Objective: To investigate the efficacy, safety, and traditional Chinese medicine (TCM) medication patterns of rituximab (RTX) combined with TCM on treating children with steroid-dependent nephrotic syndrome (SDNS). Methods: One hundred and forty-three children with SDNS who visited the Pediatric Nephrology Department of the First Affiliated Hospital of Henan University of Chinese Medicine from January 2018 to December 2022 were enrolled. A cohort study design was adopted, with " RTX treatment" as the exposure factor. Children who met this exposure factor were assigned to the RTX cohort (RTX, glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment), whereas those who did not were assigned to the basic treatment cohort (glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment ), and followed up for 6 months. The frequency of urinary protein recurrences, urinary protein remission duration, proportion and duration of steroid reduction and cessation, cumulative usage of steroids, proportion of recurrence, recurrence amount of steroid used, efficacy of TCM syndrome, and laboratory and safety indicators after treatment, and height and CD19+ B cell count before and after treatment were compared between the two cohorts. The medication patterns of TCM in the two cohorts were analyzed using frequency statistics, association rule analysis, and systematic clustering analysis. Results: Compared with the basic treatment cohort, the RTX cohort showed a decrease in the frequency of urinary protein recurrence, extended sustained remission of urinary protein, an increase in the proportion of steroid reduction and cessation, a shorter duration of steroid reduction and cessation, a decrease in cumulative steroid dosage, a lower recurrence rate, a decrease in CD19+ B cell count, and a decrease in 24-h urinary total protein quantification and the level of cholesterol (P<0.05). No significant difference in the recurrence amount of steroid used, height, TCM syndrome efficacy, albumin, aspartate transaminase, blood urea nitrogen, platelet count, and safety indicators between the two cohorts. Children with SDNS were mostly characterized by qi and yin deficiency syndrome, followed by spleen and kidney yang deficiency syndrome. A total of 175 TCMs were included, including 28 high-frequency drugs such as Huangqi, Fuling, Gancao, Baizhu, Dangshen, and Jiuyurou. The primary use of medication is to nourish the qi and spleen, nourish the kidney, and warm yang. The analysis of association rules yielded eight binary associations and ten three-phase associations, with Huangqi, Baizhu, Fuling, and Dangshen, being the most closely related. Cluster analysis identified four TCM combinations, primarily focusing on tonifying kidney and replenishing essence, benefiting qi and nourishing yin, and removing blood stasis. Conclusion RTX combined with TCM syndrome differentiation treatment can reduce the recurrence frequency of SDNS, prolong the remission period, reduce the glucocorticoid dosage, and have no marked effect on height growth. No apparent adverse reactions were observed. TCM should focus on nourishing qi and yin while removing blood stasis.

Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor that recognizes multiple pathogen-associated molecular patterns and damage-associated molecular patterns. It is a cytoplasmic immune factor that responds to cellular stress signals, and it is usually activated after infection or inflammation, forming an NLRP3 inflammasome to protect the body. Aberrant NLRP3 inflammasome activation is reportedly associated with some inflammatory diseases and metabolic diseases. Recently, there have been mounting indications that NLRP3 inflammasomes play an important role in liver injuries caused by a variety of diseases, specifically hepatic ischemia/reperfusion injury, hepatitis, and liver failure. Herein, we summarize new research pertaining to NLRP3 inflammasomes in hepatic injury, hepatitis, and liver failure. The review addresses the potential mechanisms of action of the NLRP3 inflammasome, and its regulation in these liver diseases.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/physiology* ; Animals ; Liver Diseases/metabolism* ; Liver/metabolism* ; Reperfusion Injury/metabolism*

Growth arrest DNA damage-inducible protein 45 β (GADD45B) has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes. However, its precise role and mechanism of action in stress susceptibility remain elusive. In this study, we found a significant reduction in GADD45B expression specifically in the ventral, but not the dorsal hippocampal CA1 (dCA1) of stress-susceptible mice. Furthermore, we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation (LTP) in the ventral hippocampal CA1 (vCA1). Importantly, through pharmacological inhibition using the NMDA receptor antagonist MK801, we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP. Collectively, these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
Animals ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; CA1 Region, Hippocampal/drug effects* ; Male ; Stress, Psychological/physiopathology* ; Mice ; Neuronal Plasticity/drug effects* ; Long-Term Potentiation/drug effects* ; Mice, Inbred C57BL ; Antigens, Differentiation/metabolism* ; Dizocilpine Maleate/pharmacology* ; Excitatory Amino Acid Antagonists/pharmacology* ; GADD45 Proteins

