1.Analysis of Medication Patterns for Ancient Epidemic Treatment Based on Data Mining
Peipei JIN ; Tongxing WANG ; Liping CHANG ; Bin HOU ; Ningxin HAN ; Xiaoqi WANG ; Zhenhua JIA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):287-294
ObjectiveExploring the formula rules of commonly used traditional Chinese medicines(TCMs) for epidemic treatment from the Qin and Han dynasties to the Qing dynasty through data mining, providing reference for the prevention and control of contemporary epidemics. MethodsThe articles on epidemic treatment in the electronic database of Chinese Medical Code V5.0 were systematically searched, and the contents such as source, dynasty, author, diagnosis, formula name, therapeutic method and efficacy, and composition of medicines from each article that met the inclusion criteria were extracted. Then, an Excel standardized database was established, and Python programs were used for data mining to summarize the frequency of commonly used medicines and perform hierarchical cluster analysis, Pearson correlation analysis, and association rule analysis. ResultsA total of 1 595 formulas were included, involving 558 TCMs. The efficacy of these medicines could be classified into two categories, namely, expeling pathogenic factors and reinforcing healthy Qi. According to the frequency deconstruction analysis, high-frequency medicines were mainly detoxification, Fu-organ dredging, aromatization and promoting blood circulation, followed by the medicines with the effect of treating the lungs, such as clearing the lungs and resolving phlegm, clearing heat and purging the lungs, relieving cough and asthma, and purging the lungs and relieving asthma. And the proportions of acrid-warm herbs and acrid-cold herbs varied in different periods. Hierarchical clustering and correlation analysis both suggested TCMs for expeling pathogenic factors and reinforcing healthy Qi often formed stable combinations with high association degrees. Association rule analysis showed that the core acrid-warm herb was mainly Ephedrae Herba, and the core acrid-cold herb was mainly Forsythiae Fructus, resulting in the core formulas of Maxing Shigantang and Yinqiaosan. ConclusionThroughout history, the prevention and control of epidemics have been based on the principle of "preserving healthy Qi and avoiding toxic Qi", focusing on the treatment of the causes and characteristics of epidemics through detoxification, Fu-organ dredging, and aromatization, emphasizing the use of Rhei Radix et Rhizoma and other herbs to dredge Fu-organ, eliminate toxins and pathogens, and playing the role of actively intervene with symptomatic medication. And based on the external manifestations of the body's struggle between evil and righteousness, diagnose and treatment according to syndrome differentiation was performed.
2.Analysis of Medication Patterns for Ancient Epidemic Treatment Based on Data Mining
Peipei JIN ; Tongxing WANG ; Liping CHANG ; Bin HOU ; Ningxin HAN ; Xiaoqi WANG ; Zhenhua JIA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):287-294
ObjectiveExploring the formula rules of commonly used traditional Chinese medicines(TCMs) for epidemic treatment from the Qin and Han dynasties to the Qing dynasty through data mining, providing reference for the prevention and control of contemporary epidemics. MethodsThe articles on epidemic treatment in the electronic database of Chinese Medical Code V5.0 were systematically searched, and the contents such as source, dynasty, author, diagnosis, formula name, therapeutic method and efficacy, and composition of medicines from each article that met the inclusion criteria were extracted. Then, an Excel standardized database was established, and Python programs were used for data mining to summarize the frequency of commonly used medicines and perform hierarchical cluster analysis, Pearson correlation analysis, and association rule analysis. ResultsA total of 1 595 formulas were included, involving 558 TCMs. The efficacy of these medicines could be classified into two categories, namely, expeling pathogenic factors and reinforcing healthy Qi. According to the frequency deconstruction analysis, high-frequency medicines were mainly detoxification, Fu-organ dredging, aromatization and promoting blood circulation, followed by the medicines with the effect of treating the lungs, such as clearing the lungs and resolving phlegm, clearing heat and purging the lungs, relieving cough and asthma, and purging the lungs and relieving asthma. And the proportions of acrid-warm herbs and acrid-cold herbs varied in different periods. Hierarchical clustering and correlation analysis both suggested TCMs for expeling pathogenic factors and reinforcing healthy Qi often formed stable combinations with high association degrees. Association rule analysis showed that the core acrid-warm herb was mainly Ephedrae Herba, and the core acrid-cold herb was mainly Forsythiae Fructus, resulting in the core formulas of Maxing Shigantang and Yinqiaosan. ConclusionThroughout history, the prevention and control of epidemics have been based on the principle of "preserving healthy Qi and avoiding toxic Qi", focusing on the treatment of the causes and characteristics of epidemics through detoxification, Fu-organ dredging, and aromatization, emphasizing the use of Rhei Radix et Rhizoma and other herbs to dredge Fu-organ, eliminate toxins and pathogens, and playing the role of actively intervene with symptomatic medication. And based on the external manifestations of the body's struggle between evil and righteousness, diagnose and treatment according to syndrome differentiation was performed.
