The first metatarsophalangeal joint bending plays an important role in the foot movement. However, the existing researches mainly focused on the movement scope of the joint and the clinical treatments of related foot diseases. In order to investigate the effects of the first metatarsophalangeal joint bending on human walking gait stability, the present researchers recruited 6 healthy young men to perform the first metatarsophalangeal joint constraint (FMJC) and barefoot (BF) walking tests. Data of the temporal and spatial parameters, the joint angles of lower limbs, the ground reaction forces (GRF) and utilized coefficients of friction (UCOF) were collected and analyzed. The results showed that, since hip and knee could produce compensation motions, the FMJC had no significant effects on waking gait, but the slip and fall probability increased significantly.
Friction ; Gait ; Humans ; Male ; Metatarsophalangeal Joint ; physiology ; Walking

Objective:To investigate the effect of metformin and arsenic trioxide on KG1a cells proliferation of acute myeloid leukemia and its possible mechanism.Methods:CCK-8 method was used to detect the killing effect of metformin,arsenic trioxide and combined application on KG1a cells.Annexin V-FITC/P1 Dual Stain Flow Cytometry was used to detect the effect of combined application on apoptosis of KG1 a cells.Western blot was used to detect the expression of intracellular apoptosis-,autophagy-related protein.Results:Metformin and arsenic trioxide alone or in combination could inhibit the proliferation of KG1 a cells and induce apoptosis of KG1 a cells,and the proliferation inhibition rate and apoptosis rate in the combined drug group were higher than those in the drug group alone(P＜0.05).The combination of drugs induced upregulation of Caspase 8 protein and P62 protein expression and was higher than that in the drug group alone(P＜0.05).Conclusion:Metformin can synergize with arsenic trioxide to kill KG1a cells,and its mechanism of action may be related to inducing apoptosis and enhancing autophagy.

Objective To explore the immunogenicity of recombinant chimeric 6Aβ15-T including the Aβ1-15 epitope and a T-helper epitope formulated with different adjuvants and to evaluate its feasibility as a candidate vaccine for Alzheimer disease (AD).Methods The recombinant chimeric antigen 6Aβ15-T formulated with Al adjuvant, Freund′s adjuvant or MF59 adjuvant was administered to two strains of mice .The 6Aβ15-T-immunized group without adjuvants ( Mock) and non-immunized group (Control) were included in this study as control groups .The specific antibody and cellular immune response of the chimeric antigen were evaluated .Results In BALB/c strain mice, three types of adjuvants could substan-tially boost the immunogenicity of chimeric antigen 6Aβ15-T and produce a high level of specific-Aβ(β-amyloid) antibod-ies.In C57BL/6 strain mice, the existence of adjuvants enhanced the immune response of 6Aβ15-T antigen, but the mice in Mock group also produced a strong antibody response .In two strains of mice, prevalence of anti-AβIgG1, which was an indicator of Th2 polarization, was observed in the 6Aβ15-T-immunized mice.Additionally, the Al adjuvant induced a high-er level of IgG1 antibody titers, and the ratio of IgG1/IgG2a was the largest.As expected, the 6Aβ15-T antigen formulated with or without adjuvants induced PADRE-specific, but not Aβ42-specific T cellular immune response .Conclusion The 6Aβ15-T antigens formulated with different types of adjuvants could induce strong Th 2-polarized Aβ42-specific antibody re-sponses without activating self-reactive Aβ42-specific T cells in two strains of mice .The results suggested that the recombi-nant chimeric antigen 6Aβ15-T is a good candidate vaccine for AD .

Objective:To investigate the expression of maternally expressed gene 3 (MEG3), a long non-coding RNA gene, in gastric can-cer tissues;determine the relationship of MEG3 with the prognosis of gastric cancer;and explore the relationship between MEG3 and apoptosis-associated protein P53 as well as murine double minute 2 (MDM2). Methods:Fifty-five consecutive patients with gastric cancer admitted to Qingdao Municipal Hospital for surgical treatment from September 2012 to June 2013 were included in this study. Gastric cancer and paired normal tissues were collected. The expression of MEG3 was tested through real-time quantitative poly-merase chain reaction (qRT-PCR). Western blot analysis was used to detect the expression of P53 and MDM2 in gastric cancer and eval-uate their correlations with MEG3. Results:The expression of MEG3 decreased in cancer tissues (7.98±0.19) relative to the correspond-ing normal tissues (9.47±0.18) (P<0.05). P53 and MDM2 showed negative relationships in the gastric cancer and normal tissues. A posi-tive relationship was found between P53 and MEG3 (r=0.591, P<0.05), whereas a negative relationship was found between MDM2 and MEG3 (r=?0.346, P<0.05). The median survival time was significantly prolonged in patients with high MEG3 expression compared with patients with low MEG3 expression. Conclusion:MEG3 exerts an inhibiting effect on the development of gastric cancer. MEG3, P53, and MDM2 may have important relationships in the biological mechanisms of gastric cancer development. Detecting the expression level of MEG3 may be useful for the prognosis of gastric cancer.

