1.Different retained dosage of lauromacrogol within the thyroid cyst in the sclerotherapy of thyroid cysts:an analysis of the curative effect
Xiuping QIU ; Jushun ZHANG ; Jin CAI ; Rushao HUANG ; Yang CHEN ; Mei TU ; Shihai LI ; Sihua QIU
Journal of Interventional Radiology 2024;33(1):69-73
		                        		
		                        			
		                        			Objective To analyze the effect of different retained dosage of lauromacrogol within the thyroid cyst in the sclerotherapy of thyroid cysts.Methods A total of 200 patients with thyroid cysts,who were admitted to the Longyan Municipal First Hospital of China between August 2020 and August 2021,were enrolled in this study.The patients were randomly and equally divided into group zero(suctioning out all the amount of the injected lauromacrogol),and,according to the percentage of the retained lauromacrogol dosage to the total cystic fluid,group 10%,group 20%,group 30%and group 50%,with 40 patients in each group.Thyroid color ultrasound was reviewed at 1,3,6,and 12 months after treatment.The changes of capsule volume,curative efficacy,influencing factors,and adverse reactions after the cyst became sclerosis were analyzed.Logistic regression analysis was used to analyze the factors affecting the postoperative efficacy.Results In all the 5 groups,the suctioned fluid was dark red in colour,and the patients had cystic nodules.The preoperative mean cyst volume was(20.43±5.86)cm3.In all the 5 groups,the postoperative changes in cyst volume indicated that the postoperative one-month cyst volume significantly shrank when compared with the preoperative volume,the postoperative 3-month cyst volume remarkably shrank when compared with the postoperative one-month volume,and the postoperative 6-month cyst volume strikingly shrank when compared with the postoperative 3-month volume(all P<0.05),while no statistically significant difference in the cyst volume existed between the postoperative 12-month value and the postoperative 6-month value(P>0.05).The postoperative 6-month total effective rate of all the five groups was 87%(174/200),and no statistically significant differences in the postoperative 6-month curative effect existed between each other among the 5 groups(P>0.05).Taking the postoperative 6-month curative effect as the dependent variable,and the age,sex,thick cystic wall,cystic septum,and preoperative cyst volume as independent variables,the binary logistic regression analysis was conducted,which revealed that the thick cystic wall(OR=0.24,95%CI=0.08-0.72,P=0.01)and the cystic septum(OR=0.21,95%CI=0.07-0.67,P=0.01)were the factors affecting the postoperative 6-month curative effect.The main side reaction was pain,which was tolerable by patients.There was no significant difference in the incidence of adverse reactions between each other among the five groups(all P>0.05).Conclusion In treating thyroid cysts by using ultrasound-guided lauromacrogol sclerotherapy,there is no relationship between the curative effect and the percentage of the retained lauromacrogol dosage to the total cystic fluid.The best curative effect can be achieved at 6 months after injection of lauromacrogol,which can be used as the optimal time for follow-up check.The thick cystic wall and the cystic septum are the main factors that affect the curative effect of lauromacrogol sclerotherapy.For the treatment of thyroid cyst,lauromacrogol sclerotherapy carries reliable curative effect with few adverse reactions,therefore,this therapy is worthy of clinical application.(J Intervent Radiol,2024,32:69-73)
		                        		
		                        		
		                        		
		                        	
2.Prophylactic high-flow nasal cannula oxygen therapy can reduce postoperative pulmonary complications in elderly patients with non-small cell lung cancer: A propensity score matching study
Xiuhua TU ; Mei LEI ; Yanqing CHEN ; Rongjia LIN ; Ruizhen HUANG ; Chunmei XIANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(09):1274-1280
		                        		
