Objective Mendelian randomization(MR)analysis was used to explore the genetic link between immunophenotype and breast cancer(BC)risk and how cerebrospinal fluid(CSF)metabolites play a part in mediating this.Methods We used MR to assess the genetic associations between immune cells and BC risk and their possible mediators.Genetic statistics for immune cells and CSF metabolites were obtained from the Genome-Wide Association Study(GWAS)catalog,whereas those for BC were obtained from the Japan Biobank,the UK Biobank,and FinnGen's cross-ethnic meta-analysis.We performed a two-sample MR analysis using inverse variance weighting(IVW)to investigate the genetic association between immunoepidemiology and BC.We also analyzed CSF metabolites as mediators between them.Heterogeneity was tested using the Cochran's Q statistic,horizontal pleiotropy was tested using the MR Egger intercept,and sensitivity analysis was performed using the"leave-one-out"method.Results MR analysis by the IVW method showed that HLA DR+CD4+T cells were associated with a reduced risk of BC(OR=0.972,95％ CI:0.955-0.990,P=0.003),and there was a negative genetic association between HLA DR+CD4+T cells and methylsuccinimidyl carnitine level(OR=0.922,95％ CI:0.861-0.986,P=0.018),but there was a positive genetic association between the latter and BC risk(OR=1.029,95％ CI:1.012-1.047,P＜0.001).Mediation analysis showed that the direct effect remained significant after correction for CSF methylsuccinylcarnitine level(β=-0.026,SE=0.008,P=0.002).And the indirect effect(β=-0.002,Delta Method SE=0.001)suggested that this CSF metabolite might mediate 8.36％of the association in the protective effect of immune cells against BC risk(95％ CI:-12.4％-29.1％).Conclusion Genetically predicted HLA DR+CD4+T cells may reduce the risk of BC development by modulating the level of methylsuccinylcarnitine,the CSF metabolite.

Objective Mendelian randomization(MR)analysis was used to explore the genetic link between immunophenotype and breast cancer(BC)risk and how cerebrospinal fluid(CSF)metabolites play a part in mediating this.Methods We used MR to assess the genetic associations between immune cells and BC risk and their possible mediators.Genetic statistics for immune cells and CSF metabolites were obtained from the Genome-Wide Association Study(GWAS)catalog,whereas those for BC were obtained from the Japan Biobank,the UK Biobank,and FinnGen's cross-ethnic meta-analysis.We performed a two-sample MR analysis using inverse variance weighting(IVW)to investigate the genetic association between immunoepidemiology and BC.We also analyzed CSF metabolites as mediators between them.Heterogeneity was tested using the Cochran's Q statistic,horizontal pleiotropy was tested using the MR Egger intercept,and sensitivity analysis was performed using the"leave-one-out"method.Results MR analysis by the IVW method showed that HLA DR+CD4+T cells were associated with a reduced risk of BC(OR=0.972,95％ CI:0.955-0.990,P=0.003),and there was a negative genetic association between HLA DR+CD4+T cells and methylsuccinimidyl carnitine level(OR=0.922,95％ CI:0.861-0.986,P=0.018),but there was a positive genetic association between the latter and BC risk(OR=1.029,95％ CI:1.012-1.047,P＜0.001).Mediation analysis showed that the direct effect remained significant after correction for CSF methylsuccinylcarnitine level(β=-0.026,SE=0.008,P=0.002).And the indirect effect(β=-0.002,Delta Method SE=0.001)suggested that this CSF metabolite might mediate 8.36％of the association in the protective effect of immune cells against BC risk(95％ CI:-12.4％-29.1％).Conclusion Genetically predicted HLA DR+CD4+T cells may reduce the risk of BC development by modulating the level of methylsuccinylcarnitine,the CSF metabolite.

