Malignant gastrointestinal tumors （GT） mainly include laryngeal cancer， esophageal cancer， gastric cancer， pancreatic cancer， hepatocellular carcinoma， bile duct cancer， and colorectal cancer. At present， the morbidity and mortality of GT are high. Tumor immune escape is one of the key reasons for cancer development and treatment failure， and it is also the main direction of current tumor immunotherapy research. Traditional Chinese medicine （TCM） plays a role in treating GT and alleviating systemic symptoms， especially showing potential advantages in regulating the immune escape mechanism. This article elaborates on the immune escape mechanism of GT and systematically reviews that TCM active components or compound prescriptions act on key immune checkpoints such as programmed cell death protein-1 （PD-1） and programmed cell death ligand-1 （PD-L1） to reduce the proportion of marrow-derived suppressor cells （MDSCs）， promote the polarization of M1 macrophages， activate effector immune cells， enhance CD8⁺ T cell recruitment and interferon （IFN）-γ secretion， enhance the killing activity of natural killers （NKs）， and reduce foxhead box protein P3（FoxP3⁺）-positive regulatory T （Treg） cell infiltration. TCM active components or compound prescriptions can remodel the tumor microenvironment （TME）， such as improving immunosuppressive factors， promoting vascular normalization， and regulating intestinal microbiota. Through the regulation of TME， enhancement of antigen presentation， inhibition of immune checkpoint molecules， regulation of cellular network factors and metabolites， etc.， TCM active components or compound prescriptions enhance the immune function， thereby inhibiting the immune escape of GT. This paper summarizes and reflects on the research results of TCM in regulating immune escape to treat GT in recent years， aiming to help transform TCM from empirical medication to precision treatment based on immune regulation， reduce drug resistance and enhance treatment effect.

Background Occupational stress is an important factor affecting the health of working population, wellness is a topic that has received much attention in recent years, and sleep quality and wellness have a certain impact on occupational stress. Objective To understand the current situation of occupational stress among locomotive engineers in in the Yangtze River Delta, explore the influence of well-being and sleep quality on occupational stress, and provide a theoretical basis for occupational stress intervention among locomotive engineers. Methods Sampling was conducted from October to December 2022 using stratified random sampling. The Chinese version of the Brief Occupational Tension Questionnaire based on the Job Demand-Control Model (JDC model), the World Health Organization 5-item Well-Being Index (WHO-5), and the Pittsburgh Sleep Quality Index (PSQI) scale were used to investigate the occupational stress, well-being, and sleep quality of locomotive engineers. Logistic regression was used to analyze the effects of sleep quality and well-being on occupational stress, and additive and multiplicative interaction models were applied to evaluate the interactive effects of well-being and sleep quality on occupational stress. Results A total of 8243 questionnaires were collected from five locomotive companies, and after excluding unqualified questionnaires, a total of 7976 questionnaires were included in the analysis. The number of locomotive engineers in the Yangtze River Delta reporting positive occupational stress was 4633 (58.09%), the number of low-level well-being was 4949 (62.05%), and the number of poor sleep quality was 4129 (51.77%). The distribution of occupational stress varied by age, length of service, region, technical level, nature of vehicle, education, per capita monthly family income, marital status, smoking, drinking, number of exercise sessions per week, quality of sleep, work shifts, and length of commute (P<0.01). The results of logistic regression showed that a lower level of occupational stress was associated with >11000 yuan per capita monthly household income (OR=0.795, 95%CI: 0.656, 0.964), high level of well-being (OR=0.477, 95%CI: 0.430, 0.528), and good sleep quality (OR=0.588, 95%CI: 0.531, 0.651); a higher level of occupational stress was associated with night shifts: 1 or fewer night shifts (OR=1.707, 95%CI: 1.312, 2.221), 2 to 3 night shifts (OR=2.649, 95%CI: 2.111, 3.325), and 4 or more night shifts (OR=2.804, 95%CI: 2.202, 3.571); a higher level of occupational stress was associated with 60 min or more commuting time (OR=1.353, 95%CI: 1.111, 1.646). Regarding interaction between poor sleep quality and low well-being on occupational stress, the relative excess risk ratio (RERI), attributable risk index (API), and synergy index (SI) were 1.451 (1.059, 1.844), 0.417 (0.327, 0.507), and 2.407 (1.787, 3.241), respectively, and the result of the multiplicative interaction was an OR of 1.546 (95%CI: 1.262, 1.893). Conclusion The prevalence of occupational stress among locomotive engineers in the Yangtze River Delta region is generally at a medium level compared with other industries. Good sleep quality reduces the risk of occupational stress to a greater extent than high well-being, and poor sleep quality and low well-being can interact and further increase the risk of occupational stress.

