1.Study on the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep
Ming QIAO ; Yao ZHAO ; Yi ZHU ; Yexia CAO ; Limei WEN ; Yuehong GONG ; Xiang LI ; Juanchen WANG ; Tao WANG ; Jianhua YANG ; Junping HU
China Pharmacy 2026;37(1):24-29
OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets, followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established , and the zebrafish were treated with L. ruthenicum Murr. extract (LRME) at concentrations of 0.1, 0.2 and 0.4 mg/mL, respectively; 24 h later, behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 (IL-6), IL-1β, IL-10, tumor necrosis factor-α (TNF-α)], oxidative stress markers [superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), catalase (CAT)], and neurotransmitters [5- hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), glutamic acid (Glu), dopamine (DA), and norepinephrine (NE)] were measured. The protein expression levels of protein kinase B1 (AKT1), phosphorylated AKT1 (p-AKT1), epidermal growth factor receptor (EGFR), B-cell lymphoma 2 (Bcl-2), sarcoma proto-oncogene,non-receptor tyrosine kinase (SRC), and heat shock protein 90α family class A member 1 (HSP90AA1) in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these, apigenin, naringenin and others were recognized as core active compounds, while AKT1, EGFR and others served as key targets; EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-, medium-, and high-dose groups were 54.60%, 69.03% and 77.97%, 开发。E-mail:hjp_yft@163.com respectively, while the inhibition ratios of locomotor distance were 0.57, 0.83 and 0.95, respectively. Compared with the model group, the number of resting counts, resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups (P<0.05). Neuronal damage in the brain was alleviated. Additionally, the levels of IL-6, IL-1β, TNF-α, MDA, Glu, DA and NE, as well as the protein expression levels of AKT1, p-AKT1, EGFR, SRC and HSP90AA1, were markedly reduced (P<0.05), while the levels of IL-10, SOD, GSH-Px, CAT, 5-HT and GABA, as well as Bcl-2 protein expression, were significantly elevated (P<0.05). CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects, and its specific mechanism may be related to the regulation of inflammatory responses, oxidative stress, neurotransmitter balance, and the EGFR tyrosine kinase inhibitor resistance signaling pathway.
2.Zishen Huoxue Prescription Alleviates Endoplasmic Reticulum Stress in Hippocampal Neurons of 2-VO Rats via GRP78/PERK/ATF4 Signaling Pathway
Yao SU ; Feng QIU ; Tao YI ; Hanquan LI ; Le XIE ; Xiuli ZHANG ; Dahua WU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):93-102
ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription (ZSHXP) ameliorates cognitive dysfunction in rats with vascular dementia (VD) induced by the bilateral common carotid artery ligation (2-VO model rats) through regulating the glucose-regulated protein 78 (GRP78)/protein kinase R-like endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley (SD) rats were randomly divided into six groups: Sham group, Model group, donepezil hydrochloride group (0.45 mg·kg-1), and ZSHXP groups at low (8.90 g·kg-1), medium (17.80 g·kg-1), and high (35.60 g·kg-1) doses,with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats, and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin (HE) and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy (TEM) was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen (NeuN) with GRP78 and βⅢ Tubulin with gasdermin D (GSDMD) in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress (ERS)-related proteins including GRP78, PERK, ATF4, phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), C/EBP homologous protein (CHOP), NOD-like receptor protein 3 (NLRP3), Caspase-1 and GSDMD. ResultsCompared with the sham operation group, the model group showed a significantly prolonged escape latency (P<0.01), a significant decrease in the number of platform crossings and the residence time in the target quadrant (P<0.01), and a markedly reduced recognition index (P<0.01). Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity, deformed and shrunken cell bodies, and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously, accompanied by abnormal dilation and swelling, and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78, p-PERK/PERK, ATF4, CHOP, NLRP3, GSDMD and Caspase-1 in the model group were significantly elevated (P<0.01). Compared with the model group, the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency (P<0.01) and an increased number of platform crossings (P<0.05, P<0.01). The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups (P<0.05, P<0.01), with a significantly improved recognition index (P<0.01). In the donepezil hydrochloride group and all ZSHXP groups, the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group, the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group, the protein expressions of GRP78, ATF4 and CHOP were increased (P<0.01), while the expression of p-PERK/PERK was decreased (P<0.05). In the ZSHXP low-dose group, the expressions of GRP78, p-PERK/PERK and CHOP were elevated (P<0.05, P<0.01). The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK, ATF4 and CHOP (P<0.01), and the high-dose group had a markedly reduced GRP78 protein expression (P<0.01). In the donepezil hydrochloride group, the Caspase-1 protein expression was increased (P<0.01) and the NLRP3 protein expression was decreased (P<0.01). In the ZSHXP low-dose group, the GSDMD expression was elevated (P<0.01) while the NLRP3 protein expression was reduced (P<0.01). After treatment with medium and high doses of ZSHXP, the protein expression levels of NLRP3, GSDMD and Caspase-1 were significantly decreased (P<0.01). ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway, which ameliorates ERS and inhibits neuronal pyroptosis.
