ObjectiveTo investigate the effects of exogenous nitric oxide （NO） on the accumulation and quality formation mechanism of flavonoids in Scutellariae Radix. MethodsFresh roots of Scutellaria baicalensis were treated with sodium nitroprusside （SNP） solutions at concentrations of 0.0， 7.5， and 20 mmol·L^-1， respectively. Kits and supporting reaction systems were used to determine the following indicators of samples in each group， including （1） reactive oxygen species： changes in the content of nitric oxide （NO）， superoxide anion （O2-·）， and hydrogen peroxide （H₂O₂）， （2） lipid oxidation products： changes in the content of malondialdehyde （MDA）， （3） antioxidant enzymes： changes in the activity of superoxide dismutase （SOD）， catalase （CAT）， and peroxidase （POD）， and （4） metabolic key enzymes and metabolic intermediates： Changes in the activity of phenylalanine ammonia-lyase （PAL） and the content of 1，3-diphosphoglycerate （1，3-DPG）. High-performance liquid chromatography （HPLC） was used to determine the changes in the content of secondary metabolites in flavonoids such as baicalin， wogonoside， baicalein， and wogonin in each group. ResultsCompared with that on day 0， during the treatment with 20 mmol·L^-1 SNP solution， the content of NO， O2-·， H₂O₂， and MDA in fresh roots of Scutellaria baicalensis increased significantly （P<0.01）， by 138.7%， 75.7%， 292.9%， and 140.3% respectively. The activity of SOD， CAT， and POD increased by 100.7%， 41.4%， and 70.4% respectively （P<0.01）， and that of PAL increased by 111.1% （P<0.01）. The content of the secondary metabolites baicalin and wogonoside remained basically unchanged， while that of baicalein and wogonin increased by 401.3% and 457.9% respectively （P<0.01）. The content of 1，3-DPG increased by 165.0% （P<0.01）. In the 7.5 mmol·L^-1 SNP solution treatment group， the stress degree was relatively mild. Compared with that on day 0， the content of NO， O2-·， H₂O₂， and MDA increased by 76.2%， 57.7%， 221.4%， and 99.7% respectively （P<0.01）. The activity of antioxidant enzymes SOD， CAT， and POD increased by 79.5%， 55.6%， and 51.9% respectively （P<0.01）， and that of PAL increased by 69.0% （P<0.01）. The content of baicalein and wogonin increased by 204.7% and 272.2% respectively （P<0.01）， and that of 1，3-DPG increased by 128.0% （P<0.01）. The 20 mmol·L^-1 SNP group showed better performance than the 7.5 mmol·L^-1 SNP group. ConclusionSNP can simulate the physiological state of Scutellaria baicalensis under stress conditions， activate the antioxidant protection mechanism， promote the biosynthesis of flavonoids in Scutellariae Radix， and significantly improve the quality of medicinal materials in Scutellariae Radix.

Existing nucleos（t）ide analogues and pegylated interferon exhibit limited efficacy in the functional cure of hepatitis B. Recently， small nucleic acid drugs， such as antisense oligonucleotides and small interfering RNAs， have brought unprecedented breakthroughs in the functional cure of hepatitis B with their brand-new mechanisms of action and remarkable efficacy in early clinical studies. Small nucleic acid drugs， such as antisense oligonucleotides and small interfering RNAs， can reduce the level of HBsAg and strive to achieve HBsAg seroclearance. The reduction in HBsAg may restore the hepatitis B-specific immune function of the body to some extent and may further transform the simple clearance of HBsAg into hard endpoints with clinical value， such as reducing hepatitis B-related liver events. By meticulously analyzing the dynamic trajectory of HBsAg alterations within the context of new drug applications and further optimizing combined treatment strategies and regimens， it is expected to transform the functional cure of hepatitis B into the ultimate goal of improving survival rates and quality of life.

