1.Mechanism of Xiezhuo Jiedu Prescription in Treatment of Ulcerative Colitis by Inhibiting Ferroptosis and Alleviating Intestinal Mucosal Injury Based on Nrf2/SLC7A11/GPX4 Signaling Pathway
Qiang CHUAI ; Wenjing ZHAI ; Sujie JIA ; Xiaomeng LANG ; Jie REN ; Xin KANG ; Shijie REN ; Xingchi LIU ; Xin LIU ; Xiaohong JIANG ; Jianping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):160-169
ObjectiveTo investigate the mechanism of Xiezhuo Jiedu prescription in the treatment of ulcerative colitis (UC) by inhibiting ferroptosis and alleviating intestinal mucosal injury based on the nuclear factor E2 related factor 2/solute carrier family 7 member/glutathione peroxidase 4 (Nrf2/SLC7A11/GPX4) signaling pathway. MethodsA total of 60 male SD rats were divided into a normal group, a model group, high- and low-dose Xiezhuo Jiedu prescription groups (26.64 and 13.32 g·kg-1, respectively), a ferroptosis inhibitor group (Ferrostatin-1, 0.005 g·kg-1), and a mesalazine group (0.27 g·kg-1), with 10 rats in each group. A UC rat model was established by intrarectal administration of trinitrobenzene sulfonic acid (TNBS)-ethanol. The normal group and the model group were intragastrically administered normal saline. The other groups were given intragastric administration according to the corresponding dosage for 7 d. The general condition, disease activity index (DAI) score, colon length, and mucosal injury index (CDMI) score were observed in each group. The pathological changes of colon tissue in each group were observed by hematoxylin-eosin (HE) staining. The intestinal mucosa and mitochondrial morphology in each group were observed by transmission electron microscopy. The expression levels of Occludin, Claudin-1, mucin 2 (MUC2), and E-cadherin in intestinal tissue were detected by immunofluorescence (IF). Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) in each group, and a lactic acid assay kit or ELISA was employed to detect the expression levels of reactive oxygen species (ROS), ferrous ions (Fe2+), glutathione (GSH), malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), diamine oxidase (DAO), and D-lactate (D-LA). Real-time quantitative polymerase chain reaction (Real-time PCR) was applied to detect the mRNA expression levels of Nrf2, SLC7A11, GPX4, Occludin, Claudin-1, MUC2, and E-cadherin in each group, and Western blot was adopted to detect the protein expression levels of Nrf2, p-Nrf2, SLC7A11, and GPX4 in each group. ResultsCompared with the normal group, rats in the model group exhibited listlessness, sluggish response, and mucopurulent and bloody stools. The model group also showed significantly increased DAI score, colon length, CDMI score, and expression levels of TNF-α, IL-6, ROS, Fe2+, MDA, 4-HNE, DAO, and D-LA (P<0.01). In addition, it presented significantly decreased IF values of Occludin, Claudin-1, MUC2, and E-cadherin and mRNA and protein expression levels of IL-10, GSH, Nrf2, p-Nrf2, SLC7A11, and GPX4 (P<0.01). There were different degrees of improvement in each administration group after treatment, and the improvement was the most significant in the high-dose Xiezhuo Jiedu prescription group (P<0.01). ConclusionXiezhuo Jiedu prescription may alleviate intestinal mucosal injury by inhibiting ferroptosis of intestinal epithelial cells via regulating the Nrf2/SLC7A11/GPX4 signaling pathway, thereby exhibiting efficacy in the treatment of UC.