High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

ObjectiveTo investigate the effect and mechanism of total saponins from Panax japonicus （TSPJ） on white adipose tissue （WAT） browning/brown adipose tissue （BAT） activation in C57BL6/J male mice fed on a high-fat diet （HFD）. MethodThirty-two C57BL6/J male mice （8-week-old） were randomly divided into a normal group， a model group， a low-dose TSPJ group， and a high-dose TSPJ group. The mice in the low-dose and high-dose TSPJ groups were given TSPJ for four months by gavage at 25， 75 mg·kg^-1·d^-1， respectively， and those in the other groups were given 0.5% sodium carboxymethyl cellulose （CMC-Na） accordingly. After four months of feeding， all mice were placed at 4 ℃ for acute cold exposure， and the core body temperature was monitored. Subsequently， all mice were sacrificed， and BAT and inguinal WAT （iWAT） were separated rapidly to detect the corresponding indexes. Hematoxylin-eosin （HE） staining was used to observe the morphological changes in each group. The effect of TSPJ on the mRNA expression of uncoupling protein 1 （UCP1）， fatty acid-binding protein 4 （FABP4）， cytochrome C （CytC）， PR domain-containing protein 16 （PRDM16）， elongation of very long chain fatty acids protein 3 （ELOVL3）， peroxisome proliferator-activated receptor γ （PPARγ）， and peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α） in iWAT and BAT was detected by Real-time polymerase chain reaction （Real-time PCR）. Western blot was also used to detect the protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in BAT and iWAT of each group. The effect of TSPJ on UCP1 expression in BAT and iWAT was detected by immunohistochemistry. Result① Compared with the model group， TSPJ could decrease the body weight and proportions of iWAT and BAT in the HFD-induced mice （P<0.05， P<0.01）. ② The body temperature of mice in the model group decreased compared with that in the normal group in the acute cold exposure tolerance test （P<0.05）. The body temperature in the high-dose TSPJ group increased compared with that in the model group （P<0.01）. ③ Compared with the normal group， the model group showed increased adipocyte diameter in iWAT and BAT and decreased number of adipocytes per unit area. Compared with the model group， the TSPJ groups showed significantly reduced cell diameter and increased number of cells per unit area， especially in the high-dose TSPJ group. ④ Compared with the normal group， the model group showed decreased mRNA expression of FABP4， UCP1， CytC， PRDM16， ELOVL3， PGC-1α， and PPARγ in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the mRNA expression was significantly up-regulated （P<0.05， P<0.01）. ⑤ Compared with the normal group， the model group showed decreased protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the protein expression increased significantly （P<0.05， P<0.01）. ConclusionTSPJ could induce the browning of iWAT/BAT activation and enhance adaptive thermogenesis in obese mice induced by HFD. The underlying mechanism may be attributed to the activation of the PPARγ/PGC-1α signaling pathway.

Objective To investigate the expression of long non-coding RNA(lncRNA),surfactant associated 1 pseudogene(SFTA1P)in lung squamous carcinoma and its effect on the biological functions of SFTA1P in lung squamous carcinoma cell lines.Methods Based on the cancer genome atlas(TCGA)database,the differential expression of SFTA1P in tumor and normal tissues were compared in patients diagnosed with lung squamous cell carcinoma.Then,the expression of SFTA1P was detected in human normal lung epithelial cell line BEAS-2B and lung squamous cell lines SK-MES-1 and H520 with real-time quantitative polymerase chain reaction(RT-qPCR).SK-MES-1 and H520 cells with overexpression and/or knockdown of SFTA1P were constructed by transfecting the overexpression plasmids(pcDNA3.1-SFTA1P)and small interfering RNAs(si-SFTA1P-1 and si-SFTA1P-2).CCK-8 assay and Transwell assay were used to investigate the effect of SFTA1P on biological functions in lung squamous carcinoma cells.Differential gene expression analysis,correlation analysis and functional enrichment analysis were employed to explore the potential mechanism that SFTA1P may affect biological functions of lung squamous cells.Results Analysis of TCGA showed that the expression of SFTA1P was significantly lower in lung squamous cell carcinoma tissue than adjacent normal tissue(P＜0.05).RT-PCR results showed that the expression of SFTA1P was obviously lower in lung squamous carcinoma cells than the human normal lung epithelial cells(P＜0.05).And the expression level of SFTA1P was relatively lower in the SK-MES-1 cells than the H520 cells(P＜0.05).Overexpression of SFTA1P suppressed the proliferation,migration and invasion of lung squamous carcinoma cells(P＜0.05),while its knockdown promoted these abilities(P＜0.05).Differential gene expression analysis,correlation analysis and functional enrichment analysis indicated that SFTA1P may inhibit MYC,G2m checkpoints and E2f signaling pathways in lung squamous cell carcinoma.Conclusion SFTA1P shows anti-cancer function in lung squamous cell carcinoma,and it may affect the biological functions of lung squamous cell carcinoma cells through down-regulating MYC,G2m checkpoints and E2f signaling pathways.

