1.Disulfiram alleviates cardiac hypertrophic injury by inhibiting TAK1-mediated PANoptosis.
Wei-Dong LI ; Xuan-Yang SHEN ; Xiao-Lu JIANG ; Hong-Fu WEN ; Yuan SHEN ; Mei-Qi ZHANG ; Wen-Tao TAN
Acta Physiologica Sinica 2025;77(2):222-230
The study aims to examine the effects and potential mechanisms of disulfiram (DSF) on cardiac hypertrophic injury, focusing on the role of transforming growth factor-β-activated kinase 1 (TAK1)-mediated pan-apoptosis (PANoptosis). H9C2 cardiomyocytes were treated with angiotensin II (Ang II, 1 µmol/L) to establish an in vitro model of myocardial hypertrophy. DSF (40 µmol/L) was used to treat cardiomyocyte hypertrophic injury models, either along or in combination with the TAK1 inhibitor, 5z-7-oxozeaenol (5z-7, 0.1 µmol/L). We assessed cell damage using propidium iodide (PI) staining, measured cell viability with CCK8 assay, quantified inflammatory factor levels in cell culture media via ELISA, detected TAK1 and RIPK1 binding rates using immunoprecipitation, and analyzed the protein expression levels of key proteins in the TAK1-mediated PANoptosis pathway using Western blot. In addition, the surface area of cardiomyocytes was measured with Phalloidin staining. The results showed that Ang II significantly reduced the cellular viability of H9C2 cardiomyocytes and the binding rate of TAK1 and RIPK1, significantly increased the surface area of H9C2 cardiomyocytes, PI staining positive rate, levels of inflammatory factors [interleukin-1β (IL-1β), IL-18, and tumor necrosis factor α (TNF-α)] in cell culture media and p-TAK1/TAK1 ratio, and significantly up-regulated key proteins in the PANoptosis pathway [pyroptosis-related proteins NLRP3, Caspase-1 (p20), and GSDMD-N (p30), apoptosis-related proteins Caspase-3 (p17), Caspase-7 (p20), and Caspase-8 (p18), as well as necroptosis-related proteins p-MLKL, RIPK1, and RIPK3]. DSF significantly reversed the above changes induced by Ang II. Both 5z-7 and exogenous IL-1β weakened these cardioprotective effects of DSF. These results suggest that DSF may alleviate cardiac hypertrophic injury by inhibiting TAK1-mediated PANoptosis.
Animals
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MAP Kinase Kinase Kinases/physiology*
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Rats
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Myocytes, Cardiac/pathology*
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Disulfiram/pharmacology*
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Cardiomegaly
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Apoptosis/drug effects*
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Cell Line
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Angiotensin II
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Necroptosis/drug effects*
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Interleukin-1beta/metabolism*
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Receptor-Interacting Protein Serine-Threonine Kinases/metabolism*
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Lactones
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Resorcinols
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Zearalenone/administration & dosage*
2.Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways.
Ying HUANG ; Chen-Ling CHU ; Wen-Hui QIU ; Jia-Yi CHEN ; Lu-Xi CAO ; Shui-Yu JI ; Bin ZHU ; Guo-Kun WANG ; Quan-Quan SHEN
Journal of Integrative Medicine 2025;23(6):694-705
OBJECTIVE:
Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF.
METHODS:
The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations.
RESULTS:
Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells.
CONCLUSION
AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.
Epithelial-Mesenchymal Transition/drug effects*
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Animals
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Saponins/pharmacology*
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Triterpenes/pharmacology*
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Mice
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Peritoneal Fibrosis/pathology*
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Proto-Oncogene Proteins c-akt/metabolism*
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ErbB Receptors/metabolism*
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Phosphatidylinositol 3-Kinases/metabolism*
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Signal Transduction/drug effects*
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Male
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Humans
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Molecular Docking Simulation
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Cell Line
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Mice, Inbred C57BL
3.Comprehensive Analysis of Oncogenic, Prognostic, and Immunological Roles of FANCD2 in Hepatocellular Carcinoma: A Potential Predictor for Survival and Immunotherapy.
