ObjectiveTo understand the mental health literacy levels and influencing factors among middle school students in Minhang District, Shanghai, and to provide a basis for formulating mental health promotion strategies. MethodsA multi-stage stratified cluster sampling method was adopted. From September to October 2023, middle school students (including junior and senior high school) from 14 streets, towns, and industrial zones in Minhang District, Shanghai, were recruited to participate in a questionnaire survey. The survey collected demographic information and employed the Adolescent Mental Health Literacy Assessment Scale. This scale comprises four dimensions (knowledge, recognition ability, attitude, and behavior) with a total of 22 items, using a Likert 5-point scale (1‒5 points), giving a maximum total score of 110 points. Reverse-scored items were inverted, and the sum of all item scores constituted the total scale score, with higher scores indicating better mental health literacy. A total score of ≥88 points was defined as having adequate mental health literacy. Multiple linear regression was used to analyze the factors influencing mental health literacy. ResultsThe average mental health literacy score of the 3 963 middle school students in Minhang District of Shanghai City was (85.42±11.27) points, with 45.22% of students having adequate mental health literacy. Univariate analyses showed that female students, junior high school students, and those without stressful events or physical illnesses in the past three months had higher total scores of mental health literacy. Statistically significant differences in total scores were also observed among students with different family economic statuses, parental education levels, frequency of physical exercise, parental relationships, father‑child relationships, and mother‑child relationships (all P<0.05). Multiple linear regression analyses showed that middle school students who were female, had better family economic conditions, higher maternal education levels (university degree or above), and harmonious mother-child relationships had higher mental health literacy scores. In contrast, high school students and those middle school students who participated in less physical activity had lower mental health literacy scores. Multivariate logistic regression analyses indicated that students who were female (OR=1.336, 95%CI: 1.174‒1.520), had superior family economic status (OR=2.000, 95%CI: 1.101‒3.725), had mothers with a university education level (OR=1.501, 95%CI: 1.217‒1.856), had lost one parent (OR=2.189, 95%CI: 1.176~4.158), or reported harmonious mother‑child relationships (OR=2.052, 95%CI: 1.432‒2.987) were more likely to meet the criteria for mental health literacy, whereas those who rarely engaged in physical exercise (OR=0.502, 95%CI: 0.358‒0.694) were less likely to have adequate mental health literacy. Stratified analyses showed that mental health literacy levels among junior high school students were positively correlated with being female, having a mother with a university education level, and having a mother‑child relationship that was average or harmonious and having a harmonious father‑child relationship, and negatively correlated with occasional or rare participation in physical exercise. Among senior high school students, mental health literacy levels were positively correlated with being female, having good or superior family economic status, having a mother with a university education level or above, and having a harmonious mother‑child relationship. ConclusionThe rate of adequate mental health literacy among middle school students in Minhang District, Shanghai, was approximately 45.22%. Gender, grade level, family economic status, maternal education level, physical activity participation, and mother-child relationship are independent factors associated with the level of mental health literacy among middle school students. Mother-child relationship and physical activity are potential intervention entry points. It is recommended to implement targeted health promotion initiatives focusing on key groups, such as high school boys, students from economically disadvantaged families, and those with insufficient physical activity.

BACKGROUND: The sirtuin family is well recognized for its crucial involvement in various cellular processes. Nevertheless, studies on its role in the human endometrium are limited. This study aimed to explore the expression and localization of the sirtuin family in the human endometrium, focusing on sirtuin 3 (SIRT3) and its potential role in the oxidative imbalance of the endometrium in polycystic ovary syndrome (PCOS). METHODS: Endometrial specimens were collected from both patients with PCOS and controls undergoing hysteroscopy at the Center for Reproductive Medicine, Peking University Third Hospital, from July to August 2015 and used for cell culture. The protective effects of SIRT3 were investigated, and the mechanism of SIRT3 in improving endometrial receptivity of patients with PCOS was determined using various techniques, including cellular bioenergetic analysis, small interfering ribonucleic acid (siRNA) silencing, real-time quantitative polymerase chain reaction, Western blot, immunofluorescence, immunohistochemistry, and flow cytometry analysis. RESULTS: The sirtuin family was widely expressed in the human endometrium, with SIRT3 showing a significant increase in expression in patients with PCOS compared with controls ( P <0.05), as confirmed by protein and gene assays. Concurrently, endometrial antioxidant levels were elevated, while mitochondrial respiratory capacity was reduced, in patients with PCOS ( P <0.05). An endometrial oxidative stress (OS) model revealed that the downregulation of SIRT3 impaired the growth and proliferation status of endometrial cells and reduced their receptivity to day 4 mouse embryos. The results suggested that SIRT3 might be crucial in maintaining normal cellular state by regulating antioxidants, cell proliferation, and apoptosis, thereby contributing to enhanced endometrial receptivity. CONCLUSIONS Our findings proposed a significant role of SIRT3 in improving endometrial receptivity in patients with PCOS by alleviating OS and regulating the balance between cell proliferation and apoptosis. Therefore, SIRT3 could be a promising target for predicting and improving endometrial receptivity in this patient population.
Humans ; Female ; Polycystic Ovary Syndrome/metabolism* ; Endometrium/metabolism* ; Sirtuin 3/genetics* ; Oxidative Stress/genetics* ; Adult ; Animals ; Mice ; Apoptosis/physiology* ; Immunohistochemistry ; Cell Proliferation/physiology*

