1.Neuroprotective Effects of Transcranial Magneto-acoustic Stimulation on Parkinson’s Disease Model Mice by Regulating Mitophagy and Mitochondrial Homeostasis
Shuai ZHANG ; Yan-Bin WANG ; Yi-Hao XU ; Jin-Rui MI ; Xiao-Chao LU ; Yu-Chen AN ; Ji-Zhou LIU ; Jia-Qi SUN
Progress in Biochemistry and Biophysics 2026;53(5):1457-1470
ObjectiveTranscranial magneto-acoustic stimulation (TMAS) is an emerging non-invasive neuromodulation technique that may provide a novel non-pharmacological intervention strategy for Parkinson's disease (PD). PD is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to motor impairments such as bradykinesia, tremor, and rigidity. Increasing evidence indicates that mitochondrial dysfunction and impaired mitochondrial quality control are central mechanisms underlying dopaminergic neuronal loss. In particular, abnormalities in mitophagy and mitochondrial fission-fusion balance contribute substantially to oxidative stress, energy metabolic failure, and neuronal injury. At present, most clinical treatments for PD mainly alleviate symptoms but do not effectively halt disease progression. Therefore, exploring new interventions targeting the core pathological mechanisms is of considerable significance. This study aims to investigate whether TMAS can improve neural damage and motor dysfunction in PD mice by regulating mitophagy and the fission/fusion dynamic balance, thereby providing theoretical and experimental support for its application in PD treatment. MethodsMale C57BL/6 mice were used in this study. A PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days. After model induction, mice in the intervention group received TMAS once daily for 14 consecutive days, whereas the corresponding control group received sham stimulation. The stimulation target was positioned over the primary motor cortex (M1). Motor performance was evaluated using the pole test and the open-field test. To verify the activation effect of TMAS on the target cortical region, c-Fos immunohistochemistry was performed in the M1. To assess nigral dopaminergic neuronal injury, tyrosine hydroxylase (TH) immunohistochemistry was used to quantify TH-positive neurons in the SNc. Mitochondrial function was evaluated by measuring reactive oxygen species (ROS) levels and adenosine triphosphate (ATP) content in the SNc. Western blot was further performed to determine the expression of mitophagy-related proteins, including PINK1, Parkin, LC3-II, and p62, as well as mitochondrial dynamics-related proteins, including Drp1 and Opa1. ResultsTMAS significantly increased the number of c-Fos-positive cells in M1 (P<0.000 1), indicating effective activation of neurons in the targeted cortical region. Compared with the control group, MPTP-treated mice exhibited marked motor dysfunction, including a significant reduction in total distance traveled in the open-field test (P<0.000 1) and mean speed (P=0.000 1), as well as significant prolongation of turn time and total climbing time in the pole test (P<0.000 1). These behavioral impairments were accompanied by a substantial loss of TH-positive dopaminergic neurons in the SNc, whereas TMAS significantly increased TH-positive neuron survival (P<0.000 1). In parallel, MPTP induced a pronounced increase in ROS levels and a significant reduction in ATP content, indicating severe mitochondrial dysfunction and energy metabolism impairment (P<0.01). TMAS treatment significantly improved motor performance, as reflected by the reversal of MPTP-induced impairment in the open-field and pole tests, and significantly reduced ROS accumulation (P<0.01) while restoring ATP production (P<0.001). At the molecular level, MPTP markedly downregulated PINK1 and Parkin, decreased p62 expression, increased LC3-II accumulation, elevated Drp1 expression, and reduced Opa1 expression, whereas TMAS significantly reversed these abnormalities, suggesting restoration of mitophagy-related mitochondrial quality control and re-establishment of mitochondrial fission-fusion balance. Collectively, these findings indicate that TMAS ameliorates MPTP-induced neurotoxicity and restores mitochondrial homeostasis and energy metabolism. ConclusionTMAS effectively attenuates neural damage and improves motor dysfunction in MPTP-induced PD mice. Its neuroprotective effects are closely associated with multidimensional regulation of the mitochondrial quality control system, including restoration of PINK1/Parkin-mediated mitophagy and rebalancing of Drp1/Opa1-related mitochondrial dynamics. Rather than acting only as a symptomatic neuromodulatory intervention, TMAS may influence a key pathological axis of PD by improving mitochondrial homeostasis in SNc and protecting nigral dopaminergic neurons. These findings provide experimental evidence supporting TMAS as a promising non-invasive physical intervention for PD.
