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.

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.

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