1.Staged Characteristics of Mitochondrial Energy Metabolism in Chronic Heart Failure with Heart-Yang Deficiency Syndrome and Prescription Intervention from Theory of Reinforcing Yang
Zizheng WU ; Xing CHEN ; Lichong MENG ; Yao ZHANG ; Peng LUO ; Jiahao YE ; Kun LIAN ; Siyuan HU ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):129-138
Chronic heart failure (CHF) is a complex clinical syndrome caused by ventricular dysfunction, with mitochondrial energy metabolism disorder being a critical factor in disease progression. Heart-Yang deficiency syndrome, as the core pathogenesis of CHF, persists throughout the disease course. Insufficiency of heart-Yang leads to weakened warming and propelling functions, resulting in the accumulation of phlegm-fluid, blood stasis, and dampness. This eventually causes Qi stagnation with phlegm obstruction and blood stasis with water retention, forming a vicious cycle that exacerbates disease progression. According to the theory of reinforcing Yang, the clinical experience of the traditional Chinese medicine (TCM) master Tang Zuxuan in treating CHF with heart-Yang deficiency syndrome, and achievements from molecular biological studies, this study innovatively proposes an integrated research framework of "TCM syndrome differentiation and staging-mitochondrial metabolism mechanisms-intervention with Yang-reinforcing prescriptions" which is characterized by the integration of traditional Chinese and Western medicine. Heart-Yang deficiency syndrome is classified into mild (Stage Ⅰ-Ⅱ), severe (Stage Ⅲ), and critical (Stage Ⅳ) stages. The study elucidates the precise correlations between the pathogenesis of each stage and mitochondrial metabolism disorders from theoretical, pathophysiological, and therapeutic perspectives. The mild stage is characterized by impaired biogenesis and substrate-utilization imbalance, corresponding to heart-Yang deficiency and phlegm-fluid aggregation. Linggui Zhugantang and similar prescriptions can significantly improve the expression of peroxisome proliferator-activated receptor gamma co-activator-1α(PGC-1α)/silent information regulator 2 homolog 1 (SIRT1) and ATPase activity. The severe stage centers on oxidative stress and structural damage, reflecting Yang deficiency with water overflow and phlegm-blood stasis intermingling. At this stage, Zhenwu Tang and Qiangxin Tang can effectively mitigate oxidative stress damage, increase adenosine triphosphate (ATP) content, and repair mitochondrial structure. The critical stage arises from calcium overload and mitochondrial disintegration, leading to the collapse of Yin-Yang equilibrium. At this stage, Yang-restoring and crisis-resolving prescriptions such as Fuling Sini Tang and Qili Qiangxin capsules can inhibit abnormal opening of the mitochondrial permeability transition pore (MPTP), reduce cardiomyocyte apoptosis rate, and protect mitochondrial function. By summarizing the characteristics of mitochondrial energy metabolism disorders at different stages of CHF, this study explores the application of the theory of reinforcing Yang in treating heart-Yang deficiency syndrome and provides new insights for the clinical diagnosis and treatment of CHF.
2.Effects of Zuogui Jiangtang Yishen Formula in regulating the NLRP3/caspase-1/GSDMD signaling axis on pyroptosis in rats with diabetic kidney disease
Shujuan Hu ; Xuhua Li ; Yao Peng ; Lili Chen ; Rong Yu ; Yajun Peng
Digital Chinese Medicine 2025;8(3):379-388
Objective:
To investigate the effects of Zuogui Jiangtang Yishen Formula (左归降糖益肾方, ZGJTYSF) in regulating the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) signaling axis on pyroptosis in rats with diabetic kidney disease (DKD).