2.Neuroprotective Effects of Transcranial Magneto-acoustic Stimulation on Parkinson’s Disease Model Mice by Regulating Mitophagy and Mitochondrial Homeostasis
Shuai ZHANG ; Yan-Bin WANG ; Yi-Hao XU ; Jin-Rui MI ; Xiao-Chao LU ; Yu-Chen AN ; Ji-Zhou LIU ; Jia-Qi SUN
Progress in Biochemistry and Biophysics 2026;53(5):1457-1470
ObjectiveTranscranial magneto-acoustic stimulation (TMAS) is an emerging non-invasive neuromodulation technique that may provide a novel non-pharmacological intervention strategy for Parkinson's disease (PD). PD is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to motor impairments such as bradykinesia, tremor, and rigidity. Increasing evidence indicates that mitochondrial dysfunction and impaired mitochondrial quality control are central mechanisms underlying dopaminergic neuronal loss. In particular, abnormalities in mitophagy and mitochondrial fission-fusion balance contribute substantially to oxidative stress, energy metabolic failure, and neuronal injury. At present, most clinical treatments for PD mainly alleviate symptoms but do not effectively halt disease progression. Therefore, exploring new interventions targeting the core pathological mechanisms is of considerable significance. This study aims to investigate whether TMAS can improve neural damage and motor dysfunction in PD mice by regulating mitophagy and the fission/fusion dynamic balance, thereby providing theoretical and experimental support for its application in PD treatment. MethodsMale C57BL/6 mice were used in this study. A PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days. After model induction, mice in the intervention group received TMAS once daily for 14 consecutive days, whereas the corresponding control group received sham stimulation. The stimulation target was positioned over the primary motor cortex (M1). Motor performance was evaluated using the pole test and the open-field test. To verify the activation effect of TMAS on the target cortical region, c-Fos immunohistochemistry was performed in the M1. To assess nigral dopaminergic neuronal injury, tyrosine hydroxylase (TH) immunohistochemistry was used to quantify TH-positive neurons in the SNc. Mitochondrial function was evaluated by measuring reactive oxygen species (ROS) levels and adenosine triphosphate (ATP) content in the SNc. Western blot was further performed to determine the expression of mitophagy-related proteins, including PINK1, Parkin, LC3-II, and p62, as well as mitochondrial dynamics-related proteins, including Drp1 and Opa1. ResultsTMAS significantly increased the number of c-Fos-positive cells in M1 (P<0.000 1), indicating effective activation of neurons in the targeted cortical region. Compared with the control group, MPTP-treated mice exhibited marked motor dysfunction, including a significant reduction in total distance traveled in the open-field test (P<0.000 1) and mean speed (P=0.000 1), as well as significant prolongation of turn time and total climbing time in the pole test (P<0.000 1). These behavioral impairments were accompanied by a substantial loss of TH-positive dopaminergic neurons in the SNc, whereas TMAS significantly increased TH-positive neuron survival (P<0.000 1). In parallel, MPTP induced a pronounced increase in ROS levels and a significant reduction in ATP content, indicating severe mitochondrial dysfunction and energy metabolism impairment (P<0.01). TMAS treatment significantly improved motor performance, as reflected by the reversal of MPTP-induced impairment in the open-field and pole tests, and significantly reduced ROS accumulation (P<0.01) while restoring ATP production (P<0.001). At the molecular level, MPTP markedly downregulated PINK1 and Parkin, decreased p62 expression, increased LC3-II accumulation, elevated Drp1 expression, and reduced Opa1 expression, whereas TMAS significantly reversed these abnormalities, suggesting restoration of mitophagy-related mitochondrial quality control and re-establishment of mitochondrial fission-fusion balance. Collectively, these findings indicate that TMAS ameliorates MPTP-induced neurotoxicity and restores mitochondrial homeostasis and energy metabolism. ConclusionTMAS effectively attenuates neural damage and improves motor dysfunction in MPTP-induced PD mice. Its neuroprotective effects are closely associated with multidimensional regulation of the mitochondrial quality control system, including restoration of PINK1/Parkin-mediated mitophagy and rebalancing of Drp1/Opa1-related mitochondrial dynamics. Rather than acting only as a symptomatic neuromodulatory intervention, TMAS may influence a key pathological axis of PD by improving mitochondrial homeostasis in SNc and protecting nigral dopaminergic neurons. These findings provide experimental evidence supporting TMAS as a promising non-invasive physical intervention for PD.
