P53 is a key tumor suppressor gene,which is regulated in many ways.Zinc finger 148(ZNF148)and SP5,as zinc finger transcription factors(TFs),play important roles in tumor suppression and carcinogenesis.The regulatory relationship between these two TFs and p53 has not been reported.In this paper,Ishikawa and A549 cell lines with different p53 expression levels were used as research mod-els to explore the transcriptional regulation of the P53 gene by ZNF148 and SP5.The data showed that there were differences in the expression of ZNF148 and SP5 in the two cell lines.The mRNA expression of ZNF148 in Ishikawa was 1.9 times higher than that of A549,and the mRNA expression of SP5 in A549 was 802.4 times that of ZNF148.Data showed that in Ishikawa cells,the expression of P53 de-creased(81.8％)after ZNF148 knockdown,and increased(2.6 times)after SP5 overexpression.Transfection of si-SP5 and ZNF148 expression plasmids into A549 cells increased the mRNA expression of P53 by 6.6 times and 14.6 times,respectively.These results indicate that ZNF148 could activate,whereas SP5 could inhibit,P53 expression.The conserved cis-element of ZNF148 and SP5 TFs was found in the region of the P53 promoter by bioinformatics methods.The data from dual luciferase reporter gene assay showed that the luciferase activity of ZNF148 in Ishikawa and A549 cells was increased by 2.1-fold and 4.2-fold compared with the control group(P＜0.05).Compared with the control group,the normalized relative luciferase activity of transfected SP5 decreased by 77.1％and 35.7％(P＜0.05).However,when the cis-element of ZNF148 and SP5 was mutated,the effect disappeared.Further trans-fection of ZNF148 and SP5 with different ratios revealed that SP5 could reverse the transcriptional activa-tion of P53 by ZNF148.Studies have shown that ZNF148 shares a common site with SP5,and the ratio of the two TFs may influence the transcriptional activity of P53.The expression of the Wnt pathway and the cell proliferation rate after knockdown of ZNF148 and SP5 were further studied to explore the role of the two TFs.Our data show that ZNF148 and SP5 could regulate the transcriptional activity of P53,and their expression levels and interaction may be the key factors regulating P53 expression.

P53 is a key tumor suppressor gene,which is regulated in many ways.Zinc finger 148(ZNF148)and SP5,as zinc finger transcription factors(TFs),play important roles in tumor suppression and carcinogenesis.The regulatory relationship between these two TFs and p53 has not been reported.In this paper,Ishikawa and A549 cell lines with different p53 expression levels were used as research mod-els to explore the transcriptional regulation of the P53 gene by ZNF148 and SP5.The data showed that there were differences in the expression of ZNF148 and SP5 in the two cell lines.The mRNA expression of ZNF148 in Ishikawa was 1.9 times higher than that of A549,and the mRNA expression of SP5 in A549 was 802.4 times that of ZNF148.Data showed that in Ishikawa cells,the expression of P53 de-creased(81.8％)after ZNF148 knockdown,and increased(2.6 times)after SP5 overexpression.Transfection of si-SP5 and ZNF148 expression plasmids into A549 cells increased the mRNA expression of P53 by 6.6 times and 14.6 times,respectively.These results indicate that ZNF148 could activate,whereas SP5 could inhibit,P53 expression.The conserved cis-element of ZNF148 and SP5 TFs was found in the region of the P53 promoter by bioinformatics methods.The data from dual luciferase reporter gene assay showed that the luciferase activity of ZNF148 in Ishikawa and A549 cells was increased by 2.1-fold and 4.2-fold compared with the control group(P＜0.05).Compared with the control group,the normalized relative luciferase activity of transfected SP5 decreased by 77.1％and 35.7％(P＜0.05).However,when the cis-element of ZNF148 and SP5 was mutated,the effect disappeared.Further trans-fection of ZNF148 and SP5 with different ratios revealed that SP5 could reverse the transcriptional activa-tion of P53 by ZNF148.Studies have shown that ZNF148 shares a common site with SP5,and the ratio of the two TFs may influence the transcriptional activity of P53.The expression of the Wnt pathway and the cell proliferation rate after knockdown of ZNF148 and SP5 were further studied to explore the role of the two TFs.Our data show that ZNF148 and SP5 could regulate the transcriptional activity of P53,and their expression levels and interaction may be the key factors regulating P53 expression.

