1.Heat shock protein family A member 5 regulation of ferroptosis alleviates acute-phase mucosal injury in ulcerative colitis
Jingxian YAN ; Xinyu BAI ; Hao LIANG ; Fengrui ZHANG ; Yinglei MIAO ; Junkun NIU
Chinese Journal of Internal Medicine 2025;64(7):643-651
Objective:This study aimed to investigate the role of heat shock protein family A member 5 (HSPA5) in ferroptosis at its regulatory mechanisms in ulcerative colitis (UC), using both a dextran sulfate sodium (DSS)-induced mouse model of acute colitis and in vitro cell experiments.Methods:Differentially expressed genes in UC were identified using the GSE87466 dataset from the Gene Expression Omnibus, cross-referenced with the ferroptosis-related gene database FerrDB (version 2). A protein-protein interaction (PPI) network was constructed, identifying HSPA5 as a core hub gene. To validate its role in vivo, acute colitis was induced in C57BL/6 mice using DSS, followed by treatment with the ferroptosis inhibitor Ferrostatin-1 (Fer-1). Lipid peroxidation and ferroptosis levels were assessed by measuring malondialdehyde (MDA) and iron content in colon tissues. The expression of ferroptosis-related proteins, including prostaglandin-endoperoxide synthase 2 (PTGS2), glutathione peroxidase 4 (GPX4), ferritin light chain (FTL), activating transcription factor 4 (ATF4), and HSPA5, in addition to tight junction proteins ZO-1 and Occludin, were evaluated using immunohistochemistry and Western blotting. In vitro, an inflammatory model was established using lipopolysaccharide (LPS)-stimulated Caco-2 cells. Lentiviral knockdown of HSPA5 was performed to assess its regulatory effects on ferroptosis by assessing MDA levels, GPX4 activity, and the expression of related proteins. Statistical analyses were conducted with SPSS (version 29.1), with t-tests or one-way ANOVA for normally distributed data and the Mann-Whitney U test for ordinal data. Statistical significance was set at P<0.05. Results:Based on the PPI analysis and previous research, HSPA5 emerged as a key gene linking UC and ferroptosis. In DSS-treated mice, colonic injury was accompanied by elevated MDA levels ( t=5.72, P<0.001) and iron accumulation ( t=6.32, P<0.001). DSS also increased the expression of PTGS2 and proteins in the ATF4-HSPA5 pathway, while reducing the levels of GPX4, FTL, ZO-1, and Occludin. These findings could be partially reversed by Fer-1 (MDA: t=2.92, P<0.05; iron: t=5.84, P<0.001). In Caco-2 cells, LPS treatment elevated the expression of PTGS2, ATF4, and HSPA5, and elevated the MDA content ( t=9.63, P<0.001), while reducing the expression of FTL, GPX4, ZO-1, and Occludin, as well as GPX4 enzyme activity ( t=-11.20, P<0.001). Knockdown of HSPA5 further exacerbated these changes, significantly increasing MDA levels ( t=4.15, P<0.01), decreasing GPX4 activity ( t=-9.81, P<0.001), and altering ferroptosis-related protein expression. Conclusion:HSPA5 appears to protect against intestinal damage in UC by enhancing GPX4 expression and activity, thereby reducing ferroptosis and preserving epithelial barrier integrity through the maintenance of tight junction proteins.
