1.Research progress on endogenous small-molecule phenolics and the proposal of "phenolomics"
Hong-qian KUI ; Chuan-xin LIU ; Qiang WANG ; Hai-feng ZHAI ; Jian-mei HUANG
Acta Pharmaceutica Sinica 2024;59(2):336-349
Small-molecule phenolic substances widely exist in animals and plants, and have some shared biological activities. The metabolism of phenylalanine and tyrosine in the human body, and especially the metabolism of catecholamine neurotransmitters, produces endogenous small-molecule phenols. Endogenous small-molecule phenolic substances are functionally related to the important physiological processes and the occurrence of mental diseases in humans and some animals, which are systematically sorts and summarized in this review. Integrating the previous experimental research and literature analysis on natural small-molecule phenols by our research group, the understanding of the hypothesis that "small-molecule phenol are pharmacological signal carriers" was deepened. Based on above, the concept of "phenolomics" was further proposed, analyzed the research direction and research content which can bring into the knowledge framework of phenolomics. The induction of phenolomics will provide wider perspectives on explaining the pharmacological mechanism of drugs, discovering new drug targets, and finding biomarkers of mental diseases.
2.The value of standardized patient simulation combined with OSCE model in clinical undergraduate teaching
Qi WANG ; Jing ZHANG ; Lingling ZHENG ; Kui LIU
Chinese Journal of Medical Education Research 2024;23(2):256-260
Objective:To study the value of standardized patient simulation combined with objective structured clinical examination (OSCE) in clinical undergraduate teaching.Methods:A total of 114 medical undergraduates who were interned in our hospital from January 2018 to January 2020 were selected as the research objects. All the students were randomly divided into observation group ( n=57) and control group ( n=57). Other undergraduate students were recruited as standardized patients and trained; students in the observation group were given standardized patient simulation teaching, while patients in the control group were given traditional teaching methods; experienced teachers prepared test questions and developed unified scoring standards, and OSCE model was adopted to assess the two groups. The scores of theory, medical history, humanistic communication, rehabilitation thinking, practical skills and total scores of the two groups were recorded. The evaluation of standardized patient simulation by 57 undergraduates and the evaluation of OSCE model by 114 undergraduates in the observation group were recorded. SPSS 22.0 statistical software was used for t test. Results:After teaching, the scores of medical history, humanistic communication, rehabilitation thinking and practical skills in the observation group were significantly higher than those in the control group ( P<0.05), but there was no significant difference in theoretical scores between the two groups ( P>0.05). Before teaching, there was no significant difference in the total scores between the two groups ( P>0.05); after teaching, the total scores of the two groups were both improved, with significant differences ( P<0.05); compared with the control group, the total score of the observation group was improved higher, with significant differences ( P<0.05). All the undergraduates in the observation group thought that the standardized patient simulation teaching improved themselves, and 89.47% of the undergraduates thought that the standardized patient simulation was worth promoting in the teaching of rehabilitation and therapy. Most of the undergraduates believed that OSCE model could reflect the students' comprehensive ability better than the traditional written examination, and could improve their communication ability and practical operation ability, cultivate their high-quality rehabilitation thinking, and change their tendency to lay stress on theoretical study. And 91.23% of the undergraduates thought that OSCE model was worth promoting in the courses of rehabilitation therapy. Conclusions:Standardized patient simulation combined with OSCE model is conducive to improving the comprehensive performance of undergraduates, improving their communication ability and practical operation ability, and cultivating their high-quality rehabilitation thinking, which can be promoted in clinical undergraduate teaching.
