Network pharmacological analysis on Balanophora involucrata Hook.f.in treatment of hyperuricemia and its therapeutic effect on hyperuricemia cell model and hyperuricemia model mouse / 吉林大学学报(医学版)

Objective:To investigate the efficacy of Balanophora involucrata Hook.f.in treatment of hyperuricemia(HUA)based on network pharmacology,molecular docking,and hyperuricemia models in vivo and in vitro,and to clarify the main targets of its active components and related signaling pathway mechanism.Methods:The potential targets of Balanophora involucrata Hook.f.in treatment of HUA were identified by Databases such as the Traditional Chinese Medicine Database in Taiwan,the Chinese Herbal Medicine Identification Database,Professional Chemical Database,TargetNet Database,SwissTargetPrediction Database,GeneCards,Therapeutic Target Database(TTD),DrugBank Database,DisGeNET Database,Online Mendelian Inheritance in Man(OMIM)Database,and Venny Database.STRING Database and Cytoscape software were used to construct the active component-predictive target network and protein-protein interaction(PPI)network for Balanophora involucrata Hook.f.;topological analysis was used to select the main active components and core targets;Gene Ontology(GO)functional and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were performed by R software;AutoDock Vina software was used for molecular docking validation.The NRK-52E cells were divided into blank control group,blank administration group,model group,and different concentrations(2.0,10.0,and 50.0 μmol·L-1)of erythrodiol(EDT)groups.High-performance liquid chromatography culture(HPLC)was used to detect the uric acid(UA)levels in the cell culture supernatants in various groups.The male ICR mice were divided into blank control group,blank administration group,model group,and EDT group;the mice in the last two groups were used to prepare the HUA models;kits were used to detect the levels of UA,creatinine(Cr),and blood urea nitrogen(BUN)in serum of the mice in various groups;the bilateral kidney tissue of the mice was harvested and weighed;the kidney indexes of the mice in various groups were calculated;TUNEL staining was used to observe the apoptosis in kidney tissue of the mice in various groups;Western blotting method was used to detect the expression levels of protein kinase B(AKT),phosphorylated AKT(p-AKT),phosphoinositide 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and matrix metalloproteinase-9(MMP-9)proteins in kidney tissue of the mice in various groups.Results:Six active components of Balanophora involucrata Hook.f.were identified,involving 116 intersecting targets and 14 core targets.The enrichment analysis yielded 1 828 GO terms and 145 signaling pathways.The molecular docking results showed that EDT had good binding activity with MMP-9.The high uric acid cell experiment results showed that compared with blank control group,the UA level in the cells in model group was significantly increased(P<0.01);compared with model group,the UA levels in the cells in 2.0,10.0,and 50.0 μmol·L-1 EDT groups were significantly decreased(P<0.01).Compared with blank control group,the levels of UA,Cr,and BUN in serum of the mice in model group were increased(P<0.01),and the kidney indexes were significantly increased(P<0.01);compared with model group,the levels of UA,Cr,and BUN in serum of the mice in EDT group were decreased(P<0.05 or P<0.01),and the kidney index was significantly decreased(P<0.05 or P<0.01).Compared with blank control group,the number of apoptotic cells in kidney tissue of the mice in model group was increased;compared with model group,the number of the apoptotic cells in kidney tissue of the mice in EDT group was significantly decreased.Compared with blank control group,the ratios of p-AKT/AKT and p-PI3K/PI3K and expression level of Bcl-2 protein in kidney tissue of the mice in model group were significantly decreased(P<0.05 or P<0.01),while the expression levels of Bax and MMP-9 proteins were significantly increased(P<0.01);compared with model group,the ratios of p-AKT/AKT and p-PI3K/PI3K and expression level of Bcl-2 protein in kidney tissue of the mice in EDT group were significantly increased(P<0.05 or P<0.01),and the expression levels of Bax and MMP-9 proteins were significantly decreased(P<0.01).Conclusion:The active component of Balanophora involucrata Hook.f.,EDT,has a UA-decreasing effect and may inhibit the apoptosis and alleviate the kidney injury by activating the PI3K/AKT signaling pathway.

