1.Mechanisms of Zhuyuwan in Treating both Intrahepatic Cholestasis and Ulcerative Colitis Based on Homotherapy for Heteropathy
Jun HAN ; Yueqiang WEN ; Zongying XU ; Dan LUO ; Li ZHOU ; Xueyi LI ; Yufan DAI ; Lele YANG ; Tao SHEN ; Han YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):46-53
		                        		
		                        			
		                        			ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point, this study employed gas chromatography-mass spectrometry (GC-MS) to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis (IC) and ulcerative colitis (UC) from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate (ANIT)-induced cholestasis and 2,4,6-trinitro-benzenesulfonic acid (TNBS)-induced UC were treated with low (0.6 g·kg-1) and high (1.2 g·kg-1) doses of Zhuyuwan by gavage. In the experiment regarding IC, 24 Sprague-Dawley (SD) rats were randomly assigned into four groups: normal, ANIT model, low-dose Zhuyuwan, and high-dose Zhuyuwan. In the experiment regarding UC, 24 SD rats were randomly allocated into four groups: normal, TNBS model, low-dose Zhuyuwan, and high-dose Zhuyuwan. Firstly, the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators [alanine aminotransferase (ALT), aspartate transaminase (AST), γ-glutamyltranspeptidase (γ-GT), and total bile acid (TBA)], colon damage score, colon weight index, disease activity index, and histopathological changes in rats. Secondly, the rat serum samples were analyzed by gas chromatography-mass spectrometry (GC-MS) to screen the common core pathways of the two disease models, and the expression of core genes in the pathways was determined by Real-time PCR, on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT, AST, γ-GT, and TBA levels than the normal group (P<0.01). Compared with the ANIT model group, the low-dose Zhuyuwan group showed declined ALT and TBA levels (P<0.01) and the high-dose Zhuyuwan group showed lowered ALT, TBA, AST, and γ-GT levels (P<0.01). The results of the experiment regarding UC showed that compared with the normal group, the TNBS model group presented increases in the colonic damage score, colon weight index, and disease activity index (P<0.01). Compared with the TNBS model group, the low-dose Zhuyuwan group showcased declines in colon weight index (P<0.01) and disease activity index (P<0.05), and the high-dose Zhuyuwan group showed reductions in the colon damage score, colon weight index, and disease activity index (P<0.01). GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC, and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan. 
		                        		
		                        		
		                        		
		                        	
2.Mechanisms of Zhuyuwan in Treating both Intrahepatic Cholestasis and Ulcerative Colitis Based on Homotherapy for Heteropathy
Jun HAN ; Yueqiang WEN ; Zongying XU ; Dan LUO ; Li ZHOU ; Xueyi LI ; Yufan DAI ; Lele YANG ; Tao SHEN ; Han YU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):46-53
		                        		
		                        			
		                        			ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point, this study employed gas chromatography-mass spectrometry (GC-MS) to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis (IC) and ulcerative colitis (UC) from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate (ANIT)-induced cholestasis and 2,4,6-trinitro-benzenesulfonic acid (TNBS)-induced UC were treated with low (0.6 g·kg-1) and high (1.2 g·kg-1) doses of Zhuyuwan by gavage. In the experiment regarding IC, 24 Sprague-Dawley (SD) rats were randomly assigned into four groups: normal, ANIT model, low-dose Zhuyuwan, and high-dose Zhuyuwan. In the experiment regarding UC, 24 SD rats were randomly allocated into four groups: normal, TNBS model, low-dose Zhuyuwan, and high-dose Zhuyuwan. Firstly, the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators [alanine aminotransferase (ALT), aspartate transaminase (AST), γ-glutamyltranspeptidase (γ-GT), and total bile acid (TBA)], colon damage score, colon weight index, disease activity index, and histopathological changes in rats. Secondly, the rat serum samples were analyzed by gas chromatography-mass spectrometry (GC-MS) to screen the common core pathways of the two disease models, and the expression of core genes in the pathways was determined by Real-time PCR, on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT, AST, γ-GT, and TBA levels than the normal group (P<0.01). Compared with the ANIT model group, the low-dose Zhuyuwan group showed declined ALT and TBA levels (P<0.01) and the high-dose Zhuyuwan group showed lowered ALT, TBA, AST, and γ-GT levels (P<0.01). The results of the experiment regarding UC showed that compared with the normal group, the TNBS model group presented increases in the colonic damage score, colon weight index, and disease activity index (P<0.01). Compared with the TNBS model group, the low-dose Zhuyuwan group showcased declines in colon weight index (P<0.01) and disease activity index (P<0.05), and the high-dose Zhuyuwan group showed reductions in the colon damage score, colon weight index, and disease activity index (P<0.01). GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC, and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan. 
		                        		
