1.Exploring Quality Makers of Xiaoqinglong Granules in Treating Bronchial Asthma Based on Analytic Hierarchy Process-entropy Weight Method, Network Pharmacology and Molecular Docking
Huijuan XIE ; Zhuqian TANG ; Dan HU ; Yingbi XU ; Li HAN ; Bin YANG ; Hua LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):192-200
ObjectiveTo investigate the quality markers of Xiaoqinglong granules(XQLG) for treating bronchial asthma using the analytic hierarchy process(AHP)-entropy weight method(EWM), network pharmacology and high performance liquid chromatography(HPLC) content determination. MethodsEffectiveness, testability and peculiarity component data of XQLG in treating bronchial asthma were constructed through database retrieval, literature review, and network pharmacology. Subsequently, AHP-EWM was used to quantitatively identify and weight the control layer and element layer, the relevant compounds were selected as candidate quality markers based on comprehensive scores. Further comparison of reference substances and establishment of HPLC content determination method were used to determine the potential quality markers of XQLG, which were verified by molecular docking with disease targets. ResultsA total of 13 components, including glycyrrhizic acid, paeoniflorin, schisandrol A, isoliquiritigenin, 6-gingerol, ephedrine, liquiritin, albiflorin, liquiritigenin, 6-shogaol, pseudoephedrine, cinnamic acid and cinnamaldehyde, were identified as potential quality markers of XQLG by AHP-EWM. Quantitative analysis indicated that all aforementioned quality markers could be detected in 13 batches of XQLG, indicating that it had stable testability as a quality marker. Among these 13 batches of samples, ephedrine and paeoniflorin exhibited good consistency in content, while pseudoephedrine and cinnamaldehyde showed poor consistency. Molecular docking analysis revealed that the 13 compounds exhibited binding energies with the core targets -2.11 kcal·mol-1, indicating that the 13 compounds could spontaneously bind to the disease targets, which may be the material basis for the treatment of bronchial asthma with XQLG. ConclusionIn this study, 13 compounds were screened by AHP-EWM combined with network pharmacology and HPLC as quality markers for the treatment of bronchial asthma by XQLG, laying the foundation for enhancing the quality standards of this preparation.
2. Effects of metabolites of eicosapentaenoic acid on promoting transdifferentiation of pancreatic OL cells into pancreatic β cells
Chao-Feng XING ; Min-Yi TANG ; Qi-Hua XU ; Shuai WANG ; Zong-Meng ZHANG ; Zi-Jian ZHAO ; Yun-Pin MU ; Fang-Hong LI
Chinese Pharmacological Bulletin 2024;40(1):31-38
Aim To investigate the role of metabolites of eicosapentaenoic acid (EPA) in promoting the transdifferentiation of pancreatic α cells to β cells. Methods Male C57BL/6J mice were injected intraperitoneally with 60 mg/kg streptozocin (STZ) for five consecutive days to establish a type 1 diabetes (T1DM) mouse model. After two weeks, they were randomly divided into model groups and 97% EPA diet intervention group, 75% fish oil (50% EPA +25% DHA) diet intervention group, and random blood glucose was detected every week; after the model expired, the regeneration of pancreatic β cells in mouse pancreas was observed by immunofluorescence staining. The islets of mice (obtained by crossing GCG
3.Exploration of Correlation Between Psoraleae Fructus and Precocious Puberty in Children Based on Network Pharmacology
Ling-Ling XIA ; Yao CHEN ; Shun-Li TANG ; Ying ZHANG ; Hua LIU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(4):981-987
Objective The network pharmacological methods and molecular docking technology were used for investigating the possibility of Psoraleae Fructus in promoting precocious puberty in children and its potential mechanism.Methods The main active ingredients of Psoraleae Fructus and their therapeutic targets were obtained from BATMAN-TCM online platform.The disease targets related with precocious puberty were obtained from GeneCards database.A visualized network of active ingredients-disease targets was constructed by Cytoscape 3.7.1 software.Protein-protein interaction(PPI)network diagrams were constructed based on the STRING online database.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted using Metascape online tool.The structures of the main active ingredients were obtained from PubChem database,the structures of core targets were obtained from RCSB PDB database,and then the structures were imported into Autodock for molecular docking.Finally,the mimic diagrams of the molecular docking were drawn using PYMOL software.Results A total of 12 active ingredients of Psoraleae Fructus were obtained,involving 274 targets.And there were 11 active ingredients and 98 targets associated with precocious puberty.The main active compounds were stigmasterol,bakuchiol,angelicin,bavachalcone,isobavachalcone,and xanthotoxin.The main targets were estrogen receptor 1(ESR1),estrogen receptor 2(ESR2),insulin-like growth factor 1(IGF1),and progesterone receptor(PGR),which were mainly involved in the ovarian steroidogenic pathway and Hippo signaling pathway.The molecular docking results showed that the active compounds were well binded to the targets.Conclusion It is possible that Psoraleae Fructus can promote the sexual development in children and has its potential pharmacological mechanism.The results will provide theoretical references for the clinical prevention and treatment of precocious puberty and early pubertal development in children.