Objective To investigate the potential profile of self-management behavior in patients with sudden deafness,the characteristics and influencing factors of different categories of patients,and provide reference for clin-ical management.Methods A total of 205 patients with sudden deafness who were hospitalized in the Department of Otology of a Grade 3 hospital in Beijing were selected by convenience sampling method from August 2023 to June 2024.Date were collected using the general situation questionnaire,self-management status assessment scale for sudden deafness patient and social support rating scale.Mplus 8.0 was used for potential profile analysis,and SPSS 26.0 was used for single factor analysis and multiple logistic regression analysis.Results A total of 200 valid ques-tionnaires were collected.Patients were divided into 3 categories according to their self-management level,which were respectively named as"high management—good self-efficacy group"(n=52,26.00％),"moderate manage-ment—symptoms of special concern group"(n=101,50.50％),and"low management-lack of information acquisi-tion group"(n=47,23.50％).Multiple logistic regression analysis showed that education level,sleep disorder and social support level were the influencing factors of different self-management categories in patients with sudden deaf-ness.Conclusion The overall self-management ability of patients with sudden deafness is at a moderate level and with significant heterogeneity.Education level,sleep disorders,and social support serve as stratification criteria for categorizing different patient groups and formulating corresponding intervention strategies.Priority should be given to providing information support to the"low-management group with information deficiency",implementing targe-ted interventions for the"moderate-management group with symptom focus",and fully leveraging the self-efficacy of the"high-management group with good self-efficacy"to regulate their self-management level.

Objective To explore the mechanism of Shanggan granules in suppressing pulmonary inflammation in mice infected with H1N1 influenza virus.Methods A mouse model of pulmonary influenza virus infection was established by nasal inoculation with H1N1 influenza virus.Mice were divided into a normal control group,model group,positive control group,and low-,medium-,and high-dose Shanggan granules groups.Mice were treated for 7 days and then sacrificed,and the body weight and lung wet weight were measured.Pathological changes in the lung tissues were detected by hematoxylin/eosin(HE)staining.Tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-8,and transforming growth factor-β(TGF-β)levels in lung tissues were detected by enzyme-linked immunosorbent assay,and superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)were detected using appropriate kits.Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)inflammatory signaling pathways were detected by real-time polymerase chain reaction,and TANK-binding kinase 1(TBK1)/interferon regulatory factor(IRF)signaling pathway proteins were detected by Western blot.Results Both Shanggan granules and oseltamivir phosphate reduced the lung wet weight(P＜0.05,P＜0.001)in mice infected with influenza virus H1N1 compared with the model group,decreased the infiltration of inflammatory cells in lung tissue,reduced levels of the inflammatory factors TNF-α,IL-6,IL-8,and TGF-β(P＜0.05,P＜0.01,P＜0.001),decreased levels of SOD and GSH-Px in lung tissue(P＜0.05,P＜0.01),and increased MDA levels(P＜0.05,P＜0.01).Shanggan granules and oseltamivir phosphate also reduced TLR4,MyD88,and p38 mRNA levels(P＜0.05,P＜0.01)and expression of TBK1/IRF3/7/NF-κB signaling pathway proteins(P＜0.05,P＜0.01,P＜0.001).Conclusions Shanggan granules may effectively reduce lung injury,lung inflammation,and oxidative stress,via a mechanism related to the down-regulation of TLR4/NF-κB inflammatory signaling pathways.

Objective:To investigate the effect of ERMAP on imiquimod(IMQ)-induced psoriasis-like skin inflammation in mice and its related mechanism.Methods:The experimental mice were divided into 3 groups:Sham group,WT group and ERMAP-/-group,with 9 mice in each group.The Sham group was smeared with Vaseline,and the WT group and ERMAP-/-group were smeared with IMQ to induce psoriatic dermatitis.The severity of IMQ-induced psoriasis lesions in mice were evaluated according to the psoria-sis area and severity index(PASI)and the HE staining pathology score.The expressions of F4/80 and Ki67 in mouse skin lesions were observed by immunofluorescence staining.The relative expressions of IL-1β,IL-6,IFN-γ and iNOS in skin lesions were detected by qRT-PCR.Flow cytometry was used to detect the proliferation and activation of T cells and the proportion of macrophages in spleen.Results:In the IMQ-induced mouse model of psoriasis-like dermatitis,the skin lesions of ERMAP gene knock out mice showed more severe squamous accumulation and skin bulge,more inflammatory cells aggregation and cytokine production,and the proportion of immune cells in the spleen of mice increased compared with the WT group,and the proportion of M1 macrophages increased.Conclu-sion:ERMAP deficiency aggravates IMQ-induced psoriasis-like skin inflammation in mice by enhancing immune response.