3.A Case of Multidisciplinary Treatment for Deficiency of Adenosine Deaminase 2
Jingyuan ZHANG ; Xiaoqi WU ; Jiayuan DAI ; Xianghong JIN ; Yuze CAO ; Rui LUO ; Hanlin ZHANG ; Tiekuan DU ; Xiaotian CHU ; Peipei CHEN ; Hao QIAN ; Pengguang YAN ; Jin XU ; Min SHEN
JOURNAL OF RARE DISEASES 2025;4(3):316-324
This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the
4.Effects of lncRNA DHRS4-AS1 on proliferation, invasion, migration, and apoptosis of thyroid cancer cells by regulating the miR-221-3p/SOCS3 signaling axis.
Hui WANG ; Yu GUO ; Peipei ZHANG ; Haoyu YANG ; Chuntao TIAN ; Mingming JIN
Chinese Journal of Cellular and Molecular Immunology 2025;41(9):798-805
Objective To explore the influences of long-chain noncoding RNA DHRS4-AS1 (lncRNA DHRS4-AS1) on the proliferation, invasion, migration, and apoptosis of thyroid cancer (TC) cells by regulating the microRNA-221-3p (miR-221-3p)/suppressor of cytokine signaling 3 (SOCS3) signaling axis. Methods Quantitative real-time PCR (qRT-PCR) was applied to detect the expression of lncRNA DHRS4-AS1, miR-221-3p, and SOCS3 mRNA in TC cell lines, and the optimal cell line was selected for subsequent experiments. FTC-133 cells were divided into five groups: control group, pcDNA-NC group, DHRS4-AS1 group, DHRS4-AS1 combined with agomir NC group, and DHRS4-AS1 combined with miR-221-3p-agomir group. Transfection efficiency was assessed using qRT-PCR. Dual luciferase reporter assays were applied to verify the targeting interaction between lncRNA DHRS4-AS1, SOCS3, and miR-221-3p. Western blot analysis was used to detect the expression of SOCS3 in FTC-133 cells. EdU method was used to measure cell proliferation. Flow cytometry was applied to measure the apoptosis of FTC-133 cells. Scratch experiment was applied to measure the migration of FTC-133 cells. Transwell chamber was applied to detect the invasion of FTC-133 cells. Nude mouse transplantation tumor experiment was used to observe the effect of lncRNA DHRS4-AS1 on the growth of TC transplantation tumors. Results Dual luciferase reporter assays showed a targeting relationship between lncRNA DHRS4-AS1, miR-221-3p, and SOCS3. LncRNA DHRS4-AS1 and SOCS3 were downregulated and miR-221-3p was upregulated in FTC-133 cells. Overexpression of lncRNA DHRS4-AS1 inhibited proliferation, migration, and invasion of FTC-133 cells, while inducing apoptosis. Conversely, miR-221-3p overexpression reversed these inhibitory effects, and suppressed the apoptosis. Nude mouse transplantation experiment observed that overexpression of lncRNA DHRS4-AS1 resulted in a decrease in tumor tissue quality and volume, and a decrease in miR-221-3p expression and an increase in SOCS3 expression. Conclusion LncRNA DHRS4-AS1 is downregulated in FTC-133 cells. Overexpression of lncRNA DHRS4-AS1 can inhibit the proliferation, invasion, and migration of TC cells and induce apoptosis by regulating the miR-221-3p/SOCS3 signaling axis.
MicroRNAs/metabolism*
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Suppressor of Cytokine Signaling 3 Protein/metabolism*
;
Humans
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RNA, Long Noncoding/metabolism*
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Apoptosis/genetics*
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Cell Proliferation/genetics*
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Cell Movement/genetics*
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Thyroid Neoplasms/physiopathology*
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Animals
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Signal Transduction/genetics*
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Cell Line, Tumor
;
Mice, Nude
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Neoplasm Invasiveness
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Gene Expression Regulation, Neoplastic
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Mice
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Mice, Inbred BALB C
5.Cannabidiol alleviates methamphetamine addiction via targeting ATP5A1 and modulating the ATP-ADO-A1R signaling pathway.
