OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Objective To explore the effects of different side tension pneumothorax on hemodynamics in pigs,providing data support for the optimization of on-site first-aid procedures for pneumothorax.Methods Twelve Bama pigs were randomly divided into left-sided tension pneumothorax group and right-sided tension pneumothorax group(6 in each group).During the occurrence of pneumothorax and as the pleural pressure gradually increases by 1 mmHg increments,the key indicators were collected using pulse indicator continuous cardiac output(PICCO)technology:hemodynamic indicators[global ejection fraction(GEF),cardiac output(CO),global end-diastolic volume(GEDV),intrathoracic blood volume(ITBV),stroke volume(SV),mean arterial pressure(MAP)],basic vital signs[heart rate(HR),diastolic blood pressure(DBP),systolic blood pressure(SBP)],and arterial blood gas parameters[partial pressure of oxygen(PO2),partial pressure of carbon dioxide(PCO2)].Mediastinal localization was subsequently performed using radiographs.Differences were investigated through comparison between the two groups and within each group before and after the procedure.Results By comparing the hemodynamic changes and X-ray examination results,twelve Bama pigs tension pneumothorax models were successfully constructed.Hemodynamic analysis showed that in left-sided tension pneumothorax model when the pleural pressure reached 8 mmHg,SBP,DBP,MAP,CO,GEF,SV,GEDV and ITBV were significantly lower than those during the occurrence of ipsilateral pneumothorax(P<0.05).In right-sided tension pneumothorax model,when the pleural pressure reached about 3 mmHg,SBP,DBP,MAP,SV,GEDV,and ITBV were significantly lower than those during the occurrence of ipsilateral pneumothorax(P<0.05).Blood gas analysis showed that at 8 mmHg for left-sided and 3 mmHg for right-sided tension pneumothorax,compared with the occurrence of their respective ipsilateral pneumothorax,PO2 was significantly lower(P<0.05)and PCO2 was significantly higher(P<0.05).Conclusions There are different effects on hemodynamics in different side tension pneumothorax.Compared with left tension pneumothorax,right tension pneumothorax can lead to serious consequences under a smaller pleural pressure.Different side tension pneumothorax models can be constructed according to the actual situation when performing pneumothorax related experiments.

Objective To analyze the risk factors and survival status of Epstein-Barr virus(EBV)infection in pa-tients with aplastic anemia(AA)after haploid allogeneic hematopoietic stem cell transplantation(Haplo-HSCT).Methods Clinical data of 78 AA patients who underwent Haplo-HSCT in the hematology department of a hospital from January 1,2019 to October 31,2022 were analyzed retrospectively.The occurrence and onset time of EBV viremia,EBV-related diseases(EBV diseases),and post-transplant lymphoproliferative disorders(PTLD)were ob-served,risk factors and survival status were analyzed.Results Among the 78 patients,38 were males and 40 were females,with a median age of 33(9-56)years old;53 patients experienced EBV reactivation,with a total inci-dence of 67.9％,and the median time for EBV reactivation was 33(13,416)days after transplantation.Among pa-tients with EBV reactivation,49 cases(62.8％)were simple EBV viremia,2 cases(2.6％)were possible EBV di-seases,and 2 cases(2.6％)were already confirmed EBV diseases(PTLD).Univariate analysis showed that age 1＜40 years old at the time of transplantation,umbilical cord blood infusion,occurrence of acute graft-versus-host disease(aGVHD)after transplantation,and concurrent cytomegalovirus(CMV)infection were independent risk fac-tors for EBV reactivation in AA patients after Haplo-HSCT.Multivariate analysis showed that concurrent CMV in-fection was an independent risk factor for EBV reactivation in A A patients after Haplo-HSCT(P=0.048).Ritu-ximab intervention before stem cell reinfusion was a factor affecting the duration of EBV reactivation(P＜0.05).The mortality of EBV viremia,EBV diseases,and PTLD alone were 8.2％,50.0％,and 100％,respectively.The 2-year overall survival rate of patients with and without EBV reactivation were 85.3％,and 90.7％,respectively,difference was not statistically significant(P=0.897).However,patients treated with rituximab had 2-year lower survival rate than those who did not use it,with a statistically significant difference(P=0.046).Conclusion EBV reactivation is one of the serious complications in AA patients after Haplo-HSCT,which affects the prognosis and survival of patients.