Objective::To examine the impact of hypertensive disorders of pregnancy (HDP) on offspring metabolomics.Methods::We searched five databases: PubMed, Ovid Embase, MEDLINE, Web of Science, and China National Knowledge Infrastructure, and included studies that reported metabolomics among human offspring born to HDP-complicated pregnancies.Results::Database search yielded 4054 articles, and after full-text screening, ten observational studies met inclusion criteria. Half of the studies had a sample size of less than 100 and were all observational studies in preeclampsia (PE) and gestational hypertension.Neonates were the most focused group in all included studies. Offspring born to HDP-complicated pregnancies exhibited statistically significant variations in blood metabolomics compared to their counterparts, characterized by amino acids, lipids, carnitine, and others (e.g., 1α,25-(OH) 2-D). Most studies reported a significant increase in differential metabolites of offspring born to HDP-complicated pregnancies. Four studies ( n = 1109) measured lipids-related metabolites, and all consistently showed that offspring born to PE-complicated pregnancies had significantly higher concentrations than non-PE exposed offspring. Conclusion::The existing evidence suggests an intergenerational effect of HDP on offspring metabolomics. Long-term follow-up studies are needed to advance the health effects of related adverse health outcomes and inform the prevention of offspring’s health.

Objective:To explore the RNA expression and alterations in brain structure in individuals who have experienced stressful life events (SLE), as well as the correlation patterns between them and their association with the occurrence of depression.Methods:Prospectively, a total of 80 SLE subjects were recruited from the psychiatry and psychology clinic of the Jiangsu University Affiliated Yixing Hospital between January 2021 and December 2022, with 16 normal controls (NC) enrolled concurrently. The 17 items Hamilton depression scale (HAMD-17) and social readjustment rating scale (SRRS) were used to assess depressive symptoms and stress levels. RNA sequencing information of peripheral blood and imaging data at baseline were collected. Based on whether depression occurred during the 2-year follow-up period, SLE subjects were divided into the SLE-depression group ( n=15) and the SLE-non-depression group ( n=65). Differentially expressed genes (DEGs) were screened using differential analysis and protein-protein interaction (PPI) networks. Fractional anisotropy (FA) of white matter tracts and gray matter volume (GMV) were extracted using tract-based spatial statistics and voxel-based morphometry.Using analysis of variance compared inter-group differences in gene expression, GMV and white matter FA values. Partial correlation analysis was used to explore correlations between DEGs, altered GMV and white matter microstructure. Gene set enrichment analysis (GSEA) was performed on key genes to identify potential biological pathways. Propensity score matching constructed sensitivity subgroups to verify result robustness. Results:The SLE-depression group showed significantly higher SRRS and HAMD-17 scores at baseline and at the end of follow-up compared to the SLE-non-depression group and the NC group ( H=47.773, 35.427, 41.114, all P<0.05). Expression levels of IL-10 (2.12±0.28, 2.43±0.44), EZH2 (2.11±0.43, 2.45±0.51), NCAM1 (3.60±0.30, 3.03±0.39), CD3E (4.95±0.37, 4.57±0.48), CCK (3.29±0.28, 3.02±0.42), and CX3CR1 (5.55±0.40, 5.91±0.34) were significantly different between the SLE-depression group and SLE-non-depression group( F=5.549~28.371, all P<0.05). Compared with the SLE-non-depression group, the SLE-depression group exhibited significantly lower FA values in the genu of the corpus callosum (0.29±0.04, 0.31±0.04) and the left uncinate fasciculus (0.31±0.02, 0.33±0.02), as well as significantly smaller GMV in the right hippocampus (0.29±0.07, 0.33±0.06), bilateral middle frontal gyrus (left: 0.27±0.05, 0.31±0.05; right: 0.28±0.06, 0.32±0.06), right insula (0.36±0.03, 0.38±0.04), and left precentral gyrus (0.19±0.04, 0.24±0.05) ( F=4.593-12.064, all P<0.05, FDR correction). GMV in the right anterior cingulate and paracingulate gyri was significantly larger than that in the SLE-non-depression group (0.34±0.05, 0.29±0.06) ( F=6.704, P=0.034, FDR correction). Partial correlation analysis revealed significantly stronger correlations between hub DEGs and altered brain regions in the SLE-depression group ( r=0.017-0.801) compared to the SLE-non-depression group ( r=0.002-0.382), with a statistically significant difference ( U=629, P<0.001; Cliff's Delta=0.454). GSEA indicated that the aforementioned genes were primarily involved in pathways including the ribosome, spliceosome, ribosome biogenesis in eukaryotes, and neuroactive ligand-receptor interaction. Sensitivity analysis confirmed that the above results remained statistically significant after balancing sample sizes (all P<0.05). Conclusion:The SLE-depression group showed specific RNA expression and brain structure alterations compared to the SLE-non-depression group, and the correlation between RNA and brain structure was significantly enhanced in the SLE-depression group. This suggests that the correlation between genes and brain structure in the SLE population may be related to their susceptibility to depression.

