Eight butyl-phthalides, senkyunolide K(1), senkyunolide N(2), butylphthalide(3), senkyunolide I(4), senkyunolide H(5),(Z)-butylidenephthalide(6),(Z)-ligustilide(7), and 3-butylidene-7-hydroxyphthalide(8) were isolated from the aerial part of Ligusticum sinense by column chromatography on silica gel column, ODS, Sephadex LH-20 and semi-preparative HPLC. Their structures were elucidated on the basis of spectroscopic and chemical data, especially NMR and MS. Compound 1 was a new butyl-phthalide and compounds 2-8 were isolated from the aerial part of L. sinense for the first time. Furthermore, the inhibitory activities of compounds 1-8 against the nitric oxide(NO) production induced by lipopolysaccharide(LPS) in mouse RAW264.7 macrophages in vitro were evaluated. The results showed that compounds 1-8 exerted inhibitory activities on NO production with IC_(50) of 19.34-42.16 μmol·L~(-1).
Animals ; Mice ; Nitric Oxide/biosynthesis* ; Ligusticum/chemistry* ; Benzofurans/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Macrophages/immunology* ; RAW 264.7 Cells ; Molecular Structure

Objective To analyze the expression of CREM in gastric cancer(GC)and its correlation with prognosis of the patients.Methods TCGA and GEO databases were used to analyze the expression levels of CREM mRNA in GC and adjacent tissues.Immunohistochemistry was used to examine the expression of CREM protein in 43 pairs of GC and adjacent tissues,and the correlation of CREM expression with clinicopathological features of the patients was analyzed.Kaplan-Meier survival analysis was used to explore the relationship between CREM expression and survival of GC patients.LinkedOmics database was used to annotate the GO function and KEGG pathway enrichment of CREM-related genes.Results Database analysis showed that CREM was highly expressed in GC tissues(P<0.05)and positively correlated with poor prognosis in GC patients(P=0.01).Immunohistochemistry results showed significantly higher CREM expression in GC tissues than in paired adjacent tissues(P<0.0001),and its expression level was correlated with T-stage and N-stage of the tumor(P<0.05).The overall survival of GC patients with high expression of CREM was shorter(RR=4.02,P=0.0046).Gene enrichment analysis showed that high CREM expression promotes occurrence and progression of GC very likely through the cell adhesion signaling pathway.Conclusion CREM is highly expressed in GC,and its high expression is associated with a poor prognosis of GC patients,suggesting the potential of CREM to serve as a prognostic indicator for GC.

Objective:The purpose of this study is to explore in depth the mechanism of the impact of brain drain on organizational cohesion,with a view to cracking the vicious circle problem caused by brain drain in the northeast region and eliminating the unfavorable factors affecting the core cohesion of public health institutions.Methods:A combination of convenience sampling and snowball sampling was used to survey11 912 valid questionnaires,and the data were systematically analyzed using descriptive statistics,regression analysis,and moderated mediated effects analysis.Results:Brain drain has a significant negative effect on organizational cohesion(β=-1.29,P<0.001);and role overload partially mediates between the two,with a significant mediating effect(effect value=-0.56,95%CI=-0.67～-0.46),and the indirect effect accounts for 43.4%of the total effect;and monthly income significantly moderates the effect of brain drain on organizational cohesion through role overload(β=1.00,P<0.001).Conclusion:It is recommended to alleviate the sense of role overload among public health personnel by adjusting the level of salary and benefits,and to reduce the negative impact of brain drain by adopting long-term incentive mechanisms and other strategies,thus enhancing organizational cohesion and providing theoretical and practical guidance for relevant institutions.