Objective:Comprehensively review national and provincial policies related to centralized procurement of Chinese Patent Medicines(CPM)and to compare the grouping rules and methods of centralized procurement in different regions,with the goal of providing guidance for enhancing the grouping rules for CPM.Methods:Through literature analysis and comparative analysis,the 22 policies included in the study were analyzed in depth,and the progress of centralized volume-based procurement of CPM in national and inter-provincial alliances was compared and summarized.Results:National and inter-provincial alliances'centralized volume-based procurement of CPM divides procurement groups according to functional indications,route of administration,and market conditions.The grouping rules are not closely related to drug dosage forms and quality.Dividing bidding groups based on the market competition pattern ignores the innovative value of some CPM,and does not take into account the unique brand value of the company and its drugs.The completeness of the grouping rules needs to be improved.Conclusions:There are many dosage forms of CPM and complex quality control indicators.The existing grouping rules follow the idea of grouping chemical drugs and lack a top-level design oriented to the value of CPM.It is recommended to adopt a diversified grouping method and advance the technical evaluation link in the existing shortlisting rules.This means that factors such as drug dosage form,quality and innovation value should be considered when formulating grouping rules.At the same time,it is necessary to improve and refine the current grouping rules.

Objective:To analyze the burden and changing trends of periodontal disease in adults of the mainland of China from 1990 to 2019, and to predict the incidence trends of periodontal disease in the next 25 years, with a goal to provide a basis for reducing the burden of periodontal disease and formulating relevant prevention and treatment measures.Methods:Data on the incidence, prevalence, and disability adjusted life years (DALY) rate of periodontal disease among adults in the mainland of China from 1990 to 2019 were extracted from the global burden of disease study 2019 (GBD 2019) database. The estimated annual percent change (EAPC) was used to estimate the temporal trend of periodontal disease, and the age-period-cohort model (APC) was used to predict the age-standardized incidence of periodontal disease in Chinese adults from 2020 to 2044.Results:From 1990 to 2019, the incidence, prevalence, and DALY rate of adult periodontal disease in the mainland of China showed an increasing trend, with EAPCs of 0.3 (95% CI: 0.1-0.6), 0.5 (95% CI: 0.1-0.8), and 0.5 (95% CI: 0.1-0.8), respectively. The incidence and prevalence of periodontitis among the population aged 35-39 years old and 40-44 years old increased the most significantly, with EAPCs of 0.8 and 0.7, respectively, whereas the change in periodontal disease prevalence tended to be stable and the increase trend in prevalence was lower in the elderly group (EAPC=0.4). The incidence (EAPC=2.1), prevalence (EAPC=2.6) and DALY rate (EAPC=2.6) of periodontal disease in females increased more than those in males (EAPC=1.9, 2.4, and 2.4, respectively), of which the prevalence had exceeded that of males in 2019. The APC model predicted that the prevalence of periodontal disease in the period of 2020-2044 in China would still be on an upward trend, and the increase rate would be higher in females than in males. Conclusions:The burden of periodontal disease among adults in China had been increasing over the past 30 years, especially among young and middle-aged adults as well as females, and the incidence of periodontal disease will continue to increase over the next 25 years.