Sha JIN ; Cong LIN ; Peipei LI ; Xue WANG ; Yibo WANG ; Cong ZHANG ; Xuenan WANG ; Yinghua PENG ; Haohong LI ; Yuyuan LU ; Xiaohui WANG
Acta Pharmaceutica Sinica B 2025;15(10):5261-5276
Cannabidiol (CBD), a non-psychoactive cannabinoid, shows great promise in treating methamphetamine (METH) addiction. Nonetheless, the molecular target and the mechanism through which CBD treats METH addiction remain unexplored. Herein, CBD was shown to counteract METH-induced locomotor sensitization and conditioned place preference. Additionally, CBD mitigated the adverse effects of METH, such as cristae loss, a decline in ATP content, and a reduction in membrane potential. Employing an activity-based protein profiling approach, a target fishing strategy was used to uncover CBD's direct target. ATP5A1, a subunit of ATP synthase, was identified and validated as a CBD target. Moreover, CBD demonstrated the ability to ameliorate METH-induced ubiquitination of ATP5A1 via the D376 residue, thereby reversing the METH-induced reduction of ATP5A1 and promoting the assembly of ATP synthase. Pharmacological inhibition of the ATP efflux channel pannexin 1, blockade of ATP hydrolysis by a CD39 inhibitor, and blocking the adenosine A1 receptor (A1R) all attenuated the therapeutic benefits of CBD in mitigating METH-induced behavioral sensitization and CPP. Moreover, the RNA interference of ATP5A1 in the ventral tegmental area resulted in the reversal of CBD's therapeutic efficacy against METH addiction. Collectively, these data show that ATP5A1 is a target for CBD to inhibit METH-induced addiction behaviors through the ADO-A1R signaling pathway.
6.Expert consensus on pediatric orthodontic therapies of malocclusions in children
Zhou CHENCHEN ; Duan PEIPEI ; He HONG ; Song JINLIN ; Hu MIN ; Liu YUEHUA ; Liu YAN ; Guo JIE ; Jin FANG ; Cao YANG ; Jiang LINGYONG ; Ye QINGSONG ; Zhu MIN ; Jiang BEIZHAN ; Ruan WENHUA ; Yuan XIAO ; Li HUANG ; Zou RUI ; Tian YULOU ; Gao LI ; Shu RUI ; Chen JIANWEI ; Liu RENKAI ; Zou SHUJUAN ; Li XIAOBING
International Journal of Oral Science 2024;16(2):186-196
Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of~260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.
7.High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors.
Yi ZANG ; Mingbo SU ; Qingxing WANG ; Xi CHENG ; Wenru ZHANG ; Yao ZHAO ; Tong CHEN ; Yingyan JIANG ; Qiang SHEN ; Juan DU ; Qiuxiang TAN ; Peipei WANG ; Lixin GAO ; Zhenming JIN ; Mengmeng ZHANG ; Cong LI ; Ya ZHU ; Bo FENG ; Bixi TANG ; Han XIE ; Ming-Wei WANG ; Mingyue ZHENG ; Xiaoyan PAN ; Haitao YANG ; Yechun XU ; Beili WU ; Leike ZHANG ; Zihe RAO ; Xiuna YANG ; Hualiang JIANG ; Gengfu XIAO ; Qiang ZHAO ; Jia LI
Protein & Cell 2023;14(1):17-27
The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (Mpro) and papain like protease (PLpro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851Mpro inhibitors and 205 PLpro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both Mpro and PLpro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of Mpro inhibitors and over 20% of PLpro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 Mpro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans
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Antiviral Agents/chemistry*
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COVID-19
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COVID-19 Drug Treatment
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High-Throughput Screening Assays
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Molecular Docking Simulation
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Protease Inhibitors/chemistry*
;
SARS-CoV-2/enzymology*
;
Viral Nonstructural Proteins
8.A Rat Model of Adenine-induced Chronic Renal Failure Complicated with Cardiovascular Disease
Yuanyuan ZHANG ; Peipei JIN ; Wanzhe LI ; Dengzhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(16):79-88