		                        			
		                        			Objective To investigate the clinical value of prophylactic high-flow nasal cannula oxygen therapy (HFNC) in reducing postoperative pulmonary complication (PPC) in elderly patients with non-small cell lung cancer (NSCLC). Methods  The clinical data of elderly patients (over 60 years) with NSCLC who underwent video-assisted thoracoscopic lobectomy or segmental resection at the Department of Thoracic Surgery, Fujian Provincial Hospital from January 2021 to March 2022 were retrospectively analyzed. According to whether receiving HFNC after surgery, they were divided into a conventional oxygen therapy (CO) group and a HFNC group. The CO group were matched with the HFNC group by the propensity score matching method at a ratio of 1 : 1. We compared PPC incidence, white blood cell (WBC) count, procalcitonin and C-reactive protein on postoperative day (POD) 1, 3 and 5 and postoperative hospital stay between the two groups. Results A total of 343 patients (165 males, 178 females, average age of 67.25±4.79 years) were enrolled, with 53 (15.45%) receiving HFNC. Before matching, there were statistical differences in gender, rate of combined chronic obstructive pulmonary disease, pathology type and TNM stage between the two groups (all P<0.05). There were 42 patients successfully matched in each of the two groups, with no statistical difference in baseline characteristics (P>0.05). After propensity score matching, the results showed that the PPC incidence in the HFNC group was lower than that in the CO group (23.81% vs. 45.23%, P=0.039). WBC count on POD 3 and 5 and procalcitonin level on POD 3 were less or lower in the HFNC group than those in the CO group [ (8.92±2.91)×109/L vs. (10.62±2.67)×109/L; (7.68±1.58)×109/L vs. (8.86±1.76)×109/L; 0.26 (0.25, 0.44) μg/L vs. 0.31 (0.25, 0.86) μg/L; all P<0.05]. There was no statistical difference in the other inflammatory indexes or the postoperative hospital stay between the two groups (P>0.05). Conclusion  Prophylactic HFNC can reduce the PPC incidence and postoperative inflammatory indexes in elderly patients with NSCLC, but does not shorten the postoperative hospital stay.
		                        		
		                        		
		                        		
		                        	
3.Construction,identification and efficiency detection of CX3CR1GFP reporter gene mice
Xin-Xin ZHAO ; Rong HUANG ; Lu-Yun CHEN ; Chun-Mei HUANG ; Jia-Jie TU ; Xin-Ming WANG
Chinese Pharmacological Bulletin 2024;40(12):2392-2398
		                        		
		                        			
		                        			Aim To construct CX3CR1GFP transgenic mice based on the Cre/Loxp system,and to analyze the expression efficiency of CX3CR1GFP.Methods Targeted vectors were designed using restriction enzyme-based cloning technology to create a linearized targeted vector for transfecting embryonic stem cells(ES).The ES cells with a deletion of the neomycin resistance gene(neo)were then cloned into blastocysts to generate chimeric CX3CR1+/GFPmice.These mice were subsequently bred with wild-type mice(WT),and repeated backcrossing was performed to obtain CX3CR1GFP/GFP mice.DNA and mRNA from WT and CX3CR1GFP mice were extracted and genotyped using agarose gel electrophoresis.The expression level of CX3CR1 in various tis-sues of the mice was detected by RT-qPCR.Western blot analy-sis was used to analyze the expression of GFP protein in periph-eral blood mononuclear cells(PBMC)and various tissues.The labeling efficiency of immune cells in bone marrow was detected by flow cytometry.The expression of GFP in different mouse tis-sues was observed by immunofluorescence.Results The results of agarose gel electrophoresis showed that the transgenic mouse genotype was CX3CR1GFP/GFP homozygote.RT-qPCR and West-ern blot showed that EGFP were targeted to replace CX3CR1 gene,so CX3CR1 expression was very low in CX3CR1GFP mice,while GFP expression was significantly upregulated.Flow cytom-etry and immunofluorescence showed that GFP effectively marked CX3CR1GFP mice,expressed in various tissues and cells with different expression levels.Conclusion This study con-structs and identifies the CX3CR1GFP genetic reporter mice,and GFP is stably expressed in mice,which provides a foundation for further research into the potential mechanisms of CX3CR1 in im-mune regulation.
		                        		