2.Palpitations, Shortness of Breath, Weakness in Limbs, Edema, and Dyspnea: A Rare Inflammatory Myopathy with Positive Aniti-mitochondrial Antibodies and Cardiac Involvement
Chunsu LIANG ; Xuchang ZHANG ; Ning ZHANG ; Lin KANG ; Xiaohong LIU ; Jiaqi YU ; Yingxian LIU ; Lin QIAO ; Yanli YANG ; Xiaoyi ZHAO ; Ruijie ZHAO ; Na NIU ; Xuelian YAN
Medical Journal of Peking Union Medical College Hospital 2025;16(1):248-255
This article presents a case study of a patient who visited the Geriatric Department of Peking Union Medical College Hospital due to "palpitations, shortness of breath for more than 2 years, limb weakness for 6 months, edema, and nocturnal dyspnea for 2 months". The patient exhibited decreased muscle strength in the limbs and involvement of swallowing and respiratory muscles, alongside complications of heart failure and various arrhythmias which were predominantly atrial. Laboratory tests revealed the presence of multiple autoantibodies and notably anti-mitochondrial antibodies. Following a comprehensive multidisciplinary evaluation, the patient was diagnosed with anti-mitochondrial antibody-associated inflammatory myopathy. Treatment involved a combination of glucocorticoids and immunosuppressants, along with resistance exercises for muscle strength and rehabilitation training for lung function, resulting in significant improvement of clinical symptoms. The case underscores the importance of collaborative multidisciplinary approaches in diagnosing and treating rare diseases in elderly patients, where careful consideration of clinical manifestations and subtle abnormal clinical data can lead to effective interventions.
3.Consensus recommendation on Comprehensive Geriatric Assessment for elderly cancer patients from Peking Union Medical College Hospital
Qiumei WANG ; Xiaoyuan LI ; Lin KANG ; Xiaohong SUN ; Hailong LI ; Yanping DUAN ; Ying LIU ; Mei GUAN ; Lin ZHAO
Basic & Clinical Medicine 2025;45(9):1122-1131
In the context of an aging society,the number of elderly cancer patients is constantly increasing,and geriatric oncology has garnered significant attention in recent years.Given the heterogeneity in the health status of older patients,it has become increasingly important to provide individualized diagnosis,treatment,follow-up,and care.Thus,it must be emphasized the Comprehensive Geriatric Assessment(CGA)for elderly patients,which encompasses their physical function,nutritional status,cognitive function,emotional state,comorbidities,polypharmacy,social situation,and treatment preferences.This article provides consensus recommendations on CGA tools for elderly patients prior to anticancer treatment,offering valuable references and insights for clinical practice in China.
4.Cer(d18:1/16:0)Promotes Mitochondrial Dysfunction and Fibrotic Phenotype Transformation in HK-2 Cells
Zhengwei DONG ; Kang YANG ; Xiaohong GUO ; Huan ZHAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(10):2545-2552
Objective To explore the effect of Cer(d18:1/16:0),the core marker in the development of diabetic kidney disease(DKD),on mitochondrial dysfunction and phenotypic transformation of human renal proximal tubule cells(HK-2)induced by high glucose.Methods With the help of qRT-PCR technology,the expression of ceramide synthesis related enzymes in HK-2 cells stimulated by high glucose was detected at the transcription level.The effects of different concentrations of Cer(d18:1/16:0)on the viability of HK-2 cells were detected by CCK8 method.The changes of mitochondrial number in HK-2 cells stimulated by different concentrations of Cer(d18:1/16:0)were evaluated by mitochondrial fluorescent probe.Western blot was used to detect the expression of mitochondrial related proteins and fibrosis indexes before and after the administration of Cer(d18:1/16:0).Results The expression of Ceramide synthase 2,(CERS2)in HK-2 cells increased in high glucose environment.Exogenous Cer(d18:1/16:0)can significantly inhibit the viability of HK-2 cells,can reduce the total and average fluorescence intensity of mitochondria in HK-2 cells induced by high glucose.The protein expression of CV-ATP5A and CIII-UQCRC2 decreased,while the protein expression of Coll 3,MMP9 and α-SMA increased.Conclusion Cer(d18:1/16:0)can induce mitochondrial dysfunction and fibrotic phenotype transformation in HK-2 cells stimulated by high glucose.
