AIM　To synthesize piperazine derivatives and screen anti-tumor compounds with higher activity and lower toxicity. METHODS　Selecting 1,4-bis(3-bromopropionyl)piperazine as leading compound, a series of 1,4-bis［3-(amino-dithiocarboxy)propionyl］ piperazine derivatives (4a-j) were synthesized through the use of aminodithiocarboxylate. All the synthetic compounds (4a-j) were tested for their anti-tumor activity against eight kinds of tumor cells. RESULTS　Compounds (4a-j) are new compounds, among them, compounds 4c, 4d and 4e showed anti-tumor activity against HL-60. The inhibition of compounds 4c, 4d and 4e against HL-60 are 44%, 90% and 70% respectively, at the concentration of 10 μmol.L-1. However, the inhibition of the other kinds of anti-tumor cells are not distinctive. CONCLUSION　These results suggest that this may be one of the effective routes to improve the anti-tumor activity and reduce the toxicity of 1,4-bis(3-bromopropionyl)piperazine.

Objective To evaluate the association of peripheral blood inflammatory cytokines with mild cognitive impairment ( MCI) . Methods Databases including Pubmed,Cochrane library,Ovid,Web of science,CNKI,CBM,VIP and Wan Fang were retrieved to collect case-control studies related to the concen-tration of inflammatory cytokines in peripheral blood of MCI. After extracting data and appraising the quality of the included studies,meta-analysis were conducted using RevMan 5. 3 and CMA 3. 0. Results The lev-els of CRP,TNF-α,IL-1,MCP-1 and M-CSF and other 9 kinds of inflammatory factors in 33 studies were in-cluded in the analysis. A total of 8742 subjects were enrolled,including 2398 patients and 6344 controls. The Meta-analysis showed that the levels of CRP (SMD=0. 87,95％CI (0. 48,1. 26),P<0. 0001),TNF-α(SMD=1. 16,95％CI (0. 32,2. 00),P=0. 007),IL-1β (SMD=0. 96,95％CI (0. 17,1. 76),P=0. 02),IL-6 (SMD=1. 07, 95％CI (0. 53,1. 61),P<0. 0001),IL-8 (SMD=1. 65,95％CI (0. 36,2. 93),P=0. 01) in peripheral blood of pa-tients with MCI were significantly higher than that of normal control group;however,there was no statistical differ-ence between the two groups in the levels of IL-10,IL-12,MCP-1 and M-CSF. Conclusion The patients with MCI has a higher levels of CRP,TNF-α,IL-1β,IL-6 and IL-8 in peripheral blood,which suggesting that these in-flammatory factors may be related to the occurrence and development of AD.

Objective To train health care workers (HCWs)by method of conventional training plus survey of hand contamination status,the influence of two kinds of methods in hand hygiene compliance of HCWs was evalua-ted.Methods From November 2013 to April 2014,all HCWs in a cardiovascular internal medicine department were as trained subjects,they were divided into two groups (trial group and control group).Hand hygiene compli-ance status was investigated 1 month before training.In the first month after training,conventional training method was adopted by both groups,from the second to fifth month,conventional training plus hand contamination survey was adopted by trial group,hand hygiene compliance between two groups were compared.Results Hand hygiene compliance rates of trial group and control group was 42.63% (107/251 )and 41 .80% (102/244)respectively be-fore training,there was no significant difference(P >0.05 ).In the first and second month after training,hand hygiene compliance rate of trial group was 55.70% (132/237)and 63.11 % (154/244)respectively,control group was 56.52% (130/230)and 62.61 % (149/238)respectively,compared with pre-training,the differences were sig-nificant (both P <0.05),but the difference was not significant between two groups(P >0.05);From the third to fifth month,hand hygiene compliance rates of trial group was 60.73%(150/247),61 .44%(145/236),and 61 .22%(150/245)respectively,control group was 51 .68%(123/238),51 .02%(125/245 ),and 52.32% (124/237)respec-tively,there was significant difference between two groups(P <0.05).Conclusion Conventional training combined with survey of hand contamination status can promote hand hygiene compliance of HCWs.