ObjectiveTo explore the preparation method of a rat model of adenine-induced chronic renal failure complicated with cardiovascular disease by investigating the effect of different time points of adenine gastric lavage on general vital signs, biochemical indicators, and cardiac and renal tissue structure and function of model rats. MethodRats in the model group were administered adenine at 150 mg·kg-1·d-1 by gavage for 16 weeks, while those in the normal group were given an equal volume of 0.5% carboxymethyl cellulose sodium solution by gavage. At weeks 5, 13, 17, 24-hour urinary protein quantification (24 h-UTP), biochemical indicators, cardiac ultrasound, and changes in cardiac and renal tissue structure and function were measured in both the model and normal groups. Blood pressure was measured at weeks 5 and 13 in both groups. Weekly changes in body weight were recorded, and general conditions of the rats were observed daily. Result① Compared with the normal group, the model group showed a significant decrease in body weight (P<0.05). ② Rats in the model group exhibited a significant increase in urine volume, and proteinuria appeared at week 13. ③ Compared with the normal group, the model group showed significant differences in triglyceride (TG), total cholesterol (TC), creatinine (Cr), blood urea nitrogen (BUN), blood potassium, and blood phosphorus at week 5 (P<0.05), which increased gradually over time. At week 17, uric acid levels were significantly elevated (P<0.05), and blood calcium levels were reduced at the end of week 17 (P<0.01). ④ Compared with the normal group, the model group showed a significant increase in blood pressure at week 5 (P<0.05), which progressively worsened. ⑤ There was no statistically significant difference in left ventricular wall thickness between the model and normal groups at week 5, but a significant difference was observed at week 13 (P<0.05). ⑥ Fibrosis appeared in the kidneys of rats in the model group at week 5 and gradually worsened, while obvious fibrosis occurred around the cardiovascular system at week 13 as compared with the results in the normal group. ⑦ In the proximal tubular epithelial cells of the model group, there was an increasing presence of high-density rhomboid needle-shaped crystals, damaged cell membrane integrity, increased cell spacing, increased lysosomes, increased mitochondrial proliferation, denser mitochondrial cristae, and outer mitochondrial membrane. ⑧ Compared with the rats in the normal group, rats in the model group exhibited depressed spirits, significantly reduced activity, hunched posture, dry fur, pale ears and toes, swollen cheeks, increased nocturnal urination, and dark and viscous blood. ConclusionAdenine by gavage at 150 mg
9.Mechanism of Modified Zhenwutang in Delaying Renal Interstitial Fibrosis in Chronic Renal Failure Based on Ang Ⅱ/AT1R/NOX4 Signaling Pathway
Yuanyuan ZHANG ; Peipei JIN ; Dong BIAN ; Dengzhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(16):89-99
ObjectiveTo explore the underlying mechanism of modified Zhenwutang in delaying renal interstitial fibrosis in chronic renal failure (CRF) by observing the effects of modified Zhenwutang on the expression of angiotensin Ⅱ (Ang Ⅱ), angiotensin Ⅱ type 1 receptor (AT1R), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4), transforming growth factor-β1 (TGF-β1), type I collagen (COL1A1), and type Ⅲ collagen (COL3A1) in the serum and renal tissues of adenine-induced CRF rats. MethodFifty male SPF-grade SD rats were randomly divided into a normal group (n=10) and an experimental group (n=40) using a random number table. After one week of adaptive feeding, the experimental CRF model was established in rats by administering adenine at 150 mg·kg-1·d-1 orally. Three rats from each group were randomly selected to evaluate the model induction. After successful modeling, rats in the experimental group were randomly divided into a model group, low-, medium, and high-dose modified Zhenwutang groups, and a benazepril hydrochloride group, with six rats in each group. The rats were orally administered the corresponding drugs once daily for four weeks. At the end of the first week, 13th week, and 17th week of the experiment, 24 hour urinary protein quantification (24 h-UTP) was measured. At the end of the 17th week, the rats were euthanized, and blood samples were collected from the abdominal aorta for the measurement of total protein (TP), albumin (ALB), creatinine (Cr), and blood urea nitrogen (BUN) in the serum. Enzyme-linked immunosorbent assay (ELISA) was used to measure the expression levels of serum Ang Ⅱ. Hematoxylin-eosin (HE) staining and Masson's trichrome staining were performed to observe the pathological changes in renal tissues. Immunohistochemistry (IHC) was performed to observe the expression of AT1R, NOX4, TGF-β1, COL1A1, and COL3A1. Real-time fluorescence-based quantitative polymerase chain reaction (Real-time PCR) was used to observe the mRNA expression levels of AT1R, NOX4, and TGF-β1. Western blot was conducted to measure the protein expression levels of AT1R, NOX4, and TGF-β1. Result① Compared with