3.Relationship between expressions of P21,P27 and PCNA in glomerular mesangial tissue and poor renal prognosis in patients with IgA nephropathy
Min LIAO ; Yongbo SONG ; Zhuo WEI ; Xiaobing LIU ; Kui CHENG ; Zheqi FAN ; Songtao SHUANG ; Cunhai ZHU
Chinese Journal of Immunology 2024;40(3):610-614
Objective:To explore the relationship between the expressions of P21,P27 and proliferating cell nuclear antigen(PCNA)in glomerular mesangial tissue and poor renal prognosis in patients with immunoglobulin A(IgA)nephropathy.Methods:A total of 145 patients with IgA nephropathy treated in Xiaogan Central Hospital from April 2017 to August 2019 were selected as the research object.The expressions of P21,P27 and PCNA in glomerular mesangial tissue were detected by immunohistochemistry.All patients were followed up for 24 months,and the prognosis were counted.The expressions of P21,P27 and PCNA in glomerular mesangial tissue of patients with different prognosis were compared and the influencing factors of poor prognosis in patients with IgA nephropathy were analyzed by Logistic regression analysis.Results:The expression rates of P21,P27 and PCNA positive cells in glomerular mesangial tissue of patients with IgA nephropathy were(38.69±6.83)%,(55.94±8.08)%,(33.47±5.72)%,respectively.The incidence rete of poor prognosis in patients with IgA nephropathy was 17.24%,and the expression rates of P21 and PCNA positive cells in glomerular mesangial tissue of patients with poor prognosis were higher than those in good prognosis group(P<0.05),while the expression rate of P27 positive cells was lower than that in good prognosis group(P<0.05).Logistic multiple regression analysis showed that elevated diastolic blood pressure,increased 24 h proteinuria,mesangial cell proliferation,segmental glomerulosclerosis,renal tubular atrophy/interstitial fibrosis,crescentic body,increased expression rates of P21 and PCNA positive cells and decreased expression rate of P27 positive cells were all risk factors affecting the poor prognosis of patients with IgA nephropathy(P<0.05).Conclusion:There are positive expressions of P21,P27 and PCNA in glomerular mesangial tissue of IgA nephropathy.The expression rates of P21 and PCNA positive cells in glomerular mesangial tissue of of patients with poor prognosis of IgA nephropathy are higher than those with good prognosis,while the expression rate of P27 protein positive cells is lower than those with good prognosis,which are risk factors for poor prognosis of patients with IgA nephropathy.
4.Clinical trial of rivaroxaban in the treatment of anticoagulation in patients with pulmonary embolism during maintenance period
Hui QIAN ; Kui LIU ; Ya-Lin JIANG ; Xia ZHAO
The Chinese Journal of Clinical Pharmacology 2024;40(7):959-962
Objective To compare the application effect of different doses of rivaroxaban on anticoagulation therapy in patients with pulmonary thromboembolism(PTE)during maintenance period,and to evaluate its benefit-risk.Methods The patients with PTE were divided into conventional-dose group and low-dose group according to the cohort method.Conventional-dose group were given of rivaroxaban 15 mg,twice a day and changed to 20 mg once a day after 3 weeks;low-dose group were given rivaroxaban 10 mg twice a day and changed to 15 mg once a day after 3 weeks,and the anticoagulation treatment time in both groups was ≥ 3 months.The clinical efficacy in the two groups was recorded.Serum indicators[D-dimer(D-D),N-terminal pro-brain natriuretic peptide(NT-proBNP),cardiac troponin Ⅰ(cTn Ⅰ)]and liver-kidney function[glutamic-pyruvic transaminase(GPT),glutamic-oxaloacetic transaminase(GOT),blood urea nitrogen(BUN),creatinine(Cr)]were compared before treatment and after 3 months of treatment.The patients were followed up for 3 months after treatment,and the endpoint events such as PTE recurrence and death and the bleeding events were recorded in the two groups.Results There were 42 cases in conventional-dose group,44 cases in low-dose group.After 3 months of treatment,the total effective rates in low-dose group and conventional-dose group were both 100.00%,with no significant difference(P>0.05).After 3 months of treatment,serum D-D levels in low-dose group and conventional-dose group were(0.31±0.08)and(0.29±0.07)mg·L-1,NT-proBNP levels were(125.49±24.16)and(121.39±22.08)ng·L-1,cTn Ⅰ levels were(0.02±0.00)and(0.02±0.00)μg·L-1,all with significant differences(all P>0.05).There were no significant changes in GPT,GOT,BUN and Cr in the two groups before and after treatment(all P>0.05),and there were no statistically significant differences between the two groups(all P>0.05).The total incidences of bleeding events during follow-up was 6.82%in low-dose group and was 23.81%in conventional-dose group(P<0.05).Conclusion Compared with conventional-dose rivaroxaban,low-dose rivaroxaban has similar anticoagulant effect,but the latter one can better reduce the risk of bleeding events in patients with PTE.
