The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.

Objective To observe the effect of Sishen Pills on the expression of TREK-1 signaling pathway in rats of irritable bowel syndrome with diarrhea(IBS-D);To explore its mechanism in treating IBS-D.Methods Ten SPF-grade SD rats were randomly selected as the normal group,and the remaining 30 rats were used to prepare the IBS-D rat model by senna gavage combined with water stress avoidance method,and then the modeled rats were randomly divided into the model group,Western medicine group(15.23 mg/kg pivoxyl bromide)and Chinese medicine group(7.32 g/kg Sishen Pills).The medication groups were gavaged by corresponding drugs,and the normal group and model group were given equal volume of pure water,once a day,for consecutive 14 d.The general state of the rats was observed,the contents of serum cyclic adenosine monophosphate(cAMP),protein kinase A(PKA)and phosphorylated extracellular signal-regulated kinase(p-ERK)were detected by ELISA,the positive expressions of biportal potassium channel TREK-1 and p-ERK in colonic tissue were detected by immunofluorescence,the expressions of cAMP,PKA and p-ERK protein were detected by Western blot.Results Compared with the normal group,the body mass of rats in the model group was significantly reduced,and loose stool rate significantly increased(P<0.01);the contents of cAMP,PKA and p-ERK in serum were significantly increased(P<0.05,P<0.01);the positive expression and protein expression of TREK-1 in colonic tissue were significantly reduced,while the positive expression of p-ERK significantly increased(P<0.01),and the expressions of cAMP and PKA proteins significantly increased(P<0.01).Compared with the model group,the body mass of rats in Chinese medince group significantly increased,and loose stool rate significantly decreased(P<0.01);the contents of cAMP,PKA and p-ERK in serum were significantly reduced(P<0.05,P<0.01);the positive expression and protein expression of TREK-1 in colonic tissue significantly increased(P<0.01),while the positive expression of p-ERK significantly decreased(P<0.05),and the expressions of cAMP and PKA proteins significantly decreased(P<0.01).Conclusion Sishen Pills may regulate intestinal motility by affecting the expression of the TREK-1 signaling pathway,thereby treating IBS-D.

The incomplete degradation of tumour cells by macrophages(Mφ)is a contributing factor to tumour progression and metastasis,and the degradation function of Mφ is mediated through phagosomes and lysosomes.In our preliminary experiments,we found that overactivation of NADPH oxidase 2(NOX2)reduced the ability of Mφ to degrade engulfed tumour cells.Above this,we screened out liquiritin from Glycyrrhiza uralensis Fisch,which can significantly inhibit NOX2 activity and inhibit tumours,to elucidate that suppressing NOX2 can enhance the ability of Mφ to degrade tumour cells.We found that the tumour environment could activate the NOX2 activity in Mφ phagosomes,causing Mφ to produce excessive reactive oxygen species(ROS),thus prohibiting the formation of phagolysosomes before degradation.Conversely,inhibiting NOX2 in Mφ by liquiritin can reduce ROS and promote phagosome-lysosome fusion,therefore improving the enzymatic degradation of tumour cells after phagocytosis,and subse-quently promote T cell activity by presenting antigens.We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox,blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox,thereby inhibiting the activity of NOX2.This study elucidates the specific mechanism by which Mφ cannot degrade tumour cells after phagocytosis,and indicates that liquiritin can promote the ability of Mφ to degrade tumour cells by suppressing NOX2.

Objective:To explore the mediating effect of sleep quality on the relationship between serum vitamin D3 level and depressive symptoms in community-dwelling elderly people with mild cognitive impairment(MCI).Methods:A total of 480 elderly people with MCI meeting inclusion criteria in a community health service center from Jan 2023 to Dec 2023 were selected as the research objects.The general information questionnaire,mini-mental state examination(MMSE),activity of daily living scale(ADL),Center for Epidemiological Studies Depression Scale(CES-D)and Pittsburgh sleep quality index(PSQI)were used to investigate the subjects.Serum vitamin D3 level was detected within 1 week.Spearson correlation analysis was used to explore the correlation between sleep quality,serum vitamin D3 level and depressive symptoms.The mediating effect model was tested by Model 4 in the Process plug-in.Results:Among the 480 MCI elderly,the average score of depression was(12.28±4.75),the average serum vitamin D3 level was(25.81±7.09)ng/ml,and the average score of sleep quality was(7.17±2.71).Depression severity was positively correlated with sleep quality score(r=0.294,P＜0.01),and negatively correlated with serum vitamin D3 level(r=-0.237,P＜0.01).Serum vitamin D3 level was negatively correlated with sleep quality score(r=-0.225,P＜0.01).Bootstrap analysis showed that the mediating effect of sleep quality between serum vitamin D3 level and depression level was-0.064(95%CI:-0.115--0.023),accounting for 26.57%of the total effect.Conclusion:Sleep quality partially mediates the relationship between serum vitamin D3 level and depressive symptoms in the elderly with MCI in the community.

