BACKGROUND: P16 inactivation is frequently accompanied by telomerase reverse transcriptase ( TERT ) amplification in human cancer genomes. P16 inactivation by DNA methylation often occurs automatically during immortalization of normal cells by TERT . However, direct evidence remains to be obtained to support the causal effect of epigenetic changes, such as P16 methylation, on cancer development. This study aimed to provide experimental evidence that P16 methylation directly drives cancer development. METHODS: A zinc finger protein-based P16 -specific DNA methyltransferase (P16-Dnmt) vector containing a "Tet-On" switch was used to induce extensive methylation of P16 CpG islands in normal human fibroblast CCD-18Co cells. Battery assays were used to evaluate cell immortalization and transformation throughout their lifespan. Cell subcloning and DNA barcoding were used to track the diversity of cell evolution. RESULTS: Leaking P16-Dnmt expression (without doxycycline-induction) could specifically inactivate P16 expression by DNA methylation. P16 methylation only promoted proliferation and prolonged lifespan but did not induce immortalization of CCD-18Co cells. Notably, cell immortalization, loss of contact inhibition, and anchorage-independent growth were always prevalent in P16-Dnmt&TERT cells, indicating cell transformation. In contrast, almost all TERT cells died in the replicative crisis. Only a few TERT cells recovered from the crisis, in which spontaneous P16 inactivation by DNA methylation occurred. Furthermore, the subclone formation capacity of P16-Dnmt&TERT cells was two-fold that of TERT cells. DNA barcoding analysis showed that the diversity of the P16-Dnmt&TERT cell population was much greater than that of the TERT cell population. CONCLUSION P16 methylation drives TERT -mediated immortalization and transformation of normal human cells that may contribute to cancer development.
Humans ; Telomerase/genetics* ; DNA Methylation/physiology* ; Fibroblasts/cytology* ; Cyclin-Dependent Kinase Inhibitor p16/metabolism* ; Cell Line ; Cell Transformation, Neoplastic/genetics*

Tumor-infiltrating lymphocytes（TILs）are the main anti-tumor immune cells in the tumor microenvironment and play a crucial role in the immunotherapy of solid tumors. However，the presence of an immunosuppressive microenvironment limits their clinical efficacy. As one of the most abundant immunosuppressive cells in the tumor microenvironment，tumor-associated macrophages（TAMs）have a close connection with TILs and play an important role in the immunosuppression on TILs. This review discusses the application of TILs in the field of tumor therapy and their immunosuppressive bottlenecks，elaborates on the role of TAMs in tumor immunosuppression，and summarizes the effects of TAMs on the immune function of TILs through mechanisms such as cytokine secretion，exosome release，metabolic reprogramming，and epigenetic remodeling. In addition，this article also explores the possibility of targeting TAMs as a strategy to improve the anti-tumor efficacy of TILs，aiming to provide new ideas for addressing the immunosuppressive challenges faced by TILs.

Objective:To evaluate the association between pre-pregnancy urolithiasis and pre-eclampsia and to further explore the mediating effect of hyperuricemia in early pregnancy on the relationship between urolithiasis and pre-eclampsia.Methods:Pregnant women attending prenatal care in early pregnancy at 7 Maternal and Child Health Hospitals in Hunan Province from August 2014 to December 2019 were recruited to construct a cohort of early pregnancy. The paper questionnaire collected demographic data on pregnant women, pre-pregnancy disease history, and living habits, etc. Besides, the early pregnancy laboratory examination and pregnancy outcome for this pregnancy were derived from the hospital's electronic medical record system. Logistic regression models were used to analyze the association between pre-pregnancy urolithiasis and pre-eclampsia, and causal mediation analysis was used to investigate the mediating role and magnitude of hyperuricemia in early pregnancy in the association pathway between pre-pregnancy urolithiasis and pre-eclampsia. Results:A total of 33 579 naturally conceived singleton pregnant women were included in the analysis, of which 3 230 cases (9.6%) had hyperuricemia in early pregnancy, and 666 cases (2.0%) had pre-eclampsia. The multivariate logistic regression analysis indicated that pre-pregnancy urolithiasis increased the risk of pre-eclampsia ( OR=2.65, 95% CI: 1.56-4.51). Mediation analysis showed that after controlling for confounders, hyperuricemia in early pregnancy could mediate the association between pre-pregnancy urolithiasis and pre-eclampsia, with a mediation effect proportion of 46% ( P<0.05). Conclusions:Pre-pregnancy urolithiasis is an independent risk factor for pre-eclampsia, and early pregnancy hyperuricemia has a certain mediating effect between urolithiasis and pre-eclampsia.