AIM To explore the clinical effects of Shuilu Erxian Pills combined with Modified Didang Decoction on patients with early and middle stage diabetic nephropathy.METHODS Eighty-three patients were randomly assigned into control group(42 cases)for 12-week administration of Irbesartan Tablets,and observation group(41 cases)for 12-week administration of Shuilu Erxian Pills,Modified Didang Decoction and Irbesartan Tablets.The changes in clinical effects,TCM syndrome scores,blood glucose indices(FBG,HbA1c),blood lipid indices(TC,TG),renal function indices(BUN,Scr,24 h UTP,eGFR),inflammatory factors(IL-1β,hs-CRP,IL-6,TNF-α,IL-18,TGF-β1),immune function indices(lymphocyte,neutrophil,CD8+,CD3+,CD4+,CD4+/CD8+)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the observation group displayed decreased TCM syndrome scores,blood glucose indices,blood lipid indices,BUN,Scr,24 h UTP,inflammatory factors,CD8+(P＜0.05),reduced lymphocyte,neutrophil(P＜0.05),and increased eGFR,CD3+,CD4+,CD4+/CD8+(P＜0.05),which were more obvious than those in the control group(except for HbA1c,TG,SCr,24 h UTP,lymphocyte,neutrophil)(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with early and middle stage diabetic nephropathy,Shuilu Erxian Pills combined with Modified Didang Decoction can safely and effectively improve clinical symptoms,whose mechanism may contribute to the reduction of inflammatory levels and improvement of immune functions.

AR (androgen receptor) and CCAT2 are two prostate cancer (PCa)-related genes whereas their relationship is not yet reported. AR is the classical major functional gene in PCa progression. CCAT2, a non-coding gene, was identified based on big-data GWAS (Genome-Wide Association Studies) in the year of 2013. Androgen deprivation therapy (ADT) is usually used to treat PCa in the early stage. After persistent androgen deprivation, PCa would generally lead to castration resistant prostate cancer (CRPC), whereas the mechanism is yet unclear. Here we explore the function of AR and CCAT2 in PCa progression, especially their relation in androgen sensitive and insensitive cell model LNCap and DU145. We found a loop between AR and CCAT2 transcription by over-expression and knock-down strategies. In DU145 cells, G-CCAT2 activated AR mRNA level 2. 6 times, while T-CCAT2 inhibited it to 0. 2 times (P<0. 05). In LNCaP cells, G-CCAT2 could activate AR mRNA levels 1. 5 times, and TCCAT2 had no significant effect (P<0. 05). Under overexpression of AR in DU145 cells, the expression of CCAT2 increased 2. 9 times (P < 0. 05). The abundance of CCAT2 decreased to 0. 48 (P < 0. 05) in LNCaP cells by AR knock-down. Reporter gene analysis showed that CCAT2 could function on the AR promoter. We then performed CCK8 assays and AR protein level detection as supplement for the new gene CCAT2 studies. Finally we primarily studied some target genes that are related to AR and CCAT2 . The results showed that the G-CCAT2 transcript could activate AR expression in LNCap cells while UCCAT2 had no significant effect. In DU145 cells, G-CCAT2 exhibited a more relative stronger activation effect on AR, and U-CCAT2 could inhibit AR transcription. AR activates the transcriptional activity of CCAT2 in both cell lines, suggesting a feedback regulation between them. Our data showed that there would be a feedback loop between CCAT2 and AR, which may indicate a new method for PCa treatment.

The chemical constituents of Zingiber officinale peel were isolated and purified by various chromatographic separation techniques such as Diaion HP-20, MCI Gel CHP-20, Sephadex LH-20, ODS, silica gel and semi-preparative HPLC. Seven terpenoids were identified by physicochemical properties and spectral data: (4R,6S)-1-(hydroxymethyl)-5,5-dimethylbicyclo[3.1.1]hept-2-en-4-ol (1), 4-(hydroxymethyl)-1-isopropylcyclohex-2-ene-3,4-diol (2), 3,5,6-trihydroxy-7-megastigmen-9-one (3), 3-(3-hydroxybutyl)-2,4,4-trimethyl-2,5-cyclohexadien-1-one (4), angelicoidenol (5), grasshopper ketone (6), and dihydrophaseic acid (7), in which compounds 1, 2 are new compounds, named: (4R,6S)-1-(hydroxymethyl)-5,5-dimethylbicyclo[3.1.1]hept-2-en-4-ol and 4-(hydroxymethyl)-1-isopropylcyclohex-2-ene-3,4-diol, and compounds 3-7 were obtained from this plant for the first time.

