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 observe the efficacy and safety of combined lienal polypeptide injection therapy in the treatment of Mycoplasma pneumoniae pneumonia（MPP）in children aged 3 to 14 years old in multiple clinical centers.Methods:A randomized，controlled，multi-center clinical study design was adopted.A total of 240 hospitalized children aged 3 to 14 years old with MPP from 7 hospitals from September 1，2023 to January 31，2024 were included.According to the severity of pneumonia，they were divided into the mild MPP group with 80 cases and the severe MPP/refractory MPP（SMPP/RMPP）group with 160 cases，and then randomly divided into the control group and the experimental group at a ratio of 1 ∶1，using the random number table method.After screening，subjects entered a treatment period of 5 to 7 days.The control group was treated with azithromycin，while the experimental group was treated with azithromycin plus lienal polypeptide injection .The recovery of lung CT，length of hospital stay，duration of fever，cough score，whether mild cases developed into severe or refractory cases，duration of hormone use，use of intravenous immunoglobulin（IVIG），bronchoscopy treatment，and immune function were observed between the two groups to evaluate the efficacy of lienal polypeptide injection.Adverse events after medication，vital signs，blood routine，urine routine，liver function，myocardial enzymes，renal function，and electrocardiogram were observed to evaluate the safety. Results:A total of 231 subjects have completed the trial in the 7 hospitals，including 118 cases in the experimental group and 113 cases in the control group.Main observation index：the rate of lung CT aggravation in the experimental group was lower than that in the control group（2.6% vs 15.3%， P<0.01），and the difference was statistically significant.Secondary indexes：there were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and immunoglobulin between the two groups（all P>0.05）.However，the rate of cases of plastic bronchitis（PB）found under bronchoscopy in the experimental group was lower than that in the control group（0 vs 18.8%， P=0.03），and the difference was statistically significant.Among the mild MPP（72 cases），there were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and the improvement rate of lung CT between the two groups（all P>0.05）.However，compared with the control group，the rate of cases developing into SMPP/RMPP in the experimental group was less（24.3% vs 48.6%， P=0.03），and the difference in IgG before and after treatment was small［0.53（-0.04，1.18）g/L vs 1.33（0.48，2.25）g/L， P=0.01］.Among the SMPP/RMPP cases（159 cases），the rate of cases of PB found under bronchoscopy in the experimental group was less than that in the control group（0 vs 20%， P=0.04），and the rate of cases with aggravated lung CT in the experimental group was less than that in the control group（1.3% vs 19.5%， P<0.01），and the improvement rate of lung CT in the experimental group was higher than that in the control group（88.8% vs 75.3%， P=0.03），with statistically significant differences.There were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and immunoglobulin between the two groups（all P>0.05）.Two cases in the experimental group developed rashes，which improved after the drug was discontinued.There were no serious adverse reactions such as abnormal vital signs like dyspnea and cyanosis due to the use of lienal polypeptide injection.There were no obvious changes in blood routine，liver function，myocardial enzymes，renal function，electrocardiogram，and urine routine values before and after medication compared with the baseline. Conclusion:The combined use of lienal polypeptide injection in the treatment of MPP in children can reduce the probability of the transformation from mild cases to SMPP/RMPP，reduce the rate of aggravation of the image findings，promote the absorption of lung inflammation，reduce the rate of PB found under bronchoscopy，and has good safety.

