1.Mechanism of Intervening with Diarrhea-predominant Irritable Bowel Syndrome in Rats with Spleen Deficiency by Xingpi Capsules Through Regulating 5-HT-RhoA/ROCK2 Pathway
Gang WANG ; Lingwen CUI ; Xiangning LIU ; Rongxin ZHU ; Mingyue HUANG ; Ying SUN ; Boyang JIAO ; Ran WANG ; Chun LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):60-69
ObjectiveTo investigate the efficacy of Xingpi capsules (XPC) in treating diarrhea-predominant irritable bowel syndrome (IBS-D) with spleen deficiency and elucidate its potential molecular mechanisms. MethodsA rat model of IBS-D with spleen deficiency was established by administering senna leaf in combination with restrained stress and swimming fatigue for 14 d. Ten specific pathogen free (SPF)-grade healthy rats were used as the normal control group. After successful modeling, SPF-grade rats were randomly divided into a model group, a pinaverium bromide group (1.5 mg·kg-1), and low- and high-dose XPC groups (0.135 and 0.54 g·kg-1), with 10 rats in each group. Rats in the normal control group and the model group were given distilled water by gavage, while the remaining groups were administered corresponding drug solutions by gavage once a day for 14 consecutive days. The rat body weights and fecal condition were observed every day, and the Bristol score was recorded. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of 5-hydroxytryptamine (5-HT) in serum and colon tissue. Transmission electron microscopy was used to observe the microvilli and tight junctions in the colon. The integrity of the colonic barrier, intestinal motility, and expression of related pathway proteins were evaluated by hematoxylin-eosin (HE) staining, immunohistochemistry, and Western blot. ResultsCompared with those in the normal control group, rats in the model group showed a significantly decreased body weight and increased diarrhea rate, diarrhea grade, and Bristol score (P<0.01). HE staining revealed incomplete colonic mucosa in the model group, with evident congestion and edema observed. Electron microscopy results indicated decreased density and integrity of the colonic barrier, shedding and disappearance of microvilli, and significant widening of tight junctions. The expression levels of colonic tight junction proteins Occludin and Claudin-5 were downregulated (P<0.01), and the levels of 5-HT in serum and colon tissue were elevated (P<0.01). The small intestine propulsion rate significantly increased (P<0.01), and the expression of contractile proteins Ras homolog family member A (RhoA) and Rho-associated coiled-coil containing protein kinase 2 (ROCK2) in colon and phosphorylation of myosin light chain (MLC20) were upregulated (P<0.01). Compared with the model group, the treatment groups showed alleviated diarrhea, diarrhea-associated symptoms, and pathological manifestations of colon tissue to varying degrees. Specifically, high-dose XPC exhibited effectively relieved diarrhea, promoted recovery of colonic mucosal structure, significantly reduced congestion and edema, upregulated expression of Occludin and Claudin-5 (P<0.01), decreased levels of 5-HT in serum and colon tissue (P<0.05,P<0.01), significantly slowed small intestine propulsion rate (P<0.01), and significantly downregulated expression of contractile proteins RhoA and ROCK2 in colon and phosphorylation of MLC20 (P<0.05,P<0.01). ConclusionXPC effectively alleviates symptoms of spleen deficiency and diarrhea and regulates the secretion of brain-gut peptide. The characteristics of XPC are mainly manifested in alleviating IBS-D with spleen deficiency from the aspects of protecting intestinal mucosa and inhibiting smooth muscle contraction, and the mechanism is closely related to the regulation of the 5-HT-RhoA/ROCK2 pathway expression.
2.Intelligent handheld ultrasound improving the ability of non-expert general practitioners in carotid examinations for community populations: a prospective and parallel controlled trial
Pei SUN ; Hong HAN ; Yi-Kang SUN ; Xi WANG ; Xiao-Chuan LIU ; Bo-Yang ZHOU ; Li-Fan WANG ; Ya-Qin ZHANG ; Zhi-Gang PAN ; Bei-Jian HUANG ; Hui-Xiong XU ; Chong-Ke ZHAO
Ultrasonography 2025;44(2):112-123
Purpose:
The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations.
Methods:
This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits.
Results:
Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01).
Conclusion
Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.