Objective To investigate the reversal effect and mechanism of cinobufagin(CBG)on cisplatin resist-ance in human ovarian cancer cells.Methods A2780 cell line and its cisplatin-resistant cell line A2780/DDP are common ovarian cancer cells in clinic,so these two cell lines were selected as the research objects.The cell viabil-ity was detected by cell Counting Kit-8(CCK-8)assay,and the cell proliferation ability was detected by plate clo-ning and 5-ethynyl-2′-deoxyuridine(EdU)assay.Hoechst staining was used to observe cell apoptosis.Cell scratch test and Transwell test were used to evaluate cell migration and invasion ability.Western blot and quantitative reverse transcription PCR(RT-qPCR)were used to detect the protein and mRNA expressions of phosphatidylinosi-tol 3-kinase/protein kinase(PI3K/AKT)signaling pathway and epithelial-mesenchymal transition(EMT).Re-sults Compared with A2780 cells,the drug resistance indexes of A2780/DDP cells were 5.636,5.864,5.695,respectively.After treatment of A2780/DDP cells with CBG(2,4,6 mg/ml),the reversal resistance indexes were 1.617,2.570,3.461,respectively.CBG treatment significantly increased the level of apoptosis and inhibi-ted the proliferation,migration and invasion of the cells in a concentration-dependent manner(P<0.05).Western blot results showed that compared with A2780 cells,the relative ratio of P-PI3K/PI3K and P-AKT/AKT protein levels,as well as the protein expression of N-cadherin,Vimentin,and Snail were higher in the control group(A2780/DDP)cells,while the protein expression of E-cadherin was lower(tP-PI3K/PI3K=8.115,tP-AKT/AKT=17.62,tN-cadherin=6.126,tVimentin=4.001,tSnail=17.333,tE-cadherin=4.620,P<0.01);As the dose of CBG increased,the protein expression levels of P-PI3K,P-AKT,N-cadherin,Vimentin,and Snail in drug-resistant cells de-creased,while the protein expression level of E-cadherin increased(FP-PI3K=268.5,FP-AKT=190.5,FN-cadherin=24.02,FVimentin=57.65,FSnail=87.24,FE-cadherin=135.8,P<0.05).qRT-PCR results showed that with the in-crease of CBG concentration,the mRNA expression levels of PI3K,AKT,N-cadherin,Vimentin and Snail de-creased,while the mRNA expression level of E-cadherin gradually increased(FPI3K=101.1,FAKT=558.3,FN-cadherin=86.97,FVimentin=105.9,FSnail=85.71,FE-cadherin=80.96,P<0.01).Conclusion CBG can reverse cisplatin resistance of ovarian cancer A2780/DDP cell line,and its mechanism may be related to the regulation of PI3K/AKT signaling pathway and inhibition of EMT by CBG.

Objective This study employs the Geographically and Temporally Weighted Regression(GTWR)model to assess the impact of meteorological elements and imported cases on dengue fever outbreaks,emphasizing the spatial-temporal variability of these factors in border regions. Methods We conducted a descriptive analysis of dengue fever's temporal-spatial distribution in Yunnan border areas.Utilizing annual data from 2013 to 2019,with each county in the Yunnan border serving as a spatial unit,we constructed a GTWR model to investigate the determinants of dengue fever and their spatio-temporal heterogeneity in this region. Results The GTWR model,proving more effective than Ordinary Least Squares(OLS)analysis,identified significant spatial and temporal heterogeneity in factors influencing dengue fever's spread along the Yunnan border.Notably,the GTWR model revealed a substantial variation in the relationship between indigenous dengue fever incidence,meteorological variables,and imported cases across different counties. Conclusion In the Yunnan border areas,local dengue incidence is affected by temperature,humidity,precipitation,wind speed,and imported cases,with these factors'influence exhibiting notable spatial and temporal variation.

