The innate immune system can be boosted in response to subsequent triggers by pre-exposure to microbes or microbial products, known as “trained immunity”. Compared to classical immune memory, innate trained immunity has several different features. Firstly, the molecules involved in trained immunity differ from those involved in classical immune memory. Innate trained immunity mainly involves innate immune cells (e.g., myeloid immune cells, natural killer cells, innate lymphoid cells) and their effector molecules (e.g., pattern recognition receptor (PRR), various cytokines), as well as some kinds of non-immune cells (e.g., microglial cells). Secondly, the increased responsiveness to secondary stimuli during innate trained immunity is not specific to a particular pathogen, but influences epigenetic reprogramming in the cell through signaling pathways, leading to the sustained changes in genes transcriptional process, which ultimately affects cellular physiology without permanent genetic changes (e.g., mutations or recombination). Finally, innate trained immunity relies on an altered functional state of innate immune cells that could persist for weeks to months after initial stimulus removal. An appropriate inducer could induce trained immunity in innate lymphocytes, such as exogenous stimulants (including vaccines) and endogenous stimulants, which was firstly discovered in bone marrow derived immune cells. However, mature bone marrow derived immune cells are short-lived cells, that may not be able to transmit memory phenotypes to their offspring and provide long-term protection. Therefore, trained immunity is more likely to be relied on long-lived cells, such as epithelial stem cells, mesenchymal stromal cells and non-immune cells such as fibroblasts. Epigenetic reprogramming is one of the key molecular mechanisms that induces trained immunity, including DNA modifications, non-coding RNAs, histone modifications and chromatin remodeling. In addition to epigenetic reprogramming, different cellular metabolic pathways are involved in the regulation of innate trained immunity, including aerobic glycolysis, glutamine catabolism, cholesterol metabolism and fatty acid synthesis, through a series of intracellular cascade responses triggered by the recognition of PRR specific ligands. In the view of evolutionary, trained immunity is beneficial in enhancing protection against secondary infections with an induction in the evolutionary protective process against infections. Therefore, innate trained immunity plays an important role in therapy against diseases such as tumors and infections, which has signature therapeutic effects in these diseases. In organ transplantation, trained immunity has been associated with acute rejection, which prolongs the survival of allografts. However, trained immunity is not always protective but pathological in some cases, and dysregulated trained immunity contributes to the development of inflammatory and autoimmune diseases. Trained immunity provides a novel form of immune memory, but when inappropriately activated, may lead to an attack on tissues, causing autoinflammation. In autoimmune diseases such as rheumatoid arthritis and atherosclerosis, trained immunity may lead to enhance inflammation and tissue lesion in diseased regions. In Alzheimer’s disease and Parkinson’s disease, trained immunity may lead to over-activation of microglial cells, triggering neuroinflammation even nerve injury. This paper summarizes the basis and mechanisms of innate trained immunity, including the different cell types involved, the impacts on diseases and the effects as a therapeutic strategy to provide novel ideas for different diseases.

OBJECTIVE: Poxviruses are zoonotic pathogens that infect humans, mammals, vertebrates, and arthropods. However, the specific role of ticks in transmission and evolution of these viruses remains unclear. METHODS: Transcriptomic and metatranscriptomic raw data from 329 sampling pools of seven tick species across five continents were mined to assess the diversity and abundance of poxviruses. Chordopoxviral sequences were assembled and subjected to phylogenetic analysis to trace the origins of the unblasted fragments within these sequences. RESULTS: Fifty-eight poxvirus species, representing two subfamilies and 20 genera, were identified, with 212 poxviral sequences assembled. A substantial proportion of AT-rich fragments were detected in the assembled poxviral genomes. These genomic sequences contained fragments originating from rodents, archaea, and arthropods. CONCLUSION Our findings indicate that ticks play a significant role in the transmission and evolution of poxviruses. These viruses demonstrate the capacity to modulate virulence and adaptability through horizontal gene transfer, gene recombination, and gene mutations, thereby promoting co-existence and co-evolution with their hosts. This study advances understanding of the ecological dynamics of poxvirus transmission and evolution and highlights the potential role of ticks as vectors and vessels in these processes.
Animals ; Poxviridae/physiology* ; Ticks/virology* ; Phylogeny ; Transcriptome ; Evolution, Molecular ; Poxviridae Infections/virology* ; Genome, Viral