		                        		
		                        		
		                        	
4.Expression and clinical significance of N6-methyladenosine modification-related genes in peripheral blood mononuclear cells from patients with gouty arthritis
Yanhui LI ; Tianyi LEI ; Yang WANG ; Xin TU ; Mei WANG ; Xiu LI ; Bin MING ; Zeng ZHANG ; Quanbo ZHANG ; Yufeng QING
Chinese Journal of Rheumatology 2024;28(9):640-647
		                        		
		                        			
		                        			Objective:To investigate the expression of N6-methyladenosine(m6A) modification-related genes and their possible roles in peripheral blood mononuclear cells (PBMCs) of patients with primary gouty arthritis (GA).Methods:Forty-five patients each with acute gout (AG), intermittent gout (IG), and age-and gender-matched healthy controls (HC) were collected from the outpatient clinic of the Department of Rheumatology and Immunology of the Affiliated Hospital of Chuanbei Medical College between October and December of 2023. The expression levels of m6A modification-related genes (METTL3、METTL14、WTAP、FTO、ALKBH5、IGF2BP2、IGF2BP3、YTHDF1、YTHDC2) in PBMCs among the 3 groups were detected by RT-qPCR and correlation analysis with clinical indicators was performed. Measurements conforming to normal distribution were analyzed using ANOVA or t-tests, and data were analyzed using the Kruskal-Wallis H-test and Mann-Whitney U-test for data that is not-normaly distributed. The value of m6A modification-related genes for the diagnosis of GA was evaluated using subject characterization curve ROC. Results:①There were statistically significant differences in the expression of IGF2BP2 ( Z=-3.59, P<0.001)、WTAP ( Z=-5.25, P<0.001)、METTL14 ( Z=-3.62, P<0.001)、YTHDF1 ( Z=-2.12, P=0.034)and YTHDC2 ( Z=-2.00, P=0.045) in the disease group and the normal control group. Among them, the expression of IGF2BP2 in the GA group [28.08 (17.99, 47.06)×10 -4] was significantly higher than that in the HC group [19.23 (12.90, 25.78)×10 -4], and the expressions of WTAP、METTL14、YTHDF1 and YTHDC2 in the GA group [298.61 (213.61, 377.80)×10 -4, 9.94 (6.43, 13.46)×10 -4, 52.63 (28.22, 72.77)×10 -4, 40.24 (20.74, 73.32)×10 -4] were significantly lower than those in the HC group [398.45(339.88, 454.89)×10 -4, 13.27(11.07, 15.85)×10 -4, 64.43(43.61, 87.10)×10 -4, 53.11(36.37, 79.28)×10 -4]. Further subgroup analysis revealed statistically significant differences in the expression of IGF2BP2、WTAP、METTL14、YTHDF1 and YTHDC2 among the 3 groups ( H=19.62、31.73、13.14、16.64、28.90, all P≤0.001). The expressions of WTAP and METTL14 in the AG group [311.13(234.96, 426.67)×10 -4, Z=-3.27, P=0.001; 9.64 (5.21, 15.21)×10 -4, Z=-2.71, P=0.008] and IG group [272.27 (203.29, 347.95)×10 -4, Z=-5.78, P<0.001; 10.40(6.88, 12.88)×10 -4, Z=-3.54, P=0.003] were lower than those in the HC group [398.45 (339.88, 454.89)×10 -4, 13.27(11.07, 15.85)×10 -4]. However, there was no significant difference between AG and IG group ( P>0.05). Both YTHDF1 and YTHDC2 were significantly lower in the AG group [38.10(16.19, 56.78)×10 -4, 24.31 (14.35, 42.77)×10 -4] than those in the IG group [64.13 (48.28, 74.40)×10 -4(Z=-3.54, P<0.001, 65.49 (39.89, 91.23)×10 -4(Z=-4.96, P<0.001)] and HC group [64.43 (43.61, 86.92)×10 -4(Z=-3.51, P<0.001), 53.11 (36.37, 79.28)×10 -4(Z=-4.25, P<0.001)]. But there was no statistically significant difference between IG and HC groups ( P>0.05); IGF2BP2 was significantly lower in the AG group [25.32(16.40, 40.43)×10 -4, Z=-2.46, P=0.014] and HC group [19.23 (12.90, 25.78)×10 -4, Z=-4.54, P<0.001] than in the IG group [31.10(22.60, 49.58)×10 -4], but the comparison between AG and HC showed no statistically significant difference( P>0.05). ②Spearman correlation analysis showed that in GA patients, the expression of IGF2BP2、METTL14 and YTHDF1 was positively correlated with plasma glucose、blood uric acid(sUA) and total cholesterol level respectively ( r=0.22, P=0.037; r=0.38, P=0.003; r=0.23, P=0.034), and WTAP was negatively correlated with GLU ( r=-0.25, P=0.020). ③The ROC curve for the joint prediction of the five differential genes showed that the 95% CI for area under the curve in GA was 0.90 (0.84, 0.95). Conclusion:The m6A modification-related genes are abnormally expressed in GA and are correlated with clinical indicators such as GLU and UA, which are hypothesized to be involved in the pathogenesis of GA and have a certain reference value for the evaluation of metabolism in GA patients.
		                        		
