[Gene-age interaction study of breast cancer prognosis based on epigenomic data].

Objective: Exploring gene-age interactions associated with breast cancer prognosis based on epigenomic data. Methods: Differential expression analysis of DNA methylation was conducted using multiple independent epigenomic datasets of breast cancer from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The false discovery rate (FDR) method was used for multiple corrections, retaining differentially methylated sites with q-FDR≤0.05. A three-stage analytic strategy was implemented, using a multivariable Cox proportional hazards regression model to examine gene-age interactions. In the discovery phase, signals with q-FDR ≤ 0.05 were screened out using TCGA-BRCA database. In validation phaseⅠ, the interaction was validated using GSE72245 data, with criteria of P≤0.05 and consistent effect direction. In validation phaseⅡ, the signals were further validated using GSE37754 and GSE75067 data. A prognostic prediction model was constructed by incorporating clinical indicators and interaction signals. Results: The three-stage analytic strategy identified a methylation site (cg16126280EBF1), which interacted with age to jointly affect the overall survival time of patients (interaction HR= 1.001 1,95%CI:1.000 7-1.001 5,P<0.001). Stratified analysis by age showed that the effect of hypermethylation of cg16126280EBF1 was completely opposite in younger patients (HR=0.550 5, 95%CI: 0.383 8-0.789 6, P=0.001) and older patients (HR=2.166 5, 95%CI: 1.285 2-3.652 2, P=0.004). Conclusions: The DNA methylation site cg16126280EBF1 exhibits an interaction with age, jointly influencing the prognosis of breast cancer in a complex association pattern. This finding contributes new population-based evidence for the development of age-specific targeted drugs.

[Epidemiological characteristic of viral encephalitis in children and adolescents in Henan Province, 2012-2023].

Objective: To understand the epidemiological characteristics and spatiotemporal distribution of viral encephalitis in children and adolescents in Henan Province from 2012 to 2023. Methods: The information about viral encephalitis cases from October 1, 2012 to July 26, 2023 were collected from Zhengzhou Children's Hospital (National Children's Regional Medical Center),Henan Provincial Children's Hospital for the analyses on temporal distribution the cases, the severe illness rate, age distribution, pathogen type and imaging findings of the cases. Results: A total of 6 276 cases of viral encephalitis were included in this study after excluding cases with incomplete information. The cases mainly originated from Zhengzhou (38.96%), followed by Zhoukou (9.93%), Xuchang (8.68%), Zhumadian (7.90%) and Pingdingshan (7.39%). The cases in boys accounted for 62.13% and the cases in girls accounted for 37.87%. Most cases (72.45%) occurred in age group 7-13 years. The overall rate of severe illness cases was 4.51% from 2012 to 2023. There were significant differences in severe illness cases among different areas and years (χ2=5.33,P=0.021; χ2=48.14,P<0.001). Enteroviruses were mainly detected (31.57%), in which Coxsackie virus was predominant (58.37%). Imaging findings showed that cerebral hemisphere damage was most common in children and adolescents with viral encephalitis (54.93%). Conclusions: From 2012 to 2023, more cases of viral encephalitis occurred in boys in Henan. Children and adolescents aged 7-13 years were the main affected group. The prevention of enteroviruses infection, especially Coxsackie virus, needs to be strengthened. Special attention should be paid to the prevention of cerebral hemisphere damage after viral encephalitis diagnosis.

Antioxidant effect of dimethyl fumarate in pentylenetetrazole-kindled epilepsy mice and is activated by nuclear factor erythroid 2-related factor 2 pathway.

