Fragment with some anti-pancreatic cancer activity was identified by screening our internal chemical library. Eighteen compounds in 4 classes were synthesized by systematic modification and their anti-pancreatic cancer activity were evaluated. Ⅱ-1 (IC₅₀ = 6.40 ± 0.34 μmol·L^-1) and Ⅱ-2 (IC₅₀ = 7.15 ± 0.51 μmol·L^-1) exhibited outstanding activity. Subsequently, the anti-migration ability and invasion ability of Ⅱ-1 was evaluated by wound healing assay and invasion assay, Ⅱ-1 exhibited good anti-migration ability and outstanding anti-invasion ability. Using molecular docking technology and molecular dynamics simulation technology, the potential target was locked on bispecific tyrosine phosphorylation regulates kinase 1A (DYRK1A). By enzyme activity testing, the inhibitory capacity of Ⅱ-1 and Ⅱ-2 was 48% and 32%, respectively.

WRKY transcription factor is a type of transcription factor unique to plants and plays an important role in various physiological processes of plants. This study is based on the transcriptome data of Atractylodes lancea, the correlation between the FPKM values of the AlWRKY gene and the AlTPS gene of Atractylodes lancea was analyzed. Combined with the analysis results, the candidate gene AlWRKY65 with a significant positive correlation with the expression levels of AlTPS1 and AlTPS6 genes and a relatively high FPKM value was screened. The candidate gene was cloned to obtain the open reading frame ORF of the AlWRKY65 gene, and the related information of its encoded protein was analyzed and the gene expression was studied. The results showed that AlWRKY65 contains a 681 bp open reading frame and encoding 226 amino acids. Through amino acid sequence homology analysis, it was found that AlWRKY65 amino acid sequence had high homology with several plants such as HaWRKY65 and LsWRKY65; AlWRKY65 protein had a typical WRKYGQK domain, belonging to IIe subgroup of WRKY transcription factor family; phylogenetic analysis indicated that AlWRKY65 protein had the higher homology with CcWRKY65 protein; the expression of AlWRKY65 gene in different tissues of two producing areas of Atractylodes lancea were assayed via real-time fluorescence quantitative PCR, and the results showed that all of them were highly expressed in leaves and also has tissue differences. The expression level of AlWRKY65 gene was down-regulated within 48 h of methyl jasmonate (MeJA) induction; subcellular localization and transcriptional activation assay suggested that AlWRKY65 was located in the nucleus and had no transcriptional activation activity. This study provides a reference for further elucidating the biological function of AlWRKY65 in Atractylodes lancea.

Aim To explore the effect of targeted inhi-bition of co-signaling molecule B7-H3 on the growth,migration,and angiogenesis ability of human umbilical vein endothelial cells(HUVECs).Methods Small interference RNA was used to knock down HUVECs B7-H3 molecules.CCK-8 test was used to detect cell proliferation at 24 h,48 h and 72 h.Transwell test was then used to detect 24 h cell migration,and three-dimensional cell culture was used to observe cell angio-genesis.Results Compared with the negative control group(siRNA-Control),siRNA-720,siRNA-1707 and siRNA-1690 had different inhibitory effects on the expression of B7-H3.B7-H3 inhibition of siRNA-1690 was significantly higher than that of siRNA-720 and siRNA-1707,and siRNA-1690 sequence was chosen for follow-up experiment.The results of CCK-8 cell vi-ability assay showed that the proliferation ability of HU-VECs decreased by 24％,22％(P＞0.05,compared with 24 h)and 15％(P＜0.05,compared with 48 h)respectively at 24 h,48 h and 72 h after B7-H3 knockout.The migration ability of B7-H3 for 24 h was significantly lower than that of siRNA-Control group(P＜0.01).The results of three-dimensional cell cul-ture showed that the angiogenic ability of HUVECs de-creased significantly after si-B7-H3 knockdown of B7-H3 gene(P＜0.01).Conclusion Targeting B7-H3 inhibits the growth,migration,and angiogenesis of hu-man umbilical vein endothelial cells.

Aim To disclose the subcellular localiza-tion,expression pattern,cellular physiological function and possible molecular mechanism of C12ORF56,a novel gene located at q14.2 of chromosome 12,in the pathogenesis of lung cancer.Methods ONCOMINE database was applied to investigate the mRNA level dif-fering of C12ORF56 between normal and lung cancer tissues.Analysis based on LinkedOmics,Metascape,String and GSEA database or tools provided indication of potential cellular physiological functions of C12ORF56 in the developing of lung cancer.C12ORF56 was knocked down via siRNA and the pro-liferation of NCI-H1073 cells were observed by EdU and CCK-8 assay.RT-qPCR was used to detect the ex-pression level of C12ORF56 of lung cancer cells on dif-ferent cycle phases.The core sequence regions of pro-moter affecting the transcription of C12ORF56 gene were analyzed by Jaspar online-tools and verified by dual-luciferase assay.Results C12ORF56 was highly expressed in lung cancer cells,especially in squamous cell lung cancer.C12ORF56 correlated with cell cy-cle,cancer immune,DNA replication.Knockdown of C12ORF56 reduced NCI-H1703 cell proliferation.Conclusion The up-regulation of C12ORF56 is in-volved in the development of lung cancer by enhancing lung cancer cell proliferation.