Background The development of railways has a long history, but there is limited research on the health of railway workers at home and abroad. China's high-speed railway development has attracted worldwide attention in recent years, and it is of great significance to study how to promote the health of this occupational population to ensure the safety of railway transportation. Objective To identify development trends and hotspots in the field of railway workers' health at home and abroad. Methods The research literature related to the health of railroad workers dated from January 1, 1973 to December 31, 2022 was searched using the China Knowledge Network Infrastructure (CNKI) and Web of Science Core Collection (WoS) databases. After screening and cleaning, the included literature was subjected to bibliometric analysis by applying CiteSpace 6.1R6 software to visualize and analyze literature co-citation, keyword emergence, and keyword timeline graphs, and by VOSviewer 1.6.19 to visualize and analyze country/region collaboration, keyword co-occurrence, and keyword clustering. Results During the period from 1973 until 2022, a total of 273 Chinese literature and 165 English literature were found to report studies related to the health of railway workers. The Chinese literature began to grow rapidly in 2009 and peaked in 2015, and the number of English literature published in a relatively flat state over the studied period. The country with the most papers indexed by Science Citation Index (SCI) was the United States (58 papers), which also presented the richest international collaborations. The document with the highest domestic citation frequency was published in the Chinese Journal of Mental Health in 1994, and the document with the highest SCI citation frequency was published in the American Journal of Epidemiology in 1994. The keyword co-occurrence analysis showed that the included Chinese literature mainly focused on health checkups, health management, hypertension, mental health, and chronic diseases and their prevalence; the included English literature focused on mortality, lung cancer, epidemiology, and diesel engine exhaust and its exposure. The analysis of emergent words showed that health management, frontline workers, and occupational stress were the topics of interest in Chinese literature in the last five years, while occupational stress, diesel exhaust emissions, and noise exposure were the topics of interest in English literature in the last ten years. The results of the timeline graph analysis suggested that the recent research directions in Chinese literature were health intervention, humanistic care, staff canteens, etc. There were few English-language articles related to this area after 2010. Conclusion The research hotspots of railroad practitioners' health will keep changing with the development of high-speed railways in countries around the world. The outstanding rise of Chinese literature issued in the last decade has been in striking contrast to the slow progress and decreasing of English literature. The Chinese literature has gradually expanded the hotspots from chronic diseases to health management, occupational stress, and sleep disorders.

