1.Exploring Multi-target Effect of Erzhiwan on Improving Myocardial Injury in Ovariectomized Mice Based on Non-targeted Metabolomics
Ying YANG ; Jing HU ; Pei LI ; Ruyuan ZHU ; Zhiguo ZHANG ; Haixia LIU ; Yanjing CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):74-84
ObjectiveTo explore the target of Erzhiwan in reducing myocardial injury in ovariectomized mice through non-targeted myocardial metabolomics combined with experimental verification. MethodsOvariectomized mouse model was selected, 40 female C57BL/6 mice were randomly divided into sham operation group, model group, estrogen group(estradiol valerate, 1.3×10-4 g·kg-1), Erzhiwan low and high dose groups(3.12, 9.36 g·kg-1), with 8 mice in each group. Each administration group was given the corresponding dose of Erzhiwan by gavage, and the sham operation group and model group were given equal volume of distilled water by gavage for 12 weeks. Echocardiography was used to detect cardiac function, hematoxylin-eosin(HE) staining was used to observe myocardial morphological changes, and enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of estrogen, N-terminal pro-brain natriuretic peptide(NT-proBNP), hypersensitive troponin T(hs-TnT), total cholesterol(TC), triglyceride(TG), low density lipoprotein cholesterol(LDL-C), high density lipoprotein cholesterol(HDL-C), interleukin(IL)-1β, IL-18 and tumor necrosis factor-α(TNF-α). The non-targeted metabolomics of mouse myocardium were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS), and the differential metabolites and corresponding metabolic pathways were obtained. The mRNA expression levels of phosphatidylinositol 3-kinase(PI3K) and protein kinase B(Akt) in mouse myocardial tissues were detected by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR), and the protein expression levels of PI3K, Akt, phosphorylated(p)-Akt were detected by Western blot. ResultsCompared with the sham operation group, the model group showed abnormal cardiac function, increased myocardial fiber space, cardiomyocyte atrophy, sarcoplasmic aggregation, and occasional dissolution or rupture of muscle fiber, the level of estrogen in the serum was decreased, the levels of NT-proBNP, hs-TnT, IL-1β, IL-18, TNF-α, TG, TC and LDL-C were increased, and the level of HDL-C was decreased(P<0.01). Compared with the model group, Erzhiwan could increase the level of estrogen, improve the abnormal cardiac function, reduce the pathological injury of myocardial tissue, decrease the levels of myocardial injury markers(NT-proBNP, hs-TnT) and inflammatory factors(IL-1β, IL-18, TNF-α), decrease the levels of TG, TC, LDL-C, and increased the level of HDL-C(P<0.01). The results of non-targeted myocardial metabolomics showed that 31 of the 162 differential metabolites between the model group and sham operation group were significantly adjusted after administration of Erzhiwan, which were mainly glycerol phospholipid metabolites. Pathway enrichment results showed that Erzhiwan mainly affected glycerophospholipid metabolic pathway, PI3K-Akt pathway, cyclic guanosine monophosphate(cGMP)-protein kinase G(PKG) pathway and other metabolic pathways. Compared with the sham operation group, the levels of phosphatidylcholine(PC, 11 types) and phosphatidylethanolamine(PE, 5 types) in mouse myocardial tissue of the model group were increased(P<0.05, P<0.01), and the mRNA and protein expressions of PI3K and p-Akt were decreased(P<0.05, P<0.01). Compared with the model group, the levels of PC(11 types) and PE(5 types) were decreased(P<0.05, P<0.01) in myocardial tissue of Erzhiwan group, the mRNA and protein expressions of PI3K and p-Akt were elevated(P<0.01). ConclusionErzhiwan can alleviate the pathological injury of myocardium in ovariectomized mice, improve the abnormal cardiac function, improve lipid metabolism disorder, and reduce the levels of myocardial injury markers and inflammatory factors, which involves a number of signaling and metabolic pathways in the heart, among which glycerophospholipid metabolism pathway and PI3K/Akt pathway may have key roles.