Regulatory effect of retinoid X receptor on oxidative stress response in-duced by hypoxia/reoxygenation in rat type Ⅱ alveolar epithelial cells / 中国病理生理杂志

AIM:To investigate the regulatory role of retinoid X receptor(RXR)in oxidative stress response of rat type Ⅱ alveolar epithelial cells(AECII)induced by hypoxia/reoxygenation(HR).METHODS:The AECII were di-vided into control(C)group,HR group,HR+solvent dimethyl sulfoxide(DMSO)group(HD group),HR+RXR agonist 9-cis-retinoic acid(9-RA)group(RA group),and HR+RXR antagonist HX531 group(HX group).Cell Counting Kit-8(CCK-8)method was used to measure the cell viability.Immunofluorescence staining was used to detect the expression of surfactant protein A(SP-A)and RXRα in AECII.Kits were detected to the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in cells.Transmission electron microscopy was used to observe the ultrastructural changes of the cells.Western blot was used to detect the protein level of nuclear factor E2-related factor 2(Nrf2).RT-PCR was used to detect the expression level of Nrf2 mRNA.RESULTS:Compared with C group,the cell viability and SOD activity in HR,HD,RA and HX groups were decreased significantly(P<0.05),the MDA content were increased significantly(P<0.05),the Nrf2 mRNA and protein expression levels were decreased significantly(P<0.05 or P<0.01),and the immuno-fluorescence expression of RXRα was significantly increased(P<0.01).Compared with HR and HX groups,the cells in RA group showed significantly increased cell viability(P<0.05),increased SOD activity(P<0.05),decreased MDA con-tent(P<0.05),increased Nrf2 mRNA and protein expression levels(P<0.01),and significantly increased immunofluo-rescence expression of RXRα(P<0.01).CONCLUSION:Hypoxia/reoxygenation can aggravate the oxidative stress re-sponse of rat AECII,and RXR agonist intervention can alleviate HR-induced rat AECII injury by inhibiting oxidative stress.

Methodology for Developing Rapid and Living Guidelines of Traditional Chinese Medicine （RALIG-TCM） （Part 1）：Concept and Current Practice / 中医杂志

Rapid and living guidelines are those developed in response to public health emergencies in a short period of time using a scientific and standardized approach. Subsequently， they provide timely and credible recommendations for decision makers through regular and frequent updates of clinical evidence and recommendations. In this paper， we introduced the definition of rapid and living guideline as well as analyzed the basic characteristics of eight rapid and living guidelines in the field of traditional Chinese medicine （TCM） published till 2023 June， summarizing three core methodological issues in relation to how to rapidly develop guidelines， how to formulate recommendations when there is lack of evidence， and how to ensure the timeliness of guidelines. Based on the analysis of current rapid and living guidelines， it is implicated that there is necessity to carry out rapid and living guideline in the field of TCM， and the methodology of rapid integration of multivariate evidence in the field of TCM needs to be further explored； furthermore， it is necessary to further explore the obstacles of implementation of guidelines and promote timely updating， all of which provide certain theoretical references for relevant guideline developers and researchers.

Methodology for Developing Rapid and Living Guidelines of Traditional Chinese Medicine （RALIG-TCM） （Part 4）： Evidence Monitoring and Dynamic Updates / 中医杂志

In developing rapid and living guidelines of traditional Chinese medicine （TCM） in response to public health emergencies， it is important that evidence continue to be reviewed， and clinical questions and recommendations updated if necessary， due to the rapid changes in disease progression and the continuous generation of relevant research evidence. This paper proposed that the updating scope in dynamic mode should first be identified； then evidence monitoring should be carried out in four aspects， including clinical research， related guidelines or laws and regulations， disease progression， as well as clinical use of recommendations and clinical needs； finally， based on the results of the evidence monitoring， different options should be made， including revising the clinical questions， updating the evidence and recommendations， and withdrawing the guideline.

Interpretation of the Guideline for Multi-dimensional and Multi-criteria Comprehensive Evaluation of Chinese Patent Medicine：weighting of evaluation indicators / 中国药房

OBJECTIVE To provide a detailed report and interpretation of the method and results for determining the weights of the technical indicators from the “multi-dimensional and multi-criteria comprehensive evaluation index system （first edition）” stated in Guideline for Multi-dimensional and Multi-criteria Comprehensive Evaluation of Chinese Patent Medicine. METHODS Normalization calculations were performed on the comprehensive weight values calculated by the analytic hierarchy process and expert weighting method to obtain the objective weights of the indicators. RESULTS The weight results of the six primary dimensions in the current comprehensive evaluation indicator system of Chinese patent medicine showed effectiveness dimension＞ safety dimension＞standard dimension＞application dimension＞scientific dimension＞economic dimension， with weight values of 0.281 0， 0.268 5， 0.195 8， 0.107 3， 0.096 1 and 0.051 3 respectively， consistent with the results of most researches currently. CONCLUSIONS The process of weight determination in this indicator system is scientifically reasonable， with clear methods and clear interpretations， and is worthy of further optimization and widespread application.

Application and Enlightenment of WHO Drug Pricing Method in Medical Insurance Pricing of Proprietary Chinese Medicine in China / 中国卫生经济

WHO Guideline on Country Pharmaceutical Pricing Policies,published in 2020,outlines 10 commonly used pricing methods internationally.However,due to the unique composition of costs for traditional Chinese medicine(TCM),directly applying pricing methods designed for chemical and biological drugs may lead to discrepancies.Currently,in China,drug pricing primarily in-volves internal reference pricing,tender negotiation pricing,promoting the use of quality-assured generic and biosimilar drugs,and centralized procurement.It systematically analyzes various pricing methods and identifies their applicability and underlying reasons concerning the pricing of TCMwithin the medical insurance system.The method of value-based pricing and increasing price transparency has advantages for the pricing regulation of traditional Chinese medicine under medical insurance.

