OBJECTIVE To identify core genes associated with the treatment of coronary heart disease （CHD） with Tongmai yangxin pills， and predict their potential immunological and metabolic mechanisms. METHODS Mendelian randomization （MR） analysis was conducted using protein quantitative trait loci （pQTL） data from the UK Biobank and Icelandic，and data from genome- wide association study to screen core genes related to Tongmai yangxin pills in the treatment of CHD. Gene expression changes were further validated using transcriptomic sequencing data. Mediation analyses of immune cells and plasma metabolites were subsequently performed to explore the downstream regulatory networks of these core genes. RESULTS A total of 62 positive pQTL genes showed significant causal associations with CHD. MR analysis combined with transcriptomic sequencing validation identified three core genes FAM3D，OXT， and ENPP5-associated with Tongmai yangxin pills in the treatment of CHD. The transcriptomic sequencing results showed that after treatment with Tongmai yangxin pills， the expression levels of FAM3D and OXT were significantly reduced （P＜0.01）， while the expression level of ENPP5 was significantly increased （P＜0.05）. Mediation analyses between immune cells and plasma metabolites indicated that these genes may positively or negatively regulate CHD through immune pathways involving regulatory T cells and myeloid dendritic cells expressing CD11c and CD62L， as well as through metabolic pathways related to lipid and fatty acid metabolism， cholesterol metabolism， and bile acid metabolism. CONCLUSIONS This study identified FAM3D，OXT， and ENPP5 as core genes associated with the treatment of CHD by Tongmai yangxin pills， which may exert therapeutic effects via modulation of immune cells and plasma metabolic pathways involving fatty acids and bile acids.

Objective To evaluate the protective effect of human nucleus pulposus cell by Liraglutide(Lir)under high-glucose environment via inhibition of NOD-like receptor family,pyrin domain containing 3(NLRP3)inflammasome activation and its mechanism.Methods Human nucleus pulposus cell lines were cultured and the third-generation nucleus pulposus cells were randomly divided into control group(Con group),high glucose group(HG group),and Liraglutide interference group(Lir group),and cultured for 48 h.ELISA was used to detect interleukin IL-1β;flow cytometry was used to testreactive oxygen species(ROS),and Western blot was used to evaluate the protein expressions of NLRP3,Pro-caspase-1,and Caspase-1.Results Compared with Con group,IL-1β,ROS,NLRP3,Pro-caspase-1,Caspase-1 protein expression and cell apoptosis were increased in HG and Lir groups(P<0.05).Compared with HG group,IL-1β,ROS,NLRP3,Pro-caspase-1,Caspase-1 protein expression and cell apoptosis were significantly decreased in Lir group(P<0.05).Conclusion Liraglutide protects human NPCs by inhibiting the activation of NLRP3 inflammasome,reducing IL-1β secretion,and inhibiting cell apoptosis.

Children and adults differ significantly in physiology,biochemistry and immune function,which leads to sig-nificant differences in blood transfusion strategies between children and adults.To guide the clinical transfusion practice of pediatric patients and improve the prognosis of children,the National Health Commission organized the formulation and re-lease of the health industry standard Guideline for Pediatric Transfusion(WS/T 795-2022).This paper will briefly introduce some concepts that help understand of the Standard and the preparation process of the Standard,and explain and interpret the preparation of the"scope","general provisions"and"factors to consider"of the Standard,hoping to contribute to the understanding and implementation of the Standard.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.

Objective:To explore the effect of job insecurity on work engagement, and examine the mediating role of job satisfaction and the moderating role of occupational proactive behavior.Methods:Using the convenient sampling method, nurses from Southern University of Science and Technology Hospital and Jiangyou Second People's Hospital were selected as the research objects in July 2022. General information questionnaire, Occupational Insecurity Scale, Occupational Satisfaction Scale, Work Engagement Scale and Occupational Proactive Behavior were used for questionnaire investigation. A total of 598 valid questionnaires were collected. Model 4 and Model 7 in the SPSS 22.0 Process were used to test the mediating effect and the moderated mediating effect respectively.Results:Occupational insecurity was negatively correlated with occupational satisfaction and work engagement ( r=-0.202, -0.165, P<0.01) , while occupational satisfaction was positively correlated with work engagement ( r=0.549, P<0.01) . Work satisfaction played a completely mediating role in the effect of job insecurity on work engagement (mediating effect value: -0.090 9, 95% confidence interval: -0.14 - -0.04) , accounting for 65.30% of the total effect. Occupational active behavior positively moderated the relationship between job insecurity and job satisfaction (β=0.07, P<0.01) . Conclusions:Nurses' work engagement is at a high level, but occupational insecurity will reduce nurses' job satisfaction and thus reduce their work engagement. Nurses with high occupational proactive behavior can alleviate the weakening of job insecurity on job satisfaction.