OBJECTIVES: To characterize fine particulate matter (PM _2.5)-bound polycyclic aromatic hydrocarbons (PAHs) emitted from different cooking fumes and their exposure routes and assess their health-associated impact to provide a reference for health risk prevention from PAH exposure across different age and sex groups. METHODS: Sixteen PM _2.5-bound PAHs emitted from 11 cooking styles were analyzed using GC-MS/MS. The health hazards of these PAHs in the Handan City population (stratified by age and sex) were predicted using the incremental lifetime cancer risk ( ILCR) model. The respiratory deposition doses ( RDDs) of the PAHs in children and adults were calculated using the PM _2.5 deposition rates in the upper airway, tracheobronchial, and alveolar regions. RESULTS: The total concentrations of PM _2.5-bound PAHs ranged from 61.10 to 403.80 ng/m ³. Regardless of cooking styles, the ILCR _total values for adults (1.23 × 10 ^-6 to 3.70 × 10 ^-6) and older adults (1.28 × 10 ^-6 to 3.88 × 10 ^-6) exceeded the acceptable limit of 1.00 × 10 ^-6. With increasing age, the ILCR _total value first declined and then increased, varying substantially among the population groups. Cancer risk exhibited particularly high sensitivity to short exposure to barbecue-derived PAHs under equivalent body weights. Furthermore, barbecue, Sichuan and Hunan cuisine, Chinese cuisine, and Chinese fast food were associated with higher RDDs for both adults and children. CONCLUSION ILCR _total values exceeded the acceptable limit for both females and males of adults, with all cooking styles showing a potentially high cancer risk. Our findings serve as an important reference for refining regulatory strategies related to catering emissions and mitigating health risks associated with cooking styles.
Humans ; Polycyclic Aromatic Hydrocarbons/analysis* ; Cooking/methods* ; Male ; Female ; Particulate Matter/analysis* ; Adult ; Child ; Middle Aged ; Air Pollutants/analysis* ; Adolescent ; Air Pollution, Indoor/analysis* ; Young Adult ; Child, Preschool ; Aged ; China ; Inhalation Exposure ; Age Factors ; Sex Factors ; Cities ; Infant

Objective To explore the effectiveness of an integrated laparoscopic simulation training course (best essential surgical technique training, BEST) in enhancing laparoscopic peritoneal suturing techniques in surgical residents.Methods As an integrated two-stage program, the BEST course applied basic laparoscopic training system with simple molds in phase Ⅰ training, and then adopted advanced laparoscopic training system, 3D Laparoscope and ex-vivo animal models in phase Ⅱ training. The laparoscopic suturing techniques were practiced in phase Ⅱ training. From August 2021 to July 2024, surgical residents in the second year of the national standardized training program were divided into pilot and control groups based on whether they had undergone the BEST course. Two cases of laparoscopic peritoneal suture were performed by the surgical residents under supervision in the department of gastrointestinal surgery. The operative time, quality of suture, and independent completion rate were compared between the two groups.Results A total of 33 surgical residents (19 in pilot group and 14 in control group) were included in this study, and a total of 66 cases of laparoscopic peritoneal suture were performed (38 in pilot group and 28 in control group). The operative time was significantly shorter in pilot group than that in control group (15.7 min vs. 17.5 min, P=0.025). The quality of suture was significantly better in pilot group compared to control group (P=0.023). In pilot group, all peritoneal sutures were performed by residents independently, whereas in control group, 3 cases (10.7%) were assisted by the supervisor, and the independent completion rate was different significantly (P=0.039).Conclusions The BEST course can help improve surgical residents′ laparoscopic peritoneal suturing techniques and could be promoted in the national standardized training program for surgical residents.

Objective:To investigate effective strategies to reduce the high risk of recurrence after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in patients with minimal residual disease(MRD)-positive B-lineage acute lymphoblastic leukemia(B-ALL).Methods:A retrospective analysis was performed for ten B-ALL patients with positive MRD before transplantation at our center from November 2022 to November 2024.There were four male patients and six female patients,with a median age of 30(7-56)years.Of all patients,four received transplantation from unrelated donors,and six received haploidentical transplantation from relatives.All ten patients received blinatumomab(28 μg/day for 14 days for patients≥45 kg;5 μg/m2/day for 14 days for patients<45 kg)and were bridged to the conditioning regimen for allo-HSCT within 7 days.Results:After treatment with blinatumomab,all ten patients achieved the clearance of MRD.After allo-HSCT,100%of the patients achieved donor hematopoietic reconstitution.The median time to neutrophil reconstitution was 12(9-22)days,and the median time to platelet reconstitution was 13.5(9-22)days.As of January 2025,the median observation time was 14(2-26)months;of all patients,two experienced recurrence,and one had positive MRD again,with a recurrence rate of 20%.Among the ten patients,nine survived and one died of disease recurrence.One patient achieved complete re-mission again after chimeric antigen receptor T-cell(CAR-T)therapy following recurrence,and the patient with positive MRD achieved the clearance of MRD again after interleukin-2 treatment;both patients were currently alive.During treatment,one patient developed cytokine release syndrome,one patient was comorbid with SARS-CoV-2 infection,one patient had herpes zoster and viral encephalitis,three patients developed grade Ⅰ-Ⅱ acute graft-versus-host disease,and four patients developed chronic graft-versus-host disease;no transplantation-associated thrombotic microangiopathy was observed.Conclusion:For patients with MRD-positive B-ALL,blinatumomab as a bridge therapy for allo-HSCT can significantly reduce recurrence after transplantation,with fewer complica-tions that are easy to control.Multicenter randomized controlled clinical studies can be performed to further verify its efficacy and safety.

