AIM: To investigate the effect and potential mechanism of liraglutide(LIR)combined with neural stem cells(NSCs)in alleviating diabetic retinopathy(DR)in rats.METHODS:A DR rat model was established using a high-fat diet combined with a single intraperitoneal injection of streptozotocin(STZ). Rats in the control group were fed a normal diet and received an intraperitoneal injection of citric acid-sodium citrate buffer. After modeling, the rats were divided into the control group, DR group, DR+LIR group, DR+BMSCs group, DR+NSCs group, DR+BMSCs+LIR group, and DR+NSCs+LIR group. According to the grouping instructions, rats were given intraperitoneal injection of LIR at 200 μg/(kg·d)and intravitreal injection of bone marrow mesenchymal stem cells(BMSCs), or NSCs, or the combined therapy accordingly for 8 wk. Fasting blood glucose(FBG)and serum insulin levels, as well as retinal oxidative stress indexes and serum inflammatory indexes, were detected in each group. Retinopathy was evaluated by hematoxylin-eosin(HE)staining, retinal cell apoptosis was detected by TUNEL staining, SIRT1 expression in retinal tissues was detected by immunohistochemistry, and BDNF expression in retinal tissues was detected by immunofluorescence. The transcriptional levels of cZNF532, miR-29a-3p, SIRT1, TGF-β1, NRF2, Keap1, and BDNF in retinal tissues were detected by qRT-PCR, and the protein expression levels of SIRT1, TGF-β1, SMAD2/3, p-SMAD2/3, NRF2, Keap1, p65, and p-p65 in retinal tissues were detected by Western blot. RESULTS:Compared with the other groups of rats, the retinal morphology of rats in the DR+NSCs+LIR group was significantly improved, the levels of FBG, TNF-α, IL-1β, IL-6 and MDA were decreased(all P<0.05), the serum insulin level and the levels of SOD, CAT, and GSH-Px were increased(all P<0.05), the TUNEL-positive rate of retinal cells was reduced(all P<0.05). The expression levels of cZNF532, SIRT1, NRF2, and BDNF in retinal tissue were up-regulated(all P<0.05), whereas the expression levels of miR-29a-3p, TGF-β1, p-SMAD2/3, Keap1, and p-p65 were down-regulated(all P<0.05). CONCLUSION:LIR combined with NSCs alleviates DR by regulating the cZNF532-miR-29a-3p-SIRT1 network and its downstream TGF-β/SMAD, NF-κB, and Keap1/NRF2 signaling pathways.

Objective To explore the value of a clinical diagnostic model of heart failure(HF)based on disulfidptosis-related genes.Methods The differentially expressed disulfidetosis-related genes from the training set of Gene Expression Omnibus Series(GSE)57345 were obtained,and then analyzed with Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)en-richment analysis,and Metascape disease enrichment analysis.Six male C57BL/6J mice were ran-domly divided into control group(intraperitoneal injection of normal saline)and HF group(intra-peritoneal injection of isoproterenol),with 3 mice in each group.Real-time quantitative PCR was applied to detect the expression levels of key genes.Results GO enrichment analysis revealed that the differentially expressed disulfidetosis-related genes were mainly involved in platelet aggrega-tion and other aspects.KEGG showed they were significantly enriched in tight junctions,vascular smooth muscle contraction and other signaling pathways.Metascape enrichment analysis indicated that these genes were mainly related to focal glomerulosclerosis,glomerular disease,platelet dis-ease,tumor infiltration,nephrotic syndrome and other diseases.The HF group had significantly higher heart weight-to-body weight ratio,and lower ejection fraction,fractional shortening,cardiac output and stroke volume than the control group(P＜0.05,P＜0.01).The cardiac mRNA levels of BNP and MYH10 were significantly higher[1.026±0.501 vs 0.686±0.187,P=0.038;1.469(1.782,2.670)vs 0.360(0.786,1.117),P=0.000],while those of MYL6 and TLN1 was obviously lower(0.575±0.105 vs 1.000±0.202,P=0.027;0.429±0.114 vs 1.000±0.109,P=0.000)in the HF group than the control group.Conclusion Our constructed HF diagnostic model has better di-agnostic performance.