Objective To investigate the effect of MACC1 on RSL3-induced ferroptosis in colorectal cancer cells and explore its molecular mechanism.Methods MACC1 expression was detected in SW620,HCT116,LOVO and RKO cells using Western blotting.The effects of different concentrations of RSL3(an inducer of ferroptosis)or Fer-1(an inhibitor of ferroptosis)alone,or 10 μmol/L RLS3 combined with 10 μmol/L Fer-1,on viability of SW620 cells were examined using MTT assay.The survival of SW620 cells with mRNA interference of MACC1 was analyzed following treatment with RSL3,and RT-qPCR and Western blotting were performed to detect the changes in MACC1 expressions after RSL3 treatment at different concentrations and the changes in GPX4 expression after MACC1 knockdown.Flow cytometry and laser confocal microscopy were used to analyze the changes in ROS-induced lipid peroxidation in SW620 cells after MACC1 knockdown.Results SW620 cells had the highest MACC1 expression among the 4 colorectal cancer cell lines.Treatment with RSL3 significantly inhibited the viability of SW620 cells in a dose-dependent manner,while Fer-1 did not significantly affect the survival of SW620 cells.RSL3 alone reduced SW620 cell survival by 50%(P<0.01),and the combined treatment with RSL3 and Fer-1 caused no significant changes in cell survival(P>0.05).Treatment with RSL3 concentration-dependently suppressed MACC1 expressions at both the mRNA and protein levels in SW620 cells(P<0.01).MACC1 knockdown obviously enhanced the cytotoxic effect of RSL3,inhibited the expression of GPX4,and increased ROS-induced lipid peroxidation in SW620 cells(P<0.05).Conclusion MACC1 knockdown enhances RSL3-induced ferroptosis in cultured colorectal cancer cells by inhibiting the expression of GPX4.

Objective To investigate the effect of MACC1 on RSL3-induced ferroptosis in colorectal cancer cells and explore its molecular mechanism.Methods MACC1 expression was detected in SW620,HCT116,LOVO and RKO cells using Western blotting.The effects of different concentrations of RSL3(an inducer of ferroptosis)or Fer-1(an inhibitor of ferroptosis)alone,or 10 μmol/L RLS3 combined with 10 μmol/L Fer-1,on viability of SW620 cells were examined using MTT assay.The survival of SW620 cells with mRNA interference of MACC1 was analyzed following treatment with RSL3,and RT-qPCR and Western blotting were performed to detect the changes in MACC1 expressions after RSL3 treatment at different concentrations and the changes in GPX4 expression after MACC1 knockdown.Flow cytometry and laser confocal microscopy were used to analyze the changes in ROS-induced lipid peroxidation in SW620 cells after MACC1 knockdown.Results SW620 cells had the highest MACC1 expression among the 4 colorectal cancer cell lines.Treatment with RSL3 significantly inhibited the viability of SW620 cells in a dose-dependent manner,while Fer-1 did not significantly affect the survival of SW620 cells.RSL3 alone reduced SW620 cell survival by 50%(P<0.01),and the combined treatment with RSL3 and Fer-1 caused no significant changes in cell survival(P>0.05).Treatment with RSL3 concentration-dependently suppressed MACC1 expressions at both the mRNA and protein levels in SW620 cells(P<0.01).MACC1 knockdown obviously enhanced the cytotoxic effect of RSL3,inhibited the expression of GPX4,and increased ROS-induced lipid peroxidation in SW620 cells(P<0.05).Conclusion MACC1 knockdown enhances RSL3-induced ferroptosis in cultured colorectal cancer cells by inhibiting the expression of GPX4.