3.Zishen Huoxue Prescription Alleviates Endoplasmic Reticulum Stress in Hippocampal Neurons of 2-VO Rats via GRP78/PERK/ATF4 Signaling Pathway
Yao SU ; Feng QIU ; Tao YI ; Hanquan LI ; Le XIE ; Xiuli ZHANG ; Dahua WU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):93-102
ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription (ZSHXP) ameliorates cognitive dysfunction in rats with vascular dementia (VD) induced by the bilateral common carotid artery ligation (2-VO model rats) through regulating the glucose-regulated protein 78 (GRP78)/protein kinase R-like endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley (SD) rats were randomly divided into six groups: Sham group, Model group, donepezil hydrochloride group (0.45 mg·kg-1), and ZSHXP groups at low (8.90 g·kg-1), medium (17.80 g·kg-1), and high (35.60 g·kg-1) doses,with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats, and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin (HE) and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy (TEM) was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen (NeuN) with GRP78 and βⅢ Tubulin with gasdermin D (GSDMD) in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress (ERS)-related proteins including GRP78, PERK, ATF4, phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), C/EBP homologous protein (CHOP), NOD-like receptor protein 3 (NLRP3), Caspase-1 and GSDMD. ResultsCompared with the sham operation group, the model group showed a significantly prolonged escape latency (P<0.01), a significant decrease in the number of platform crossings and the residence time in the target quadrant (P<0.01), and a markedly reduced recognition index (P<0.01). Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity, deformed and shrunken cell bodies, and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously, accompanied by abnormal dilation and swelling, and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78, p-PERK/PERK, ATF4, CHOP, NLRP3, GSDMD and Caspase-1 in the model group were significantly elevated (P<0.01). Compared with the model group, the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency (P<0.01) and an increased number of platform crossings (P<0.05, P<0.01). The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups (P<0.05, P<0.01), with a significantly improved recognition index (P<0.01). In the donepezil hydrochloride group and all ZSHXP groups, the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group, the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group, the protein expressions of GRP78, ATF4 and CHOP were increased (P<0.01), while the expression of p-PERK/PERK was decreased (P<0.05). In the ZSHXP low-dose group, the expressions of GRP78, p-PERK/PERK and CHOP were elevated (P<0.05, P<0.01). The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK, ATF4 and CHOP (P<0.01), and the high-dose group had a markedly reduced GRP78 protein expression (P<0.01). In the donepezil hydrochloride group, the Caspase-1 protein expression was increased (P<0.01) and the NLRP3 protein expression was decreased (P<0.01). In the ZSHXP low-dose group, the GSDMD expression was elevated (P<0.01) while the NLRP3 protein expression was reduced (P<0.01). After treatment with medium and high doses of ZSHXP, the protein expression levels of NLRP3, GSDMD and Caspase-1 were significantly decreased (P<0.01). ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway, which ameliorates ERS and inhibits neuronal pyroptosis.
4.SIRT5 Potentiates Hepatocarcinogenesis by Modulating Protein Acylation in Mice
Yu ZHANG ; Feng-Rui REN ; Jia-Yun LI ; Xiang-Yu CHEN ; Zi-Yi WANG ; Qi SUN ; Jun-Cheng ZHAO ; Ye ZHANG ; Zhen HUANG ; Hao HU ; Tao-Tao WEI ; Min XIAO
Progress in Biochemistry and Biophysics 2026;53(6):1712-1722
ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.
5.Robot-assisted percutaneous coronary intervention: a prospective, multicenter, randomized controlled, non-inferiority clinical trial.
Yi YU ; Zheng CHEN ; Zhi-Jian WANG ; Yue-Ping LI ; Li-Xia YANG ; Jing QI ; Jing XIE ; Tao HUANG ; Dong-Mei SHI ; Yu-Jie ZHOU
Journal of Geriatric Cardiology 2025;22(8):725-735
OBJECTIVE:
To evaluate the safety and effectiveness of robot-assisted percutaneous coronary intervention (R-PCI) compared to traditional manual percutaneous coronary intervention (M-PCI).