Objective To explore the mechanism by which soybean isoflavone(SI)reduces calcium overload induced by cerebral ischemia-reperfusion(I/R).Methods Forty-eight SD rats were randomized into 4 groups to receive sham operation,cerebral middle artery occlusion for 2 h followed by 24 h of reperfusion(I/R model group),or injection of adeno-associated virus carrying Frizzled-2 siRNA or empty viral vector into the lateral cerebral ventricle after modeling.Western blotting was used to examine Frizzled-2 knockdown efficiency and changes in protein expressions in the Wnt/Ca2+signaling pathway.Calcium levels and pathological changes in the ischemic penumbra(IP)were measured using calcium chromogenic assay and HE staining,respectively.Another 72 SD randomly allocated for sham operation,I/R modeling,or soy isoflavones pretreatment before modeling were examined for regional cerebral blood flow using a Doppler flowmeter,and the cerebral infarct volume was assessed using TTC staining.Pathologies in the IP area were evaluated using HE and Nissl staining,and ROS level,Ca2+level,cell apoptosis,and intracellular calcium concentration were analyzed using immunofluorescence assay or flow cytometry;the protein expressions of Wnt5a,Frizzled-2,and P-CaMK II in the IP were detected with Western blotting and immunohistochemistry.Results In rats with cerebral I/R,Frizzled-2 knockdown significantly lowered calcium concentration(P<0.001)and the expression levels of Wnt5a,Frizzled-2,and P-CaMK II in the IP area.In soy isoflavones-pretreated rats,calcium concentration,ROS and MDA levels,cell apoptosis rate,cerebral infarct volume,and expression levels of Wnt/Ca2+signaling pathway-related proteins were all significantly lower while SOD level was higher than those in rats in I/R model group.Conclusion Soy isoflavones can mitigate calcium overload in rats with cerebral I/R by inhibiting the Wnt/Ca2+signaling pathway.

Objective To explore the mechanism by which soybean isoflavone(SI)reduces calcium overload induced by cerebral ischemia-reperfusion(I/R).Methods Forty-eight SD rats were randomized into 4 groups to receive sham operation,cerebral middle artery occlusion for 2 h followed by 24 h of reperfusion(I/R model group),or injection of adeno-associated virus carrying Frizzled-2 siRNA or empty viral vector into the lateral cerebral ventricle after modeling.Western blotting was used to examine Frizzled-2 knockdown efficiency and changes in protein expressions in the Wnt/Ca2+signaling pathway.Calcium levels and pathological changes in the ischemic penumbra(IP)were measured using calcium chromogenic assay and HE staining,respectively.Another 72 SD randomly allocated for sham operation,I/R modeling,or soy isoflavones pretreatment before modeling were examined for regional cerebral blood flow using a Doppler flowmeter,and the cerebral infarct volume was assessed using TTC staining.Pathologies in the IP area were evaluated using HE and Nissl staining,and ROS level,Ca2+level,cell apoptosis,and intracellular calcium concentration were analyzed using immunofluorescence assay or flow cytometry;the protein expressions of Wnt5a,Frizzled-2,and P-CaMK II in the IP were detected with Western blotting and immunohistochemistry.Results In rats with cerebral I/R,Frizzled-2 knockdown significantly lowered calcium concentration(P<0.001)and the expression levels of Wnt5a,Frizzled-2,and P-CaMK II in the IP area.In soy isoflavones-pretreated rats,calcium concentration,ROS and MDA levels,cell apoptosis rate,cerebral infarct volume,and expression levels of Wnt/Ca2+signaling pathway-related proteins were all significantly lower while SOD level was higher than those in rats in I/R model group.Conclusion Soy isoflavones can mitigate calcium overload in rats with cerebral I/R by inhibiting the Wnt/Ca2+signaling pathway.

Objective:To re-evaluate the systematic evaluation and meta-analysis of safety of statins in pregnancy and provide reference for the safe use of statins in pregnant women.Methods:The systematic reviews/meta-analysis on the safety of statins during pregnancy were retrieved from databases (up to October 8, 2023). The preferred reporting items for systematic reviews and meta-analyse (PRISMA) were used to evaluate the quality of the included literature, a measure tool to assess systematic reviews 2 (AMSTAR 2) scale was used to evaluate the methodological quality of the included literature, and the grading of recommendations assessment, development, and evaluation (GRADE) tool was used to evaluate the evidence quality of the included literature. The results of quantitative analysis of outcome indicators were expressed by relative risk, odds ratio, mean difference and their 95% confidence interval.Results:A total of 12 systematic reviews/meta-analysis were included. There were 5, 4 and 3 documents with high quality, medium quality, and low quality, respectively, which were evaluated by PRISMA. There were 2 and 10 documents with high and very low quality, which were evaluated by AMSTAR 2 scale. The GRADE tool evidence quality evaluation results showed that among the 48 evidence bodies, 4 were of intermediate quality (8.3%), 37 were of low quality (77.1%), and 7 were of very low quality (14.6%). The re-evaluation results of systematic review/meta-analysis showed that statins exposure during pregnancy did not increase the risk of fetal birth defects and premature delivery, but increased the risk of spontaneous abortion. Pravastatin might reduce the incidence of preeclampsia with uteroplacental insufficiency and neonatal intensive care unit occupancy in patients. There were inconsistent results of statin exposure on fetal cardiac abnormalities and the risk of artificial abortion.Conclusion:Statins exposure during pregnancy does not increase the risks of fetal birth defects and premature birth, but increases the risk of spontaneous abortion.

