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.].

Objective:To describe the positive rates of high-risk human papillomavirus (HR-HPV) DNA and serum-neutralizing antibody in cervical intraepithelial neoplasia (CIN) tissues of rural women in Xiangyuan County, Shanxi Province, and evaluate the association of HR-HPV DNA and neutralizing antibody positive status with the occurrence of CIN.Methods:In a cohort of 1 897 women aged 35-45 years established by the Shanxi Province Cervical Cancer Screening StudyⅠ, DNA typing (SPF10 PCR-DEIA-LiPA25) was performed by using tissue samples of women with positive HR-HPV test results [Hybrid CaptureⅡ(HC2)] or abnormal cytological or pathological results. Serum HR-HPV neutralizing antibody detection was conducted with multicolor pseudovirion-based neutralization assay. Cochran-Armitage trend test was used to analyze the changing trend of the positive rate of HR-HPV DNA and neutralizing antibody with the progression of CIN. Multivariate logistic regression models were used to evaluate the influence and multiplicative interaction of HR-HPV DNA and neutralizing antibody positive status on the occurrence of CIN. The relative excess risk ( RERI), attributable proportion of interaction ( AP), and the synergy index ( SI) of the interaction were calculated to evaluate the additive interaction of HR-HPV DNA and neutralizing antibody on the occurrence of CIN. Results:The positive rate of any type of HR-HPV DNA (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68) in 479 women who were HC2 positive or had abnormal cytological or pathological detection results was 37.16%. In normal, CIN1, CIN2, and CIN3+ groups, the HR-HPV DNA positive rates were 18.03%, 49.53%, 90.24% and 94.59%, respectively. The positive rate of any type of HR-HPV neutralizing antibody was 63.88%. In normal, CIN1, CIN2, and CIN3+ groups, the positive rates of HR-HPV neutralizing antibody were 63.95%, 57.94%, 70.73%, and 72.97%, respectively. The positive rate of any type of HR-HPV neutralizing antibody was 53.31% in 1 418 women who were HC2 negative and had normal cytopathology, and the most common types were HPV51 (27.36%) and HPV39 (24.96%). Multivariate logistic regression analysis showed that any type of HR-HPV DNA positive status ( OR=9.15, 95% CI: 5.99-14.20, P<0.001) was the independent factor for the occurrence of CIN, HR-HPV neutralizing antibody positive status was not associated with the occurrence of CIN ( OR=0.95, 95% CI: 0.61-1.48, P=0.815). The OR value of the multiplication of HR-HPV DNA and neutralizing antibody positive status of the occurrence of CIN was 1.63 (95% CI: 0.67-3.95), P=0.283. Quantitative analysis of interaction showed that RERI was 1.65 (95% CI:-3.56-6.86), SI was 1.28 (95% CI: 0.58-2.82), and AP was 0.19 (95% CI:-0.36-0.75). Conclusions:HR-HPV DNA positive status was a risk factor for the occurrence of CIN, but neutralizing antibody positive status was not associated with the occurrence of CIN. They had no significant multiplicative or additive interaction with the occurrence of CIN.

BACKGROUND:As an emerging treatment method,stem cell therapy is expected to improve the ovarian environment,delays the aging of ovarian granulosa cells,and brings new hope to older pregnant women.OBJECTIVE:To review the mechanism and research progress of stem cells against ovarian granulosa cell senescence.METHODS:CNKI and PubMed databases were retrieved for articles on stem cell therapy for ovarian granulosa cell senescence.Chinese and English search terms were"stem cells,ovary granulosa cells,aging."Finally,67 articles were included for analysis.RESULTS AND CONCLUSION:(1)This review summarizes five mechanisms of ovarian granulosa cell senescence:DNA damage and decreased repair capacity,oxidative stress,impaired mitochondrial function,inflammatory response,and changes in hormone levels.(2)This article summarizes five main mechanisms of stem cells in the treatment of ovarian granulosa cell senescence:promoting proliferation and inhibiting apoptosis,differentiation potential and regeneration ability,secreting factors,anti-oxidation,anti-inflammatory response,and immune regulation.(3)At present,there are various types of stem cells that can cooperate to treat ovarian granulosa cell senescence through a variety of ways,and stem cell therapy has broad prospects in restoring female fertility.

