Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.

[This corrects the article DOI: 10.1016/j.apsb.2025.02.029.].

Dental treatments for children and adolescents have unique clinical characteristics that differ from dental care for adults in terms of children's physiology, psychology, and behavior. These differences impose specific requirements on the application of local anesthesia in pediatric dental procedures. This article presents expert consensus on the principles of local anesthesia techniques in pediatric dental therapies, including the use of common anesthetic drugs and dosage control, safety and efficacy evaluation, and prevention and management of complications. The aim is to improve the safety and quality of pediatric dental treatments and offer guidance for clinical application by dentists.
Humans ; Child ; Anesthesia, Local/methods* ; Consensus ; Anesthesia, Dental/methods* ; Adolescent ; Anesthetics, Local/administration & dosage* ; Dental Care for Children

Objective:To analyze the effect of recombinant human thrombopoietin(rhTPO)on platelet(PLT)reconstitution after autologous peripheral blood stem cell transplantation(APBSCT)in patients with multiple myeloma(MM).Methods:The clinical data of 147 MM patients who were diagnosed in the First Affiliated Hospital of Soochow University and received APBSCT as the first-line therapy were retrospectively analyzed.According to whether rhTPO was used during APBSCT,the patients were divided into rhTPO group(80 cases)and control group(67 cases).The time of PLT engraftment,blood product infusion requirements,the proportion of patients with PLT recovery to ≥ 50 × 109/L and ≥ 100 × 109/L at+14 days and+100 days after transplantation,and adverse reactions including the incidence of bleeding were compared between the two groups.Results:There were no significant differences between the two groups in sex,age,M protein type,PLT count at the initial diagnosis,median duration of induction therapy before APBSCT,and number of CD34+cells reinfused(all P＞0.05).The median time of PLT engraftment in the rhTPO group was 10(6-14)days,which was shorter than 11(8-23)days in the control group(P＜0.001).The median PLT transfusion requirement in the rhTPO group during APBSCT was 15(0-50)U,which was less than 20(0-80)U in the control group(P=0.001).At+14 days after transplantation,the proportions of patients with PLT 2 50 × 109/L in the rhTPO group and the control group were 66.3％and 52.2％,while the proportions of patients with PLT ≥ 100 × 109/L were 23.8％and 11.9％,respectively,with no significant differences(all P＞0.05).At+100 days after transplantation,the proportion of patients with PLT ≥ 50 × 109/L in rhTPO group and control group was 96.3％and 89.6％,respectively(P＞0.05),but the proportion of patients with PLT ≥ 100 × 109/L in rhTPO group was higher than that in control group(75.0％vs 55.2％,P=0.012).There was no difference in the overall incidence of bleeding events in different locations during period of low PLT level of patients between the two groups.In rhTPO group,the rhTPO administration was well tolerated,and the incidences of abnormal liver and kidney function and infection were similar to those in the control group.Conclusion:When MM patients undergo first-line APBSCT,subcutaneous injection of rhTPO can shorten the time of platelet engraftment,reduce the transfusion volume of blood products,and be well tolerated,moreover,more patients have achieve a high level of PLT recovery after transplantation,which is very important for ensuring the safety of APBSCT and maintenance therapy.

Objective:To investigate the relationship between preoperative plasma fibrin degradation products (FDP) level and clinicopathological features of patients with completely resected non-small cell lung cancer (NSCLC).Methods:A retrospective case series study was performed. The clinical data of 521 patients who were pathologically diagnosed with NSCLC in Beijing Friendship Hospital Affiliated to Capital Medical University from January 2016 to December 2017 were retrospectively analyzed. Among 521 cases, 406 cases were postoperatively pathologically confirmed as non-lymph node and non-distant metastasis (non-metastasis group) and 115 cases were postoperatively pathologically confirmed as lymph node or distant metastasis (metastasis group). The preoperative FDP level and clinicopathological characteristics as well as the clinicopathological characteristics of NSCLC patients with different FDP levels were compared between the two groups. The correlation between preoperative FDP level and TNM staging was analyzed by using Spearman correlation analysis.Results:Among 521 NSCLC patients, 266 cases were female, 255 cases were male; the age [ M( Q1, Q3)] was 59 years (54 years, 65 years); 441 cases were adenocarcinoma and 70 cases were squamous cell carcinoma. The preoperative median FDP level was 2.78 mg/L (2.35 mg/L, 3.13 mg/L) and 2.99 mg/L (2.56 mg/L, 4.16 mg/L), respectively of NSCLC patients in non-metastasis group and metastasis group, and the difference was statistically significant ( Z = 6.13, P < 0.001). The preoperative FDP level was 2.56 mg/L (2.35 mg/L, 3.20 mg/L) and 2.99 mg/L (2.56 mg/L, 3.20 mg/L), respectively in the early-stage NSCLC (stage Ⅰ-Ⅱ) and advanced NSCLC (stage Ⅲ-Ⅳ) patients, and the difference was statistically significant ( Z = 8.42, P < 0.001). Spearman correlation analysis showed that preoperative FDP level was positively correlated with tumor diameter ( r = 0.287, P < 0.001). There was a positive correlation between preoperative FDP level and the number of metastatic lymph nodes in 115 patients with lymph node metastasis ( r = 0.679, P < 0.001). According to the preoperative median FDP (2.78 mg/L), all patients were divided into FDP ≤2.78 mg/L group and FDP >2.78 mg/L, and there were statistically significant differences in age, metastasis, tumor staging, tumor diameter, the metastatic number of lymph node and histological types of NSCLC patients in both groups (all P < 0.05). Conclusions:The increase of preoperative plasma FDP level may be related to the tumor metastasis and clinical stage of NSCLC patients

