ObjectiveTo investigate the heterogeneity and transcriptomic characteristics of T-cell subsets in the liver of mice with nonalcoholic steatohepatitis （NASH） at the single-cell level using single-cell RNA sequencing （scRNA-seq）， and to provide a reference for studying the mechanism of action of T cells in NASH. MethodsSix male C57BL/6 mice were randomly divided into control group fed with regular diet and NASH group fed with methionine-choline-deficient （MCD） diet， with three mice in each group， and liver tissue was collected for scRNA-seq after 6 weeks of modeling. Specific differentially expressed genes were analyzed between T-cell subsets， and related analyses were performed， including dimension clustering， cell type annotation， t-distributed stochastic neighbor embedding （t-SNE）， violin plot， gene ontology （GO） functional enrichment analysis， and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. Immunofluorescent staining was used to observe the expression of the T cell marker Tcrα and the specific marker genes Tcf7 and Cxcr6 in the liver of mice in the two groups. The independent-samples t test was used for comparison of continuous data between two groups. ResultsTwo T cell subsets were identified in the liver of mice， and the percentage of cluster 6 decreased from 58.5% in the control group to 48.7% in the NASH group. The top four specific genes were Nsg2， Cd8b1， Cd8a， and Tcf7. Tcf7， a characteristic marker gene for cluster 6， was expressed in 65% of cells in cluster 6， and therefore， cluster 6 was defined as Tcf7⁺ T cells. The GO and KEGG enrichment analyses showed that the differentially expressed genes of cluster 6 were involved in T cell activation， leukocyte adhesion， binding ubiquitin-like protein ligase， and the signaling pathways for Th17， Th1， and Th2 cell differentiation. The percentage of cluster 7 increased from 41.5% in the control group to 51.3% in the NASH group. The top four specific genes of cluster 7 were Cd40lg， Tcrg-C1， Il2rα， and Cxcr6. Cxcr6 was expressed in 90% of cells in cluster 7， and therefore， cluster 7 was defined as Cxcr6⁺ T cells. The GO and KEGG enrichment analyses showed that cluster 7 was involved in T cell activation， cytokine production， the T cell receptor signaling pathway， and the Th17 cell differentiation and MAPK signaling pathway. Immunofluorescence assay showed that compared with the control group， the NASH group showed a significant reduction in the area with positive co-expression of Tcf7 protein and Tcrα protein （1.80%±0.67% vs 0.33%±0.13%， P<0.05） and a significant increase in the area with positive co-expression of Cxcr6 protein and Tcrα protein （0.50%±0.09% vs 2.66%± 0.33%， P<0.001）. ConclusionThere is a reduction in the percentage of Tcf7⁺ T cells and an increase in the percentage of Cxcr6⁺ T cells in NASH mice， revealing the characteristics and differences of T cells in the liver of NASH mice.

Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy characterized by an abnormal proliferation of primitive and naive myeloid cells in the bone marrow and peripheral blood. Patients vary enormously in molecular biological features, clinical manifestations and prognosis, leading to therapeutic difficulties. Increasing evidence indicates that the tumor microenvironment plays an important role in the development and progression of AML. Immunometabolism reveals the metabolic network of immune cells, which has important implications in tumor research. This work reviews the research progress on the metabolic alterations of immune cells in the AML microenvironment and the therapeutic strategies targeting immune metabolism in AML to present a part of the blueprint of immune metabolism regulation in the bone marrow microenvironment of AML.

Biliary tract cancers (BTC), a heterogeneous disease with poor prognosis, including gallbladder cancer (GBC), intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (ECC). Although surgery is currently the primary regimen to treat BTC, most BTC patients are diagnosed at an advanced stage and miss the opportunity of surgical eradication. As a result, non-surgical therapy serves as the main intervention for advanced BTC. In recent years, immunotherapy has emerged as one of the most promising therapies in a number of solid cancers, and it includes immune checkpoint inhibitors (ICIs) monotherapy or combined therapy, tumor vaccines, oncolytic virus immunotherapy, adoptive cell therapy (ACT), and cytokine therapy. However, these therapies have been practiced in limited clinical settings in patients with BTC. In this review, we focus on the discussion of latest advances of immunotherapy in BTC and update the progress of multiple current clinical trials with different immunotherapies.

