Female ; Humans ; Infant ; Mitochondrial Proton-Translocating ATPases ; deficiency ; genetics ; Mutation

Objective To investigate the role of TLR4/NF-kB signaling pathway in inhibited invasion ability of pancreatic cancer cells caused by triptolide (TP).Methods PANC1 cells were divided into parental cells group,TP group,lipopolysaccharide (LPS) group and TP + LPS group.50 ng/ml of TP was added in culture medium in TP group,and 1 μg/ml of LPS was added in culture medium in LPS group,while 50 ng/ml of TP was pretreated for 2 h and 1 μg/ml of LPS was added in culture medium in TP + LPS group.All the ceils were cultured for 24 h.The TLR4 and matrix metalloproteinase-9 (MMP-9) mRNA and protein expression were evaluated by real-time PCR and Western blot.The NF-kB activity was determined by dual-luciferase reporter assay system.The invasion ability of pancreatic cancer cells was evaluated by transwell invasion chamberassay.Results The TLR4 mRNA expressions in parental cells group,TP group,LPS group and TP + LPS group were 0.41 ± 0.06,0.46 ± 0.10,0.20 ± 0.04,0.25 ± 0.06 ; the TLR4 protein expressions were 0.55 ±0.06,0.55 ±0.06,0.18 ±0.04,0.13 ±0.00; the activities of NF-kB were 13.0 ±3.0,31.6 ±4.3,7.3 ±1.5 and 10.8 ± 2.1,and the numbers of invasion cell were (56.8 ± 8.6),(104.5 ± 12.8),(32.0 ± 5.7) and (46.8 ± 7.0) ; the MMP-9 mRNA expressions were 0.36 ± 0.05,0.58 ± 0.07,0.18 ± 0.03,0.30 ± 0.004 ;the MMP-9 protein expressions were 0.31 ± 0.04,0.53 ± 0.08,0.11 ± 0.02,0.15 ± 0.00.In LPS group,TLR4 mRNA and protein expressions were not statistic significant when compared with those in parental cells group,but the activities of NF-kB,the numbers of invasion cell,MMP 9 mRNA and protein expressions were statistically increased when compared with those in parental cells group (t =8.654,7.593,6.655,4.982,P ＜0.01).TLR4 mRNA and protein expressions,activities of NF-kB,the numbers of invasion cell,MMP 9 mRNA and protein expressions in TP group were significantly lower than those in parental cells group (t =-7.609,-9.948,-4.176,-5.915,-8.179,-9.948,P＜ 0.01).TLR4 mRNA and protein expressions,activities of NF-kB,the numbers of invasion cell,MMP 9 mRNA and protein expressions in TP +LPS group were significantly lower than those in LPS group (t =-4.437,-14.805,-10.506,-9.700,-9.055,-8.932,P＜ 0.01).Conclusions TP can inhibit pancreatic cancer cell invasion,and the mechanism is related to the inhibition of TLR4/NF-kB signaling pathway and down-regulation of MMP-9 expression.

Objective To observe the relationship between Toll-like receptor 4 (TLR4) and the sensitivity of PANC1 cells to gemcitabine (GEM),and to analyze the potential mechanism.Methods PANC1 cells were divided into GEM group,lipopolysaccharide (LPS) + GEM group and TLR4-siRNA + GEM group.GEM group was treated by GEM alone.LPS + GEM group was pretreated with 1 mg/L LPS for 4 h and then treated by GEM.TLR4-siRNA + GEM group was transfected with 100 pmol/mL TLR4-siRNA for 4 h and then treated by GEM.The untreated cells were used as the control group.MTT method was used to detect the cell proliferation.Morphological changes and apoptosis rate of the cells were examined by Hoechst33258 staining and flow cytometry,respectively.The protein expression of TLR4,phosphorylated AKT (p-AKT) and activated Caspase-3 were detected by Western blot.Results The median inhibition concentration (ICs0) of GEM in the GEM group,LPS + GEM group and TLR4-siRNA + GEM group was (8.9 ± 0.32),(14.21 ±0.95),(3.96 ± 0.27) mg/L,respectively.The IC50 in LPS + GEM group was significantly higher than that in GEM group (P ＜ 0.01),and the IC50 of GEM in TLR4-siRNA + GEM group was significantly lower than that in GEM group (P ＜0.01).Compared with that in GEM group,the cells with typical apoptotic morphological changes were decreased in LPS + GEM group,which was increased in TLR4-siRNA + GEM group.The apoptotic rate in control group,GEM group,LPS + GEM group,TLR4-siRNA + GEM group was (2.1 ± 0.3) ％,(15.1 ± 2.3) ％,(9.8 ± 1.5) ％,(22.9 ± 3.1) ％,respectively.Compared with that in GEM group,the cells apoptotic rate was significantly reduced in LPS + GEM group (P ＜0.01),which was significantly increased in TLR4-siRNA + GEM group (P ＜0.01).TLR4 protein level in the 4 groups was 0.83 ±0.08,0.81 ±0.07,0.85 ±0.07 and 0.16 ±0.03;p-AKT protein level 0.61 ±0.05,0.36 ±0.03,0.73 ± 0.07 and 0.21 ± 0.02;activated Caspase-3 protein level was 0.66 ± 0.05,0.73 ± 0.07,0.45 ± 0.04 and 0.91 ± 0.07,respectively.The expression of TLR4 and p-AKT in TLR4-siRNA + GEM group was significantly lower than that in GEM group (P ＜0.01),while the expression of activated Caspase-3 protein was increased significantly (P ＜ 0.05).Compared with the GEM group,the expression of p-AKT protein in LPS + GEM group was significantly increased (P＜0.01),and the expression of activated Caspase-3 protein was significantly decreased (P＜0.01).Conclusions TLR4 can inhibit the sensitivity of pancreatic cancer PNAC1 cells to GEM,and the mechanism is related to the activation of PI3K/AKT pathway and downregulation of activated Caspase-3.

