Objective:To evaluate the differential expression of RNA in blood monocytes in patients with Juvenile idiopathic arthritis (JIA) treated with TNF antagonists (TNFi), and to explore the effect and mechanism of gene expression on the efficacy of JIA.Methods:A total of 29 children with JIA treated with methotrexate (MTX) and TNFi in Guangzhou Women and Children′s Medical Center of Guangzhou Medical University from April 2021 to November 2023 were enrolled. After 6 months, the children were divided into two groups according to the treatment effect, 13 cases in the ineffective group and 16 cases in the effective group, the peripheral blood of the children was collected, the blood mononuclear cells were isolated for transcriptome sequencing, the differentially expressed genes between the groups were analyzed, the signaling pathways and metabolic pathways related to the efficacy of TNFi were analyzed by GO and KEGG enrichment, and the mechanism related to the efficacy of TNFi was explored. This study was approved by Medical Ethics Committee of the Guangzhou Women and Children′s Medical Center of Guangzhou Medical University (Ethics No.: 2023-330B00).Results:There was a statistically significant difference in the gender and age distribution between the two groups of children ( P<0.05), while no statistically significant differences were observed in disease duration, rheumatoid antibody levels, or JIA subtypes ( P> 0.05). After sequencing data quality control and comparison of reference genomes, a total of 18 523 protein-coding genes were identified in all children′s samples. A total of 705 differentially expressed genes (DEGs) were identified between the effective group and the invalid group through differential analysis, of which 579 were up-regulated in the effective group and 126 in the inactive group. GO function and KEGG pathway enrichment analysis showed that DEG was significantly enriched in 55 GO entries and 32 KEGG metabolic pathways, which were mainly related to IL-1β; production and regulation, cytokine production and regulation, cytokine-cytokine receptor interaction, immune response regulation, and Toll-like receptor signaling pathway. Conclusion:DEG between the effective and ineffective groups of TNFi treatment may be involved in the biological processes such as cytokine production and regulation, cytokine-receptor interaction, and immune response regulation, which will be helpful to predict the efficacy and prognosis of TNFi treatment for JIA.

OBJECTIVE: To evaluate the differential expression of RNA in blood monocytes in patients with Juvenile idiopathic arthritis (JIA) treated with TNF antagonists (TNFi), and to explore the effect and mechanism of gene expression on the efficacy of JIA. METHODS: A total of 29 children with JIA treated with methotrexate (MTX) and TNFi in Guangzhou Women and Children's Medical Center of Guangzhou Medical University from April 2021 to November 2023 were enrolled. After 6 months, the children were divided into two groups according to the treatment effect, i.e., 13 cases in the ineffective group and 16 cases in the effective group, the peripheral blood of the children was collected, the blood mononuclear cells were isolated for transcriptome sequencing, the differentially expressed genes between the groups were analyzed, the signaling pathways and metabolic pathways related to the efficacy of TNFi were analyzed by GO and KEGG enrichment, and the mechanism related to the efficacy of TNFi was explored. This study was approved by Medical Ethics Committee of the Guangzhou Women and Children's Medical Center of Guangzhou Medical University (Ethics No.: 2023-330B00). RESULTS: There was a statistically significant difference in the gender and age distribution between the two groups of children (P < 0.05), while no statistically significant differences were observed in disease duration, rheumatoid antibody levels, or JIA subtypes (P > 0.05). After sequencing data quality control and comparison of reference genomes, a total of 18 523 protein-coding genes were identified in all children's samples. A total of 705 differentially expressed genes (DEGs) were identified between the effective group and the invalid group through differential analysis, of which 579 were up-regulated in the effective group and 126 in the inactive group. GO function and KEGG pathway enrichment analysis showed that DEG was significantly enriched in 55 GO entries and 32 KEGG metabolic pathways, which were mainly related to IL-1β production and regulation, cytokine production and regulation, cytokine-cytokine receptor interaction, immune response regulation, and Toll-like receptor signaling pathway. CONCLUSION DEG between the effective and ineffective groups of TNFi treatment may be involved in the biological processes such as cytokine production and regulation, cytokine-receptor interaction, and immune response regulation, which will be helpful to predict the efficacy and prognosis of TNFi treatment for JIA.
Humans ; Arthritis, Juvenile/blood* ; Female ; Male ; Child ; Methotrexate/therapeutic use* ; Child, Preschool ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Transcriptome ; Adolescent ; RNA/genetics* ; Signal Transduction ; Gene Expression Profiling