Objective To investigate the effects and mechanisms of melatonin(MT)on improving oocyte quality in mice exposed to benzophenone-3(BP-3).Methods In this study,6～12-week-old female ICR mice were cultured in vitro in M16 culture,0.8 μmol/L BP-3 medium and 1 × 10-7 mol/L MT+0.8 μmol/L BP-3 mixed culture.Female ICR mice were randomly segregated into three groups:control,BP-3,and BMT.The control group received 0.5 mL of purified water,the BP-3 group was administered 0.5 mL of a 0.8 μmol/L BP-3 solution,and the BMT group received 0.5 ml of a combination of 0.8 μmol/L BP-3 and 15 mg/kg MT solution via gavage once daily for four weeks,to facilitate in vivo experimentation.Subsequently,the oocyte maturity rate,transcription levels and protein expression levels of mitochondrial dynamics-related genes Mfn1,Opa1,Fis1 and Drp1,mitochondrial membrane potential and spindle morphology were detected in the three groups to explore the rescue effect of MT on the mitochondria of BP-3-exposed mice.Results Compared to the control group,MT treatment markedly enhanced the transcription and protein levels of the mitochondrial fusion genes Mfn1 and Opa1 in oocytes,while concurrently down-regulating the mRNA and protein levels of the mitochondrial fission genes Fis1 and Drp1.Additionally,the BMT group exhibited significantly lower levels of ROS and abnormal spindle morphology in their oocytes compared to the BP-3 group,yet their mitochondrial membrane potential was notably elevated.Conclusion Physiological concentration of BP-3 exposure was toxic for reproduction,but the addition of appropriate concentrations of MT could significantly improve the mitochondrial dynamics and developmental potential of oocytes in BP-3-exposed mice.

Objective To investigate the effects and mechanisms of melatonin(MT)on improving oocyte quality in mice exposed to benzophenone-3(BP-3).Methods In this study,6～12-week-old female ICR mice were cultured in vitro in M16 culture,0.8 μmol/L BP-3 medium and 1 × 10-7 mol/L MT+0.8 μmol/L BP-3 mixed culture.Female ICR mice were randomly segregated into three groups:control,BP-3,and BMT.The control group received 0.5 mL of purified water,the BP-3 group was administered 0.5 mL of a 0.8 μmol/L BP-3 solution,and the BMT group received 0.5 ml of a combination of 0.8 μmol/L BP-3 and 15 mg/kg MT solution via gavage once daily for four weeks,to facilitate in vivo experimentation.Subsequently,the oocyte maturity rate,transcription levels and protein expression levels of mitochondrial dynamics-related genes Mfn1,Opa1,Fis1 and Drp1,mitochondrial membrane potential and spindle morphology were detected in the three groups to explore the rescue effect of MT on the mitochondria of BP-3-exposed mice.Results Compared to the control group,MT treatment markedly enhanced the transcription and protein levels of the mitochondrial fusion genes Mfn1 and Opa1 in oocytes,while concurrently down-regulating the mRNA and protein levels of the mitochondrial fission genes Fis1 and Drp1.Additionally,the BMT group exhibited significantly lower levels of ROS and abnormal spindle morphology in their oocytes compared to the BP-3 group,yet their mitochondrial membrane potential was notably elevated.Conclusion Physiological concentration of BP-3 exposure was toxic for reproduction,but the addition of appropriate concentrations of MT could significantly improve the mitochondrial dynamics and developmental potential of oocytes in BP-3-exposed mice.

BACKGROUND: Ischemic acute kidney injury (AKI) is a common syndrome associated with considerable mortality and healthcare costs. Up to now, the underlying pathogenesis of ischemic AKI remains incompletely understood, and specific strategies for early diagnosis and treatment of ischemic AKI are still lacking. Here, this study aimed to define the transcriptomic landscape of AKI patients through single-cell RNA sequencing (scRNA-seq) analysis in kidneys. METHODS: In this study, scRNA-seq technology was applied to kidneys from two ischemic AKI patients, and three human public scRNA-seq datasets were collected as controls. Differentially expressed genes (DEGs) and cell clusters of kidneys were determined. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as the ligand-receptor interaction between cells, were performed. We also validated several DEGs expression in kidneys from human ischemic AKI and ischemia/reperfusion (I/R) injury induced AKI mice through immunohistochemistry staining. RESULTS: 15 distinct cell clusters were determined in kidney from subjects of ischemic AKI and control. The injured proximal tubules (PT) displayed a proapoptotic and proinflammatory phenotype. PT cells of ischemic AKI had up-regulation of novel pro-apoptotic genes including USP47 , RASSF4 , EBAG9 , IER3 , SASH1 , SEPTIN7 , and NUB1 , which have not been reported in ischemic AKI previously. Several hub genes were validated in kidneys from human AKI and renal I/R injury mice, respectively. Furthermore, PT highly expressed DEGs enriched in endoplasmic reticulum stress, autophagy, and retinoic acid-inducible gene I (RIG-I) signaling. DEGs overexpressed in other tubular cells were primarily enriched in nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, estrogen signaling, interleukin (IL)-12 signaling, and IL-17 signaling. Overexpressed genes in kidney-resident immune cells including macrophages, natural killer T (NKT) cells, monocytes, and dendritic cells were associated with leukocyte activation, chemotaxis, cell adhesion, and complement activation. In addition, the ligand-receptor interactions analysis revealed prominent communications between macrophages and monocytes with other cells in the process of ischemic AKI. CONCLUSION Together, this study reveals distinct cell-specific transcriptomic atlas of kidney in ischemic AKI patients, altered signaling pathways, and potential cell-cell crosstalk in the development of AKI. These data reveal new insights into the pathogenesis and potential therapeutic strategies in ischemic AKI.