Objective To explore the value of a clinical diagnostic model of heart failure(HF)based on disulfidptosis-related genes.Methods The differentially expressed disulfidetosis-related genes from the training set of Gene Expression Omnibus Series(GSE)57345 were obtained,and then analyzed with Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)en-richment analysis,and Metascape disease enrichment analysis.Six male C57BL/6J mice were ran-domly divided into control group(intraperitoneal injection of normal saline)and HF group(intra-peritoneal injection of isoproterenol),with 3 mice in each group.Real-time quantitative PCR was applied to detect the expression levels of key genes.Results GO enrichment analysis revealed that the differentially expressed disulfidetosis-related genes were mainly involved in platelet aggrega-tion and other aspects.KEGG showed they were significantly enriched in tight junctions,vascular smooth muscle contraction and other signaling pathways.Metascape enrichment analysis indicated that these genes were mainly related to focal glomerulosclerosis,glomerular disease,platelet dis-ease,tumor infiltration,nephrotic syndrome and other diseases.The HF group had significantly higher heart weight-to-body weight ratio,and lower ejection fraction,fractional shortening,cardiac output and stroke volume than the control group(P＜0.05,P＜0.01).The cardiac mRNA levels of BNP and MYH10 were significantly higher[1.026±0.501 vs 0.686±0.187,P=0.038;1.469(1.782,2.670)vs 0.360(0.786,1.117),P=0.000],while those of MYL6 and TLN1 was obviously lower(0.575±0.105 vs 1.000±0.202,P=0.027;0.429±0.114 vs 1.000±0.109,P=0.000)in the HF group than the control group.Conclusion Our constructed HF diagnostic model has better di-agnostic performance.

Narrative is the cornerstone of interpersonal relationships and life safety. However， its important value in daily life， school education， health management， personal happiness， career development， and other aspects has been ignored. The narrative ecology of families， schools， hospitals， workplaces， and elderly care institutions is worrying， the narrative connection between parent-child and intergenerational is broken， the narrative nature of adolescents is ignored， the narrative demands of patients are neglected， narrative relationships in the workplace are indifferent， and the narrative capital of the elderly is idle. These issues have resulted in serious social problems， such as depression and suicide among adolescents， conflicts between doctors and patients， workplace and life burnout among middle-aged people， and the inability of the elderly to achieve healthy aging， which have become a “stumbling block” to the realization of holistic health. Advocating the construction of narrative ecology and interpersonal narrative connections is an important measure of achieving holistic health. Taking the “narrative concept” as the overall framework， and based on the research， education， and practice carried out by the Alliance of Narrative Medicine in Higher Education Institutions， this paper proposed that actively build China’s narrative system of life and health， to enable narrative play an active and dynamic role in the construction of narrative ecology in different spaces， such as the families， the schools， the hospitals， the workplaces， and the elderly care institutions， as well as practically improve the quality of life of the people.

Objective: To explore the facilitating and hindering factors of mental health promotion activities in junior and senior high schools from teachers perspectives, as well as coping strategies, so as to provide evidence for implementing teacher led mental health promotion programs. Methods: From September 2023 to September 2024, by using purposive sampling method, 5 junior high schools, 5 regular high schools, 2 vocational high schools in four provinces and municipalities (Tianjin, Shanxi, Shandong, and Jiangxi) were selected. A total of 92 teachers (78 homeroom teachers and 14 full time or part time psychological counselors) were interviewed using semi structured focus group discussions (one session per school, totaling 12 sessions). Thematic analysis was applied to code and analyze the interview transcripts. Results: The implementation of mental health promotion activities in middle schools was influenced by three levels: teachers, schools and society. Specifically, teachers exhibited a high support low capability phenomenon (81 participants supported conducting such activities, but 71 felt lacking in professional capacity); activity effectiveness and support systems were imbalanced (42 mentioned significant effects, while 78 reported insufficient support); there was a mismatch between student demand and activity content (9 mentioned students had psychological needs, but 11 indicated existing activities failed to meet these needs); administrative support and sustainability showed disparities (14 believed sufficient administrative support existed, while 37 noted sustainability issues); parental awareness and participation remained inadequate (11 highlighted parents need for mental health knowledge, and 37 perceived insufficient understanding of psychological issues among parents). Effective strategies included enhancing teachers effectiveness, providing essential skill training, focusing on the needs of teenagers,enhancing program sustainability, and eliminating misconceptions about mental health among parents. Conclusion Mental health promotion activities in junior and senior high schools should focus on enhancing teachers skills, improving activity sustainability, reducing stigma among parents, and establishing a collaborative network for school based mental health promotion.