Objective:To evaluate the differential expression of RNA in blood monocytes in patients with Juvenile idiopathic arthritis (JIA) treated with TNF antagonists (TNFi), and to explore the effect and mechanism of gene expression on the efficacy of JIA.Methods:A total of 29 children with JIA treated with methotrexate (MTX) and TNFi in Guangzhou Women and Children′s Medical Center of Guangzhou Medical University from April 2021 to November 2023 were enrolled. After 6 months, the children were divided into two groups according to the treatment effect, 13 cases in the ineffective group and 16 cases in the effective group, the peripheral blood of the children was collected, the blood mononuclear cells were isolated for transcriptome sequencing, the differentially expressed genes between the groups were analyzed, the signaling pathways and metabolic pathways related to the efficacy of TNFi were analyzed by GO and KEGG enrichment, and the mechanism related to the efficacy of TNFi was explored. This study was approved by Medical Ethics Committee of the Guangzhou Women and Children′s Medical Center of Guangzhou Medical University (Ethics No.: 2023-330B00).Results:There was a statistically significant difference in the gender and age distribution between the two groups of children ( P<0.05), while no statistically significant differences were observed in disease duration, rheumatoid antibody levels, or JIA subtypes ( P> 0.05). After sequencing data quality control and comparison of reference genomes, a total of 18 523 protein-coding genes were identified in all children′s samples. A total of 705 differentially expressed genes (DEGs) were identified between the effective group and the invalid group through differential analysis, of which 579 were up-regulated in the effective group and 126 in the inactive group. GO function and KEGG pathway enrichment analysis showed that DEG was significantly enriched in 55 GO entries and 32 KEGG metabolic pathways, which were mainly related to IL-1β; production and regulation, cytokine production and regulation, cytokine-cytokine receptor interaction, immune response regulation, and Toll-like receptor signaling pathway. Conclusion:DEG between the effective and ineffective groups of TNFi treatment may be involved in the biological processes such as cytokine production and regulation, cytokine-receptor interaction, and immune response regulation, which will be helpful to predict the efficacy and prognosis of TNFi treatment for JIA.

Immunotherapy has become the first-line standard treatment option for driver gene-negative advanced non-small cell lung cancer (NSCLC). But not all patients can benefit from immunotherapy, and can even have serious adverse reactions. It is crucial to identify the predictors of clinical response to immunotherapy. Several studies have shown that elevated baseline C-reactive protein (CRP) or persistent elevation of CRP during the treatment process may indicate a poorer prognosis for patients, and high CRP may be correlated with adverse reactions. Attention to the dynamic changes of CRP during immunotherapy for NSCLC may become an important predictor of prognosis.

Objective To investigate the effect of fluid shear(FS)on apoptosis of glomerular epithelial cells(GECs)and the role of Piezo 1 protein in it.Methods GECs(glomerular epithelial cells)of SD rat were cul-tured.Fluid shear stimulation was simulated by a Flexcell-T5000 tensiometer.Apoptosis level was detected by flow cytometry.The expression of Piezo 1 proteins in GECs was detected by immunofluorescence staining.The activating of Piezo 1 channels by fluid shear was observed using Ca2+indicator(Cal-590 AM).The effect of Piezo 1 on apop-tosis in GECs was analyzed after modulating the function or expression of Piezo 1 protein using the chemical activa-tor Yoda1,the inhibitor GsMtx 4 was regulated by lentivirus Lv-shPiezo 1.Results Compared with the blank controlgroup,apoptosis increased in the fluid shear group(P＜0.05).The rate of apoptosis increased with the enhancing of fluid shear strength;Piezo 1 was commonly expressed in GECs.Fluid shear activated Piezo 1 chan-nel and enhanced expression of Piezo 1.The agonist Yoda1 promoted the apoptosis of GECs GsMtx 4 inhibited the apoptosis induced by fluid shear.Lv-shPiezo 1 knocked down the expression of Piezo 1 in GECs and the apoptosis rate of GECs in the knockdown group was reduced as compared to that in the control group and Lv-Ctrl group(P＜0.05).Conclusions Fluid shear may promote apoptosis of GECs by activation of Piezo 1 and by enhancing expression of Piezo 1.