ObjectiveTo investigate the prevalence of cardiovascular diseases and their influencing factors in community-based schizophrenia patients in Shanghai, and to provide a scientific basis for the early identification and prevention of cardiovascular disease in this population. MethodsBased on the Shanghai community cohort with severe mental disorders in 2022, a total of 3 954 community-based schizophrenia patients were identified and included in this study through a stratified cluster sampling method. Basic information and relevant clinical data (including metabolic index data) were collected through questionnaire survey, physical examination and laboratory testing. Univariate analyses were performed using the chi-square tests, and multivariate logistic regression analyses were employed to identify influencing factors of comorbid cardiovascular diseases. ResultsA total of 3 954 community-based schizophrenia patients were included, of which a total of 1 237 (31.28%) patients had comorbid cardiovascular diseases. Multivariate logistic regression analyses showed that age 60 years old or above (OR=5.524, 95%CI: 3.716‒8.214), smoking behavior (OR=1.328, 95%CI: 1.042‒1.692), overweight (OR=1.900, 95%CI: 1.046‒3.451) or obesity (OR=2.678, 95%CI: 1.439‒4.985), elevated blood pressure (OR=1.546, 95%CI: 1.294‒1.846), abnormal fasting blood glucose (OR=1.552, 95%CI: 1.322‒1.823) and high-density lipoprotein cholesterol abnormalities (OR=1.283, 95%CI: 1.025‒1.606) were positively associated with the risk of comorbid cardiovascular diseases in patients with schizophrenia, while educational attainment of college/bachelor’s degree or above (OR=0.640, 95%CI: 0.450‒0.910) and being unmarried (OR=0.552, 95%CI: 0.457‒0.667) were negatively associated with the risk of cardiovascular diseases comorbidity. ConclusionAdvanced age, unhealthy behaviors and lifestyles, as well as abnormalities in blood pressure, blood glucose, and blood lipids, could all increase the risk of comorbid cardiovascular diseases in community schizophrenia patients. It is suggested to strengthen the monitoring and management of these risk factors in this population in the future, so as to achieve early detection, early diagnosis and early intervention of cardiovascular diseases.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy predominantly managed via chemotherapy. Our clinical sample analysis revealed a significant correlation between elevated CD24 expression in TNBC tumor cells and patient survival rates. We developed a novel antibody-drug conjugate (ADC), named HN03, consisting of an antibody with engineered cysteines for site-specific conjugation with a low toxic nitric oxide (NO) precursor as its payload through a novel Pt(IV)-mediated bioorthogonal self-cleavable linker. HN03 specifically targets tumor cells expressing high levels of CD24, concurrently generating cisplatin and releasing NO upon activation. HN03 also exhibited potent in vitro and in vivo antitumor activity. It significantly reduced tumor growth at various doses, prevented tumor metastasis, with markedly lower toxicity than traditional chemotherapy agents. We found that a key mechanism of its action involved inducing apoptosis and endoplasmic reticulum stress, substantially decreasing the number of M2-type macrophages. Overall, HN03 stands out as a promising therapeutic option for TNBC, offering a targeted treatment with reduced side effects and the potential for improved outcomes. Furthermore, using Pt(IV) in the linker and an NO precursor as the payload enhances the versatility of the Antibody-NO donor Conjugate (ANC), offering new avenues for the design of the next generation of ADCs.

BACKGROUND:Bone relies on the close connection between blood vessels and bone cells to maintain its integrity.Bones are in a physiologically hypoxic environment.Therefore,the study of angiogenesis and osteogenesis in hypoxic environment is closer to the microenvironment in vivo. OBJECTIVE:To explore the influence of Wenshen Tongluo Zhitong(WSTLZT)formula on H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell co-culture system in hypoxia environment and its related mechanism. METHODS:Enzyme digestion method and flow sorting technique were used to isolate and identify H-type bone microvascular endothelial cells.Mouse bone marrow mesenchymal stem cells were isolated and obtained by bone marrow adhesion method.H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell hypoxic co-culture system was established using Transwell chamber and anoxic culture workstation.WSTLZT formula powder was used to intervene in each group at a mass concentration of 50 and 100 μg/mL.The angiogenic function of H-type bone microvascular endothelial cells in the co-culture system was evaluated by scratch migration test and tube formation test.The osteogenic differentiation ability of bone marrow mesenchymal stem cells in the co-cultured system was evaluated by alkaline phosphatase staining and alizarin red staining.The protein and mRNA expression changes of PDGF/PI3K/AKT signal axis related molecules in H-type bone microvascular endothelial cells in the co-cultured system were detected by Western Blotting and q-PCR,respectively. RESULTS AND CONCLUSION:(1)Compared with the normal oxygen group,the scratch mobility and new blood vessel length of H-type bone microvascular endothelial cells were significantly higher(P<0.05);the osteogenic differentiation capacity of bone marrow mesenchymal stem cells was higher(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular protein and mRNA increased(P<0.05)in the hypoxia group.(2)Compared with the hypoxia group,scratch mobility and new blood vessel length were significantly increased in the H-type bone microvascular endothelial cells(P<0.05);bone marrow mesenchymal stem cells had stronger osteogenic function(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular proteins and mRNA further increased(P<0.05)after treatment with different dose concentrations of WSTLZT formula.These findings conclude that H-type angiogenesis and osteogenesis under hypoxia may be related to the PDGF/PI3K/AKT signaling axis,and WSTLZT formula may promote H-type vasculo-dependent bone formation by activating the PDGF/PI3K/AKT signaling axis,thereby preventing and treating osteoporosis.