5.Effects and mechanism of rhubarb Tangluo pill on liver injury in type 2 diabetic rats
Dong AN ; Yong-Lin LIANG ; Yan-Kui GAO ; Feng-Zhe YAN ; Min BAI ; Si-Chen ZHAO ; Zhong-Tang LIU ; Xiao NIE
The Chinese Journal of Clinical Pharmacology 2024;40(9):1282-1286
Objective To investigate the effect and mechanism of rhubarb Tangluo pill on liver injury in type 2 diabetic rats.Methods ZDF(fa/fa)rats were given high-fat diet to induce type 2 diabetes model,and were randomly divided into model group,positive control group(0.18 g·kg-1 metformin)and experimental-L,-M,-H groups(0.54,1.08 and 2.16 g·kg-1 rhubarb Tangluo pill),with 8 rats in each group.Eight ZDF(fa/+)rats were selected as control group.The control group and model group were given equal volume of pure water once a day for 12 weeks.An oral glucose tolerance test(OGTT)was performed after administration.Fasting blood glucose level,body mass and liver mass of rats were measured and liver index was calculated.The contents of glutamic-pyruvic transaminase(GPT),glutamic oxalacetic transaminase(GOT),triglyceride(TG)and total cholesterol(TC)in serum were detected.The histomorphologic changes of liver were observed by hematoxylin-eosin(HE)staining and Masson staining.The protein expression of phosphorylated insulin receptor substrate 1(p-IRS1),phosphorylated protein kinase B(p-Akt)and glucose transporter 4(GLUT4)were detected by Western blotting.Results After administration,the fasting blood glucose levels of control group,model group,positive control group and experimental-H group were(4.71±0.45),(29.9±2.97),(15.28±4.52)and(13.84±1.55)mmol·L-1,respectively;the liver index were 2.31±0.46,4.03±0.18,3.37±0.23 and 3.38±0.24;the relative expression level of p-IRS1 protein were 1.00±0.36,4.00±0.11,1.62±0.27 and 1.90±0.17,respectively;the relative expression levels of p-Akt protein were 1.00±0.25,0.21±0.04,0.73±0.15 and 0.54±0.04,respectively;GLUT4 protein relative expression levels were 1.00±0.11,0.40±0.08,0.86±0.04 and 0.70±0.06,respectively.Compared with the model group,the above indexes in the experimental-H group were statistically significant(P<0.01,P<0.05).Conclusion Rhubarb Tanglu pill can effectively improve glycolipid metabolism and liver injury in type 2 diabetes mellitus,and its mechanism may be related to the activation of IRS1/Akt signaling pathway.
6.Research status of Chinese medicine in improving diabetic cardiomyopathy by regulating cellular autophagy
Lei LIU ; Li-Xia YANG ; Yong-Lin LIANG ; Xiang-Dong ZHU ; Yan-Kui GAO
The Chinese Journal of Clinical Pharmacology 2024;40(10):1530-1534
The pathogenesis of diabetic cardiomyopathy(DCM)is complex.Autophagy plays a pivotal role in the development of DCM,and whether its level is stable or not is closely related to the development of the course of DCM.Numerous active components found in traditional Chinese medicines and compound formulations have demonstrated the ability to modulate autophagy levels.These interventions occur through various mechanisms,such as hypoglycemic,anti-apoptotic,anti-inflammatory,and anti-oxidative stress pathways.By mitigating autophagy-induced myocardial damage,enhancing cardiac function,and slowing the progression of DCM,these compounds offer promising avenues for DCM management.This paper aims to consolidate and present research findings from the last 5 years.Our goal is to provide valuable insights and references for the research,development,and clinical application of Chinese medicine in the context of combating DCM.
