Objective:To investigate immunomodulatory effects of methionine enkephalin(MENK)on macrophages,and to explore effect of opsonizing receptors in anti-influenza virus infection of macrophages.Methods:Potential targets for antiviral effects of MENK on macrophages were explored by network pharmacology.Proteomics analysis was used to identify differentially expressed pro-teins(DEPs)in macrophages of MENK-PR8 and PR8 groups.DEPs were analyzed by bioinformatics,and key factors were verified by qPCR and Western blot.Results:MENK had 85 intersection targets with macrophages and influenza viruses,of which 7 were related to phagosome pathway(mmu04145).A total of 215 DEPs were identified by mass spectrometry,which were highly enriched in phago-some(mmu04145)and interaction of viral proteins with cytokines and cytokine receptors(mmu04061)pathways.qPCR and Western blot showed that Fc gamma receptor(FcγR)and complement receptor(CR3)related to phagosome were highly expressed.Conclu-sion:MENK enhances function of phagocytosis and killing virus by upregulating opsonizing receptors via opioid receptor,suggesting that MENK can serve as an immune modulator or a novel preventive drug for influenza viruses.

Objective To analyze the transcriptome sequencing results of Nelson Bay virus(NBV)-infected murine RAW264.7 mac-rophages,and to screen for differentially expressed genes(DEGs)to provide a theoretical basis for exploring the mechanism of innate immune response in reovirus infection.Methods RAW264.7 cells were infected with the NBV-Miyazaki virus strain at a multiplicity of infection(MOI)of 30.We used transcriptome sequencing technologies,with q＜0.05 and|log2FC|≥ 1,for screening the DEGs in the infection and control groups.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases were used for enrichment analysis of DEGs.Results A total of 442 genes were differentially expressed in the infection group,of which 381 genes were significantly upregulated and 61 genes were significantly downregulated.In the GO analysis,the enrichment of DEGs was primarily related to the innate immune response,defense response to viruses,cytokine production,and cell response to cytokine stimulation.In the KEGG analysis,the enrichment of DEGs were primarily related to the Toll-like receptor,retinoid acid inducible gene Ⅰ-like receptor,PI3K/Akt,and other signaling pathways.Conclusion RAW264.7 macrophages infected with the NBV-Miyazaki virus can activate pattern recognition receptors;promote the release of cytokines,chemokines,and other immune-related factors;and enhance antibody-dependent cell-mediated cytotoxicity to exert an immune effect.This study provides a theoretical basis for exploring the mechanisms of innate immu-nity during NBV-Miyazaki virus infection.

Objective:To investigate immunomodulatory effects of methionine enkephalin(MENK)on macrophages,and to explore effect of opsonizing receptors in anti-influenza virus infection of macrophages.Methods:Potential targets for antiviral effects of MENK on macrophages were explored by network pharmacology.Proteomics analysis was used to identify differentially expressed pro-teins(DEPs)in macrophages of MENK-PR8 and PR8 groups.DEPs were analyzed by bioinformatics,and key factors were verified by qPCR and Western blot.Results:MENK had 85 intersection targets with macrophages and influenza viruses,of which 7 were related to phagosome pathway(mmu04145).A total of 215 DEPs were identified by mass spectrometry,which were highly enriched in phago-some(mmu04145)and interaction of viral proteins with cytokines and cytokine receptors(mmu04061)pathways.qPCR and Western blot showed that Fc gamma receptor(FcγR)and complement receptor(CR3)related to phagosome were highly expressed.Conclu-sion:MENK enhances function of phagocytosis and killing virus by upregulating opsonizing receptors via opioid receptor,suggesting that MENK can serve as an immune modulator or a novel preventive drug for influenza viruses.

Objective To analyze the transcriptome sequencing results of Nelson Bay virus(NBV)-infected murine RAW264.7 mac-rophages,and to screen for differentially expressed genes(DEGs)to provide a theoretical basis for exploring the mechanism of innate immune response in reovirus infection.Methods RAW264.7 cells were infected with the NBV-Miyazaki virus strain at a multiplicity of infection(MOI)of 30.We used transcriptome sequencing technologies,with q＜0.05 and|log2FC|≥ 1,for screening the DEGs in the infection and control groups.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases were used for enrichment analysis of DEGs.Results A total of 442 genes were differentially expressed in the infection group,of which 381 genes were significantly upregulated and 61 genes were significantly downregulated.In the GO analysis,the enrichment of DEGs was primarily related to the innate immune response,defense response to viruses,cytokine production,and cell response to cytokine stimulation.In the KEGG analysis,the enrichment of DEGs were primarily related to the Toll-like receptor,retinoid acid inducible gene Ⅰ-like receptor,PI3K/Akt,and other signaling pathways.Conclusion RAW264.7 macrophages infected with the NBV-Miyazaki virus can activate pattern recognition receptors;promote the release of cytokines,chemokines,and other immune-related factors;and enhance antibody-dependent cell-mediated cytotoxicity to exert an immune effect.This study provides a theoretical basis for exploring the mechanisms of innate immu-nity during NBV-Miyazaki virus infection.

