1.Herbal Textual Research on Houttuyniae Herba in Famous Classical Formulas
Dan ZHAO ; Changgui YANG ; Chuanzhi KANG ; Chenghong XIAO ; Zhikun WU ; Hongliang MA ; Jiwen WANG ; Xiufu WAN ; Sheng WANG ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):250-259
This article systematically analyzes the historical evolution of the name, medicinal parts, origin, harvesting, processing and other aspects of Houttuyniae Herba(HH) by referring to the medical books, prescription books and other documents of the past dynasties, combined with the research materials related to modern and contemporary times, in order to provide a basis for the development of famous classical formulas containing this herb. In ancient literature, HH was often referred to as "Ji" and "Jicai", the name of "Ji" was first recorded in Mingyi Bielu during the Han and Wei dynasties, and the name of Yuxingcao was first seen in Lyuchanyan Bencao during the southern Song dynasty and has continued to this day. The origin of HH used throughout history is consistent, all of which are the whole herb or aboveground parts of Houttuynia cordata in Saururaceae family. HH recorded throughout history has a wide range of production areas, mostly self-produced self-marketing. In ancient times, fresh HH was often used as medicine by pounding its juice without involving any processing steps. Both fresh and dried products can be used as medicine, the fresh products uses the whole plant, while the dried products uses the aboveground parts, which are cleaned, selected and processed before use. Fresh products are harvested regardless of season, while dried products are harvested in both summer and autumn, with summer as the best. In ancient times, there were no specific requirements for the quality of HH, while in modern times, "intact stems and leaves with a strong fishy smell" are preferred. In addition, the medicinal properties of HH have undergone significant changes from ancient to modern times. In the early period, it was believed that its medicinal property was slightly warm, until the 1977 edition of Chinese Pharmacopoeia officially changed it to slightly cold. Both ancient and modern literature states that HH can be used for the treatment of carbuncle and malignant sores, Lyuchanyan Bencao for the first time introduced HH fresh juice can relieve summer heat, since Diannan Bencao recorded that it can be used for lung carbuncle, and gradually developed into the first choice for the treatment of lung carbuncle. Based on the research results, it is suggested that fresh herb or dried aboveground parts of H. cordata are used as medicine when developing famous classical formulas.
2.Exploration of pharmacodynamic material basis and mechanism of Jinbei Oral Liquid against idiopathic pulmonary fibrosis based on UHPLC-Q-TOF-MS/MS and network pharmacology.
Jin-Chun LEI ; Si-Tong ZHANG ; Xian-Run HU ; Wen-Kang LIU ; Xue-Mei CHENG ; Xiao-Jun WU ; Wan-Sheng CHEN ; Man-Lin LI ; Chang-Hong WANG
China Journal of Chinese Materia Medica 2025;50(10):2825-2840
This study aims to explore the pharmacodynamic material basis of Jinbei Oral Liquid(JBOL) against idiopathic pulmonary fibrosis(IPF) based on serum pharmacochemistry and network pharmacology. The ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technology was employed to analyze and identify the components absorbed into rat blood after oral administration of JBOL. Combined with network pharmacology, the study explored the pharmacodynamic material basis and potential mechanism of JBOL against IPF through protein-protein interaction(PPI) network construction, "component-target-pathway" analysis, Gene Ontology(GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. First, a total of 114 compounds were rapidly identified in JBOL extract according to the exact relative molecular mass, fragment ions, and other information of the compounds with the use of reference substances and a self-built compound database. Second, on this basis, 70 prototype components in blood were recognized by comparing blank serum with drug-containing serum samples, including 28 flavonoids, 25 organic acids, 4 saponins, 4 alkaloids, and 9 others. Finally, using these components absorbed into blood as candidates, the study obtained 212 potential targets of JBOL against IPF. The anti-IPF mechanism might involve the action of active ingredients such as glycyrrhetinic acid, cryptotanshinone, salvianolic acid B, and forsythoside A on core targets like AKT1, TNF, and ALB and thereby the regulation of multiple signaling pathways including PI3K/AKT, HIF-1, and TNF. In conclusion, JBOL exerts the anti-IPF effect through multiple components, targets, and pathways. The results would provide a reference for further study on pharmacodynamic material basis and pharmacological mechanism of JBOL.
Drugs, Chinese Herbal/pharmacokinetics*
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Animals
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Tandem Mass Spectrometry
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Network Pharmacology
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Rats
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Chromatography, High Pressure Liquid
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Rats, Sprague-Dawley
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Male
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Idiopathic Pulmonary Fibrosis/metabolism*
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Humans
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Administration, Oral
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Protein Interaction Maps/drug effects*
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Signal Transduction/drug effects*
3.Studies on pharmacological effects and chemical components of different extracts from Bawei Chenxiang Pills.
