1.Mechanisms of Chinese herbal medicine in modulating gut microbiota on primary open-angle glaucoma: a study based on data mining, network pharmacology, and Mendelian randomization
Yu TANG ; Bingyao ZHU ; Qianhong LIU ; Kai WU ; Pai ZHOU ; Xiaolei YAO ; Qinghua PENG
Digital Chinese Medicine 2025;8(4):491-503
Objective:
To elucidate the potential mechanisms by which Chinese herbal medicine (CHM) regulates gut microbiota (GM) to influence the development of primary open-angle glaucoma (POAG).
Methods:
Data mining, network pharmacology, and Mendelian randomization (MR) analyses (two-sample design) were conducted in integration to systematically explore the CHM-GM-POAG axis. Literature-based data mining method was applied to identify frequently used herbs and herb pairs for POAG, and the properties and meridian tropism of the herbs were analyzed as well. Target prediction and pathway enrichment analyses were performed to identify shared molecular pathways among CHM components, GM, and POAG. MR analysis was performed to assess the genetically predicted causal associations between specific microbial taxa and POAG risk.
Results:
Our data mining work indicated that commonly used CHMs were mainly bitter and sweet in flavors and cold in property, with meridian tropism toward the liver, lung, and kidney. The predominant therapeutic effects of the CHMs included soothing the liver and regulating Qi, promoting blood circulation, and reducing fluid retention. Representative herb pairs were Shudihuang (Rehmanniae Radix Praeparata)-Gouqi (Lycii Fructus) with Zexie (Alismatis Rhizoma), Gouqi (Lycii Fructus)-Fuling (Poria) with Shudihuang (Rehmanniae Radix), and Juhua (Chrysanthemi Flos)-Gouqi (Lycii Fructus) with Zexie (Alismatis Rhizoma). Network pharmacology revealed overlapping targets involving antioxidative, anti-inflammatory, and metabolic regulation pathways. MR analysis demonstrated that higher abundances of Ruminiclostridium 6 [odds ratio (OR) = 0.73, 95% confidence interval (CI): 0.58 – 0.92, P = 0.007], Ruminococcaceae UCG-002 (OR = 0.77, 95% CI: 0.63 – 0.96, P = 0.018), Ruminococcus torques group (OR = 0.71, 95% CI: 0.57 – 0.90, P = 0.004), and Victivallis (OR = 0.82, 95% CI: 0.70 – 0.96, P = 0.016) were causally associated with reduced POAG risk, whereas Actinomyces (OR = 1.34, 95% CI: 1.06 – 1.68, P = 0.013) and Blautia (OR = 1.39, 95% CI: 1.01 – 1.90, P = 0.042) showed positive associations.
Conclusion
This study revealed potential causal links between GM and POAG and provided integrative evidence that CHM may modulate the microbiota to exert neuroprotective effects. These findings offer new integrative insights into the gut-eye axis and a theoretical basis for developing microbiota-targeted CHM strategies in glaucoma management.
2.Comparative study of RECIL2017 and Lugano classification in prediction of prognosis at the end of treatment in patients with diffuse large B-cell lymphoma
Jianqiang ZHAO ; Xinming ZHAO ; Fenglian JING ; Huanxin ZHU ; Yifan AN ; Bingyao LIU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(8):456-461
Objective:To compare the predictive values of response evaluation criteria in lymphoma (RECIL)2017 and Lugano classification for the prognosis of patients with diffuse large B-cell lymphoma(DLBCL) at the end of treatment.Methods:A total of 107 patients (50 males, 57 females, age (49.3±17.4) years) with DLBCL who underwent PET/CT at the end of chemotherapy in the Fourth Hospital of Hebei Medical University between February 2014 and December 2021 were analyzed retrospectively. The RECIL2017 and Lugano classification were used to evaluate the response. Kaplan-Meier survival analysis was used to evaluate progression-free survival (PFS) and overall survival (OS). The Kappa test was used to evaluate the consistency of the two criteria after chemotherapy, and ROC curve (Delong test)was used to compare the predictive values of the two criteria for PFS and OS. Results:The median follow-up time was 47.5(33.4, 57.5) months. Kaplan-Meier analysis showed that the 5-year PFS rates (74.5%(35/47), 71.4%(15/21), 57.1%(12/21), 4/18; χ2=38.85, P<0.001) and OS rates (89.4%(42/47), 81.0%(17/21), 61.9%(13/21), 7/18; χ2=29.52, P<0.001) in complete metabolic response (CMR), partial metabolic response (PMR), no metabolic response (NMR) and progressive metabolic disease (PMD) groups evaluated by Lugano classification were statistically different, as well as those in complete response (CR), partial response (PR), minor response (MR), stable disease (SD) and progressive disease (PD) groups evaluated by the RECIL2017 (5-year PFS rates: 76.9%(40/52), 8/12, 6/11, 6/12, 30.0%(6/20), χ2=29.05, P<0.001; 5-year OS rates: 90.4%(47/52), 8/12, 6/11, 9/12, 45.0%(9/20), χ2=23.63, P<0.001). The RECIL2017 and Lugano classification had good consistency in the efficacy evaluation of DLBCL patients at the end of chemotherapy (70.1%(75/107); Kappa=0.57, P<0.001). The AUCs of Lugano classification for predicting PFS and OS were 0.730 (95% CI: 0.625-0.834, P<0.001) and 0.908 (95% CI: 0.845-0.970, P<0.001) respectively, and those of RECIL2017 were 0.717 (95% CI: 0.612-0.822, P<0.001) and 0.880 (95% CI: 0.812-0.949, P<0.001). The AUCs of the Lugano classification for PFS and OS were slightly higher than those of RECIL2017, without significant differences ( z values: 0.44, 1.09, both P>0.05) . Conclusion:Both RECIL2017 and Lugano classification can evaluate the prognosis of patients with DLBCL at the end of treatment, and Lugano classification is more accurate.
