SENP1 induced protein deSUMO modification increased the chemotherapy sensitivity of endometrial cancer side population cells / 中华肿瘤杂志

Objective: To inhibit the stemness maintenance potential of endometrial cancer and increase the sensitivity of endometrial cancer side population cells to chemotherapy drugs by inducing extensive deSUMOylation modification of proteins. Methods: Flow cytometry was used to sort and culture CD133(+) CD44(+) KLE endometrial cancer cell clone spheres. Protein expression level of small ubiquitin-related modifier 1 (SUMO1) and two stemness maintenance genes of tumor side population cells, octamer binding transcription factor-4 (Oct4) and sex determining region Y-box2 (Sox2), were detected by western blotting method. Lentivirus-mediated Sentrin/SUMO-specific proteases 1 (SENP1) gene was stably transfected into KLE side population cells. Western blotting was used to detect the protein expressions of SENP1, SUMO1, Oct4 and Sox2. The clone formation rate was compared between KLE side population cells with or without SENP1 overexpression. Flow cytometry was applied to detect cell cycle changes. 3-(4, 5-Dimethylthiazole-2)-2, 5-diphenyl-tetrazolium bromide (MTT) experiment and flow cytometry apoptosis method were used to detect the chemosensitivity of the side population of endometrial cancer cells to cisplatin. Tumor-bearing mouse models of endometrial cancer were established to detect the effect of SENP1 overexpression on the chemotherapy sensitivity of cisplatin. Results: Compared with CD133(-)CD44(-) KLE cells, CD133(+) CD44(+) KLE side population cells could form clonal spheres and express higher levels of SUMO1, Oct4 and Sox2 proteins (P<0.05). Compared with KLE side population cells that were not transfected with SENP1 gene, the expression level of SENP1 protein in KLE side population cells overexpressing SUMO1、Oct4 and Sox2 were lower. The clonal sphere formation rate was reduced from (25.67±5.44)% to (7.46±1.42)%, and cell cycle shifted from G(0)/G(1) phase to G(2) phase. IC(50) of cisplatin decreased from (55.46±6.14) μg/ml to (11.55±3.12) μg/ml, and cell apoptosis rate increased from (9.76±2.09)% to (16.79±3.44)%. Overexpression of SENP1 could reduce the tumorigenesis rate of KLE side population cells in vivo and increase their chemotherapy sensitivity to cisplatin (P<0.05). Conclusion: Overexpression of SENP1 can induce protein deSUMOylation modification, inhibit the stemness maintenance potential of endometrial cancer side population cells, and enhance their chemotherapy sensitivity, which provides a new reference for gene therapy of endometrial cancer.

A study of the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg- positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA / 中华肝脏病杂志

Objective: To investigate the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg-positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA. Methods: Treatment-naïve chronic hepatitis B patients who were followed up at the Center of Infectious Diseases, West China Hospital of Sichuan University from January 2019 to January 2020 were selected as subjects. Demographic characteristics, the results of laboratory examination before treatment and one year after treatment were retrospectively collected. Patients were divided into tenofovir dipivoxil (TDF) and propofol fumurate tenofovir (TAF) treatment group according to different types of medication. The changes of serum HBV DNA level, HBeAg serological conversion and HBsAg quantitative level were analyzed and compared between the two groups. Results: A total of 38 cases were enrolled. Among them, there were 16 and 22 cases in the TDF and TAF group, respectively. There was no statistically significant difference in demographic characteristics, baseline HBV DNA levels and HBsAg quantitative levels between the two groups. Virological response was achieved in 60.5% (23/38) of patients after one year of antiviral therapy. Serum HBV DNA levels below the lower limit of detection [68.2% (15/22) vs. 50.0% (8/16), P=0.258] and higher HBeAg seroconversion rate [18.2%] (4/22) vs. 6.3% (1/16), P=0.374] was obtained in TAF than TDF group; however, there was no statistically significant differences between the two. Serum HBsAg quantitative level was significantly reduced with TDF and TAF treatment. In addition, alanine aminotransferase elevation was reduced in TAF than TDF treated group. Multivariate logistic regression analysis showed that patient age was an independent predictor of a virological response to antiviral therapy. Conclusion: HBeAg-positive CHB patients with normal alanine aminotransferase, and high HBV DNA level can obtain better curative effect after TDF and TAF treatment.