BACKGROUND:Adipose-derived stem cells have anti-aging effects,but whether adipose-derived stem cells from donors of different ages are different needs further study. OBJECTIVE:To compare the biological properties of adipose-derived stem cells in old and young mice. METHODS:Adipose-derived stem cells were extracted from adipose tissue of C57BL mice aged 8 and 14 weeks,respectively.The differences of cell cycle,apoptosis,and proliferation of adipose-derived stem cells in old and young mice were compared.The expression levels of aging-related P21 and P27 genes and proteins of adipose-derived stem cells in old and young mice were detected by quantitative PCR and western blot assay. RESULTS AND CONCLUSION:Compared with old mouse adipose-derived stem cells,young mouse adipose-derived stem cells were more active,more regular in morphology,less apoptosis,faster proliferation,and lower in expression of age-related P21 and P27 genes and proteins.It has been proven that adipose-derived stem cells from young mice have better anti-aging effects.

ObjectiveTo investigate the application value of a multimodal model integrating radiomics features， deep learning features， and clinical structured data in predicting severe acute pancreatitis （SAP）， and to provide more accurate tools for the early identification of SAP in clinical practice. MethodsThe patients with acute pancreatitis （AP） who attended The First Affiliated Hospital of Soochow University， Jintan Hospital Affiliated to Jiangsu University， and Suzhou Yongding Hospital from January 1， 2017 to December 31， 2023 were included. Related data were collected， including demographic information， previous medical history， etiology， laboratory test data， and systemic inflammatory response syndrome （SIRS） within 24 hours after admission， as well as imaging data within 72 hours after admission， while related scores were calculated， including Ranson score， modified CT severity index （MCTSI）， bedside index for severity in acute pancreatitis （BISAP）， and systemic inflammatory response syndrome， albumin， blood urea nitrogen and pleural effusion （SABP） score. The model was constructed in the following process： （1） three-dimensional CT images were used to extract and identify radiomics features， and a radiomics classification model was established based on the extreme gradient Boost （XGBoost） algorithm； （2） U-Net is used to perform semantic segmentation of three-dimensional CT images， and then the results of segmentation were imported into 3D ResNet50 to construct a deep learning classification model； （3） the predicted values of the above two models were integrated with clinical structured data to establish a multimodal model based on the XGBoost algorithm. The variable importance plot and local interpretability plot were used to perform visual interpretation of the model. The independent samples t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the chi-square test or Fisher’s exact test was used for comparison of categorical data between groups. The receiver operating characteristic （ROC） curve was plotted for each model and existing scoring systems， and the area under the ROC curve （AUC） was calculated to assess their performance； the Delong test was used for comparison of AUC. ResultsA total of 609 patients who met the criteria were included， among whom 114 （18.7%） developed SAP. In this study， the data of 426 patients from The First Affiliated Hospital of Soochow University was used as the training set， and the data of 183 patients from Jintan Hospital Affiliated to Jiangsu University and Suzhou Yongding Hospital were used as the independent test set. The multimodal model had an AUC of 0.914 in the test set， which was significantly higher than the AUC of traditional scoring systems such as MCTSI （AUC=0.827）， Ranson score （AUC=0.675）， BISAP （AUC=0.791）， and SABP score （AUC=0.648）； in addition， the multimodal model showed a significant improvement in performance compared with the radiomics classification model （AUC=0.739） and the deep learning classification model （AUC=0.685） （the Delong test： Z=-3.23， -4.83， -3.48， -4.92， -4.31， and -4.59， all P <0.01）. The top 10 variables in terms of importance in the multimodal model were pleural effusion， predicted value of the deep learning model， predicted value of the radiomics model， triglycerides， calcium ions， SIRS， white blood cell count， age， platelets， and C-reactive protein， suggesting that the above variables had significant contributions to the performance of the model in predicting SAP. ConclusionBased on structured data， radiomic features， and deep learning features， this study constructs a multicenter prediction model for SAP based on the XGBoost algorithm， which has a better predictive performance than existing traditional scoring systems and unimodal models.