According to the theory of 'Xingben Dazao' of Psoralea corylifolia Linn. (BL), the susceptible syndromes and biomarkers of liver injury caused by BL were searched. Rat models of kidney-yin deficiency syndrome (M_yin) and kidney-yang deficiency syndrome (M_yang) were established, and all animal experimental operations and welfare following the provisions of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Traditional Chinese Medicine (No. YFYDW2020017). The results showed that BL significantly decreased the body weight, water intake, and urine weight of M_yin rats and increase the organ indexes of the liver, testis, adrenal gland, and spleen and the expression of alanine aminotransferase (ALT). Meantime, BL significantly increased the urine weight of M_yang rats and decreased the expression of ALT and aspartate aminotransferase (AST). Hematoxylin and eosin (HE) staining showed that BL could aggravate inflammatory infiltration of hepatocytes in rats with M_yin and alleviate liver injury in rats with M_yang. Metabolomics identified 17 BL co-regulated significant differential metabolic markers in M_yin and M_yang rats. Among them, 8 metabolites such as glutamine, quinolinate, biliverdin, and lactosylceramide showed opposite trends, mainly involving cysteine and methionine metabolism, tyrosine metabolism, tryptophan metabolism, purine metabolism, sphingolipid metabolism, glycerol phospholipid metabolism, glutamine metabolism, and other pathways. M_yin/M_yang may be the susceptible constitution of BL for liver damage or protection, which may be related to the regulation of amino acid metabolism and sphingolipid metabolism. The study can provide some experimental data support for the safe and accurate use of BL in the clinical practice of traditional Chinese medicine.

With the advances in medicine, people have deeply understood the complex pathogenesis of diseases. Revealing the mechanism of action and therapeutic effect of drugs from an overall perspective has become the top priority of drug design. However, the traditional drug design methods cannot meet the current needs. In recent years, with the rapid development of systems biology, a variety of new technologies including metabolomics, genomics, and proteomics have been used in drug research and development. As a bridge between traditional pharmaceutical theory and modern science, computer-aided drug design(CADD) can shorten the drug development cycle and improve the success rate of drug design. The application of systems biology and CADD provides a methodological basis and direction for revealing the mechanism and action of drugs from an overall perspective. This paper introduces the research and application of systems biology in CADD from different perspectives and proposes the development direction, providing reference for promoting the application.
Humans ; Systems Biology ; Drug Design ; Drug Development ; Genomics ; Medicine

Ultra-performance liquid chromatography-quadrupole time of fight/mass spectrometry(UPLC-Q-TOF-MS) and UNIFI were employed to rapidly determine the content of the components in Liangxue Tuizi Mixture. The targets of the active components and Henoch-Schönlein purpura(HSP) were obtained from SwissTargetPrediction, Online Mendelian Inheritance in Man(OMIM), and GeneCards. A "component-target-disease" network and a protein-protein interaction(PPI) network were constructed. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the targets by Omishare. The interactions between the potential active components and the core targets were verified by molecular docking. Furthermore, rats were randomly assigned into a normal group, a model group, and low-, medium-, and high-dose Liangxue Tuizi Mixture groups. Non-targeted metabolomics was employed to screen the differential metabolites in the serum, analyze possible metabolic pathways, and construct the "component-target-differential metabolite" network. A total of 45 components of Liangxue Tuizi Mixture were identified, and 145 potential targets for the treatment of HSP were predicted. The main signaling pathways enriched included resistance to epidermal growth factor receptor tyrosine kinase inhibitors, phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT), and T cell receptor. The results of molecular docking showed that the active components in Liangxue Tuizi Mixture had strong binding ability with the key target proteins. A total of 13 differential metabolites in the serum were screened out, which shared 27 common targets with active components. The progression of HSP was related to metabolic abnormalities of glycerophospholipid and sphingolipid. The results indicate that the components in Liangxue Tuizi Mixture mainly treats HSP by regulating inflammation and immunity, providing a scientific basis for rational drug use in clinical practice.
Animals ; Rats ; IgA Vasculitis/drug therapy* ; Network Pharmacology ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Metabolomics