5.Cer(d18:1/16:0)Promotes Mitochondrial Dysfunction and Fibrotic Phenotype Transformation in HK-2 Cells
Zhengwei DONG ; Kang YANG ; Xiaohong GUO ; Huan ZHAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(10):2545-2552
Objective To explore the effect of Cer(d18:1/16:0),the core marker in the development of diabetic kidney disease(DKD),on mitochondrial dysfunction and phenotypic transformation of human renal proximal tubule cells(HK-2)induced by high glucose.Methods With the help of qRT-PCR technology,the expression of ceramide synthesis related enzymes in HK-2 cells stimulated by high glucose was detected at the transcription level.The effects of different concentrations of Cer(d18:1/16:0)on the viability of HK-2 cells were detected by CCK8 method.The changes of mitochondrial number in HK-2 cells stimulated by different concentrations of Cer(d18:1/16:0)were evaluated by mitochondrial fluorescent probe.Western blot was used to detect the expression of mitochondrial related proteins and fibrosis indexes before and after the administration of Cer(d18:1/16:0).Results The expression of Ceramide synthase 2,(CERS2)in HK-2 cells increased in high glucose environment.Exogenous Cer(d18:1/16:0)can significantly inhibit the viability of HK-2 cells,can reduce the total and average fluorescence intensity of mitochondria in HK-2 cells induced by high glucose.The protein expression of CV-ATP5A and CIII-UQCRC2 decreased,while the protein expression of Coll 3,MMP9 and α-SMA increased.Conclusion Cer(d18:1/16:0)can induce mitochondrial dysfunction and fibrotic phenotype transformation in HK-2 cells stimulated by high glucose.
6.Effects of Salvianolic Acid B on Mitochondrial Dysfunction and Fibrous Phenotype Transformation in HK-2 Cells Induced by High Glucose
Zhengwei DONG ; Kang YANG ; Xiaohong GUO ; Huan ZHAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(12):3145-3152
Objective To investigate the effect of Salvianolic acid B(SalB)on mitochondrial function and fibrosis phenotype of human renal proximal tubule cells(HK-2)induced by high glucose.Methods The dose of SalB in HK-2 was evaluated by CCK8 detection,and the effects of SalB on mitochondrial dysfunction and phenotypic transformation of cell fibrosis induced by high glucose were explored by qRT-PCR,Western blot and mitochondrial fluorescence probe.Results Compared with the control group,the number of mitochondria in HK-2 cells induced by high glucose decreased significantly(P<0.01),and high dose of SalB could significantly reduce the number of mitochondria.Compared with the control group,the expression level of CV-ATP5A protein in HK-2 cells induced by high glucose was significantly inhibited(P<0.01),and the expression of CV-ATP5A was significantly increased by low and high doses of SalB(P<0.01).Compared with the control group,the transcription levels of FN1,Coll3 and α-SMA in HK-2 cells induced by high glucose were significantly increased(P<0.05),and the intervention of SalB could significantly reduce the transcription levels of FN1,Coll3,MMP9 and α-SMA.Compared with the control group,the levels of FN1,Coll3 and α-SMA protein in HK-2 cells induced by high glucose were significantly increased,and the expression levels of FN1 and Coll3 protein could be significantly decreased by the intervention of SalB.Conclusion SalB,the main active component of Salvia miltiorrhiza,can improve the mitochondrial dysfunction of HK-2 cells induced by high glucose and effectively inhibit the phenotypic transformation of fibrosis.