Objective To investigate the effect of Saikosaponin A(SSA)on the differentiation,apoptosis and function of mouse bone marrow derived macrophages(BMDM)-derived M1/M2 macrophages,and to explore its molecular mechanism.Methods BMDM was induced to differentiate into M1/M2 macrophages in vitro,and SSA was added at the same time:CCK-8 assay was used to detect the viability of BMDM and M1/M2 macrophages.The morphology of M1/M2 macrophages was observed by inverted fluorescence microscopy.Flow cytometry(FCM)and ELISA were used to detect the levels of surface markers and cytokines in M1/M2 macrophages.Real-time fluorescent quantitative PCR(qPCR)was used to detect the mRNA levels of IL-6,TNF-α and arginase-1(Arg-1).FCM was used to detect the phagocytosis of peritoneal macrophages to fluorescent microsphere particles.Immunofluorescence(IF)assay and Western blotting were used to detect the molecular mechanism of SSA regulating M1/M2 macrophages.Results No significant effect on viability of M1/M2 macrophages was observed at SSA concentration of 10.0 mg/L,and obvious inhibition was seen at a concentration of 15.0 mg/L(P<0.01).Treatment of 10.0 mg/L SSA induced obvious morphologic changes in M1/M2 macrophages,with M1 macrophages in irregular shape,a few having pseudopods,and some showing unclear boundaries;while some M2 macrophages presenting round or irregular(P<0.001)with unclear boundaries.SSA treatment also resulted in significantly decreased proportion of M1/M2 macrophages after BMDM differentiation(P<0.05),with reduced contents of IL-6 and TNF-α secreted by M1 macrophages and their mRNA levels(P<0.05),but increased secretion of Arg-1 and mRNA levels by M2 macrophages(P<0.05).SSA treatment also inhibited the phagocytosis ability of peritoneal macrophages to fluorescent microsphere particles(P<0.01)in a concentration-dependent manner.SSA decreased the phosphorylation of NF-kappaB(p-NF-κB)(P<0.01)and enhanced the phosphorylation of signal transducer and activator of transcription 6(p-STAT6)in M2 macrophages(P<0.05).Conclusion SSA may affect the differentiation and function of M1/M2 macrophages by regulating NF-κB and STAT6 signaling pathways.

Objective To investigate the relationship between serum cyclophilin A(CypA),ischemia modi-fied albumin(IMA),galectin-3(Gal-3)levels and oxidative stress and cognitive impairment(CI)in patients with acute cerebral infarction(ACI)complicated with obstructive sleep apnea hypopnea syndrome(OSAHS).Methods A total of 168 patients with ACI complicated with OSAHS who were admitted to the hospital from December 2020 to October 2023 were selected,and the levels of serum CypA,IMA,Gal-3 and oxidative stress indexes[superoxide dismutase(SOD),malondialdehyde(MDA)]in patients with different severity(mild group,moderate group,severe group)were compared.The correlation between serum CypA,IMA,Gal-3 lev-els and oxidative stress indexes were analyzed by Pearson method.The incidence of CI in patients with ACI complicated with OSAHS were statistically analyzed,the levels of serum CypA,IMA and Gal-3 were com-pared between normal cognitive group and CI group,and the risk factors of CI in patients with ACI complicat-ed with OSAHS were analyzed by multivariate Logistic regression model.Results The levels of serum CypA,IMA,Gal-3 and MDA in mild group,moderate group and severe group increased in turn(P<0.05),and ser-um SOD level decreased in turn(P<0.05).Serum CypA,IMA and Gal-3 in ACI patients complicated with OSAHS were negatively correlated with SOD(P<0.05),and positively correlated with MDA(P<0.05).Of 168 ACI patients complicated with OSAHS,79 cases(47.02%)had CI and were included in the CI group.Compared with normal cognitive group,the serum levels of CypA,IMA and Gal-3 in CI group were signifi-cantly increased(P<0.05).Multivariate Logistic regression model analysis showed that apnea hypopnea in-dex(AHI)≥20 times/h,frontal and temporal lobe infarction,elevated CypA level,elevated IMA level,and el-evated Gal-3 level were risk factors for CI in ACI patients complicated with OSAHS(P<0.05).Conclusion The high expression of serum CypA,IMA and Gal-3 in patients with ACI complicated with OS-AHS is significantly correlated with oxidative stress and CI.The increase of serum CypA,IMA and Gal-3 lev-els indicates an increased risk of CI in patients with ACI complicated with OSAHS,and early detection of the three has good clinical value in evaluating the condition of patients with ACI complicated with OSAHS.