Objective:To investigate the long-term prognosis and related factors in children with multiphasic myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).Methods:A bidirectional cohort study was conducted. This study included 41 children with MOGAD who were treated at the Children′s Medical Center of Peking University First Hospital between January 2013 and December 2024, with a disease duration of ≥5 years. Demographic characteristics, clinical episodes, therapy, and prognostic indicators (including the expanded disability status scale (EDSS) and modified Rankin scale (mRS)) were collected. Children were stratified into relapse and non-relapse groups based on the presence or absence of relapse within 5 years of the last follow-up. χ2 test or Mann-Whitney U test was used to analyze factors associated with relapse. The Log-rank test was used to compare relapse-free rates between children with disease onset 0-<5 years and those with onset at 5-10 years. Results:A total of 41 children were enrolled, including 20 boys and 21 girls. The age at onset was 5.3 (3.8, 8.5) years, the age at last follow-up was 16.1 (13.2, 17.5) years, and the disease duration was 9.4 (8.1, 10.9) years. The annualized relapse rate (ARR) during follow-up was 0.34 (0.19, 0.56) times/year. The duration to first relapse was 0.8 (0.4, 1.5) years. At the last follow-up, the EDSS score was 0.0 (0.0, 0.0) score, and the mRS score was 0 (0, 0) score. A total of 40 children (98%) experienced relapses within the first 5 years after onset, while only 1 child (2%) relapsed at 6.7 years. The relapse rate between 5-10 years was lower than that between 0-<5 years ( HR=0.27, 95% CI 0.16-0.47, P<0.001). A total of 25 children (61.0%) exhibited clustered relapses during the disease course. There were 20 children (49%) in non-relapse groups, who were aged 16.6 (14.8, 17.6) years, disease duration 9.8 (9.3, 10.8) years at the last follow-up. Among those 20 children, 15 children (75%) had discontinued corticosteroids and immunosuppressants. The relapse group had higher clinical event rates and ARR compared to the relapse-free group (both P<0.01), the age at last follow-up was yonger ( P<0.05), while no significant differences were observed in age at onset, disease duration, or timing of immunosuppressant use (all P>0.05). Conclusions:Pediatric multiphasic MOGAD generally has a favorable prognosis, about half of patients remain relapse-free for ≥5 years at last follow-up. Relapses predominantly occur early in the disease course (mostly within 5 years of onset) and often exhibit a clustered pattern.

Objective:To explore the mediating effect of sleep quality on the relationship between serum vitamin D3 level and depressive symptoms in community-dwelling elderly people with mild cognitive impairment(MCI).Methods:A total of 480 elderly people with MCI meeting inclusion criteria in a community health service center from Jan 2023 to Dec 2023 were selected as the research objects.The general information questionnaire,mini-mental state examination(MMSE),activity of daily living scale(ADL),Center for Epidemiological Studies Depression Scale(CES-D)and Pittsburgh sleep quality index(PSQI)were used to investigate the subjects.Serum vitamin D3 level was detected within 1 week.Spearson correlation analysis was used to explore the correlation between sleep quality,serum vitamin D3 level and depressive symptoms.The mediating effect model was tested by Model 4 in the Process plug-in.Results:Among the 480 MCI elderly,the average score of depression was(12.28±4.75),the average serum vitamin D3 level was(25.81±7.09)ng/ml,and the average score of sleep quality was(7.17±2.71).Depression severity was positively correlated with sleep quality score(r=0.294,P＜0.01),and negatively correlated with serum vitamin D3 level(r=-0.237,P＜0.01).Serum vitamin D3 level was negatively correlated with sleep quality score(r=-0.225,P＜0.01).Bootstrap analysis showed that the mediating effect of sleep quality between serum vitamin D3 level and depression level was-0.064(95%CI:-0.115--0.023),accounting for 26.57%of the total effect.Conclusion:Sleep quality partially mediates the relationship between serum vitamin D3 level and depressive symptoms in the elderly with MCI in the community.