METHODS:
This prospective, multicenter, randomized controlled, non-inferior clinical trial enrolled patients with coronary heart disease who met the inclusion criteria and had indications for elective percutaneous coronary intervention. Participants were randomly assigned to either the R-PCI group or the M-PCI group. Primary endpoints were clinical and technical success rates. Clinical success was defined as visually estimated residual post-percutaneous coronary intervention stenosis < 30% with no 30-day major adverse cardiac events. Technical success in the R-PCI group was defined as successful completion of percutaneous coronary intervention using the ETcath200 robot-assisted system, without conversion to M-PCI in the event of a guidewire or balloon/stent catheter that was unable to cross the vessel or was poorly supported by the catheter. Secondary endpoints included total procedure time, percutaneous coronary intervention procedure time, fluoroscopy time, contrast volume, operator radiation exposure, air kerma, and dose-area product.
RESULTS:
The trial enrolled 152 patients (R-PCI: 73 patients, M-PCI: 79 patients). Lesions were predominantly B2/C type (73.6%). Both groups achieved 100% clinical success rate. No major adverse cardiac events occurred during the 30-day follow-up. The R-PCI group had a technical success rate of 100%. The R-PCI group had longer total procedure and fluoroscopy times, but lower operator radiation exposure. The percutaneous coronary intervention procedure time, contrast volume, air kerma, and dose-area product were similar between the two groups.
CONCLUSIONS
For certain complex lesions, performing percutaneous coronary intervention using the ETcath200 robot-assisted system is safe and effective and does not result in conversion to M-PCI.
6.Dahuang Zhechong Pill Improves Pulmonary Fibrosis through miR-29b-2-5p/HK2 Mediated Glycolysis Pathway.
Xiao-Yan HE ; Jing-Tao LIANG ; Jing-Yi XIAO ; Xin LI ; Xiao-Bo ZHANG ; Da-Yi CHEN ; Li-Juan WU
Chinese journal of integrative medicine 2025;31(7):600-612
OBJECTIVE:
To explore the preventive and therapeutic effects of Dahuang Zhechong Pill (DZP) on pulmonary fibrosis and the underlying mechanisms.
METHODS:
The first key rate-limiting enzyme hexokinase 2 (HK2) of glycolysis was silenced and over-expressed through small interfering RNA and lentivirus using lung fibroblast MRC-5 cell line, respectively. The cell viability, migration, invasion and proliferation were detected by cell counting kit-8, wound healing assay, transwell assay, and flow cytometry. The mRNA and protein expression levels of HK2 were detected by RT-PCR and Western blotting, respectively. The contents of glucose, adenosine triphosphate (ATP) and lactate in MRC-5 cells were determined by enzyme-linked immunosorbnent assay (ELISA). Then, the relationship between miR-29b-2-5p and HK2 was explored by luciferase reporter gene assay. Pulmonary fibrosis cell model was induced by transforming growth factor-β 1 (TGF-β 1) in MRC-5 cells, and the medicated serum of DZP (DMS) was prepared in rats. MRC-5 cells were divided into control, TGF-β 1, TGF-β 1+10% DMS, TGF-β 1+10% DMS+miR-29b-2-5p inhibitor, TGF-β 1+10% DMS+inhibitor negative control, TGF-β 1+10% DMS+miR-29b-2-5p mimic and TGF-β 1+10% DMS+mimic negative control groups. After miR-29b-2-5p mimics and inhibitors were transfected into MRC-5 cells, all groups except control and model group were treated with DMS. The effect of DMS on MRC-5 cells were detected using aforementioned methods and immunofluorescence. Similarly, the contents of glucose, ATP and lactate in each group were measured by ELISA.
RESULTS:
The mRNA and protein expressions of HK2 in MRC-5 cells were successfully silenced and overexpressed through si-HK2-3 and lentiviral transfection, respectively. After silencing HK2, the mRNA and protein expressions of HK2 were significantly decreased (P<0.01), and the concentrations of glucose, ATP and lactate were also significantly decreased (P<0.05). The proliferation, migration and invasion of MRC-5 cells were significantly declined (P<0.05 or P<0.01), while the apoptosis of MRC-5 cells was significantly increased (P<0.01). After overexpressing HK2, the mRNA and protein expressions of HK2 were significantly increased (P<0.05), and the concentrations of glucose, ATP and lactate were also significantly increased (P<0.05 or P<0.01). The proliferation, migration and invasion of MRC-5 cells were significantly increased (P<0.05 or P<0.01), while the apoptosis of MRC-5 cells was significantly decreased (P<0.05). The relative luciferase activity of 3'UTR-WT+hsa-miR-29b-2-5p transfected with HK2 was significantly decreased (P<0.01). After miR-29b-2-5p mimic and inhibitor were transfected into the MRC-5 cells, DMS intervention could significantly reduce the concentration of glucose, ATP and lactate, and the mRNA and proteins expressions of HK2, phosphofructokinase and pyruvate kinase isoform M2 (P<0.05 or P<0.01). The proliferation, migration and invasion of MRC-5 cells were alleviated (P<0.05 or P<0.01), and the deposition of fibronectin, α-smooth muscle actin, and collagen I were significantly decreased (P<0.05 or P<0.01).