2.Effects of C3435T polymorphism in ABCB1 gene on lipid-lowering efficacy of statins:a meta-analysis
Zhiguo HUANG ; Rongtian LI ; Shun GUO ; Guihua LI ; Nuan JIA
China Pharmacy 2024;35(8):991-996
OBJECTIVE To systematically evaluate the effects of C3435T polymorphism in ABCB1 gene on lipid-lowering efficacy of statins. METHODS Retrieved from PubMed, Web of Science, the Cochrane Library, CNKI and VIP, the cohort studies on the use of statins were collected from the inception to November 1, 2023. After literature screening, data extraction and quality evaluation, meta-analysis was performed by using RevMan 5.4 software. RESULTS A total of 11 literature involving 1 575 patients were included. The results showed that under the dominant genetic model, the reduction of low-density lipoprotein cholesterol (LDL-C) [MD=-1.87, 95%CI (-3.62, -0.13), P=0.04], total cholesterol (TC) [MD=-1.42, 95%CI (-2.80, -0.04), P=0.04] in patients with CT+TT genotype was significantly higher than CC genotype. There was no significant difference in the increase of high-density lipoprotein cholesterol (HDL-C) [MD=-0.65, 95%CI (-2.48, 1.18), P=0.49] or the decrease of triglyceride (TG) [MD=-0.05, 95%CI (-2.94, 2.84), P=0.97] between patients with CT+TT genotype and CC genotype. Under the recessive genetic model, the reduction of TC [MD=2.26, 95%CI (0.97, 3.56), P=0.000 6] and the increase of HDL-C [MD=2.38, 95%CI (0.42, 4.35), P=0.02] in patients with TT genotype were significantly higher than CC+ CT genotype. There was no significant difference in the reduction of LDL-C [MD=1.53, 95%CI (-0.10, 3.15), P=0.07] or TG [MD=0.06, 95%CI (-2.98, 3.10), P=0.97] between CC+CT genotype and TT genotype. Under the additive genetic model, the reduction of TC [MD=2.98, 95%CI (1.27, 4.69), P=0.000 6] and LDL-C [MD=2.84, 95%CI (0.67, 5.01), P=0.01] in patients with TT genotype were significantly higher than CC genotype. There was no significant difference in the increase of HDL-C [MD=2.40, 95%CI (-0.17, 4.97), P=0.07] or the decrease of TG [MD=0.97, 95%CI (-2.93, 4.87), P=0.63] between patients with TT genotype and CC genotype. CONCLUSIONS The reduction of LDL-C and TC in patients with dyslipidemia treated with statins may be related to the heterozygous and homozygous mutation of C3435T in ABCB1 gene, and the reduction of LDL-C and TC in patients with CT or TT genotype is more obvious, compared with patients with CC genotype. The elevation of HDL-C may be related to homozygous mutation, and the effect of HDL-C elevation may be more obvious in patients with TT genotype, compared with CC+CT genotype. However, the change of TG may not be related to the C3435T polymorphism in ABCB1 gene.
3.Quantitative evaluation of gender differences in supraclavicular fat related to fat metabolism with IDEAL-IQ in healthy young adults
Jicheng FANG ; Li LI ; Yang LI ; Zhanying JIAO ; Zhiguo ZHOU
Journal of Practical Radiology 2024;40(1):131-134
Objective To evaluate the gender differences in fat water fraction(FWF)related to fat metabolism in supraclavicular region of neck with iterative decomposition of water and fat with echo asymmetry and least square estimation iron quantification(IDEAL-IQ)sequence quantitatively.Methods Twenty healthy female and twenty healthy male volunteers were selected for a MRI examination with IDEAL-IQ,then the FWF of R2*,brown adipose tissue(BAT)and white adipose tissue(WAT)were obtained by post-processing.The differences of FWF between the two groups were compared by Mann-Whitney U test.Results There was sig-nificant difference in the FWF of BAT and WAT between the two groups(P<0.05).The FWF of BAT in the female was higher than that the male,and the FWF of WAT in the male was higher than that the female,there was no significant difference in the R2*between the two groups(P>0.05).Conclusion IDEAL-IQ sequence can be used to evaluate the FWF in supraclavicular region of neck quantitatively,and classify BAT and WAT,then provide clinical according to the quantitative study of fat content.