Objective To analyze the international research results of artificial intelligence in the medical field by the double clustering method, and to explore the hot trends in the topic field. Methods The Web of Science core collection database was searched for the research literature of artificial intelligence in the field of medicine, and the high-frequency keywords were extracted by Co-Occurrence13.4 to generate the word matrix. The gCluto1.0 clustering toolkit was used for the double cluster analysis. Results A total of 7 803 articles were included, and the annual number of publications showed an overall upward trend. The United States ranked the first in the total number of publications. A total of 30 high-frequency subject words were extracted to form 6 clusters such as artificial intelligence applied to biomarker detection. The research hotspots focused on six topics: health care, disease outcome, whole-course disease monitoring, auxiliary diagnosis of cancer, model validity and differential biomarkers. Conclusion Artificial intelligence has been widely used in clinical diagnosis and treatment technology, which provides targeted support for genetic testing and public health events. However, related domestic research is still in developing stage. In the future, we need to rely on multidisciplinary and inter-institutional communication and cooperation to promote the development of intelligent medical in China, so that it truly becomes an important tool to promote the development of medical and health services.

Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.
Animals ; Humans ; Squamous Cell Carcinoma of Head and Neck/therapy* ; Heterografts ; Photothermal Therapy ; Biomimetics ; Disease Models, Animal ; Head and Neck Neoplasms/therapy* ; Cell Line, Tumor ; Tumor Microenvironment

The first global outbreak of monkeypox in non-epidemic regions occurred in May 2022, and the World Health Organization defined it as a public health emergency of international concern in July 2022. Compared with previous outbreaks of monkeypox in Africa, the current one is different in etiology, epidemiology and clinical characteristics. This article reviews the features of the latest outbreak of monkeypox, and the currently available antiviral treatment and vaccines, so as to provide reference for the prevention and treatment of monkeypox.

Purpose: In non-metastatic prostate cancer (nmPCa) setting, it is important to early identify the patients at risk of biochemical recurrence (BCR) for immediate postoperative intervention. Our study aimed to evaluate the potential clinical utility of circulating tumor DNA (ctDNA) for predicting disease recurrence. Materials and Methods: This real-world observational study evaluated 161 cases of nmPCa undergoing next-generation sequencing at our institution. A total of 139 ctDNA samples and 31 biopsied tumor tissue underwent genomic profiling. The study endpoint was BCR after radical prostatectomy. Relationships between the ctDNA status and the biochemical progression-free survival (bPFS) were analyzed by log-rank test and multivariate Cox regression. Results: Of 161 enrolled patients, 19 (11.8%) harbored deleterious alterations in NCOR2, followed by BRCA2 (3.7%), ATR (2.5%), and CDK12 (2.5%). Of available pre-operative blood samples (n=139), ctDNA was detectable in 91 (65.5%). Until last follow-up, 56 of 68 patients (85.3%) with detectable ctDNA had achieved BCR, whereas only eight of 39 patients (20.5%) with undetectable ctDNA had achieved BCR. Patients who had undetectable ctDNA experienced significantly longer bPFS compared with those who had detectable ctDNA (not available vs. 8.2 months; hazard ratio, 0.14; p < 0.01). Pre-operative ctDNA status was a significant prognostic factor of disease recurrence. Conclusion Pre-operative ctDNA detection could identify patients at high risk of recurrence and has the potential to inform immediate postoperative interventions, but these approaches remain to be validated in prospective studies. ctDNA studies can provide insights into accurate monitoring and precise treatment rather than simply following routine clinical care.

