Objective To investigate the therapeutic effects of interleukin 23p19(IL-23p19) monoclonal antibody in the MRL/lpr lupus-like mouse model. Methods A total of 36 female MRL/lpr mice aged 8 weeks were randomly divided into 6 groups: PBS group (blank control), IgG group (isotype IgG), dexamethasone (DEX) group (positive control), and three IL-23p19 monoclonal antibody treatment groups with different dose gradients: low dose (LD, 1 mg/kg), medium dose (MD, 3 mg/kg), and high dose (HD, 10 mg/kg). Drug intervention began at 12 weeks of age via tail vein injection. Urine protein levels were measured using urine protein test strips; serum anti-dsDNA antibody levels were detected by ELISA; serum creatinine and blood urea nitrogen levels were measured using an automatic biochemical analyzer; renal histopathological changes were analyzed by H&E and PAS staining; immunofluorescence was used to assess IgG and C3 immune complex deposition in kidney tissues; flow cytometry was employed to examine the expression of T helper 1(Th1), Th2, Th17, T follicular helper (Tfh), and regulatory T cells(Treg) cell subsets in the spleen; and RT-qPCR was used to detect the expression of related transcription factors in the spleen. Results IL-23p19 monoclonal antibody reduced urine protein levels, alleviated splenomegaly, improved renal function, and decreased anti-dsDNA antibody levels in MRL/lpr mice. It also mitigated glomerulonephritis and reduced renal immune complex deposition. Furthermore, IL-23p19 monoclonal antibody significantly suppressed the proportion of Th1 and Th17 cells while upregulating Treg cell proportion in the spleen. Additionally, it downregulated T-bet and retinoic acid receptor-related orphan receptor γt (RORγt) mRNA levels and upregulated forkhead box P3(FOXP3) mRNA levels in the spleen. Conclusions IL-23p19 monoclonal antibody demonstrates significant therapeutic effects in MRL/lpr mice, likely through modulation of the Th17/Treg cell balance.
Animals ; Female ; Mice, Inbred MRL lpr ; T-Lymphocytes, Regulatory/drug effects* ; Th17 Cells/drug effects* ; Antibodies, Monoclonal/therapeutic use* ; Interleukin-23 Subunit p19/immunology* ; Mice ; Lupus Nephritis/drug therapy* ; Kidney/drug effects* ; Antibodies, Antinuclear/blood*

Objective:To investigate whether kisspeptin can influence the maternal-fetal interface regulatory T cells(Treg),thereby participating in the pathogenesis of recurrent spontaneous abortion(RSA).Methods:Normal pregnancy(NP)and RSA mice models were established,where NP mice received a tail vein injection of PBS(NP-PBS group),and RSA mice received a tail vein in-jection of PBS(RSA-PBS group)and active fragment of kisspeptin KP10(RSA-KP10 group),observing embryo absorption rates.Im-munohistochemistry was employed to assess expressions of kisspeptin and Foxp3 in mice uterine tissues.Peripheral blood Treg cells were isolated and expanded through magnetic bead separation.Intervention with KP10 and KP234(kisspeptin receptor antagonist)was administered,and flow cytometry was used to detect levels of IL-10 and TGF-β1 secretion by Treg cells,as well as differences in proliferation and apoptosis.RNA-Seq transcriptomic sequencing was conducted on uterine tissues from RSA-PBS group and RSA-KP10 group of mice.Differentially expressed genes(DEGs)were subjected to GO,KEGG and GSEA enrichment analyses.Results:Embryo absorption rate in RSA mice was higher than that in NP mice,the embryo absorption rate was decreased after tail vein injec-tion of KP10.Expressions of kisspeptin and Foxp3 in uterus of RSA mice was lower than that in NP mice,while increased after injec-tion of KP10.Kisspeptin could modulate the secretion of IL-10 and TGF-β1 by Treg cells,influencing their proliferation without affect-ing apoptosis.Enrichment analysis results showed that DEGs were mainly enriched in reproductive structure development,IL-17,and TGF-β signaling pathways.Conclusion:Kisspeptin can influence both the quantity and function of Treg cells,offering a new theoreti-cal foundation for investigating the pathogenesis and treatment of RSA.