This work was aimed at analyzing the protein characteristics of Coiled-Coil Domain-Containing Protein 115(CCDC115)and using Ccdc115-deficient mouse monocyte-macrophage leukemia cells(RAW264.7)to explore the influence of CCDC115 on the intracellular survival of Salmonella Typhimurium.Bioinformatics analysis was conducted to examine the fundamental attributes of CCDC115,which was determined to be an unstable protein consisting of two α-helices and an intervening disordered re-gion,devoid of any transmembrane structural domains.A RAW264.7-Ccdc115-KO cell line was successfully established with CRISPR/Cas9 gene-editing technology.To elucidate the effects of CCDC115 on the intracellular survival of Salmonella Typhimurium,we infected RAW264.7 cells with Salmonella Typhimurium.The expression of CCDC115 was found to be upregulated at both the mRNA and protein levels post-infection,according to RT-qPCR and western blot analysis.Via counting of colony-forming units(CFU),the proliferation rate of Salmonella Typhimurium within RAW264.7-Ccdc115-KO cells was found to be 1.5-fold higher than that in RAW264.7 cells.Acidification imaging studies indicated that,whereas Salmonella Typhimurium phagosomes underwent acidifi-cation in RAW264.7 cells,this process was absent in RAW264.7-Ccdc115-KO cells.In conclusion,the study successfully estab-lished a RAW264.7-Ccdc115-KO cell line and demonstrated that the expression of CCDC115 is elevated during Salmonella Ty-phimurium infection,thus potentially inhibiting the intracellular survival of Salmonella Typhimurium by facilitating phagosome acidifi-cation.This study lay a theoretical foundation for functional studies of CCDC115 and the investigation of mechanisms regulating the survival of intracellular Salmonella Typhimurium.

Objective:To investigate the application of the conjugate gradient (CG) algorithm to treatment plan optimization for intensity-modulated brachytherapy (IMBT).Methods:The general Monte Carlo software TOPAS was utilized to simulate the 192Ir source of IMBT, and the unit dose contribution matrix was calculated. An objective function was established using the weighted least squares method and was solved using the CG algorithm to achieve optimized IMBT treatment plans. The optimization was validated using five clinical cervical cancer cases under modulation width 60°. The dose distributions of IMBT treatment plans under 45°, 60°, 90°, 120°, and 180° modulation widths were compared using the Wilcoxon test to determine the optimal IMBT treatment plan for cervical cancer treatment. Results:The CG algorithm successfully optimized IMBT treatment plans under modulation width 60° for five cases within 22.2 s on average. On the premise of sufficient target dose coverage, the average D2 cm 3 values of the bladder and rectum in IMBT treatment plans were 3.66 and 1.97 Gy, respectively, representing reductions of 0.54 and 0.69 Gy compared to traditional brachytherapy plans. For the five modulation widths, the D90% values of all IMBT treatment plans reached 6 Gy, without statistically significant differences ( P > 0.05). The average D2 cm 3 values of the bladder in IMBT treatment plans were significantly lower than those in the traditional brachytherapy plans( P<0.05), with modulation width 60° associated with the greatest reduction of 0.61 Gy. In contrast, the average D2 cm 3 values of the rectum under 45°, 60°, and 90° modulation widths decreased by 0.63, 0.54, and 0.45 Gy, respectively, compared to traditional plans, with statistically significant differences( P<0.05). Conclusions:The CG method enables rapid achievement of optimized IMBT treatment plans that meet clinical requirements, and modulation width 60° contributes to valid dosimetric optimization. This study can serve as a guide for the clinical implementation of IMBT.

The contents of the female inguinal hernia include abdominal organs such as ovaries and fallopian tubes, and most of these are the result of sliding hernias. However, it is worth noting for surgeons specialized in hernia and abdominal wall surgery that there is a rare clinical diagnosis of hernia uterine inguinale, which is commonly seen in the Müllerian anomaly. Combined with relevant research progress at home and abroad, as well as the clinical experience in the diagnosis and treatment of patients with inguinal uterine hernia caused by Müllerian duct anomaly, the authors systematically introduce the clinical manifes-tations, key diagnosis and treatment points of female Müllerian duct anomaly in the inguinal region.

