Probiotics are natural systems bridging synthetic biology, physical biotechnology, and immunology, initiating innate and adaptive anti-tumor immune activity. We previously constructed an all-in-one engineered food-grade probiotic Lactococcus lactis (FOLactis) which could boost the crosstalk among different immune cells such as dendritic cells (DCs), natural killer cells, and T cells. Herein, considering the limited clinical efficacy of naked personalized neoantigen peptide vaccines, we decorate FOLactis with tumor antigens by employing a Plug-and-Display system comprising membrane-inserted peptides. Intranodal injection of FOLactis coated with neoantigen peptides (Ag-FOLactis) induces robust DCs presentation and neoantigen-specific cellular immunity. Notably, Ag-FOLactis not only triggers a 45-fold rise in the quantity of locally reactive neoantigen-specific T cells but also induces epitope spreading in both subcutaneous and metastatic tumor-bearing models, leading to potent inhibition of tumor growth. These findings imply that Ag-FOLactis represents a powerful platform to rapidly and easily display antigens, facilitating the development of a bio-activated platform for personalized therapy.

BACKGROUND: Cervical squamous cell carcinoma (CESC), the most common subtype of cervical cancer, is primarily caused by the high-risk human papillomavirus (HPV) infection and genetic susceptibility. Single-cell RNA sequencing (scRNA-seq) has been widely used in CESC research to uncover the diversity of cell types and states within tumor tissues, enabling a detailed study of the tumor microenvironment (TME). This technology allows precise mapping of HPV infection in cervical tissues, providing valuable insights into the initiation and progression of HPV-mediated malignant transformation. METHODS: We performed the scRNA-seq to characterize gene expression in tumor tissues and paired adjacent para-cancerous tissues from four patients with early-stage CESC using the 10× Genomics platform. The HPV infection and its subtypes were identified using the scRNA data and viral sequence mapping, and trajectory analyses were performed using HPV+ or HPV- cells. Interactions between different types of keratinized cells and their interactions with other cell types were identified, and pathways and specificity markers were screened for proliferating keratinized cells. The Cancer Genome Atlas (TCGA) dataset was used to verify the prognostic correlation between tumor-specific PI3+S100A7+ keratinocyte infiltration and CESC, and the localization relationship between PI3+S100A7+ keratinocytes and macrophages was verified by immunofluorescence staining. RESULTS: Various types of keratinocytes and fibroblasts were the two cell types with the most significant differences in percentage between the tumor tissue samples and paired adjacent non-cancerous tissue samples in the early stages of CESC. We found that PI3+S100A7+ keratinocytes were associated with early HPV-positive CESC, and PI3+S100A7+ keratinocytes were more abundant in tumors than in adjacent normal tissues in the TCGA-CESC dataset. Analysis of clinical information revealed that the infiltration of PI3+S100A7+ keratinocytes was notably higher in tumors with poor prognosis than in those with good prognosis. Additionally, multiplex immunofluorescence analysis showed a specific increase in PI3+S100A7+ expression within tumor tissues, with PI3+S100A7+ keratinocytes and CD163+ macrophages being spatially very close to each other. In the analysis of cell-cell interactions, macrophages exhibited strong crosstalk with PI3+S100A7+ proliferating keratinocytes in HPV-positive CESC tumors, mediated by tumor necrosis factor (TNF), CCL2, CXCL8, and IL10, highlighting the dynamic and tumor-specific enhancement of macrophage-keratinocyte interactions, which are associated with poor prognosis and immune modulation. Using CIBERSORTx, we discovered that patients with high infiltration of both PI3+S100A7+ proliferating keratinocytes and macrophages had the shortest overall survival. In the analysis of cell-cell interactions, PI3+S100A7+ proliferating keratinocytes and macrophages were found to be involved in highly active pathways that promote differentiation and structure formation, including cytokine receptor interactions, the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway, and TNF signaling pathway regulation. Further subtyping of fibroblast populations identified four subtypes. The C1 group, characterized by its predominance in tumor tissues, is a subtype enriched with cancer-associated fibroblasts (CAFs), whereas the C3 group is primarily enriched in adjacent non-cancerous tissues and consists of undifferentiated cells. Moreover, the distinct molecular and cellular differences between HPV16- and HPV66-associated tumors were demonstrated, emphasizing the unique tumor-promoting mechanisms and microenvironmental influences driven by each HPV subtype. CONCLUSIONS We discovered a heterogeneous population of keratinocytes between tumor and adjacent non-cancerous tissues caused by HPV infection and identified macrophages and specific CAFs that play a crucial role during the early stage in promoting the inflammatory response and remodeling the cancer-promoting TME. Our findings provide new insights into the transcriptional landscape of early-stage CESC to understand the mechanism of HPV-mediated malignant transformation in cervical cancer.
Humans ; Female ; Papillomavirus Infections/genetics* ; Uterine Cervical Neoplasms/genetics* ; Carcinoma, Squamous Cell/pathology* ; Keratinocytes/metabolism* ; Single-Cell Analysis/methods* ; Tumor Microenvironment/genetics*