Jia-Tong WANG ; Lu-Lu KANG ; Feng ZHOU ; Luo-Bu GESANG ; Ya-Na LIANG ; Guo-Dong YANG ; Xiao-Li GAO ; Hui-Chao WU ; Xing-Yun CHAI
China Journal of Chinese Materia Medica 2025;50(11):3035-3042
The medicinal materials of Bawei Chenxiang Pills(BCPs) were extracted via three methods: reflux extraction by water, reflux extraction by 70% ethanol, and extraction by pure water following reflux extraction by 70% ethanol, yielding three extracts of ST, CT, and CST. The efficacy of ST(760 mg·kg~(-1)), CT(620 mg·kg~(-1)), and CST(1 040 mg·kg~(-1)) were evaluated by acute myocardial ischemia(AMI) and p-chlorophenylalanine(PCPA)-induced insomnia in mice, respectively. Western blot was further utilized to investigate their hypnosis mechanisms. The main chemical components of different extracts were identified by the UPLC-Q-Exactive-MS technique. The results showed that CT and CST significantly increased the ejection fraction(EF) and fractional shortening(FS) of myocardial infarction mice, reduced left ventricular internal dimension at end-diastole(LVIDd) and left ventricular internal dimension at end-systole(LVIDs). In contrast, ST did not exhibit significant effects on these parameters. In the insomnia model, CT significantly reduced sleep latency and prolonged sleep duration, whereas ST only prolonged sleep duration without shortening sleep latency. CST showed no significant effects on either sleep latency or sleep duration. Additionally, both CT and ST upregulated glutamic acid decarboxylase 67(GAD67) protein expression in brain tissue. A total of 15 main chemical components were identified from CT, including 2-(2-phenylethyl) chromone and 6-methoxy-2-(2-phenylethyl) chromone. Six chemical components including chebulidic acid were identified from ST. The results suggested that chromones and terpenes were potential anti-myocardial ischemia drugs of BCPs, and tannin and phenolic acids were potential hypnosis drugs. This study enriches the pharmacological and chemical research of BCPs, providing a basis and reference for their secondary development, quality standard improvement, and clinical application.
Animals
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Drugs, Chinese Herbal/isolation & purification*
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Mice
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Male
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Sleep Initiation and Maintenance Disorders/physiopathology*
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Humans
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Myocardial Infarction/drug therapy*
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Myocardial Ischemia/drug therapy*
4.Current situation of medicinal animal breeding and research progress in sustainable utilization of resources.
Cheng-Cai ZHANG ; Jia WANG ; Yu-Jie ZHOU ; Xiao-Yu DAI ; Xiu-Fu WAN ; Chuan-Zhi KANG ; De-Hua WU ; Jia-Hui SUN ; Sheng WANG ; Lan-Ping GUO
China Journal of Chinese Materia Medica 2025;50(16):4397-4406
Traditional Chinese medicine(TCM) is the pillar for the development of motherland medicine, and animal medicine has a long history of application in China, characterized by wide resources, strong activity, definite efficacy, and great benefits. It has significant potential and important status in the consumption market of raw materials of TCM. In the context of global climate change, farming system alterations, and low renewability, the depletion of wild medicinal animal resources has accelerated. Accordingly, the conservation and sustainable utilization of wild resources of animal medicinal materials has become a problem that garners increasing attention and urgently needs to be solved. This paper summarizes the current situation of domestic and foreign medicinal animal breeding and research progress in industrial application in recent years and points out the issues related to standardized breeding, germplasm selection and breeding, and quality evaluation standards for medicinal animals. Furthermore, this paper discusses standardized breeding, quality standards, resource protection and utilization, and the search for alternative resources for rare and endangered medicinal animals. It proposes that researchers should systematically carry out in-depth basic research on animal medicine, improve the breeding scale and level of medicinal animals, employ modern technology to enhance the quality standards of medicinal materials, and strengthen the research and development of alternative resources. This approach aims to effectively address the relationship between protection and utilization and make a significant contribution to the sustainable development of medicinal animal resources and the animal-based Chinese medicinal material industry.
Animals
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Breeding
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China
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Medicine, Chinese Traditional
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Conservation of Natural Resources
5.Beneficial Effects of Dendrobium officinale Extract on Insomnia Rats Induced by Strong Light and Noise via Regulating GABA and GABAA Receptors.