Humans ; Mice ; Animals ; Transcriptome/genetics* ; Ligands ; Kidney/metabolism* ; Acute Kidney Injury/metabolism* ; Ischemia/metabolism* ; Reperfusion Injury/metabolism* ; Sequence Analysis, RNA ; Adaptor Proteins, Signal Transducing/metabolism* ; Tumor Suppressor Proteins/metabolism*

Objective To investigate the effect of Echinococcus granulosus cyst fluid(EgCF) on the cytoskeletal rearrangement and phagocytosis and the migration of macrophages induced by lipopolysaccharide(LPS). Methods Peritoneal macrophages of C57BL/6 mice were isolated and cultured in vitro, and divided into control group and LPS group and LPS combined with EgCF group. After 48 hours of treatment, filamentous actin (F-actin) changes were observed with rhodamine-labelled phalloidin staining and fluorescence microscopy; Transwell^TM chamber was used to test cell migration ability and flow cytometry to test cell phagocytosis. After 1 hour of treatment, PI3K and AKT, phosphorylated AKT (p-AKT), Rac1, guanosine triphospho-Rac1 (GTP-Rac1), WASP and Arp2 protein expressions were detected with Western blot analysis. Results Compared with the control group, after LPS stimulation, macrophages were deformed significantly; pseudopodia increased; actin cytoskeleton increased and was more distributed in pseudopodia; the ability of migration and phagocytosis were significantly improved, and the expression of PI3K, p-AKT, GTP-Rac1, WASP and Arp2 proteins significantly increased. EgCF treatment caused cell shrinkage and disappearance of pseudopodia protrusions of LPS-activated cells, and led to the reduced phagocytic and migratory of cells; the protein expression of PI3K, p-AKT, GTP-Rac1, WASP and Arp2 decreased significantly compared with the LPS group. Conclusion LPS induces the migration and enhances phagocytosis of macrophages while EgCF inhibits these effects, which is related to actin cytoskeleton rearrangement.
