1.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.
2.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.
3.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
4.A Rapid Non-invasive Method for Skin Tumor Tissue Early Detection Based on Bioimpedance Spectroscopy
Jun-Wen PENG ; Song-Pei HU ; Zhi-Yang HONG ; Li-Li WANG ; Kai LIU ; Jia-Feng YAO
Progress in Biochemistry and Biophysics 2024;51(5):1161-1173
ObjectiveIn recent years, with the intensification of environmental issues and the depletion of ozone layer, incidence of skin tumors has also significantly increased, becoming one of the major threats to people’s lives and health. However, due to factors such as high concealment in the early stage of skin tumors, unclear symptoms, and large human skin area, most cases are detected in the middle to late stage. Early detection plays a crucial role in postoperative survival of skin tumors, which can significantly improve the treatment and survival rates of patients. We proposed a rapid non-invasive electrical impedance detection method for early screening of skin tumors based on bioimpedance spectroscopy (BIS) technology. MethodsFirstly, we have established a complete skin stratification model, including stratum corneum, epidermis, dermis, and subcutaneous tissue. And the numerical analysis method was used to investigate the effect of dehydrated and dry skin stratum corneum on contact impedance in BIS measurement. Secondly, differentiation effect of different diameter skin tumor tissues was studied using a skin model after removing the stratum corneum. Then, in order to demonstrate that BIS technology can be used for detecting the microinvasion stage of skin tumors, we conducted a simulation study on the differentiation effect of skin tumors under different infiltration depths. Finally, in order to verify that the designed BIS detection system can distinguish between tumor microinvasion periods, we conducted tumor invasion experiments using hydrogel treated pig skin tissue. ResultsThe simulation results show that a dry and high impedance stratum corneum will bring about huge contact impedance, which will lead to larger measurement errors and affect the accuracy of measurement results. We extracted the core evaluation parameter of relaxed imaginary impedance (Zimag-relax) from the simulation results of the skin tumor model. When the tumor radius (Rtumor) and invasion depth (h)>1.5 mm, the designed BIS detection system can distinguish between tumor tissue and normal tissue. At the same time, in order to evaluate the degree of canceration in skin tissue, the degree of tissue lesion (εworse) is defined by the relaxed imaginary impedance (Zimag-relax) of normal and tumor tissue (εworse is the percentage change in virtual impedance of tumor tissue relative to that of normal tissue), and we fitted a Depth-Zimag-relax curve using relaxation imaginary impedance data at different infiltration depths, which can be applied to quickly determine the infiltration depth of skin tumors after being supplemented with a large amount of clinical data in the future. The experimental results proved that when εworse=0.492 0, BIS could identify microinvasive tumor tissue, and the fitting curve correction coefficient of determination was 0.946 8, with good fitting effect. The simulation using pig skin tissue correlated the results of real human skin simulation with the experimental results of pig skin tissue, proving the reliability of this study, and laying the foundation for further clinical research in the future. ConclusionOur proposed BIS method has the advantages of fast, real-time, and non-invasive detection, as well as high sensitivity to skin tumors, which can be identified during the stage of tumor microinvasion.
5.Mixed reality combined with surgical navigation technology assisted in parapharyngeal space tumors surgery: a clinical study
Zunan TANG ; Leihao HU ; Shuo LIU ; Yao YU ; Wenbo ZHANG ; Xin PENG
Chinese Journal of Stomatology 2024;59(11):1107-1113
Objective:To assess the feasibility and application of mixed reality combined with surgical navigation technology in parapharyngeal space tumor surgery, and to provide a reference for the development and promotion of this technology.Methods:In this study, retrospective data collection was conducted on 16 patients with parapharyngeal space tumors who were treated at the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from June 2020 to June 2023. The patient′s age was (39.6±17.8) years, with 4 males and 12 females. Mixed reality combined with surgical navigation technology was utilized to assist physicians in the treatment of these patients. Mixed reality combined with surgical navigation technology was used to assist physicians in treatment of these patients. The application steps included acquisition of image data, processing of image data [three-dimensional (3D) reconstruction, image fusion, and virtual surgical design], development of surgical navigation plan, connection of mixed reality and navigation system, automatic registration and intraoperative guidance and validation. In the preoperative plan, landmark points were placed on the virtual tumor and surrounding important structures reconstructed using digital software, serving to guide the localization of crucial anatomical structures. Intraoperative positioning deviation, surgical time, intraoperative blood loss, and postoperative complications were recorded and analyzed to evaluate the clinical application effectiveness of mixed reality combined with surgical navigation technology.Results:With the assistance of mixed reality combined with surgical navigation technology, 16 patients successfully underwent tumor resection. All patients were accurately diagnosed preoperatively by 3D reconstruction and image fusion technology, and a comprehensive preoperative plan was formulated; intraoperatively, mixed reality combined with surgical navigation technology was utilized for the localization of important structures. The average localization deviation of 38 landmark points during the operation were (4.43±1.96) mm, with 62% (26/42) of the points having a deviation of ≥0 and<5 mm. The average duration of the operation was (149.6±53.9) min and the blood loss was 70 (45, 150) ml. The average postoperative follow-up was 16 months, and five patients experienced postoperative complications involving facial paralysis, hoarseness, and choking.Conclusions:Mixed reality combined with surgical navigation technology can achieve the three-dimensional visualization of oral and maxillofacial anatomical structures to achieve precise preoperative diagnosis. During surgery, the technology can real-time display the relationship between soft tissue tumors and the surrounding important anatomical structures, guide surgical operation, and enhance the safety of surgery.
6.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.
7.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.
8.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]
9.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.
10.Efficacy evaluation of extending or switching to tenofovir amibufenamide in patients with chronic hepatitis B: a phase Ⅲ randomized controlled study
Zhihong LIU ; Qinglong JIN ; Yuexin ZHANG ; Guozhong GONG ; Guicheng WU ; Lvfeng YAO ; Xiaofeng WEN ; Zhiliang GAO ; Yan HUANG ; Daokun YANG ; Enqiang CHEN ; Qing MAO ; Shide LIN ; Jia SHANG ; Huanyu GONG ; Lihua ZHONG ; Huafa YIN ; Fengmei WANG ; Peng HU ; Xiaoqing ZHANG ; Qunjie GAO ; Chaonan JIN ; Chuan LI ; Junqi NIU ; Jinlin HOU
Chinese Journal of Hepatology 2024;32(10):883-892
Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

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