3.Polarity-extended Liquid Chromatography-Mass Spectrometry System for Prostate Cancer Biomarker Screening Based on Extracellular Vesicles
Lu-Lu XIAO ; Meng-Xuan CHEN ; Shan-Shan PAN ; Yi-Chen WANG ; Tao-Hong HUANG ; Qi-Sheng ZHONG ; Yong CHEN ; Teng-Fei XU ; Jia-Hui ZHAO ; Xue-Song LIU
Chinese Journal of Analytical Chemistry 2025;53(11):1848-1859,中插4-中插29
Integrated metabolomic and lipidomic profiling,utilizing liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS),has emerged as a pivotal strategy for biomarker discovery.However,the inherent polarity disparity between metabolites and lipids complicates simultaneous analysis.To address this,a dual-stationary phase polarity-extended liquid chromatography(PELC)system was developed,which surpassed conventional one-dimensional LC(1D-LC)by enabling comprehensive coverage of both polar and non-polar compounds within a single injection.This system enhanced chromatographic resolution,peak capacity,and throughput while minimizing analytical variability.Extracellular vesicles(EVs),lipid bilayer-enclosed nanoparticles ubiquitously present in biofluids,had gained prominence as reservoirs of cancer biomarkers due to their cargo stability and pathophysiological relevance.Herein,the application of PELC-HRMS for concurrent metabolome-lipidome profiling in EVs was pioneered.A total of 193 metabolites were identified using this technique coupled with MS-DIAL software and Human Metabolome Database.Subsequently,this technique was employed to explore potential biomarkers for prostate cancer(PCa).Multivariate analysis identified 17 differentially abundant metabolites in PCa,implicating dysregulated pathways including purine metabolism,starch and sucrose metabolism,galactose metabolism,cysteine and methionine metabolism,and biosynthesis of unsaturated fatty acids.Notably,creatine(AUC=0.92)and DG 42:5(AUC=0.80)demonstrated robust diagnostic efficacy,attributable to their broad polarity ranges and EV-specific enrichment.This study established PELC as a high-fidelity platform for multi-omics integration in complex biospecimens,advancing mechanistic insights into metabolic rewiring and disease pathophysiology.
4.Multi-center clinical study on the efficacy and safety of combined lienal polypeptide injection therapy in children with Mycoplasma pneumoniae pneumonia
Qi CHENG ; Yunxiao SHANG ; Han ZHANG ; Jiujun LI ; Ning CHEN ; Lishen SHAN ; Nan YANG ; Lihua NING ; Xuemei BAI ; Jianhua LIU ; Yuling HAN ; Jichun WANG ; Jing LI ; Yong FENG ; Liyun LIU ; Li CHEN ; Si LIU ; Qinzhen ZHANG ; Jia ZHENG ; Fengchao LI ; Sukun LU ; Yun ZHANG ; Xiaoyi CHAI
International Journal of Pediatrics 2025;52(3):204-210
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.
5.Research on the association of breast cancer patients'prognosis with internal mammary sentinel lymph node biopsy
Ruijie JIA ; Zhiqiang SHI ; Qi ZHANG ; Yongjin LU ; Junsheng ZHENG ; Jing SUN ; Zhao BI ; Xiao SUN ; Yongsheng WANG ; Pengfei QIU
China Oncology 2025;35(4):394-403
Background and purpose:Internal mammary sentinel lymph node biopsy(IMSLNB)is a minimally invasive diagnostic technique for regional lymph nodes in breast cancer,which can provide accurate lymph staging and guide adjuvant treatment decision,but its clinical application has been controversial.The purpose of this study was to investigate the prognosis of IMSLNB in early breast cancer.Methods:In this study,a retrospective cohort of 7 949 patients with breast cancer from January 1,2016 to December 31,2021 was analyzed.After applying propensity score matching,the patients were divided into IMSLNB group and no-IMSLNB group,and the regional recurrence-free survival(RRFS),local recurrence-free survival(LRFS),distant metastasis-free survival(DMFS),disease-free survival(DFS)and overall survival(OS)of the two groups were compared.This study was approved by the Clinical Research Ethics Committee of the Affiliated Tumor Hospital of Shandong First Medical University(approval number:SDTHEC20130324).Results:A total of 990 patients were included in the final analysis(330 in the IMSLNB group and 