Objective:To evaluate association of peripheral blood brain-derived neurotrophic factor (BDNF) with Alzheimer's disease (AD) .Methods:Databases including Pubmed, Cochrane library, Web of science, Embase, China National Knowledge Infrastructure, CBM disc, VIP-CSTJ and Wanfang Data were used to collect case-control studies related to the concentration of BDNF in peripheral blood of dementia patients with Alzheimer's type(DAT) and mild cognitive impairment(MCI). After extracting data and appraising the quality of the included studies, meta-analysis were conducted using Review Manager 5.3 and CMA 3.0.Results:A total of 51 articles were included in the analysis, with a total subjects of 7 182, including 2 673 subjects in DAT group, 1 506 subjects in MCI group, and 3 003 subjects in control group.The Meta-analysis showed that the levels of peripheral blood BDNF in patients with DAT were significantly lower than normal control group(SMD=-0.71, 95% CI : -0.99--0.43, P<0.001) ( n=5 111), and there were no statistical differences in peripheral blood BDNF levels between MCI group and control group and between DAT group and MCI group.The subgroup analysis showed that the level of serum BDNF in patients with DAT (SMD=-0.85, 95% CI: -1.15--0.55, P<0.001)( n=4 425) and MCI(SMD=-0.38, 95% CI: -0.62--0.14, P=0.002)( n=2 476) was significantly lower than that in normal control group, and the level of serum BDNF (SMD=-0.76, 95% CI: -1.37--0.16), P=0.01)( n=1 630) in patients with DAT was lower than that in MCI; However, there were no statistical difference among DAT, MCI and control groups in the level of plasma BDNF( P>0.05). Conclusion:The patients with DAT and mild cognitive impairment have lower level of serum BDNF, which suggesting that serum BDNF level may be a potential biomarker for early diagnosis of AD.

Hepatitis B is a major global public health issue. Through the implementation of comprehensive prevention and control strategies centered on hepatitis B vaccination， China has achieved remarkable progress in hepatitis B prevention and control， while there are still many issues and challenges. This article reviews the development of hepatitis B vaccination strategies in China， analyzes the goal and advances in vaccination in different populations， and problems and challenges， in order to provide a reference for further optimizing vaccination strategies and improving the levels of prevention and control.

【Objective】 To analyze the frequency and profile of irregular antibodies in different ethnic groups through screening and identification of irregular antibodies in 67 552 blood recipients in the Affiliated Hospital of Guizhou Medical University. 【Methods】 Irregular antibody screening was carried out in patients with different ethnic groups from August 1, 2016 to July 31, 2019 by microcolumn gel anti human globulin method, and the irregular antibody specificity were identified by panel cells. 【Results】 1)307 out of 67 552 cases were positive for irregular antibody, with the positive rate at 0.45%(307/67 552). Among them, Chuanqing was 1.27%(6/473), Yi 1.15%(4/348), Buyi 1.03%(10/975), Dong 0.58%(3/514), Han 0.44%(273/62 365), Miao 0.42%(5/1 187) and Tujia 0.34%(2/596), with significant differences among nationalities. Irregular antibody detection: the positive rate of female patients(0.56%, 223/41 359) was higher than that of male patients(0.32%, 84/26 193)(P<0.05). The positive rate of patients transfused before(1.22%, 129/10 553) was higher than non-transfusion patients(0.31%, 178/56 999)(P<0.05). The positive rate of female patients with pregnancy history(0.52%, 192/37 176) was higher than non-pregnancy females(0.17%, 7/4 183)(P<0.05). The positive rate increased with age, without any significant differences(P>0.05). The yields of irregular antibodies did not differ by ABO blood groups(P>0.05). 3)The specificity of 307 irregular antibody positive cases involved 7 blood group systems, including Rh system 59.28%(182/307), MNSs system 9.12%(28/307), Kidd system 0.65%(2/307), Duffy system 0.98%(3/307), Lewis system 5.86%(18/307), P system 0.65%(2/307), and Digeo system 0.33%(1/307). In addition, 15.64%(48/307) of autoantibodies, 0.65%(2/307) of cold antibodies and 4.93%(15/307) of unclear antibodies were detected. 4)The distribution of anti-D, anti-C and autoantibodies were statistically significant among the Han, Buyi, Chuanqing, Miao, Yi and Dong nationalities(P<0.05), while the others were similar(P>0.05). 【Conclusion】 The distribution of irregular antibodies in Guizhou is different by nationalities. Routine screening of irregular antibodies for transfused or pregnant patients can increase the safety and efficacy of blood transfusion. Most of the irregular antibodies detected are Rh blood group system. The exposure to irregular antibodies can be reduced by additional detection of blood group antigen other than RhD for blood recipients and donors, as well as the blood transfusion with matched blood group antigens.

Urea transporters (UT) play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics. Thus, UT inhibitors are promising for development as novel diuretics. In the present study, a novel UT inhibitor with a diarylamide scaffold was discovered by high-throughput screening. Optimization of the inhibitor led to the identification of a promising preclinical candidate,