Objective:To explore the impact of early and late antibody-mediated rejection (AMR) on treatment options and allograft outcomes after kidney transplantation (KT).Methods:From January 2013 to December 2022, the study retrospectively enrolled 141 KT allograft recipients receiving allograft biopsy and diagnosed as AMR according to the Banff 2019 criteria. Recipients with a diagnosis of AMR within 30 days post-KT were classified into early AMR group (n=19) while the remainders assigned as late AMR group (n=122). The outcome endpoints included recipient survival rate, death-censored graft survival rate, follow-up estimated glomerular filtration rate (eGFR) and immunodominant donor-specific antibody (DSA) intensity. Wilcoxon's test was utilized for assessing the differences in eGFR and DSA intensity while Kaplan-Meier curve and Log-rank test were employed for evaluating graft survival impact. Treatment regimens for AMR were collected and categorized.Results:The median follow-up duration was 2.6(1.2, 5.2) year. No graft failure was noted in early AMR group while 44 recipients in late AMR group experienced graft failure, with 34 cases (77.2%) due to AMR progression. The 5-year death-censored graft survival rate was significantly better in early AMR group than that in late AMR group [100% vs 60.1%(50.5%, 71.6%), P=0.002]. The one-year change in eGFR for early AMR group was significantly superior to that of late AMR group [19.3(-2.6, 38.1) vs -3.3(-14.0, 5.4), P=0.001]. One-year mean fluorescent intensity (MFI) of early AMR group was 1 158(401.5, 3 126.5). It was significantly lower than that when diagnosed with early AMR [3 120.5(2 392.8, 9 340.0)] and one-year MFI of late AMR group [8 094(2 251.5, 13 560.5)] ( P=0.005, P<0.001). Early AMR group primarily received standard treatment (3/19, 15.8%) and regimens centered on rituximab and/or bortezomib (7/19, 43.8%). Late AMR group mainly received standard (16/122, 13.1%) or intensified regimens (9/122, 7.4%) and regimens focused upon rituximab and/or bortezomib (32/122, 26.2%) and MP monotherapy (21/122, 17.2%). Conclusion:The outcome for early AMR is significantly better than that for late AMR. For early AMR, early and robust immunosuppression is recommended. For late AMR, early detection and timely treatment are crucial and individualized strategies should be implemented.

Objective:To evaluate the clinical application of urine sediment score (USS) in early diagnosis, etiological differentiation, staging and prognosis of acute kidney injury (AKI), and to investigate the diagnostic efficacy of independent USS and its combination with blood urea nitrogen(Bun) serum creatinine(sCr) and uric acid(UA) in AKI.Methods:From August 23 to September 28, 2023, 9 020 morning urine samples of hospitalized patients in the First Hospital of Jilin University were detected by Sysmex UF5000.A total of 3 226 ssamples with small and round cell (SRC) > 1/μl and/or CAST>1/μl were screened for microscopic examination, and 404 cases with positive renal tubular epithelial cells and/or cast were enrolled in this study. There were 218 males and 186 females, aged 59.5 (49.0, 71.0) years. The 404 cases were divided into the USS AKI group (345 cases) and the USS non-AKI group (59 cases) according to the USS results based on the microscopic findings. According to Kidney Disease: Improving Global Outcomes (KDIGO) criteria, they were divided into KDIGO criteria AKI group (63 cases) and KDIGO criteria non-AKI group (341 cases), and the AKI group was divided into renal AKI group (33 cases) and non-renal AKI group (30 cases). According to the clinical diagnosis recorded in the medical records, they were divided into clinically diagnosed AKI group (29 cases) and clinically diagnosed non-AKI group (375 cases).The χ 2 test or Fisher exact test was used to compare USS in different AKI causes and stages. Logistic regression was used to calculate the odds ratio of renal AKI and stage 3 AKI. The area under the receiver operating characteristic curve was used to evaluate the sensitivity and specificity of USS, sCr, UA and Bun alone and in combination in the diagnosis of AKI, and the best cut-off value, sensitivity and specificity in the diagnosis of AKI were calculated. P < 0.05 was considered statistically significant. Results:The USS was used to identify the etiology of KDIGO standard AKI group,and there were significant differences in USS between renal AKI group and non-renal AKI group (χ 2=11.070, P<0.001). Compared to USS=1, the odds ratio of renal AKI was 8.125 when USS≥2 (95% CI 2.208—29.901). There was a statistically significant difference in the comparison of USS between groups in each stage of the AKI staging study based on USS (χ 2=15.724, P<0.05). Compared to USS=1, the odds ratio of stage 3 AKI was 9.714 when USS≥2 (95% CI 1.145-82.390). The AUC of independent USS in the diagnosis of AKI was 0.687 (95% CI 0.618-0.757, P<0.001), the specificity was 65.7% and the sensitivity was 61.9%. The AUC of USS combined with Bun, sCr, UA in the diagnosis of AKI was 0.794 (95% CI 0.608-0.980, P<0.05), the specificity was 82.4%, and the sensitivity was 88.9%. Conclusions:There wasan increased likelihood of renal AKI or stage 3 AKI while USS≥2,and whose combination with Bun, sCr and UA will improve the diagnostic efficiency of AKI.