Objective To observe the effect of Sishen Pills on the expression of TREK-1 signaling pathway in rats of irritable bowel syndrome with diarrhea(IBS-D);To explore its mechanism in treating IBS-D.Methods Ten SPF-grade SD rats were randomly selected as the normal group,and the remaining 30 rats were used to prepare the IBS-D rat model by senna gavage combined with water stress avoidance method,and then the modeled rats were randomly divided into the model group,Western medicine group(15.23 mg/kg pivoxyl bromide)and Chinese medicine group(7.32 g/kg Sishen Pills).The medication groups were gavaged by corresponding drugs,and the normal group and model group were given equal volume of pure water,once a day,for consecutive 14 d.The general state of the rats was observed,the contents of serum cyclic adenosine monophosphate(cAMP),protein kinase A(PKA)and phosphorylated extracellular signal-regulated kinase(p-ERK)were detected by ELISA,the positive expressions of biportal potassium channel TREK-1 and p-ERK in colonic tissue were detected by immunofluorescence,the expressions of cAMP,PKA and p-ERK protein were detected by Western blot.Results Compared with the normal group,the body mass of rats in the model group was significantly reduced,and loose stool rate significantly increased(P<0.01);the contents of cAMP,PKA and p-ERK in serum were significantly increased(P<0.05,P<0.01);the positive expression and protein expression of TREK-1 in colonic tissue were significantly reduced,while the positive expression of p-ERK significantly increased(P<0.01),and the expressions of cAMP and PKA proteins significantly increased(P<0.01).Compared with the model group,the body mass of rats in Chinese medince group significantly increased,and loose stool rate significantly decreased(P<0.01);the contents of cAMP,PKA and p-ERK in serum were significantly reduced(P<0.05,P<0.01);the positive expression and protein expression of TREK-1 in colonic tissue significantly increased(P<0.01),while the positive expression of p-ERK significantly decreased(P<0.05),and the expressions of cAMP and PKA proteins significantly decreased(P<0.01).Conclusion Sishen Pills may regulate intestinal motility by affecting the expression of the TREK-1 signaling pathway,thereby treating IBS-D.

Objective:To investigate the long-term prognosis and related factors in children with multiphasic myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).Methods:A bidirectional cohort study was conducted. This study included 41 children with MOGAD who were treated at the Children′s Medical Center of Peking University First Hospital between January 2013 and December 2024, with a disease duration of ≥5 years. Demographic characteristics, clinical episodes, therapy, and prognostic indicators (including the expanded disability status scale (EDSS) and modified Rankin scale (mRS)) were collected. Children were stratified into relapse and non-relapse groups based on the presence or absence of relapse within 5 years of the last follow-up. χ2 test or Mann-Whitney U test was used to analyze factors associated with relapse. The Log-rank test was used to compare relapse-free rates between children with disease onset 0-<5 years and those with onset at 5-10 years. Results:A total of 41 children were enrolled, including 20 boys and 21 girls. The age at onset was 5.3 (3.8, 8.5) years, the age at last follow-up was 16.1 (13.2, 17.5) years, and the disease duration was 9.4 (8.1, 10.9) years. The annualized relapse rate (ARR) during follow-up was 0.34 (0.19, 0.56) times/year. The duration to first relapse was 0.8 (0.4, 1.5) years. At the last follow-up, the EDSS score was 0.0 (0.0, 0.0) score, and the mRS score was 0 (0, 0) score. A total of 40 children (98%) experienced relapses within the first 5 years after onset, while only 1 child (2%) relapsed at 6.7 years. The relapse rate between 5-10 years was lower than that between 0-<5 years ( HR=0.27, 95% CI 0.16-0.47, P<0.001). A total of 25 children (61.0%) exhibited clustered relapses during the disease course. There were 20 children (49%) in non-relapse groups, who were aged 16.6 (14.8, 17.6) years, disease duration 9.8 (9.3, 10.8) years at the last follow-up. Among those 20 children, 15 children (75%) had discontinued corticosteroids and immunosuppressants. The relapse group had higher clinical event rates and ARR compared to the relapse-free group (both P<0.01), the age at last follow-up was yonger ( P<0.05), while no significant differences were observed in age at onset, disease duration, or timing of immunosuppressant use (all P>0.05). Conclusions:Pediatric multiphasic MOGAD generally has a favorable prognosis, about half of patients remain relapse-free for ≥5 years at last follow-up. Relapses predominantly occur early in the disease course (mostly within 5 years of onset) and often exhibit a clustered pattern.