Background: Inflammation indices are emerging predictors of diseases. Monoclonal gammopathy of undetermined significance (MGUS) is a precancerous state and chronic inflammation may drive MGUS progression. This study aimed to evaluate the association between inflammatory markers and MGUS. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) III and 1999–2004 were collected from 6,383 participants. MGUS subtypes were identified using immunofixation electrophoresis. Seven inflammatory indices [lymphocyte count (LC), neutrophil count (NC), platelet-neutrophil product (PPN), systemic immune inflammation index (SII), platelet-lymphocyte ratio (PLR), and C-reactive protein (CRP)] were calculated. Weighted multivariate regression and subgroup analyses assessed the relationships, reported as odds ratios (ORs) and 95% confidence intervals (CIs). Results: Of the 6383 patients included in the study, 157 (2.45%) underwent MGUS. There was a significant correlation trend between ln PPN level and the development of MGUS, especially at low levels (OR: 2.62, 95% CI: 1.54–4.75, p-trend = 0.001), while the correlation between PLR level and MGUS was not obvious. In the subgroup analysis, a significant association between PPN level and MGUS was mainly found in the overall population, female sex, nonHispanic black, non-hypercholesterolemia, non-type 2 diabetes (T2D), high school education or above, and divorced or widowed; however, there was no significant interaction between PPN level and MGUS in each subgroup. Conclusion PPN levels were significantly associated with MGUS development. Our study identified PPN as a novel and convenient inflammatory marker with potential clinical relevance. Although preliminary, the observed associations highlight the need for validation through longitudinal studies before considering their clinical applications.

As a receptor protein,GPR120 is activated by long-chain fatty acids(such as omega-3 fat-ty acids,alpha-linolenic acid,eicosapentaenoic acid,and docosahexaenoic acid.It plays an important regulatory role in gastrointestinal peptide release,inflammation,lipogenesis,glucose tolerance,and insulin sensitivity.In order to study the synergistic regulation of the GPR120 gene on milk fat me-tabolism and its anti-inflammatory effects in dairy cow MAC-T cells,the GPR120 activator TUG-891 and the inhibitor AH7614 were used to treat both dairy cow MAC-T cells and LTA-induced inflammatory dairy cow MAC-T cells.This treatment aimed to detect the expression of key genes involved in milk fat synthesis and inflammatory factors.The results showed that the GPR120 gene activator significantly increased the relative expression levels of cholesterol regulatory element binding protein(SREBP1)and fatty acid synthase(FASN),key genes for milk fat synthesis.Addi-tionally,the expression levels of the inflammatory factor interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were reduced in the inflammatory dairy cow MAC-T cell model,which prelimi-natively reveals that GPR120 co-regulates milk fat and mammary inflammation in dairy cows,thereby laying a foundation for subsequent molecular mechanism research.

Objective:To evaluate the efficacy of omalizumab in the treatment of chronic spontaneous urticaria (CSU), and to analyze its influencing factors.Methods:CSU patients treated with omalizumab were prospectively enrolled from the Department of Dermatology, General Hospital of Ningxia Medical University from October 2021 to October 2023. These patients received subcutaneous injections of omalizumab at a dose of 300 mg every 4 weeks (150 mg for patients aged under 12 years) for at least 3 consecutive sessions. Data on general information, blood routine test, and serum total IgE levels were collected, and the 7-day Urticaria Activity Score (UAS7), Urticaria Control Test (UCT), Dermatology Life Quality Index (DLQI), Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL), and the Beck Anxiety Inventory (BAI) were evaluated by dermatologists at baseline, and after 4, 8, and 12 weeks of treatment. A decrease in UAS7 score of ≥ 11 points was defined as good disease control, while a decrease in UAS7 score of < 11 points was defined as poor control. Univariate binary logistic regression and multivariate logistic regression models were used to identify factors influencing the efficacy.Results:A total of 81 CSU patients were enrolled, including 34 males (42.0%) and 47 females (58.0%) ; their ages ranged from 6 to 66 years (39.2 ± 17.9 years), and the disease duration was 42.3 ± 6.9 months; the serum total IgE levels were 249.5 ± 216.3 IU/ml, with 54 patients (66.7%) showing elevated IgE levels (> 100 IU/ml). Compared with baseline levels, the UAS7, DLQI, and CU-Q2oL scores all significantly decreased at weeks 4, 8, and 12, while the UCT scores significantly increased (all P < 0.05). According to the UAS7 change values, 68 patients (83.9%) were well controlled, and 13 (16.1%) were poorly controlled. Univariate logistic regression analysis showed that higher total IgE levels and higher mean platelet volume (MPV) were associated with better efficacy, while higher body mass index (BMI), higher BAI, and the complication of other allergic diseases were associated with poorer efficacy (all P < 0.05). Multivariate logistic regression analysis indicated that BMI, BAI, and MPV significantly affected efficacy: higher MPV was associated with better efficacy ( OR = 3.36, 95% CI: 1.196 - 9.465, P = 0.020), while higher BMI ( OR = 0.76, 95% CI: 0.599 - 0.957, P = 0.016) and higher BAI ( OR = 0.92, 95% CI: 0.870 - 0.985, P = 0.021) were associated with poorer efficacy. During the whole study, only 4 patients (5%) experienced drowsiness, low fever, redness or discomfort at the injection sites, and no serious adverse events were reported. Conclusion:Omalizumab exhibited significant efficacy and high safety in the 12-week treatment of CSU, and BMI and BAI appeared to be risk factors for efficacy, while MPV seemed to be a protective factor affecting efficacy.