2.Heat shock protein family A member 5 regulation of ferroptosis alleviates acute-phase mucosal injury in ulcerative colitis
Jingxian YAN ; Xinyu BAI ; Hao LIANG ; Fengrui ZHANG ; Yinglei MIAO ; Junkun NIU
Chinese Journal of Internal Medicine 2025;64(7):643-651
Objective:This study aimed to investigate the role of heat shock protein family A member 5 (HSPA5) in ferroptosis at its regulatory mechanisms in ulcerative colitis (UC), using both a dextran sulfate sodium (DSS)-induced mouse model of acute colitis and in vitro cell experiments.Methods:Differentially expressed genes in UC were identified using the GSE87466 dataset from the Gene Expression Omnibus, cross-referenced with the ferroptosis-related gene database FerrDB (version 2). A protein-protein interaction (PPI) network was constructed, identifying HSPA5 as a core hub gene. To validate its role in vivo, acute colitis was induced in C57BL/6 mice using DSS, followed by treatment with the ferroptosis inhibitor Ferrostatin-1 (Fer-1). Lipid peroxidation and ferroptosis levels were assessed by measuring malondialdehyde (MDA) and iron content in colon tissues. The expression of ferroptosis-related proteins, including prostaglandin-endoperoxide synthase 2 (PTGS2), glutathione peroxidase 4 (GPX4), ferritin light chain (FTL), activating transcription factor 4 (ATF4), and HSPA5, in addition to tight junction proteins ZO-1 and Occludin, were evaluated using immunohistochemistry and Western blotting. In vitro, an inflammatory model was established using lipopolysaccharide (LPS)-stimulated Caco-2 cells. Lentiviral knockdown of HSPA5 was performed to assess its regulatory effects on ferroptosis by assessing MDA levels, GPX4 activity, and the expression of related proteins. Statistical analyses were conducted with SPSS (version 29.1), with t-tests or one-way ANOVA for normally distributed data and the Mann-Whitney U test for ordinal data. Statistical significance was set at P<0.05. Results:Based on the PPI analysis and previous research, HSPA5 emerged as a key gene linking UC and ferroptosis. In DSS-treated mice, colonic injury was accompanied by elevated MDA levels ( t=5.72, P<0.001) and iron accumulation ( t=6.32, P<0.001). DSS also increased the expression of PTGS2 and proteins in the ATF4-HSPA5 pathway, while reducing the levels of GPX4, FTL, ZO-1, and Occludin. These findings could be partially reversed by Fer-1 (MDA: t=2.92, P<0.05; iron: t=5.84, P<0.001). In Caco-2 cells, LPS treatment elevated the expression of PTGS2, ATF4, and HSPA5, and elevated the MDA content ( t=9.63, P<0.001), while reducing the expression of FTL, GPX4, ZO-1, and Occludin, as well as GPX4 enzyme activity ( t=-11.20, P<0.001). Knockdown of HSPA5 further exacerbated these changes, significantly increasing MDA levels ( t=4.15, P<0.01), decreasing GPX4 activity ( t=-9.81, P<0.001), and altering ferroptosis-related protein expression. Conclusion:HSPA5 appears to protect against intestinal damage in UC by enhancing GPX4 expression and activity, thereby reducing ferroptosis and preserving epithelial barrier integrity through the maintenance of tight junction proteins.
3.Clinical Analysis of 311 Cases with Giant Ovarian Mass
Hua LIU ; Jingxian LING ; Xianghong ZHU ; Rong LI ; Xiaoqiu TANG ; Yan ZHANG ; Huaijun ZHOU
Journal of Practical Obstetrics and Gynecology 2024;40(1):73-77
Objective:To analyze the clinicopathological features of giant ovarian masses(mean diameter≥10 cm)and analyze the clinical characteristics of patients in different age groups.Methods:The clinicopathological characteristics of 311 patients diagnosed with giant ovarian masses by surgery at Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University from January 2014 to December 2022 were retrospectively analyzed.Patients were further stratified by age and mass size to compare the differences of clinical and patho-logical features among different age groups and different mass diameter groups.Results:①The median age of thepatients were 44(24,60)years old.The first symptoms were as follows:ovarian mass discovered during physi-cal examination,abdominal pain,bloating,conscious abdominal distension,and symptoms of compression.②The surgical methods were as follows:unilateral oophorectomy(30.5%,95/311),ovarian cystectomy(28.9%,90/311),tumor staging or cytoreductive surgery(28.0%,87/311),total hysterectomy with bilateral adnexectomy(12.5%,39/311).③The pathological types were benign(49.5%,154/311),malignant(31.8%,99/311)and borderline(18.7%,58/311).④ Patients complained abdominal distension in<20 years old group were signifi-cantly higher than the other two groups(P<0.05).The ovarian resection rate in the>50-year-old group was higher than that of the other two groups(P<0.05),and the rate of unilateral ovarian resection in the<20-year-old group was still as high as 30.1%(15/49).⑤ The size of the mass correlated with the duration of the disease.When the disease course was between 1 to 6 months,the mass diameter line>30 cm was the most common(P<0.05).The incidence of borderline tumors in the>30 cm group was significantly higher than that in the other two groups,and the difference was statistically significant(P<0.05).Conclusions:Ovarian mucinous and mucinous borderline tumors are the most common types of giant adnexal masses.The size of the mass tends to increase with the prolongation of the disease course.The incidence of borderline tumors increases with the in-crease of mass.Health education for young people should be strengthened.When abdominal pain,abdominal bloating,especially lower abdominal distension occurs,they should seek medical treatment in time to avoid adnex-ectomy due to borderline tumors.