Heng-Pu ZHOU ; Jie SU ; Ke-Jian WEI ; Su-Xiang WU ; Jing-Jing YU ; Yi-Kang YU ; Zhuang-Wei NIU ; Xiao-Hu JIN ; Mei-Qiu YAN ; Su-Hong CHEN ; Gui-Yuan LYU
Chinese journal of integrative medicine 2025;31(6):490-498
OBJECTIVE:
To explore the therapeutic effects and underlying mechanisms of Dendrobium officinale (Tiepi Shihu) extract (DOE) on insomnia.
METHODS:
Forty-two male Sprague-Dawley rats were randomly divided into 6 groups (n=7 per group): normal control, model control, melatonin (MT, 40 mg/kg), and 3-dose DOE (0.25, 0.50, and 1.00 g/kg) groups. Rats were raised in a strong-light (10,000 LUX) and -noise (>80 db) environment (12 h/d) for 16 weeks to induce insomnia, and from week 10 to week 16, MT and DOE were correspondingly administered to rats. The behavior tests including sodium pentobarbital-induced sleep experiment, sucrose preference test, and autonomous activity test were used to evaluate changes in sleep and emotions of rats. The metabolic-related indicators such as blood pressure, blood viscosity, blood glucose, and uric acid in rats were measured. The pathological changes in the cornu ammonis 1 (CA1) region of rat brain were evaluated using hematoxylin and eosin staining and Nissl staining. Additionally, the sleep-related factors gamma-aminobutyric acid (GABA), glutamate (GA), 5-hydroxytryptamine (5-HT), and interleukin-6 (IL-6) were measured using enzyme linked immunosorbent assay. Finally, we screened potential sleep-improving receptors of DOE using polymerase chain reaction (PCR) array and validated the results with quantitative PCR and immunohistochemistry.
RESULTS:
DOE significantly improved rats' sleep and mood, increased the sodium pentobarbital-induced sleep time and sucrose preference index, and reduced autonomic activity times (P<0.05 or P<0.01). DOE also had a good effect on metabolic abnormalities, significantly reducing triglyceride, blood glucose, blood pressure, and blood viscosity indicators (P<0.05 or P<0.01). DOE significantly increased the GABA content in hippocampus and reduced the GA/GABA ratio and IL-6 level (P<0.05 or P<0.01). In addition, DOE improved the pathological changes such as the disorder of cell arrangement in the hippocampus and the decrease of Nissel bodies. Seven differential genes were screened by PCR array, and the GABAA receptors (Gabra5, Gabra6, Gabrq) were selected for verification. The results showed that DOE could up-regulate their expressions (P<0.05 or P<0.01).
CONCLUSION
DOE demonstrated remarkable potential for improving insomnia, which may be through regulating GABAA receptors expressions and GA/GABA ratio.
Animals
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Dendrobium/chemistry*
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Rats, Sprague-Dawley
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Male
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Sleep Initiation and Maintenance Disorders/blood*
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Plant Extracts/therapeutic use*
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Receptors, GABA-A/metabolism*
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Noise/adverse effects*
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Light/adverse effects*
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gamma-Aminobutyric Acid/metabolism*
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Sleep/drug effects*
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Rats
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Receptors, GABA/metabolism*
6.Endoplasmic reticulum membrane remodeling by targeting reticulon-4 induces pyroptosis to facilitate antitumor immune.
Mei-Mei ZHAO ; Ting-Ting REN ; Jing-Kang WANG ; Lu YAO ; Ting-Ting LIU ; Ji-Chao ZHANG ; Yang LIU ; Lan YUAN ; Dan LIU ; Jiu-Hui XU ; Peng-Fei TU ; Xiao-Dong TANG ; Ke-Wu ZENG
Protein & Cell 2025;16(2):121-135
Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology*
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Humans
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Endoplasmic Reticulum/immunology*
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Animals
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Nogo Proteins/antagonists & inhibitors*
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Mice
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Cell Line, Tumor
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Xanthones/pharmacology*
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Neoplasms/pathology*
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Mice, Nude
7.Genome-wide investigation of transcription factor footprints and dynamics using cFOOT-seq.
Heng WANG ; Ang WU ; Meng-Chen YANG ; Di ZHOU ; Xiyang CHEN ; Zhifei SHI ; Yiqun ZHANG ; Yu-Xin LIU ; Kai CHEN ; Xiaosong WANG ; Xiao-Fang CHENG ; Baodan HE ; Yutao FU ; Lan KANG ; Yujun HOU ; Kun CHEN ; Shan BIAN ; Juan TANG ; Jianhuang XUE ; Chenfei WANG ; Xiaoyu LIU ; Jiejun SHI ; Shaorong GAO ; Jia-Min ZHANG
Protein & Cell 2025;16(11):932-952
Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics*
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Humans
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Chromatin/genetics*
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Animals
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Binding Sites
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Mice
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DNA Footprinting/methods*
8.Gender-Specific Prevalence and Risk Factors of Hypertension in a Chinese Rural Population: The Henan Rural Cohort Study.