Lipophosphatidic acid(LTA)was used to stimulate Mac-T cells,and the expression lev-els and phosphorylation levels of key proteins of nuclear factor-κB(NF-κB)and mitogen-activated protein kinase(MAPK)signaling pathway and the expression levels of upstream key action factors TLR4 and MyD88 proteins were detected by Western blot,and EDU assay was used to detect cell proliferation levels and flow cytometry was used to detect apoptosis.The results showed that acti-vation of GPR120 significantly decreased the phosphorylation levels of LTA-induced NF-κB(P65 and IκBα)(P＜0.01)and MAPK(JNK,ERK,p38)(P＜0.01)in Mac-T cells;inhibition of GPR120 was able to upregulate LTA-induced NF-κB(p65 and IκBα)in Mac-T cells(P＜0.01)and MAPK(JNK,ERK,p38)phosphorylation levels(P＜0.01);and activation of GPR120 significantly allevia-ted LTA-induced upregulation of TLR4 and MyD88(P＜0.01);inhibition of GPR120 significantly exacerbated LTA-induced upregulation of TLR4 and MyD88(P＜0.05);LTA stimulation led to a trend of diminished Mac-T cell proliferation and significantly increased apoptosis,whereas activa-tion of the GPR120 gene significantly increased cell activity(P＜0.01),promoted cell proliferation and significantly reduced apoptosis(P＜0.05)thereby alleviating the damage to Mac-T cells by LTA;LTA stimulation led to a highly significant increase in apoptosis(P＜0.01).In contrast,acti-vation of the GPR120 gene significantly reversed the increase in the apoptosis rate of Mac-T cells induced by LTA(P＜0.01),while inhibition of the GPR120 gene enhanced the apoptosis-promo-ting effect of LTA(P＜0.05),indicating that activation of the GPR120 gene attenuated the in-crease of apoptosis rate caused by LTA-induced inflammatory Mac-T cells.The results suggest that GPR120 can regulate inflammation by mediating TLR4 and MyD88 expression to inhibit NF-κB/MAPK inflammatory pathway activation and can promote cell proliferation.

Objective:The distribution characteristics of intrathecal drugs and the limitation of current catheterization techniques make traditional intrathecal analgesic treatment nearly useless for refractory craniofacial pain,such as trigemina neuralgia.This technical guideline aims to promote the widespread and standardize the application of intra-prepontine cisternal drug delivery via spinal puncture and catheterization. Methods:A modified Delphi approach was used to work for this guideline.On the issues related to the intra-prepontine cisternal targeted drug delivery technique,the working group consulted 10 experts from the field with 3 rounds of email feedback and 3 rounds of conference discussion. Results:For the efficacy and safety of the intra-prepontine cisternal targeted drug delivery technique,a consensus was formed on 7 topics(with an agreement rate of more than 80%),including the principles of the technique,indications and contraindications,patient preparation,surgical specifications for intra-prepontine cisternal catheter placement,analgesic dosage coordination,analgesic management,and prevention and treatment of complications. Conclusion:Utilizing the intra-prepontine cisternal drug infusion system to manage refractory craniofacial pain could provide advantages in terms of minimally invasive,secure,and effective treatment.This application can not only alleviate the suffering of individuals experiencing the prolonged pain but also support the maintenance of quality of life and dignity in their final moments,justifiing its widespread dissemination and standardized adoption in domestic and international professional fields.