Objective To analyze the trends in incidence and mortality of breast cancer among Chinese women from 1992 to 2021,assess the impact of age,period,and cohort on its incidence and mortality rates,and predict future trends to provide a basis for developing effective intervention strategies.Methods Utilizing the 2021 Global Burden of Disease(GBD2021)database,the Joinpoint regression model was employed to analyze the trends in age-standardized incidence and mortality rates of breast cancer among Chinese women from 1992 to 2021.The age-period-cohort model was applied to estimate the age,period,and cohort effects on the incidence and mortality of breast cancer among Chinese women during the same period.The autoregressive integrated moving average(ARIMA)model was used to predict the age-standardized incidence and mortality rates of breast cancer among Chinese women from 2022 to 2026.A stratified analysis was conducted to explore the impact of different risk factors[including smoking,alcohol consumption,high body mass index(BMI),hyperglycemia,physical inactivity,and diet]on breast cancer mortality.Results From 1992 to 2021,the incidence and mortality rates of breast cancer among Chinese women showed an overall upward trend,with incidence rates rising from 15.95/100,000 in 1992 to 55.54/100,000 in 2021,and mortality rates increasing from 7.35/100,000 to 12.41/100,000.The age-standardized incidence rate also exhibited an upward trend,rising from 18.51/100,000 to 37.00/100,000,with an average annual percentage change(AAPC)of 2.43%.However,the age-standardized mortality rate showed an overall downward trend,decreasing from 9.05/100,000 to 8.24/100,000,with an AAPC of-0.35%.The APC model analysis revealed that the age,period,and cohort effects on incidence and mortality were statistically significant(P<0.001).Within the same birth cohort,breast cancer incidence increased in women aged 15-89 years but decreased in those≥90 years.Breast cancer mortality showed a steady increase with age.With the increase in years,the risk of breast cancer incidence gradually increased,reaching the highest between 2017 and 2021,with a relative risk(RR)value of 1.37.Conversely,the risk of breast cancer mortality decreased with the increase in years,with the lowest mortality between 2012 and 2016,and an RR value of 0.86.With the increase in the birth cohort year,the risk of breast cancer incidence gradually increased,while the risk of mortality gradually decreased.The ARIMA model prediction results showed that the age-standardized incidence rate of breast cancer among women would continue to rise from 2022 to 2026,reaching 40.25/100,000 by 2026,while the age-standardized mortality rate would tend to stabilize at 8.28/100,000 by 2026.Among the risk factors for breast cancer,diet was found to have the highest impact on breast cancer mortality.Conclusions The incidence rate of breast cancer among Chinese women continues to rise,indicating that the prevention and control situation remains severe.Future efforts should focus on developing precise screening programs for high-risk populations and optimizing early screening strategies and treatment resource allocation based on predicted trend.

Objective : To investigate the effect and mechanism of M2 macrophage polarization induced by HCT116 with highly metastatic colorectal cancer cells on immune escape in colorectal cancer. Methods : After the co-culture of colorectal cancer cells conditioned medium(CM) and PMA-induced M0 macrophages, the polarization of M2 macrophages was observed by flow cytometry, real-time polymerase chain reaction(qPCR) and enzyme-linked immunosorbent assay(ELISA) experiments. The CMM0, CMSW480-Mφ and CMHCT116-Mφ were co-cultured with HCT116 cells, and the expression of programmed death-ligand 1(PD-L1) was detected by Western blot and qPCR. At the same time, the stimulated HCT116 cells were co-cultured with human T lymphocytes to detect the survival of HCT116 cells and the levels of tumor necrosis factor-α(TNF-α) and interferon-γ(IFN-γ). The difference of kruüppel-like factor 4(KLF4) expression between SW480 and HCT116 cells was detected by Western blots, qPCR and ELISA. After pretreatment of HCT116 cells with KFL4 inhibitor Kenpaullone(Ken), the CMHCT116 and CMHCT116+Ken were co-cultured with M0 macrophages and the polarization of M2 macrophages was observed by flow cytometry, qPCR and ELISA. The CMHCT116-Mφ and CM_((HCT116+Ken)-Mφ) was co-cultured with HCT116 cells, and the PD-L1 expression of HCT116 cells was detected by Western blot and qPCR. Results: After the stimulation of M0 macrophages with CM, the proportion of CD11b+CD206+ cells in HCT116-Mφ cells was higher, and the expression of M2 macrophage markers interleukin(IL-10) and transforming growth factor-β(TGF-β) were higher. Compared with the CMSW480-Mφ group, the PD-L1 protein expression level was higher in the CMHCT116-Mφ group. After co-culture with T lymphocytes, the cell survival rate are the most in CMHCT116-Mφ group, while the levels of TNF-α and IFN-γ were the lowest. After the addition of Ken, the polarization ratio and markers of M2 macrophages decreased. Compared with CMHCT116-Mφ group, the expression of PD-L1 in HCT116 cells of the CM_((HCT116+Ken)-Mφ) group decreased. Conclusion Highly metastatic colorectal cancer cells induce polarization of M2 macrophages by secreting KLF4, promote PD-L1 expression in colorectal cancer cells, facilitate tumor immune escape, and provide potential targets for clinical immunotherapy.

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.