660 in the no-IMSLNB group).IMSLN metastasis was found in 54 patients in the IMSLNB group,including 47 patients with axillary lymph node(ALN)metastasis and 7 patients with IMSLN metastasis only.The IMSLN transfer rate was 16.4%.The median follow-up of 41 months showed that the IMSLNB group demonstrated better 3-year DFS[98.4%vs 94.2%,hazard ratio(HR)=0.509;95%CI:0.312-0.828,P=0.007]and 5-year DFS(92.5%vs 87.3%,HR=0.214,95%CI:0.206-0.222,P=0.011)compared with no-IMSLNB group.However,no significant differences were observed in 3-year OS(99.1%vs 99.4%,HR=0.618,95%CI:0.231-1.655,P=0.338)or 5-year OS(98.5%vs 99.1%,HR=0.52,95%CI:0.51-0.53,P=0.392)between the two groups.The 3-year RRFS in the IMSLNB group was better compared with the no-IMSLNB group(99.09%vs 97.73%,HR=0.066;95%CI:0.061-0.071,P=0.048),while no significant differences were observed in 3-year LRFS(99.70%vs 98.19%,HR=0.209;95%CI:0.201-0.217,P=0.130)or DMFS(95.76%vs 96.06%,HR=0.865,95%CI:0.858-0.872,P=0.820)between the two groups.The exploratory subgroup analysis of DFS revealed that patients in the following subgroups could significantly benefit from IM-SLNB(P<0.05):diagnosis age(≤50 years),premenopausal status,BMI(≤24),lymphovascular invasion(LVI,present),tumor location(lateral),molecular subtype[hormone receptor positive(HR+)/human epidermal growth factor receptor 2 negative(HER2-)],histological type(invasive ductal carcinoma),and axillary lymph node status(positive).Conclusion:IMSLNB can provide more accurate regional lymph node staging for early breast cancer,help optimize adjuvant radiotherapy strategies,and improve patients'DFS and RRFS.It can be promoted as a minimally invasive staging technique for regional lymph nodes.
6.Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer.
Dan FENG ; Jian ZHANG ; Huanmin NIU ; Xiaoxue ZHENG ; Mengqi JIA ; Qiqi LU ; Jing WANG ; Wenxue GUO ; Qi SUN ; Huiqing YUAN ; Hongxiang LOU
Acta Pharmaceutica Sinica B 2025;15(4):2095-2113
The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe2+ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe2+, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.
7.Research on the association of breast cancer patients'prognosis with internal mammary sentinel lymph node biopsy
Ruijie JIA ; Zhiqiang SHI ; Qi ZHANG ; Yongjin LU ; Junsheng ZHENG ; Jing SUN ; Zhao BI ; Xiao SUN ; Yongsheng WANG ; Pengfei QIU
China Oncology 2025;35(4):394-403
Background and purpose:Internal mammary sentinel lymph node biopsy(IMSLNB)is a minimally invasive diagnostic technique for regional lymph nodes in breast cancer,which can provide accurate lymph staging and guide adjuvant treatment decision,but its clinical application has been controversial.The purpose of this study was to investigate the prognosis of IMSLNB in early breast cancer.Methods:In this study,a retrospective cohort of 7 949 patients with breast cancer from January 1,2016 to December 31,2021 was analyzed.After applying propensity score matching,the patients were divided into IMSLNB group and no-IMSLNB group,and the regional recurrence-free survival(RRFS),local recurrence-free survival(LRFS),distant metastasis-free survival(DMFS),disease-free survival(DFS)and overall survival(OS)of the two groups were compared.This study was approved by the Clinical Research Ethics Committee of the Affiliated Tumor Hospital of Shandong First Medical University(approval number:SDTHEC20130324).Results:A total of 990 patients were included in the final analysis(330 in the IMSLNB group and 660 in the no-IMSLNB group).IMSLN metastasis was found in 54 patients in the IMSLNB group,including 47 patients with axillary lymph node(ALN)metastasis and 7 patients with IMSLN metastasis only.The IMSLN transfer rate was 16.4%.The median follow-up of 41 months showed that the IMSLNB group demonstrated better 3-year DFS[98.4%vs 94.2%,hazard ratio(HR)=0.509;95%CI:0.312-0.828,P=0.007]and 5-year DFS(92.5%vs 87.3%,HR=0.214,95%CI:0.206-0.222,P=0.011)compared with no-IMSLNB group.However,no significant differences were observed in 3-year OS(99.1%vs 99.4%,HR=0.618,95%CI:0.231-1.655,P=0.338)or 