This study was designed to examine the anti-oxidative stress effect of dimethyl fumarate (DMF) on pentylenetetrazole (PTZ)-induced epileptic mice, and to evaluate the correlation of its mechanism with the nuclear factor E2-related factor 2 (Nrf2)-mediated signaling pathway. The experimental mice were separated into three groups: control, model, and DMF groups. Mice in the model group were administered PTZ to establish an epilepsy model, mice in the DMF group were administered DMF concurrently when modeling, and mice in the control group were administered a 0.9% NaCl solution. The latency, severity, and frequency of epileptic seizures in mice after each treatment were recorded, and the modelling success rate was computed at the conclusion of the experiment. The mice were euthanized, their levels of malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD), 8-hydroxy-deoxyguanosine (8-OHdG), and Nrf2 were measured, and the electron microscope was used to examine the mitochondrial damage of brain tissue. The latency of epileptic seizures was longer in the DMF group compared to the model group (P<0.05). The levels of MDA and ROS in the DMF group were lower than those in the model group (P<0.0001), and the activity of SOD in the DMF group was higher than that in the model group (P<0.0001); however, the levels of MDA and ROS were elevated and the activity of SOD was lower in both groups relative to the control group. The levels of 8-OHdG were lower in the DMF group than the model group (P<0.0001), however, the levels were higher in both groups compared to the control group. Mitochondrial abnormalities were more prevalent in the model group than in the DMF group, and more prevalent in both groups compared to the control group. The DMF group contained more Nrf2 content than the model group (P<0.0001), and both groups contained more Nrf2 than the control group. We concluded that the mechanism by which DMF reduced the level of oxidative stress in epileptic mice might involve the Nrf2-mediated signaling pathway.

TLR4-MyD88-NF-κB signaling imbalances Th17 and Treg cells in thymoma with myasthenia gravis.

OBJECTIVE: Thymus is an immune organ in which pathological changes may cause autoimmune diseases, including myasthenia gravis (MG). Recent studies have focused on Toll-like receptor 4 (TLR4) signaling as the cause of such changes. In our previous study, an imbalance of T helper 17 (Th17) cells and T regulatory (Treg) cells was found in MG thymoma. These results suggest the involvement of TLR4 in the pathogenesis of thymoma MG via an alteration of the Th17/Treg balance. Here, we aimed to assess whether the TLR4-MyD88-NF-κB pathway is upregulated in MG thymoma and its relationship with Th17/Treg cells. PATIENTS AND METHODS: We collect thymoma samples from 54 patients with or without MG, detecting the expression level of TLR4, MyD88, and NF-κB in thymoma tissues. Next, we established an in vitro experiment of coculturing thymoma cells with CD4+ T cells and detected the differentiation of Th17 cells and Treg cells and their marker protein, retinoid-related orphan receptor gamma t (RORγt) and forkhead transcription factor 3 (Foxp3). RESULTS: We found TLR4, MyD88, and NF-κB expressed more in MG thymoma compared with simple thymoma. After the transwell coculturing, we observed an imbalance of Th17/Treg cells after TLR4 stimulation. CONCLUSIONS: TLR4 is stimulated in thymoma, causing an increase of Th17 cells and a decrease of Treg cells, namely an imbalance of Th17/Treg cells, resulting in MG.

[Advances in the role of autoimmune mechanisms in chronic obstructive pulmonary disease].

Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease whose pathogenesis mainly involves airway remodelling and alveolar destruction caused by inflammation, protease-antiprotease imbalance, oxidative stress, and imbalance between apoptosis and compensatory repair of lung tissue structure cells. In recent years, the role of the autoimmune response in COPD has attracted widespread attention, but there is still some controversy. This article reviewed the role of autoimmunity in COPD from different perspectives, starting with the relationship between autoimmunity and the pathogenesis of COPD.

Electroacupuncture Stimulation Alleviates Inflammatory Pain in Male Rats by Suppressing Oxidative Stress.