		                        		
		                        		
		                        	
3.Effect of ab-externo circumferential suture trabeculotomy on 24-hour pattern of intraocular pressure in patients with primary open angle glaucoma
Tao LIN ; Jiaqi WANG ; Yufan DING ; Gang LIU
International Eye Science 2024;24(8):1324-1327
		                        		
		                        			
		                        			 AIM: To evaluate the effect of ab-externo circumferential suture trabeculotomy(CST)on the 24 h pattern of intraocular pressure(IOP)in primary open angle glaucoma(POAG).METHODS: This retrospective study included 18 POAG patients who had poor control of IOP from March 2021 to May 2022. The ab-externo CST was performed, and IOP was tested preoperatively and 1 a postoperatively(9:00 a.m., 12:00 a.m., 3:00 p.m., 6:00 p.m., 9:00 p.m., 12:00 p.m., 3 a.m., and 6:00 a.m.). The mean, peak, trough, and range of IOP, as well as the average diurnal-nocturnal IOP change were calculated and compared.RESULTS: The 24 h IOP curves exhibited a decreasing trend during the diurnal period and an increasing trend during the nocturnal period, reaching a trough in the afternoon and peaking at night; the time of trough and peak IOP occurred several hours earlier compared to preoperative eyes. Postoperatively, the mean, peak, and trough IOP values were significantly lower compared to preoperative levels. The range of fluctuation showed no significant difference, while the average diurnal-nocturnal IOP change increased significantly.CONCLUSION: CST could reduce IOP of patients with POAG, but could not change the range of IOP fluctuation. However, an increase in the average diurnal-nocturnal IOP change was observed, indicating that CST might not necessarily reduce diurnal-nocturnal IOP fluctuations. 
		                        		
		                        		
		                        		
		                        	
		                				4.In vitro  heat insulation efficacy of 5% dextrose versus 0.9% saline during radiofrequency ablation
		                			
		                			Yanping MA ; Jinfen WANG ; Tao WU ; Bowen ZHENG ; Tinghui YIN ; Yufan LIAN ; Jie REN
Ultrasonography 2024;43(5):376-383
		                        		
		                        			 Purpose:
		                        			This study compared the efficacy of heat insulation between 5% dextrose and 0.9% saline in radiofrequency ablation (RFA). Accordingly, temperature variations and maximum temperatures were assessed at identical distances and heat field distributions. 
		                        		
		                        			Methods:
		                        			Cubes of porcine liver tissue, measuring 10 mm across, were selected to precisely align the ablation boundary with the tissue boundary. An 18-gauge electrode with a 7-mm tip was inserted into each cube (10 per group) in a stainless-steel cup containing 40 mL of 5% dextrose or 0.9% saline. Fixed ablation was performed for 3 minutes using continuous mode at 30 W, simulating the typical thermal environment during thyroid RFA. Real-time temperature measurements were recorded by sensors positioned 0, 1, 3, and 5 mm from the cube’s edge. A comparative analysis was conducted to assess the maximum temperature, temperature variation, and duration of temperatures exceeding 42℃. 
		                        		