Meng Jiao XU ; Wen DENG ; Ting Ting JIANG ; Shi Yu WANG ; Ru Yu LIU ; Min CHANG ; Shu Ling WU ; Ge SHEN ; Xiao Xue CHEN ; Yuan Jiao GAO ; Hongxiao HAO ; Lei Ping HU ; Lu ZHANG ; Yao LU ; Wei YI ; Yao XIE ; Ming Hui LI
Biomedical and Environmental Sciences 2025;38(3):313-327
OBJECTIVE:
Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy.
METHODS:
Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death.
RESULTS:
FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism.
CONCLUSION
To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans
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Carcinoma, Hepatocellular/diagnosis*
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Liver Neoplasms/diagnosis*
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Immunotherapy
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Fanconi Anemia Complementation Group D2 Protein/metabolism*
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Prognosis
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Male
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Female
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Middle Aged
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Biomarkers, Tumor/metabolism*
4.The clinical characteristics and microbial distribution of sepsis-induced myocardial injury
Sun YU ; Chunyang XU ; Hongwei YE ; Shun WEN ; Liang YANG ; Caiyun YANG ; Shiqi LU ; Meili SHEN
Chinese Journal of Emergency Medicine 2025;34(2):173-179
Objective:To investigate the clinical characteristics of sepsis-induced myocardial injury and microbial distribution.Methods:It was a retrospective observational study conducted from Jan 2023 to Dec 2023 in the Department of Emergency Intensive Care Medicine, Changshu Hospital Affiliated to Soochow University. Patients meeting the sepsis 3.0 criteria were included, excluding those with underlying cardiovascular diseases or incomplete data. Patients were categorized into myocardial injury (SIMI) and non-myocardial injury (Non-SIMI) groups based on troponin levels. General patient information, laboratory results, microbial findings, and prognostic indicators were collected. Differences in clinical parameters between the two groups were compared. Factors showing statistical differences in univariate analysis were further analyzed using multivariable logistic regression to identify risk factors for SIMI. Conduct propensity score matching among Pulmonary infection patients who underwent bronchoalveolar lavage high-throughput sequencing to compare microbial distribution between groups. Bracken was used to estimate species-level abundance from Kraken2 results, and α and β diversity analyses were conducted on the metagenomic samples.Results:A total of 179 patients were included in the study, with 98 (54.4%) in the Non-SIMI group and 81 (45.5%) in the SIMI group. There were 69 deaths overall (38.5%), with 23 (23.7%) in the Non-SIMI group and 46 (56.8%) in the SIMI group (χ 2=20.347, P<0.01). The 28-day survival curve indicated survival rates in the SIMI group were significantly lower compared to the Non-SIMI group (Log Rank χ 2=21.270, P<0.01). Univariate analysis revealed that fungal infection rate ( P=0.007), C-reactive protein ( P=0.021), procalcitonin, blood urea nitrogen, creatinine, alanine transaminase, and lactate levels were higher in the SIMI group compared to the Non-SIMI group (all P<0.01), prothrombin time was prolonger ( P<0.01) and APACHEⅡ scores were higher ( P<0.01), while serum albumin, base excess, and platelet levels were lower (all P<0.01). Multivariable logistic regression analysis indicated that fungal infection ( OR=3.441, P=0.015) was a risk factor for SIMI, whereas base excess and platelets were protective factors ( OR=0.845, 0.988, both P<0.01). Comparison of bronchoalveolar lavage high-throughput sequencing results in the pulmonary infection subgroup showed the relative abundance of Haemophilus paraininfluenzae in Non-SIMI group was higher than SIMI group among the top 20 species ( P=0.013). There were no statistically significant differences in microbial αand β-diversity between the two groups. Conclusions:The incidence of SIMI is relatively highamong sepsis patients and it affects their prognosis. Risk factors for SIMI include fungal infection, decreased platelet count, and reduced base excess levels. Among patients with pulmonary infections, there is a lower risk of SIMI associated with Haemophilus influenzae infection.