In the present study, we focused on whether the analgesic effect of Electroacupuncture (EA) is related to the regulation of oxidative stress. We established a chronic inflammatory pain model in male rats by a single injection of complete Freund's adjuvant (CFA) and then treated the animals with daily EA stimulation at the site of "zusanli". The analgesic effect of EA was evaluated by measuring the paw withdrawal threshold (PWT) when rats received mechanical and thermal pain stimulation. The levels of inflammation-related molecules and oxidative stress-related markers in the spinal cord were measured by western blotting or ELISA kits. EA stimulation and antioxidants effectively increased the PWT in CFA rats. Co-treatment of CFA rats with the ROS donor t-butyl hydroperoxide (t-BOOH) further decreased the PWT and weakened the analgesic effect of EA. EA treatment inhibited inflammation and oxidative stress, as shown by decreased levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, and MDA and increased activity of SOD and catalase. Moreover, EA reduced the expression of p-p38, p-ERK, and p-p65 and simultaneously downregulated the expression of TRPV1 and TRPV4 in CFA rats. In an in vitro study, direct stimulation with t-BOOH to the C6 cells increased the production of TNF-alpha, IL-1beta, IL-6, activated p38, ERK, and p65 and up-regulated the expression of TRPV1 and TRPV4, and these effects could be prevented by the ROS scavenger PBN. Taken together, our data indicate that the inhibition of oxidative stress and the generation of ROS contribute to the analgesic effect of EA in male CFA rats.

Decreased serum voriconazole levels caused by hepatic enzyme induction after rifapentine discontinuation: a case report and literature review.

BACKGROUND: Rifapentine is a rifamycin with unique bactericidal activity against Mycobacterium tuberculosis. It is also a potent inducer of CYP3A activity. However, the duration of rifapentine-induced hepatic enzyme activity after withdrawal is unclear. CASE REPORT: We report a case of a patient with Aspergillus meningitis treated with voriconazole after discontinuing rifapentine. Within ten days of rifapentine discontinuation, serum levels of voriconazole failed to reach the effective treatment range. CONCLUSIONS: Rifapentine is a potent inducer of hepatic microsomal enzymes. The induction of hepatic enzymes may exceed ten days after rifapentine discontinuation. Clinicians should be reminded of residual enzyme induction by rifapentine, especially when treating critically ill patients.

[New progress of excimer laser corneal refractive surgery for presbyopia].

Presbyopia refers to the decline in the accommodation of eye that occurs with age, symptoms begin to appear after the age of 40 and the clarity of vision at near is insufficient to satisfy an individual's requirements. The correction of presbyopia include restoring natural accommodation and improving symptom. The former is still difficult to achieve at present, while the latter mainly involves wearing convex lens, and with more and more patients wanting to get rid of frame glasses, refractive surgery is gradually promoted and applied. Corneal refractive surgery, especially laser-assisted in situ keratomileusis, is one of the most common methods for surgical correction of presbyopia. We reviewed the recent literature to introduce the mechanism of corneal refractive surgery treating presbyopia and the efficacy of different surgical algorithms.

[Progress in application of deep learning in orthodontic diagnosis and treatment].

In recent years, the application of artificial intelligence technology in the field of orthodontics has gradually increased, and deep learning, as a hot direction, has also been rapidly applied in the detection, evaluation, diagnosis, prediction and effect evaluation. At present, deep learning research has the advantages of high efficiency and accuracy, but it also has limitations such as weak interpretability and insufficient data volume. This paper reviewed the proposal and development of deep learning, the application in orthodontic diagnosis and treatment, as well as the limitations and countermeasures of the popularization, and prospect of the future research.

[Metabolic reprogramming in pulmonary hypertension].

Pulmonary hypertension is a pathophysiological disorder with elevated pulmonary artery pressures that may involve multiple clinical conditions, yet the mechanism of pulmonary hypertension remains unclear. Metabolic reprogramming of structural cells (smooth muscle cells, endothelial cells, fibroblasts etc.) and immune cells (macrophages etc.) is a hallmark of pulmonary hypertension and leads to pulmonary vascular remodeling. Many studies have investigated the metabolic reprogramming in pulmonary hypertension and some potential therapeutic targets have been developed. In this review, recent work on metabolic programming in pulmonary hypertension is summarized.

[Efficacy and safety of oral pyrotinib in HER2 positive metastatic breast cancer: real-world practice].