AIM: To delineate the specific mutation responsible for retinitis pigmentosa(RP)in a Yi pedigree, and to analyze the correlation of RHO gene mutation with clinical phenotype.METHODS:A comprehensive clinical evaluation was conducted on the proband diagnosed with RP and other familial members, complemented by a thorough ophthalmic examination. Peripheral blood samples were obtained from the proband and familial members, from which genomic DNA was extracte. Subsequent whole exome sequencing(WES)was employed to identify the variant genes in the proband. The identified variant gene was validated through Sanger sequencing, then an in-depth analysis of the mutation genes was carried out using genetic databases to ascertain the pathogenic mutation sites. Furthermore, an exhaustive analysis was performed to delineate the genotype and phenotype characteristics.RESULTS:The RP pedigree encompasses 5 generations with 42 members, including 19 males and 23 females. A total of 13 cases of RP were identified, consisting of 4 males and 9 females, which conforms to the autosomal dominant inheritance pattern. The clinical features of this family include an early onset age, rapid progression, and a more severe condition. The patients were found to have night blindness around 6 years old, representing the earliest reported case of night blindness in RP families. The retina was manifested by progressive osteocytoid pigmentation of the fundus, a reduced visual field, and significantly decreased or even vanished a and b amplitudes of ERG. The combined results of WES and Sanger sequencing indicated that the proband had a heterozygous missense mutation of the RHO gene c.1040C>T:p.P347L, where the 1 040 base C of cDNA was replaced by T, causing codon 347 to encode leucine instead of proline. Interestingly, this mutation has not been reported in the Chinese population.CONCLUSION:This study confirmed that the mutant gene of RP in a Yi nationality pedigree was RHO(c.1040C>T). This variant leads to the change of codon 347 from encoding proline to encoding leucine, resulting in a severe clinical phenotype among family members. This study provides a certain molecular, clinical, and genetic basis for genetic counseling and gene diagnosis of RHO.

AIM: To delineate the specific mutation responsible for retinitis pigmentosa(RP)in a Yi pedigree, and to analyze the correlation of RHO gene mutation with clinical phenotype.METHODS:A comprehensive clinical evaluation was conducted on the proband diagnosed with RP and other familial members, complemented by a thorough ophthalmic examination. Peripheral blood samples were obtained from the proband and familial members, from which genomic DNA was extracte. Subsequent whole exome sequencing(WES)was employed to identify the variant genes in the proband. The identified variant gene was validated through Sanger sequencing, then an in-depth analysis of the mutation genes was carried out using genetic databases to ascertain the pathogenic mutation sites. Furthermore, an exhaustive analysis was performed to delineate the genotype and phenotype characteristics.RESULTS:The RP pedigree encompasses 5 generations with 42 members, including 19 males and 23 females. A total of 13 cases of RP were identified, consisting of 4 males and 9 females, which conforms to the autosomal dominant inheritance pattern. The clinical features of this family include an early onset age, rapid progression, and a more severe condition. The patients were found to have night blindness around 6 years old, representing the earliest reported case of night blindness in RP families. The retina was manifested by progressive osteocytoid pigmentation of the fundus, a reduced visual field, and significantly decreased or even vanished a and b amplitudes of ERG. The combined results of WES and Sanger sequencing indicated that the proband had a heterozygous missense mutation of the RHO gene c.1040C>T:p.P347L, where the 1 040 base C of cDNA was replaced by T, causing codon 347 to encode leucine instead of proline. Interestingly, this mutation has not been reported in the Chinese population.CONCLUSION:This study confirmed that the mutant gene of RP in a Yi nationality pedigree was RHO(c.1040C>T). This variant leads to the change of codon 347 from encoding proline to encoding leucine, resulting in a severe clinical phenotype among family members. This study provides a certain molecular, clinical, and genetic basis for genetic counseling and gene diagnosis of RHO.