Molecular Characterization of Two Novel Defensins from Mytilus coruscus / 中国生物化学与分子生物学报

Mytilus is a bivalve species with important economic and ecosystem value over worldwide. Mytilus antimicrobial peptides‚ with strong molecular diversity‚ has become a research focus. Two novel antimicrobial peptides were identified from Mytilus‚ with structural features that similar to arthropod defensins. However‚ the functional features and the immune mechanism of these two mussel defensins are unknown. For this reason‚ the two novel defensins‚ Arthropod like defensn-1 and -2 (ALD-1 and ALD-2‚ respectively)‚ were studied for the sequence features‚ expression profiles‚ and the dynamic expression pattern after different microbe induction. In addition‚ solid phase chemical synthesis technology was used for the synthesis of these two novel ALDs‚ and the function of synthesized peptides of ALD was verified. The results indicated that‚ two ALDs of M. coruscus have classical structure features similar to those of other arthropod defensins. These two ALDs are mainly presented in the tissues of mantle and digestive gland of mussel. The results also suggest that ALD-1 was expressed at higher levels in the gonads of males than in females (P<0. 05). The expression of two ALDs is developmentally regulated‚and both ALD-1 and ALD-2 were undetectable in larvae‚ but can be detected with high expression level at adult mussel with age of six months. The dynamic changes in the expression level of two ALDs after microbial induction were examined‚ and the results showed a marked increase in expression level observed in vivo for both ALDs. Interestingly‚ two ALDs showed different sensitivities to different microbes‚ indicating very complex responses during the mussel immune response. This observation strongly suggests the existence of different recognition mechanism or signal transduction pathway in mussels for the expression of ALD-1 and ALD-2. Moreover‚ both of two chemical synthesized ALDs showed significant antimicrobial activities against five tested microbes with an inhibition ratio of 20%-80%. These results provided basis for understanding the molecule mechanism of Mytilus immunology‚ and the function of novel Mytilus defensins‚ and thusly provided basis for the development of molecular resource for mussel antimicrobial peptides.

Research advances of small molecule inhibitors in the treatment of mixed lineage leukemia / 药学学报

Acute leukemia (AL) is a kind of malignant clonal disease of hematopoietic stem cells. Rearrangement of mixed lineage leukemia (MLL) gene can be observed in about 5%-10% of AL patients. Currently, AL patients with MLL-rearrangements (MLL-r) lack effective treatment and are usually associated with poor prognoses. Recent studies have shown that many epigenetic regulators are directly or indirectly involved in the occurrence and development of AL carrying MLL-r (MLL), which provides a biological basis for the use of epigenetic regulation strategies to treat MLL. In this review, we start from the epigenetic regulation mechanism of MLL, and select representative drug targets to briefly analyze the relationship between each target and MLL and summarize the development progress of their inhibitors, hoping to provide reference for the subsequent research and development of drugs for the treatment of MLL.

Effect of Salvianolate Lyophilized Injection and Xueshuantong Injection (Lyophilized) on Permeability of Blood-brain Barrier via Inhibition of MMPs in Cerebral Ischemia/Reperfusion Injury Rats / 中国实验方剂学杂志

Objective:To investigate the effect of salvianolate lyophilized injection and Xueshuantong injection (lyophilized) on the permeability of blood-brain barrier (BBB) via inhibition of metallomatrix protease（MMPs） in cerebral ischemia/reperfusion injury rats. Method:The focal cerebral ischemia/reperfusion model in rats was built by middle cerebral artery occlusion/reperfusion (MCAO/R) technique. Male Wistar rats were randomly divided into sham operation group, ischemia/reperfusion (I/R) group, edaravone (Eda, 6 mg·kg-1) group, salvianolate lyophilized injection (SLI, 21 mg·kg-1) group, Xueshuantong (XST, 100 mg·kg-1) group and SLI combined with XST (SLI+XST, 21 mg·kg-1+100 mg·kg-1) group. Drugs were injected via tail vein for 2 d, while sham group and I/R group were injected with the same amount of normal saline. Neurological deficit score, hematoxylin-eosin (HE) staining and Nissl staining were assessed 2 d after MCAO/R. The permeability of BBB was observed by the leakage of IgG/CD31. The expressions of Claudin-5，Occludin，collagen-Ⅳ（Col- Ⅳ），Laminin，Fibronectin were observed by immunofluorescence staining，and MMP-2 and MMP-9 were observed by Western blot. Result:Compared with the I/R group, SLI group, XST group and SLI+XST group showed improvements in neurological deficit score, HE staining and Nissl staining. The leakage of IgG was alleviated; The positive expressions of Claudin-5，Occludin，Col-Ⅳ，Laminin，Fibronectin in ischemic penumbra were significantly up-regulated, while the expressions of MMP-2 and MMP-9 were down-regulated. The effect in improving SLI combined with XST was much better than a single factor. Conclusion:Salvianolate lyophilized injection and Xueshuantong injection (lyophilized) can alleviate cerebral ischemia/reperfusion injury and exert the synergistic effect when they are used in combination. The mechanisms might be associated with the improvement in the permeability of blood-brain barrier by inhibiting MMPs in cerebral ischemia/reperfusion injury rats.