Objective: To investigate the chemical constituents in the the above-ground part of the plant Achyranthes bidentata Bl. in Amarathaceae. Methods: The raw materials were extracted by heating with 70% ethanol, and the extract was prepared by column chromatography on Diaion HP-20, MCI Gel CHP-20P, Toyopearl HW-40, Sephadex LH-20, ODS and silica gel, coupled with the semi-preparative HPLC, to isolate the chemical constituents. The isolated compounds were identified according to their MS, 1H NMR and 13C NMR data. Results: Twenty one compounds were isolated and identified: haploperoside A(1), sweroside(2), 1'-O-benzyl-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside(3), 2-ethyl-3-methyl-maleimide-N-β-D-glucopyranoside(4), 3-eth- ylidene-4-methyl-2, 5-pyrrolidinedione(5), methyl-5-hydroxy-2-pyridinecarboxylate(6), pericampylinone A(7), syringaresinol(8), episyringaresinol(9), methyl 3, 4-dihydroxybenzoate(10), 4-hydroxyphenylacetone(11), 3, 4-dihydroxyphenylacetic acid methyl ester(12), 2-(4-hydroxyphenyl)-ethanol(13), homovanillyl alcohol(14), dihydrosinapyl alcohol(15), 4-hydroxybenzoic acid (16), caffeic acid(17), 3-(4-hydroxy-3, 5-dimethoxyphenyl)propane-1, 2-diol(18), methyl(E)-3-(4-hydroxyphenyl)acrylate (19), trans-ferulic acid(20)and vanillic acid(21). Conclusion: Compounds 1-7 and 9-19 were isolated from the title plant for the first time.

Objective To investigate clinical efficacy of Xiaotan Tongluo Gel combined with mecobalamin tablets in treating chemotherapy-induced peripheral neuropathy (CIPN). Methods Totally 67 cases of CIPN were divided into the treatment group (36 cases) and the control group (31 cases). Both groups were given mecobalamin tablets, 0.5 mg each time, three times a day, orally. Patients in the treatment group were treated with Xiaotan Tongluo Gel for external use at the same time. The patients in control group were treated with placebo gel for external use, 1 mL/cm2, rubbed on the skin 1 cm more than sensory obstruction in diameter. The treatment for both groups lasted for 14 d as a treatment course, and the treatment lasted for 2 courses. The changes of peripheral nerve toxicity, TCM syndrome scores and the nerve conduction velocity were observed in the two groups. Results On the 14th and 28th days of treatment, the total effective rates of peripheral nerve toxicity were 75.00% and 91.67% in the treatment group, and 38.71% and 67.74% in the control group, and the treatment group was significantly better than those of the control group (P=0.002, P=0.005); On the 14th and 28th days of treatment, the total effective rate of TCM efficacy in the treatment group was 75.00% and 94.44% respectively, and that in the control group was 45.16% and 64.52% respectively, and the treatment group was significantly better than the control group (P=0.018, P=0.005). Compared with before treatment, the TCM syndrome scores in both groups were significantly reduced on the 14th and 28th days (P＜0.01); The TCM syndrome scores in the treatment group were significantly lower than those in the control group at the same time points after treatment (P＜0.01). Compared with before treatment, the sensory and motor nerve conduction speeds of the peroneal and median nerves in the two groups at 14th and 28th days were significantly increased (P＜0.01); Comparing the two groups at the same time point after treatment, the sensory and motor nerve conduction velocity of the peroneal and median nerves in the treatment group was significantly better than that in the control group (P＜0.05, P＜0.01). Conclusion Xiaotan Tongluo Gel combined with mecobalamin tablets can effectively improve the peripheral neurotoxicity induced by chemotherapy, TCM syndrome scores, and the nerve conduction velocity.

BACKGROUND: Although mesenchymal stem cells (MSCs) from different sources share many similar characteristics, they also exhibit individual properties. OBJECTIVE: To compare the biological characteristics of MSCs derived from umbilical cord and decidua parietalis. METHODS: Growth curve, cell doubling time, clone formation rate, immune phenotype, differentiation capacity and secreted cytokine levels were analyzed in MSCs derived from umbilical cord and decidua parietalis. RESULTS AND CONCLUSION: MSCs from umbilical cord and the decidua basalis exhibited similar morphology, spiral growth, S-shaped growth curve, immunophenotype, and differentiation potentials to osteogenesis and adipogenesis. For two kinds of MSCs, the positive rates of CD73, CD90 and CD105 were over 95% and the positive rates of CD34 and CD45 were below 1%. The growth rate, cell doubling time and clone formation rate of umbilical cord derived MSCs at passages 2 and 5 were significantly higher than those of decidua parietalis derived MSCs at passages 2 and 5 (P < 0.05). The level of epidermal growth factor secreted from umbilical cord MSCs was significantly higher that that from decidua basalis derived MSCs, while the levels of vascular endothelial growth factor and stem cell growth factor from umbilical cord derived MSCs was significantly lower those from decidua basalis derived MSCs (P < 0.05). These findings indicate that MSCs from both sources have similar biological properties, but umbilical cord derived MSCs are deemed to have better application prospects.