3.Analysis of Mechanism of Xingpi Capsules in Treatment of Functional Dyspepsia Based on Transcriptomics
Rongxin ZHU ; Mingyue HUANG ; Keyan WANG ; Xiangning LIU ; Yinglan LYU ; Gang WANG ; Fangfang RUI ; Qiong DENG ; Jianteng DONG ; Yong WANG ; Chun LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):164-172
ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia(FD) and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats(7 days old) were randomly divided into the normal group(n=12) and the modeling group(n=48), and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared, the rats in the modeling group were randomly divided into the model group, the low-dose and high-dose groups of Xingpi capsules(0.135, 0.54 g·kg-1) and the domperidone group(3 mg·kg-1), with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water, and rats in the rest of the groups were gavaged with the corresponding medicinal solution, once a day for 7 d. The general survival condition of the rats was observed, and the water intake and food intake of the rats were measured, the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment, the pathological damage of the rat duodenum was examined by hematoxylin-eosin(HE) staining, and the expressions of colonic tight junction protein(Occludin) and zonula occludens protein-1(ZO-1) were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group, and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration, and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out. The transcriptomic results were validated by Western blot, immunofluorescence, and real-time fluorescence quantitative polymerase chain reaction(Real-time PCR), and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group, the general survival condition of rats in the model group was poorer, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly reduced(P<0.05), inflammatory infiltration was seen in duodenal pathology, and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced(P<0.01). Compared with the model group, the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly increased(P<0.05), the duodenal pathology showed a decrease in inflammatory infiltration, and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased(P<0.01). Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) through the key genes such as Slc5a1, Abhd6. The validation results showed that compared with the normal group, the phosphorylation levels of PI3K and Akt proteins, the protein expression level of interleukin(IL)-1β, and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3, Slc5a9 and other key genes were significantly increased(P<0.01). Compared with the model group, the phosphorylation levels of PI3K and Akt, the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3 and Slc5a9 were significantly reduced(P<0.05). Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein, and linarionoside A, valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats, its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum, and E-nerolidol, Z-nerolidol, linarionoside A, valerosidatum and senkirkine may be its key active ingredients.
4.Analysis of Mechanism of Xingpi Capsules in Treatment of Functional Dyspepsia Based on Transcriptomics
Rongxin ZHU ; Mingyue HUANG ; Keyan WANG ; Xiangning LIU ; Yinglan LYU ; Gang WANG ; Fangfang RUI ; Qiong DENG ; Jianteng DONG ; Yong WANG ; Chun LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):164-172
ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia(FD) and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats(7 days old) were randomly divided into the normal group(n=12) and the modeling group(n=48), and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared, the rats in the modeling group were randomly divided into the model group, the low-dose and high-dose groups of Xingpi capsules(0.135, 0.54 g·kg-1) and the domperidone group(3 mg·kg-1), with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water, and rats in the rest of the groups were gavaged with the corresponding medicinal solution, once a day for 7 d. The general survival condition of the rats was observed, and the water intake and food intake of the rats were measured, the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment, the pathological damage of the rat duodenum was examined by hematoxylin-eosin(HE) staining, and the expressions of colonic tight junction protein(Occludin) and zonula occludens protein-1(ZO-1) were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group, and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration, and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out. The transcriptomic results were validated by Western blot, immunofluorescence, and real-time fluorescence quantitative polymerase chain reaction(Real-time PCR), and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group, the general survival condition of rats in the model group was poorer, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly reduced(P<0.05), inflammatory infiltration was seen in duodenal pathology, and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced(P<0.01). Compared with the model group, the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly increased(P<0.05), the duodenal pathology showed a decrease in inflammatory infiltration, and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased(P<0.01). Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) through the key genes such as Slc5a1, Abhd6. The validation results showed that compared with the normal group, the phosphorylation levels of PI3K and Akt proteins, the protein expression level of interleukin(IL)-1β, and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3, Slc5a9 and other key genes were significantly increased(P<0.01). Compared with the model group, the phosphorylation levels of PI3K and Akt, the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3 and Slc5a9 were significantly reduced(P<0.05). Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein, and linarionoside A, valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats, its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum, and E-nerolidol, Z-nerolidol, linarionoside A, valerosidatum and senkirkine may be its key active ingredients.