Objective To evaluate the efficacy of uterine artery embolization(UAE)combined with ultrasound-guided curettage in the treatment of type Ⅱ and type Ⅲ caesarean scar pregnancy(CSP).Methods The clinical data of 90 patient with CSP in our hospital were analyzed retrospectively,the patients were divided into type Ⅱ group and type Ⅲ group according to preoperative vaginal color Doppler ultrasound.Patients in both groups were treated with UAE combined with ultrasound-guided curettage.The intraoperative and postoperative conditions of patients between the two groups were compared and analyzed.Results The cure rate of type Ⅱ group(92.5%)was higher than that of type Ⅲ group(65.2%),the intraoperative blood loss,time of postoperative serum β-hCG turned negative,postoperative mass disappearance time of patients in type Ⅱ group were less/shorter than those in type Ⅲ group,the differences were statistically significant(P<0.05);there was no statistical difference in length of hospitalization or time to menstruation recovery of patients between the two groups(P>0.05).Conclusion UAE combined with ultrasound-guided curettage is ideal for patients with type Ⅱ CSP at 8 to 10 weeks of gestation,and can be used as a recommended treatment.However,the cure rate of this method for type Ⅲ CSP is low,the comprehensive choice should be considered,including the specific situation of the patient and the local medical level.

Objective:To explore the optimal storage condition and time of umbilical cord blood from collection to preparation.Methods:Collect cord blood samples from 30 healthy newborns,with each new born's umbilical cord blood was divided into two parts on average.One part was stored in cold storage(4 ℃)and the other was stored at room temperature(20-24 ℃).Samples were taken at 24,36,48,60 and 72 h,respectively,total nucleated cells(TNC)count and TNC viability was analyzed.Flow cytometry was used to detect the ratio of viable CD34+cells to viable CD45+cells and viability of CD34+cells,and colony-forming unit-granulocyte-macrophage(CFU-GM)count was performed by hematopoietic progenitor cell colony culture.The change trend of each index over time was observed,and the differences in each index was compared between cold storage and room temperature storage under the same storage time.Results:The TNC count(r4℃=-0.9588,r20-24℃=-0.9790),TNC viability(r4℃=-0.9941,r20 24 ℃=-0.9970),CD34+cells viability(r4℃=-0.9932,r20-24℃=-0.9828)of cord blood stored in cold storage(4 ℃)and room temperature storage(20-24 ℃)showed a consistent downward trend with the prolongation of storage time.The percentage of viable CD34+cells(r4℃=0.9169,r20-24 ℃=0.7470)and CFU-GM count(r4℃=-0.2537,r20-24℃=-0.8098)did not show consistent trends.When the storage time was the same,the TNC count,TNC viability,CD34+cells viability and CFU-GM count of cord blood stored in cold storage were higher than those stored at room temperature.Under the same storage time(24,36,48,60 or 72 h),TNC viability in room temperature storage was significantly lower than that in cold storage(P＜0.001),but TNC count,percentage of viable CD34+cells and CFU-GM count were not significantly different between room temperature storage and cold storage.When stored at room temperature for 24 h and 36 h,the viability of CD34+cells was significantly lower than that in cold storage(P＜0.001,P＜0.01),when the storage time for 48,60 and 72 h,there was no significant difference in the CD34+cells viability between room temperature storage and cold storage.Conclusion:It is recommended that cord blood be stored in cold storage(4 ℃)from collection to preparation,and processed as soon as possible.

Objective:To investigate the effect of feeder layer cells expressing interleukin(IL)-21 on the amplification of NK cells in vitro.Methods:The K562 cell line with IL-21 expression on its membrane was constructed by electroporation,and co-cultured with NK cells after inactivation.The proliferation of NK cells was observed.The killing function of the amplified NK cells in vitro was evaluated by the lactate dehydrogenase(LDH)and interferon-γ(IFN-y)release assay.A colorectal cancer xenograft model in NOD/SCID mice was established,and a blank control group,a NK cell group and an amplified NK cell group were set up to detect the tumor killing effect of amplified NK cells in vivo.Results:K562 cells expressing IL-21 on the membrane were successfully constructed by electroporation.After co-culturing with K562 cells expressing IL-21 on the membrane for 17 days,the NK cells increased to 700 times,which showed an enhanced amplification ability compared with control group(P＜0.001).In the tumor cell killing experiment in vitro,there was no significant difference in the killing activity on tumor cells between NK cells and amplified NK cells,and there was also no significant difference in mice in vivo.Conclusion:K562 cells expressing IL-21 on the membrane can significantly increase the amplification ability of NK cells in vitro,but do not affect the killing function of NK cells in vitro and in vivo.It can be used for the subsequent large-scale production of NK cells in vitro.