Discrimination of Rana dybowskii,Its Analogues and Counterfeits Based on Polyacrylamide Gel Electrophoretograms Combined with Cluster Analysis and Multivariate Statistical Analysis / 中国实验方剂学杂志

Objective:To establish an effective classification and identification method for sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) maps of Rana dybowskii,its analogues and counterfeits based on cluster analysis and multivariate statistical analysis. Method:SDS-PAGE maps of 18 batches of R. dybowskii,its analogues and 2 counterfeits were obtained by SDS-PAGE method. SDS-PAGE maps were transformed into data matrix. NTSYSpc 2.10e statistical analysis software was used for cluster analysis,and SMICA-P 14.1 software was used for multivariate statistical analysis. Unsupervised Principal Component Analysis (PCA),Supervised Partial Least Squares Discriminant Analysis (PLS-DA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) were performed for multivariate analysis and evaluation. Result:SDS-PAGE maps technology combined with cluster analysis and multivariate statistical analysis could accurately classify and identify R. dybowskii,its analogues and counterfeits. Cluster analysis could cluster four kinds of medicinal materials into four branches except No.1 medicinal materials. PCA results were superior to cluster analysis. Supervised PLS-DA and OPLS-DA results in multivariate statistical analysis were superior to unsupervised PCA. The classification and identification efficiencies of OPLS-DA were better than those of unsupervised PCA. OPLS-DA aggregated R. dybowskii,its analogues and 2 counterfeits into four groups. Six different protein components were obtained by comprehensive analysis of variable importance in projection (VIP) value, and OPLS-DA Bi load diagram,with relative molecular weights were 51.363,35.838,14.565,17.563,15.358 and 21.696 kDa,respectively. Conclusion:SDS-PAGE maps combined with cluster analysis and multivariate statistical analysis can be used as an effective method to classify and identify R. dybowskii,its analogues and counterfeits. This study provides a reference for the quality evaluation and screening of R. dybowskii.

Short-Term Therapeutic Efficacy, Survival Time and Side Effects in Treatment of Newly Diagnosed Multiple Myeloma Patients with Different Chemotherapeutic Regimens / 中国实验血液学杂志

OBJECTIVE@#To investigate the short-term therapeutic efficacy, survival time and side effects in newly diagnosed multiple myeloma patients treated with TCD regimen consisted of thalidomide, cyclophosphiamide and dexamethasone, and BCD reginen consisted of bortezomib, cyclophsphamide and dexamethasone.@*METHODS@#The clinical data of newly diagnosed MM patients admitted in our hospital from January 2011 to January 2018 were collected and analyzed retrospectively. According to chemotherapectic regimen, 106 patients were divided into 2 groups: 53 cases in one group were treated with TCD regimen (TCD group), and 53 cases in another group were treaded with BCD regimen (BCD group). The therapeutic efficacy, median PFS and OS time and incidence of side effects in 2 groups were compared, at the same time the relationship of the remission degree and the factors in different subgroups with the therapeutic efficacy was analyzed in 2 groups.@*RESULTS@#There was no significant difference in the ≥MR rate between 2 groups (P＞0.05). The ≥PR rate, ≥VGPR rate and CR rate of BCD group were significantly higher than TCD group (P＜0.05). The median PFS time of patients in BCD group were significantly longer than that in TCD group (P＜0.05). There was no significant difference in the median OS time of patients between 2 groups (P＜0.05). The median OS time of ≥MR patients in TCD group was significantly longer than that of ＜MR patients (P＜0.05). The median OS time of ≥PR patients in TCD group were significantly longer than that of ＜PR patients (P＜0.05). The median OS time of ≥VGPR patients in BCD group was significantly longer than that of ＜VGPR patients (P＜0.05). There was no significant difference in the median OS time of ≥PR and ＜PR patients in BCD group (P＞0.05). The ORR of ≥VGPR patients in BCD group was significantly higher than that in TCD group (P＜0.05). There was no significant difference in the incidence of infection, fatigue, gastrointestinal reactions and bone marrow suppression between 2 groups (P＜0.05). The incidence of numbness in distal extremities and herpes zoster in BCD group was significantly higher than that in TCD group (P＜0.05).@*CONCLUSION@#TCD and BCD in the treatment of patients with NDMM possess the same disease control effects; BCD regimen application can efficiently improve remission degree and prolong PFS time; but TCD regimen application have the advantages in reducing the side effects risk and improving treatment tolerance.