In the past two decades,with the increase of smoking population,more and more people are suffering from small cell lung cancer(SCLC).Besides,it is difficult to find an effective way to cure SCLC,since patience can easily develop drug resistance.On the other hand,with the development of science and technology,people began to study the anti-cancer strategy to increase apoptosis,such as inhibiting the overexpression of survival factors.In these survival factors,BCL-2 family has attracted a lot of attention.BH3-only protein is a member of BCL-2 family and it can directly inhibit the expression of BCL-2 protein,thereby prompting apoptosis.Since the BH3-only protein itself is difficult to become a clinical drug, to find alternatives BH3-only protein-BH3 mimetics is particularly important. Plus, more and more researchers have paid attention on the natural BH3 mimetic since it has less side-effect than artificial BH3 mimetics.To find possible BH3 mimetics,we made a primary screening with this pharma-cophore on a small molecular compounds library via Discovery Studio software. And then MTS assay were introduced to verify the activity of compounds. After that, we use Western Blot and Co-IP meth-ods to test the effect of BH3 mimetics.And finally use CDOCKER to predict the further mechanism on autophagy and apoptosis.In our studies, we found 3 possible BH3 mimetics compounds from 170,000 natural small molecular compounds via pharmacophore-based virtual screening.Furthermore,we dem-onstrated AD23,one of the 3 possible natural BH3 mimetics,induced autophagy and apoptosis simulta-neously in dose-time dependence in SCLC cell line. Finally, we use Molecular Docking to predict the further mechanism on autophagy and apoptosis. We believe our works would provide evidences and clues for the structural optimizing and further study of new drugs in the future.

Pancreatic ductal adenocarcinoma (PDAC) is one of the five most malignant cancer. ZX-1201 is one of the active constituents in Alismatis Rhizoma,a well-known traditional Chinese medi-cine with a wide variety of pharmacological properties including diuretic,anti-hyperlipidemic,anti-atheroscle-rotic,anti-cancer,anti-inflammatory and anti-oxidative activities.We investigated the inhibitory effect of ZX-1201 on pancreatic cancer and the relevant molecular mechanism in vitro and in vivo. ZX-1201 inhibited the growth and metastasis of PANC-1 cells in BALB/c nude mice significantly.ZX-1201 inhibited the function of AQP1 via directly interaction and involved in the reversion process of ZX-1201 on TGF-β1. CTGF was an important protein in the reversion process of ZX-1201 on TGF-β1.ZX-1201 inhibited the migration of PANC-1 and CPFAC-1 cells induced by TGF-β1in vitro.ZX-1201 reversed the down-regu-lated of epithelial markers and up-regulated of mesenchymal markers, as well as the up-regulated of Snail and p-Smad2/3 induced by TGF-β1.And ZX-1201 reversed Epithelial-Mesenchymal Transition by down-regulating AQP1 and inhibiting translocation of β-catenin, the promotor of CTGF. According to these,ZX-1201 inhibited the migration of pancreatic cancer cells.We concluded that ZX-1201 inhibited the growth and metastasis of PANC-1 cells in vivo significantly.And AQP1,β-catenin and CTGF were the pivotal proteins in the process of ZX-1201 inhibiting PANC-1 cells migration induced by TGF-β1.

Objective:To investigate the expression of chemokine receptor CXCR4 in hepatocellular carcinoma tissues,hepatocellular carcinoma cell line-MHCC97,human umbilical vein endothelial cells(HUVECs)and the ascites level of CXCL12,ligand of CXCR4,so as to lay a foundation for studying the role of CXCR4 in the metastasis of hepatocellular carcinoma.Methods:The expression of CXCR4 mRNA and protein was examined by RT-PCR and Western blotting in 21 specimens of hepatocellular carcinoma tissues,MHCC97 cells,HUVECs,and 17 specimens of normal hepatic tissues.Meanwhile,the levels of CXCL12 in ascitic fluids were assayed by ELISA in 18 hepatic cancer patients.Results:The relative expression values of CXCR4 mRNA in hepatocellular carcinoma tissues,MHCC97 cells,and HVECs were 2.21?1.09,2.14?1.15 and 1.72?1.20,respectively;and those of CXCR4 protein were 1.51?0.12,1.76?0.25,and 1.89?0.24,respectively;and those of CXCR4 protein were 1.51?0.12,1.76?0.25,and 1.89?0.24,respectively.CXCR4 mRNA and protein were not detected in normal hepatic tissues.ELISA results showed that the 18 hepatocellular carcinoma samples had a CXCL12 concentration range of 783-8 364 pg/ml(median value 6 871 pg/ml)in ascitic fluids.Conclusion:CXCR4 is highly expressed in the hepatocellular carcinoma tissues and cells,which is not associated with the clinical staging of the cancer.The elevated CXCL12 level in the ascitic fluid of cancer patients indicate that CXCR4 may play an important role in the metastasis of hepatocellular carcinoma.