3.Effects of Qingguang’an Granules on mitochondrial autophagy of retinal ganglion cells in rats with chronic ocular hypertension
TANG Yu ; ZHU Bingyao ; SHI Jian ; LIU Qianhong ; CHEN Lihao ; PENG Qinghua ; PENG Jun ; YAO Xiaolei
Digital Chinese Medicine 2022;5(3):295-304
Objective To investigate the effect and underlying mechanism of Qingguang’an Granules (青光安颗粒剂, QGAG) on mitochondrial autophagy (mitophagy) of retinal ganglion cells (RGCs) in rats with chronic ocular hypertension (COH). Methods Sixty Sprague Dawley (SD) rats, half males and half females, were randomly assigned to three groups: the control, model, and QGAG (2.5 g/kg) groups, with 20 rats in each group. Rats’ model of COH was established by cauterizing episcleral veins in the model group and QGAG group. Three weeks after successful modeling, rats in the QGAG group were intragastrically administered with QGAG, while rats in the control group and the model group received an equal dose of normal saline. After three months of intragastric administration, intraocular pressure (IOP) of all rats was measured. The mitophagy was monitored by the immunofluorescence method, the mitochondrial membrane potential was measured using the JC-1 method, and the morphological changes of mitophagy in RGCs were observed by transmission electron microscopy. Meanwhile, rat RGCs were labeled using the fluorescent gold method, and RGCs density in each group was calculated. Moreover, RGCs apoptosis was observed by TdT-mediated dUTP Nick-End Labeling (TUNEL) assay. Finally, the expression levels of Parkin, optineurin, microtubule-associated protein 1 light chain 3-II/microtubule-associated protein 1 light chain 3-I (LC3-II/LC3-I), recombinant lysosomal associated membrane protein 1 (LAMP1), and B-cell lymphoma-2 (Bcl-2) in RGCs were determined by Western blot assay. The corresponding mRNAs were detected through quantitative real-time polymerase chain reaction (qRT-PCR). Results The QGAG reduced IOP in COH rats, and inhibited mitophagy and apoptosis of RGCs (P < 0.05). Besides, the QGAG significantly increased the expression levels of Parkin and Bcl-2 (P < 0.05), and inhibited the expression levels of optineurin, LAMP1, and LC3-II/LC3-I (P < 0.05) in RGCs of COH rats. Conclusion The QGAG can inhibit mitophagy in RGCs of COH rats and show a protective effect against optic nerve damage caused by glaucoma, which may be mediated through the mitophagy ubiquitination via the Parkin/PINK1-related pathway.
4.Network pharmacology predicts the mechanism and related experimental research on the effective components of Salvia miltiorrhiza and Carthamus tinctorius against cerebral ischemic stroke
Huiyuan ZHU ; Qi MIAO ; Jiang WANG ; Bin LUO ; Haitong WAN ; Wenxuan WANG ; Bingyao DONG ; Shengbin XIAO ; Shan DANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2021;42(3):474-483
【Objective】 To explore the effect mechanism of Salvia miltiorrhiza and safflower on combined anti-ischemic stroke and verify relevant action targets in middle cerebral artery occlusion (MCAO) rat model based on network pharmacology. 【Methods】 ①Traditional Chinese Medicine Systems Pharmacology (TCMSP) and GeneCards databases were used to screen the active components, component targets and ischemic stroke targets of Salvia miltiorrhiza and safflower respectively. The above data were imported into STRING database for protein interaction network analysis, and Cytoscape3.8.0 software was used to construct protein interaction network (PPI) and component target interaction network. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation analysis of target genes were performed using David online analysis tool. ② In this experiment, a rat model of ischemic stroke was prepared by using improved MCAO method, and immunohistochemical method and Real-time quantitative polymerase chain reaction (REAL-TIME PCR) to detect the positive expressions of NLRP3 inflammatory body and NF P65 protein in the brain tissue of rats in each group so as to explore the functional mechanism of anti-inflammation reaction against cerebral ischemia injury. 【Results】 ① A total of 87 effective components, corresponding to 253 targets, 1448 targets for ischemic stroke and 161 targets related to drugs and diseases, were screened from the Salvia milticorrhiza and safflower drug pairs. We obtained 730 biological processes, 81 cell components and 128 molecular functions through GO analysis, and 127 signal pathways through KEGG analysis. ②Immunohistochemical method and Real-time PCR determination results showed that compared with control group rats, model group rats had significantly increased tissue NLRP3 inflammatory body and NFkBp65 protein expressions (P<0.01). Compared with those in the model group, NLRP3 inflammatory body and NFkBp65 protein expressions significantly decreased in Dan red compatibility groups and nim horizon groups (P<0.01). 【Conclusion】 Compatibility of effective components in salvia miltiorrhiza, and carthamus tinctorius can further downregulate the release of inflammatory corpuscle NLRP3 through NFkB signaling pathway by blocking inflammatory lesions and thus plays the role of fighting against inflammatory damage.

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