Objective To analyze the expression of CREM in gastric cancer(GC)and its correlation with prognosis of the patients.Methods TCGA and GEO databases were used to analyze the expression levels of CREM mRNA in GC and adjacent tissues.Immunohistochemistry was used to examine the expression of CREM protein in 43 pairs of GC and adjacent tissues,and the correlation of CREM expression with clinicopathological features of the patients was analyzed.Kaplan-Meier survival analysis was used to explore the relationship between CREM expression and survival of GC patients.LinkedOmics database was used to annotate the GO function and KEGG pathway enrichment of CREM-related genes.Results Database analysis showed that CREM was highly expressed in GC tissues(P<0.05)and positively correlated with poor prognosis in GC patients(P=0.01).Immunohistochemistry results showed significantly higher CREM expression in GC tissues than in paired adjacent tissues(P<0.0001),and its expression level was correlated with T-stage and N-stage of the tumor(P<0.05).The overall survival of GC patients with high expression of CREM was shorter(RR=4.02,P=0.0046).Gene enrichment analysis showed that high CREM expression promotes occurrence and progression of GC very likely through the cell adhesion signaling pathway.Conclusion CREM is highly expressed in GC,and its high expression is associated with a poor prognosis of GC patients,suggesting the potential of CREM to serve as a prognostic indicator for GC.

Objective:To explore the efficacy and safety of dual targeted therapy（DTT）in the treatment of refractory inflammatory bowel disease（IBD）in children.Methods:The diagnosis and treatment processes of refractory IBD children treated with DTT in the Department of Gastroenterology,Beijing Children's Hospital Affiliated to Capital Medical University from April 2022 to May 2024 were analyzed retrospectively,and their clinical characteristics were summarized.Results:A total of ten children with refractory IBD were included,including five males and five females,with a median onset age of 12.58 (5.25,13.33) years old,and seven cases of Crohn's disease (CD) and three cases of ulcerative colitis (UC),with a median disease course of 1.25 (0.91,4.00) years，were treated with DTT for a median time of 6.08 (6.00,13.40)months.Two (2/7) cases of CD patients were partially effective with infliximab(IFX) treatment,while five (5/7) cases were partially effective with a combination of IFX and azathioprine treatment.These patients received DTT with UST in addition to continuous using of IFX.When the seven CD patients were treated with DTT for four weeks,12 weeks and 24 weeks,and the clinical remission rates were 42.9%(3/7),71.4%(5/7) and 100%(7/7)，respectively.The pediatric Crohn's disease activity index gradually decreased,which were significantly lower than those before treatment( P<0.05).Fecal calprotectin,C-reactive protein,erythrocyte sedimentation rate,and blood white blood cells all gradually decreased,which were lower than those before treatment,while hemoglobin and serum albumin were higher than those before treatment.Three children with UC were all resistant to glucocorticoids.One case was partially effective with adalimumab treatment,one case was partially effective with IFX combined with immunosuppressive agents,and one case was partially effective with vedolizumab.All the three UC patients received DTT treatment with UST in addition to continuous using of the original biological preparation.When the three UC patients were treated with DTT for four weeks and 12 weeks,one case showed clinical remission,one case showed clinical response,and one case showed no clinical response.After 24 weeks of DTT treatment,two cases achieved clinical remission and one case had no clinical response.Re-examination of colonoscopy showed that one case of clinical remission had mucosal healing and one case had mild disease activity.However,there was a slight improvement in disease activity under endoscopy compared with that before DTT in patient who had no clinical response.During DTT treatment,no adverse events occurred in all patients. Conclusion:DTT is effective and relatively safe for children with refractory IBD,and can be one of the attempts for children with IBD when they are partially effective with one biological agent.