Objective To evaluate the value of endorectal ultrasonography (ERUS) in assessment of mesorectal fascia (MRF) invasion in rectal cancer.Methods Data of 44 patients who accepted preoperative ERUS and total mesorectal excision surgery within a week were retrospective analyzed.There were 18 patients who accepted preoperative neoadjuvant chemotherapy and 26 patients didn't acceped.Taking the pathological diagnosis of circumferential resection margin (CRM) as the gold standard,the diagnostic efficiency of ERUS for the MRF invasion in rectal cancer was evaluated.Results The final pathological T staging was T1 in 2 cases,T2 in 17 cases and T3 in 25 cases.There were 2 cases of CRM positive results,and 42 cases of CRM negative results.With regard to the location of tumor,there were 16 cases located in low,and 28 cases in mid rectum.There were 26 cases located in anterior or antero-lateral wall of rectum,13 cases in posterior or postero-lateral wall,and 5 cases with a circle of rectum.The diagnostic accuracy were 83.33 ％ (15/18) and 92.31％ (24/26) for cases of accepting and not accepting the preoperative neoadjuvant chemotherapy;80.77％ (21/26) for cases located in anterior or antero-lateral wall,and 100％ (13/13) for cases located in posterior or postero-lateral wall;75.00％ (12/16)and 96.43 ％ (27/28) for low position and mid position tumors.The total diagnostic accuracy was 88.64％ (39/44).Conclusion ERUS can be an effective method in preoperative assessment of the MRF invasion in rectal cancer.

Objective To investigate the pathogenic mutations of BRCA1 and BRCA2 in patients with early-onset breast cancer(≤35 years) and explore the relationships between BRCA1/2 mutations and clinical features.Methods Seventy-four patients with early-onset breast cancer were enrolled,who were treated in Hospital 307 between September 2014 and June 2016.High-throughput sequencing was used to test the 49 exon sequences and adjacent sequences of BRCA1 and BRCA2.χ2 test was used to analyze the distribution of BRCA1/2 pathogenic mutations in each group that was set up according to clinical features.Results Fifteen mutations(20.27%) were identified,including 5(6.76%) in BRCA1 and 10(13.51%) in BRCA2.Eleven new pathogenic mutations were discovered,and BRCA1:c.5470_5477delTGCCCAAT was found in one patient.The frequency of BRCA1/2 mutations in the group with a family history of breast cancer or ovarian cancer was higher than in the group without a family history (40.91% vs 11.54%) (χ2=6.534,P=0.011).Conclusion BRCA1/2 pathogenic mutation is significant for early-onset breast cancer,especially for those with a family history of breast or ovarian cancer.The new mutations may be specific to Chinese people.BRCA1:c.5470_5477delTGCCCAAT may be the ancestor mutation among the Chinese.

This study was purposed to analyze the clinical features and evaluate the efficacy of thalidomide combined with VAD regimen for treatment of osteosclerotic myeloma (POEMS syndrome). The data of 27 patients with POEMS syndrome in the First Affiliated Hospital of Zhengzhou University were analyzed retrospectively, including clinical manifestations, laboratory tests, treatments and prognosis. The results showed that the polyneuropathy was observed in 27 patients (27/27), hepato-spleno-lymphadenectasis was found in 15 patients (15/27), endocrinopathy was found in 24 patients (24/27), skin changes was observed in 22 patients (22/27). M protein was found in 23 patients (23/27); in addition to these clinical manifestations, the papilledema serous cavity effusion and sclerotic bone lesion were also frequently observed in patients with POEMS syndrome. The remission rates of treatment of POEMS syndrome with thalidomide combined with VAD regimen for organomegaly, edema, skin changes, and endocrinopathy were 60, 58.3, 41 and 45.8 respectively. The level of serum M protein and the nervous system ODSS value decreased greatly after treatment (P < 0.01). It is concluded that the clinical characteristics of POEMS syndrome are complicated and easy to be misdiagnosed, and the evidence of monoclonal plasma cell hyperplasia should be actively searched for those patients whose serum M protein is negative. Thalidomide combined with VAD regimen for treatment of patients with POEMS syndrome has advantages such as significant curative effects, less side-effects, good tolerance, and higher safety and can be chosen as a preferred approach.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; Cytarabine ; Dexamethasone ; Female ; Humans ; Male ; Middle Aged ; POEMS Syndrome ; drug therapy ; Retrospective Studies ; Thalidomide ; therapeutic use ; Vincristine