Artificial intelligence (AI) in human assisted reproductive technology (ART) is gaining attention. AI technologies have been applied in ART clinical practice to assist doctors in performing semen analysis, embryo selection, and endometrial receptivity assessment, improving patient's outcomes and physician efficiency. However, most researches are experimental. Standardizing AI development, enhancing understanding among physicians and patients, and integrating AI with clinical practice are crucial. This review summarizes AI researches and applications in ART, discusses challenges, and explores future directions.

Objective:To screen potential comorbid genes shared between inflammatory bowel disease(IBD)and colorectal cancer(CRC),and to explore the relationship between the key gene a disintegrin and metalloprotease 8(ADAM8)and the pathogenesis of IBD and CRC,as well as the underlying mechanisms.Methods:Transcriptomic data and corresponding clinical information for IBD and CRC were downloaded from the GEO database and TCGA database.Differential expression analysis,prognostic gene screening,and intersection analysis were performed to identify shared genes.Multiple datasets were used to analyze and validate the expression patterns of ADAM8 in IBD and CRC and its correlation with clinicopathological features.Survival analysis was conducted to evaluate the prognostic value of ADAM8 in CRC.Functional and pathway enrichment analyses were conducted to explore the potential mechanisms by which ADAM8 influences CRC progression.The correlation between ADAM8 and tumor microenvironment components was further assessed using tumor microenvironmental algorithms.The database data was validated by detecting the expression in Chinese CRC tissues using immunohistochemistry(IHC).Results:ADAM8 was identified as a potential shared comorbidity gene in IBD and CRC.ADAM8 was significantly upregulated in both IBD and CRC tissues(all P<0.01),and its high expression was associated with disease progression(P<0.01).CRC patients with high ADAM8 expression had shorter overall survival(OS)(P<0.05 or P<0.01).ADAM8 was also significantly highly expressed in Chinese CRC tissues(P<0.01).Pathway analysis revealed that ADAM8 expression was closely linked to immune cell migration,cytokine production,and immune receptor interactions.Additionally,ADAM8 expression positively correlated with immune cell infiltration,including neutrophils and macrophages(P<0.01 or P<0.001).Conclusion:ADAM8 is highly expressed in IBD and CRC tissues and is closely associated with patient prognosis,disease progression,and immune cell infiltration.It holds promise as a common therapeutic target for both diseases.

Objective:To explore the effectiveness of interprofessional cooperative simulation in teaching emergency care for shock patients among intensive care unit (ICU) undergraduate nursing students.Methods:An interprofessional cooperative simulation-based teaching faculty team was established for ICU undergraduate nursing students, and a shock case library was developed. Using convenience sampling, 32 ICU undergraduate nursing students in 2022 were selected as the control group and received conventional simulation-based teaching, with students rotating through roles as nurses, standardized patients, doctors, and family members. In the experimental group, 34 ICU undergraduate nursing students in 2023 and 24 ICU clinical medicine interns were recruited to act as doctors for interprofessional cooperative simulation-based teaching. Each group was divided into subgroups, with each subgroup consisting of 4-5 nursing students. One group completed simulation-based training per month for a total of 8 sessions, with each session lasting 3 hours. The teaching adopted the on-site "tidal ward" in situ simulation, and the scenarios included patient history collection and health assessment, shock emergency care, nursing evaluation, and health education. The differences between the two groups of nursing students were compared in terms of ICU exit theoretical assessment score, objective structured clinical examination skill assessment score, and satisfaction with simulation-based teaching. SPSS 22.0 was used for independent samples t test and Mann-Whitney U test. Results:The experimental group achieved significantly higher scores in theoretical assessment (84.65±8.06), total score of satisfaction with simulation-based teaching (101.00±5.13), and clinical learning and multiprofessional team dimensions (47.32±3.35) compared to the control group ( P<0.001). The experimental group achieved higher scores in objective structured clinical examination skill assessment (81.40±7.22), guiding feedback and reflection (37.50±3.04), and judgmental thinking and clinical reasoning (16.00±2.03) compared to the control group, though the differences were not significant ( P=0.977, 0.668, and 0.636). Conclusions:Interprofessional cooperative simulation enhances the shock patient emergency care abilities and satisfaction with simulation-based teaching for undergraduate nursing students.