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.

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 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.

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.

ObjectiveTo investigate the correlation between mild cognitive impairment (MCI) and traditional Chinese medicine (TCM) body constitution types in the elderly, and to provide an evidence for the control of cognitive impairment in the elderly. MethodsThe elderly aged 65 and above who participated in the community physical examinations in a community of Changning District, Shanghai were selected as the research subjects. The cognitive function was assessed by using the Clock Drawing Test combined with the Ascertain Dementia 8-item Questionnaire (AD8), the Montreal Cognitive Assessment (MoCA) and the Mini-mental State Examination (MMSE). The diagnostic criteria for MCI was identified based on the 2018 Chinese Guidelines for the Diagnosis and Treatment of Dementia and Cognitive Disorders, along with the assessment results and clinical history information. The current investigation method was used to collect the basic information and the prevalence of chronic disease of the subjects through questionnaire inquiries. The elderly subjects’ ability to take care of themselves was evaluated based on the Elderly Self⁃Care Ability Evaluation Scale, while the TCM body constitution types were determined based on the Chinese Medicine Health Care Management Service Specification. The association of the detection rate of MCI with gender, education level, history of chronic disease and TCM body constitution types were analyzed lastly. ResultsA total of 2 351 elderly people were investigated, including 1 037 males and 1 314 females, with an average age of (74.11±6.15) years. 174 subjects, accounting for 7.40%, were identified with MCI. The highest detection rate of MCI in the elderly are those with a Qi stagnation constitution (10.8%), followed by those with a dampness-heat constitution (9.1%) and a Qi deficiency constitution (8.4%). Multivariate logistic regression analysis showed that advanced age, lower educational level, a history of tuberculosis, and TCM constitutions such as dampness-heat, Qi stagnation, and Qi deficiency were the potential risk factors for MCI. ConclusionThere is a significant association between TCM constitution types such as dampness-heat, Qi stagnation, and Qi deficiency with MCI. TCM techniques can be integrated into the health management services for the elderly population, and targeted interventions can be provided to those with imbalanced constitution types so as to reduce the risk of MCI.

Objective:To investigate the risk factors of acute symptomatic seizures (ASS) and epilepsy in children with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).Methods:A ambispective cohort study was used including 74 children with MOGAD who were admitted to the Department of Pediatrics of Peking University First Hospital from January 2013 to June 2023 and were followed up. Demographic information, clinical information, treatment status, ASS and epilepsy status were collected. The clinical phenotypes were classified. According to the presence or absence of ASS in the course of disease, the children and the course of disease were divided into groups with and without ASS. Chi-square test, Fisher exact test and Mann Whitney U test were used to analyze the correlation between symptoms and auxiliary examination characteristics and the occurrence of ASS in the two groups of children. Multivariate Logistic regression analysis was used for multivariate analysis. Results:The onset age of the 74 children with MOGAD was 6.58 (3.80, 9.67) years, including 38 females (51.4%) and 36 males (48.6%). The duration of the final follow-up was 2.67 (1.10, 4.12) years, with a total of 239 times acute clinical episodes. ASS occurred in 39.2% (29/74) children during the course of disease and in 29.3% (70/239) of attacks. The common phenotypes were ADEM (67 times (28.0%)), optic neuritis (37 times (15.4%)) and cerebral cortical encephalitis (31 times (13.0%)) in 239 times acute clinical episodes. The incidence of ASS in ADEM and cerebral cortical encephalitis phenotype was 28.4%(19/67) and 100.0% (31/31), respectively. Multivariate analysis showed that cortical involvement on magnetic resonance imaging during clinical attacks was an independent risk factor for ASS ( β=-1.49, OR=0.23) after excluding attacks involving only optic nerve or spinal cord (49 episodes). During the follow-up, 5 children (6.8%) had epilepsy, and all children with epilepsy had multiple clinical attacks of MOGAD and previous ASS. Conclusions:Cortical involvement on magnetic resonance imaging during clinical episodes is an independent risk factor for ASS in children with MOGAD. All MOGAD children with epilepsy had ASS and multiple MOGAD clinical episodes in the past.

Objective To study both non-invasive continuous cardiac index (CCI) and risk factors of coronary heart disease related with left ventricular ejection fraction (LVEF). Methods Retrospective study was done at VIP Health Center with 90 patients with preanesthesia assessment for gastrointestinal endoscopy under intravenous anesthesia between January and March 2022 in our hospital. CCI was measured using non-invasive real-time arterial blood pressure and hemodynamic monitoring system. Risk factors of coronary heart disease were collected. There were three groups of patients according to the results of LVEF gotten from echocardiography examination including group of LVEF 40%-49% (n=15), group of LVEF 50%-59% (n=38) and group of LVEF >60% (n=37). Results The group of LVEF 40%-49% had the highest rate of smoking (60.0%), hypertension (80.0%), diabetes (73.3%), hyperlipidemia (86.6%), obesity (53.3%), family history of early onest cardiovascular disease (33.3%) and the highest rate of ≥3 risk factors of coronary heart disease (80.0%)(P<0.05). The CCI in the group of LVEF 40%-49% was the lowest among three groups (P<0.05). There was a significant positive correlation between CCI and LVEF (r>0.95, P<0.05). Conclusions It was suggested that non-invasive real-time arterial blood pressure and hemodynamic monitoring system could be used for preanesthesia assessment, and CCI related to LVEF, which improves the safety of anesthesia for patients.