Objective To investigate the effect of cinobufacini on inhibiting colorectal cancer metastasis by regula-ting the polarization of M2 macrophages.Methods THP-1 was induced into M0 type macrophages.The condi-tioned medium of HCT116 cells was collected to stimulate M0 type macrophages.The polarization of M2 type mac-rophages was observed by flow cytometry,real-time quantitative PCR and ELISA experiments.The conditioned me-dium of M0 type macrophages and HCT116-Mφ cells was collected to stimulate HCT116 cells.The ability of migra-tion and invasion was observed by wound healing assay and Transwell assay.The effect of cinobufacini on the via-bility of HCT116 cells was detected by CCK-8 assay.The conditioned medium of HCT116 and HCT116+cinobufa-cini was collected to stimulate M0 type macrophages.The polarization of M2 type macrophages was observed by flow cytometry,real-time quantitative PCR and ELISA experiments.The conditioned media of HCT116-Mφ cells and(HCT116+cinobufacini)-Mφ cells were collected to stimulate HCT116 cells.The changes of migration and inva-sion ability were observed by wound healing assay and Transwell assay.Results After stimulation of M0 type mac-rophages in HCT116 cell conditioned medium,the morphology of M0 macrophages turned into fusiform cells,the proportion of CD11b+CD206+cells increased,and the expression of M2 macrophage markers IL-10 and TGF-β in-creased.The migration and invasion ability of HCT116 cells were significantly enhanced after stimulation in the conditioned medium of HCT1 16-Mφ cells.After the addition of cinobufacini,not only the polarization proportion of M2 macrophages decreased,but also the metastatic effect mediated by M2 macrophages was inhibited.Conclusion HCT116 cells can induce the polarization of M2 macrophages,while cinobufacini can inhibit the tumor metastasis mediated by M2 macrophages by inhibiting the polarization of M2 macrophages.

Objective To investigate the role of bufalin(BU)in inhibiting M2-type macrophage-mediated colorec-tal cancer metastasis.Methods Human acute leukemia mononuclear cells(THP-1)were differentiated into M0 macrophages using phorbol ester induction(PMA)for 48 hours.The M0 macrophages were then treated with IL-4 and IL-13 medium.Surface markers and morphological changes were observed through ELISA,morphology,and RT-qPCR experiments.RT-PCR and ELISA experiments were conducted to detect the surface markers TGF-β and IL-10 of M2 macrophages.The secretion level of IL-6 in the supernatant of M2 macrophages and colorectal cancer cells HCT116 was compared using ELISA.Additionally,the effect of conditioned medium on colorectal cancer cell HCT116 was assessed through Transwell,Wound healing,RT-qPCR,and Western blot experiments.Subsequent-ly,bufalin was added to the conditioned medium and the changes in AKT/PI3K protein,migration,and epithelial-mesenchymal transition ability in HCT116 were observed using Western blot,Transwell,Wound healing and RT-qPCR experiments.Results THP-1 were successfully differentiated into M2 macrophages.The activation of AKT/PI3K protein in HCT116 cells was induced by the secretion of IL-6 from M2 macrophages,which in turn promoted the migration and epithelial-mesenchymal transition ability of the HCT116 cells.The migration and epithelial-mes-enchymal transition mediated by M2 macrophages in HCT116 cells were effectively inhibited by Bufalin.Conclu-sion The release of IL-6 from M2 macrophages activates the AKT/PI3K signaling pathway in colorectal cancer cells,thereby promoting their migration and epithelial-mesenchymal transition capacity.Moreover,bufalin exhibits inhibitory effects on this effect.

With the rapid advancement and wide application of microwave technology, it enhances convenience while potentially endangering health. The immune system, as a vital shield, is an important protective barrier and also one of the sensitive targets of microwave radiation. The immune system is particularly affected by microwave radiation via innate and adaptive immune responses, which is supported by both population surveys and experimental studies; however, the precise mechanism of immunotoxicity of microwave radiation remains under investigation. In light of recent scientific advances in the correlation between microwave radiation and the immune system, the deleterious impact of microwave radiation on innate immunity was delineated. Microwave radiation can induce irregular innate immune function by damaging macrophages, neutrophils, natural killer cells, and dendritic cells. The effects of microwave radiation on adaptive immunity were also elucidated. Microwave radiation can impair cellular immune response by influencing T cell proliferation, maturation and activation, and distribution of T cell subpopulation, and also hinder humoral immune function by influencing B lymphocyte protein expression, maturation during development, and number of B cells. Disparity in the immune function of the body can precipitate the onset of various immune-associated diseases, so the immunotoxic effects of microwave radiation and associated protection need considerable attention and detailed investigation. This article reviewed the shortcomings of existing studies, and suggested that future experimental studies should use experimental parameters that are more similar to the actual scene of life and work, pay more attention to the biological effects of combined multi-frequency microwave exposure on the immune system, use standardized and unified experimental methods, and incorporate more sophisticated experimental technologies to further elucidate the laws of damage effect and exact mechanism of microwave radiation on the immune system, so as to provide a scientific basis for potent protection against the damage effect of microwave radiation on the immune system.