4.Research progress on the clinical classification correlation between liver cirrhosis and liver failure
Hua-Qian XU ; Chun-Yan LI ; Shan-Hong TANG
Medical Journal of Chinese People's Liberation Army 2024;49(3):355-359
The essence of cirrhosis is the over-repairing reaction of liver tissue damage in the process of chronic liver disease.During repair,the liver parenchyma is gradually replaced by fibrosis tissue,resulting in changes in liver tissue morphology,followed by portal hypertension and other related manifestations.Liver failure are serious disorder of liver functions(synthesis,metabolism,transformation,regeneration,etc.)caused by various factors,often mainly manifested as jaundice,coagulation disfunction,hepatic encephalopathy,ascites,etc.The naming and typing of the two are different,and they can exist independently of each other or intersect with each other.In recent years,with the in-depth exploration of cirrhosis and liver failure,many new definitions and classification methods have been put forward in the research.However,due to the confusion of classification methods,there is still a lack of summary,so this article briefly reviews the current progress of clinical classification of liver cirrhosis and liver failure and their differences and intersections.
5.Clinical Analysis of 311 Cases with Giant Ovarian Mass
Hua LIU ; Jingxian LING ; Xianghong ZHU ; Rong LI ; Xiaoqiu TANG ; Yan ZHANG ; Huaijun ZHOU
Journal of Practical Obstetrics and Gynecology 2024;40(1):73-77
Objective:To analyze the clinicopathological features of giant ovarian masses(mean diameter≥10 cm)and analyze the clinical characteristics of patients in different age groups.Methods:The clinicopathological characteristics of 311 patients diagnosed with giant ovarian masses by surgery at Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University from January 2014 to December 2022 were retrospectively analyzed.Patients were further stratified by age and mass size to compare the differences of clinical and patho-logical features among different age groups and different mass diameter groups.Results:①The median age of thepatients were 44(24,60)years old.The first symptoms were as follows:ovarian mass discovered during physi-cal examination,abdominal pain,bloating,conscious abdominal distension,and symptoms of compression.②The surgical methods were as follows:unilateral oophorectomy(30.5%,95/311),ovarian cystectomy(28.9%,90/311),tumor staging or cytoreductive surgery(28.0%,87/311),total hysterectomy with bilateral adnexectomy(12.5%,39/311).③The pathological types were benign(49.5%,154/311),malignant(31.8%,99/311)and borderline(18.7%,58/311).④ Patients complained abdominal distension in<20 years old group were signifi-cantly higher than the other two groups(P<0.05).The ovarian resection rate in the>50-year-old group was higher than that of the other two groups(P<0.05),and the rate of unilateral ovarian resection in the<20-year-old group was still as high as 30.1%(15/49).⑤ The size of the mass correlated with the duration of the disease.When the disease course was between 1 to 6 months,the mass diameter line>30 cm was the most common(P<0.05).The incidence of borderline tumors in the>30 cm group was significantly higher than that in the other two groups,and the difference was statistically significant(P<0.05).Conclusions:Ovarian mucinous and mucinous borderline tumors are the most common types of giant adnexal masses.The size of the mass tends to increase with the prolongation of the disease course.The incidence of borderline tumors increases with the in-crease of mass.Health education for young people should be strengthened.When abdominal pain,abdominal bloating,especially lower abdominal distension occurs,they should seek medical treatment in time to avoid adnex-ectomy due to borderline tumors.
6.Prognosis and influencing factors analysis of patients with initially resectable gastric cancer liver metastasis who were treated by different modalities: a nationwide, multicenter clinical study
Li LI ; Yunhe GAO ; Liang SHANG ; Zhaoqing TANG ; Kan XUE ; Jiang YU ; Yanrui LIANG ; Zirui HE ; Bin KE ; Hualong ZHENG ; Hua HUANG ; Jianping XIONG ; Zhongyuan HE ; Jiyang LI ; Tingting LU ; Qiying SONG ; Shihe LIU ; Hongqing XI ; Yun TANG ; Zhi QIAO ; Han LIANG ; Jiafu JI ; Lin CHEN
Chinese Journal of Digestive Surgery 2024;23(1):114-124
Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.