The association between baseline blood pressure, collaterals and outcome in acute ischemic stroke / 中华神经科杂志

Objective To explore the association between post-stroke blood pressure and collaterals and functional outcome in acute ischemic stroke (AIS) patients with large vessel occlusion/stenosis.Methods Consecutive AIS patients with large vessel occlusion/stenosis who had symptom onset within 6 hours in Huashan Hospital from July 2011 to October 2017 were retrospectively recruited and enrolled.Collaterals were analyzed through CT perfusion imaging.And all the patients were followed up for 3 months.And the association between baseline blood pressure,collaterals and outcomes was analyzed using multivariate linear and Logistic models.A total of 126 patients were enrolled for multivariate Logistic and linear regression analysis.Results Multivariate Logistic regression analysis revealed that with every increment of 10 mmHg (1 mmHg =0.133 kPa) systolic blood pressure,the odds of poor functional outcome increased by 20％ (unadjusted OR =1.20,95％ CI 1.02-1.42,P =0.03).After adjusting for age and sex,the odds increased by 21％ (OR =1.21,95％ CI 1.01-1.46,P =0.04).However,no statistical significance was shown after multivariate adjustment (OR--1.02,95％ CI 0.99-1.05,P =0.06).Multivariate linear regression analysis demonstrated that diastolic blood pressure (DBP) was negatively associated with the volume of hypoperfused and severely hypoperfused lesion.With every increment of 10 mmHg DBP,the volume of delay time (DT) ＞ 6 s lesion downsized by 7.6 ml (unstandardized coefficient -7.56,95％ CI-14.89--0.24,P =0.04).The DT ＞6 s/DT ＞3 s ratio was also decreased with the elevation of DBP (unstandardized coefficient-0.03,95 ％ CI-0.06--0.01,P =0.01).Conclusions For AIS patients,though higher DBP seems to be associated with better collaterals,it may still relate with poor functional outcome.

Intravenous thrombolysis treatment compliance with alteplase in patients with acute ischemic stroke in Huashan Hospital / 中华神经科杂志

Objective To clarify the intravenous thrombolysis utilization of acute ischemic stroke patients in Huashan hospital,and to analyze the factors affecting thrombolytic therapy compliance.Methods The data from a prospective cohort were analyzed.Consecutive acute stroke and transient ischemic attack patients from Huashan Hospital emergency room were recruited in 2014.Eligible ischemic stroke patients were divided into two groups according to intravenous thrombolysis or not.Results Totally 220 patients from emergency room were assessed in 2014.Among eligible patients,43 patients refused intravenous thrombolysis,whereas 59 patients chose this therapy.After multiple analysis,age,baseline NIHSS score,limb weakness,hemiplegic paralysis,facial paralysis or speech symptoms were significantly different between the two groups (U =936.000,P =0.024;U =284.500,P ＜ 0.01;x2 =8.824,P =0.003;x2 =7.732,P=0.005;x2 =5.169,P=0.038;x2 =5.040,P=0.025).Patients with NIHSS score ＜7 tended to refuse thrombolysis therapy in the receiver operating characteristic curve analysis (sensitivity 0.93,specificity 0.71).From 2008 to 2014,244 cases were analyzed in the thrombolysis database.Compared with patients with higher baseline NIHSS score,intracranial hemorrhage rate (2.6％ vs 19.4％;x2 =12.466,P ＜0.01),7-day mortality rate (1.3％ vs 16.9％;x2 =12.308,P ＜0.01) and 3-month mortality rate (3.8％ vs 21.1％;x2 =11.993,P ＜0.01) were lower in patients whose baseline NIHSS score ＜ 7 (minor group).A higher rate of excellent outcome (3-month modified Rankin Scale score ≤ 1)was observed in minor group (78.2％ vs 38.0％;x2 =34.403,P ＜ 0.01).Conclusions Intravenous thrombolysis was performed in 54.6％ of eligible ischemic stroke patients.Age,baseline NIHSS score,limb weakness,hemiplegic paralysis,facial paralysis or speech symptoms were associated with patients' decision of thrombolysis.The effectiveness and safety of intravenous thrombolysis were promising for patients with mild stroke.