Objective To provide the evidence for the development of personalized health education courses for twin pregnant women.We explored the health education and psychosocial demand of twin pregnant women from the perspective of social ecosystem theory.Methods By purposive sampling,18 twin pregnant women hospitalized in the twin medical center of a tertiary A hospital in Shenyang from January to March 2023 to conduct for semi-structured interviews,and Colaizzi's 7-step analysis method was used to sort out and analyze the data.Results 3 themes were extracted from the health education and psychosocial needs of twin pregnant women.Microsystem:the content needs of twin pregnant women's health education(the guidance needs of nutrition intake and weight growth;the needs for fetus health monitoring guidance;the cognitive needs of twin pregnancy complications;the needs for health education knowledge related to puerperium and the diversification of the choice of teaching methods).Mesosystem:the emotional support needs of twin pregnant women during prenatal and puetperal(the needs of family support and peer education support).Macrosystem:seeking social support and network information support(the demand of community support;the needs of information related to twin pregnant women's hierarchical management system and maternal fetal medical referral process and the needs for network health education information).Conclusion The women with twin pregnancy have different needs for health education content in each stage of pregnancy and puerperium,and there are urgent needs for emotional support and social support.Clinical nurses should construct health education courses according to the needs of twin women,and innovate in content and form,so as to improve the self-care ability of twin pregnant women and the knowledge level of family caregivers,and improve the pregnancy outcome.

Objective:To investigate whether long non-coding RNA(lncRNA) AW112010 can improve insulin resistance in aging adipocytes through the miR-204/POU2F2 signaling pathway.Methods:In vivo experiment: C57BL/6 mice were divided into young control group(4 months old) and aging model group(18 months old) based on body weight. The expression levels of AW112010, miR-204-5p, POU2F2, aging related indicators(p16, p21), and insulin signaling pathway genes [insulin receptor(INSR), insulin receptor substrate 1(IRS1), phosphatidylinositol kinase(PI3K), protein kinase B(AKT)] in epididymal adipose tissue were detected using real-time fluorescence quantitative PCR(RT-qPCR) and Western blotting. In vitro experiment: Using adriamycin(ADR) to induce 3T3-L1 aging adipocyte model, β-gal staining was used to observe cellular senescence, and miR-204 inhibitor and miR-204 mimic small interfering RNA were successfully constructed and transfected into 3T3-L1 adipocytes. Results:RT-qPCR and Western blot results showed that compared with the young group, the expression of AW112010 in the adipose tissue of aging mice was increased, while the expression of miR-204-5p was decreased. The expressions of POU2F2, p16, and p21 in the adipose tissue of aging mice were increased, while the expressions of INSR, IRS1, PI3K, GLUT4 mRNA and protein were decreased. The β-gal stainging results showed that the number of 3T3-L1 senescent adipocytes induced by ADR was significantly increased, and the expression levels of AW112010, POU2F2, p16, and p21 in ADR-induced senescent adipocytes were increased compared with the control group, while the expression levels of miR-204-5p, INSR, IRS1, PI3K, GLUT4 were decreased, and remaining glucose in the culture medium was increased. Compared with control, overexpression of miR-204 resulted in decreased expressions of aging indicators p16, p21, and target gene POU2F2 while the expressions of INSR and GLUT4 were increased.Conclusion:Upregulation of lncRNA AW112010 in adipocytes of aging mice may induce insulin resistance by targeting miR-204-5p/POU2F2/IRS1.