7.Construction and application of a risk index of Echinococcus infection based on the classification of echinococcosis lesions
Chuizhao XUE ; Canjun ZHENG ; Yan KUI ; Yue SHI ; Xu WANG ; Baixue LIU ; Weiping WU ; Shuai HAN
Chinese Journal of Schistosomiasis Control 2024;36(3):259-271
Objective To investigate the feasibility of constructing the risk index of Echinococcus infection based on the classification of echinococcosis lesions, so as to provide insights into the management of echinococcosis. Methods The imaging data of echinococcosis cases were collected from epidemiological surveys of echinococcosis in China from 2012 to 2016, and the detection of incident echinococcosis cases was captured from the annual echinococcosis prevention and control reports across provinces (autonomous regions) and Xinjiang Production and Construction Corps in China from 2017 to 2022. After echinococcosis lesions were classified, a risk index of Echinococcus infection was constructed based on the principle of discrete distribution marginal probability and multi-group classification data tests. The correlation between the risk index of Echinococcus infection and the detection of incident echinococcosis cases was evaluated in the provinces (autonomous regions and corps) from 2017 to 2022, and the correlations between the short and medium-term risk indices and between the medium and long-term risk indices of Echinococcus infection were examined using a univariate linear regression model. Results A total of 4 014 echinococcosis cases in China from 2012 to 2016 were included in this study. The short-, medium- and long-term risk indices of E. granulosus infection varied in echinococcosis-endemic provinces (autonomous regions and corps) of China (χ2 = 4.12 to 708.65, all P values < 0.05), with high short- (0.058), medium- (0.137) and long-term risk indices (0.104) in Tibet Autonomous Region, and the short-, medium- and long-term risk indices of E. multilocularis infection varied in echinococcosis-endemic provinces (autonomous regions and corps) of China (χ2 = 6.74 to 122.60, all P values < 0.05), with a high short-term risk index in Sichuan Province (0.016) and high medium- (0.009) and long-term risk indices in Qinghai Province (0.018). There were no significant correlations between the risk index of E. granulosus infection and the detection of incident cystic echinococcosis cases during the study period (t = −0.518 to 2.265, all P values > 0.05), and strong correlations were found between the risk indices of E. multilocularis infection and the detection of incident alveolar echinococcosis cases (including mixed type) in 2018, 2020, 2021, 2022, during the period from 2017 through 2020, from 2017 through 2021, from 2017 through 2022 (all r values > 0.7, t = 2.521 to 3.692, all P values < 0.05). Linear regression models were established between the risk index of E. multilocular infection and the detection of alveolar echinococcosis cases (including mixed type), and the models were all statistically significant (b = 0.214 to 2.168, t = 2.458 to 3.692, F = 6.044 to 13.629, all P values < 0.05). The regression coefficients for the correlations between the medium- and short-term, and between the long- and medium-term risk indices of E. granulosus infection were 2.339 and 0.765, and the regression coefficients for the correlations between the medium- and short-term, and between the long- and medium-term risk indices of E. multilocular infection were 0.280 and 1.842, with statistical significance seen in both the regression coefficients and regression models (t = 16.479 to 197.304, F = 271.570 to 38 928.860, all P values < 0.05). Conclusions The risk index of Echinococcus infection has been successfully established based on the classification of echinococcosis lesions, which may provide insights into the prevention and control, prediction, diagnosis and treatment, and classified management of echinococcosis.
8.Rapid screening the chemical components in Jiawei Dingzhi pills using precursor ion selection UHPLC-Q-TOF-MS/MS
Zu-ying WEI ; Cong FANG ; Kui CHEN ; Hao-lan YANG ; Jie LIU ; Zhi-xin JIA ; Yue-ting LI ; Hong-bin XIAO
Acta Pharmaceutica Sinica 2024;59(8):2350-2364
A precursor ion selection (PIS) based ultra high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-Q-TOF-MS) analytical method was used to screen the chemical components in Jiawei Dingzhi pills (JWDZP) comprehensively and rapidly. To compile the components of the compound medicine, a total of 1 921 components were found utilizing online databases and literature. After verifying the sources, unifying the component names, merging the multi-flavor attributed components, and removing the weak polar molecules, 450 components were successfully retained. The Acquity UPLC HSS T3 column (100 mm × 2.1 mm, 1.8 μm) was used, with a 0.1% formic acid water (A)-acetonitrile (B) as the mobile phase. The flow rate was 0.35 mL·min-1, the column temperature was 35 ℃, and an electrospray ion source was used. Data was collected with the PIS strategy in both positive and negative ion modes. Compounds were screened through matching accurate molecular weight of the database, and identified according to MS/MS data (characteristic fragment ions and neutral loss), with comparison of reference. Some compounds were confirmed using standard products. A total of 176 compounds were screened out in the extract of JWDZP, among which 26 compounds were confirmed by standard products. These compounds include 96 components from the sovereign drug, and 34 coefflux components with low ion intensity. The PIS-UHPLC-Q-TOF-MS/MS method established in this study can quickly and comprehensively screen the chemical components of JWDZP, which enhanced the screening rate of components with co-elution compounds of low ion intensities and provided a basis for the study of the material foundation of JWDZP.