CONCLUSIONS
Glycolysis is closely related to pulmonary fibrosis. DZP reduced glycolysis and inhibited fibroblasts' excessive differentiation and abnormal collagen deposition through the miR-29b-2-5p/HK2 pathway, which played a role in delaying the process of pulmonary fibrosis.
MicroRNAs/genetics*
;
Glycolysis/genetics*
;
Animals
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Pulmonary Fibrosis/metabolism*
;
Humans
;
Drugs, Chinese Herbal/therapeutic use*
;
Hexokinase/genetics*
;
Cell Line
;
Cell Proliferation/drug effects*
;
Rats, Sprague-Dawley
;
Rats
;
Cell Movement/drug effects*
;
Male
;
Cell Survival/drug effects*
;
Signal Transduction/drug effects*
7.Expert consensus on the application of nasal cavity filling substances in nasal surgery patients(2025, Shanghai).
Keqing ZHAO ; Shaoqing YU ; Hongquan WEI ; Chenjie YU ; Guangke WANG ; Shijie QIU ; Yanjun WANG ; Hongtao ZHEN ; Yucheng YANG ; Yurong GU ; Tao GUO ; Feng LIU ; Meiping LU ; Bin SUN ; Yanli YANG ; Yuzhu WAN ; Cuida MENG ; Yanan SUN ; Yi ZHAO ; Qun LI ; An LI ; Luo BA ; Linli TIAN ; Guodong YU ; Xin FENG ; Wen LIU ; Yongtuan LI ; Jian WU ; De HUAI ; Dongsheng GU ; Hanqiang LU ; Xinyi SHI ; Huiping YE ; Yan JIANG ; Weitian ZHANG ; Yu XU ; Zhenxiao HUANG ; Huabin LI
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(4):285-291
This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans
;
Nasal Cavity/surgery*
;
Nasal Surgical Procedures
;
China
;
Consensus
;
Sinusitis/surgery*
;
Dermal Fillers
8.BRD4 regulates m6A of ESPL1 mRNA via interaction with ALKBH5 to modulate breast cancer progression.
Haisheng ZHANG ; Linlin LU ; Cheng YI ; Tao JIANG ; Yunqing LU ; Xianyuan YANG ; Ke ZHONG ; Jiawang ZHOU ; Jiexin LI ; Guoyou XIE ; Zhuojia CHEN ; Zongpei JIANG ; Gholamreza ASADIKARAM ; Yanxi PENG ; Dan ZHOU ; Hongsheng WANG
Acta Pharmaceutica Sinica B 2025;15(3):1552-1570
The interaction between m6A-methylated RNA and chromatin modification remains largely unknown. We found that targeted inhibition of bromodomain-containing protein 4 (BRD4) by siRNA or its inhibitor (JQ1) significantly decreases mRNA m6A levels and suppresses the malignancy of breast cancer (BC) cells via increased expression of demethylase AlkB homolog 5 (ALKBH5). Mechanistically, inhibition of BRD4 increases the mRNA stability of ALKBH5 via enhanced binding between its 3' untranslated regions (3'UTRs) with RNA-binding protein RALY. Further, BRD4 serves as a scaffold for ubiquitin enzymes tripartite motif containing-21 (TRIM21) and ALKBH5, resulting in the ubiquitination and degradation of ALKBH5 protein. JQ1-increased ALKBH5 then demethylates mRNA of extra spindle pole bodies like 1 (ESPL1) and reduces binding between ESPL1 mRNA and m6A reader insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), leading to decay of ESPL1 mRNA. Animal and clinical studies confirm a critical role of BRD4/ALKBH5/ESPL1 pathway in BC progression. Further, our study sheds light on the crosstalks between histone modification and RNA methylation.
9.Sub-committee of Anesthesiology of Guangzhou Integrated Traditional Chinese and Western Medicine Society.