5-year OS(98.5%vs 99.1%,HR=0.52,95%CI:0.51-0.53,P=0.392)between the two groups.The 3-year RRFS in the IMSLNB group was better compared with the no-IMSLNB group(99.09%vs 97.73%,HR=0.066;95%CI:0.061-0.071,P=0.048),while no significant differences were observed in 3-year LRFS(99.70%vs 98.19%,HR=0.209;95%CI:0.201-0.217,P=0.130)or DMFS(95.76%vs 96.06%,HR=0.865,95%CI:0.858-0.872,P=0.820)between the two groups.The exploratory subgroup analysis of DFS revealed that patients in the following subgroups could significantly benefit from IM-SLNB(P<0.05):diagnosis age(≤50 years),premenopausal status,BMI(≤24),lymphovascular invasion(LVI,present),tumor location(lateral),molecular subtype[hormone receptor positive(HR+)/human epidermal growth factor receptor 2 negative(HER2-)],histological type(invasive ductal carcinoma),and axillary lymph node status(positive).Conclusion:IMSLNB can provide more accurate regional lymph node staging for early breast cancer,help optimize adjuvant radiotherapy strategies,and improve patients'DFS and RRFS.It can be promoted as a minimally invasive staging technique for regional lymph nodes.
8.Correlation between estrogen metabolism of intestinal flora and liver fibrosis based on fecal microbiota transplantation
Na PAN ; Xue-ping QI ; Hui-jie SHENG ; Xiao-yu LYU ; Lu-yao GAO ; Hao-yang CHEN ; Yan-yan YIN ; Jia-jia WANG
Chinese Pharmacological Bulletin 2025;41(8):1508-1516
Aim To study the correlation between es-trogen metabolism function of intestinal flora and liver fibrosis disease phenotype and differential intestinal bacteria by fecal microbiota transplantation(FMT).Methods C57BL/6J male mice were divided into normal group(Control-M),liver fibrosis Model group(Model),FMT-1 group(normal mice fecal microbiota transplantation from liver fibrosis mice),and FMT-2 group(liver fibrosis mice fecal microbiota transplanta-tion from female mice).The model group was induced by high fat and high glucose combined with low dose of CCl4 for 16 weeks.In the FMT group,the bacteria were destroyed by mixed antibacterial solution and then the corresponding fecal microbiota solution was given.The model group was established in the FMT-2 group and the model group at the same time.Liver function(ALT,AST)was detected by biochemical methods;liver inflammation(IL-1α,IL-6)was detected by ELISA;liver pathology was detected by HE and Mas-son methods;the expressions of α-SMA,collagen Ⅰ,estrogen receptor ERα,ERβ and GPER were detected by Western blot;estrogen metabolic enzymes β-glucu-ronidase and β-glucosidase in intestinal flora were de-tected by double antibody sandwich assay;gut microbi-ota was detected by 16S rDNA method;the correlation between estrogen metabolic enzymes,estrogen receptors and disease phenotypes and disease-related differential bacteria was analyzed by Pearson correlation analysis.Results Liver function,inflammation and fibrosis in-dices were significantly higher in the model group than those in the control-M group and significantly lower in the FMT-2 group than in the model group;estrogen metabolic enzymes of the intestinal flora significantly increased in the model group compared to the control-M group and significantly decreased in the FMT-2 group compared to the model group;the model group showed a significant increase in ERβ and GPER and a significant decrease in ERα compared to the control-M group,while the FMT-2 group showed a significant de-crease in ERβ and GPER and a significant increase in ERα compared to the model group;the FMT-2 group increased the enterobacterial abundance and diversity reduced by modelling;estrogen metabolic enzymes,es-trogen receptor ERβ and GPER were all positively cor-related with the disease phenotype,while the opposite was true for ERα;estrogen metabolic enzymes were positively correlated with Allobaculum,Ruminococcus and Alistipes,and negatively correlated with Akkerman-sia,Lactobacillus and Prevotella.Conclusions Fecal microbiota transplantation in female mice can alleviate liver fibrosis in male mice,which is related to the im-provement of estrogen metabolism of intestinal flora.