Methods:
Fifty male specific pathogen-free (SPF) grade Goto-Kakizaki (GK) rats (12 weeks old) were fed a high-fat diet for one month to establish an early DKD model. Model establishment was confirmed when fasting blood glucose (FBG) ≥ 11.1 mmol/L and urinary albumin-to-creatinine ratio (uACR) ≥ 30 mg/g. The successfully modeled early DKD rats were randomly divided by random number table into five groups (n = 10 per group): model group; dapagliflozin group (1.0 mg/kg, by gavage, served as positive control); and low-, medium-, and high-dose of ZGJTYSF groups (4.9, 9.9, and 19.9 g/kg, respectively, by gavage). Age-matched male SPF Wistar rats (n = 10) served as control group. Rats in control and model groups were gavaged with equivalent volumes of distilled water. Treatment lasted 12 weeks. Changes in uACR, FBG, and renal function were observed in all groups. Hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and Masson staining were used to observe renal histopathological changes. Immunohistochemistry was performed to detect the localization and expression of caspase-1, GSDMD, and NLRP3 in rat renal tissues. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) was utilized to detect pyroptosis in renal tissues. Quantitative real-time polymerase chain reaction (qPCR) and Western blot were applied to detect mRNA and protein expression levels of NLRP3, caspase-1, GSDMD, interleukin (IL)-1β, and IL-18.
Results:
Compared with model group, all doses of ZGJTYSF showed reductions in FBG, with medium- and high-dose of ZGJTYSF groups demonstrating significant decreases at week 8 and 12 (P < 0.05). For uACR, all doses of ZGJTYSF groups exhibited a decreasing trend, with high-dose of ZGJTYSF group being significantly lower than low- and medium-dose of ZGJTYSF groups at week 12 (P < 0.05) and showing no significant difference from dapagliflozin group (P > 0.05). No significant differences in renal function parameters (serum creatinine, blood urea nitrogen, and uric acid) were observed among groups (P > 0.05). Histopathological examination revealed milder glomerular and tubular lesions in both ZGJTYSF groups and dapagliflozin group, with renal pathological changes in high-dose of ZGJTYSF group resembling those in dapagliflozin group. Immunohistochemistry demonstrated significantly reduced expression of caspase-1, GSDMD, and NLRP3 in renal tissues of dapagliflozin group and high-dose of ZGJTYSF group compared with model group (P < 0.05 or P < 0.01), while the differences in low- and medium-dose of ZGJTYSF groups were not statistically significant (P > 0.05). TUNEL assay showed significantly fewer TUNEL-positive cells in renal tissues of dapagliflozin and high-dose of ZGJTYSF groups (P < 0.01), indicating a marked reduction in pyroptotic cells. Molecular analysis revealed that compared with model group, both dapagliflozin and high-dose of ZGJTYSF groups showed significantly downregulated mRNA and protein expression levels of NLRP3, caspase-1, GSDMD, IL-1β, and IL-18 in renal tissues (P < 0.01), while low- and medium-dose of ZGJTYSF groups showed downward trends without statistical significance (P > 0.05).
Conclusion
ZGJTYSF may inhibit renal pyroptosis by regulating the NLRP3/caspase-1/GSDMD signaling axis, thereby preventing and treating early renal injury in DKD and delaying the onset and progression of DKD.
3.Advances in the role of protein post-translational modifications in circadian rhythm regulation.
Zi-Di ZHAO ; Qi-Miao HU ; Zi-Yi YANG ; Peng-Cheng SUN ; Bo-Wen JING ; Rong-Xi MAN ; Yuan XU ; Ru-Yu YAN ; Si-Yao QU ; Jian-Fei PEI
Acta Physiologica Sinica 2025;77(4):605-626
The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology*
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Circadian Rhythm/physiology*
;
Humans
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Animals
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CLOCK Proteins/physiology*
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Circadian Clocks/physiology*
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Phosphorylation
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Acetylation
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Ubiquitination
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Sumoylation
4.Evaluation of augmented reality technology in the recognizing of oral and maxillofa-cial anatomy
Zunan TANG ; Leihao HU ; Zhen CHEN ; Yao YU ; Wenbo ZHANG ; Xin PENG
Journal of Peking University(Health Sciences) 2024;56(3):541-545