		                        		
		                        		
		                        	
5.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
		                        		
		                        			
		                        			Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
		                        		
		                        		
		                        		
		                        	
6.Prognostic and clinical value of circPRKCI expression in diverse human cancers
Zhongyue LIU ; Xiaolei REN ; Zhimin YANG ; Lin MEI ; Wenyi LI ; Chao TU ; Zhihong LI
Chinese Medical Journal 2024;137(2):152-161
		                        		
		                        			
		                        			Background::Highly expressed in various human cancers, circular RNA Protein Kinase C Iota (circPRKCI) has been reported to play an important role in cancer development and progression. Herein, we sought to reveal the prognostic and clinical value of circPRKCI expression in diverse human cancers.Methods::We searched the Pubmed, Web of Science, and the Cochrane Library databases from inception until May 16, 2021. The relationship between circPRKCI expression and cancer patients’ survival, including overall survival (OS) and disease-free survival (DFS), was assessed by pooled hazard ratios (HR) with corresponding 95% confidence interval (CI). The correlation between circPRKCI expression and clinical outcomes was evaluated using odds ratios (OR) with corresponding 95% CI. The data were analyzed by STATA software (version 12.0) or Review Manager (RevMan 5.3).Results::A total of 15 studies with 1109 patients were incorporated into our meta-analysis. The results demonstrated that high circPRKCI expression was significantly related to poor OS (HR = 1.96, 95% CI: 1.61, 2.39, P <0.001) when compared with low circPRKCI expression in diverse human cancers. However, elevated circPRKCI expression was not associated with DFS (HR = 1.34, 95% CI: 0.93, 1.95, P = 0.121). Furthermore, the patient with a higher circPRKCI expression was prone to have a larger tumor size, advanced clinical stage, and lymph node metastasis, but it was not significantly correlated with age, gender, and distant metastasis. Conclusion::Elevated circPRKCI expression was correlated with worse OS and unfavorable clinical features, suggesting a novel prognostic and predictive role of circPRKCI in diverse human cancers.
		                        		
		                        		
		                        		
		                        	
7.Effects and mechanisms of total flavones of Abelmoschus manihot in inhibiting podocyte necroptosis and renal fibrosis in diabetic kidney disease.
Jia-Xin CHEN ; Qi-Jun FANG ; Yi-Gang WAN ; Ying-Lu LIU ; Yu WANG ; Wei WU ; Yue TU ; Mei-Zi WANG ; Dian-Guang WANG ; Hai-Tao GE
China Journal of Chinese Materia Medica 2023;48(15):4137-4146
		                        		