7.Improvement effects of poria acid on insulin resistance in rats with polycystic ovary syndrome and its mechanism
Hong TANG ; Linxia LI ; Yu HUA ; Xiaomei JIANG ; Shiwen ZHANG ; Jinrong FU
China Pharmacy 2024;35(1):57-62
OBJECTIVE To study the improvement effects of poria acid on insulin resistance in rats with polycystic ovary syndrome (PCOS) and its mechanism. METHODS One hundred and twenty-six female rats were randomly separated into blank group, PCOS group, poria acid low-dose group (8.33 mg/kg), pachymic acid high-dose group (33.32 mg/kg), ethinylestradiol cyproterone group (positive control group, 0.34 mg/kg), recombinant rat high mobility group protein B1 protein (rHMGB1) group (8 μg/kg), and poria acid high dose+rHMGB1 group (33.32 mg/kg poria acid+8 μg/kg rHMGB1), with 18 rats in each group. Except for the blank group, the rats in all other groups were given Letrozole suspension intragastrically to construct the PCOS model. After successful modeling, administration was performed once a day for 4 weeks. After medication, the fasting blood glucose and fasting insulin levels, and insulin resistance index (HOMA-IR) were measured in rats; the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) in rat serum, and the levels of interleukin-1β (IL-1β) and tumor necrosis factor- α (TNF- α) in ovarian tissue were detected; ovarian coefficients of rats were calculated; the pathological changes of ovarian tissue were observed; the expressions of HMGB1, receptor for advanced glycosylation elaine_ tanghong@sina.com end product (RAGE) and phosphorylated nuclear factor κB p65 (p-NF-κB p65) proteins were determined in ovarian tissue of rats. RESULTS Compared with the blank group, the pathological injury of ovarian tissue of rats in the PCOS group was serious, the levels of fasting blood glucose and fasting insulin, HOMA-IR and ovarian coefficient were increased, the levels of serum LH and T were increased, while the levels of FSH were decreased; the levels of IL-1β and TNF-α, the expressions of HMGB1, RAGE and p-NF-κB p65 protein in ovarian tissue were increased, with statistical significance (P<0.05). Compared with the PCOS group, pathological damage of ovarian tissue was reduced in poria acid low-dose and high-dose groups and ethinylestradiol cyproterone group, and fasting blood glucose, fasting insulin levels, HOMA-IR and ovarian coefficient were decreased; serum LH and T levels were decreased, while FSH levels were increased; the levels of IL-1β and TNF-α and the expressions of HMGB1, RAGE and p-NF-κB p65 protein in ovarian tissue were decreased, with statistical significance (P<0.05). The trend of corresponding indexes in rHMGB1 group was opposite to the above (P<0.05). Compared with poria acid high-dose group, the changes of the above indexes were reversed significantly in poria acid high-dose+rHMGB1 group (P<0.05). CONCLUSIONS Poria acid may improve insulin resistance and inhibit inflammatory reaction in PCOS rats by inhibiting HMGB1/ RAGE pathway.
8.The impact and predictive value of DCSI, CRP/albumin on all-cause death in patients with diabetic foot ulcers
Wei Liu ; Yutong Li ; Jing Qian ; Zhenyi Yu ; Ying Tang ; Hua Ji ; Mingwei Chen
Acta Universitatis Medicinalis Anhui 2024;59(12):2183-2189
Objective:
To explore the correlation between Diabetes Complication Severity Index(DCSI), C-reactive protein/albumin ratio(CAR) and death in patients with diabetic foot ulcer(DFU) and to clarify their predictive value for all-cause death in DFU patients.
Methods:
Retrospectively analyzed the clinical data of 354 DFU patients who were treated in the Endocrinology Department of the First Affiliated Hospital of Anhui Medical University from July 2019 to December 2022. Based on survival status during follow-up, patients were divided into a survival group(n=268) and a death group(n=86). Univariate and multivariate Cox regression analyses were used to identify risk factors for all-cause death in DFU patients. Receiver operating characteristic(ROC) curves were plotted to evaluate the predictive value of DCSI, CAR, and their combination for all-cause death in DFU patients. Kaplan-Meier curves were used to explore the impact of different DCSI and CAR levels on survival in DFU patients.