Objective:To explore the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) from imaging perspective by analyzing voxel-based morphology (VBM) and functional connectivity (FC) in resting state functional magnetic resonance imaging (rs-fMRI).Methods:Thirty-five patients with NPSLE and 30 patients with non-NPSLE admitted to Department of Rheumatology and Immunology, Taizhou People's Hospital Affiliated to Nanjing Medical University from June 2020 to March 2023 were enrolled; 31 healthy subjects were included as healthy control group during the same period. All subjects completed routine MRI and rs-fMRI, laboratory tests (C3, C4, IgA, IgM and IgG levels), mini-mental state examination (MMSE), hospital anxiety and depression scale (HADS), and fatigue scale for motor and cognitive functions (FSMC). Whole brain gray matter volume in subjects of the 3 groups was analyzed by VBM method, and the brain regions enjoying significant differences in gray matter volume between the NPSLE group and non-NPSLE group were selected as regions of interest (ROIs) for whole brain FC analysis. Partial correlation method was used to analyze the correlations of imaging indexes in brain regions enjoying significant differences with clinical indexes and imaging scores between NPSLE group and non-NPSLE group. Efficacy of imaging indexes in brain regions enjoying significant difference in differentiating NPSLE from non-NPSLE was analyzed by receiver operating characteristic (ROC) curve.Results:(1) Covariance analysis among the 3 groups showed that the gray matter volume in the left inferior frontal gyrus of orbit, left superior frontal gyrus, right rectus gyrus, right transverse temporal gyrus, and right superior frontal gyrus was significantly different among the 3 groups ( P<0.001, FDR corrected); compared with the healthy control group, the NPSLE group had significantly reduced gray matter volume in the left inferior frontal gyrus of orbit, left superior frontal gyrus of orbit, right rectus gyrus, right transverse temporal gyrus, and right superior frontal gyrus ( P<0.001, FDR corrected); compared with the non-NPSLE group, the NPSLE group had significantly decreased gray matter volume in the left inferior frontal gyrus of orbit, right rectus gyrus, and right transverse temporal gyrus ( P<0.001, FDR corrected). (2) Whole brain FC analysis with brain regions enjoying significant differences as seed points showed that Fisher z-transformed FC (zFC) in the right transverse temporal gyrus and bilateral postcentral gyrus of the NPSLE group were significantly decreased ( P<0.001, FDR corrected). (3) Partial correlation analysis showed that, in the NPSLE group, zFC from the right transverse temporal gyrus to left posterior central gyrus was negatively correlated with disease course ( r=-0.390, P=0.027); gray matter volume in the right orbital superior frontal gyrus was negatively correlated with FSMC-cognitive ( r=-0.401, P=0.023); the gray matter volume in the right orbital superior frontal gyrus was negatively correlated with FSMC-motor ( r=-0.374, P=0.035). (4) ROC curve found that gray matter volume in the right rectus gyrus and zFC from the right transverse temporal gyrus to the right posterior central gyrus had relatively high efficacy in differentiating NPSLE from non-NPSLE, with AUC of 0.771 (95% CI: 0.658-0.885, P<0.001) and 0.794 (95% CI: 0.685-0.904, P<0.001), respectively. Conclusion:NPSLE patients have reduced gray matter volume in multiple brain regions (concentrating in the prefrontal limbic system); and reduced FC with some brain regions is noted; multiple indexes are correlated with clinical indexes.

Early distinction of bipolar disorder (BD) from major depressive disorder (MDD) is difficult since no tools are available to estimate the risk of BD. In this study, we aimed to develop and validate a model of oxidative stress injury for predicting BD. Data were collected from 1252 BD and 1359 MDD patients, including 64 MDD patients identified as converting to BD from 2009 through 2018. 30 variables from a randomly-selected subsample of 1827 (70%) patients were used to develop the model, including age, sex, oxidative stress markers (uric acid, bilirubin, albumin, and prealbumin), sex hormones, cytokines, thyroid and liver function, and glycolipid metabolism. Univariate analyses and the Least Absolute Shrinkage and Selection Operator were applied for data dimension reduction and variable selection. Multivariable logistic regression was used to construct a model for predicting bipolar disorder by oxidative stress biomarkers (BIOS) on a nomogram. Internal validation was assessed in the remaining 784 patients (30%), and independent external validation was done with data from 3797 matched patients from five other hospitals in China. 10 predictors, mainly oxidative stress markers, were shown on the nomogram. The BIOS model showed good discrimination in the training sample, with an AUC of 75.1% (95% CI: 72.9%-77.3%), sensitivity of 0.66, and specificity of 0.73. The discrimination was good both in internal validation (AUC 72.1%, 68.6%-75.6%) and external validation (AUC 65.7%, 63.9%-67.5%). In this study, we developed a nomogram centered on oxidative stress injury, which could help in the individualized prediction of BD. For better real-world practice, a set of measurements, especially on oxidative stress markers, should be emphasized using big data in psychiatry.
Biomarkers/metabolism* ; Bipolar Disorder/metabolism* ; Depressive Disorder, Major/diagnosis* ; Early Diagnosis ; Humans ; Oxidative Stress