Mice ; Animals ; Lipopolysaccharides/pharmacology* ; Echinococcus granulosus/metabolism* ; Proto-Oncogene Proteins c-akt ; Cyst Fluid/metabolism* ; Mice, Inbred C57BL ; Macrophages/metabolism* ; Phagocytosis ; Actins/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Guanosine Triphosphate/pharmacology*

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Objective: To check Forkhead box M1 (FoxM1) expression in nasal mucosal of chronic rhinosinusitis (CRS) patients and the effect of inflammatory factors on FoxM1 expression, in order to research the significance of FoxM1 in CRS. Methods: From January to October of 2018, 50 patients hospitalized in the Department of Otorhinolaryngology, Head and Neck Surgery, First Affiliated Hospital of Nanchang University were enrolled in this study. Twenty CRS patients with polyps (CRSwNP), 20 CRS patients without nasal polyps (CRSsNP) and 10 patients with simple deviation of nasal septum (the control groups) were selected. The expression of FoxM1 in nasal mucosa of these patients was detected by immunohistochemistry (IHC) and real-time fluorescent quantitative PCR (qRT-PCR). Meanwhile, HE stain was used to observe the pathologic changes in each sample. By establishing human nasal epithelium cells cultivating model in vitro and identifying via immumofluorescence method, experimental group and control group were set up, then activation factors including interleukin (IL)-1β, IL-4, IL-5, IL-17, interferon-γ (IFN-γ) and staphylococcal entemtoxin B (SEB) were added in the models after stabilizing passage, and qRT-PRC and Western blot method were applied to check the expressing change of FoxM1. Software SPSS 18.0 was used for statistical analysis. Results: HE stain showed that the mainly pathologic change in nasal mucosa of CRS patients with or without nasal polyp was mucosal epithelial cells, goblet cell and submucosal gland hyperplasia, accompanied by a large number of inflammatory cells infiltration. The result of IHC demonstrated that both of the expression of FoxM1 in nasal mucosal tissue of CRS patients in the CRSwNP and CRSsNP groups exceed that of the control group (80% vs 75% vs 20%, χ² value was 10.000, 8.213, respectively, all P<0.05); there was no difference of expression between the two groups of CRS patients (χ²=0.143, P>0.05). The result of qRT-PCR demonstrated that the expression of FoxM1 mRNA in nasal mucosa of CRSwNP and CRSsNP was increased compared with that of the control group (3.309±1.511 vs 3.261±1.336 vs 1.000±0.774, t value was 4.519, 4.928, respectively, all P<0.05), but the difference between the two groups of CRS patients had no statistic significance (t=0.107, P=0.909). Nasal mucosa epithelial cells cultivating models was established successfully. Q-RT PCR and Western blot were conducted after stimulation of 100 ng/ml IL-1β, IL-4, IL-5, IL-17, IFN-γ and SEB for 36 h, and the proteins expression levels of FoxM1 exceeded the groups without stimulation with statistic significance. Conclusions The expression of FoxM1 in CRS increases and many types of cytokine can induce the increase of FoxM1 in human nasal epithelial cells. FoxM1 may participate in the process of pathogenesis in CRS.

Objective: To compare the differences in the stress distribution in simulated first molars prepared with three rotary nickel-titanium instruments. Methods : Four simulated first molars were prepared without instruments and with Reciproc, WaveOne and Protaper. Before and after preparation, each simulated molar was scanned by Micro-CT. The data were imported to Mimics 16.0 software to establish three-dimensional models. Finite element analysis was processed with Abaqus 6.14 software under conditions of longitudinal and lateral load. Results: Under vertical load conditions, the maximum von Mises stress of the enamel increased by 1.36%, 21.48% and 20.99% in the Reciproc, WaveOne and Protaper groups, respectively, after preparation, while the maximum von Mises stress of the cementum increased by 55.98%, 41.18% and 33.04%, respectively, and the maximum von Mises stress of the alveolar bone increased by 45.55%, 40.37% and 24.09%, respectively. Under 45° lateral load conditions, the maximum von Mises stress of the enamel increased by 1.79%, -4.58% and 3.82% in the Reciproc, WaveOne and Protaper groups, respectively, after preparation, while the maximum von Mises stress of cementum increased by 16.33%, 7.58% and 4.32%, respectively, and the maximum von Mises stress of the alveolar bone increased by 46.82%, 36.40% and 8.29%, respectively. Under the same conditions, the von Mises stresses of the cementum and alveolar bones of the simulated molars were higher after preparation than before preparation, especially under lateral load conditions. The stress was focused on the border between the crown and the root. The von Mises stress of the cementum and alveolar bones increased much more in the Reciproc group than in the other two groups under both conditions. Conclusion The von Mises stress of simulated molars was greater after preparation than before preparation. The von Mises stress of the cementum and alveolar bones increased much more in the Reciproc group than in the other two groups.