A SNP in 5′ untranslated region of CD40 gene is associated with an increased risk of ischemic stroke in a Chinese population: a case-control study

Abstract Cluster of differentiation 40 (CD40), the receptor for CD154, is a member of the tumor necrosis factor (TNF) receptor superfamily. Several studies have been conducted to investigate the effect of the CD40 rs1883832 polymorphism on atherosclerotic disease in different population; however, inconsistent results were obtained. In this study, we investigated the association of four polymorphisms (rs1883832, rs13040307, rs752118 and rs3765459) of CD40 gene and their effect on CD40 expression with the risk of ischemic stroke (IS) in a Chinese population. Three hundred and eighty patients with IS and 450 control subjects were included in the study. The CD40 polymorphisms were discriminated by Snapshot SNP genotyping assay. Serum soluble CD40 (sCD40) levels were detected by ELISA. We found that the rs1883832CT and rs1883832TT genotypes were associated with an increased risk of IS compared with the rs1883832CC genotype (OR = 1.42, 95% CI: 1.03-1.95, p = 0.030 and OR = 1.91, 95% CI: 1.29-2.82, P = 0.001, respectively), and the rs1883832T allele was associated with a significantly increased risk of IS compared with rs1883832C allele (OR = 1.40, 95% CI: 1.15-1.70, P = 0.001). Elevated serum sCD40 levels were observed in patients with IS compared with the control gropu (P < 0.01). Individuals carrying the rs1883832TT or rs1883832CT genotypes showed significantly higher sCD40 levels compared with the rs1883832CC genotype in the IS group [(64.8 ± 25.4 pg/mL, TT = 94); (63.9 ± 24.3 pg/mL, CT = 185) vs (53.3 ± 22.5 pg/mL, CC = 101), P < 0.01]. The TCCA haplotype was associated with an increased risk of IS compared with the control group (OR = 2.10, 95% CI: 1.23-3.58, p = 0.005). However, we did not find a significant association between the other three polymorphisms and IS risk. In conclusion, after a comprehensive comparison with other studies, we confirmed that the rs1883832T allele but not the rs1883832C allele is associated with an increased risk of IS. The rs1883832 polymorphism may exert influences on abnormal CD40 expression in IS patients among the Chinese population.

Development and evaluation of a new questionnaire for factors influencing the quality of nursing interns / 中国实用护理杂志

Objective To develop a questionnaire for factors influencing the quality of nursing interns.Methods The factors influencing the quality of nursing interns were formulated through literature review,interview and expert consultation.The pre-questionnaire was developed after modification.Exploratory factor analysis and correlation analysis were used to examine the reliability and validity of this questionnaire.Results Six common factors were extracted by exploratory factor analysis.Factor loading ranged from 0.487 to 0.889 for each item.The Cronbach α of the total scale was 0.814,and that of subscales ranged from 0.802 to 0.863.Retest-reliability coefficient of the total scale was 0.863,and that of subscales ranged from 0.794 to 0.931.Conclusions The self-designed questionnaire for factors influencing the quality of nursing interns has good reliability and validity,and can be used to measure the influencing factors for nursing interns.

Study on reduced folate carrier gene (RFC1) polymorphism in the southern and northern Chinese population / 中华流行病学杂志

<p><b>OBJECTIVE</b>To describe the distribution of reduced folate carrier gene (RFC1)genotype and allele frequency between southern and northern, female and male Chinese population.</p><p><b>METHOD</b>RFC1 (A80G) genotype was detected, using polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) on 720 blood spot DNA from the normal subjects.</p><p><b>RESULTS</b>The frequencies of the northern population with AA, GG and GA genotypes were 22.28%, 31.09% and 46.63%, and the frequencies of the southern population were 18.56%, 22.75% and 58.68%, respectively. Findings showed that there were significant differences between southerners and northerners in RFC1 (A80G) genotype (P < 0.01). There was no significant difference between G allele frequency of the northern (52.10%) and southern population (54.40%). The frequencies of male with RFC1 (A80G) AA, GG and GA genotype were 24.88%, 25.85% and 49.27%, and among female were 18.83%, 27.77% and 53.40%, respectively. There were no significant differences between male and female in RFC1 genotype (P > 0.05), or between G allele frequency in female (50.49%) and that in male (54.47%).</p><p><b>CONCLUSIONS</b>The distribution of RFC1 genotype seemed to be consistent with neural tube defects (NTDs) while its prevalence among the northerners was higher than that of southerners, with female having a higher NTDs prevalence. This study provided genetic epidemiological data for etiological hypothesis between RFC1 and diseases relative to folate metabolism.</p>