Industry-university-research cooperation is not only the core of technological innovation,but also an important way to enhance industrial competitiveness and achieve high-quality development.Industry-university-research cooperation in Liaoning Province has achieved significant results in promoting technological innovation and economic development,but there are still some problems and challenges.The main problems include insufficient depth of industry-university-research cooperation,scattered innovation resources,lack of long-term stable cooperation mechanisms,as well as talent loss and lack of high-quality innovative talents.Through systematically sorting out the existing models of industry-university-research cooperation,it proposes a series of targeted and operable countermeasures and suggestions.These measures and suggestions provide solid theoretical support for the healthy development of industry-university-research cooperation in Liaoning Province.

Objective:To study the situation of legal regulations for the integration of industry-university-research in Liaoning,improve the concept of legal regulation,optimize the legal regulation methods,so as to promote the deep integration of industry-university-research in Liaoning.Method:Problem-oriented approach was used,and the problems of the current legal regulations for the integration of industry-university-research in Liaoning were reviewed.Result:It was found that legal regulations for the deep integration of industry-university-research in Liaoning were not yet perfect,which was manifested in insufficient coverage of policies and regulations,relatively lagging update of regulations,and insufficient highlighting of local characteristics.Conclusion:In response to the above issues,it is proposed to use measures such as collaborative regulation,incentive regulation and moderate regulation to establish and improve the legal system of the integration of industry-university-research in Liaoning province.

Objective:To explore the morbidity features and therapeutic outcomes of rejections in pediatric kidney transplantation (KT) recipients.Methods:Between January 2013 and June 2022, 360 children undergoing KT were recruited.The relevant clinical data were collected for examining the morbidity features and therapeutic outcomes of rejections.The serum levels of creatinine were compared among groups by non-parametric rank test.And Kaplan-Meier and Log-rank methods were employed for examining the incidence of rejection and comparing mortality-censored graft survival rates among patients with different times of rejection.Results:A total of 58 recipients had 82 incidents of rejection with a cumulative incidence of 6.3%, 9.2% and 11.3% at 3/6/12 months respectively.Among 50 incidents of biopsy-proved rejections, the types were T cell-mediated rejection [TCMR, 42.0%(21/50)], antibody-mediated rejection [20.0%(10/50), ABMR] and mixed rejection [38.0%(19/50)].Among 58 incidents of initial rejection, 69% had maintained graft function (MGF) and 31% impaired graft function (IGF) after anti-rejection regimens.Among 80.8%, 85.7% and 75% of recipients with clinical rejection, ABMR or borderline rejection while 36.4% in TCMR patients had MGF.Fifteen kidney allografts lost function in 58 recipients with rejection.Five-year death-censored graft survival was significantly lower in patients with two or more incidents of rejection (30.5%, 95% CI: 12.3%-75.4%) than in those without rejection (92.9%, 95% CI: 89.3%-96.6%) ( P<0.000 1) or with only one rejection (82.9%, 95% CI: 65.9%-100%)( P<0.001). Conclusions:The rejection rate remains high in KT children and it affects graft survival.And TCMR is more likely to cause impaired graft function.Recurrent rejections have a more pronounced impact upon graft survival.

Objective:To explore the diagnosis and treatment of transplanted renal artery stenosis(TRAS)in children.Methods:From January 2016 to August 2021, clinical data of 7 TRAS patients were collected.A definite diagnosis was confirmed by Doppler ultrasound and computed tomography angiography.Results:Patient age was significantly higher than donor age(11.9±3.7 vs 1.0±0.5 years, P<0.001); 5 patients had a widened diameter at stenotic grafted renal artery after intervention(1.98±0.47 vs 4.64±1.19 mm, P=0.002). A reduction in peak systolic flow velocity in stenotic segment of artery(463.3±90.6 vs 183.6±58.9 cm/s, P<0.001)and lower systolic blood pressure(137.2±15.5 vs 129.7±12.3 mmHg, P=0.029)were observed.Resistance index rose(0.38±0.22 vs 0.60±0.03, P=0.063). Significant difference of estimated glomerular filtration rate was observed at Week 4 post-operation as compared with pre-intervention.Two patients developed complications after intervention, including perirenal hematoma and stent-attached thrombus.Two patients were treated conservatively with a gradual increase in blood pressure and three antihypertensive drugs prescribed. Conclusions:Doppler ultrasound should be performed regularly after renal transplantation for detecting TRAS at an early stage in children.Interventional treatment is ideal for severe TRAS to improve perfusion and renal function.Clinicians should pay more attention to complications.