Is it necessary to wait for platelet count and coagulation results before intravenous thrombolysis in acute ischemic stroke ? / 中华神经科杂志

Objective To assess the incidence of thrombocytopenia and abnormal coagulation,door to needle time (DNT),and safety in patients with ischemic stroke who receive intravenous thrombolytic treatment prior to the availability of blood platelet (PLT) and coagulation results.Methods Consecutive acute ischemic stroke (AIS) or transient ischemic attack patients within 12 hours of symptom onset who were admitted from January 2009 to March 2013 were retrospectively recruited.First laboratory reports in their medical charts were collected to assess the incidence of thrombocytopenia and abnormal coagulation.In the mean time,consecutive AIS patients who received intravenous thrombolysis at Huashan Hospital during the same period were retrospectively recruited.The thrombolytic procedures were further optimized since June 10.3760/cma.j.issn.1006-7876.2014.07.00626,2012.With informed consent,intravenous thrombolysis was initiated without PLT and coagulation results after certain previous history and medications were ruled out.Thrombolytic patients were divided into two groups based on the initiation of thrombolysis before or after PLT and coagulation results.Baseline demographic data,symptomatic intracerebral hemorrhage rates,mortality on the 7th day as well as functional outcome at 3 months were collected.DNT as well as efficacy and safety of thrombolysis therapy were compared between the two groups.Results Of 298 AIS patients within 12 hours of onset,8 had thrombocytopenia or abnormal coagulation.One hundred and twenty cases of intravenous thrombolysis patients were recruited.Waiting for PLT and coagulation results prolonged DNT than without waiting for them (90 min vs 59 min; U =870.000,P ＜0.01).There was no statistically significant difference in the rate of symptomatic intracerebral hemorrhage (sICH),early efficacy,7 d mortality and 3-month good outcome between two groups.Conclusions The incidence of thrombocytopenia and abnormal coagulation is low in AIS patients.Initiating intravenous thrombolysis prior to the availability of coagulation results can shorten DNT,while increased risks of sICH and 7 d mortality were not observed.

Efficacy and outcome predictors of intravenous thrombolysis for patients with acute ischemic stroke / 中华神经科杂志

Objective To determine factors associated with favorable clinical outcome in acute ischemic stroke patients who received intravenous thrombolysis.Methods Patients treated with intravenous recombinant tissue plasminogen activator (rt-PA) between January 1,2008 and May 31,2013 were recruited.Favorable outcome was defined as modified Rankin scale (mRS) score ＜ 2 at 3 months.The baseline characteristics were compared by univariate and multivariate analysis.Results Of all the 148 patients studied,within the 4.5-hour time window,the rate of patients with a favorable outcome was 52.4％ (65/124),significantly better than those beyond the time window(20.8％ (5/24),x2 =8.048,P =0.005).Univariate analysis showed that age (U =2 146.000,P =0.025),TOAST classification (x2 =11.412,P =0.010),Oxfordshire Community Stroke Project (OCSP) classification (x2 =17.409,P =0.001),baseline blood glucose (U =1 446.500,P ＜ 0.01),baseline fibrinogen (U =1 689.000,P =0.038),admission NIHSS score (U =1 140.000,P ＜ 0.01),24-hour NIHSS score (U =458.000,P ＜0.01),and early symptom improvement (24-hour NIHSS score decreased ≥ 4 points,or down to 0 point;x2 =19.576,P ＜ 0.01) were the factors associated with clinical outcomes.Multivariate analysis revealed that age (odds ratio (OR) =0.943,95％ confidence interval (CI) 0.892-0.996,P =0.024),baseline fibrinogen (OR =0.448,95％ CI 0.208-0.963,P =0.040),baseline NIHSS score (OR =0.749,95％ CI 0.663-0.845,P ＜ 0.01),and early symptom improvement (OR =14.970,95％ CI 4.460-50.249,P ＜ 0.01) were independent predictors of clinical outcomes.Conclusions The effect of intravenous thrombolysis on clinical outcomes of acute ischemic stroke patients is time-dependent.Age,baseline NIHSS score,baseline fibrinogen level,and early symptom improvement are independent predictors of clinical outcomes after intravenous thrombolysis.

Evaluation of cerebrovascular reserve by xenon computed tomography in patients with ischemic stroke / 中华内科杂志

Objective To evaluate the cerebrovascular reserve(CVR) in patients of ischemic stroke with cerebrovascular stenosis by Xenon-enhanced CT. Methods Twenty subjects of ischemic stroke with cerebrovascular stenosis were recruited. All subjects were examined by Xenon-enhanced CT before and after acetazolamide (ACZ) challenge test to quantitatively measure the regional cerebral blood flow (rCBF) and CVR. Results We compared the rCBF in the corresponding region supplied with stenosed artery (divided manually) with that in the region of normal side. There was no significant difference in resting rCBF but in CVR [ipsilateral side vs. normal side ( 5.9 ± 24. 3 ) % vs ( 25.9 ± 32. 6 ) % , P ＜ 0. 05]. Conclusion Impaired CVR is an important character of the patients with cerebrovascular stenosis suffered from ischemic stroke.