Objective:To re-evaluate the systematic evaluation and meta-analysis of safety of statins in pregnancy and provide reference for the safe use of statins in pregnant women.Methods:The systematic reviews/meta-analysis on the safety of statins during pregnancy were retrieved from databases (up to October 8, 2023). The preferred reporting items for systematic reviews and meta-analyse (PRISMA) were used to evaluate the quality of the included literature, a measure tool to assess systematic reviews 2 (AMSTAR 2) scale was used to evaluate the methodological quality of the included literature, and the grading of recommendations assessment, development, and evaluation (GRADE) tool was used to evaluate the evidence quality of the included literature. The results of quantitative analysis of outcome indicators were expressed by relative risk, odds ratio, mean difference and their 95% confidence interval.Results:A total of 12 systematic reviews/meta-analysis were included. There were 5, 4 and 3 documents with high quality, medium quality, and low quality, respectively, which were evaluated by PRISMA. There were 2 and 10 documents with high and very low quality, which were evaluated by AMSTAR 2 scale. The GRADE tool evidence quality evaluation results showed that among the 48 evidence bodies, 4 were of intermediate quality (8.3%), 37 were of low quality (77.1%), and 7 were of very low quality (14.6%). The re-evaluation results of systematic review/meta-analysis showed that statins exposure during pregnancy did not increase the risk of fetal birth defects and premature delivery, but increased the risk of spontaneous abortion. Pravastatin might reduce the incidence of preeclampsia with uteroplacental insufficiency and neonatal intensive care unit occupancy in patients. There were inconsistent results of statin exposure on fetal cardiac abnormalities and the risk of artificial abortion.Conclusion:Statins exposure during pregnancy does not increase the risks of fetal birth defects and premature birth, but increases the risk of spontaneous abortion.

OBJECTIVE To evaluate the effects of gene polymorphism on the efficacy and safety of citalopram/escitalopram， and to provide evidence-based reference for precision medication. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI， Wanfang data and SinoMed， clinical studies about the association of gene polymorphism with efficacy and safety of citalopram/escitalopram were collected. Meta-analysis was performed with RevMan 5.3 software after literature screening， data extraction and quality evaluation based on Newcastle-Ottawa scale. RESULTS Totally 35 pieces of literature were included， all of which were cohort studies， with a total of 9 836 patients. Meta-analysis showed that the SLC6A4 gene 5-serotonin transporter linked polymorphic region （HTTLPR） LL genotype was associated with high response rate of citalopram/escitalopram [LS/SS vs. LL： OR＝0.47， 95%CI （0.22， 0.98）， P＝0.05]； results of subgroup analysis suggested a higher correlation in white people with LL genotype and escitalopram； there was no significant correlation of HTTLPR genotype with remission rate [LS/SS vs. LL： OR＝ 0.92，95%CI（0.77， 1.10）， P＞0.05； SS vs. LL/LS：OR＝0.73， 95%CI（0.45， 1.19）， P＞0.05] or overall incidence of ADR in patients with gene SLC6A4； but high expression of rs25531 LA was significantly associated with reduced incidence of ADR（P＜ 0.05）. CYP2C19*2/*3 allele was significantly associated with slowed metabolism， higher response rate and increased incidence of ADR. CONCLUSIONS HTTLPR LL genotype is associated with the increased response rate of citalopram/escitalopram， but no significant correlation with safety is found， while CYP2C19*2/*3 allele is significantly associated with higher response rate and reduced tolerability.