【Objective】 To explore the relationship between the methylation level of CNR1 and autism spectrum disorder (ASD), in order to provide a theoretical basis for the etiology of ASD. 【Methods】 A case-control study was conducted, recruiting 30 children with ASD from the Child Development and Behavior Research Center of Harbin Medical University and a rehabilitation facility, and 30 matched typically developed children from June 2017 to December 2018. The methylation levels of CNR1 in peripheral blood were measured by the Agena MassArray^® Mass Spectrometry System. A univariate conditional Logistic regression model was used to analyze the potential association between the methylation level of CNR1 and the risk of ASD with adjustment for age, BMI, body fat percentage and body fat. The correlations between the methylation level of CNR1 and the score of Social Responsiveness Scale (SRS) were evaluated by Pearson/Spearman correlation analysis. 【Results】 The methylation levels of the average methylation (t=2.224), CpG_3.4 (Z=2.187), CpG_9.10.11 (t=2.308), and CpG_28.29 (t=2.943) of the CNR1 promoter region in ASD children were significantly higher than controls (P<0.05). The methylation levels of the average methylation (OR=1.117, 95%CI: 1.003 - 1.245), CpG_9.10.11 (OR= 1.072, 95%CI:1.006 - 1.142), and CpG_28.29 (OR=1.078, 95%CI: 1.018 - 1.141) of the CNR1 promoter region were positively correlated with the risk of ASD (P<0.05). The methylation level of CpG_28.29 in ASD children was positively correlated with the scores of social motivation in SRS (r=0.421, P<0.05). 【Conclusions】 The methylation levels of CNR1 in peripheral blood are abnormal in ASD children and might be correlated with the risk of ASD and social function. The underlying mechanism needs to be further explored.

Objective:To construct a comprehensive and targeted risk assessment index system for central venous catheter (CVC) dysfunction in patients undergoing continuous renal replacement therapy (CRRT) .Methods:The risk assessment indicators for CVC dysfunction in CRRT patients were determined based on literature review and Delphi expert consultation. From July to September 2023, 19 experts in hemodialysis were selected for expert consultation. Based on expert opinions and screening criteria, corresponding indicators were added, deleted, or modified. After the second round of consultation, the expert opinions tended to be consistent.Results:A total of 17 experts completed two rounds of consultation. In the two rounds of consultation, the effective response rates of the questionnaires were 89.5% (17/19) and 100.0% (19/19), respectively, and the expert authority coefficients were 0.87 and 0.88, respectively. The Kendall harmony coefficients were 0.131 and 0.138 ( P<0.05). The final risk assessment index system included seven primary indicators and 44 secondary indicators. Conclusions:The risk assessment index system for CVC dysfunction in CRRT patients constructed is scientific, reliable, and practical, which can provide reference for clinical medical and nursing staff to improve catheter risk management in CRRT patients.