Objective:To investigate impact of PD-L2 gene knockout on splenic immune phenotype of C57BL/6 mice.Methods:Body weight of female and male wild-type(WT)and PD-L2 gene knockout(KO)mice aged 3～12 weeks were continuously measured.Tissue structure differences in heart,liver,spleen,lung,kidney,thymus,ovary,uterus and testis of four groups of mice were observed by HE staining.Urease UV rate method was employed to measure urea level in mouse serum,and creatinine concentra-tion in serum was determined by creatine oxidase method.Flow cytometry was used to assess proportions of immune cells and cytokine differences in spleens of mice.Results:PD-L2 gene knockout had no apparent effect on body weight or organ structure of mice.Serum urea and creatinine levels were higher in female KO mice compared to WT mice,but no significant differences were observed among males.Female KO mice exhibited reduced proportions of CD4+T cells,CD8+T cells,Treg,NK cells and dendritic cells(DC)in spleen compared to WT mice.Conversely,proportions of Tfh,B cells,plasma cells,na?ve B cells and B2 cells were elevated,proin-flammatory cytokines such as IL-17,IL-6 and IL-22 were increased,while anti-inflammatory cytokines like IL-10 and IL-4 were decreased.Differences among male mice were either not significant or absent.Conclusion:PD-L2 gene knockout primarily affects splenic immune phenotype of female mice,leading to increased inflammatory responses and weakened immune suppression after knockout.

Objective:To analyze the correlation between sex hormone levels and micropenis after mild hypospadias surgery in children.Methods:A case control study was carried out.The clinical data of 71 children aged 1 to 13 years who underwent mild hypospadias surgery at the First Affiliated Hospital of Xinxiang Medical University from April 2022 to April 2024 were analyzed.Preoperatively, the children were divided into a mild hypospadias group (Group A) and a mild hypospadias with micropenis group (Group B) based on the stretched penile length (SPL).Prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone, and testosterone (TES) levels of the 2 groups were measured.Multivariate Logistic regression analysis was used to construct a risk prediction model.The discrimination capability of the model was evaluated using the receiver operating characteristic (ROC) curve.SPL and sex hormone levels were measured again 6 months after surgery.The children were divided into a normal penile group (Group AA) and a micropenis group (Group BB) after mild hypospadias according to SPL.Multivariate Logistic regression analysis was used to construct a risk prediction model, which was evaluated using the ROC curve.Results:The levels of FSH, LH and TES in group A before the operation were 3.28(2.02, 4.46) IU/L, 0.53(0.25, 0.79) IU/L and 25.24(17.94, 36.67) ng/dL, respectively, and those in group B were 1.42(1.10, 1.84) IU/L, 0.14(0.09, 0.23) IU/L and 15.73 (12.92, 17.00) ng/dL, respectively.The difference was all statistically significant (all P<0.05).Multivariate Logistic regression analysis showed statistical significance ( OR=0.515, 95% CI: 0.271-0.977; OR=0.035, 95% CI: 0.002-0.542; OR=0.883, 95% CI: 0.796-0.980).The area under the ROC curve (AUC) of the prediction model was 0.906, with a sensitivity of 75.00% and a specificity of 95.74%.The levels of FSH, LH and TES in the postoperative AA group were 2.97 (1.88, 4.28) IU/L, 0.46 (0.23, 0.78) IU/L and 20.92 (17.34, 33.27) ng/dL, respectively.The median levels of FSH, LH and TES in the BB group were 1.52 (1.27, 1.82) IU/L, 0.17 (0.12, 0.26) IU/L and 15.08(11.68, 16.68) ng/dL, respectively.The difference was all statistically significant (all P<0.05).Multivariate Logistic regression analysis showed statistical significance ( OR=0.484, 95% CI: 0.236-0.992; OR=0.061, 95% CI: 0.004-0.939; OR=0.891, 95% CI: 0.795-0.999).The AUC of the prediction model constructed was 0.877, with a sensitivity of 94.12% and a specificity of 68.52%. Conclusions:Lower FSH, LH and TES levels are risk factors for the micropenis after mild hypospadias surgery, and preoperative hormone levels have higher predictive value.

Objective:To investigate whether kisspeptin can influence the maternal-fetal interface regulatory T cells(Treg),thereby participating in the pathogenesis of recurrent spontaneous abortion(RSA).Methods:Normal pregnancy(NP)and RSA mice models were established,where NP mice received a tail vein injection of PBS(NP-PBS group),and RSA mice received a tail vein in-jection of PBS(RSA-PBS group)and active fragment of kisspeptin KP10(RSA-KP10 group),observing embryo absorption rates.Im-munohistochemistry was employed to assess expressions of kisspeptin and Foxp3 in mice uterine tissues.Peripheral blood Treg cells were isolated and expanded through magnetic bead separation.Intervention with KP10 and KP234(kisspeptin receptor antagonist)was administered,and flow cytometry was used to detect levels of IL-10 and TGF-β1 secretion by Treg cells,as well as differences in proliferation and apoptosis.RNA-Seq transcriptomic sequencing was conducted on uterine tissues from RSA-PBS group and RSA-KP10 group of mice.Differentially expressed genes(DEGs)were subjected to GO,KEGG and GSEA enrichment analyses.Results:Embryo absorption rate in RSA mice was higher than that in NP mice,the embryo absorption rate was decreased after tail vein injec-tion of KP10.Expressions of kisspeptin and Foxp3 in uterus of RSA mice was lower than that in NP mice,while increased after injec-tion of KP10.Kisspeptin could modulate the secretion of IL-10 and TGF-β1 by Treg cells,influencing their proliferation without affect-ing apoptosis.Enrichment analysis results showed that DEGs were mainly enriched in reproductive structure development,IL-17,and TGF-β signaling pathways.Conclusion:Kisspeptin can influence both the quantity and function of Treg cells,offering a new theoreti-cal foundation for investigating the pathogenesis and treatment of RSA.