Objective:To evaluate the outcome of Augmented reality technology in the recognizing of oral and maxillofacial anatomy.Methods:This study was conducted on the undergraduate students in Peking University School of Stomatology who were learning oral and maxillofacial anatomy.The image da-ta were selected according to the experiment content,and the important blood vessels and bone tissue structures,such as upper and lower jaws,neck arteries and veins were reconstructed in 3D(3-dimension-al)by digital software to generate experiment models,and the reconstructed models were encrypted and stored in the cloud.The QR(quick response)code corresponding to the 3D model was scanned by a net-worked mobile device to obtain augmented reality images to assist experimenters in teaching and subjects in recognizing.Augmented reality technology was applied in both the theoretical explanation and cadaveric dissection respectively.Subjects'feedback was collected in the form of a post-class question-naire to evaluate the effectiveness of augmented reality technology-assisted recognizing.Results:In the study,83 undergraduate students were included as subjects in this study.Augmented reality technology could be successfully applied in the recognizing of oral and maxillofacial anatomy.All the subjects could scan the QR code through a connected mobile device to get the 3D anatomy model from the cloud,and zoom in/out/rotate the model on the mobile.Augmented reality technology could provide personalized 3D model,based on learners'needs and abilities.The results of likert scale showed that augmented reality technology was highly recognized by the students(9.19 points),and got high scores in terms of forming a three-dimensional sense and stimulating the enthusiasm for learning(9.01 and 8.85 points respective-ly).Conclusion:Augmented reality technology can realize the three-dimensional visualization of impor-tant structures of oral and maxillofacial anatomy and stimulate students'enthusiasm for learning.Be-sides,it can assist students in building three-dimensional space imagination of the anatomy of oral and maxillofacial area.The application of augmented reality technology achieves favorable effect in the recog-nizing of oral and maxillofacial anatomy.
5.Effect and Mechanism of Zuogui Jiangtang Yishen Prescription on Diabetic Kidney Disease in Rats via Regulation of MiRNA-27a/Wnt/β-catenin Pathway
Shujuan HU ; Xuhua LI ; Xiu LIU ; Yao PENG ; Lili CHEN ; Rong YU ; Yajun PENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):90-97
ObjectiveTo explore the protective effects and potential mechanism of Zuogui Jiangtang Yishen prescription (ZJYP) in Goto-Kakizaki (GK) rats with early-stage diabetic kidney disease (DKD). MethodFifty 12-week-old male GK rats were included in this study. DKD was induced after one month of high-fat feeding, with fasting blood glucose (FBG) ≥ 11.1 mmol·L-1 and urinary albumin/creatinine ratio (ACR) ≥ 30 mg·g-1 used as model criteria. After successful modeling, DKD rats were randomly divided into five groups (n=10 in each group): the model group, the western medicine group treated with dapagliflozin (1.0 mg·kg-1·d-1), low-, medium-, and high-dose ZJYP groups (4.9, 9.9, 19.9 g·kg-1·d-1 by gavage). Ten Wistar rats served as normal controls, with both the normal and model groups receiving physiological saline in the same volume as the treatment groups by gavage for 8 weeks. The urinary ACR, FBG, body weight, and liver and kidney functions of the rats were observed. Renal tissues were subjected to haematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining and examined under an electron microscope to observe pathological changes. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect miRNA-27a, Wnt, and β-catenin mRNA and protein expression levels in renal tissues. ResultCompared with the results in the normal group, the FBG levels in DKD rats of the model group increased significantly at 0, 2, 4, 6, and 8 weeks of drug intervention (P<0.05), and urinary ACR increased significantly at 0, 4, 8 weeks (P<0.05). Renal pathological staining and electron microscopy revealed an increase in mesangial cells and matrix, slight thickening of the basement membrane, and increased interstitial fibrosis and renal tubular atrophy in the model group. The mRNA expression levels of miRNA-27a, Wnt, and β-catenin were significantly higher in the model group than in the normal group (P<0.05). Renal Wnt and β-catenin protein levels were also significantly higher in the model group (P<0.05). After drug intervention, the FBG levels in the low-, medium-, and high-dose ZJYP groups showed a dose-dependent decrease compared with those in the model group at 6 and 8 weeks (P<0.05). The urinary ACR also showed a dose-dependent decrease in the low-, medium-, and high-dose ZJYP groups, but the differences were not statistically significant. There were no significant differences in liver function, renal function, renal index, or routine blood lipid test results among the low-, medium-, and high-dose ZJYP groups. Renal glomerular and tubular lesions were milder in the ZJYP groups and the western medicine group than in the model group, with similar pathological changes observed in the high-dose ZJYP group and the western medicine group. The renal mRNA levels of miRNA-27a, Wnt, and β-catenin were significantly lower in the high-dose ZJYP group (P<0.05), and renal Wnt and β-catenin protein levels were significantly lower in both the western medicine group and the high-dose ZJYP group compared with the levels in the model group (P<0.05). The Wnt and β-catenin protein levels were lower in the renal tissues of the low- and medium-dose ZJYP groups compared with the levels in the model group, but the differences were not statistically significant. ConclusionZJYP can effectively improve glucose metabolism and alleviate early damage in DKD rats, thereby delaying the progression of DKD. Its mechanism may be related to the inhibition of the miRNA-27a/Wnt/β-catenin signaling pathway in renal tissues.