OBJECTIVE: Pyrotinib, a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor, showed promising antitumor activity and acceptable tolerability in phase II and phase III randomized clinical trials. We assessed the activity and safety of oral pyrotinib for human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer patients in the real world. METHODS: We retrospectively analyzed 72 HER2 positive metastatic breast cancer (MBC) patients who received oral pyrotinib based regimens at Beijing Cancer Hospital and other four hospitals (Peking University First Hospital, China-Japan Friendship Hospital, General Hospital of PLA, Peking University Third Hospital) from August 2018 to September 2019. Progression free survival (PFS), objective response rate (ORR), adverse events (AE) of pyrotinib were investigated. RESULTS: Seventy-two patients with HER2 positive MBC were enrolled. The median age of the patients was 55 years (range: 32-79 years). Sixty-nine (95.8%) patients had received anti-HER2 treatment in the metastatic and/or (neo) adjuvant settings; 61 (84.7%) patients had received anti-HER2 treatments in the metastatic setting in terms of trastuzumab 56 (77.8%) patients, lapatinib 36 (50.0%) patients, and T-DM1 4 (5.6%) patients. Among these 72 patients who received oral pyrotinib based regimens, 62 (86.1%) patients received pyrotinib (±trastuzumab) in combination with chemotherapy, 6 (8.3%) patients received pyrotinib (± trastuzumab) in combination with endocrine therapy and 4 (5.6%) patients received pyrotinib (±trastuzumab). Sixty-five (90.3%) patients received 400 mg pyrotinib once daily as initial dose, and 7 (9.7%) patients received 320 mg. OBJECTIVE response and safety to pyrotinib based therapy were evaluable in all the 72 patients. One (1.4%) patient achieved complete response (CR), 18 (25.0%) patients achieved partial response (PR), 41 (56.9%) patients had stable disease (SD), and 12 (16.7%) patients had progressive disease (PD). The ORR (CR+PR) was 26.4% and the median PFS was 7.6 months (95%CI: 5.5-9.7 months). Among the 36 patients with prior lapatinib therapy, the median PFS was 7.9 months (95%CI: 4.1-11.7 months). Among the 15 patients with brain metastasis, the median PFS was 6.0 months (95%CI: 2.2-9.8 months). The main toxicities related to pyrotinib were diarrhea in 57 (79.2%) cases, and 48 (66.7%) cases with grade 1-2 as well as 9 (12.5%) cases with grade 3. CONCLUSION: Pyrotinib based therapy is an effective treatment for patients with HER2 positive MBC, including patients with lapatinib treatment failure and brain metastasis, and the toxicities can be tolerated.

[The value of adenosine triphosphate in CD4(+)T lymphocytes in predicting repeated respiratory tract infections in silicosis patients].

Objective: To explore the value of the concentration of adenosine triphosphate (ATP) in CD4(+)T lymphocytes in predicting repeated respiratory tract infections (RRTI) in silicosis patients. Methods: In April 2020, 614 silicosis patients admitted from March 2016 to March 2018 were included in the study, and they were divided into the RRTI group (n=105) and the non RRTI group (n=509) according to whether the occurrence of RRTI, another 30 healthy cases taken from body check were served as control group, and the concentrations of ATP produced by CD4(+)T lymphocytes was measured by ImmuKnow assay, and were compared between the three groups. And drawed the receiver operating characteristic (ROC) curve, and the Logistic regression analysis was used to explore the risk factors of RRTI. Results: The incidence of RRTI in silicosis patients was 17.10% (105/614) . The concentration of ATP produced by CD4(+)T lymphocytes in the RRTI group [ (260.42±90.36) mg/L] was significantly lower than that in the non RRTI group [ (413.66±138.74) mg/L] (t=-10.849, P<0.01) . The area under the ROC curve was 0.834, the cutoff value was 284 mg/L, the sensitivity was 0.88, and the specificity was 0.83. Logistic regression analysis showed that the concentration of ATP produced by CD4(+)T lymphocytes≤284 mg/L, impaired pulmonary ventilation function, serum albumin<40 g/L and diabetes were the risk factors of RRTI in silicosis patients (OR=2.126, 1.217, 1.164, 1.125, P<0.05) . Conclusion: Low CD4(+)T lymphocyte ATP value was a risk factor of RRTI in silicosis patients, and can predict the risk of RRTI in patients with silicosis.