Yi LU ; Cunzhi LIU ; Wujun GENG ; Xiaozhen ZHENG ; Jingdun XIE ; Guangfang ZHANG ; Chao LIU ; Yun LI ; Yan QU ; Lei CHEN ; Xizhao HUANG ; Hang TIAN ; Yuhui LI ; Hongxin LI ; Heying ZHONG ; Ronggui TAO ; Jie ZHONG ; Yue ZHUANG ; Junyang MA ; Yan HU ; Jian FANG ; Gaofeng ZHAO ; Jianbin XIAO ; Weifeng TU ; Jiaze SUN ; Yuting DUAN ; Bao WANG
Journal of Southern Medical University 2025;45(8):1800-1808
OBJECTIVES:
To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and.
RESULTS:
Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.
CONCLUSIONS
The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans
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Medicine, Chinese Traditional
;
Cancer Pain/therapy*
;
Drugs, Chinese Herbal/therapeutic use*
;
Drug Delivery Systems
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Pain Management/methods*
;
China
10.Multicenter randomized controlled trial of Yiqi Huoxue formula() for the treatment of ruptured lumbar disc herniation.
Yu ZHU ; Zhi-Qiang WANG ; Shun LIN ; Ying-Ying YAO ; Xue-Qiang SHEN ; Xiao-Chun LI ; Feng YU ; Xiao-Yang XIONG ; Yi SONG ; Meng-Fei CHEN ; Peng-Fei YU ; Hong JIANG ; Jin-Tao LIU
China Journal of Orthopaedics and Traumatology 2025;38(11):1112-1118
OBJECTIVE:
To observe the clinical symptoms and MRI outcomes of patients with ruptured lumbar disc herniation(LDH) through a multicenter randomized controlled study, and to evaluate the clinical efficacy and safety of Yiqi Huoxue formula() in the treatment of this disease.
METHODS:
A total of 160 outpatients and inpatients with ruptured LDH admitted to 4 medical centers from January 2023 to June 2023 were selected and randomly divided into the Yiqi Huoxue formula group and the control group, with 80 patients in each group. In the Yiqi Huoxue formula group, there were 43 males and 37 females, with an age of (41.03±9.56) years and a disease duration of (10.45±25.37) days, and the patients were treated with Yiqi Huoxue formula. In the control group, there were 34 males and 46 females, with an age of (42.14±8.73) years and a disease duration of (11.31±21.14) days;during the acute phase, patients in this group could take celecoxib capsules orally, and methylcobalamin orally at the same time. The Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), changes in the volume of herniated disc tissue on MRI, herniation rate, and absorption rate were recorded at the time of enrollment and during follow-ups at the 3rd, 6th, and 12th month after treatment.
RESULTS:
A total of 156 patients completed the clinical follow-up, and 4 patients withdrew midway. The clinical symptoms of all patients who completed the study were relieved to varying degrees, and reabsorption of herniated disc tissue was observed in all patients in the Yiqi Huoxue formula group after treatment. For the JOA score:in the Yiqi Huoxue formula group, it was (10.73±2.76) points before treatment and (24.65±2.19) points at the 12th month after treatment;in the control group, it was (11.01±1.20) points before treatment and (17.07±3.26) points at the 12th month after treatment. For the ODI score:in the Yiqi Huoxue formula group, it was (26.21±3.55) points before treatment and (5.65±2.19) points at the 12th month after treatment;in the control group, it was (27.92±2.51) points before treatment and (9.09±2.15) points at the 12th month after treatment. At the 12th month after treatment, the JOA and ODI scores of both groups were better than those before treatment, and the scores of the Yiqi Huoxue formula group were better than those of the control group, with statistically significant differences (P<0.05). In terms of the herniated disc volume and herniation rate on MRI, the Yiqi Huoxue formula group was superior to the control group, with statistically significant differences(P<0.05). Reabsorption occurred in 56.96%(45/79) of patients in the Yiqi Huoxue formula group, which was significantly higher than the 37.66%(29/77) in the control group.
CONCLUSION
After treatment with Yiqi Huoxue formula, patients with ruptured LDH show significant improvement in clinical symptoms and a marked reduction in the volume of herniated discs. During the follow-up period, no obvious adverse drug reactions are observed in patients, and no recurrence of symptoms is found at the last follow-up, indicating that the formula has safe and reliable efficacy.
Humans
;
Male
;
Female
;
Intervertebral Disc Displacement/drug therapy*
;
Adult
;
Drugs, Chinese Herbal/adverse effects*
;
Middle Aged
;
Lumbar Vertebrae

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