7.Mechanism of LINC01410 promoting proliferation and migration in esophageal squamous cell carcinoma
Fei CAO ; Wenhao YU ; Xiaonan TANG ; Zidong MA ; Tingmin CHANG ; Yabin GONG ; Mingjuan LIAO ; Xiaohong KANG
China Oncology 2024;34(8):753-762
Background and purpose:Long non-coding RNA(lncRNA)LINC01410,with a length of 647 bp,participates in a variety of tumor biological processes.However,the role and mechanism of LINC01410 involved in esophageal squamous cell carcinoma(ESCC)remain unclear.This study aimed to explore the potential mechanism of LINC01410 promoting ESCC proliferation and invasion,to provide a potential prognostic indicator and therapeutic target for individuals with ESCC.Methods:Gene Expression Profiling Interactive Analysis 2(GEPIA2)databases were used to analyze the expression of LINC01410 and overall survival in esophageal squamous cell carcinoma data set in the Cancer Genome Atlas(TCGA).Gene Set Enrichment Analysis(GSEA)was performed to identify the underlying signaling pathways involved in the biological effects of LINC01410 in ESCC.A total of 62 pairs of ESCC tissues and paracancerous tissues from ESCC patients who underwent radical surgery in the Department of Thoracic Surgery at the First Affiliated Hospital of Xinxiang Medical College and the First People's Hospital of Pingdingshan City from January 2020 to December 2021 were collected.This project has been approved by the Hospital Ethics Committee(First Affiliated Hospital of Xinxiang Medical College,No.2018036;First People's Hospital of Pingdingshan City,No.2019-018).The expression of LINC01410 in ESCC tissues was detected by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR).We transfected EC109 cells with LV-NC or LV-over/LINC01410 and EC9706 cells with shRNA-NC or shRNA-LINC01410.Stable transfected cells(EC109/NC,EC109/OE,EC9706/NC and EC9706/KD)were selected in primary cell culture medium containing puromycin.The expression of LINC01410 was detected by RTFQ-PCR.The impact of LINC01410 on ESCC cell proliferation was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and colony formation assays.The effect of LINC01410 on ESCC cell invasion was detected by transwell migration assay.T cell factor/lymphoid enhancer factor 1(TCF/LEF1)luciferase reporter assay was performed to validate the effect of LINC01410 on the activity of canonical Wnt/β-catenin signaling pathway.The expressions of Wnt/β-catenin and epithelial-mesenchymal transition(EMT)signal pathway related proteins in ESCC cells were detected by Western blot.Results:By analyzing the LINC01410 expression from ESCC samples in TCGA by GEPIA2,we found LINC01410 was consistently increased in ESCC tumors compared with normal tissues(P<0.05),and high LINC01410 expression was associated with poorer overall survival(OS).RTFQ-PCR assay showed that expressions of LINC01410 were higher in esophageal cancer tissues and esophageal cancer cells(EC109 and EC9706)than in precancerous tissues and HEEC cells(P<0.05).The expression level of LINC01410 was significantly correlated with invasion range,lymph node metastasis and TNM stage in ESCC patients(P<0.01).LINC01410 expression was also upregulated in EC109/OE,however the expression of LINC01410 in EC9706/KD was decreased(P<0.01).MTT assay showed overexpression of LINC01410 increased the viability of EC109 cells,while knockdown of LINC01410 decreased the viability of EC9706 cells(P<0.01).Colony formation assay indicated that overexpression of LINC01410 enhanced the clonogenic ability of ESCC cells,while knockdown of LINC01410 reduced colony formation(P<0.01).Transwell migration assay showed that LINC01410 overexpression drastically increased the number of migratory cells,while silencing of LINC01410 suppressed the migration in EC9706 cells(P<0.01).GSEA revealed that Wnt/β-catenin and EMT pathways were significantly enriched in ESCC samples with a high level of LINC01410.TCF/LEF1 luciferase reporter assay showed higher levels of Wnt-dependent activities were observed in EC109/OE cells,whereas silenced LINC01410 in EC9706 cells led to contrary results(P<0.01).Western blot analysis showed that overexpression of LINC01410 in EC109 cell significantly increased the expression levels of N-cadherin,β-catenin,cyclin D1,c-Myc and decreased E-cadherin expression,while knockdown LINC01410 resulted in opposite results.Conclusion:LINC01410 promotes proliferation and metastasis of ESCC,which might be caused by activation of Wnt/β-catenin and EMT signaling pathways.