Results:
Univariate Cox regression analysis showed that older age, history of hypertension, higher Wagner classification levels, and elevated levels of CRP, Scr, FDP, DCSI score, and CAR were associated with a higher risk of death in DFU patients(P<0.05). Higher levels of HGB, HCT, ALB, or eGFR were associated with a lower risk of death. Patients receiving combined insulin and oral hypoglycemic medication had a lower risk of death compared to those receiving only insulin therapy(P<0.05). Multivariate Cox regression analysis indicated that older age, higher levels of Scr, DCSI, and CAR were independent risk factors for all-cause death in DFU patients, while higher levels of ALB and combined insulin and oral hypoglycemic therapy were protective factors. ROC curve analysis showed that the AUC values for DCSI, CAR, and their combination were 0.652, 0.633, and 0.686, respectively. Kaplan-Meier curve analysis revealed that patients with high DCSI scores(≥4.5) had a lower survival rate compared to those with lower DCSI scores(<4.5). Similarly, patients with high CAR levels(≥0.124) had a lower survival rate compared to those with lower CAR levels(<0.124).
Conclusion
High levels of DCSI and CAR are independent risk factors for all-cause death in DFU patients. DCSI, CAR, and their combination have predictive value for all-cause mortality in DFU patients.
9.Study on the effect of different administration regimens of iprrazole enteric-coated tablets on inhibiting gastric acid secretion
Ting-Yuan PANG ; Zhi WANG ; Zi-Shu HU ; Zi-Han SHEN ; Yue-Qi WANG ; Ya-Qian CHEN ; Xue-Bing QIAN ; Jin-Ying LIANG ; Liang-Ying YI ; Jun-Long LI ; Zhi-Hui HAN ; Guo-Ping ZHONG ; Guo-Hua CHENG ; Hai-Tang HU
The Chinese Journal of Clinical Pharmacology 2024;40(1):92-96
Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH>3 after 20 mg qd and 10 mg bid were 82.64%and 61.92%,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.
10.Sulforaphane inhibits lipid accumulation in atherosclerotic macrophages by regulating OGG1 gene
Yi-Ming ZHANG ; Guo-Hua WANG ; Li-Ming TANG
The Chinese Journal of Clinical Pharmacology 2024;40(7):985-989
Objective To investigate the effect of sulforaphane on lipid accumulation in macrophages induced by oxidized low-density lipoprotein(ox-LDL)and its mechanism.Methods The cells were divided into control group,ox-LDL group(100 μg·mL-1 ox-LDL),sulforaphane-L group(100 μg·mL-1 ox-LDL+5 μg·mL-1 sulforaphane),sulforaphane-H group(100 μg·mL-1 ox-LDL+10 μg·mL-1 sulforaphane)and si-OGG1 group(100 μg·mL-1 ox-LDL+10 μg·mL-1 sulforaphane+transfected with si-OGG1).Western blot assay was used to detect the expression level of protein in each group,enzyme linked immunosorbent assay was used to detect the expression of inflammatory factors and 8-hydroxydeoxyguanosine(8-OHdG)in each group,oxidase assay was used to detect intracellular cholesterol level,and reactive oxygen species(ROS)level was detected by probe method,apoptosis was detected by flow cytometry.Results The OGG1 protein expression levels of control group,ox-LDL group,sulforaphane-L group,sulforaphane-H group and si-OGG1 group were 0.80±0.03,0.26±0.02,0.43±0.03,0.68±0.05 and 0.29±0.04;the 8-OHdG levels were(3.02±0.16),(23.02±1.07),(18.28±1.40),(13.05±1.42)and(17.39±1.53)ng·mL-1;total cholesterol content were(0.08±0.01),(0.39±0.01),(0.28±0.01),(0.17±0.02)and(0.30±0.02)mmol·g-1;ROS levels were 1.66±0.10,8.23±0.78,5.41±0.15,3.27±0.24 and 7.01±0.41;the apoptosis rates were(3.64±0.31)%,(21.72±2.70)%,(16.60±1.18)%,(10.04±0.52)%and(16.07±1.46)%,respectively.Compared between control group and ox-LDL group,compared between ox-LDL group and sulforaphane-L,sulforaphane-H groups,compared between si-OGG1 group and sulforaphane-H group,the differences of the above indexes were all statistically significant(all P<0.05).Conclusion Sulforaphane may inhibit ox-LDL-induced lipid accumulation in macrophages by up-regulating OGG1 expression.


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