Objective:To evaluate ward nurses′ understanding of nuclear medicine and assess whether they can prepare for scintigraphy procedures and answer patient′s questions about nuclear medicine examinations.Methods:An online questionnaire was provided to nurses in 11 wards of Wuxi Second Hospital Affiliated to Nanjing Medical University where nuclear medicine examinations were frequently undergone. The questionnaire contained 3 parts: general data, self-assessment, objective testing of knowledge about nuclear medicine. Professional titles, educations, working years, self-assessment and objective testing for knowledge of nuclear medicine for patients′ preparation and question of involvers were collected. Results of objective knowledge test among different professional titles, educations and the results of self-assessment were analyzed using one-way analysis of variance and independent-sample t test. Pearson correlation analysis was used to evaluate the correlation between objective testing results and working years. Results:The effective receiving rate of questionnaire was 96.4%(267/277). There were 96.3%(257/267) involvers did not receive any specific training in nuclear medicine, and only 4.9%(13/267) considered they knew nuclear medicine well. There were 50.2%(134/267) involvers thought that their knowledge of nuclear medicine was enough to prepare nuclear medicine examination for patients and 49.8%(133/267) involvers thought that they were able to explain nuclear medicine examination for patients. In objective knowledge test, (14.6±2.8) questions answered correctly for each person, with a correct rate of (54.9±10.5)%. There were (14.1±2.8), (15.5±2.3) and (16.8±3.9) questions answered correctly in involvers with primary title, mid-level title and senior title respectively ( F=9.789, P<0.001), and (15.8±2.5), (14.2±2.8) in involvers with bachelor degree or above and college degree ( t=3.477, P<0.001). There was only subtle correlation between objective testing results and working years ( r=0.257, P<0.01). The main way that involvers obtained nuclear information was through experience-based teaching methods such as introductions from colleagues(57.7%, 154/267) and department education(18.0%, 48/267). Conclusions:Lacking of formal nuclear medicine orientation is common in ward nurses, and their understanding of nuclear medicine examinations is insufficient. Working characteristics and learning patterns of ward nurses should be considered when providing information on nuclear medicine treatments for them.

Objective:To investigate the mechanism by which Melittin-K1 reverses multidrug resistance of BEL-7402/5-FU cells.Methods:CCK-8 assay was used to evaluate the effect of Melittin-K1 on the growth of BEL-7402/5-FU cells and to explore whether Melittin-K1 could reverse the drug resistance of BEL-7402/5-FU cells. The expression of MDR1 mRNA level was detected by real-time fluorescence quantitative PCR assay. The flow cytometry was used to measure the expression of P-glycoprotein (P-gp) on the cell membrane surface and the accumulation of rhodamine-123 in cells.Results:Melittin-K1 significantly inhibited the growth of BEL-7402/5-FU cells in vitro in a time and dose-dependent manner. Melittin-K1 suppressed the level of MDR1 mRNA and inhibited the surface expression and function of P-gp in BEL-7402/5-FU cells. Conclusions:Melittin-K1, a novel peptide, exhibited the activity of reversing multidrug resistance of liver cancer cells.

Objective:To investigate the relevance between spatial learning and memory impairment and the changes of inducible nitric oxide synthase (iNOS) activity,superoxide dismutase (SOD) activity and malondiadehyde (MDA) content in hippocampus from Type 1 diabetic mice.Methods:Sixty male mice were randomly assigned into a control group (NC group,20 mice) and a Type 1 diabetic group (DM group,40 mice).Type 1 diabetic mouse models were established by a large dose intraperitoneal injection of streptozotocin (100 mg/kg).The spatial learning and memory abilities of mice were assessed by Morris water maze (MWM) test.After MWM test,we chose 20 mice (diabetic encephalopathy mice) with the worst spatial learning and memory abilities from diabetic model group,and detected the iNOS activity,SOD activity and MDA content in hippocampus in both groups.Results:Compared with the NC group,the escape latency was significantly extended and platform crossings were significantly declined in diabetic mice (P＜0.01).Furthermore,the activity of iNOS and the content of MDA were markedly increased,and the activity of SOD was significantly decreased in hippocampus of diabetic encephalopathy mice (P＜0.01).Conclusion:The established Type 1 diabetic mice show symptoms of cognitive dysfunction,which might be related to the increase of oxidative stress in hippocampus.