4.Lipid metabolomic changes in liver injury in BTBR ob/ob mice with type 2 diabetes mellitus
Mingyu Sun ; Wenjing Zhao ; Jing Xin ; Zhiguo Li ; Xiuli Xiuli1
Acta Universitatis Medicinalis Anhui 2024;59(1):77-85
Objective :
To investigate the changes of lipid biomarkers and lipid metabolic pathways related to liver injury in BTBR ob/ob mice with type 2 diabetes mellitus by biochemical and metabolomics methods.
Methods :
16 BTBR wild-type (WT) mice (WT group) and 14 BTBR ob/ob obese mice (ob / ob group) at 7 weeks of age were selected and fed in SPF environment until 20 weeks of age.Liver injury was compared between the two groups : The activities of mitochondrial respiratory enzyme complex in liver tissue were detected by high-resolution respirators,and the lipid metabolomic analysis of liver tissue samples in the two groups of mice was performed by ultra-perform- ance liquid chromatography-quadrupole time-of-flight mass spectrometry,mainly detecting endogenous metabolites. Principal component analysis (PCA) ,orthogonal partial least squares discriminant analysis ( OPLS-DA) and other models were used to screen potential biomarkers,and the metabolic pathway analysis of the identified metabolites was performed by MetaboAnalyst 5. 0 .
Results :
Compared with the WT group,the ob / ob group had significantly increased body weight,fasting blood glucose ,serum levels of aspartate aminotransferase ( AST) ,alanine amin- otransferase (ALT) ,low-density lipoprotein (LDL-C) and cholesterol ( CHO) (P<0. 01) .Liver hematoxylin-eo- sin staining (HE) staining showed that the mice in ob / ob group had structural disorder of liver lobules,swelling of liver cells ,a large number of fat vacuoles in cells ,diffuse distribution and loose cytoplasm. Oil red O staining showed that there was a large amount of lipid deposition in the hepatocytes ofob/ob mice.The high resolution spi- rometer showed that the ob/ob mice had mitochondrial oxidative phosphorylation disorder and the activity of complex Ⅳ decreased.Lipid metabolomic analysis showed that the lipid metabolic profile of ob/ob mice changed,and the metabolic pathways involved mainly included glycerophospholipid metabolism,glycosylphosphatidylinositol ( GPI) anchor biosynthesis,triglyceride metabolism,linoleic acid metabolism,α-linolenic acid metabolism and arachidon- ic acid metabolism.
Conclusion
The liver injury of ob / ob group mice may be related to the disorder of lipid me- tabolism,in which the disorder of glycerophospholipid metabolism is the most critical metabolic pathway.
5.Standard for the management of hyperkalemia—whole-process management mode of multi- department cooperation
Zhiming YE ; Jianfang CAI ; Wei CHEN ; Hong CHENG ; Qiang HE ; Rongshan LI ; Xiangmin LI ; Xinxue LIAO ; Zhiguo MAO ; Huijuan MAO ; Ning TAN ; Gang XU ; Hong ZHAN ; Hao ZHANG ; Jian ZHANG ; Xueqing YU
Chinese Journal of Nephrology 2024;40(3):245-254
Hyperkalemia is one of the common ion metabolism disorders in clinical practice. Hyperkalemia is defined as serum potassium higher than 5.0 mmol/L according to the guidelines at home and abroad. Acute severe hyperkalemia can cause serious consequences, such as flaccid paralysis, fatal arrhythmia, and even cardiac arrest. The use of renin-angiotensin- aldosterone system inhibitors, β-blockers and diuretics, low-sodium and high-potassium diets, and the presence of related comorbidities increase the occurrence of hyperkalemia. Hyperkalemia risk exist in all clinical departments, but there is a lack of a standardization in the management of multi- department cooperation in hospital. Therefore, a number of domestic nephrology and cardiology department experts have discussed a management model for multi-department cooperation in hyperkalemia, formulating the management standard on hospital evaluation, early warning, diagnosis and treatment, and process. This can promote each department to more effectively participate in nosocomial hyperkalemia diagnosis and treatment, as well as the long-term management of chronic hyperkalemia, improving the quality of hyperkalemia management in hospital.