Objective:To investigate impact of PD-L2 gene knockout on splenic immune phenotype of C57BL/6 mice.Methods:Body weight of female and male wild-type(WT)and PD-L2 gene knockout(KO)mice aged 3～12 weeks were continuously measured.Tissue structure differences in heart,liver,spleen,lung,kidney,thymus,ovary,uterus and testis of four groups of mice were observed by HE staining.Urease UV rate method was employed to measure urea level in mouse serum,and creatinine concentra-tion in serum was determined by creatine oxidase method.Flow cytometry was used to assess proportions of immune cells and cytokine differences in spleens of mice.Results:PD-L2 gene knockout had no apparent effect on body weight or organ structure of mice.Serum urea and creatinine levels were higher in female KO mice compared to WT mice,but no significant differences were observed among males.Female KO mice exhibited reduced proportions of CD4+T cells,CD8+T cells,Treg,NK cells and dendritic cells(DC)in spleen compared to WT mice.Conversely,proportions of Tfh,B cells,plasma cells,na?ve B cells and B2 cells were elevated,proin-flammatory cytokines such as IL-17,IL-6 and IL-22 were increased,while anti-inflammatory cytokines like IL-10 and IL-4 were decreased.Differences among male mice were either not significant or absent.Conclusion:PD-L2 gene knockout primarily affects splenic immune phenotype of female mice,leading to increased inflammatory responses and weakened immune suppression after knockout.

Objective:To analyze the correlation between sex hormone levels and micropenis after mild hypospadias surgery in children.Methods:A case control study was carried out.The clinical data of 71 children aged 1 to 13 years who underwent mild hypospadias surgery at the First Affiliated Hospital of Xinxiang Medical University from April 2022 to April 2024 were analyzed.Preoperatively, the children were divided into a mild hypospadias group (Group A) and a mild hypospadias with micropenis group (Group B) based on the stretched penile length (SPL).Prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone, and testosterone (TES) levels of the 2 groups were measured.Multivariate Logistic regression analysis was used to construct a risk prediction model.The discrimination capability of the model was evaluated using the receiver operating characteristic (ROC) curve.SPL and sex hormone levels were measured again 6 months after surgery.The children were divided into a normal penile group (Group AA) and a micropenis group (Group BB) after mild hypospadias according to SPL.Multivariate Logistic regression analysis was used to construct a risk prediction model, which was evaluated using the ROC curve.Results:The levels of FSH, LH and TES in group A before the operation were 3.28(2.02, 4.46) IU/L, 0.53(0.25, 0.79) IU/L and 25.24(17.94, 36.67) ng/dL, respectively, and those in group B were 1.42(1.10, 1.84) IU/L, 0.14(0.09, 0.23) IU/L and 15.73 (12.92, 17.00) ng/dL, respectively.The difference was all statistically significant (all P<0.05).Multivariate Logistic regression analysis showed statistical significance ( OR=0.515, 95% CI: 0.271-0.977; OR=0.035, 95% CI: 0.002-0.542; OR=0.883, 95% CI: 0.796-0.980).The area under the ROC curve (AUC) of the prediction model was 0.906, with a sensitivity of 75.00% and a specificity of 95.74%.The levels of FSH, LH and TES in the postoperative AA group were 2.97 (1.88, 4.28) IU/L, 0.46 (0.23, 0.78) IU/L and 20.92 (17.34, 33.27) ng/dL, respectively.The median levels of FSH, LH and TES in the BB group were 1.52 (1.27, 1.82) IU/L, 0.17 (0.12, 0.26) IU/L and 15.08(11.68, 16.68) ng/dL, respectively.The difference was all statistically significant (all P<0.05).Multivariate Logistic regression analysis showed statistical significance ( OR=0.484, 95% CI: 0.236-0.992; OR=0.061, 95% CI: 0.004-0.939; OR=0.891, 95% CI: 0.795-0.999).The AUC of the prediction model constructed was 0.877, with a sensitivity of 94.12% and a specificity of 68.52%. Conclusions:Lower FSH, LH and TES levels are risk factors for the micropenis after mild hypospadias surgery, and preoperative hormone levels have higher predictive value.

