Objective To investigate the efficacy of Qihuang Jianpi Zishen Granules(QJZ)for inhibiting renal B cell differentiation in MRL/lpr mice and explore its underlying mechanism.Methods Thirty 8-week-old female MRL/lpr mice were randomly divided into model group,QJZ group,prednisone(Pred)group,QJZ+Pred group,and AIM2 inhibitor group(n=6),with 6 8-week-old female C57BL/6 mice as the normal control group.After treatments with normal saline,QJZ,Pred,or AIM2 inhibitor for 8 weeks,the mice were examined for urinary total protein-to-creatinine ratio(TPCR)and albumin-to-creatinine ratio(ACR),serum creatinine(Cr)and blood urea nitrogen(BUN)levels,and renal histopathology(with HE,Masson,and PAS staining)and ultrastructural changes(with electron microscopy).ELISA,immunohistochemistry,immunofluorescence staining and flow cytometry were used to detect blood levels of anti-dsDNA antibodies,cytokines and chemokines,renal deposition of complement components C3 and C4,renal expressions of AIM2,CD19,CD27 and CD138,and changes in splenic B lymphocyte subsets.The effect of QJZ on the AIM2/Blimp-1/Bcl-6 signaling axis was examined using Western blotting.Results QJZ treatment significantly improved Cr,BUN,TPCR and ACR in MRL/lpr mice,ameliorated renal pathologies,reduced the expressions of ds-DNA,BAFF,IL-21,CXCL12,CXCL13,C3 and C4,and increased IL-10 levels.QJZ significantly downregulated renal expressions of the key B-cell transcription factors Blimp-1 and XBP-1,upregulated Bcl-6 and PAX5 expressions,inhibited B-cell differentiation,and lowered the expressions of AIM2,CD27,CD138 and CD69.Inhibition of AIM2 similarly reduced renal Blimp-1 and XBP-1 expressions,increased Bcl-6 and PAX5 levels,suppressed B-cell differentiation,decreased IgG production,reduced C3 and C4 deposition,and alleviated renal pathology in MRL/lpr mice.Conclusion QJZ inhibits B cell differentiation and alleviates renal damage in systemic lupus erythematosus possibly by suppressing the AIM2/Blimp-1/Bcl-6 signaling pathway.

Objective To investigate the mechanism of Qihuang Jianpi Zishen Granules(QJZ)for ameliorating renal damage in MRL/lpr mice.Methods With 6 female C57BL/6 mice as the normal control group,30 female MRL/lpr mice were randomized into model group,QJZ treatment groups at low,moderate and high doses,and prednisone treatment group(n=6).After 8 weeks of treatment,the mice were examined for 24-h urine protein,creatinine and albumin levels,serum levels of IgG,complement 3(C3),C4,anti-dsDNA,interferon γ(IFN-γ)and interleukin 17(IL-17).Kidney tissues were sampled for histopathological examination with HE staining and observation of glomerular ultrastructure changes using transmission electron microscopy(TEM).The expressions of MyD88/NF-κB pathway-related molecules in the kidney tissue were detected using RT-qPCR,Western blotting and immunohistochemistry.Results Compared with those in the model group,the mice treated with QJZ at the 3 doses and prednisone showed significant reductions in the renal injury biomarkers and serum IgG,anti-dsDNA,IFN-γ and IL-17 levels and elevation of serum C3 and C4 levels.HE staining revealed lessened glomerular endothelial cell proliferation and mesangial thickening in all the treatment groups.TEM observation further demonstrated reduced electron-dense deposits and diminished inflammatory cell infiltration in the glomeruli in the intervention groups.QJZ at the 3 doses and prednisone treatment all significantly lowered renal expression levels of MyD88,NF-κB,p65 and p52 in the mouse models.Conclusion QJZ can improve renal damage in MRL/lpr mice possibly by inhibiting overactivation of the MyD88/NF-κB pathway.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective:To assess the safety,efficacy and potential impact of stem cell therapy(SCT)in improving erectile dys-function(ED).Methods:A comprehensive search strategy was used to search the literatures on safety and efficacy evaluation of stem cell(SC)in the treatment of ED by human clinical trials from PubMed,Embase and Web of science databases with a search time frame from database creation to July 4,2024.The exclusion criteria were as follows:reviews,conference abstracts,animal experi-ments,and duplicate sample literature.Results:The study initially screened 1 773 papers,and 17 were included in the final analy-sis.These studies involved a total of 269 ED patients,and a variety of sources of stem cells had been used in the treatment