5.Intelligent handheld ultrasound improving the ability of non-expert general practitioners in carotid examinations for community populations: a prospective and parallel controlled trial
Pei SUN ; Hong HAN ; Yi-Kang SUN ; Xi WANG ; Xiao-Chuan LIU ; Bo-Yang ZHOU ; Li-Fan WANG ; Ya-Qin ZHANG ; Zhi-Gang PAN ; Bei-Jian HUANG ; Hui-Xiong XU ; Chong-Ke ZHAO
Ultrasonography 2025;44(2):112-123
Purpose:
The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations.
Methods:
This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits.
Results:
Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01).
Conclusion
Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.
6.Intelligent handheld ultrasound improving the ability of non-expert general practitioners in carotid examinations for community populations: a prospective and parallel controlled trial
Pei SUN ; Hong HAN ; Yi-Kang SUN ; Xi WANG ; Xiao-Chuan LIU ; Bo-Yang ZHOU ; Li-Fan WANG ; Ya-Qin ZHANG ; Zhi-Gang PAN ; Bei-Jian HUANG ; Hui-Xiong XU ; Chong-Ke ZHAO
Ultrasonography 2025;44(2):112-123
Purpose:
The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations.
Methods:
This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits.
Results:
Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01).
Conclusion
Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.
7.Intelligent handheld ultrasound improving the ability of non-expert general practitioners in carotid examinations for community populations: a prospective and parallel controlled trial
Pei SUN ; Hong HAN ; Yi-Kang SUN ; Xi WANG ; Xiao-Chuan LIU ; Bo-Yang ZHOU ; Li-Fan WANG ; Ya-Qin ZHANG ; Zhi-Gang PAN ; Bei-Jian HUANG ; Hui-Xiong XU ; Chong-Ke ZHAO
Ultrasonography 2025;44(2):112-123
Purpose:
The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations.
Methods:
This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits.
Results:
Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01).
Conclusion
Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.
8.Intelligent handheld ultrasound improving the ability of non-expert general practitioners in carotid examinations for community populations: a prospective and parallel controlled trial
Pei SUN ; Hong HAN ; Yi-Kang SUN ; Xi WANG ; Xiao-Chuan LIU ; Bo-Yang ZHOU ; Li-Fan WANG ; Ya-Qin ZHANG ; Zhi-Gang PAN ; Bei-Jian HUANG ; Hui-Xiong XU ; Chong-Ke ZHAO
Ultrasonography 2025;44(2):112-123
Purpose:
The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations.
Methods:
This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits.
Results:
Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01).
Conclusion
Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.
9.Analysis of syncopal DRVR in blood donors: multicenter hemovigilance data (2020—2023)
Junhong YANG ; Qing XU ; Wenqin ZHU ; Fei TANG ; Ruru HE ; Zhenping LU ; Zhujiang YE ; Fade ZHONG ; Gang WU ; Guoqiang FENG ; Xiaojie GUO ; Jia ZENG ; Xia HUANG
Chinese Journal of Blood Transfusion 2025;38(8):1071-1076
Objective: Data on syncopal donation-related vasovagal reaction (DRVR) collected from 74 blood centers between 2020 and 2023 was statistically analyzed to provide a reference for developing preventive strategies against syncopal DRVR. Methods: Data on blood donation adverse reactions and basic information of donors from 2020 to 2023 were collected through the information management system at monitoring sentinel sites. Statistical analysis was performed on the following aspects of syncopal DRVR: characteristics of donors who experienced syncope, reported incidence, triggers, duration, presence and occurrence time of syncope-related trauma, clinical management including outpatient and inpatient treatment, and severity grading. Results: From 2020 to 2023, 45 966 donation-related adverse reactions were recorded. Of these, 1 665 (3.72%) cases were syncopal DRVR. The incidence of syncopal DRVR decreased with age, being the highest in the 18-22 age group. Incidence was significantly higher in female donors than male donors, in first-time donors than repeat donors, and in university and individual donors than group donors (all P<0.05). There was no statistically significant difference among different blood donation locations (P>0.05). The top three triggers were tension, fatigue, and needle phobia or fear of blood. Among syncopal DRVR cases, 60.36% occurred during blood collection, 87.63% lasted for less than 60 seconds, and 5.05% were accompanied by trauma. Notably, 57.14% of these traumas occurred after donor had left the blood collection site. Syncope severity was graded based on required treatment: grade 1 (fully recovered without treatment, 95.50%); grade 2 (recovered after outpatient treatment, 4.02%); and grade 3 (recovered after inpatient treatment, 0.48%). Conclusion: By analyzing the data of syncopal DRVR cases, it is possible to provide a reference for formulating blood donor safety policies.