Objective To provide a good anatomical foundation for transposition of the branch of median nerve superficial flexor muscle repairing the movement branch of ulnar nerve to recover the function of intrinsic muscle, by anatomic study of the muscle branch of the superficial flexor muscle of the median nerve and the movement branch of ulnar nerve. Methods Twenty adult upper limb specimens immersed fixed by formalin were elected and expose the midian nerve and ulnar nerve. Then every anatomical index was measured. Simulate to manipulate that the branch of superficial flexor muscle repair the motor b ranch of ulnar nerve. Calculate the number of myelinated nerve fibers of the branch of superficial flexor muscle. Results The distance between the position into muscle and styloid process of radius and styloid process of ulna: (21.4±1.8)mm, the distance that can be separated: (27.1±1.2)mm, the transverse diameter: (1.2±0.2)mm, anteroposterior diameter: (0.7 ± 0.1 )mm. No injury separated distance between the sensory branch and motor branch of ulnar nerve: (7.1 ± 0.7)cm. The 4th muscular branches of median nerve flexor digitorum superficialis was 1378.9± 107.9. Conclusion The 4th muscular branches of median nerve flexor digitorum superficialis can be used to repair the motor branch of the ulnar nerve to recover the function of intrinsic muscle of hand.

Evidence has indicated that low doses of anti-tumor regimens can induce cell apoptosis in vitro, although different regimens induce apoptosis by different mechanism and pathway. In recent years, new tumor treatment strategy has been mainly focused on inducing tumor cell apoptosis. The present review discusses the advantages and disadvantages of inducing tumor cell apoptosis. The benefit of inducing apoptosis is not to cause inflammatory reaction, but as its disadvantage, it inhibits immune responses, and the phagocytosis of apopotic bodies may result in horizontal transfer of genes (including oncogenes and other oncogenic materials), which can be one of the causes of tumor relapse. This paper proposes that the tumor treatment strategy should be turn into promoting tumor cell necrosis and inducing anti-tumor immune responses.
Antineoplastic Agents ; therapeutic use ; Apoptosis ; drug effects ; Humans ; Necrosis ; chemically induced ; Neoplasms ; drug therapy ; immunology ; pathology

Up to date, eight types of human herpes viruses have been identified, all of which are ubiquitous, and usually establish latent infection in the host after primary infection. Since most of the herpes viruses are maintained in an asymptomatic form, they are often neglected. However, under some circumstances, these herpes viruses can cause fatal or severe diseases. Furthermore, the association of herpes viruses with hematopoietic malignancies is attracting researchers' attention. With the extensive development of hematopoietic stem cell and organ transplantation, reports regarding transplantation failure and complication caused by infection of human herpes virus has been increasing. Cytokine storm was firstly suggested as the mechanism of graft-versus-host diseases. In recent years, which has also been applied in the pathogenesis research of inflammation, and is supposed to play an important role in severe virus infection. In this paper, through discussing the possible role of latent infection of human herpes virus in the failure or complication of bone marrow or hematopoietic stem cell transplantation, and in refractory leukemia, the function and significance of latent infection of human herpes virus and the cytokine storm it caused were investigated.
Cytokines ; immunology ; Hematopoietic System ; immunology ; virology ; Herpesviridae Infections ; Humans ; Virus Latency