Myeloid-derived cells (MDCs) are crucial in immune response and tissue homeostasis. They have high functional plasticity and can be polarized according to microenvironment signals. These cells, including macrophages, neutrophils, and dendritic cells (DCs), exhibit different functional polarization states in different pathological environments and are involved in the occurrence and development of diseases such as inflammation and tumors. Studies have shown that metabolic reprogramming plays a key role in the functional polarization of MDCs, affecting the cellular energy supply and regulating immune function. This paper reviews classification, function and polarization mechanism of MDCs and discusses metabolic reprogramming. In addition, the therapeutic strategies targeting MDC are summarized, which is expected to provide new targets for tumor immunotherapy.
Humans ; Tumor Microenvironment/immunology* ; Myeloid Cells/metabolism* ; Neoplasms/pathology* ; Animals ; Immunotherapy/methods* ; Dendritic Cells/immunology* ; Macrophages/immunology*

Astrocytes and microglia engage in extensive and complex communication and mutual effect, which referrs to microglia-astrocyte crosstalk. Recent studies have highlighted that this crosstalk plays a pivotal role in neurodegenerative diseases, exerting either protective or detrimental effects. This review briefly introduces the molecular mechanism of microglia-astrocyte crosstalk and its research progress in Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Parkinson's disease, aiming to provide new research directions and therapeutic targets for clinical improvement of neurodegenerative diseases from perspective of microglia-astrocyte crosstalk.

Objective To identify the reasons why the monitored personal doses of radiation worker A in an institution exceeded the investigation level in 2023 and 2024, and remind workers to wear personal dosimeters in a standardized manner in scenarios such as work and business trips to ensure the authenticity and reliability of the monitoring data. Methods A thermoluminescence measurement system was used to read the personal dosimeters worn by radiation workers. Investigations were carried out on personnel whose doses exceeded the investigation level described in the “Specifications for individual monitoring of occupational external exposure” (GBZ 128—2019). The reasons for doses exceeding the investigation level were analyzed using additional dosimeters and conducting on-site experiments. Results In 2023 and 2024, radiation worker A recorded a total of 5 personal dose equivalents exceeding the investigation level (1.23 mSv) over a total of 8 monitoring cycles (each lasting 90 days). Following one cycle where the dose exceeded the investigation level, two additional dosimeters (each for a 30-day cycle) were issued to worker A, revealing readings below the investigation level for the 30-day monitoring cycle (0.41 mSv). The reading for the dosimeter was 2-3 μSv per time when passing through an X-ray security scanner, and approximately 2.10 mSv per time when passing through a computed tomography security scanner. Conclusion Within a 90-day monitoring cycle, a single exposure of a personal dosimeter to a computed tomography security scanner can result in a dose exceeding the investigation level. Radiation workers should avoid placing dosimeters in backpacks or suitcases that pass through computed tomography security scanners during business trips, so as to reduce the impact of security scanner irradiation on personal dose monitoring.