Objective:To investigate the dynamics of articles published in the Chinese Journal of Psychiatry since 1996 through bibliometrics and visual analysis.Methods:The studies published in the Chinese Journal of Psychiatry between 1996 and 2024 were retrieved from the Wanfang Database. Bibliometric analysis was used to statistically examine the publication year distribution, geographic regions, institutions, authorship, keywords, and citation frequencies. VOSviewer software was utilized for network visualization analysis.Results:A total of 2 843 articles were included for analysis.Publications originated from 22 provinces, 4 municipalities, 4 autonomous regions, and the Hong Kong Special Administrative Region. First authors were affiliated with 672 institutions, encompassing medical centers, universities, research institutes, academic societies, administrative agencies, and pharmaceutical companies. A total of 13 356 authorship instances, including 1 879 first authors, were identified. The overall collaboration index was 4.70, with a collaboration rate of 88.39%. Keyword co-occurrence analysis revealed nine major research hotspots in psychiatry.Conclusion:The Chinese Journal of Psychiatry has steadily enhanced its academic reputation and influence over the past three decades, attracting a cohort of influential core researchers. The journal′s publications cover a wide range of topics, reflecting the major research hotspots in psychiatry.

Artificial intelligence (AI) technologies are being widely applied in radiotherapy. However, the integration of AI into clinical workflows of radiotherapy faces a series of challenges, such as poor model interpretability, domain shifts between clinical application and training data, and the inherent model uncertainties. Therefore, case-specific quality assurance (QA) is essential before deploying AI models in clinical practice. This paper reviews and summarizes QA methodologies for the application of AI models in radiotherapy across four key areas: image registration, image generation, region of interest segmentation, and treatment planning.

Objective:To investigate the therapeutic effect of combined extracranial-intracranial revascularization on elderly patients with symptomatic chronic internal carotid artery occlusion, and to evaluate its safety and efficacy in the elderly population.Methods:A retrospective analysis was conducted on 35 elderly patients(aged ≥60 years)who underwent combined extracranial-intracranial revascularization for symptomatic chronic internal carotid artery occlusion in the Department of Neurosurgery, Renmin Hospital of Wuhan University from January 2017 to June 2022.The clinical data during hospitalization, as well as the follow-up data within 2 years after operation, were collected and analyzed.Results:A total of 35 cases of combined extracranial-intracranial revascularization were performed on 35 patients.The age at surgery ranged from 60 to 74 years(mean age 65.5 ± 4.2 years). The incidence of reversible neurological deficits within 2 weeks postoperation was 34.3%, and the incidence of focal cerebral infarction within 30 days postoperation was 5.7%.The patency rate of the bridging vessel was 97.1% at 3 months postoperation., and the incidence of focal cerebral infarction during the follow-up period of 30 days to 2 years postoperation was 2.9%.At 3 months after surgery, computed tomography perfusion imaging showed that regional cerebral blood flow(rCBF), regional cerebral blood volume(rCBV), regional mean transit time(rMTT), and regional time to peak(rTTP)were improved compared with those before surgery.The modified Rankin scale score decreased compared to preoperative values, while the Montreal Cognitive Assessment showed improvement in cognitive function compared to preoperative levels(all P<0.05). From 6 months to 1-year postoperation, cerebral angiography showed that 38.7% of the patients had neovascularization of Matsushima grade A or grade B. No cases of cerebral hemorrhage or death was observed during the treatment and follow-up. Conclusions:Combined extracranial-intracranial revascularization is safe and effective for elderly patients with symptomatic chronic internal carotid artery occlusion, which can improve the patient′s hemodynamic disorders, prevent infarction events, and improve the patients′ neurological function and cognitive ability.

Objective To explore the applications and effects of professional training-based peer support on self-management of women with gestational diabetes mellitus.Methods A total of 96 patients diagnosed with gestational diabetes mellitus in a tertiary A-level women's hospital in Nanjing from March to June 2023 were conveniently selected as the research subjects,among which 48 patients with gestational diabetes mellitus diagnosed from May to June 2023 were divided into an experimental group,and 48 patients with gestational diabetes mellitus diagnosed from March to April 2023 were included into a control group.The experimental group received professional training-based peer support based on routine nursing,and the control group received routine nursing.The status of self-management,health literacy,quality of life and blood glucose in 2 groups were compared and analyzed.Results 45 patients in the experimental group and 48 patients in the control group completed the study.After intervention,the Self-Management Scale score of the experimental group was(115.11±9.48),which was higher than(78.46±6.27)of the control group;the score of Health Literacy Scale was(145.38±5.22),higher than(92.19±5.75)of the control group;the Quality of Life Scale score was(79.47±4.11),higher than(60.85±2.80)of the control group;the fasting blood glucose concentration and two-hour postprandial glucose concentration in the experimental group were lower than those in the control group,and the difference between 2 groups was statistically significant(P＜0.001).Conclusion Nursing intervention of the professional training-based peer support can effectively improve the levels of self-management,health literacy and quality of life,as well as reduce concentration of blood glucose.