4.Construction and validation of a risk model for colorectal cancer prognosis based on N6-methyladenosine modification and immune infiltration
Jingjing YANG ; Huaijuan GUO ; Jingxian MAO ; Jiaxin WANG ; Ying WANG ; Xuebing YAN ; Xiaoping PAN
Journal of Clinical Medicine in Practice 2024;28(7):1-8
Objective To investigate the prognostic value of N6-methyladenosine (m6A) modification related genes and immune infiltration in colorectal cancer (CRC) and construct a risk model for predicting outcome of patients. Methods The transcriptome data and matched clinical information of CRC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The prognostic value of m6A modification related genes and immune infiltration were investigated using the consensus clustering method and single sample gene set enrichment analysis. The weighted gene co-expression network analysis (WGCNA) was used to identify prognostic genes related with m6A modification and immune infiltration. Lasso regression analysis was used to construct a multi-gene risk model. The expression differences of prognostic genes identified were further validated through expression differential analysis in the Gene Expression Profiling Interactive Analysis (GEPIA) database. Finally, the Kaplan-Meier was used to evaluate the predicting performance of the model in different subgroups and external validation cohorts. Results Both the m6A modification and immune infiltration phenotype could effectively stratify the prognosis of CRC patients from the TCGA cohort. Most m6A modification related genes were significantly correlated with immune infiltration in CRC tissues. Four following prognostic genes were selected using the WGCNA method combined with Lasso regression analysis: intelectin-1, lymphocyte antigen 6 complex locus G6D, atonal homolog 1 and matrix metalloproteinase 28. In colorectal cancer tissues, the expression levels of lymphocyte antigen 6 complex locus G6D and matrix metalloproteinase 28 exhibited significant differences compared to adjacent non-cancerous tissues (
5.Application of Linear Accelerator on Boarding Kilovolt Fan Beam CT and Megavolt Cone Beam CT System on Set-up Errors During Radiation Treatment
Yong ZHOU ; Zeying JIANG ; Baofeng SU ; Jianfeng ZHOU ; Qian WANG ; Anting WANG ; Jingxian LIU ; Yan XUE ; Huiyi FENG ; Xiaoliang WU ; Mingxing XIAO ; Wenyong TAN
Cancer Research on Prevention and Treatment 2023;50(11):1097-1102
Objective To quantify the setup errors for the different anatomical sites of patients who received intensity-modulated radiotherapy (IMRT) with linear accelerator on-board kilovolt fan beam CT(kV-FBCT) as non-isocenter IGRT and megavolt cone beam CT (MV-CBCT) as isocenter IGRT. Methods A retrospective analysis was performedon 70 patients who underwent radiotherapy, kV-FBCT, and/or MV-CBCT scans after each routine setup prior to IMRT. The average displacement (M), systematic error (Σ), and random error (б) at different treatment sites in the left-right, anterior-posterior, and cranial-caudal directions were calculated according to the individual displacements. The formula 2.5Σ+0.7б was used to estimate the PTV margin in respective direction. For each single patient, the root mean square in three directions was used as 3D displacement. Results A total of 1130 displacements were recorded in the 70 patients. The PTV margin was estimated to be 1.9-3.1 mm in head and neck cancer, 2.8-5.1 mm in thoracic cancer, 4.6-5.1 mm in breast cancer, 3.0-5.5 mm in upper abdominal cancer, and 3.5-6.8 mm in pelvic tumor. For the 3D mean displacements, the head and neck, thoracic, breast, upper abdominal, and pelvic cancer were 2.4±1.0, 4.0±1.6, 4.1±2.0, 4.6±2.1, and 4.6±2.1 mm, respectively. The average 3D displacement obtained by kV-FBCT and MV-CBCT were 4.1 and 3.4 mm, respectively (
6.Professor ZHANG Boli's Experience in Treating Stubborn Bi (痹) with Ruxiang (Olibanum)-Moyao (Myrrha) Pair
Hongchang JI ; Xianglong HUANG ; Yaoyuan LIU ; Lu XIAO ; Xiao LI ; Zhaoqi WANG ; Jingxian YAN ; Yajun YU ; Feng JIANG
Journal of Traditional Chinese Medicine 2023;64(19):1961-1963