		                        			Results:
		                        			In both groups, the temperature curve declined with increasing distance from the edge of the ablated tissue. However, 0.9% saline exhibited higher maximum temperatures at 1, 3, and 5 mm compared to 5% dextrose (1 mm: 44.55°C±5.25°C vs. 34.68°C±3.07°C; 3 mm: 39.64°C±2.53°C vs. 29.22°C±2.21°C; 5 mm: 38.86°C±2.14°C vs. 28.74°C±2.51°C; all P<0.001). Considering a nerve injury threshold of 42°C, the 0.9% saline also displayed a greater proportion of samples reaching this temperature and a longer duration of temperatures exceeding it (P<0.05). 
		                        		
		                        			Conclusion
		                        			The heat insulation efficacy of 5% dextrose at 1-5 mm exceeds that of 0.9% saline at identical distances and in a common thermal environment during thyroid RFA. 
		                        		
		                        		
		                        		
		                        	
		                				5.In vitro  heat insulation efficacy of 5% dextrose versus 0.9% saline during radiofrequency ablation
		                			
		                			Yanping MA ; Jinfen WANG ; Tao WU ; Bowen ZHENG ; Tinghui YIN ; Yufan LIAN ; Jie REN
Ultrasonography 2024;43(5):376-383
		                        		
		                        			 Purpose:
		                        			This study compared the efficacy of heat insulation between 5% dextrose and 0.9% saline in radiofrequency ablation (RFA). Accordingly, temperature variations and maximum temperatures were assessed at identical distances and heat field distributions. 
		                        		
		                        			Methods:
		                        			Cubes of porcine liver tissue, measuring 10 mm across, were selected to precisely align the ablation boundary with the tissue boundary. An 18-gauge electrode with a 7-mm tip was inserted into each cube (10 per group) in a stainless-steel cup containing 40 mL of 5% dextrose or 0.9% saline. Fixed ablation was performed for 3 minutes using continuous mode at 30 W, simulating the typical thermal environment during thyroid RFA. Real-time temperature measurements were recorded by sensors positioned 0, 1, 3, and 5 mm from the cube’s edge. A comparative analysis was conducted to assess the maximum temperature, temperature variation, and duration of temperatures exceeding 42℃. 
		                        		
		                        			Results:
		                        			In both groups, the temperature curve declined with increasing distance from the edge of the ablated tissue. However, 0.9% saline exhibited higher maximum temperatures at 1, 3, and 5 mm compared to 5% dextrose (1 mm: 44.55°C±5.25°C vs. 34.68°C±3.07°C; 3 mm: 39.64°C±2.53°C vs. 29.22°C±2.21°C; 5 mm: 38.86°C±2.14°C vs. 28.74°C±2.51°C; all P<0.001). Considering a nerve injury threshold of 42°C, the 0.9% saline also displayed a greater proportion of samples reaching this temperature and a longer duration of temperatures exceeding it (P<0.05). 
		                        		
		                        			Conclusion
		                        			The heat insulation efficacy of 5% dextrose at 1-5 mm exceeds that of 0.9% saline at identical distances and in a common thermal environment during thyroid RFA. 
		                        		
		                        		
		                        		
		                        	
		                				6.In vitro  heat insulation efficacy of 5% dextrose versus 0.9% saline during radiofrequency ablation
		                			
		                			Yanping MA ; Jinfen WANG ; Tao WU ; Bowen ZHENG ; Tinghui YIN ; Yufan LIAN ; Jie REN
Ultrasonography 2024;43(5):376-383
		                        		
		                        			 Purpose:
		                        			This study compared the efficacy of heat insulation between 5% dextrose and 0.9% saline in radiofrequency ablation (RFA). Accordingly, temperature variations and maximum temperatures were assessed at identical distances and heat field distributions. 
		                        		
		                        			Methods:
		                        			Cubes of porcine liver tissue, measuring 10 mm across, were selected to precisely align the ablation boundary with the tissue boundary. An 18-gauge electrode with a 7-mm tip was inserted into each cube (10 per group) in a stainless-steel cup containing 40 mL of 5% dextrose or 0.9% saline. Fixed ablation was performed for 3 minutes using continuous mode at 30 W, simulating the typical thermal environment during thyroid RFA. Real-time temperature measurements were recorded by sensors positioned 0, 1, 3, and 5 mm from the cube’s edge. A comparative analysis was conducted to assess the maximum temperature, temperature variation, and duration of temperatures exceeding 42℃. 
		                        		