Objective To investigate the nutritional status of children with Crohn's Disease (CD) at diagnosis and its association with clinical characteristics. Methods A retrospective analysis was performed for the clinical data and nutritional status of 118 children with CD who were admitted to Beijing Children's Hospital,Capital Medical University,from January 2016 to January 2024. A multivariate logistic regression analysis was used to investigate the risk factors for malnutrition. Results A total of 118 children with CD were included,among whom there were 68 boys (57.6％) and 50 girls (42.4％),with a mean age of (11±4) years. Clinical symptoms mainly included recurrent abdominal pain (73.7％,87/118),diarrhea (37.3％,44/118),and hematochezia (32.2％,38/118),and 63.6％ (75/118) of the children had weight loss at diagnosis. The incidence rate of malnutrition was 63.6％ (75/118),and the children with moderate or severe malnutrition accounted for 67％ (50/75). There were 50 children (42.4％) with emaciation,8 (6.8％) with growth retardation,and 9 (7.6％) with overweight or obesity. Measurement of nutritional indices showed a reduction in serum albumin in 83 children (70.3％),anemia in 74 children (62.7％),and a reduction in 25 hydroxyvitamin D in 15 children (60％,15/25). The children with malnutrition had significantly higher disease activity,proportion of children with intestinal stenosis,and erythrocyte sedimentation rate and a significant reduction in serum albumin (P<0.05). The multivariate logistic regression analysis showed that intestinal stenosis was an independent risk factor for malnutrition in children with CD (OR=4.416,P<0.05). Conclusions There is a high incidence rate of malnutrition in children with CD at diagnosis,which is associated with disease activity and disease behavior. The nutritional status of children with CD should be closely monitored.

Objective To observe the value of diffusion kurtosis imaging(DKI)radiomics for evaluating Parkinson disease(PD).Methods Totally 76 PD patients(PD group)and 80 healthy controls(HC group)were retrospectively analyzed.The subjects were divided into training set(n=125,including 61 PD and 64 HC)and test set(n=31,including 15 PD and 16 HC)at the ratio of 8:2.ROI of bilateral substantia nigra,caudate nucleus,putamen,globus pallidus and thalamus were automatically delineated on mean kurtosis(MK)images of cerebral DKI.The mean MK values(MKmean)of the above ROIs were obtained and compared between groups.Support vector machine(SVM)model was constructed based on 50 selected optimal texture features.Receiver operating characteristic(ROC)curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of SVM model for evaluating PD.Results MKmean of bilateral substantia nigra,caudate nucleus and thalamus in PD group were all significantly lower than those in HC group(all P＜0.05).No significant difference of MKmean of bilateral putamen nor globus pallidus was found between groups(all P＞0.05).The sensitivity,specificity,accuracy and AUC of SVM model for evaluating PD in training set was 86.89％,93.75％,90.40％and 0.982,respectively,which in test set was 86.67％,93.75％,90.32％and 0.958,respectively.Conclusion DKI radiomics could be used to effectively evaluate PD through description of microstructural changes of cerebral nuclei.

Objective:To evaluate the efficacy and safety of oral sulfate solution (OSS) for bowel preparation.Methods:A multi-center, randomized, single-blinded, positive-controlled and non-inferiority clinical study was conducted. Participants were randomized to receive two bottles of OSS or 4-liter polyethylene glycol (Ⅲ) (PEG) regimen. The primary indicator was efficacy for bowel preparation. Boston bowel preparation scale (BBPS) ≥2 scores in each segment was determined as effective. Secondary endpoints included subjects' compliance, colonoscopy bubble evaluation, time interval of defecation after medication, time interval of defecation type Ⅶ (Bristol stool classification), the number of defecation, and the positive rate of colonoscopy (detection rate of polyps, non-polyp eminence, ulcers, etc.) were also recorded. The safety was evaluated by the incidence of adverse events and severe adverse events.Results:A total of 240 subjects from 4 hospitals were enrolled in the study, with 120 subjects in the experimental group (the OSS group) and 120 subjects in the control group (the PEG group). The full analysis set (FAS) showed that the bowel preparation success rates were 92.44% (110/119) in the OSS group and 91.60% (109/119) in the PEG group ( χ2=0.058, P=0.809) . The total BBPS score and the scores of each bowel segment were all higher in the OSS group than those in the PEG group ( P<0.05) in both FAS and per protocol set (PPS) except the score of left colon in the FAS. The satisfaction rate of bubble evaluation in the OSS group was higher ( 95.80% VS 89.08%, P=0.025). The compliance, positive rate of colonoscopy and safety of the two groups were comparable. Conclusion:Compared with 4-liter PEG regimen, OSS regimen shows similar bowel preparation quality, superior anti-foaming effect with acceptable safety.