Objective To investigate the effect of sterol regulating element binding protein (SREBP1c) and its ac-tive form (SREBP1cm) on human protein kinase R-like endoplasmic reticulum kinase (PERK).Methods Re-porter victors of PERK promoter and its truncations were constructed with pGL 3-basic and co-transfected with internal reference pRL-SV40 into cell and luciferase activity was detected .pcDNA3.1 ( -)-SREBP1c or pcDNA3.1 ( -)-SREBP1cm was co-transfected with PERK promoter transcriptional activity core regions and the detection of dual -lu-ciferase reporter gene was used to analyze the regulation of SREBP 1c/1cm on PERK promoter transcriptional activity . The expression level of PERK mRNA and protein were detected by RT-PCR and Western blot .Results PERK pro-moter and truncations were successfully constructed into pGL 3-basic, and PERK promoter core area of transcription-al activity had determined;Dual-luciferase report gene showed that SREBP 1c inhibited PERK promoter transcrip-tional activity and SREBP1cm promoted PERK promoter transcriptional activity .RT-PCR and Western blot showed that SREBP1c decreased PERK mRNA and protein expression , but SREBP1cm increased PERK mRNA and protein expression, which was consistent with the detection of dual-luciferase report gene .Conclusions SREBP1c and SREBP1cm have a opposite regulation effect on PERK promoter transcriptional activity and its expression .

OBJECTIVETo analyze a girl with moderate mental retardation and speech and language disorders with cytogenetics technique and next-generation sequencing (NGS).

METHODSG-banding chromosome analysis was used to ascertain the karyotype of the child and her parents, and NGS was used for determining the size and origin of the abnormal chromosome fragment. Mate-pair and PCR were used to determine its parental origin.

RESULTSThe karyotype of the child was determined to be 46,XX,add(1)(q44)dn, while her parents were both normal. NGS revealed that the child has harbored a partial trisomy of 6q24.3-q27, and the breakpoint was mapped to at 6q24.3q27. In addition, a 2.5 Mb microdeletion at 1q44 was found in the patient.

CONCLUSIONNo recognizable phenotype was associated with 1q44 deletion. The abnormal phenotypes presented by the child may be attributed to the 6q24.3-q27 triplication. Compared with conventional cytogenetic analysis, NGS has a much higher resolution and great accuracy.

Adult ; Child ; Chromosome Banding ; Chromosome Disorders ; genetics ; Chromosomes, Human, Pair 1 ; genetics ; Chromosomes, Human, Pair 6 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Intellectual Disability ; genetics ; Male ; Monosomy ; genetics ; Trisomy ; genetics

Objective:To explore the assessment value of echocardiogram combined with serum high-sensitivity C-reactive protein(hs CRP)and N-terminal pro brain natriuretic peptide(NT proBNP)levels on cardiac function of patients with coronary heart failure.Methods:A total of 306 patients with coronary heart failure admitted to Beijing Daxing District People's Hospital from November 2021 to November 2022 were selected as the study group.Among of them,144 cases were grade Ⅱ,103 cases were grade Ⅲ and 59 cases were grade Ⅳ as the classification of New York Heart Association(NYHA)for cardiac function.A total of 108 healthy examinees who underwent physical examinations in our hospital during the same period were selected as the healthy control group.All examinees were classified as the NYHA for cardiac function,and left ventricular end diastolic volume(LVEDV),left ventricular end systolic volume(LVESV),left ventricular ejection fraction(LVEF),peak ejection rate(PER)and peak filling rate(PFR)of them were measured by echocardiogram.The NT proBNP and hs CRP levels of all examinees were measured.Receiver operating characteristic(ROC)curve was used to analyze the values of single LVEDV,LVESV,LVEF,PER,PFR,hs CRP and NT-proBNP,and the combination of them.Results:LVEDV(122.69±18.24)ml and LVESV(70.79±10.03)ml of the study group were significantly higher than(92.27±15.22)ml and(33.16±7.22)ml of the healthy control group,and the LVEF(42.26±5.13)％,PER(2.49±0.22)EDV/s and PFR(1.79±0.26)EDV/s of the study group were significantly lower than(69.34±5.27)％,(3.56±0.27)EDV/s,and(2.59±0.23)EDV/s of the healthy control group,with statistical significances(t=15.526,35.837,46.828,40.825,28.302,P<0.05),respectively.The levels of hs CRP and NT proBNP of the study group were significantly higher than those of the healthy control group,with statistical significance(t=88.000,29.099,P<0.05),respectively.The LVEDV and LVESV of grade Ⅱ/Ⅲ patients were significantly lower than those of grade Ⅳ patients,while LVEF,PER and PFR of grade Ⅱ/Ⅲ patients were significantly higher than those of grade Ⅳ patients,with statistically significant differences(t=53.391,92.658,32.140,240.474,116.921,P<0.05),respectively.The levels of hs CRP and NT proBNP of grade Ⅱ/Ⅲ patients were significantly lower than those in grade Ⅳ patients,with statistical significance(t=41.037,5.955,P<0.05),respectively.The results of ROC curve analysis showed that the sensitivities of single LVEDV,LVESV,LVEF,PER,PFR,hs CRP,NT proBNP and the combined examination of them were respectively 45.00％,50.00％,70.00％,70.00％,75.00％,70.00％and 90.00％,and the specificities of them were respectively 76.70％,57.00％,82.60％,44.20％,58.10％,52.30％and 96.50％.The area under curve(AUC)values of LVEDV,LVESV,LVEF,PER,PFR,hs CRP,NT proBNP and the combined examination of them were 0.592(95％CI:0.441-0.743),0.615(95％CI:0.468-0.761),0.766(95％CI:0.634-0.899),0.717(95％CI:0.575-0.860),0.674(95％CI:0.536-0.812),0.734(95％CI:0.592-0.876),0.581(95％CI:0.469-0.694)and 0.978(95％CI:0.947-1.000),respectively.Conclusion:The serum hs CRP,NT proBNP levels and function parameters of left heart in patients with coronary heart failure have occurred corresponding changes,and the above indicators have higher assessment value for the heart function of coronary heart failure,and the value of combined assessment is higher.