Objective To investigate the effect of phenformin combined with hexokinase inhibitor 2-deoxyglucose (2-DG) on the treatment of triple-negative breast cancer cell lines 4T1 and MDA-MB-231. Methods Following treatment with phenformin, 2-DG or phenformin combined with 2-DG on 4T1 and MDA-MB-231 cells for 48 h, the cell proliferation in each group was detected by SRB and the apoptosis of cells was detected by flow cytometry. The concentration of glucose and lactic acid in cell culture supernatant was detected by ELISA. The activity of mitochondrial respiratory chain complex Ⅰ was detected by FlexStation3 and the mitochondrial oxygen consumption (OCR) was assayed with the Seahorse X Fe Analyzer. Results The hexokinase expression (4.6±0.17,3.73±0.21), glucose consumption (356±31，397±42) μg/10⁵ cells , Lactic acid concentration (5.59±0.52, 7.83±0.78) μmol/L in the supernatant of 4T1 and MDA-MB-231 cells in Phenformin group were higher than that in control group ( 1±0.15，1±0.12 ) , ( 289±25，301±32) μg/10⁵cells , ( 2.37±0.18，4.01±0.45) μmol/L (P < 0.01). Even if the dose was reduced by 90%, the cell viability of phenformin combined with 2-DG group (64.63±2.28, 51.97±2.29) % was still higher than that of phenformin group (86.70±1.83, 85.53±1.46) % (P<0.001). The combination of the two drugs significantly promoted the apoptosis of 4T1 and MDA-MB-231. In addition, compared with the phenformin group (5.59±0.52, 7.83±0.78) μmol/L, the phenformin combined with 2-DG group (3.46±0.37, 5.18±0.62) μmol/L cell lactic acid production also greatly reduced (P<0.01). Compared with the phenformin or 2-DG single-drug group, the phenformin combined with 2-DG group can significantly inhibit the growth rate of tumors in tumor-bearing mice (P<0.01). The median survival time of tumor-bearing mice in the phenformin combined with 2-DG group was 72.5 d, which was higher than that in the phenformin group 57 d and 2-DG group 55.5 d (P<0.01). Conclusion Hexokinase inhibitor 2-DG significantly enhances the therapeutic effects of phenformin on triple-negative breast cancer cells.

Objective:To summarize the clinical characteristics of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and compare the differences in efficacy of different disease-modifying drugs.Methods:An ambispective cohort study was conducted in 42 children diagnosed with MOGAD at Department of Pediatrics, Peking University First Hospital from January 2012 to March 2021 and conducted long-term follow-up to analyze clinical phenotypes and compare the efficacy of different disease-modifying drugs such as rituximab, mycophenolate mofetil and azathioprine. Kruskal-Wallis H test was used to compare the annual relapse rate of disease-modifying drugs at different times, expanded disability status scale (EDSS) score at the last follow-up, and Wilcoxon rank test was used to compare the annual relapse rate before and after modified disease therapy. The Log-rank (Mantel-Cox) survival curve was used to compare the relapse rate of different disease-modifying drugs. Results:Of the 42 cases, 22 were male and 20 were female, with the age at disease onset of 5.96 (2.33-12.90) years. The disease duration was 4.46 (1.25-13.00) years at the last follow-up with 161 clinical acute attacks. Acute disseminated encephalomyelitis (ADEM) was the most common phenotype of first attack and all attacks during disease course ((60% (25/42) for first attack, 38% (61/161) for all attacks). The most common clinical syndrome was neuromyelitis optica spectrum disorders (NMOSD) (50%, 21/42). Of the 42 children, 5 (12%) showed encephalitis and 6 (14%) combined with anti-N-methyl-D-aspartate receptor (NMDAR) antibody overlap syndrome. The most commonly involved areas of brain magnetic resonance imaging (MRI) were subcortical white matter (71%, 88/124), cortex (26%, 32/124) and periventricular white matter (25%, 32/124). Spinal cord MRI was most frequently involved in cervical (70%, 16/23) and thoracic (61%, 14/23) medulla, and 43% (10/23) longitudinally extensive transeverse myelitis. Disease-modifying drugs were used in 34 patients. The annual relapse rate after treatment with rituximab, mycophenolate mofetil and azathioprine decreased (all P<0.05) and there was no statistically significant difference in the annual relapse proportion among the groups ( P=0.307). Conclusions:The most common clinical attack of first and all of MOGAD in children is ADEM, and the most common clinical syndrome is NMOSD. Rituximab, mycophenolate mofetil and azathioprine can reduce the annual relapse rate, but it is not clear effect of which treatment is better.

Objective: To analyze the clinical characteristics and treatment of pseudohypoparathyroidism(PHP) in children and to increase clinicians′understanding of this disorder. Methods: From January 2008 to November 2018, a total of 14 PHP patients at our hospital were retrospectively analyzed, as regarding the clinical manifestation, laboratory examination and imaging data.The patients were further divided into two groups according to onset age: group A(under 1 year) and group B(over or equal to 1 year). The laboratory findings were compared between the two groups. Results: Of the 14 patients(10 boys and 4 girls), the median age of onset was 12 years(range: 1 day to 16 years). Epilepsy is one of the most common manifestations of PHP.Laboratory findings include hypocalcemia(1.06-2.18mmol/L), hyperphosphatemia(2.1-3.5 mmol/L), and elevated concentrations of PTH(105.6-733.0 pg/ml). PTH levels were significantly lower in the group A than in group B(Z=2.07, P=0.042). Five patients were found to have calcifications in bilateral basal ganglia and cerebral parenchyma by head CT.All the patients were improved after treatment, which included calcium gluconate injection to control tetany, calcium supplement combined with vitamin D and/or calcitriol orally. Conclusion For children who presented frequent hypocalcemia tetany and calcifications in head CT, serum calcium, phosphorus, PTH levels should be further investigated to make a correct diagnosis.Calcium supplement combined with vitamin D or its metabolites is an effective therapy for PHP children.