of ED,in-cluding adipose-derived stem cells,bone marrow-derived stem cells,placental stroma-derived stem cells,umbilical cord-derived stem cells,dental pulp-derived stem cells,and oral mucosa-derived stem cells.All studies were conducted by injecting stem cells into the cavernous body of the penis,but there is no fixed standard for the amount of injection,injection site and number of injections.The op-timal treatment mode was still being explored.Patients' International Index of Erectile Function(IIEF)scores and Erection Hardness Score(EHS),peak systolic velocity(PSV),and end diastolic velocity(EDV)improved after treatment.But some studies showed that the efficacy of the treatment diminished with increasing time.No serious adverse effects were reported in any of the studies and none of the adverse effects persisted for a long period of time.The most common adverse effects included injection site reactions,and SCT showed a good safety and tolerability profile.Conclusion:SCT has the potential to be a promising and innovative regenerative therapy option for ED patients.In the future,with the advancement of stem cell technology,larger randomized controlled studies should continue to be conducted to explore standardized treatments,so as to further evaluate the long-term efficacy and safety of SCT for ED.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To screen for microRNAs(miRNAs)highly expressed in the serum exosomes(Exo)of esophageal squamous cell carcinoma(ESCC)patients and analyze their relationship with the clinicopathological characteristics of the patients,and to explore the potential of Exo-derived miRNAs as clinical auxiliary diagnostic markers for ESCC.Methods:Serum and relevant clinical data of 50 healthy subjects and 45 newly diagnosed ESCC patients admitted to the Fourth Hospital of Hebei Medical University between December 2021 and June 2023 were collected,serving as the control group and the ESCC group respectively.The Gene Expression Omnibus(GEO)database and qPCR were used to screen and identify the candidate miRNA for increased expression in the serum of ESCC patients-miR-1246.The diagnostic efficacy of serum miR-1246 for ESCC was analyzed by the receiver operating characteristic curve.The relationship between miR-1246 and the clinical feature progression of ESCC patients was analyzed by Logistic regression,and the relationship between miR-1246 and the clinicopathological characteristics of ESCC patients was analyzed by the χ2 test.Exosomes in the serum of the subjects were isolated,purified and characterized for verification.The expression of miR-1246 in Exo was detected by qPCR.ESCC KYSE150 and KYSE30 cells were routinely cultured.mimics-NC and miR-1246 mimics were transfected respectively into KYSE150 cells using Lipofectamine 2000.Inhibitor-NC and miR-1246 inhibitor were transfected into KYSE30 cells,which were respectively denoted as the minics-NC,miR-1246 mimics,inhibitor-NC and miR-1246-inhibitor groups.KYSE150 and KYSE30 cells were treated with Exo derived from KYSE150 cells in the mimics-NC and miR-1246 mimics groups.The proliferation,migration and invasion abilities of cells in each group were detected by the CCK-8 assay,scratch wound healing assay and Transwell chamber assay respectively.The expressions of Exo markers,epithelial-mesenchymal transition-related proteins,TET family methylcytosine dioxygenase 2(TET2)and cell adhesion molecule 1(CADM1)proteins in each group of cells were detected by WB assay.The targeting binding relationship between miR-1246 and TET2 and CADM1 was verified by the dual-luciferase reporter gene assay.Results:Bioinformatics screening showed that the miRNA with the most significant differential expression in the serum of ESCC patients was miR-1246.The serum Exo extracted from the patients conformed to the typical Exo characteristics.The expression level of serum Exo-miR-1246 in ESCC patients at stages Ⅰ-Ⅱ was significantly higher than that in healthy subjects(P<0.01);the level of serum Exo-miR-1246 in ESCC patients at stages Ⅲ-Ⅳ was significantly higher than that in patients at stages Ⅰ-Ⅱ(P<0.01).ROC curve analysis showed that Exo-miR-1246 in serum had a high value for auxiliary differential diagnosis of ESCC(P<0.05),and the auxiliary diagnostic efficacy of Exo-miR-1246 for the clinical progression of ESCC patients was higher than that of CEA and SCC-Ag(P<0.05).The combined detection of the three could further