Fayaz AHMAD ; Tahir MEHMOOD ; Xiao Tian LIU ; Ying Hao YUCHI ; Ning KANG ; Wei LIAO ; Rui Yu WU ; Bota BAHETI ; Xiao Kang DONG ; Jian HOU ; Sohail AKHTAR ; Chong Jian WANG
Biomedical and Environmental Sciences 2025;38(11):1417-1429
OBJECTIVE:
To investigate hypertension (HTN) trends, key risk factors, and gender disparities in rural China, and to propose targeted strategies for improving HTN control in resource-limited settings.
METHODS:
This longitudinal study used data from the Henan Rural Cohort Study, including baseline (2015-2017; n = 39,224) and follow-up (2018-2022; n = 28,621) participants. HTN was defined as systolic/diastolic blood pressure ≥ 140/90 mmHg, self-reported diagnosis, or use of antihypertensive medication. Severity was classified using a 7-tier blood pressure (BP) staging system (optimal, normal, high normal, and HTN stages 1-4). A generalized linear mixed-effects model (GLMM) identified associated risk factors.
RESULTS:
HTN prevalence increased modestly from 32.7% (95% CI: 32.2-33.2) to 33.9% (95% CI: 33.3%-34.4%). Awareness and treatment improved from 20.1% to 25.3%, and from 18.8% to 24.4%, respectively, but control rates remained low (6.2% to 12.3%). After adjustment, women had a 1.53-fold higher HTN risk than men ( OR = 1.53, 95% CI: 1.43-1.63), revealing gender-specific trends. Key risk factors included alcohol use ( OR = 1.37, 95% CI: 1.27-1.47) and overweight status ( OR = 1.76, 95% CI: 1.66-1.86). BP staging showed an increase in optimal BP (42.3% to 45.8%), but stagnant management of advanced HTN stages.
CONCLUSION
Hypertension in rural China is shaped by behavioral risk factors and healthcare access gaps. Gender-sensitive, community-based interventions, including task-shifting models, are necessary to mitigate the growing burden of hypertension.
Humans
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Hypertension/etiology*
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China/epidemiology*
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Female
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Male
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Rural Population/statistics & numerical data*
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Prevalence
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Risk Factors
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Middle Aged
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Adult
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Aged
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Longitudinal Studies
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Sex Factors
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Cohort Studies
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East Asian People
9.Interaction analysis of mismatch repair protein and adverse clinicopathological features on prognosis of colon cancer
Kexuan LI ; Fuqiang ZHAO ; Qingbin WU ; Junling ZHANG ; Shuangling LUO ; Shidong HU ; Bin WU ; Heli LI ; Guole LIN ; Huizhong QIU ; Junyang LU ; Lai XU ; Zheng WANG ; Xiaohui DU ; Liang KANG ; Xin WANG ; Ziqiang WANG ; Qian LIU ; Yi XIAO
Chinese Journal of Digestive Surgery 2024;23(6):826-835
Objective:To investigate the interactive effect of mismatch repair (MMR) protein status and adverse clinicopathological features on prognosis of stage Ⅰ-Ⅲ colon cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 650 patients with colon cancer of stage Ⅰ-Ⅲ who were admitted to 7 hospitals in China from January 2016 to December 2017 were collected. There were 963 males and 687 females, aged 62(53,71)years. Patients were classified as 230 cases of MMR deficiency (dMMR) and 1 420 cases of MMR proficiency (pMMR) based on their MMR protein status. Observation indicators: (1) comparison of clinicopathological characteristics between patients of different MMR protein status; (2) analysis of factors affecting the survival outcomes of patients of dMMR; (3) analysis of factors affecting the survival outcomes of patients of pMMR; (4) interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The random forest interpolation method was used for missing values in data interpolation. Univariate analysis was conducted using the COX proportional risk regression model, and multivariate analysis was conducted using the COX stepwise regression with forward method. The coefficient of multiplication interaction effect was obtained using the interaction term coefficient of COX proportional risk regression model. Evaluation of additive interaction effects was conducted using the relative excess risk due to interaction ( RERI). Results:(1) Comparison of clinicopathological characteristics