OBJECTIVETo investigate the correlation between a diverse of clinical factors and bone metastases of prostate cancer.

METHODSThe clinical data of 80 patients with prostate cancer were collected and analyzed. The correlations of age, alkaline phosphotase (ALP), prostate specific antigen (PSA), erythrocyte sedimentation rate (ESR), Gleason score, and expressions of androgen receptor (AR) and Ki-67 with bone metastases were analyzed by one-way ANOVA and Logistic regression analysis. The cutoff value, sensitivity and specificity of the independent correlation factors were calculated.

RESULTSForty-five of the 80 patients (56%) were found to have bone metastasis, who had significantly older age and higher levels of ALP, PSA, ESR, Gleason score, and expressions of AR and Ki-67 than those without bone metastasis (P<0.05). Logistic regression analysis identified PSA, Gleason score and AR expression as independent factors correlated with bone metastasis with OR (95% CI) of 1.005 (1.001, 1.009) (P=0.008), 5.356 (1.431, 20.039) (P=0.013), and 18.594 (2.460, 140.524) (P=0.005), respectively. The cutoff values of PSA, Gleason Score and AR were 67.1 ng/ml, 7.5, and 2.5, respectively; their sensitivities were 55.6%, 75.6%, and 84.0% for predicting bone metastasis with specificities of 97.1%, 82.9%, and 91.4%, respectively.

CONCLUSIONOf the factors analyzed, PSA, Gleason score and AR expression, but not age, ALP, PSA, ESR, or Ki-67 expression, are the predictive factors of bone metastasis of prostate cancer.

Alkaline Phosphatase ; metabolism ; Bone Neoplasms ; diagnosis ; secondary ; Humans ; Male ; Neoplasm Grading ; Predictive Value of Tests ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; pathology ; Receptors, Androgen ; metabolism ; Sensitivity and Specificity

OBJECTIVETo evaluate the impact of Jinlongshe Granule (, JLSG) on quality of life (QOL) of stage IV gastric cancer patients.

METHODSThis randomized, double-blind and placebo-controlled clinical trial included 50 patients with advanced gastric cancer. They were equally randomized into a JLSG group and a placebo group. Patients in both groups received routine Chinese herbal decoctions according to Chinese medicine (CM) treatment based on syndrome differentiation. Patients in JLSG group received additional JLSG, and those in the placebo group received an additional placebo. In the JLSG group, 19 patients who completed the study were used for analysis. In the placebo group, finally the data of 20 patients who completed the study were used for analysis. The treatment course was at least 3 months, and the follow-up duration was at least 6 months in 5 interviews. Repeated measurements of the subscale items and individual items in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (EORTC QLQ-C30) obtained at the 5 interviews were compared using different patient groups, changes over time and changes within one group over time independently to observe the tendency of changes in the scores.

RESULTSUsing time as the variant, there was signifificant difference in 4 functional scales (physical, role, emotional and social, P<0.05), 3 symptom scales (fatigue, nausea and vomiting and pain,P<0.05) and a global health status/QOL scale (P<0.05) and 6 single symptoms dyspnoea (P>0.05), insomnia (P<0.05), appetite loss (P<0.05), constipation (P<0.05), diarrhea (P>0.05) and financial difficulties (P<0.05). There was also signifificant difference in these items between the two groups when the placebo group and group over time were used as variants (P<0.05 or P<0.01).

CONCLUSIONAdditional use of JLSG on the basis of routine CM treatment could improve the somatic function, role function, emotional function, social function, cognitive function and general QOL of patients with advanced gastric cancer, and relieve the symptoms of fatigue, nausea and vomiting, pain, loss of appetite and constipation.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Middle Aged ; Placebos ; Quality of Life ; Stomach Neoplasms ; drug therapy ; physiopathology ; Young Adult