5.Formulation and Analysis on the Standard of Construction of Medication Safety Culture
Wenjing HOU ; Su SHEN ; Aiping WEN ; Jin LU ; Jiancun ZHEN ; Wei ZHANG ; Dan MEI ; Zhicheng GONG ; Yubo WU ; Qunhong SHEN ; Weiyi FENG ; Ling TAN ; Yanhua ZHANG ; Fang LIU ; Xiaole ZHANG
Herald of Medicine 2024;43(7):1079-1083
The construction of a medication safety culture is important for medication safety management and rational drug use.The construction of medication safety culture standards is formulated based on relevant national policies and regulations,accreditation standards for hospitals,expert opinions,the current situation,and the development trend of the healthcare industry.With scientificity,general applicability,instructive guidance,and practicality,they standardized basic requirements,management processes,and improvement of the construction of medication safety culture.To facilitate understanding and the implementation of the standards,we describe the process of standards formulation and explain the key points of the standards.
6.Correlation of nutritional status with clinical characteristics and lung function in children with cystic fibrosis
Dong-Dan LI ; Yue-Lin SHEN ; Mei-Chen WANG ; Wen-Li YANG ; Lu-Lu XIA ; Yu-Qing ZHANG ; Shun-Ying ZHAO ; Jie YAN
Chinese Journal of Contemporary Pediatrics 2024;26(3):275-281
Objective To investigate the nutritional status of children with cystic fibrosis(CF)and understand the correlation between malnutrition and clinical characteristics as well as lung function.Methods A retrospective analysis was performed on clinical data of CF children admitted from January 2016 to June 2023.Clinical characteristics of CF children with different nutritional statuses were compared,and the correlation between malnutrition and lung function was analyzed.Results A total of 52 CF children were included,comprising 25 boys(48%)and 27 girls(52%),aged between 7 months and 17 years.Respiratory symptoms were the predominant clinical manifestations(96%,50/52).The prevalence of malnutrition was 65%(34/52),with moderate/severe malnutrition being the most common(65%,22/34).The malnutrition group had a longer duration of illness,higher proportion of digestive system symptoms,and lower levels of serum albumin(P<0.05).Pulmonary function parameters,including forced expiratory volume in one second as a percentage of the predicted value,ratio of forced expiratory volume in one second to forced vital capacity,forced expiratory flow at 25%of forced vital capacity exhaled,forced expiratory flow at 50%of forced vital capacity exhaled,forced expiratory flow at 75%of forced vital capacity exhaled,and maximum mid-expiratory flow as a percentage of the predicted value,were lower in the malnutrition group compared to the normal nutrition group(P<0.05).Correlation analysis showed body mass index Z-score was positively correlated with the above six pulmonary function parameters(P<0.05).Conclusions The prevalence of malnutrition is high in CF children and is associated with decreased lung function.CF children with higher body mass index have better lung function.Therefore,screening and evaluation of nutritional status as well as appropriate nutritional intervention should be emphasized in CF children.[Chinese Journal of Contemporary Pediatrics,2024,26(3):275-281]
7.Disease characteristics and costs of pediatric Mycoplasma Pneumoniae pneumonia hospitalization:a retrospective study at municipal hospitals from 2019 to 2023 in Shanghai
Ying-Wen WANG ; Feng WANG ; Li-Bo WANG ; Ai-Zhen LU ; Yi WANG ; Yong-Hao GUI ; Quan LU ; Yong YIN ; Jian-Hua ZHANG ; Ying-Zi YE ; Hong XU ; Bing SHEN ; Dan-Ping GU ; Xiao-Yan DONG ; Jia-Yu WANG ; Wen HE ; Xiao-Bo ZHANG
Fudan University Journal of Medical Sciences 2024;51(4):515-521
Objective To investigate disease characteristics and hospitalization costs of children with Mycoplasma Pneumoniae pneumonia(MPP)admitted to Shanghai municipal medical hospitals from 2019 to 2023.Methods Depending on the Shanghai Municipal Hospital Pediatric Alliance,we retrospectively investigated community acquired MPP pediatric patients hospitalized in 22 municipal hospitals with pediatric qualifications(including 4 children's hospitals)in Shanghai from Jan 2019 to Dec 2023.We collected the patients'diagnosis codes,gender,age,length of hospital stay,hospitalization costs,and whether they progressed to severe Mycoplasma pneumoniae pneumonia(SMPP).Results From 2019 to 2023,a total of 29 045 hospitalized children with MPP were treated,with 6 