		                        			
		                        			Previous studies have shown that high blood glucose-induced chronic microinflammation can cause inflammatory podocyte injury in patients with diabetic kidney disease(DKD). Therein, necroptosis is a new form of podocyte death that is closely associated with renal fibrosis(RF). To explore the effects and mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese herbal medicine Abelmoschus manihot for treating kidney diseases, on podocyte necroptosis and RF in DKD, and to further reveal its scientific connotation with multi-pathway and multi-target, the authors randomly divided all rats into four groups: a namely normal group, a model group, a TFA group and a rapamycin(RAP) group. After the modified DKD rat models were successfully established, four group rats were given double-distilled water, TFA suspension and RAP suspension, respectively by gavage every day. At the end of the 4th week of drug treatment, all rats were sacrificed, and the samples of their urine, blood and kidneys were collected. And then, the various indicators related to podocyte necroptosis and RF in the DKD model rats were observed, detected and analyzed, respectively. The results indicated that, general condition, body weight(BW), serum creatinine(Scr), urinary albumin(UAlb), and kidney hypertrophy index(KHI) in these modified DKD model rats were both improved by TFA and RAP. Indicators of RF, including glomerular histomorphological characteristics, fibronectin(FN) and collagen type Ⅰ(collagen Ⅰ) staining extent in glomeruli, as well as the protein expression levels of FN, collagen Ⅰ, transforming growth factor-β1(TGF-β1) and Smad2/3 in the kidneys were improved respectively by TFA and RAP. Podocyte damage, including foot process form and the protein expression levels of podocin and CD2AP in the kidneys was improved by TFA and RAP. In addition, tumor necrosis factor-α(TNF-α)-mediated podocyte necroptosis in the kidneys, including the morphological characteristics of podocyte necroptosis, the extent and levels of the protein expression of TNF-α and phosphorylated mixed lineage kinase domain like pseudokinase(p-MLKL) was improved respectively by TFA and RAP. Among them, RAP had the better effect on p-MLKL. More importantly, the activation of the receptor interacting serine/threonine protein kinase 1(RIPK1)/RIPK3/MLKL signaling axis in the kidneys, including the expression levels of its key signaling molecules, such as phosphorylated receptor interacting serine/threonine protein kinase 1(p-RIPK1), p-RIPK3, p-MLKL and cysteinyl aspartate specific proteinase-8(caspase-8) was improved respectively by TFA and RAP. Among them, the effect of TFA on p-RIPK1 was superior. On the whole, in this study, the authors demonstrated that TFA alleviates podocyte necroptosis and RF in DKD through inhibiting the activation of the TNF-α-mediated RIPK1/RIPK3/MLKL signaling axis in diabetic kidneys. The authors' findings provide new pharmacological evidence to reveal the scientific connotation of TFA in treating RF in DKD in more depth.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Rats
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Diabetic Nephropathies/drug therapy*
		                        			;
		                        		
		                        			Abelmoschus
		                        			;
		                        		
		                        			Flavones/pharmacology*
		                        			;
		                        		
		                        			Podocytes
		                        			;
		                        		
		                        			Tumor Necrosis Factor-alpha/metabolism*
		                        			;
		                        		
		                        			Necroptosis
		                        			;
		                        		
		                        			Receptor-Interacting Protein Serine-Threonine Kinases/metabolism*
		                        			;
		                        		
		                        			Fibrosis
		                        			;
		                        		
		                        			Threonine/pharmacology*
		                        			;
		                        		
		                        			Collagen/metabolism*
		                        			;
		                        		
		                        			Serine/pharmacology*
		                        			;
		                        		
		                        			Diabetes Mellitus/drug therapy*
		                        			
		                        		
		                        	
8.Discrimination of different processing degrees and quantitative study of processing end point of vinegar-processing Cyperi Rhizoma pieces based on electronic sensory technology.
Ya-Bo SHI ; Rao FU ; Ming-Xuan LI ; Yu LI ; Jiu-Ba ZHANG ; De JI ; Lian-Lin SU ; Chun-Qin MAO ; Tu-Lin LU ; Xi MEI
China Journal of Chinese Materia Medica 2023;48(18):5003-5013
		                        		