Objective:To explore the characteristics of ovarian torsion in in vitro fertilization-embryo transfer (IVF-ET) cycles and identify factors that may affect the outcome. Methods:Patients who underwent surgery for ovarian torsion during IVF treatment in the Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital from January 2010 to December 2019 were included. The general information, IVF cycle characteristics, and intraoperative findings of patients were retrospectively analyzed. The diagnosis and treatment process were summarized. The pregnancy outcomes were followed up, and the possible influencing factors were analyzed.Results:There were 141 539 cycles of controlled ovarian stimulation (COS) and 75 585 cycles of frozen-thawed embryo transfer (FET) during the study period. A total of 50 patients were diagnosed with ovarian torsion and treated surgically, 90.0% of them occurred in the COS cycles (39 cases in fresh embryo transfer cycles and 6 cases in embryo freezing cycles), and 10.0% (5/50) occurred in the FET cycles (endometrial preparation in natural cycles or ovulation induction cycles). About 86.0% (43/50) of the patients occurred during pregnancy assisted with IVF-ET and 81.4% (35/43) occurred in the first trimester of pregnancy. All patients except one had abdominal pain as the first symptom, only 34.0% (17/50) of the patients had definite inducements, and all patients had signs of tenderness in the lower abdomen and adnexal area. Preoperative ultrasound examination showed that the average diameter of the torsional ovaries was (78.17±15.98) mm, compared with (48.69±15.96) mm in the controls, with an average difference of (30.13±19.69) mm (-3.5-80.0 mm). About 76.2% (32/42) of the torsional ovaries showed blood flow signals by color doppler ultrasound. All patients underwent surgery, and the coincidence rate between the preoperative diagnosis and the surgical diagnosis was 96%. Totally 22 torsional ovaries (44%) were found to be purplish-black, of which 16 cases underwent adnexectomy by laparoscopy or laparotomy. Totally 34 cases (68%) underwent ovarian detorsion. The average torsional degree of ovaries in the adnexectomy group was higher than that in the ovarian detorsion group [(727.50±206.54)° vs. (477.35±262.92)°, P=0.002]. There were no statistical differences between the two groups in the duration from onset to operation and the ratio of ovarian blood signal deficiency (all P>0.05). Among 44 patients with the embryo transfer, 84.1% (37/44) of patients obtained live birth, 1 case had implantation failure, and 6 cases had a spontaneous abortion. Patients with an adverse pregnancy outcome and patients with a live birth did not have significantly different ovarian torsion time, surgical methods, the duration from onset to operation, and other factors. Conclusion:Ovarian torsion in patients with IVF-ET treatment mostly occurs in the first trimester of pregnancy after fresh embryo transfer. Abdominal pain accompanied by differential enlargement of bilateral ovaries may suggest the possibility of ovarian torsion. We are unable to rule out ovarian torsion by observation of ovarian blood flow with color Doppler ultrasound. Active surgery was helpful to make a clear diagnosis and protect the fertility of patients. Patients with long torsional durations, purplish-black ovaries, or ovarian blood deficiency still have the opportunity to retain the torsional ovary. The pregnancy outcome of patients with ovarian torsion was satisfactory after surgical treatment.

Objective:To explore the efficacy of online problem management plus (PM+) intervention on the mental health among adults with anxiety.Methods:Ninety subjects with anxiety (Generalized Anxiety Disorder-7 (GAD-7) total score≥5) were enrolled and randomly allocated into either waiting group or online PM+group. Participants in the online PM+intervention group received online PM+intervention twice a week for 3 weeks, while participants in the waiting group received general psychological supports. Psychological evaluation was performed at the end of the 3-week treatment and at 6 months after treatment. Outcome measures included GAD-7, Patient Health Questionnaire -(PHQ-9), Patient Health Questionnaire-15 (PHQ-15), Perceived Stress Scale-14 (PSS-14), and Insomnia Severity Index (ISI). Two-factor repeated measure analysis of variance (ANOVA) was used to compare the scores of the two groups at baseline and after intervention. Single-factor repeated measure analysis of variance was used to compare the differences of scores at baseline,3-week post-intervention, and 6-month follow-up in the online PM+ group.Results:A total of 37 (37/45) pations in the online PM+intervention group and 30 (30/45) patients in the waiting group completed the psychological evaluation after intervention. After 3-week intervention, compared with baseline, no significant change was found in the scores of GAD-7 ( F=0.08, P=0.782), PHQ-9 ( F=0.33, P=0.570), PHQ-15 ( F=0.20, P=0.660), PSS-14 ( F=0.14, P=0.05) and ISI ( F=0.02, P=0.880) in the waiting group. The changes of GAD-7 ( F=22.61, P<0.001), PHQ-9 ( F=19.49, P<0.001), PHQ-15 ( F=12.67, P=0.001), PSS-14 ( F=16.69, P<0.001) and ISI ( F=5.59, P=0.022) scores in the online PM+group were statistically significant. There were significant differences in GAD-7 (9.7±5.2 vs. 5.0±3.5, F=17.11, P<0.001), PHQ-9 (11.4±5.9 vs. 6.9±4.7, F=11.65, P=0.002), PHQ-15 (10.4±5.4 vs. 6.3±4.1, F=12.24, P=0.002) and PSS-14 (26.0±7.5 vs.31.8±9.9, F=6.59, P=0.016) scale scores between the online PM+group and the waiting group after intervention. In addition, the scores of GAD-7 (95% CI=1.25-6.47, P=0.002) and PHQ-9 (95% CI=2.21-9.10, P=0.005) scales in the online PM+group still had statistically significant differences compared to the baseline at the 6-month follow-up. Conclusions:In this study, online PM+intervention significantly alleviated symptoms of anxiety, depression, somatization, stress, and insomnia in adults, and the therapeutic benefits of PM+persisted for at least 6 months.