10.Medication rules and mechanisms of treating chronic renal failure by Jinling medical school based on data mining, network pharmacology, and experimental validation.
Jin-Long WANG ; Wei WU ; Yi-Gang WAN ; Qi-Jun FANG ; Yu WANG ; Ya-Jing LI ; Fee-Lan CHONG ; Sen-Lin MU ; Chu-Bo HUANG ; Huang HUANG
China Journal of Chinese Materia Medica 2025;50(6):1637-1649
This study aims to explore the medication rules and mechanisms of treating chronic renal failure(CRF) by Jinling medical school based on data mining, network pharmacology, and experimental validation systematically and deeply. Firstly, the study selected the papers published by the inherited clinicians in Jinling medical school in Chinese journals using the subject headings named "traditional Chinese medicine(TCM) + chronic renal failure", "TCM + chronic renal inefficiency", or "TCM + consumptive disease" in China National Knowledge Infrastructure, Wanfang, and VIP Chinese Science and Technology Periodical Database and screened TCM formulas for treating CRF according to inclusion and exclusion criteria. The study analyzed the frequency of use of single TCM and the four properties, five tastes, channel tropism, and efficacy of TCM used with high frequency and performed association rule and clustering analysis, respectively. As a result, a total of 215 TCM formulas and 235 different single TCM were screened, respectively. The TCM used with high frequency included Astragali Radix, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Poria, and Atractylodis Macrocephalae Rhizoma(top 5). The single TCM characterized by "cold properties, sweet flavor, and restoring spleen channel" and the TCM with the efficacy of tonifying deficiency had the highest frequency of use, respectively. Then, the TCM with the rules of "blood-activating and stasis-removing" and "diuretic and dampness-penetrating" appeared. In addition, the core combination of TCM [(Hexin Formula, HXF)] included "Astragali Radix, Rhei Radix et Rhizoma, Poria, Salviae Miltiorrhizae Radix, and Angelicae Sinensis Radix". The network pharmacology analysis showed that HXF had 91 active compounds and 250 corresponding protein targets including prostaglandin-endoperoxide synthase 2(PTGS2), PTGS1, sodium voltage-gated channel alpha subunit 5(SCN5A), cholinergic receptor muscarinic 1(CHRM1), and heat shock protein 90 alpha family class A member 1(HSP90AA1)(top 5). Gene Ontology(GO) function analysis revealed that the core targets of HXF predominantly affected biological processes, cellular components, and molecular functions such as positive regulation of transcription by ribonucleic acid polymerase Ⅱ and DNA template transcription, formation of cytosol, nucleus, and plasma membrane, and identical protein binding and enzyme binding. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis revealed that CRF-related genes were involved in a variety of signaling pathways and cellular metabolic pathways, primarily involving "phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) pathway" and "advanced glycation end products-receptor for advanced glycation end products". Molecular docking results showed that the active components in HXF such as isomucronulatol 7-O-glucoside, betulinic acid, sitosterol, and przewaquinone B might be crucial in the treatment of CRF. Finally, a modified rat model with renal failure induced by adenine was used, and the in vivo experimental confirmation was performed based on the above-mentioned predictions. The results verify that HXF can regulate mitochondrial autophagy in the kidneys and the PI3K-Akt-mammalian target of rapamycin(mTOR) signaling pathway activation at upstream, so as to alleviate renal tubulointerstitial fibrosis and then delay the progression of CRF.
Data Mining
;
Drugs, Chinese Herbal/chemistry*
;
Network Pharmacology
;
Humans
;
Kidney Failure, Chronic/metabolism*
;
Medicine, Chinese Traditional
;
China

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