		                        			
		                        			In this study, CM-5 spectrophotometer and Heracles NEO ultra-fast gas-phase electronic nose were used to analyze the changes in color and odor of vinegar-processed Cyperi Rhizoma(VPCR) pieces. Various analysis methods such as DFA and partial least squares discriminant analysis(PLS-DA) were combined to identify different processing degrees and quantify the end point of processing. The results showed that with the increase in vinegar processing, the brightness parameter L~* of VPCR pieces decreased gradua-lly, while the red-green value a~* and yellow-blue value b~* initially increased and reached their maximum at 8 min of processing, followed by a gradual decrease. A discriminant model based on the color parameters L~*, a~*, and b~* was established(with a discrimination accuracy of 98.5%), which effectively differentiated different degrees of VPCR pieces. Using the electronic nose, 26 odor components were identified from VPCR samples at different degrees of vinegar processing. DFA and PLS-DA models were established for different degrees of VPCR pieces. The results showed that the 8-min processed samples were significantly distinct from other samples. Based on variable importance in projection(VIP) value greater than 1, 10 odor components, including 3-methylfuran, 2-methylbuty-raldehyde, 2-methylpropionic acid, furfural, and α-pinene, were selected as odor markers for differentiating the degrees of vinegar processing in VPCR. By combining the changes in color and the characteristic odor components, the optimal processing time for VPCR was determined to be 8 min. This study provided a scientific basis for the standardization of vinegar processing techniques for VPCR and the improvement of its quality standards and also offered new methods and ideas for the rapid identification and quality control of the end point of processing for other traditional Chinese medicine.
		                        		
		                        		
		                        		
		                        			Acetic Acid
		                        			;
		                        		
		                        			Drugs, Chinese Herbal/analysis*
		                        			;
		                        		
		                        			Rhizome/chemistry*
		                        			;
		                        		
		                        			Quality Control
		                        			;
		                        		
		                        			Electronics
		                        			
		                        		
		                        	
9.Effect and mechanism of Dahuang Zhechong Pills in improving liver aging in rats by regulating ROS-mediated PI3K/Akt/FoxO4 signaling pathway.
Yan FU ; Wei WU ; Yi-Gang WAN ; Hai-Ming YANG ; Yue TU ; Si-Yi LIU ; Qi-Jun FANG ; Ying-Lu LIU ; Mei-Zi WANG ; Huang HUANG
China Journal of Chinese Materia Medica 2023;48(11):3014-3021
		                        		
		                        			
		                        			Recent studies have shown that the occurrence and development of common liver diseases, including non-alcoholic fatty liver disease, cirrhosis, and liver cancer, are related to liver aging(LA). Therefore, to explore the effect and mechanism of Dahuang Zhechong Pills(DHZCP), a traditional classic prescription in improving LA with multiple targets, the present study randomly divided 24 rats into a normal group, a model group, a DHZCP group, and a vitamin E(VE) group, with six rats in each group. The LA model was induced by continuous intraperitoneal injection of D-galactose(D-gal) in rats. For the LA model rats, the general situation was evaluated by aging phenotype and body weight(BW). LA was assessed by the pathological characteristics of hepatocyte senescence, hepatic function indexes, the staining characteristics of phosphorylated histone family 2A variant(γ-H2AX), and the expression levels of cell cycle arrest proteins(P21, P53, P16) and senescence-associated secretory phenotype(SASP) in the liver. The activation of the reactive oxygen species(ROS)-mediated phosphatidylinositol-3 kinase(PI3K)/protein kinase B(Akt)/forkhead box protein O4(FoxO4) signaling pathway was estimated by hepatic ROS expression feature and the protein expression levels of the key signaling molecules in the PI3K/Akt/FoxO4 signaling pathway. The results showed that after the treatment with DHZCP or VE for 12 weeks, for the DHZCP and VE groups, the characterized aging phenotype, BW, pathological characteristics of hepatocyte senescence, hepatic function indexes, relative expression of ROS in the liver, protein expression levels of key signaling molecules including p-PI3K, p-Akt, and FoxO4 in the liver, staining characteristics of γ-H2AX, and the protein expression levels of P16, P21, P53, interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in the liver were improved, and the effects of DHZCP and VE were similar. Based on the D-gal-induced LA model in rats, this study demonstrates that DHZCP can ameliorate LA with multiple targets in vivo, and its effects and mechanism are related to regulating the activation of the ROS-mediated PI3K/Akt/FoxO4 signaling pathway in the liver. These findings are expected to provide new pharmacological evidence for the treatment of DHZCP in aging-related liver diseases.
		                        		