035 cases(20.8%)identified as SMPP in the 22 hospitals.Trend analysis revealed a rising trend with years in the proportion of SMPP patients(χ2trend=365.498,P<0.001).Among the 4 children's hospitals,there were 18 710 cases with MPP,including 4 078 cases(21.8%)of SMPP.The proportion of SMPP patients also showed an increasing trend with years(χ2trend=14.548,P<0.001),and the proportion in 2023(23.0%)was higher than that in previous years with statistical significance.There were statistical differences in the seasonal distribution of MPP cases between different years,with higher proportions in summer and autumn overall.The age distribution of hospitalized MPP children varied among different years,with school-age children accounting for the majority(56.8%)in 2023.There was no difference in the distribution of severe cases between different genders,but there were differences in the proportion of severe cases among different age groups in different years,with a gradual increase in severe cases among children aged 1 to 3 years(χ2trend=191.567,P<0.001).The average length of hospital stay for MPP during the epidemic was higher than that during non-epidemic periods,and there were statistically significant differences in the average length of hospital stay between different years(P<0.001).The individual hospitalization costs during the epidemic were higher than in other years,and there were statistically significant differences in individual hospitalization costs between different years(P<0.001).The total hospitalization costs were still higher in 2019 and 2023.The individual hospitalization costs for SMPP were higher than for non-SMPP cases.Conclusion MPP outbreaks occurred in Shanghai in 2019 and 2023,with the higher proportions in summer and autumn overall.Compared to previous years,the number of hospitalized MPP children in Shanghai was higher in 2023,with a higher proportion of SMPP cases,especially among children under 3 years old.The individual per capita hospitalization expenses for SMPP cases were higher than for non-SMPP cases.
8.A multicenter, randomized, controlled study on the treatment of pediatric influenza (wind-heat invading lung) with Qingxuan Zhike granules
Xi MING ; Xiaodong SHEN ; Jinni CHEN ; Jinya WANG ; Jiemin WANG ; Fengzhan CHEN ; Huiping SHEN ; Huihui HUANG ; Yingzhu LU ; Jialin ZHENG ; Ziwei WANG ; Ji BIAN ; Zihao FENG ; Naichao FENG ; Siqi CHEN ; Xunzhou LIU ; Xiaohua YAN ; Xiaoyan WANG ; Wen XIE ; Lei XIONG
Chinese Journal of Applied Clinical Pediatrics 2024;39(8):597-601
Objective:To evaluate the efficacy and safety of Qingxuan Zhike granules in improving cough symptoms and shortening the course of influenza (wind-heat invading lung) in children.Methods:In this multicenter, randomized, controlled clinical trial, a total of 240 outpatient influenza patients from 7 hospitals, including the First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, from April 2023 to December 2023 were collected.The subjects were randomly divided into the control group and the experimental group via SAS software using the block randomization method.The differences between two groups were compared with t test, corrected t test and χ2 test.Subjects in the control group were given Oseltamivir phosphate granules, orally, twice a day (weight ≤15 kg, 30 mg/time; weight >15-23 kg, 45 mg/time; weight >23-40 kg, 60 mg/time; weight >40 kg, 75 mg/time; age≥13 years, 75 mg/time).In addition to Oseltamivir phosphate granules, subjects in the experimental group were also given Qingxuan Zhike granules, orally, 3 times a day (1-3 years old, 1/2 bag each time; >3-6 years old, 3/4 bag each time; >6-14 years old, 1 bag each time).After 5 days of treatment, the medication was suspended for 2 days.The effect of cough, antipyretic effect, clinical recovery rate, clinical recovery time, Canadian Acute Respiratory Illness and Flu Scale (CARIFS) score, traditional Chinese medicine (TCM) syndrome effect, complication rate, and adverse reactions were evaluated between the two groups. Results:Finally, 232 cases were included in the study, including 115 cases in the experimental group and 117 cases in the control group.Before and after treatment, there were no significant difference in CARIFS cough score between the experimental group and the control group (all P>0.05).After treatment, the change in CARIFS cough score in the experimental group [(-1.00±0.91) scores]was significantly higher than that in the control group [(-0.75±0.98) scores] ( t=-1.995, P=0.047).After