Objective:To identify risk factors associated with endoscopic atrophic progression of gastric mucosa after Helicobacter pylori ( HP) eradication and to develop a risk scoring system for establishing an individualized endoscopic follow-up strategy for patients with chronic gastritis. Methods:This retrospective cohort study included chronic gastritis patients with successful HP eradication at the Department of Gastroenterology, Beijing Friendship Hospital between January 2018 and October 2021. Demographic characteristics, endoscopic findings, and other clinical data were analyzed. Endoscopic outcomes of gastric mucosal atrophy before and after follow-up were compared to classify patients into progression and non-progression groups. Univariate and multivariate analyses were performed to identify independent risk factors for endoscopic atrophic progression. A risk scoring system was then constructed based on these factors. Results:A total of 218 patients with chronic gastritis were included, including 153 in the non-progression group and 65 in the progression group. Multivariate logistic regression analysis showed that gastric ulcer ( P=0.008, OR=4.24, 95% CI: 1.46-12.25), history of proton pump inhibitor use ( P=0.007, OR=4.06, 95% CI: 1.46-11.27), alcohol consumption ( P=0.002, OR=3.77, 95% CI: 1.64-8.67), high-salt diet ( P=0.008, OR=2.90, 95% CI: 1.32-6.41), and high red meat intake ( P=0.025, OR=2.33, 95% CI: 1.11-6.31) were independent risk factors for endoscopic atrophic progression after HP eradication. The predictive model based on these 5 factors demonstrated strong discriminative capacity, with an area under the receiver operating characteristic curve of 0.813 (95% CI: 0.755-0.876, P<0.001). The optimal cut-off value was 1.5 points, stratifying patients into low-risk (0-2 points) and high-risk (3-5 points) groups. Conclusion:Patients with chronic gastritis remain susceptible to progression even after successful HP eradication. Individualized endoscopic follow-up strategies should be considered based on patients' medical history, medication use, lifestyle, and dietary habits.

Objective:To investigate the distribution characteristics of CTLA-4 on the surface of CD4+T cells in patients with breast cancer at different stages,and to evaluate its predictive value for the efficacy of radical mastectomy.Methods:A retrospective study was conducted on 200 breast cancer patients admitted between January 2020 and December 2022.Patients were divided into four groups based on clinical staging:stage Ⅰ(64 cases),stage Ⅱ(57 cases),stage Ⅲ(43 cases),and stage Ⅳ(36 cases).The clinical pathological characteristics of the four groups were compared,and the expression level of CTLA-4 on the surface of CD4+T cells in peripheral venous blood(CTLA-4+CD4+)was detected.Patients were divided into a poor prognosis group(52 cases)and a good prognosis group(148 cases)based on their prognosis,and the clinical pathological characteristics of the two groups were compared.A stratified regression model was used to analyze the relationship between CTLA-4+CD4+expression levels and different clinical characteristics.Logistic regression analysis was employed to evaluate the independent correlation between CTLA-4+CD4+expression levels and the risk of poor prognosis.An unconditional logistic regression model was used to analyze the multiplicative interaction effect of CTLA-4+CD4+expression levels and clinical staging on prognosis prediction.Restricted cubic spline analysis was used to investigate the relationship between CTLA-4+CD4+expression levels and poor patient prognosis.Results:Significant differences were observed in tumor diameter,ECOG score,lesion multiplicity,lymph node metastasis,tumor differentiation degree,ER,PR,HER2,Ki-67,CA125,CA153,and CEA among patients with different clinical stages(P<0.05).Significant differences were also observed in CD3+,CD4+,CD8+,and CTLA-4+CD4+(P<0.05).As the clinical stage increased,the proportions of CD3+,CD4+,and CD8+decreased,while the proportion of CTLA-4 on the surface of CD4+T cells increased(P<0.05).Significant differences were observed in clinical stage,tumor diameter,lymph node metastasis,tumor differentiation degree,ECOG score,ER,PR,HER2,and CTLA-4+CD4+among patients with different prognosis groups(P<0.05).Hierarchical regression analysis indicated that clinical stage,tumor diameter,lymph node metastasis,tumor differentiation degree,ECOG score,and HER2 had a significant positive impact on CTLA-4+CD4+(P<0.05),while ER and PR had a significant negative impact on CTLA-4+CD4+(P<0.05).Logistic regression analysis showed that CTLA-4+CD4+was positively correlated with poor prognosis(P<0.05).CTLA-4+CD4+and clinical stage had multiplicative and additive interactions on prognosis.Regardless of the clinical stage,CTLA-4+CD4+on the surface of CD4+T cells was significantly positively correlated with poor prognosis.Conclusion:The expression level of CTLA-4+CD4+in patients with advanced breast cancer is significantly elevated,playing a crucial role in the clinical pathological characteristics of breast cancer.An elevated level may indicate a poor prognosis.