6.Regulatory effect of Kangxian Yiai Prescription in a rat model of precancerous lesions of liver cancer:A study based on the mTOR/HIF-1α/VEGF signaling pathway
Zhiguo LI ; Xun MA ; Yongan YE ; Xianzhao YANG
Journal of Clinical Hepatology 2024;40(10):2049-2054
Objective To investigate the effect of Kangxian Yiai Prescription(KXYA)on the mTOR/HIF-1α/VEGF signaling pathway in a rat model of precancerous lesions of liver cancer.Methods A total of 40 male Wistar rats were divided into normal group,model group,KXYA group,and Biejia Rangan Tablets(BJRG)group,with 10 rats in each group.The rats in the normal group were given intraperitoneal injection of normal saline at a dose of 0.4 mL/100 g,and those in the other three groups were given intraperitoneal injection of diethylnitrosamine at a dose of 50 mg/kg to establish a rat model of the precancerous lesions of liver cancer.Immunohistochemistry and Western Blot were used to measure the expression level of GST-Pi,and quantitative real-time PCR and Western Blot were used to measure the mRNA and protein expression levels of mTOR,HIF-1α,VEGF,PKM2,and GLUT1.A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the normal group,the model group had a significant increase in the protein expression level of GST-Pi in liver tissue(P<0.01),and compared with the model group,the KXYA group had a significant reduction in the protein expression level of GST-Pi(P<0.05).Compared with the normal group,the model group had significant increases in the mRNA expression levels of GLUT1 and PKM2 in liver tissue(P<0.01),and compared with the model group,the BJRG group and the KXYA group had a significant reduction in the mRNA expression level of GLUT1(P<0.05).Compared with the normal group,the model group had significant increases in the protein expression levels of GLUT1 and PKM2 in liver tissue(P<0.01).Compared with the normal group,the model group had significant increases in the mRNA expression levels of mTOR,HIF-1α,and VEGF in liver tissue(P<0.01);compared with the model group,the BJRG group had significant reductions in the mRNA expression levels of mTOR and VEGF(P<0.05),and the KXYA group also had significant reductions in the mRNA expression levels of mTOR and VEGF(P<0.01).Compared with the normal group,the model group had significant increases in the protein expression levels of mTOR,HIF-1α,and VEGF in liver tissue(P<0.01);compared with the model group,the BJRG group had a significant reduction in the protein expression level of mTOR(P<0.01),and the KXYA group had significant reductions in the protein expression levels of mTOR,HIF-1α,and VEGF(P<0.05);compared with the BJRG group,the KXYA group had a significantly higher protein expression level of mTOR(P<0.01).Conclusion KXYA can inhibit the precancerous lesions of liver cancer by regulating the mTOR/HIF-1α/VEGF signaling pathway.