This paper summarized professor ZHANG Boli's experience in treating stubborn bi (痹) with the herbal pair of Ruxiang (Olibanum)- Moyao (Myrrha). The basic pathogenesis of stubborn bi is channel and collateral stasis and obstruction. Ruxiang and Moyao are thus used in mutual reinforcement to rectify qi and diffuse bi, activate blood and relieve pain, thereby removing static and obstructed qi and blood, unblocking the obstructed channels and colla-terals, which is especially suitable for stubborn bi caused by channel and collateral obstruction. In clinical practice, the herbal pair of Ruxiang-Moyao is used together with qi-moving and blood-activating medicinals to treat chest bi by expelling stasis and diffusing stagnation, dissipating cold and unblocking vessels. To treat long-term wither and weakness in late stage of stroke, the medicinals of boosting qi and invigorating blood, unblocking channels and venting collaterals can be added to the herbal pair so as to soothe and drain vessels and collaterals, harmonize and regulate qi and blood. Simiao Yongan Decoction (四妙勇安汤) can be integrated in the treatment of vessel bi by moving qi and dissolving stasis, and for the long-term stubborn vessel bi, integrated internal and external treatment is suggested by external use of Ruxiang-Moyao to vent bi with aromatics. Moreover, it is emphasized to use the herbal pair of Ruxiang-Moyao in accordance with indications and cautions.
7.Research progress in the treatment of Alzheimer's disease by regulating brain-gut-microbiome axis with "Sanjiao" acupuncture method
Hong LI ; Long YAN ; Yulin QIAN ; Tao YU ; Shan CONG ; Yu WANG ; Jingxian HAN ; Meng WANG
Chinese Journal of Geriatrics 2023;42(4):484-488
Recent studies have found that the brain-gut-microbiome axis(BGMA)is closely related to the occurrence and development of Alzheimer's disease(AD). BGMA can affect AD in various aspects such as neuro-immune regulation and intestinal microflora, and is a potential new target for the treatment of AD.The "Sanjiao" acupuncture method is proposed by professor Han Jingxian, a famous Chinese medicine practitioner, based on his theory of "dysfunction of Qi activity of Sanjiao leads to aging" , and has been widely used in the treatment of AD and other age-related diseases in clinical practice.This article reviews the theory of "dysfunction of Qi activity of Sanjiao leads to aging" and the relationship between the "Sanjiao" acupuncture method and BGMA, with the hope that the "San Jiao" acupuncture method can become a new target for treatment of AD in the future.
8.Neuroprotective effect and the mechanism of Shenzao jiannao oral liquid on Alzheimer ’s disease model mice
Xian JIN ; Jicong CHEN ; Yuying XIN ; Honghe XIAO ; Yan LI ; Yan DENG ; Jingxian YANG
China Pharmacy 2022;33(7):836-841
OBJECTIVE To study the neuroprotective effects of Shenzao jianna o oral liquid (SZJN)on Alzheimer ’s disease (AD)model mice and its mechanism. METHODS The mice were randomly divided into sham operation group ,model group , Donepezil hydrochloride tablet group (0.65 mg/kg),SZJN low-dose ,medium-dose and high-dose groups (0.3,1.5 and 7.5 g/kg, calculated by crude drug quantity ),with 12 mice in each group ,half male and half female. Each group was given relevant medicine(intragastric administration of water at constant volume in sham operation group and model group ),twice a day ,for consecutive 28 d. On the 15th day of administration ,intracerebroventricular injection of β-amyloid 1-42(Aβ1-42)combined with intraperitoneal injection of scopolamine hydrobromide were used to induce AD model. Morris water maze was used to detect the learning and memory ability of mice. HE staining and Nissl staining were used to evaluate the pathological changes of brain tissue in mice. The levels of MDA and SOD in brain tissue of mice were detected. The phosphorylation level of cyclic adenosine monophosphate response element binding protein (CREB) and expression of brain-derived neurotrophic factor (BDNF) in hippocampal tissues were detected by Western blot. RESULTS Compared with sham operation group ,the escape latency of the model group was significantly prolonged ,and the number of crossing the platform and the percentage of residence time in the target quadrant were significantly reduced (P<0.01). The level of SOD in brain tissue ,the phosphorylation level of CREB and the expression level of BDNF in hippocampus decreased significantly (P<0.01),while the level of MDA increased significantly (P< 0.01). In hippocampal CA 1 area and cortical tissue ,nerve cells showed significantly decreased number ,the disordered arrangement and large gap ;the shape of nucleus was irregular and deeply stained ,and Nissl body was blurred ,loosely arranged and the number decreased. Compared with model group ,the escape latency of mice in each dose group of SZJN was significantly shortened ,and the times of crossing the platform and the percentage of residence time in the target quadrant were significantly jing- increased(P<0.01). Above indexes of brain tissue in mice were reversed sig nificantly in SZJN high-dose group (P<0.01),and pathological damage of brain tiss ue was improved. CONCLUSIONS SZJN can significantly improve the learning and memory ability of AD model mice ,and alleviate the pathological injury and oxidative stress of brain tissue ,which may be related to the activation of CREB/BDNF signaling pathway.
