BackgroundSocial support can help alleviate depressive symptoms in patients with major depressive disorder （MDD） and improve individual levels of empathy. The higher the level of empathy， the lower the probability of depressive symptoms. At present， the relationship between social support， empathy and depressive symptoms in MDD patients is unclear. ObjectiveTo explore the pathway of empathy in the relationship between social support and depressive symptoms in patients with MDD， so as to provide references for clinical treatment of MDD patients. MethodsA total of 126 patients who visited the outpatient clinic of Tianjin Anding hospital from July 2020 to September 2022 and met the diagnostic criteria for Major Depressive Disorder （MDD） according to the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were selected as the study subjects. Hamilton Depression Scale-17 item （HAMD-17）， Interpersonal Reactivity Index （IRI） and Social Support Rating Scale （SSRS） were used for assessment. Pearson correlation analysis was conducted to examine the correlations among the scale scores. Path analysis was performed using Model 4 of the Process 3.4.1. Bootstrap method was used to test the path effects. ResultsAmong MDD patients， HAMD-17 total score was positively correlated with IRI total score and its subscales of fantasy and personal distress （r=0.225， 0.213， 0.220， P<0.05）. HAMD-17 total score was negatively correlated with SSRS total score and its subscales of subjective support and support utilization （r=-0.211， -0.181， -0.208， P<0.05）. The score of support utilization subscale of SSRS was positively correlated with IRI total score and its subscale of perspective taking and empathic concern （r=0.257， 0.261， 0.331， P<0.01）. Empathy served as a pathway between support utilization and depressive symptoms， with an indirect effect of 0.217 （95% CI： 0.060~0.426）， and the effect size was 36.90%. ConclusionEmpathy may serve as a pathway between support utilization and depressive symptoms in patients with MDD.

[摘 要] 目的：构建程序性死亡受体1（PD-1）高表达的细菌质膜纳米囊泡（BMV）BMV-PD-1，评估其对小鼠肺癌移植瘤组织的靶向性。方法：通过质粒转化将PD-1与膜孔蛋白细胞溶素A（ClyA）融合质粒ClyA-PD-1-EGFP转入大肠杆菌BL21-Codonplus，使用激光共聚焦显微镜、SDS-PAGE和WB法检测融合蛋白ClyA-PD-1-EGFP的表达。提取质膜并采用挤出法，利用挤出器制备BMV-PD-1。采用透射电子显微镜（TEM）、纳米粒子跟踪分析（NTA）技术分别对BMV-PD-1的形态、粒径和膜电位进行检测，用WB鉴定PD-1蛋白的携带情况。采用激光共聚焦成像检测Lewis肺癌LLC细胞对BMV-PD-1的摄取。建立肺癌LLC细胞C57BL/6J小鼠皮下移植瘤模型，采用小动物活体成像系统评估BMV-PD-1的肿瘤靶向性。结果：激光共聚焦显微成像结果显示，质粒ClyA-PD-1-EGFP被转入BL21-Codonplus并成功表达蛋白。SDS-PAGE结果表明，ClyA-PD-1-EGFP在BL21-Codonplus中过表达。WB分析表明，PD-1在细菌中表达且在BMV-PD-1上呈高表达（P < 0.001）状态。NTA和TEM分析表明，BMV-PD-1是一种粒径为（145 ± 14） nm、表面呈负电性的球状囊泡。激光共聚焦成像显示，PD-1高表达能显著提升肺癌细胞对BMV-PD-1的摄取（P < 0.01），小动物活体成像也进一步证实PD-1高表达能有效提升BMV-PD-1的肿瘤靶向性（P < 0.01）。结论：本研究成功构建了PD-1高表达的细菌纳米囊泡BMV-PD-1，发现PD-1高表达可显著提高BMV-PD-1的肺癌LLC细胞移植瘤组织的靶向性，为进一步开发以BMV-PD-1为载体的肿瘤靶向药物递送系统奠定基础。

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective : To investigate the mechanism of puerarin in the treatment of rheumatoid arthritis(RA) by network pharmacology and animal experiments. Methods : Traditional Chinese Medicine Systems Pharmcolog Database(TCMSP) and SwissTargetPrediction database were used to collect puerarin targets, and the targets of RA were obtained from GeneCards database and OMIM database. The PPI network was established by Cytoscape 3.7.2 software. Gene ontology(GO) function and Kyotoencyclopedia of genes(KEGG) enrichment analysis were performed through the Metascape database. RA rat-collagen-induced arthritis(CIA) model was reproduced using type Ⅱ collagen emulsion, 49 Wistar rats were randomly assigned to seven groups: control group, CIA model group, low-dose, medium-dose and high-dose puerarin group, methotrexate group, Tripterysium Glycosides Tablets group. Except for the control group, the other groups were given continuous gavage for 28 days after the CIA in rats model were prepared. The redness and swelling of the joints and ankle joint pathological changes were observed in each group. Western blot was used to detect the expression of Glycogen synthase kinase3β(GSK-3β), beta-catenin(β-catenin) proteins in the synovium. Real-time quantitative polymerase chain reaction(qPCR) was used to detect the expression of GSK-3β, β-catenin and c-Myc mRNA in the synovium. Results : Puerarin had 134 targets genes, RA had 5 821 target genes, and there were 102 overlapping target genes of puerarin and RA. It involved 184 signaling pathways, including JAK-STAT signaling pathway, NF-κB signaling pathway, Wnt signaling pathway, et al. The results of animal experiments showed that after the intervention of M-puerarin and MTX, the symptoms of redness and swelling of the hind foot were alleviated, the inflammatory cell infiltration in the synovium of the joint was significantly reduced, and the damage of cartilage and bone tissue was reduced. Compared with CIA group, the expressions of GSK-3β, β-catenin protein and GSK-3β, β-catenin and c-Myc mRNA in synovial tissue of rats after M-puerarin intervention decreased(P<0.05). Conclusion Puerarin has the characteristic of multi-components, multi-targets and multi-pathway intervention in RA. Puerarin may alleviate synovial hyperplasia, reduce articular cartilage erosion and bone destruction in CIA in rats by inhibiting Wnt/β-catenin signaling pathway.