Objective To explore whether miR-146b can participate in the brain injury process of diabetic rats with cerebral infarction(DM-CI)by regulating the extracellular regulatory protein kinase(ERK1/2)-activated protein-1(AP-1)signaling pathway.Methods 80 SD rats were randomly divided into sham operation group,DM-CI group,low miR-146b expression group and ERK1/2 inhibition group,with 20 rats in each group.The National Institutes of Health Stroke Scale(NIHSS)score measures brain function in rats.The mRNA levels of miR-146b,ERK1/2 and AP-1 in rat brain tissue were detected by RT-qPCR.Western blotting detected ERK1/2,AP-1 protein levels in rat brain tissue.TTC staining was used to detect cerebral infarction volume in rats.H&E staining was used to detect brain histopathological changes.Random blood glucose levels were detected by glucose meter in rats.Results Compared with sham operation group,mRNA expression levels of miR-146b,ERK1/2 and AP-1 in brain tissue of rats in DM-CI group were significantly increased,with statistically differences(t=10.86,15.62,9.87,all P<0.05).ERK1/2 and AP-1 protein levels increased,with statistically differences(t=11.18,23.81,P<0.05).NIHSS score increased and random blood glucose level increased(t=44.49,30.02,all P<0.05),and increased cerebral infarction volume(t=51.05,P<0.05),the structure of brain tissue was disorganized and loose,and edema can be seen in the pericellular space.Compared with the DM-CI group,the mRNA expression levels of miR-146b,ERK1/2 and AP-1 in the brain tissue of rats with low expression of miR-146b were decreased,with statistically differences(t=38.00,20.03,24.25,all P<0.05).the protein expression of EPK1/2 and AP-1 decreased,and the differences were statistically significant(t=12.30,26.70,all P＜0.05).NIHSS score and random blood glucose level were decreased,with statistically differences(t=38.11,33.77,all P<0.05),cerebral infarction volume decreased(t=16.70,P<0.05),the degree of brain tissue in jury and edema was improved,and the expression levels of ERK1/2 and AP-1 protein and mRNA in brain tissue of rats inhibited by ERK1/2 were decreased,with statistically differences(t=13.61～38.00,all P<0.05),the NIHSS score of rats was decreased,and the random blood glucose level was decreased,with statistically differences(t=16.48,26.61,all P<0.05).Conclusion MiR-146b may be involved in brain functional and structural damage in DM-CI rats by regulating ERK1/2-AP-1 signaling pathway.

Objective:To explore the relapse-related genes and their clinicopathological connections of diffuse large B cell lymphoma (DLBCL).Methods:Targeted panel sequencing was conducted on 32 eligible DLBCL samples; the patients were diagnosed, treated, and went into complete remission at the First Affiliated Hospital of Nanjing Medical University from January 2015 to December 2019, including 14 cases with recurrence (relapsed group) and 18 cases with long-term complete remission of over five years (remission group). Clinical and pathological data were further reviewed. Fisher′s exact test was employed to compare the differences in clinicopathological characteristics and mutation patterns between the two groups.Results:Among the 32 patients, there were 18 males and 14 females, with a male to female ratio of 1.3∶1.0 and a median age of 53 (45.5, 67.0) years. In the relapsed group, PIM1 (11/14), KMT2D (7/14), PRDM1 (6/14), MYD88 (6/14), DTX1 (6/14) emerged as the most frequently mutated genes. In the remission group, while recurrent PIM1, KMT2D and MYD88 mutations were also observed, the TP53 gene exhibited the highest mutation frequency (6/18). Compared to the remission group, relapsed group showed elevated mutation frequencies of PIM1 ( P=0.013) and FAT4 ( P=0.010), alongside a reduced incidence of TP53 mutations. In all 32 patients, DLBCL with CD79B, CCND3, DTX1, KMT2D and PRDM1 mutations demonstrated a propensity towards advanced clinicopathologic stage. Conclusions:Relapsed DLBCL has distinctive clinicopathological and genetic features. PIM1 and FAT4 may be served as potential biomarkers for screening relapsed DLBCL-NOS and as targets for novel therapeutic strategies.

The aging trend is intensifying currently,but there is still a lack of standardized diagnosis and treat-ment schemes for severe infections in elderly people.This paper focuses on the recommendations for immune-related clinical diagnosis and treatment routes as well as the idea of risk stratified diagnosis and treatment for elderly peo-ple,aiming to effectively prevent infectious diseases in elderly people and perform stratified management through systematic and scientific means of immune function monitoring and regulation,so as to enhance the standardized level of diagnosis and treatment as well as clinical treatment effect of infection in elderly people.