9.Effect and potential mechanism of clarithromycin in treatment of inflammatory enteritis
Jia-qi CHEN ; Xu-wen MAO ; Yong-xing HUANG ; Xiang-tian TAN ; GULIRUOYI·PAERHATI ; Lu-feng CHENG
Chinese Pharmacological Bulletin 2025;41(6):1125-1134
Aim To explore the mechanism of clar-ithromycin in treating inflammatory bowel disease(IBD)by inhibiting Kv1.3 channel protein in colonic epithelial cells.Methods A chronic IBD rat model was induced using dextran sulfate sodium(DSS)in vi-vo experiments,with clarithromycin intervention.The physical signs of each group of rats were observed,and the disease activity index(DAI)score and colonic mu-cosal damage index(CMDI)score were calculated.RT-qPCR was used to detect the levels of relevant cyto-kines in colonic tissue of rats.Flow cytometry was em-ployed to detect the relative proportions of immune cells in the peripheral blood and colonic tissue of each group of rats.Lipopolysaccharide(LPS)was used to establish an inflammation model of colon epithelial cells(NCM460)to clarify the inhibitory effect of clar-ithromycin on Kv1.3 channel protein.Results In vi-vo experiments:compared to the model group,the clar-ithromycin intervention group exhibited a reduced de-gree of weight loss(P<0.01),and a significant de-crease in DAI scores(P<0.01).There was an in-crease in colon length,a reduction in weight,and a de-crease in CMDI scores(P<0.05).Levels of TNF-α,IL-1 β,and IL-6 in colon tissue were significantly re-duced(P<0.01).The numbers of peripheral blood and colonic regulatory T lymphocytes(Th),cytotoxic T lymphocytes(CTL),natural killer cells(NK),B lym-phocytes(B),and dendritic cells(DC)were signifi-cantly decreased(P<0.05).Clarithromycin reduced the expression of Kv1.3 channel protein in colon tissue(P<0.05).In vitro experiments:compared to the model group,the clarithromycin group significantly pro-moted the proliferation of NCM460 cells(P<0.01)and simultaneously significantly reduced the levels of TNF-α and IL-6 in cells(P<0.05).Clarithromycin also reduced the expression of Kv1.3 channel protein in NCM460 cells(P<0.05).Conclusions Clar-ithromycin may play an immunomodulatory role by in-hibiting the expression of Kv1.3 channel protein,re-ducing inflammation in the body,and playing a role in the treatment of IBD.
10.Fluorescence labeling for simulation of contamination with operators and their surroundings during debridement and dressing
Huijuan LI ; Hui GUAN ; Jin LIU ; Peiying ZHANG ; Huixue JIA ; Qian LU ; Xin QI
Chinese Journal of Nosocomiology 2025;35(14):2200-2203
OBJECTIVE To stimulate the debridement and dressing process under the approximately real clinical scene by fluorescence labeling and understand the contamination status of the operators' bodies and their surround-ings so as to improve the strategies.METHODS A total of 41 trainees were recruited from Enterostomal Therapist Nursing Education Program of Peking University School of Medicine and International School of Wound Thera-pists of Peking University First Hospital in 2023.The examination was designed by stimulating the debridement and dressing operations with fluorescence labeling,the orange was used to simulate the wound of the patients,and the pad towel was placed under the orange to represent the contaminated surroundings of the wound.A round le-sion area with diameter of 2 cm was uniformly marked on the surface of the orange peel by the operators,the trai-nees were asked to remove the lesion tissues and take dressings.The fluorescent powders were smeared evenly on the orange and pad towel before the examination,and no fluorescence labeling for the surroundings was guaranteed.The trainees were required to wear hats,masks,isolation gowns and gloves during the operations,and take off the gloves and trace the scope of fluorescent contamination with ultraviolet radiator after the examina-tion.RESULTS The contamination rate was 92.68%for the trainees' bodies,100.00%for their surroundings.The hands and forearms were the most severe contaminated body sites,and the contamination rates were 85.37%(35/41)and 34.15%(14/41),respectively.The downside of the pad towel was the most frequently contaminated area of the surroundings,with the proportion of 90.24%(37/41);the right side of the pad towel was the area with the contamination disseminated farthest,with the median distance of dissemination 13.50 cm.In addition,the dressing change carts of 75.61%(31/41)of the trainees were contaminated.CONCLUSIONS The operations of de-bridement and dressing change may lead to varying degrees of contamination of their bodies and surroundings.It is necessary to strengthen the hand hygiene and protective isolation during the process of dressing change and pay attention to the disinfection of the dressing change carts so as to minimize the risk of hospital-associated infec-tions.

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