Background Tricresyl phosphate (TCP) is mainly used as a flame retardant. Studies have confirmed that it has cytotoxicity and neurotoxicity, but its reproductive toxicity is not clear. Objective To investigate the reproductive toxicity and potential mechanism of TCP subacute exposure on Caenorhabditis elegans. Methods Caenorhabditis elegans were exposed to solvent control and 0.1, 1, 10, 100, and 1000 μg·L⁻¹ TCP respectively for 72 h. Brood size and number of fertilized eggs in the uterus were detected to evaluate reproductive ability. The number of total germline cells and the relative area of gonad arm were measured to evaluate the development of gonads. The body length and body width of Caenorhabditis elegans were detected to evaluate growth and development. The activities of reactive oxygen species (ROS) and superoxide dismutase (SOD) in Caenorhabditis elegans, and the mitochondrial active oxygen metabolism genes (mev-1 and gas-1) of N2 nematodes were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) to evaluate oxidative stress. WS1433 transgenic nematodes and wild-type nematodes N2 were exposed to solvent control or TCP (0.1, 1, 10, 100, and 1000 μg·L⁻¹) respectively. DNA damage in germ cells of WS1433 transgenic nematodes was detected, the relative expressions of DNA damage-related genes (hus-1, clk-2, cep-1, and egl-1) in N2 nematodes were detected by qRT-PCR to evaluate the effect of TCP exposure on genetic damage. Results Compared with the solvent control group (217.00 ± 12.20), the brood size of N2 nematodes in the 100 μg·L⁻¹ and 1000 μg·L⁻¹ TCP groups decreased (170.80 ± 11.51, 169.60 ± 10.52, P < 0.05). Compared with the solvent control group (18.43 ± 1.69), the number of fertilized eggs of N2 nematodes in the 100 μg·L⁻¹ and 1000 μg·L⁻¹ TCP groups decreased (13.47 ± 0.81, 11.95 ± 0.90, P < 0.05). Compared with the solvent control group (312.46 ± 77.4), the number of total germline cells of N2 nematodes in the 100 μg·L⁻¹ and 1000 μg·L⁻¹ TCP groups decreased (281.80 ± 12.98, 273.50 ± 8.53, P < 0.05). Compared with the solvent control group, the relative area of gonads of N2 nematodes in the 100 μg·L⁻¹ and 1000 μg·L⁻¹ TCP groups decreased by 13.83% and 17.25% respectively (P<0.05). Compared with the solvent control group [(1058.10±80.12) μm, (78.21±14.69) μm], the body length and body width of N2 nematodes in the 100 μg·L⁻¹ and 1000 μg·L⁻¹ TCP groups decreased (P<0.05). Compared with the solvent control group, the relative fluorescence intensity of ROS in nematodes in the 10, 100, and 1000 μg·L⁻¹ TCP groups increased significantly (107.60%±1.02%, 105.90%±1.40%, and 106.40%±1.85%, respectively, P<0.05), and the activities of SOD were reduced (by 20.66%, 15.88%, and 16.44%, respectively, P<0.05). Compared with the solvent control group (1.3±1.3), the number of DNA-damaged germ cells of WS1433 nematodes in the 100 and 1000 μg·L⁻¹ TCP groups increased significantly (2.4±0.3, 2.7±0.3, P<0.05); the expressions of mev-1 and gas-1 genes in N2 nematodes in the 10, 100 and 1000 μg·L⁻¹ TCP groups decreased significantly (P<0.05); the expressions of hus-1 in the 0.1-1000 μg·L⁻¹ TCP groups significantly increased (P<0.05); the expressions of clk-2 and egl-1 in the 100 and 1000 μg·L⁻¹ TCP groups increased significantly (P<0.05); the expressions of cep-1 in the 1, 10, and 100 μg·L⁻¹ TCP groups increased significantly (P<0.05). Conclusion TCP may cause reproductive damage to nematodes through oxidative stress and germ cell DNA damage.

Objective:To investigate the status and the influencing factors of influenza vaccination during the COVID-19 pandemic among community-dwelling elderly in Shanghai.Methods:A questionnaire survey on influenza vaccination among community-dwelling elderly was conducted in Shanghai Taikang elderly community in November 2020. The information on demographic characteristics, reasons for refusal of vaccination, and measures for increasing vaccination rates were collected. Multiple logistic regression was used to analyze the correlation between influenza vaccination and sociodemographic and health-related characteristics.Results:Among 520 respondents, the vaccination rate was 30.58% (159/520). Compared with unvaccinated group, elderly in vaccinated group was older ( t=16.04, P=0.003)and more educated(χ2=8.16, P=0.043). The elderly with comorbid heart disease, chronic obstructive pulmonary disease, tumor, asthma, Parkinson′s disease were likely to have vaccination ( OR=1.45, 2.16, 1.23, 1.64, 5.83; all P<0.05).The reasons for the elderly not to be vaccinated were concerns of side effects (46.26%, 167/361), lack of doctors′ recommendations (24.10%, 87/361), and unnecessary for people with good health conditions (19.39%, 70/361). The independent factors of influenza vaccine awareness rate were healthcare providers′ recommendations ( OR=9.18, 95% CI:5.47-16.32), vaccination at home( OR=11.79, 95% CI:6.87-21.66),vaccination available in community( OR=8.08, 95% CI:8.08-15.45),the mandatory requirement ( OR=4.61,95% CI:4.61-10.11),free of charge( OR=7.48, 95% CI:4.08-15.12). Conclusion:Influenza vaccination coverage among the elderly in Shanghai is still low even during the COVID-19 pandemic. Policy interventions, awareness education and strengthening the primary healthcare resources may contribute to achieving a high influenza vaccine coverage rate in the community-dwelling elderly