Objective To investigate the protective effect and mechanism of Danshen Tongluo Jiedu Decoction medicated serum for hypoxia/reoxygenation rat myocardial microvascular endothelial cells(CMECs)by regulating MALAT1.Methods Rats CMECs cells were cultured in vitro to establish a model of hypoxia/reoxygenation damaged cells,and were transfected overexpressing/silencing blank MALAT1 slow virus,cells were divided into overexpressed blank + TCM group,overexpressed MALAT1 + TCM group,overexpressed MALAT1 group,silenced blank + TCM group,silenced MALAT1 group,and silenced MALAT1 + TCM group.They were cultured with corresponding serum separately.Beclin-1 protein expression was detected by immunofluorescence method,and SRPK1,SRSF1,VEGF and Bax protein expressions were detected by Western blot,MALAT1,SRPK1 and SRSF1 mRNA expressions were detected by RT-PCR.Results Compared with the overexpressed blank + TCM group,Beclin-1 protein expression increased in the overexpressed MALAT1 + TCM group,the protein expressions of SRPK1,SRSF1 and Bax significantly increased(P<0.05,P<0.01),VEGF protein expression significantly decreased(P<0.01),while MALAT1,SRPK1 and SRSF1 mRNA expressions significantly increased(P<0.05,P<0.01).Compared with the overexpressed MALAT1 group,the protein expression of Beclin-1 in overexpressed MALAT1 + TCM group decreased,the expressions of SRPK1,SRSF1 and Bax protein significantly decreased(P<0.01,P<0.05),the expression of VEGF protein significantly increased(P<0.01),the mRNA expressions of MALAT1,SRPK1 and SRSF1 significantly decreased(P<0.05).Compared with the silenced blank + TCM group,the protein expression of Beclin-1 in silenced MALAT1 + TCM group decreased,the expressions of SRPK1,SRSF1 and Bax protein significantly decreased(P<0.01),while the expression of VEGF protein significantly increased(P<0.01),the mRNA expressions of MALAT1,SRPK1 and SRSF1 significantly decreased(P<0.01).Compared with the silenced MALAT1 group,the protein expression of Beclin-1 in silenced MALAT1 + TCM group decreased,the expressions of SRPK1,SRSF1 and Bax protein significantly decreased(P<0.05),the expression of VEGF protein significantly increased(P<0.01),the mRNA expressions of MALAT1,SRPK1 and SRSF1 significantly decreased(P<0.01,P<0.05).Conclusion Upregulation of MALAT1 expression can promote autophagy in hypoxia/reoxygenation model CMECs,while Danshen Tongluo Jiedu Decoction medicated serum can inhibit MALAT1 expression,thus inhibiting autophagy and promoting angiogenesis,and the mechanism may be related to the downregulation of SRPK1 and SRSF1 expressions.

Objective To analyze the situation and study trend of large-scale nurses'health cohort studies based on Web of Science,to help design clinical guidelines and scientific research for nursing staff in China.Methods Articles of large nurses'health cohort studies published from 1993 to 2023 were retrieved from Web of Science(WOS)Core Collection.Citespace and Bibilometrix were used to perform the bibliometric analysis.Results 2882 studies were included in this study.Total volume of papers was enlarging by year.Clustering results showed that the main keywords could be divided into 3 categories:risks of women's health,risks of cardiovascular disease and reproducibility.Results of keywords burst showed that lifestyle,cardiovascular disease,women reproductive health and mental health were the highlights of studies in recent 5 years.Conclusion Research on large-scale nurse health cohorts holds significant scientific significance.It is recommended to establish a nationwide large-scale nurse health cohort as soon as possible.In the study,appropriate exposure factors should be selected,with reproductive health,mental health,and psychiatric disorders being the primary outcome measures,and chronic physical illnesses being the secondary outcome measures.By systematically describing the factors influencing the physical and mental health of nurses in China,we can better safeguard their well-being and promote the development of the nursing discipline.