between patients of different MMR protein status. There were significant differences in age, T staging, the number of lymph node harvest, the number of lymph node harvest <12, high grade tumor between patients of dMMR and pMMR ( P<0.05). (2) Analysis of factors affecting the survival outcomes of patients of dMMR. Results of multivariate analysis showed that T staging, N staging, the number of lymph node harvest <12 were independent factors affecting the disease-free survival (DFS) of colon cancer patients of dMMR ( hazard ratio=3.548, 2.589, 6.702, 95% confidence interval as 1.460-8.620, 1.064-6.301, 1.886-23.813, P<0.05). Age and N staging were independent factors affecting the overall survival (OS) of colon cancer patients of dMMR ( hazard ratio=1.073, 10.684, 95% confidence interval as 1.021-1.126, 2.311-49.404, P<0.05). (3) Analysis of factors affecting the survival outcomes of patients of pMMR. Results of multivariate analysis showed that age, T staging, N staging, vascular tumor thrombus were independent factors affecting the DFS of colon cancer patients of pMMR ( hazard ratio=1.018, 2.214, 2.598, 1.549, 95% confidence interval as 1.006-1.030, 1.618-3.030, 1.921-3.513, 1.118-2.147, P<0.05). Age, T staging, N staging, high grade tumor were independent factors affecting the OS of colon cancer patients of pMMR ( hazard ratio=1.036, 2.080, 2.591, 1.615, 95% confidence interval as 1.020-1.052, 1.407-3.075, 1.791-3.748, 1.114-2.341, P<0.05). (4) Interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Results of interaction analysis showed that the multiplication interaction effect between the number of lymph node harvest <12 and MMR protein status was significant on DFS of colon cancer patients ( hazard ratio=3.923, 95% confidence interval as 1.057-14.555, P<0.05). The additive interaction effects between age and MMR protein status, between high grade tumor and MMR protein status were significant on OS of colon cancer patients ( RERI=-0.033, -1.304, 95% confidence interval as -0.049 to -0.018, -2.462 to -0.146). Conclusions:There is an interaction between the MMR protein status and the adverse clinicopathological features (the number of lymph node harvest <12, high grade tumor) on prognosis of colon cancer patients of stage Ⅰ-Ⅲ. In patients of dMMR, the number of lymph node harvest <12 has a stronger predictive effect on poor prognosis. In patients of pMMR, the high grade tumor has a stronger predictive effect on poor prognosis.
10.Wogonin induces ferroptosis of rat CIA-FLS cells via NRF2/HO-1 sig-naling pathway
Lingfei HE ; Chaofan ZHANG ; Jie LIAN ; Aoxuan SHEN ; Qiannan DONG ; Xiao KANG ; Hao WU
Chinese Journal of Pathophysiology 2024;40(7):1276-1282
AIM:To investigate the mechanism by which wogonin(WOG)induces ferroptosis in collagen-in-duced arthritis rat fibroblast-like synoviocytes(rat CIA-FLS cells)through the nuclear factor E2-related factor 2(NRF2)/heme oxygenase-1(HO-1)signaling pathway.METHODS:Rat CIA-FLS cells were divided into:control group,low,medium,and high dose of(25,50 and 100 μmol/L)WOG group,ferroptosis inhibitor(LIP-1)group,LIP-1+high dose WOG group,HO-1 agonist cobalt protoporphyrin(COPP)group,and COPP+high dose WOG group.CCK-8 assay was used for cell viability.Crystal violet staining was used for for cell morphology.The levels of oxidative stress markers gluta-thione(GSH),malondialdehyde(MDA),and superoxide dismutase(SOD)were measured.DCFH-DA fluorescent probe was used to detect the intracellular reactive oxygen species(ROS)content as well as Western blot to detect the protein ex-pression levels of Kelch-like ECH-associated protein 1(KEAP-1),NRF2 and HO-1.RESULTS:Compared with the nor-mal control group,administration of WOG treatment resulted in a significant decrease in CIA-FLS cell viability(P<0.01),a significant increase in the level of oxidative stress(P<0.01),a significant increase in the content of ROS(P<0.01),a significant decrease in the level of expression of NRF2 and HO-1 proteins(P<0.01),and a significant increase in the level of KEAP-1(P<0.01)in the rat.Compared with the WOG group,the LIP-1-treated group showed a significant increase in cell viability(P<0.01),a significant decrease in the level of oxidative stress(P<0.01),and a significant de-crease in the content of ROS(P<0.01).Compared with the WOG group,the addition of COPP resulted in a significant in-crease in the protein expression levels of NRF2 and HO-1(P<0.01)and a significant decrease in KEAP-1 levels(P<0.01).CONCLUSION:WOG can induce ferroptosis in rat CIA-FLS cells by promoting oxidative stress through the NRF2/HO-1 signaling pathway.

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