Objective:To investigate the therapeutic effect of combined extracranial-intracranial revascularization on elderly patients with symptomatic chronic internal carotid artery occlusion, and to evaluate its safety and efficacy in the elderly population.Methods:A retrospective analysis was conducted on 35 elderly patients(aged ≥60 years)who underwent combined extracranial-intracranial revascularization for symptomatic chronic internal carotid artery occlusion in the Department of Neurosurgery, Renmin Hospital of Wuhan University from January 2017 to June 2022.The clinical data during hospitalization, as well as the follow-up data within 2 years after operation, were collected and analyzed.Results:A total of 35 cases of combined extracranial-intracranial revascularization were performed on 35 patients.The age at surgery ranged from 60 to 74 years(mean age 65.5 ± 4.2 years). The incidence of reversible neurological deficits within 2 weeks postoperation was 34.3%, and the incidence of focal cerebral infarction within 30 days postoperation was 5.7%.The patency rate of the bridging vessel was 97.1% at 3 months postoperation., and the incidence of focal cerebral infarction during the follow-up period of 30 days to 2 years postoperation was 2.9%.At 3 months after surgery, computed tomography perfusion imaging showed that regional cerebral blood flow(rCBF), regional cerebral blood volume(rCBV), regional mean transit time(rMTT), and regional time to peak(rTTP)were improved compared with those before surgery.The modified Rankin scale score decreased compared to preoperative values, while the Montreal Cognitive Assessment showed improvement in cognitive function compared to preoperative levels(all P<0.05). From 6 months to 1-year postoperation, cerebral angiography showed that 38.7% of the patients had neovascularization of Matsushima grade A or grade B. No cases of cerebral hemorrhage or death was observed during the treatment and follow-up. Conclusions:Combined extracranial-intracranial revascularization is safe and effective for elderly patients with symptomatic chronic internal carotid artery occlusion, which can improve the patient′s hemodynamic disorders, prevent infarction events, and improve the patients′ neurological function and cognitive ability.

Objective To explore the applications and effects of professional training-based peer support on self-management of women with gestational diabetes mellitus.Methods A total of 96 patients diagnosed with gestational diabetes mellitus in a tertiary A-level women's hospital in Nanjing from March to June 2023 were conveniently selected as the research subjects,among which 48 patients with gestational diabetes mellitus diagnosed from May to June 2023 were divided into an experimental group,and 48 patients with gestational diabetes mellitus diagnosed from March to April 2023 were included into a control group.The experimental group received professional training-based peer support based on routine nursing,and the control group received routine nursing.The status of self-management,health literacy,quality of life and blood glucose in 2 groups were compared and analyzed.Results 45 patients in the experimental group and 48 patients in the control group completed the study.After intervention,the Self-Management Scale score of the experimental group was(115.11±9.48),which was higher than(78.46±6.27)of the control group;the score of Health Literacy Scale was(145.38±5.22),higher than(92.19±5.75)of the control group;the Quality of Life Scale score was(79.47±4.11),higher than(60.85±2.80)of the control group;the fasting blood glucose concentration and two-hour postprandial glucose concentration in the experimental group were lower than those in the control group,and the difference between 2 groups was statistically significant(P＜0.001).Conclusion Nursing intervention of the professional training-based peer support can effectively improve the levels of self-management,health literacy and quality of life,as well as reduce concentration of blood glucose.

Objective:To investigate the dynamics of articles published in the Chinese Journal of Psychiatry since 1996 through bibliometrics and visual analysis.Methods:The studies published in the Chinese Journal of Psychiatry between 1996 and 2024 were retrieved from the Wanfang Database. Bibliometric analysis was used to statistically examine the publication year distribution, geographic regions, institutions, authorship, keywords, and citation frequencies. VOSviewer software was utilized for network visualization analysis.Results:A total of 2 843 articles were included for analysis.Publications originated from 22 provinces, 4 municipalities, 4 autonomous regions, and the Hong Kong Special Administrative Region. First authors were affiliated with 672 institutions, encompassing medical centers, universities, research institutes, academic societies, administrative agencies, and pharmaceutical companies. A total of 13 356 authorship instances, including 1 879 first authors, were identified. The overall collaboration index was 4.70, with a collaboration rate of 88.39%. Keyword co-occurrence analysis revealed nine major research hotspots in psychiatry.Conclusion:The Chinese Journal of Psychiatry has steadily enhanced its academic reputation and influence over the past three decades, attracting a cohort of influential core researchers. The journal′s publications cover a wide range of topics, reflecting the major research hotspots in psychiatry.