		                        			Results:
		                        			In both groups, the temperature curve declined with increasing distance from the edge of the ablated tissue. However, 0.9% saline exhibited higher maximum temperatures at 1, 3, and 5 mm compared to 5% dextrose (1 mm: 44.55°C±5.25°C vs. 34.68°C±3.07°C; 3 mm: 39.64°C±2.53°C vs. 29.22°C±2.21°C; 5 mm: 38.86°C±2.14°C vs. 28.74°C±2.51°C; all P<0.001). Considering a nerve injury threshold of 42°C, the 0.9% saline also displayed a greater proportion of samples reaching this temperature and a longer duration of temperatures exceeding it (P<0.05). 
		                        		
		                        			Conclusion
		                        			The heat insulation efficacy of 5% dextrose at 1-5 mm exceeds that of 0.9% saline at identical distances and in a common thermal environment during thyroid RFA. 
		                        		
		                        		
		                        		
		                        	
		                				7.In vitro  heat insulation efficacy of 5% dextrose versus 0.9% saline during radiofrequency ablation
		                			
		                			Yanping MA ; Jinfen WANG ; Tao WU ; Bowen ZHENG ; Tinghui YIN ; Yufan LIAN ; Jie REN
Ultrasonography 2024;43(5):376-383
		                        		
		                        			 Purpose:
		                        			This study compared the efficacy of heat insulation between 5% dextrose and 0.9% saline in radiofrequency ablation (RFA). Accordingly, temperature variations and maximum temperatures were assessed at identical distances and heat field distributions. 
		                        		
		                        			Methods:
		                        			Cubes of porcine liver tissue, measuring 10 mm across, were selected to precisely align the ablation boundary with the tissue boundary. An 18-gauge electrode with a 7-mm tip was inserted into each cube (10 per group) in a stainless-steel cup containing 40 mL of 5% dextrose or 0.9% saline. Fixed ablation was performed for 3 minutes using continuous mode at 30 W, simulating the typical thermal environment during thyroid RFA. Real-time temperature measurements were recorded by sensors positioned 0, 1, 3, and 5 mm from the cube’s edge. A comparative analysis was conducted to assess the maximum temperature, temperature variation, and duration of temperatures exceeding 42℃. 
		                        		
		                        			Results:
		                        			In both groups, the temperature curve declined with increasing distance from the edge of the ablated tissue. However, 0.9% saline exhibited higher maximum temperatures at 1, 3, and 5 mm compared to 5% dextrose (1 mm: 44.55°C±5.25°C vs. 34.68°C±3.07°C; 3 mm: 39.64°C±2.53°C vs. 29.22°C±2.21°C; 5 mm: 38.86°C±2.14°C vs. 28.74°C±2.51°C; all P<0.001). Considering a nerve injury threshold of 42°C, the 0.9% saline also displayed a greater proportion of samples reaching this temperature and a longer duration of temperatures exceeding it (P<0.05). 
		                        		
		                        			Conclusion
		                        			The heat insulation efficacy of 5% dextrose at 1-5 mm exceeds that of 0.9% saline at identical distances and in a common thermal environment during thyroid RFA. 
		                        		
		                        		
		                        		
		                        	
		                				8.In vitro  heat insulation efficacy of 5% dextrose versus 0.9% saline during radiofrequency ablation
		                			
		                			Yanping MA ; Jinfen WANG ; Tao WU ; Bowen ZHENG ; Tinghui YIN ; Yufan LIAN ; Jie REN
Ultrasonography 2024;43(5):376-383
		                        		
		                        			 Purpose:
		                        			This study compared the efficacy of heat insulation between 5% dextrose and 0.9% saline in radiofrequency ablation (RFA). Accordingly, temperature variations and maximum temperatures were assessed at identical distances and heat field distributions. 
		                        		