The Death Cafe has promoted globally, breaking the silence and taboo surrounding death, allowing the public to freely discuss topics related to death and end-of-life, raising public awareness of death, and promoting public thinking and understanding of death. This paper reviews the overview of Death Cafe and its application in palliative care, in order to provide reference for the research and practice of palliative care in China.

Objective:To explore the therapeutic effect and psychological influence of biofeedback pelvic floor muscle training on fecal incontinence after anorectal surgery in children.Methods:A retrospective case-control study.A total of 37 children who were admitted to the First Affiliated Hospital of Xinxiang Medical University from July 2021 to April 2023 for fecal incontinence after anorectal surgery were collected.Biofeedback pelvic floor muscle training was performed with a Laborie biofeedback therapy device, and pelvic floor muscle contraction function exercise was performed no less than 200 times a day.The anal canal current intensity, basic motion myoelectric value, contractile myoelectric difference and continuous anal contraction time were measured at before treatment, at the end of 1 course, 1 month and 1 year after treatment.Ten healthy children of the same age were selected as the healthy control group.The Strengths and Difficulties Questionnaire was used for psychological evaluation at before treatment and 1 year after treatment.Paired sample t test and independent sample t test were used to compare and analyze the results of this study. Results:Before treatment, at the end of 1 course, 1 month and 1 year after treatment, the anal canal current intensity of children with fecal incontinence were(11.32±1.92) mA, (10.22±1.28) mA, (8.45±1.09) mA, and(7.80±1.23) mA, respectively; the anal canal basic motion myoelectric value were(235.58±55.03) μV, (185.65±34.30) μV, (124.81±36.56) μV, and(93.99±28.29) μV, respectively; the anal canal contractile myoelectric difference were(45.64±20.38) μV, (64.20±16.59) μV, (93.63±25.53) μV, and(109.83±26.95) μV, respectively; the continuous anal contraction time were(1.27±0.43) s, (1.58±0.40) s, (2.04±0.39) s, and(2.47±0.38) s, respectively.These parameters before treatment, at the end of 1 course and 1 month after treatment were significantly different from those in the healthy control group[(7.20±1.09) mA, (88.65±21.76) μV, (120.73±27.57) μV, (2.68±0.29) s](all P<0.05).These parameters at 1 year after treatment were significantly different from those before treatment and 1 month after treatment(all P<0.05).However, there were no significant differences in these parameters between the healthy control group and the treatment group at 1 year after treatment(all P>0.05).There were statistically significant differences in emotional symptoms, hyperactivity symptoms, peer interaction, prosocial behavior and difficulty scores before and after treatment[(3.46±1.88) points vs.(2.59±1.32) points, (5.78±2.12) points vs.(3.70±1.78) points, (3.05±1.72) points vs.(2.49±1.30) points, (7.30±1.54) points vs.(8.27±1.39) points, (21.57±4.57) points vs.(18.54±3.14) points](all P<0.05). Conclusions:Biofeedback pelvic floor muscle training is a reliable and non-invasive method for the treatment of postoperative fecal incontinence after anorectal surgery in children and can effectively relieve the psychological and behavioral problems caused by fecal incontinence in children.

Objective:To evaluate the influence of different teaching modes in the creativity of nursing students in China.Methods:A systematic search of PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database and VIP Database were carried out. Randomized control trials (RCTs) examining the influence of different teaching modes in the creativity of nursing students were included from inception to March 5, 2023. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies according to the Cochrane Handbook for Systematic Reviews of Interventions and combined with the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE), then network Meta-analysis with random effects was performed by using WinBugs 1.4.3 and Stata 17.0 software.Results:A total of 63 studies involving 22 teaching modes were included. The network Meta-analysis showed that Case-based Learning Mode, Evidence-based Nursing Teaching Mode, 3D Printing Model Teaching Mode, Hands-on Inquiry Based Learning, Quality Control Circle Teaching Mode, Six Thinking Hats Teaching Mode, Theory, Drill, Practice, Combine (TDPC, T:theory; D:drill; P:practice; C:combine) Teaching Mode were more effective than Lecture-based Learning Mode ( SMD values were 4.61-22.51, all P<0.05). Sensitivity analysis showed the effectiveness of TDPC Teaching Mode was the greatest in nursing theoretical teaching[surface under the cumulative ranking (SUCRA)=98.08%], the Quality Control Circle Teching Mode was the second most effective (SUCRA=83.13%). The effectiveness of Six Thinking Hats Teaching Mode was the greatest in nursing practical teaching (SUCRA=95.73%), followed by the 3D Printing Model Teching Mode (SUCRA=86.97%). Conclusions:TDPC Teaching Mode, Six Thinking Hats Teaching Mode, 3D Printing Model, Quality Control Circle Teaching Mode were superior to other teaching modes in improving creativity of nursing students.