6.Effect and Mechanism of Sishenjian on Synovial Lesions in Knee Osteoarthritis Rats
Zixuan HU ; Xuejun HUANG ; Nan YAO ; Sha PENG ; Dan'e HUANG ; Tao JIANG ; Haining GAN ; Xiaodan HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):18-26
ObjectiveTo explore the effect and mechanism of Sishenjian on synovial lesions induced by monosodium iodoacetate (MIA) in rats with knee osteoarthritis (KOA). MethodSixty female Sprague-Dawley (SD) rats were randomly divided into the following six groups: normal group, model group, celecoxib group, and high-, medium-, and low-dose Sishenjian group. The KOA rat model was established by intra-articular injection of MIA. Celecoxib (18 mg·kg-1) and Sishenjian (14.4, 7.2, 3.6 g·kg-1) were administered by gavage according to the groups. All rats were euthanized after four weeks of continuous administration. The transverse diameter of the bilateral knee joints of rats was measured, and gross observation of the knee joint was performed. Pathological changes in knee joint synovial tissue were observed by hematoxylin-eosin (HE) staining and picrosirius red staining. Immunohistochemistry (IHC) was used to detect the expression of vascular endothelial growth factor A (VEGFA) in synovial tissue. The levels of inflammatory cytokines in the joint synovial fluid were detected by enzyme-linked immunosorbent assay (ELISA). Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the expression of mRNA and proteins related to the transforming growth factor-β1 (TGF-β1)/Smad2/3 pathway in knee joint synovium. ResultCompared with the normal group, the transverse diameter of the knee joint in the model group significantly increased (P<0.01). Compared with the model group, the transverse diameter of the knee joint in rats of each Sishenjian group significantly decreased (P<0.01). Compared with the normal group, the expression levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the knee joint synovial fluid of model group significantly increased (P<0.01). Compared with the model group, the expression levels of IL-1β and TNF-α in the knee joint synovial fluid of rats in each Sishenjian group significantly decreased (P<0.01). Compared with the normal group, the expression levels of TGF-β1, Smad2/3, phosphorylation(p)-Smad2/3, type Ⅰ collagen α1 (ColⅠα1), type Ⅲ collagen α1 (ColⅢα1), VEGFA proteins and TGF-β1, Smad2/3, ColⅠα1, ColⅢα1 mRNA in knee joint synovium of model group significantly increased (P<0.01). Compared with the model group, the expression levels of TGF-β1, Smad2/3, phosphorylation (p)-Smad2/3, ColⅠα1, ColⅢα1, VEGFA proteins and TGF-β1, Smad2/3, ColⅠα1, ColⅢα1 mRNA in knee joint synovium of rats in each Sishenjian group significantly decreased (P<0.05, P<0.01). ConclusionSishenjian can inhibit synovial inflammation and angiogenesis, and may become a potential drug for treating synovial lesions in KOA by regulating the TGF-β1/Smad2/3 pathway.
