white blood cell (WBC) count and significantly higher percentages of children with increased WBC, abnormal serum sodium, and abnormal serum potassium than those caused by IVB alone (P<0.05). However, there were no significant differences in age, sex, underlying diseases, clinical manifestations, and co-infection rate with bacteria or atypical pathogens between the two groups (P>0.05). The rate of co-infection with respiratory syncytial virus (RSV) was significantly higher in the IVB group than in the IVA group (P<0.01).

CONCLUSIONSIVA is prevalent in winter and spring every year and has small peaks in summer every other year, while IVB is prevalent in winter and spring every other year. Compared with IVB, IVA causes more cases of increased WBC and electrolyte disturbance. The children infected with IVB are more likely to be co-infected with RSV. The children with LRTI caused by IVA and IVB have similar clinical manifestations.

Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Infant ; Infant, Newborn ; Influenza A virus ; genetics ; isolation & purification ; physiology ; Influenza B virus ; genetics ; isolation & purification ; physiology ; Influenza, Human ; diagnosis ; epidemiology ; virology ; Male ; Respiratory Tract Infections ; diagnosis ; epidemiology ; virology ; Retrospective Studies ; Seasons

Objective To investigate the effect of microglia activation regulated by C-X3-C motif chemokine ligand 1(CX3CL1)-C-X3-C motif chemokine receptor 1(CX3CR1)pathway on memory function in hemorrhagic shock/resuscitation rats.Methods The experiment was divided into two parts.In the first part,the rats were randomly divided into sham group,model-0.5 hour group,model-1.5 hour group,model-3 hour group,10 rats in each group.There were differences in the time of hemorrhagic shock among each group.In the second part,rats were randomly divided into control group and CX3CL1 group,10 rats in each group.The rats in CX3CL1 group were treated with CX3CL1 protein factor(intraventricular injection),and the rats in control group were treated with saline.All rats were trained in Morris water maze experiments before model construction,and tests of Morris water maze experiments were carried out after 4 days of model construction.After completion,the whole brains were taken for HE staining and immunohistochemical staining.Cerebrospinal fluid was taken for detection of inflammatory cytokines,and hippocampus tissues were taken for Real-time PCR detection and Western blotting detection.Results Compared with the sham group,the escape latency of rats in model group increased,the number of platform crossings and the resident time in the third quadrant decreased.The neuronal state was impaired in HE staining in model group.In addition,compared with the sham group,the expression of ionized calcium binding adaptor molecule-1(Iba1)in the brain of the rats in model group increased,the contents of tumor necrosis factor-α(TNF-α)and interleukin(IL)-6 in the cerebrospinal fluid increased,and the M1-type microglia markers CD16,TNF-α,IL-1β and inducible nitric oxide synthase(iNOS)mRNA content increased.At the same time,compared with the sham group,the expressions of CX3CL1 and CX3CR1 in the brain of model group decreased,and the expressions of phosphorylated nuclear factor-κB(p-NF-κB)and nucleotide binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)increased.However,compared with the control group,rats in CX3CL1 group had reduced escape latency,increased platform crossing times and quadrantⅢresident time,and recovered neuronal states.In addition,the expression of Iba1 in the brain of CX3CL1 group decreased,the contents of TNF-α and IL-6 in the cerebrospinal fluid decreased,the mRNA contents of M1-type microglia markers like CD16,TNF-α,IL-1β and iNOS decreased,and the mRNA contents of markers of M2-type microglia glial like CD206,transforming growth factor-β(TGF-β),arginase-1(Arg1),Chitinase 3-like protein 1(Ym 1)increased.Conclusion CX3CL1 can help inhibit the excessive activation of microglia,induce the polarization of microglia to M2 type,inhibit the polarization of M1 type,reduce the release of inflammatory cytokines,and alleviate the memory function damage induced by hemorrhagic shock/resuscitation.