treatment, the change in TCM syndrome cough score in the experimental group [(-1.69±1.51) scores] was significantly higher than that in the control group [(-0.97±1.63) scores] ( t′=-0.035, P=0.001).The time of complete regression of fever in the experimental group [(44.82±22.72) h] was shorter than that in the control group [(51.35±27.07) h], and the difference between the two groups was statistically significant ( t=-1.966, P=0.050).The fever score showed that the area under the curve between the CARIFS symptom fever score and time in the experimental group was 4.40±2.42, while that in the control group was 5.12±2.44, and the difference between the two groups was statistically significant ( t=-2.252, P=0.025).The clinical recovery rate was 93.91%(108/115) in the experimental group and 92.31%(108/117) in the control group, and there was no significant difference between the two groups ( χ2=0.233, P>0.05).The clinical recovery time in the experimental group [(2.93±1.21) d] was shorter than that in the control group [(3.29±1.15) d], and the difference between the two groups was statistically significant ( t=-2.279, P=0.024).After treatment, there was a significant difference in TCM syndrome score variation between the experimental group [(-12.00±4.13) scores] and the control group [(-10.85±4.31) scores] ( t′=-2.067, P=0.040).No complication occurred in both groups, and there was no significant difference in the incidence of adverse events between the two groups ( χ2=1.299, P>0.05). Conclusions:Qingxuan Zhike granules combined with Oseltamivir phosphate can effectively improve the cough symptoms associated with influenza in children, shorten the time and course of fever, and improve the TCM syndrome score; thus, they are safe in clinical application.
9.Traditional Chinese Medicine Regulates Tumor-associated Macrophages in Colorectal Cancer: A Review
Meixuan GUO ; Yuxing LIN ; Mengyuan CAI ; Aling SHEN ; Wen LU ; Li LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):279-288
Colorectal cancer (CRC), a most common malignant tumor of the digestive tract, is often manifested by abdominal pain, changes in stool quality, blood in the stool, and weight loss, with rising morbidity and mortality year by year. The onset and development of CRC involve a variety of mechanisms, in which tumor microenvironment (TME) and tumor-associated macrophages (TAMs) have received increasing attention. TAMs influence the tumor development via immune escape and angiogenesis promotion and are associated with the prognosis of tumors. In recent years, traditional Chinese medicine (TCM) has been widely researched and applied in the treatment of cancers. Studies have discovered that TCM mainly exerts the therapeutic effects on CRC by inhibiting the proliferation, metastasis, and angiogenesis, promoting the apoptosis, and inducing autophagy of tumor cells and boosting the immune function. TCM as an effective treatment approach can regulate TAMs to inhibit tumor growth. Moreover, the active components and targets of TCM can be taken as new research directions of immunotherapy. This review describes TAMs and their roles in CRC progression and summarizes the molecular targets and mechanisms of different active components, compound prescriptions, and novel preparations of TCM against CRC, aiming to provide a mechanism reference for the clinical treatment of CRC with TCM and give new insights into the in-depth research on the prevention and treatment of CRC-related diseases with TCM.
10.Simultaneous content determination of twelve constituents in Bushen Huoxue Sanjie Capsules by HPLC
Ji-Yao YIN ; Jing HU ; Xia SHEN ; Xiao-Min CUI ; Hui REN ; Tong QU ; Ning LI ; Wen-Jin LU ; Zhi-Yong CHEN ; Kai QU
Chinese Traditional Patent Medicine 2024;46(1):1-6
AIM To establish an HPLC method for the simultaneous content determination of gallic acid,protocatechuic acid,morroniside,loganin,sweroside,paeoniflorin,hypericin,astragalin,salvianolic acid B,salvianolic acid A,epimedin C and icariin in Bushen Huoxue Sanjie Capsules.METHODS The analysis was performed on a 30℃thermostatic Agilent 5 TC-C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 240 nm.RESULTS Twelve constituents showed good linear relationships within their own ranges(r≥0.999 8),whose average recoveries were 97.11%-101.14%with the RSDs of 0.60%-2.65%.CONCLUSION This simple,accurate and reproducible method can be used for the quality control of Bushen Huoxue Sanjie Capsules.

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