the normal group, the model group showed a significant increase in 24 h-UTP (P<0.01). The levels of Cr and BUN in the model group were significantly higher (P<0.01), while the levels of TP and ALB were significantly lower (P<0.01). The serum Ang Ⅱ level in the model group was significantly elevated (P<0.01). The model group exhibited widening of the renal glomerular mesangial space, necrotic glomeruli, increased interstitial width with extensive inflammatory cell infiltration, brownish precipitates blocking the renal tubular lumens, irregular renal tubules, and significant deposition of collagen fibers in the renal interstitium. Additionally, the collagen fibers around the renal vessels, outside the parietal layer of the renal sacs, glomerular basement membrane, and tubular basement membrane increased significantly. The expression of AT1R and NOX4 in the glomeruli and renal tubules of the model group was significantly enhanced, and TGF-β1 expression also significantly increased in the renal tubules. The expression of COL1A1 and COL3A1 in the renal interstitium significantly increased. The mRNA expression of AT1R and TGF-β1 in the model group significantly increased (P<0.01), while NOX4 mRNA expression significantly decreased (P<0.01). The protein expression of AT1R, NOX4, and TGF-β1 was significantly enhanced (P<0.01). ② Compared with the model group, modified Zhenwutang significantly reduced 24h-UTP (P<0.01), decreased levels of Cr and BUN (P<0.01), increased levels of TP and ALB (P<0.01), reduced serum Ang Ⅱ level (P<0.01), alleviated renal pathological damage, reduced expression of AT1R, NOX4, TGF-β1, COL1A1, and COL3A1 in the glomeruli, renal tubules, and renal interstitium, reduced mRNA expression of AT1R and TGF-β1 (P<0.01), increased NOX4 mRNA expression (P<0.01), and weakened protein expression of AT1R, NOX4, and TGF-β1 (P<0.01). The modified Zhenwutang groups showed a significant dose-effect trend. ConclusionModified Zhenwutang may delay renal interstitial fibrosis in CRF rats by reducing the expression of Ang Ⅱ, AT1R, NOX4, and TGF-β1 in the serum and renal tissues, thereby alleviating renal pathological damage, reducing proteinuria, protecting renal function, and delaying the progression of CRF. The modified Zhenwutang group exhibited a dose-effect trend.
10.Based on Oxidative Stress/NF-κB Exploration of Mechanism of Modified Zhenwutang in Delaying Progression of Chronic Renal Failure Complicated with Cardiac Disease by Inflammatory Factors
Yuanyuan ZHANG ; Peipei JIN ; Jingya SONG ; Dengzhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(16):100-113
ObjectiveBy observing the effect of modified Zhenwutang on the expression of superoxide dismutase 1(SOD1), malondialdehyde(MDA), advanced oxidation protein product(AOPP), nuclear factor kappa-B(NF-κB) p65,p-p65,IL-1β, TNF-α in serum and renal tissue of adenine-induced chronic renal failure rats and the pathology of heart and kidney tissue, the possible mechanism of modified Zhenwutang delaying the progression of chronic renal failure complicated with heart disease was discussed. MethodFifty SPF male SD rats were divided into normal group 10 and model group 40 according to the random number table method. After one week of adaptive feeding, the experimental chronic renal failure complicated with cardiovascular disease rat model was established by intragastric administration of adenine 150 mg·kg-1·d-1. After the model was completed, 3 rats in the normal group and the model group were randomly selected to detect whether the model was successful. After successful modeling, the rats in the model group were divided into model group , modified Zhenwutang low-dose group , modified Zhenwutang medium-dose group, modified Zhenwutang high-dose group and Benazepril hydrochloride group according to the random number table method, with 6 rats in each group. Drugs were administered once a day for 4 weeks. At the end of the 17th week of the experiment, 24-hour urinary total protein(24 h-UTP) and urine creatinine(UCr)were detected. At the end of the 17th week, the rats in each group were anesthetized and the abdominal aorta was taken. After centrifugation, the supernatant was taken to detect triglyceride(TG), total cholesterol(TC), serum calcium(Ca), serum potassium, serum phosphate, serum creatinine(Scr), blood urea nitrogen(BUN); the expression levels of serum AOPP, IL-1β and TNF-α were detected by enzyme linked immunosorbent assay(ELISA). The pathological changes of heart and kidney tissues were observed