7.Application of HPLC multi-components quantification combined with chemometrics and entropy weight-TOPSIS method in comprehensive quality evaluation of Solanum nigrum
Sha LI ; Guanting LU ; Jun CHEN ; Gaoqi ZHAO ; Zhiguo LI
China Pharmacist 2024;27(1):36-45
Objective To establish a method for simultaneous determination of 11 components of Solanum nigrum from different producing areas,and to evaluate the quality by chemometrics and entropy weight-technique for order preference by similarity to ideal solution(EW-TOPSIS).Methods The 17 batches of Solanum nigrum samples from 8 provinces were collected.The high performance liquid chromatography(HPLC)method was used to simultaneously determine the contents of medioresino,pinoresinol,quercetin,rutoside,solasonine,solamargine,khasianine,solasodine,desgalactotigonin,diosgenin and β-sitosterol,and the multi-components quantitative control mode of Solanum nigrum was established.The quality evaluation model of Solanum nigrum was established by using chemical recognition pattern and EW-TOPSIS method,and the overall quality was evaluated comprehensively.Results When the 11 components were in the 0.78-39.00,0.55-27.50,0.34-17.00,0.21-10.50,41.87-2 093.50,60.95-3 047.50,2.58-129.00,1.02-51.00,0.46-23.00,1.05-52.50 and 0.42-21.00 μg/mL(r>0.999 0),their linear relationships were good.The average recovery was 96.81%-100.28%with the RSD<2.0%(n=9).17 batches of samples clustered into 3 categories.Solamargine,solasonine,desgalactotigonin and medioresino may be the main potential markers affecting the quality of Solanum nigrum.The results of EW-TOPSIS method showed that,the quality evaluation closeness of 17 batches of Solanum nigrum were 0.433 6,0.416 8,0.624 2,0.500 8,0.479 1,0.636 1,0.568 3,0.250 0,0.190 9,0.222 1,0.170 7,0.720 0,0.698 3,0.744 7,0.717 9,0.720 9 and 0.718 3,respectively,indicating that the overall quality of Solanum nigrum from Liaoning,Jilin and Heilongjiang were better,followed by Jiangsu,Henan and Anhui.Conclusion The established HPLC method for simultaneous determination of 11 components in Solanum nigrum is convenient and accurate.Chemometrics and EW-TOPSIS method are objective and comprehensive,which can be used for the overall quality evaluation of Solanum nigrum.
8.Study on Efficacy and Preliminary Mechanism of Qinggan Sanjie Xiaoying Decoction in the Treatment of Hashimoto's Thyroiditis
Xin'ai LI ; Zhiguo DING ; Xiaoheng CHEN ; Zhe LI ; Shuo QI
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(2):154-159
Objective To explore the clinical efficacy and mechanism of Qinggan Sanjie Xiaoying Decoction in the treatment of Hashimoto's thyroiditis with syndrome of stagnation heat of liver meridian and stagnation of spleen deficiency and phlegm.Methods Totally 70 patients were divided into control group and medicine group according to their wishes,with 35 patients in each group.Both groups were restricted to an iodine diet.The medicine group was given Qinggan Sanjie Xiaoying Granules,1 sachet at a time,twice a day,orally.The treatment for both groups lasted for 4 weeks.20 healthy people were chosen as the healthy group.The clinical efficacy of both groups was observed.TCM symptom score,thyroid antibody titer levels(TPOAb,TGAb),changes in thyroid volume and isthmus of both groups before and after treatment were compared.Levels of serum IKKα,IKBα and TNF-α of the three groups were compared.Adverse reactions of patients daring the treatment period were monitored.Results The total effective rate of the medicine group was 85.71%(30/35),while the control group was 20.00%(7/35).The medicine group was superior to the control group(P<0.05).Compared with before treatment,the medication group showed significant improvement in TCM symptom scores,TPOAb and TGAb titer levels,thyroid volume,and thyroid isthmus thickness after treatment(P<0.05).After treatment,TCM symptom score,thyroid volume in the medicine group were lower than those in the control group(P<0.05),and the decrease rate of TPOAb titer was higher than that in the group(P<0.05).The levels of IKKα and TNF-α before treatment of medicine group and control group were higher than that in the healthy control group,and the level of IKBα was lower than that of the healthy control group(P<0.05);compared with before treatment,the levels of IKKα and TNF-α in the medicine group decreased,and the level of IKBα increased(P<0.05);after treatment,the levels of IKKα and TNF-α in the medicine group were lower than that in the control group,and IKBα was higher than the control group(P<0.05).No adverse events were observed during the treatment period in both groups of patients.Conclusion Qinggan Sanjie Xiaoying Decoction can reduce the antibody titer level,thyroid enlargement,isthmus thickness,and TCM syndrome score in the treatment of Hashimoto's thyroiditis.It is safe and effective in clinical practice.Qinggan Sanjie Xiaoying Decoction may play a therapeutic role by interfering with NF-κB signaling pathway.