		                        		
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Rats
		                        			;
		                        		
		                        			Proto-Oncogene Proteins c-akt/genetics*
		                        			;
		                        		
		                        			Phosphatidylinositol 3-Kinases/genetics*
		                        			;
		                        		
		                        			Reactive Oxygen Species
		                        			;
		                        		
		                        			Tumor Suppressor Protein p53/genetics*
		                        			;
		                        		
		                        			Signal Transduction
		                        			;
		                        		
		                        			Liver
		                        			;
		                        		
		                        			Aging
		                        			;
		                        		
		                        			Cell Cycle Proteins
		                        			;
		                        		
		                        			Interleukin-6
		                        			
		                        		
		                        	
10.Core connotation of compatibility of Aconiti Lateralis Radix Praeparata-Glycyrrhizae Radix et Rhizoma herb pair under physiological/ pathological conditions based on metabolomics and network pharmacology.
Wei PENG ; Xiao WANG ; Shu FU ; Ming-Quan WU ; Chao-Mei FU ; He TU
China Journal of Chinese Materia Medica 2023;48(14):3793-3805
		                        		
		                        			
		                        			This study aims to explore the core connotation of the compatibility of Aconiti Lateralis Radix Praeparata(Fuzi)-Glycyrrhizae Radix et Rhizoma(Gancao) herb pair under physiological and pathological conditions. The biochemical indicators of serum/myocardial tissue, pathological changes of the myocardial tissue, and serum metabolic profiles of normal rats and heart failure model rats treated with Fuzi Decoction and Fuzi Gancao Decoction were determined. Network pharmacology and metabolomics were employed to establish the metabolite-target-pathway network for Glycyrrhizae Radix et Rhizoma in enhancing the efficacy and reducing the toxicity of Aconiti Lateralis Radix Praeparata, Western blotting was employed to verify the representative pathways in the network. The results showed that both decoctions lowered the levels of creatine kinase and other indicators and mitigate myocardial pathological injury in model rats. However, they caused the abnormal rises in creatine kinase and other indicators and myocardial pathological injury in normal rats. The results indicated that the compatibility reduced the toxicity in normal rats and enhanced the efficacy in model rats. The results of metabolomics showed that Fuzi Gancao Decoction recovered more metabolites in model rats and had weaker effect on interfe-ring with the metabolites in normal rats than Fuzi Decoction. The association analysis showed that the network of Glycyrrhizae Radix et Rhizoma enhancing the efficacy of Aconiti Lateralis Radix Praeparata involved 112 metabolites, 89 targets, and 15 pathways, including calcium and cAMP signaling pathways. The network of Glycyrrhizae Radix et Rhizoma reducing the cardiotoxicity of Aconiti Lateralis Radix Praeparata involved 36 metabolites, 59 targets, and 11 pathways, including adrenergic signaling and tricarboxylic acid cycle in cardiomyocytes. The experimental results of protein expression verified the reliability of the association analysis. This study demonstrated that the core connotation of the herb pair of Aconiti Lateralis Radix Praeparata-Glycyrrhizae Radix et Rhizoma changed under physio-logical and pathological states, and the compatibility results of enhancing efficacy and reducing toxicity were achieved with different metabolic pathways and biological processes.
		                        		
		                        		
		                        		
		                        	
            
Result Analysis
Print
Save
E-mail