With the rapid development of social economy and the continuous improvement of human living standard, the incidence, fatality and recurrence rates of cardiovascular disease (CVD) are increasing year by year, which seriously affects people's life and health. Conventional therapeutic drugs have limited improvement on the disability rate, so the search for new therapeutic drugs and action targets has become one of the hotspots of current research. In recent years, the therapeutic role of the natural compound rosmarinic acid (RA) in CVD has attracted much attention, which is capable of preventing CVD by modulating multiple signalling pathways and exerting physiological activities such as antioxidant, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, as well as anti-coagulation and endothelial function protection. In this paper, the role of RA in the prevention of CVD is systematically sorted out, and its mechanism of action is summarised and analysed, with a view to providing a scientific basis and important support for the in-depth exploration of the prevention value of RA in CVD and its further development as a prevention drug.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

ObjectiveThe U6 promoter is an essential element for driving sgRNA expression in the clustered regularly interspaced short palindromic repeat sequences/CRISPR-associated protein 9（CRISPR/Cas9）gene editing system in dicotyledonous plants. Endogenous U6 promoters typically exhibit higher transcriptional activity， which can significantly improve gene editing efficiency. This study aims to identify endogenous U6 promoters in Artemisia annua to optimize its CRISPR/Cas9 gene editing system， which holds significant importance for its molecular breeding. MethodsOn the basis of the highly conserved U6 snRNA sequences in Arabidopsis thaliana， endogenous U6 promoters were screened in the A. annua genome. Expression vectors were constructed with candidate AaU6 promoter driving the firefly luciferase （LUC） reporter gene， and then transiently transformed into Nicotiana benthamiana. Transcriptional activities of the promoters were measured and compared by in vivo imaging and the Dual Luciferase Reporter assay. ResultsEight endogenous U6 promoters were successfully cloned from A. annua. Sequences alignment revealed that all these promoters contained the two conserved cis-acting elements， upstream sequence element （USE） and TATA-box， which affected their transcriptional activity. Dual-luciferase activity assays indicated that the transcriptional activities of AaU6-3， AaU6-1， and AaU6-5 were significantly higher than that of the Arabidopsis AtU6-26 promoter， with AaU6-3 exhibiting the highest activity. ConclusionThis study identified three endogenous AaU6 promoters with high transcriptional activity in A. annua， providing key functional elements for establishing an efficient gene editing system in A. annua. These findings will contribute to advancing precision molecular breeding and high-quality germplasm innovation in A. annua.

Calcium-activated chloride channels(CaCCs)are a class of channel proteins that trans-port chloride ions activated by intracellular calcium,which play a crucial role in regulating membrane potential,intracellular calcium balance,and cell excitability,particularly in neurons and muscle cells.In the Anoctamin(Ano)family,Ano1 is the most classic CaCC.Targeted modulators of Ano1 have poten-tial therapeutic effects against such diseases as cancer,cystic fibrosis,hypertension,diarrhea,and asthma.Since the discovery of Ano1 in 2008,several methods for screening CaCC-specific modulators have emerged including high-throughput primary screening of fluorescent proteins,electrophysiological patch clamp technique and virtual screening,and identification of small molecule modulators with diverse pharmacological effects.This paper summarizes the principles,advantages and disadvantages of the mainstream screening methods,and reviews the chemical structures and potential applications of Ano1-specific modulators discovered to date.

Objective:To construct an evaluation framework with detailed indices for demonstration units (wards) of enteral nutrition nursing, in order to improve the competence of nurses in enteral nutrition nursing and inform the specialized development of enteral nutrition demonstration units (wards).Method:On the basis of literature review and expert discussion, a preliminary draft was developed, and the Delphi expert consultation method was used to conduct two rounds of consultation with 15 clinical experts in the field of enteral nutrition nursing from 15 tertiary hospitals.Results:The effective response rates of questionnaires in two rounds of consultations were both 100%. The first round of expert consultation showed an authority coefficient of 0.90 and a coefficient of variation of 0 to 0.167, while the second round showed an authority coefficient of 0.93 and a coefficient of variation of 0 to 0.113. The Kendall harmony coefficients were 0.338 and 0.368, respectively. Finally, the evaluation framework with detailed indices for the demonstration unit (ward) of enteral nutrition nursing was formed, which consisted of 3 primary indicators, 16 secondary indicators, 54 tertiary indicators, and 62 detailed items.Conclusions:The evaluation framework we developed for the demonstration unit of enteral nutrition nursing follows the diagnosis and treatment process of enteral nutrition management for inpatients, including the triad of structure, process, and outcome. The framework is objective and practical, and can inform the daily practice of enteral nutrition nursing demonstration units (wards) and the development of enteral nutrition nursing specialties.