9.Effects of Mild Moxibustion on Proteins Expression of BDNF/TrkB Signaling Pathway in Hypothalamus of Primary Dysmenorrhea Rats with Cold and Dampness Stagnation Syndrome
Xiangyun MENG ; Fei GAO ; Di WANG ; Yulei LIANG ; Xuan ZHANG ; Yanqiu SUN ; Yanxue XING ; Zhiguo ZHAO ; Xinhua LI
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(3):127-131
Objective To observe the analgesic effects of mild moxibustion on primary dysmenorrhea(PD)rats with cold and dampness stagnation syndrome and its effect on BDNF/TrkB signaling pathway in hypothalamus;To explore its mechanism for the treatment of PD.Methods A total of 32 Wistar non-pregnant female rats were randomly divided into blank group,model group,Western medicine group and mild moxibustion group,with 8 rats in each group.Except for the blank group,the other groups received estradiol benzoate intraperitoneal injection combined with ice bath treatment + oxytocin intraperitoneal injection to establish PD with cold and dampness stagnation syndrome model.The mild moxibustion group received treatment at"Shenque"and"Guanyuan"from the eighth day of modeling for 10 min,and the Western medicine group was given ibuprofen solution intragastically for 4 days.The latency period of rats twisting was observed and the twisting score was calculated,Western blot and PCR were used to detect the expressions of c-fos,BDNF,TrkB protein and mRNA in hypothalamic tissue.Results Compared with the blank group,the model group showed a shortened latency period and an increased twisting score(P<0.01),the expressions of c-fos,BDNF,TrkB protein and mRNA in hypothalamic tissue increased(P<0.01,P<0.05).Compared with the model group,the mild moxibustion group had a longer latency period and lower twisting score(P<0.01),while the expressions of c-fos,BDNF,TrkB protein and mRNA in hypothalamic tissue increased(P<0.01,P<0.05).Conclusion Mild moxibustion may effectively improve the pain state of PD rats with cold and dampness stagnation syndrome.This mechanism may be related to downregulating c-fos expression,inhibiting BDNF/TrkB signaling pathway activation,thereby inhibiting pain signal transmission,regulating pain occurrence and maintenance.
10.Efficacy analysis of 125I seeds implantation combined with transcatheter arterial chemoembolization therapy for primary liver cancer
Wenwen ZHANG ; Shanhu HAO ; Zhiguo WANG ; Liqiu JI ; Gen LI ; Youchao WANG ; Xiangyan GE ; Guoxu ZHANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(1):16-19
Objective:To explore the clinical efficacy of 125I seeds implantation combined with transcatheter arterial chemoembolization (TACE) in the treatment of primary liver cancer. Methods:A retrospective analysis of data from 40 patients with primary liver cancer at the Northern Theater General Hospital from January 2018 to December 2020 (26 males, 14 females, age 41 to 82 years) was performed. Among them, 21 patients were in treatment group and underwent 125I seeds implantation combined with TACE treatment, while 19 patients were in control group and received TACE treatment. Alpha-fetoprotein (AFP) levels between the two groups were compared, effective rate and disease control rate (DCR) of the two groups were analyzed, and overall survival (OS) and progression-free survival (PFS) were observed. Data were analyzed by using Mann-Whitney U test, χ2 test, Kaplan-Meier method and log-rank test. Results:Two months after 125I seeds implantation, the effective rates of treatment group and control group were 76.19%(16/21) and 8/19, respectively ( χ2=4.83, P=0.028); the DCRs were 90.48%(19/21) and 11/19, respectively ( χ2=4.21, P=0.040). AFP levels in both groups decreased significantly, with treatment group showing a greater decrease rate (0.87(0.84, 0.90) and 0.66(0.65, 0.67); z=5.42, P<0.001). No serious adverse reaction was observed in either group. The median OS of treatment group and control group were 18.2 and 10.6 months, respectively ( χ2=10.98, P=0.037); the median PFS of the two groups were 8.4 and 6.1 months, respectively ( χ2=7.54, P=0.041). Conclusion:125I seeds implantation combined with TACE treatment can exert a synergistic and enhancing effect in the treatment of primary liver cancer.


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