Objective To systematically evaluate the application efficacy of failure mode and effect analysis(FMEA)management mode in the prevention and control of healthcare-associated infection(HAI).Methods Li-terature on the application of FMEA management mode in HAI prevention and control were retrieved from PubMed,Embase,the Cochrane Library,China National Knowledge Infrastructure(CNKI),VIP Database,Wanfang Data-base,and China Biomedical Literature Database(CBM).Two researchers independently screened the literature,ex-tracted data,and conducted cross checking.Risk and quality assessments were performed on the included studies of randomized controlled trials by ROB tool,the included cohort studies were scored by Newcastle-Ottawa(NOS)scale,and Meta-analysis was conducted by RevMan 5.4 software.Results A total of 22 studies involving 42 815 patients were included in the analysis,with 21 784 in the FMEA management mode group and 21 031 in the control group.Meta-analysis results showed that the incidence of HAI in the FMEA management mode group was lower than that in the control group(OR=0.31,95％CI[0.24,0.40]).Compared with the conventional management mode,incidences of superficial surgical site infection(OR=0.53,95％CI[0.36,0.78]),respiratory system infec-tion(OR=0.44,95％CI[0.35,0.56]),urinary system infection(OR=0.45,95％CI[0.38,0.53]),and blood system infection(OR=0.29,95％CI[0.18,0.45])in the FMEA management mode group were all lower(all P＜0.01).Conclusion The application of FMEA management mode in HAI prevention and control can reduce the inci-dence of HAI,which should be actively promoted in hospital management.

Objective:To explore the impact of rehabilitation exercise intervention mode based on cardiac function classification on clinical effect and quality of life(QOL)in patients with chronic heart failure(CHF).Methods:A total of 160 CHF patients who visited our hospital from Dec 2021 to Jan 2023 were selected,and 154 cases were fi-nally enrolled.According to the random number table method,patients were divided into study group and control group with 77 cases in each group.Control group received routine nursing program,while the study group received rehabilitation exercise intervention based on cardiac function classification on the basis of control group,both groups were intervened for three months.Clinical total effective rate,and cardiopulmonary function,serum oxidative stress indicators and MLHFQ score before and after intervention were compared between two groups.Results:Total effective rates of study subgroups of class Ⅱ and Ⅲ were significantly higher than those of control group(class Ⅱ:100.00％vs.83.78％;class Ⅲ:97.37％vs.80.00％)(P＜0.05 both).Compared with control subgroup of classⅢ after intervention,there were significant rise in peak VO2[(16.98±2.03)ml·min-1·kg-1 vs.(18.61±2.41)ml·min-1·kg-1],LVEF[(41.73±4.53)％vs.(48.03±5.22)％]and 6MWD[(351.34±61.00)m vs.(391.53±64.42)m](P＜0.01 all);and significant reductions in LVEDd[(57.55±3.91)mm vs.(53.18±3.07)mm],LVESd[(35.90±2.91)mm vs.(30.50±2.67)mm],levels of LPO[(6.00±0.99)mg/L vs.(3.95±0.61)mg/L],MPO[(3.83±0.58)mg/L vs.(2.03±0.28)mg/L],and MLHFQ total score[(57.05±4.57)points vs.(45.29±3.94)points]in study subgroup of class Ⅲ(P=0.001 all).Compared with control subgroup of class Ⅱ after intervention,there were significant rise in peak VO2,LVEF and 6MWD,and significant reductions in LVEDd,LVESd,levels of LPO,MPO and MLHFQ score in study subgroup of class Ⅱ,P＜0.05 or＜0.01.There was no significant difference in the incidence rate of adverse events during follow-up between two groups(3.90％vs.6.49％,P=0.717).Conclusion:Rehabilitation exercise intervention based on cardiac function classifi-cation can significantly improve cardiopulmonary function,inhibit oxidative stress response in vivo and improve quality of life in CHF patients,which is worthy of promotion and application in clinical practice.

AIM To optimize the extraction process for Jigen Standard Decoction,and to establish its quality standard.METHODS With soaking time,water addition and first decoction time as influencing factors,comprehensive score for 3,6'-disinapoyl sucrose content and yield rate as an evaluation index,the extraction process was optimized by response surface method on the basis of single factor test.The content and transfer rate of 3,6'-dimustayl sucrose were determined,after which HPLC characteristic chromatograms were established,cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were performed.RESULTS The optimal conditions were determined to be 60 min for soaking time,(12+11)times for water addition,and(47+20)min for decoction time,the comprehensive score was 97.98.Fifteen batches of standard decoctions demonstrated the average yield rate and transfer rate of 14.182％and 20.468％,respectively,whose characteristic chromatograms existed six common peaks with the similarities of more than 0.9(except for S4,S8).Various batches of standard decoctions were clustered into two types,three principal components displayed the acumulative variance contribution rate of 91.4％,peaks 2,6 were quality markers.CONCLUSION This precise,stable and reproducible method can be used for the preparation and quality control of Jigen Standard Decoction.