8.The effect of intrinsic capacity and comorbidity on adverse outcomes in community-dwelling older adults: path analysis based on structure equation model
Shuo LIU ; Xiaohong LIU ; Lin KANG ; Shan JIANG ; Jiaojiao LI ; Xinxiu YU
Chinese Journal of Geriatrics 2024;43(3):366-371
Objective:To examine the impact of intrinsic capacity(IC), comorbidity, and their interaction on the occurrence of adverse outcomes in community-dwelling older adults.Methods:This 2-year observational cohort study included 230 residents aged 75 and above who lived in the Beijing Taikang Yanyaun community active area from June to August 2018.The study evaluated the IC scale, Charlson comorbidity index(CCI), and activity of daily living(ADL).In September 2020, adverse outcomes such as functional decline(defined as a decline of at least one point on the ADL scores at 2-year follow-up compared with baseline)and falls were assessed.The structure equation model(SEM)path analysis was employed to examine the direct and indirect effects of IC and CCI on adverse outcomes.Results:Among the 212 older adults who completed a 2-year follow-up, aged 75-93(mean age 83.8±4.4)years, 59.4%(126 cases)were female.Out of these participants, 51.4%(109 cases)experienced functional decline and 33.5%(71 cases)had falls.Path analysis revealed that the direct effects of IC on functional decline and falls were significantly positive, with standardized coefficients of 0.430 and 0.369, respectively.However, the effect of CCI was not found to be significant.The multi-variable Logistic regression model showed that the total effect of IC on functional decline and falls remained significantly positive, with values of 1.184 and 0.915, respectively.CCI acted as a mediating factor, with indirect effects on functional decline and falls accounting for 5.4% and 0.8%, respectively.In terms of the relationship between age and adverse outcomes, the indirect effect of IC was significantly higher than that of CCI(functional decline: 0.192 vs.0.037; falls: 0.158 vs.0.017). Conclusions:The maintenance of IC in the health management of community-dwelling older adults should be given more attention as it can significantly affect the incidence of functional decline and falls.Comorbidity, on the other hand, has a weaker influence.
9.Impact of Sarcopenia on Long-term Outcomes in Elderly Inpatients with Type 2 Diabetes Mellitus: A Prospective Cohort Study
Ning ZHANG ; Xiaohong LIU ; Lin KANG ; Wei CHEN ; Xuan QU ; Minglei ZHU ; Xiaohong SUN
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1348-1355
To investigate the collective influence of sarcopenia on the extended prognosis of hospitalized elderly individuals with type 2 diabetes mellitus(T2DM). Patients with T2DM aged 65 years and older, who were admitted to the Geriatrics Department of Peking Union Medical College Hospital between January 2017 and January 2021, were consecutively enrolled in the study. The presence of sarcopenia was evaluated based on the diagnostic criteria established by the Asian Working Group for Sarcopenia(AWGS) in 2014. Additionally, assessments were made on the patients' comorbidities, functional status, nutritional status, and geriatric syndromes. Follow-up was conducted through outpatient visits and telephone calls to monitor outcomes such as severe disability, rehospitalization, and all-cause mortality. Cox regression analysis was performed to investigate the impact of concurrent sarcopenia on the long-term prognosis of hospitalized elderly individuals with T2DM. A total of 244 elderly inpatients with T2DM who met specific criteria were included in the study, comprising 110 males(45.1%) and 134 females(54.9%), with ages ranging from 65 to 93 years and a median age of 74 years. Sarcopenia was observed in 25.4%(62/244) of patients. Over a follow-up period of three to seven years(median 5.6 years), elderly T2DM patients with sarcopenia exhibited significantly higher rates of severe disability, rehospitalization, and all-cause death compared to those without sarcopenia(all The prevalence of sarcopenia is notably high among hospitalized elderly patients with T2DM, greatly affecting their long-term prognosis. It is imperative for clinicians to prioritize screening and implement interventions for sarcopenia in elderly T2DM patients to improve their quality of life and overall prognosis.
10.Cronkhite-Canada Syndrome Combined with Asymptomatic Novel Coronavirus Infection: A Case Report
Ning ZHANG ; Chenhao YANG ; Liangrui ZHOU ; Xiaohong SUN ; Xiaohong LIU ; Lin KANG ; Ji LI ; Hailong LI
Medical Journal of Peking Union Medical College Hospital 2024;15(2):406-412
This article presents a case study of a patient who had Cronkhite-Canada syndrome in combination with an asymptomatic novel coronavirus infection. The patient exhibited clinical symptoms of loss of appetite, hair and nail loss, and skin pigmentation. Digestive endoscopy revealed widespread and varying-sized polypoid changes in the mucosa of the stomach, duodenum, and colon. During the course of the illness, the patient tested positive for novel coronavirus nucleic acid. Treatment with moderate doses of prednisone resulted in the patient's hair regrowth and decreased skin hypopigmentation. The article provides a summary of the patient's diagnosis and treatment and a review of relevant literature, with the aim of enhancing clinicians' understanding of the disease.

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