9.Analysis of perioperative bleeding and its related factors in patients undergoing transurethral plasma kinetic prostatectomy
Keke ZHU ; Kui LIU ; Zengli WANG
International Journal of Surgery 2024;51(9):636-640
Objective:To investigate the perioperative bleeding of patients undergoing transurethral plasma kinetic prostatectomy (TUPKP) and analyze the related influencing factors.Methods:Retrospectively analyzed the clinical data of 206 patients with TUPKP admitted to Xi′an Lintong District People′s Hospital from March 2021 to March 2024, all patients were aged from 51 to 83 years old, with an average of (64.33±9.74) years; patients′ course of disease was 1 to 7 years, averaged (4.57±1.59) years. and the perioperative bleeding of patients was observed and divided into bleeding group ( n=108) and non-bleeding group( n=98). By comparing the general data and laboratory data between groups, the influencing factors of perioperative bleeding in TUPKP patients were analyzed by multivariate Logistic regression. Results The proportion of diabetes and postoperative constipation in bleeding group was higher than that in non-bleeding group, and the prostate volume and operation time were higher than that in non-bleeding group ( P<0.05). Serum calcium, platelet count (PLT) and activated partial thromboplastin time (APTT) in bleeding group were lower than those in non-bleeding group ( P<0.05). Multivariate Logistic regression analysis showed that diabetes ( OR=4.283), prostate volume ( OR=1.111), operation time ( OR=1.091) and postoperative constipation ( OR=4.144) were the risk factors for perioperative bleeding in TUPKP patients ( P<0.05). Serum calcium ( OR=0.001) and PLT ( OR=0.980) are the protective factors for perioperative bleeding in TUPKP patients ( P<0.05). Conclusion:The rate of perioperative bleeding in TUPKP patients is of great risk. Diabetes, prostate volume, operation time and postoperative constipation are its risk factors, and serum calcium and PLT are its protective factors.
10.Efficacy and safety of dapagliflozin combined with sacubitril valsartan in the treatment of heart failure after acute myocardial infarction:a Meta-analysis
Longfei BI ; Yao LIU ; Bingxia LIU ; Kui LI
Chinese Journal of Pharmacoepidemiology 2024;33(11):1254-1264
Objective To systematically review the efficacy and safety of dapagliflozin combined with sacubitril valsartan in the treatment of heart failure after acute myocardial infarction.Methods PubMed,Embase,Web of Science,Cochrane Library,CNKI,WanFang Data and VIP databases were electronically searched to collect randomized controlled trials(RCTs)on dapagliflozin combined with sacubitril valsartan(combination treatment group)vs.sacubitril valsartan(monotherapy group)for the treatment of heart failure after acute myocardial infarction from inception to June 18,2024.Two reviewers independently screened the literature,extracted data and assessed the risk of bias of the included studies.Meta-analysis was performed using RevMan 5.4 software.Results A total of 11 RCTs involving 1 060 patients were included.Meta-analysis results showed that compared with the monotherapy group,the efficiency of clinical treatment(OR=5.08,95%CI 2.81 to 9.16,P<0.001),left ventricular ejection fraction(MD=5.02,95%CI 4.08 to 5.95,P<0.001),6-minute walking distance(MD=56.45,95%CI 32.83 to 80.07,P<0.001)significantly increased in the combination treatment group,and the levels of N-terminal brain natriuretic peptide precursor(MD=-249.28,95%CI-414.78 to-83.78,P=0.003)and the incidence of major adverse cardiovascular events(OR=0.24,95%CI 0.15 to 0.41,P<0.001)significantly decreased in the combination treatment group.However,there was no statistically significant difference between the two groups in terms of reducing the incidence of adverse effects(OR=0.66,95%CI 0.31 to 1.38,P=0.27).Conclusion Current evidence shows that the use of the combination of dapagliflozin and sacubitril valsartan for heart failure after acute myocardial infarction is more effective clinically and does not increase the incidence of adverse drug reactions compared with the treatment of sacubitril valsartan alone.Due to the limited quality and quantity of the included studies,more high-quality studies are needed to verify the above conclusion.

Result Analysis
Print
Save
E-mail