7.Structural Characteristics and Antioxidant Activity Analysis of Polysaccharides from Pinelliae Rhizoma and Its Processed Products Before and After Hydrolysis (Enzymolysis) by Sugar Spectrum
Meibian HU ; Kuixu GAO ; Yao WANG ; Xi PENG ; Jingya WANG ; Xianglong MENG ; Shuosheng ZHANG ; Jianghua LI ; Yujie LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):192-201
ObjectiveThe glycosidic linkage structural characteristics of polysaccharides from Pinelliae Rhizoma(PR) and its processed products were analyzed by sugar spectrum, high performance thin layer chromatography(HPTLC), fluorescence-assisted carbohydrate gel electrophoresis(PACE) based on partial acid hydrolysis and specific glycosidase hydrolysis, and the antioxidant activities of polysaccharides before and after hydrolysis(enzymolysis
8.Treating Asthenopia from the Perspective of “the Liver is the Basis of Resistance to Fatigue”
Jiangwei LI ; Xiaolei YAO ; Lihao CHEN ; Yi HU ; Qinghua PENG
Journal of Traditional Chinese Medicine 2024;65(6):649-651
By exploring the theory of “the liver is the basis of resistance to fatigue”, it is believed that liver with its physiological function of storing blood and governing the free flow of qi plays an important role in the body's tole-rance to physical fatigue and mental fatigue, and it is also related to the physiological activities of eyes and tendons. The formation of asthenopia is related to the dysfunction of liver, spleen and kidney. The liver plays a key role in the occurrence and development of asthenopia. The deficiency of liver blood and liver dysfunction will cause the abnormal circulation of qi and blood, which leads to the loss of malnutrition of eyes and affects the normal physiological function of eyes. During treatment, we pay attention to nourishing the blood and soothing the liver to nourish the spirit, regulating and tonifying liver qi to stimulate the liver yang, strengthening the spleen and soothing liver to replenish qi and promoting yang, nourishing the liver and kidney to harmonize yin and yang, which are meant to restore the physiological characteristics of liver being yin in form but yang in function, so as to cure asthenopia.
9.Current status and prospects of exoskeletons applied in medical service support
Yao-Rui YU ; Xue-Jun HU ; Kun-Peng WU ; Jing-Guang PAN ; Huo-Liang CHEN ; Jie REN ; Wei JIANG
Chinese Medical Equipment Journal 2024;45(3):71-75
The current status of exoskeletons was introduced in enhancing individual soldier's battlefield rescue capabilities,promoting the integrated use of battlefield rescue equipment,protecting medical personnel on the battlefield and assisting injured soldiers in rehabilitation training.The challenges of exoskeletons faced in human-machine interaction,power supply endurance,heavy overall structure,restricted movement and high cost were analyzed when applied to medical service support,and some suggestions were proposed accordingly including enhancing technology research and development,integrated application,communication and cooperation and personnel training.References were provided for the application of exoskeletons in China's medical service support.[Chinese Medical Equipment Journal,2024,45(3):71-75]
10.Clinical efficacy of repeated transcranial magnetic stimulation combined with acupuncture for chronic insomnia
Fenfen YAO ; Tao XU ; Hongling HU ; Jian CHEN ; Xiaoyan YOU ; Qing GUO ; Junyan CHEN ; Peng YU
China Modern Doctor 2024;62(27):12-16
Objective To explore the clinical efficacy of repeated transcranial magnetic stimulation(rTMS)and acupuncture therapy in the treatment of chronic insomnia disorder(CID)patients.Methods A total of 80 patients with CID,who were treated at Nanchang First Hospital from January 2022 to December 2023,were selected for the study.The patients were randomly divided into control group and treatment group,with 40 cases in each group.The control group patients were treated with dexmedetomidine,while the treatment group patients received rTMS and acupuncture therapy in addition to control group.The treatment course was 4 weeks,and the sleep quality,sleep related indicators,and psychological condition improvement of both groups of patients were observed before and after treatment.Results After treatment,the Pittsburgh sleep quality index scores of both groups of patients decreased(P<0.05);The sleep latency and number of awakenings were lower than before treatment(P<0.05),and the total sleep time,sleep efficiency,and proportion of rapid eye movement sleep were higher than before treatment,treatment group showed more significant improvement than control group(P<0.05).After treatment,the Hamilton anxiety and depression scale scores of both groups of patients decreased compared to before treatment,but there was no statistically significant difference in control group before and after treatment(P>0.05).However,there was a statistically significant difference in treatment group before and after treatment(P<0.05).Conclusion The combination of rTMS and acupuncture treatment can significantly improve the sleep quality of CID patients,while also reducing the accompanying symptoms of anxiety and depression.

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