Relapse, which puzzled several generations of hematologists, is the bottle-neck of radical treatment for leukemias. The progress of Human Microbiome Project at the beginning of 21st century suggested that human body was a super-organism constituted by the core of human cells and symbiotic microorganisms. The elucidation and characterization of endogenous retrovirus and prion protein suggested the possible effects of co-evolutional microorganisms on human health. Recently, the elucidation of the roles of tunneling nanotubes in intercellular communication and transportation suggested a novel way for cellular communication and transport of oncogenic materials. The role and significance of in vivo cell fusion have been studied in more detail. On the other hand, donor cell leukemia was reported. All of these approaches provide novel insights for studying the mechanism of leukemia relapse. Based on previous work, the authors suggest the hypothesis: there are two possible mechanisms for the relapse of leukemias: the minimal residual disease (MRD) and intercellular transportation of oncogenic materials.
Cell Fusion ; Humans ; Leukemia ; pathology ; Neoplasm, Residual ; pathology ; Recurrence

As pioneer of tumor stem cell research, leukemia stem cell research has not only important theoretical significance, but also clinical application potential. The survival and development of stem cells are directly impacted by their microenvironment. The research on leukemia stem cells and their microenvironment are now becoming a hot topic. The author presumes that stem cells are a population with heterogenecity and hierarchy; any single cell from the population is difficult to form a clone; the interaction between the leukemia stem cell and its microenvironment can be described by the concept of leukemia stem cell niche. In this article, the leukemia cell population with heterogenecity and hierarchy as well as leukemia stem cell niche were summarized and discussed.
Cell Line, Tumor ; Humans ; Leukemia ; genetics ; pathology ; Neoplastic Stem Cells ; metabolism ; pathology ; Stem Cell Niche ; cytology ; Stromal Cells ; cytology ; immunology

Objective To estimate the security and effectiveness of double access technique to treat chronic total occlusion in lower extremity artery. Method Fifty four patients,who had lower limb arteriosclerosis and accepted failed endovascular treatment because of unable to reenter true lumen through antegrade access,were treated immediately in double access style to recanalize occluded artery (including 27 patients of dorsalis pedis artery puncture,17 patients of posterior tibial artery punctrue,5 patients of proximal anterior tibial artery puncture and 5 patients of distal superficial femoral artery puncture). Evaluate the revascularization rate,complication rate and 6-month limb salvage rate of double access technique,t test was used to compare the ABI.Results Revascularization rate was 98.2％ (53/54),average puncture frequency of every case was 6 ( the first access was 2 in every patient,the second access was 4 in every patient ),average treatment time was 167 minutes,complication rate was 5.6％ (3/54),2 patients were occlusion in puncture segment of the second access,1 patient was hematoma in the second access point. 6-month ABI after intervention increased from 0.44 ±0.13 to 0.69 ±0.15,6-month limb salvage rate was 100％. Conclusion For chronic total occlusion,double access is a feasible technique to deal with unable to reenter true lumen throughantegrade access,the complication rate is low,the primary limb salvage rate is relatively high.

Objective To seauch the ideal management for gross hematuria in autosomal dominant polycystic kidney disease (ADPKD).Methods ADPKD patients who were ever hospitalized and followed up in our department since 1993 were enrolled in the study.Demographic and clinical data were colloected,such as gender,age of gross hematuria,level of renal function,causative factors,management strategies,duration of gross hematuria,blood platelet count,activated partial thromboplastin time,prothrombin time,international normalized ratio,size of kidney cyst and so on.ADPKD patients were divided into different groups according to causative factors or management.The clinical data were compared among groups.Results A total of 905 ADPKD patients were screened,among whom 279 patients ever had gross hematuria (male/female:150/129),One hundred and forty-six patients had integrated therapeutic process records,while only 101patients could provide relevant laboratory examination results.In these 101 patients,gross hematuria was found in any stage of chronic kidney disease (CKD); the average eGFR was (56.4±44.1) mml·min-1 ·(1.73 m2)-1; the duration of gross hematuria was (8.8±8.0) d; no significant difference between male and female in duration of gross hematuria existed [(8.2±7.3) d vs (9.5±8.8) d,P=0.426]; coagulation parameters were all normal.The platelet count was also normal in 91 patients.Duration of gross hematuria among groups divided according to different causative factors was significantly different (P＜0.05).The patients in bed rest group had significantly shorter duration of gross hematuria compared with other groups (P＜0.05).The platelet count,prothromhin time and international normalized ratio were all at similar level in different groups.Conclusions The causative factors in ADPKD patients with gross hematuria should be confirmed as the first step of management strategies.Bed rest is the key point in management.Antifibrinolytic agent is a proper choice in the cases receiving bemostatic drugs.It is unnecessary to use antibiotic agent for prevention.