Objective:To discuss the inhibitory effect of Schisandrin B on the proliferation of pancreatic cancer Pan02 cells,and to clarify the mechanism.Methods:CCK-8 method was used to detect the proliferation rates of the Pan02 cells after treated with different concentrations(0,0.78,1.56,3.12,6.25,12.50,and 25.00 mg·L-1)of Schisandrin B to select the optimal concentration and treatment time of Schisandrin B.The mouse pancreatic cancer Pan02 cells were divided into control group(0 mg·L-1 Schisandrin B),2.5 mg·L-1 Schisandrin B group,5.0 mg·L-1 Schisandrin B group,and 10.0 mg·L-1 Schisandrin B group.The morpholoy of Pan02 cells invarious groups was observed with light microscope;5-ethynyl-2'-deoxyuridine(EdU)staining assay was used to detect the positive expression rates of the Pan02 cells in various groups;flow cytometry was used to detect the percentages of the Pan02 cells at different cell cycles and the apoptotic rates of the cells in various groups;Western blotting method was used to detect the expression levels of cell cycle and apoptosis-related proteins in the cells in various groups.Results:The CCK-8 method results showed that after treated with Schisandrin B for 48 and 72 h,compared with 0 mg·L-1 Schisandrin B,the proliferation rates of the Pan02 cells after treated with different concentrations of Schisandrin B were decreased(P<0.01),especially at 72 h.0.25,5.0,and 10.0 mg·L-1 Schisandrin B were selected to treat the Pan02 cells,and 72 h was the treatment time.In control group,the Pan02 cells had a spindle shape,with good condition,and grew closely adhered to the wall with normal organelles and cytoplasm,in 2.5 and 5.0 mg·L-1 Schisandrin B groups,the cell volume was decreased,the intercellular adhesion was disappeared,and the cell membrane was intact but more permeable;the cytoplasm shrank and vacuolar structures appeared inside the cells,with some fragmented and floating on the surface of the solution;in 10.0 mg·L-1 Schisandrin B group,the Pan02 cells exhibited notable apoptotic bodies,indicating an apoptotic state.The EdU staining results showed that compared with control group,the rates of EdU positive cells in 2.5,5.0,and 10.0 mg·L-1 Schisandrin B groups were significantly decreased(P<0.01).The flow cytometry results showed that compared with control group,the percentages of the cells at S phase in 2.5,5.0,and 10.0 mg·L-1 Schisandrin B groups were significantly increased(P<0.01),while the percentages of the cells at G2/M phase were significantly decreased(P<0.01),and the percentages of the cells at G0/G1 phase in 5.0 amd 1.0 mg·L-1 Schisandrin groups were decreased(P<0.01);compared with control group,the apoptotic rates of the cells in 2.5,5.0,and 10.0 mg·L-1 Schisandrin B groups were significantly increased(P<0.01).The Western blotting results showed that compared with control group,the expression levels of p27,B-cell lymphoma 2(Bcl-2)associated X protein(Bax),cleaved cysteine aspartic acid protease-3(cleaved Caspase-3),and cleaved poly adenosine diphosphate(ADP)ribose polymerase(cleaved PARP)proteins in the cells in 2.5 mg·L-1 Schisandrin B group were significantly increased(P<0.05 or P<0.01),the expression levels of cyclin A2,cyclin E2,and Bcl-2 proteins in the cells in 5.0 and 10.0 mg·L-1 Schisandrin B groups were significantly decreased(P<0.05 or P<0.01),while the expression levels of p27,Bax,cleaved Caspase-3,and cleaved PARP proteins in the cells in 5.0 and 10.0 mg·L-1 Schisandrin B groups were significantly increased(P<0.01).Conclusion:Schisandrin B has an inhibitory effect on proliferation of the pancreatic cancer Pan02 cells,and its mechanism may be related to the activation of the cysteine aspartic acid protease-3(Caspase-3)pathway to induce the apoptosis and activating p27 protein to induce the arrest of cell cycle at S phase.