		                        			Methods:
		                        			Cubes of porcine liver tissue, measuring 10 mm across, were selected to precisely align the ablation boundary with the tissue boundary. An 18-gauge electrode with a 7-mm tip was inserted into each cube (10 per group) in a stainless-steel cup containing 40 mL of 5% dextrose or 0.9% saline. Fixed ablation was performed for 3 minutes using continuous mode at 30 W, simulating the typical thermal environment during thyroid RFA. Real-time temperature measurements were recorded by sensors positioned 0, 1, 3, and 5 mm from the cube’s edge. A comparative analysis was conducted to assess the maximum temperature, temperature variation, and duration of temperatures exceeding 42℃. 
		                        		
		                        			Results:
		                        			In both groups, the temperature curve declined with increasing distance from the edge of the ablated tissue. However, 0.9% saline exhibited higher maximum temperatures at 1, 3, and 5 mm compared to 5% dextrose (1 mm: 44.55°C±5.25°C vs. 34.68°C±3.07°C; 3 mm: 39.64°C±2.53°C vs. 29.22°C±2.21°C; 5 mm: 38.86°C±2.14°C vs. 28.74°C±2.51°C; all P<0.001). Considering a nerve injury threshold of 42°C, the 0.9% saline also displayed a greater proportion of samples reaching this temperature and a longer duration of temperatures exceeding it (P<0.05). 
		                        		
		                        			Conclusion
		                        			The heat insulation efficacy of 5% dextrose at 1-5 mm exceeds that of 0.9% saline at identical distances and in a common thermal environment during thyroid RFA. 
		                        		
		                        		
		                        		
		                        	
9.Hollow copper sulfide nanoparticles carrying ISRIB for the sensitized photothermal therapy of breast cancer and brain metastases through inhibiting stress granule formation and reprogramming tumor-associated macrophages.
Fan TONG ; Haili HU ; Yanyan XU ; Yang ZHOU ; Rou XIE ; Ting LEI ; Yufan DU ; Wenqin YANG ; Siqin HE ; Yuan HUANG ; Tao GONG ; Huile GAO
Acta Pharmaceutica Sinica B 2023;13(8):3471-3488
		                        		
		                        			
		                        			As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.
		                        		
		                        		
		                        		
		                        	
10.Study on Mechanism of Fermentation of Astragalus Membranaceus on Serum Metabonomics in Hyperuricemia Based on UHPLC-HRMS
GE Xueli ; WANG Yuqi ; ZHANG Wenwen ; SHI Zhongqi ; TAO Yufan ; LIN Zhaozhou ; SU Zhenguo ; ZHANG Jiayu
Chinese Journal of Modern Applied Pharmacy 2023;40(14):1897-1905
		                        		
		                        			
		                        			OBJECTIVE To research the effect and mechanism of fermentation of Astragalus membranaceus on endogenous metabolites in hyperuricemia model rats using serum UHPLC-HRMS. METHODS The SD rats were randomly divided into different groups, including blank group, model group, benzbromarone group(20 mg·kg-1), as well as fermentation of Astragalus membranaceus high-dose(3 g·kg-1) and low-dose group(1.5 g·kg-1). Model group and each treatment group were disposed with 300 mg·kg-1 oxonic acid potassium to establish hyperuricemia models. At the time of 1 h after modeling, rats in each treatment group were given corresponding drugs for intervention. Collected rat serum after 14 d. The serum of different groups were collected for endogenous metabolites research using UHPLC-HRMS. After multivariate statistical analysis, the different metabolites and metabolic pathways were selected. RESULTS The hyperuricemia rat modes were successfully established by oxonic acid potassium 14 d, and fermentation of Astragalus membranaceus showed good uric acid reducing effect. Compared with the blank group, 17 potential biomarkers associated with hyperuricemia were found in the model group. Among them, 9 potential biomarkers were significantly recalled by fermentation of Astragalus membranaceus. It mainly involved sphingolipid metabolism, pyrimidine metabolism, tryptophan metabolism, pantothenic acid and CoA biosynthesis, glycine, serine and threonine metabolism and other pathway. CONCLUSION This study can provide a basis for revealing the mechanism of reducing uric acid by fermentation of Astragalus membranaceus, and lay a foundation for the further development and utilization of Astragalus.
		                        		
		                        		
		                        		
		                        	
            

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