improve the efficacy of auxiliary diagnosis of patient staging(P<0.01).Exo-miR-1246 might be an independent risk factor for the clinical progression of ESCC patients(P<0.05).The expression level of serum Exo-miR-1246 was associated with the T-stage,N-stage and clinical stage of ESCC(P<0.01).Overexpression of miR-1246 could promote the proliferation,migration,invasion,epithelial-mesenchymal transition and inhibit apoptosis of ESCC cells,while inhibition of miR-1246 had the opposite effect.Database data analysis found that TET2 and CADM1 were the target genes of miR-1246.The dual-luciferase reporter gene assay confirmed that miR-1246 could directly bind to TET2 and CADM1 mRNA and inhibit their expressions(P<0.01).Treatment of KYSE150 and KYSE30 cells with Exo derived from cells overexpressing miR-1246 had the same effect as overexpressing miR-1246 in these cells.Conclusion:Exo-derived miR-1246 has the potential to be a clinical auxiliary diagnostic marker for ESCC.It may affect the occurrence and development of ESCC by regulating the expression levels of TET2 and CADM1.

Rabbit syndrome (RS), characterized by fine, rapid, rhythmic movements along the mouth’s vertical axis, is typically linked to prolonged antipsychotic medication use. Emerging evidence suggests newer antipsychotics’ involvement in RS, prompting investigation into its association with long-acting injectable antipsychotics (LAIs) for schizophrenia or bipolar disorder. We report a case of RS observed in a patient diagnosed with bipolar I disorder and treated with Abilify Maintena, highlighting the importance of vigilance in monitoring adverse effects. The patient, a 53-year-old male, experienced persistent manic episodes despite prior treatments. Upon initiation of Abilify Maintena 400 mg, RS symptoms manifested seven months later, remaining resistant to medication adjustments. This case emphasizes the significance of RS in LAIs-treated patients and emphasizes the need for further research into its mechanisms and optimal management strategies. Additionally, an updated review of RS associated with newer generation antipsychotics is provided to enhance understanding and clinical management.

Rabbit syndrome (RS), characterized by fine, rapid, rhythmic movements along the mouth’s vertical axis, is typically linked to prolonged antipsychotic medication use. Emerging evidence suggests newer antipsychotics’ involvement in RS, prompting investigation into its association with long-acting injectable antipsychotics (LAIs) for schizophrenia or bipolar disorder. We report a case of RS observed in a patient diagnosed with bipolar I disorder and treated with Abilify Maintena, highlighting the importance of vigilance in monitoring adverse effects. The patient, a 53-year-old male, experienced persistent manic episodes despite prior treatments. Upon initiation of Abilify Maintena 400 mg, RS symptoms manifested seven months later, remaining resistant to medication adjustments. This case emphasizes the significance of RS in LAIs-treated patients and emphasizes the need for further research into its mechanisms and optimal management strategies. Additionally, an updated review of RS associated with newer generation antipsychotics is provided to enhance understanding and clinical management.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Rabbit syndrome (RS), characterized by fine, rapid, rhythmic movements along the mouth’s vertical axis, is typically linked to prolonged antipsychotic medication use. Emerging evidence suggests newer antipsychotics’ involvement in RS, prompting investigation into its association with long-acting injectable antipsychotics (LAIs) for schizophrenia or bipolar disorder. We report a case of RS observed in a patient diagnosed with bipolar I disorder and treated with Abilify Maintena, highlighting the importance of vigilance in monitoring adverse effects. The patient, a 53-year-old male, experienced persistent manic episodes despite prior treatments. Upon initiation of Abilify Maintena 400 mg, RS symptoms manifested seven months later, remaining resistant to medication adjustments. This case emphasizes the significance of RS in LAIs-treated patients and emphasizes the need for further research into its mechanisms and optimal management strategies. Additionally, an updated review of RS associated with newer generation antipsychotics is provided to enhance understanding and clinical management.