Objective:To analyze the distribution of clinically isolated fungal strains and their resistance to common antifungal drugs in Shandong province.Methods:Through the Shandong Children’s Bacterial & Fungal Drug Resistance Surveillance and Research Collaborative Network, a total of 1 030 fungi were collected in 46 hospitals of Shandong province from January 1 to December 31, 2018. The source and type of strains were analyzed, and antifungal drug sensitivity tests were performed by using the micro-dilution method. Whonet 5.6 and SPSS 22.0 were applied to analyze the data.Results:The overall main strains were Candida albicans (38.74%, 399/1 030), Candida tropicalis (16.99%, 175/1 030) and Candida parapsilosis (16.41%, 169/1 030); the main fungi strains in child patients were C. albicans (52.50%, 63/120), C. parapsilosis (12.50%, 15/120) and C. tropicalis (9.17%, 11/120); the main fungi strains in adult patients were C. albicans (36.37%, 331/910), C. tropicalis (17.03%, 155/910) and C. parapsilosis (15.27%, 139/910). The isolation rate of main Candida strains from January to March and August to December was much higher than that of other months. The drug resistance rates of C. albicans to fluconazole and voriconazole were 7.14% and 7.43%, respectively, and the drug resistance rates to itraconazole were 50.44%. The resistance rates of C. tropicalis to fluconazole, voriconazole and itraconazole were 29.05%, 23.29% and 48.65%, respectively. The sensitivity rates of C. parapsilosi to fluconazole, voriconazole and itraconazole were 93.06%, 93.75% and 94.44%, respectively. Candida glabrata showed a dose-dependent sensitivity rate of 2.33% to fluconazole. Analysis of 244 blood fungi strains showed that non-candida albicans bacteremia accounted for 70.08%. In the pathogen spectrum covering 92.22%, fluconazole was sensitive to 64.65% of the pathogens, voriconazole was 68.88%, and amphotericin B was 88.75%. After quantification, the effective rates of fluconazole, voriconazole and amphotericin B in the clinical treatment of fungal bacteremia were 70.10%, 74.69% and 96.23%, respectively. Among them, the sensitivity rate of voriconazole to C. tropicalis was lower than that of fluconazole. Conclusions:Candida is the main clinical fungus isolates in hospitals of Shandong province. The resistance rate of C. tropicalis to azole antifungal drugs is on the rise, and the sensitivity of other Candida species to clinically used antifungal drugs is basically stable.

Objective To evaluate the role of μ-δ heterodimer in down-regulation of the expression of excitatory amino acid transporter 3 (EAAT3) in hippocampi caused by reinstatement of morphine-induced conditioned place preference (CPP) in rats.Methods Thirty-two healthy clean-grade male Sprague-Dawley rats,weighing 200-240 g,were assigned into 4 groups (n =8 each) using a random number table method:control group (group C),extinction group (group E),reinstatement group (group R) and reinstatement plus interference plasmid group (group RI).The model of morphine-induced CPP was established,and extinction of CPP was gradually induced by stopping administration.A small dose of morphine 5 mg/kg was intraperitoneally injected again to induce CPP reinstatement,and dwell time around the medicine box was recorded.μ-δ heterodimer interference plasmid 5 μl was injected into the lateral cerebral ventricle after successful establishment of CPP model in group RI.The content of glutamate (Glu) in hippocampi was measured using high-performance liquid chromatography.The EAAT3 expression in hippocampal CA1 and CA3 regions was detected using Western blot.Results Compared with group C,no significant change was found in the dwell time around the medicine box or content of Glu in hippocampi (P＞0.05),and the expression of EAAT3 in hippocampal CA1 and CA3 regions was significantly up-regulated in group E,and the dwell time around the medicine box was significantly prolonged,the content of Glu in hippocampi was increased (P＜0.05),and no significant change was found in the expression of EAAT3 in hippocampal CA1 and CA3 regions in group R (P＞0.05).Compared with group E,the dwell time around the medicine box was significantly prolonged,the content of Glu in hippocampi was increased,and the expression of EAAT3 in hippocampal CA1 and CA3 regions was down-regulated in group R (P＜0.05).Compared with group R,the dwell time around the medicine box was significantly shortened,the content of Glu in hippocampi was decreased,and the expression of EAAT3 in hippocampal CA 1 and CA3 regions was upregulated in group RI (P＜0.05).Conclusion μ-δ heterodimer is involved in down-regulation of EAAT3 expression in the hippocampus caused by reinstatement of morphine-induced CPP in rats.

Objective To observe the value of speckle-tracking imaging (STI) in evaluation on degree of coronary artery stenosis in patients with coronary artery disease (CAD).Methods Totally 74 CAD patients,including 59 with coronary artery stenosis (coronary artery stenosis group) and 15 without coronary artery stenosis (no coronary artery stenosis group) underwent STI and echocardiography.Based on Gensini scores,the patients in coronary artery stenosis group were further divided into mild,moderate and severe subgroups.The average global longitudinal strain (GLS-Avg),basement global longitudinal strain (GLS-Bas),middle global longitudinal strain (GLS-Mid) and apical global longitudinal strain (GLS-AP) value were measured and compared.Results GLS-Avg,GLS-Bas,GLS-Mid and GLS-AP value in coronary artery stenosis group were lower than those in no coronary artery stenosis group (all P ＜ 0.001).In coronary artery stenosis group,with the increase of stenosis severity,GLS-Avg,GLS-Bas,GLS-Mid and GLS-AP value decreased,and statistical differences were found between each two subgroups (all P＜0.05).In coronary artery stenosis group,there were positive correlations between GLS-Avg,GLS-Bas,GLS-Mid,GLS-AP value and Gensini scores (r=0.861,0.847,0.819 and 0.778,all P＜ 0.05).Conclusion GLS value of STI can reflect the severity of coronary artery stenosis in CAD patients.