9.Development of symptom assessment questionnaire for embolization syndrome after transcatheter hepatic arterial chemoembolization in patients with liver cancer and the test of its reliability and validity
Yan GUO ; Shoumei JIA ; Anni WANG ; Jingxian YU ; Ying′e ZHU
Chinese Journal of Practical Nursing 2022;38(22):1721-1727
Objective:To establish a questionnaire to assess symptom of embolization syndrome after transcatheter hepatic arterial chemoembolization (TACE) in patients with liver cancer, so as to provide a tool of assessing and managing symptom management after TACE.Methods:From March 2020 to June 2021, through literature review, qualitative interview and Delphi expert consultation, the first draft of symptom assessment questionnaire for TACE post-operative embolism syndrome was prepared. The reliability and validity of the questionnaire were tested in 200 patients with liver cancer treated by TACE in department of Liver Oncology, Zhongshan Hospital affiliated to Fudan University.Results:According to the feedback from Delphi expert consultation a draft questionnaire with 9 items of physiological symptoms and 6 items of psychological and social symptoms was formed. Item analysis showed that each item in the questionnaire had a good degree of differentiation. There was significant correlation between each item and the total score of the questionnaire. Three factors were extracted by exploratory factor analysis, naming psychosocial symptom group as factor 1, somatic discomfort symptom group as factor 2 and gastrointestinal reaction symptom group as factor 3, and the cumulative variance contribution rate was 62.592%. Spearman correlation coefficient between this questionnaire and the Anderson Symptom Assessment Scale was 0.855( P<0.05). The Cronbach α of the total questionnaire was 0.898, and. The Cronbach α of the three factors were 0.885, 0.771 and 0.870 respectively. Conclusions:The symptom assessment questionnaire of embolization syndrome after TACE in liver cancer patients prepared in this study has good reliability and validity, which can provide an evaluation basis for the symptom management of TACE.
10.Customized orthotic insoles improve the gait and balance of hemiplegic stroke survivors more effectively than an ankle-foot orthosis
Jie WANG ; Weidong NI ; Jingxian PAN ; Yanmin WANG ; Jianzhong YANG ; Long YU ; Yan WANG ; Furong WANG ; Pufeng HUANG ; Lei QIAO ; Ying ZHANG
Chinese Journal of Physical Medicine and Rehabilitation 2022;44(11):999-1003
Objective:To observe the effect of customized orthotic insoles on the gait and balance of hemiplegic stroke survivors.Methods:Sixty stroke survivors with gait abnormalities were randomly divided into a group fitted with ankle foot orthoses (AFO) ( n=30) and a group who received customized orthotic insoles ( n=30). All received conventional rehabilitation training for 4 weeks. Before the fitting, as well as 8 hours and 4 weeks afterward, both groups were evaluated using the Tinetti gait scale (TGS), the plantar pressure balance index, the difference in length between their right and left step, step width, the Timed Up and Go test (TUGT), the Fugl-Meyer lower extremity assessment (FMA-LE), the 6-minute walk test (6MWT), a trunk impairment scale (TIS), the Berg Balance Scale (BBS) and the Barthel Index (BI). Results:At 8 hours after the fitting all of the insole group′s measurements were better than those of the AFO group, on average, but the differences were not statistically significant. After 4 weeks the average TGS, balance index barefoot and wearing the orthosis, step length difference, BBS and BI of the insoles group were significantly better than the AFO group′s averages. The other indicators were not significantly different.Conclusions:Customized orthotic insoles are more effective than an AFO in relieving the biomechanical abnormalities in hemiplegic patients′ feet and ankles, and enhancing their balance and gait.


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