Objective To explore the level characteristics of high mobility group protein B1(HMGB1)in patients with gestational diabetes mellitus(GDM)and its correlations with inflammation,insulin resistance,and placental vascular density.Methods A total of 70 patients with GDM who were hospitalized and delivered in the department of obstetrics of this hospital from August 2021 to May 2024 were selected as the study group,and another 70 healthy pregnant women during the same period were selected as the control group.The general clinical data,fasting plasma glucose(FPG),insulin resistance-related indicators[fasting insulin(FINS),homeostasis model assessment of insulin resistance(HOMA-IR)],serum inflammatory factors[C reactive protein(CRP),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)],the levels of HMGB1 in pla-cental tissues and peripheral blood,and the placental microvascular density were compared between the two groups.Pearson correlation analysis was used to evaluate the correlations between the levels of HMGB1 in se-rum and placental tissues and insulin resistance,inflammatory factors,and placental vascular density.Results The levels of FPG,FINS,HOMA-IR,CRP,TNF-α,IL-6,the average integrated optical density(IOD)value of HMGB1 in serum and placental tissues,and the percentage of HMGB1-positive cells in the study group were all higher than those in the control group(P＜0.05),while the placental microvascular den-sity was lower than that in the control group(P＜0.05).Pearson correlation analysis showed that the serum HMGB1 level,the average IOD value of HMGB1 in placental tissues,and the percentage of HMGB1-positive cells in the study group were all positively correlated with the levels of HOMA-IR,CRP,TNF-α,and IL-6(P＜0.05),and negatively correlated with the placental microvascular density(P＜0.05).Conclusion The level of HMGB1 in peripheral blood and placental tissues of GDM patients is higher than that of healthy preg-nant women,and it is correlated with inflammatory factors,HOMA-IR and the placental microvascular density.

Objective Hypobaric chamber and simulated weightless bed are essential methods for aerospace medical research,and conducting state assessment of volunteers before and after hypobaric chamber and simulated weightless bed tests is an essential guideline for aerospace implementation medicine.To further improve the efficiency of human condition assessment,in addition to the conventional biochemical and physiological indicators,the human oral exhaled gas can be used for condition assessment,and the olfactometry acquisition equipment and analysis software can collect and detect most volatile gases to complete the human oral exhaled gas data acquisition.Conducting comparative analysis of olfactory mapping data from different populations may be a means to assess the status of the body.Methods The olfactometry acquisition equipment was used to collect the oral exhaled breath olfactometry profiles of the general population,hypobaric cabin volunteers,and ambulatory volunteers.The olfactometry analysis software was used to calculate the 12 eigenvalues of the olfactometry profiles and the t-SNE downscaling,and the radar plots were used to analyze the olfactometry profiles of the general population,low-pressure cabin volunteers,and ambulatory volunteers respectively.A comparative analysis of different populations was conducted.Results(1)The t-SNE mapping data of the general population and the ambulatory volunteers were almost indistinguishable;(2)the t-SNE mapping data of the hypobaric cabin volunteers and the general population had a slight overlap,but the distinguishability of the vast majority of the t-SNE mapping data was obvious;(3)the t-SNE mapping data of the hypobaric cabin volunteers and the ambulatory volunteers were distinguishable with no overlap,and the ambulatory t SNE data are highly aggregated,and the distribution of t-SNE data in low-pressure cabin is more discrete;(4)there are 2-3 sensors with large eigenvalues and a large range of variation for both low-pressure cabin volunteers and recumbent volunteers after training activities,and the common sensor with a large range of variation is S6.Conclusion Olfactory diagnostic analysis mapping may be a means to assess the health status of the body and may be useful for spaceflight health status assessment in the future.The analysis and application of flight health state assessment can be a reference in the future.

The elimination of biofilms is a crucial step in controlling hospital-acquired infections.Once biofilms colonize luminal instruments,it is difficult to remove them using traditional disinfection methods.Conventional disinfection approaches now face a series of challenges,including microbial resistance,corrosiveness,cytotoxicity,residual disinfection byproducts,and environmental pollution.Therefore,developing novel disinfection technologies specifically targeting biofilm removal is vitally important.New disinfection technologies,such as slightly acidic electrolyzed water,plasma technology,surface modification techniques,nanomaterial-based disinfection,bacteriophage disinfection,and enzymatic disinfection,are constantly emerging.These technologies exhibit excellent performance against biofilms by leveraging the synergistic effects of multiple mechanisms,including the reactive oxygen species(ROS)burst,photocatalytic oxidation,physical disruption,and biological targeting.This review summarizes the characteristics,underlying mechanisms,and potential application scenarios of these novel disinfection technologies,with a particular focus on their effects against biofilms formed by common pathogenic bacteria on surfaces in hospital settings.It aims to provide a reference basis for the practical application and translation of these disinfection technologies and the development of new disinfection strategies.