by hematoxylin-eosin(HE)/Masson method. The ultrastructural changes of proximal renal tubules were observed by transmission electron microscopy . The kidney tissue expressions of SOD1, MDA, AOPP, NF-κB p65,p-p65,IL-1β and TNF-α were observed by immunohistochemistry. The kidney tissue expression levels of SOD1, NF-κB p65, IL-1β and TNF-α mRNA were observed by real-time polymerase chain reaction(Real-time PCR). The kidney tissue expression levels of SOD1, MDA, NF-κB p65 and p-p65 were detected by Western blot. Result①Compared with the normal group, the experimental rats in the model group showed an increase in 24-hour UTP (P<0.01)and a decrease in UCr(P<0.01). The experimental rats in the model group showed an increase in Cr, BUN, TG, TC, serum phosphate, and serum potassium(P<0.01).The levels of AOPP, IL-1β and TNF-α in serum of rats in the model group were significantly increased(P<0.01). In the model group, the glomerular balloon space was significantly widened, the renal interstitium was significantly widened with a large number of inflammatory cell infiltration, a large number of renal tubular lumens were blocked by brown deposits, and there were a large number of collagen fiber deposition in the renal interstitium. The collagen fibers around the renal vessels, outside the capsule wall of the renal capsule wall, glomerular basement membrane and renal tubular basement membrane were significantly increased, and the cardiac muscle fibers were significantly thickened. There was a small amount of inflammatory cell infiltration around the blood vessels, and a large number of collagen fibers around the cardiac vessels and between the myocardial cells. In the model group, high-density diamond-shaped needle-like crystals were observed in the proximal renal tubular epithelial cells of rats, with increased lysosomes, mitochondrial proliferation, mitochondrial cristae and dense mitochondrial outer membrane. The left ventricular diastolic wall thickness and systolic wall thickness of the experimental rats in the model group was increased in proximal renal tubular epithelial cells and their nuclei.In the model group, the expression of MDA, AOPP, NF-κB p65,p-p65 IL-1β and TNF-α in proximal renal tubular epithelial cells was significantly increased(P<0.01), the expression of p-p65 in the nucleus of proximal renal tubular epithelial cells was significantly increased(P<0.01), and the expression of SOD1 in proximal renal tubular epithelial cells was significantly decreased(P<0.01). The kidney tissue expression of NF-κB p65, IL-1β and TNF-α mRNA in the model group was increased(P<0.01), and the expression of SOD1 mRNA was decreased(P<0.01). The kidney tissue expression of SOD1 protein in the model group was significantly decreased(P<0.01). The kidney tissue expression of MDA, NF-κB p65 and p-p65 protein was increased (P<0.01). ② Compared with the model group, after the intervention of modified Zhenwutang, 24 h-UTP was decreased (P<0.01)and UCr was increased(P<0.01). Cr, BUN, TG, TC, serum phosphate, serum potassium was decreased (P<0.01). Serum AOPP, IL-1β and TNF-α levels were decreased(P<0.01). Cardiac and Renal pathological damage was reduced; mitochondrial damage in proximal renal tubules was reduced; the expression of MDA, AOPP, NF-κB p65, IL-1β, TNF-α in proximal renal tubular epithelial cells was decreased (P<0.01), the expression of p-p65 in the nucleus of proximal renal tubular epithelial cells was significantly decreased (P<0.01), and the expression of SOD1 in proximal renal tubular epithelial cells was significantly increased (P<0.01). The kidney tissue expression of NF-κB p65, IL-1β, TNF-α mRNA was decreased (P<0.01), and the expression of SOD1 mRNA was increased(P<0.01). The kidney tissue expression of SOD1 protein was significantly increased (P<0.01), and the expression of MDA, NF-κB p65 and p-p65 protein was decreased (P<0.01). The Chinese medicine group showed a significant dose-effect trend. ConclusionModified Zhenwutang may reduce the production of oxidative stress and mitochondrial damage in proximal renal tubular epithelial cells, thereby reducing oxidative stress products and inhibiting the release of inflammatory factors caused by the activation of NF-κB signaling pathway, reducing the damage to heart and kidney tissues and functions, and delaying the progression of chronic renal failure complicated with heart disease, and the traditional Chinese medicine group has a dose-effect trend.

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