Objective:To explore the characteristics of ovarian torsion in in vitro fertilization-embryo transfer (IVF-ET) cycles and identify factors that may affect the outcome. Methods:Patients who underwent surgery for ovarian torsion during IVF treatment in the Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital from January 2010 to December 2019 were included. The general information, IVF cycle characteristics, and intraoperative findings of patients were retrospectively analyzed. The diagnosis and treatment process were summarized. The pregnancy outcomes were followed up, and the possible influencing factors were analyzed.Results:There were 141 539 cycles of controlled ovarian stimulation (COS) and 75 585 cycles of frozen-thawed embryo transfer (FET) during the study period. A total of 50 patients were diagnosed with ovarian torsion and treated surgically, 90.0% of them occurred in the COS cycles (39 cases in fresh embryo transfer cycles and 6 cases in embryo freezing cycles), and 10.0% (5/50) occurred in the FET cycles (endometrial preparation in natural cycles or ovulation induction cycles). About 86.0% (43/50) of the patients occurred during pregnancy assisted with IVF-ET and 81.4% (35/43) occurred in the first trimester of pregnancy. All patients except one had abdominal pain as the first symptom, only 34.0% (17/50) of the patients had definite inducements, and all patients had signs of tenderness in the lower abdomen and adnexal area. Preoperative ultrasound examination showed that the average diameter of the torsional ovaries was (78.17±15.98) mm, compared with (48.69±15.96) mm in the controls, with an average difference of (30.13±19.69) mm (-3.5-80.0 mm). About 76.2% (32/42) of the torsional ovaries showed blood flow signals by color doppler ultrasound. All patients underwent surgery, and the coincidence rate between the preoperative diagnosis and the surgical diagnosis was 96%. Totally 22 torsional ovaries (44%) were found to be purplish-black, of which 16 cases underwent adnexectomy by laparoscopy or laparotomy. Totally 34 cases (68%) underwent ovarian detorsion. The average torsional degree of ovaries in the adnexectomy group was higher than that in the ovarian detorsion group [(727.50±206.54)° vs. (477.35±262.92)°, P=0.002]. There were no statistical differences between the two groups in the duration from onset to operation and the ratio of ovarian blood signal deficiency (all P>0.05). Among 44 patients with the embryo transfer, 84.1% (37/44) of patients obtained live birth, 1 case had implantation failure, and 6 cases had a spontaneous abortion. Patients with an adverse pregnancy outcome and patients with a live birth did not have significantly different ovarian torsion time, surgical methods, the duration from onset to operation, and other factors. Conclusion:Ovarian torsion in patients with IVF-ET treatment mostly occurs in the first trimester of pregnancy after fresh embryo transfer. Abdominal pain accompanied by differential enlargement of bilateral ovaries may suggest the possibility of ovarian torsion. We are unable to rule out ovarian torsion by observation of ovarian blood flow with color Doppler ultrasound. Active surgery was helpful to make a clear diagnosis and protect the fertility of patients. Patients with long torsional durations, purplish-black ovaries, or ovarian blood deficiency still have the opportunity to retain the torsional ovary. The pregnancy outcome of patients with ovarian torsion was satisfactory after surgical treatment.