1.Signal mining for bleeding risk associated with the concomitant use of direct oral anticoagulants and triazole antifungals
Ziyang WU ; Ying ZHU ; Menghua ZHANG ; Na HE ; Qiong QIN ; Cheng XIE
China Pharmacy 2026;37(9):1185-1189
OBJECTIVE To assess the bleeding risk signals associated with the concomitant use of direct oral anticoagulants (DOACs) and triazole antifungals, and to provide pharmacovigilance evidence for the safety evaluation and monitoring of combined clinical use. METHODS Adverse event reports involving the concomitant use of DOACs and triazole antifungals were extracted from the US FDA Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the third quarter of 2025. Nine bleeding-related preferred terms (PTs) were selected. The Ω shrinkage measure, additive model, multiplicative model, and combined risk ratio method were employed to detect drug-drug interaction signals. The strength of positive signals was further analyzed based on the Ω shrinkage measure. RESULTS A total of 790 adverse event reports involving the concomitant use of DOACs and triazole antifungals were included, among which 229 reports involved nine bleeding-related PTs. A total of 13 signals were consistently identified as posit ive by all four methods. These signals involved six drug combinations: apixaban-fluconazole, apixaban-posaconazole, rivaroxaban-itraconazole, dabigatran etexilate-fluconazole, apixaban-voriconazole, and dabigatran etexilate-itraconazole. The Ω shrinkage measure showed that the apixaban-posaconazole combination exhibited stronger signals for bleeding ( Ω =2.73, Ω 025 =2.05) and hemoptysis ( Ω =2.17, Ω 025 =0.83); the apixaban-fluconazole combination exhibited stronger signals for hematoma ( Ω =2.30, Ω 025 =1.47) and hematuria ( Ω =1.71, Ω 025 =0.74); the rivaroxaban-itraconazole combination exhibited stronger signals for epistaxis ( Ω =2.01, Ω 025 =0.90) and hematoma ( Ω =1.93, Ω 025 =0.42); no positive Ω signals were observed for intracranial hemorrhage or upper gastrointestinal hemorrhage. CONCLUSION S This study suggests that the concomitant use of DOACs and triazole antifungals may increase the risk of bleeding-related events, with differences in signal strength and signal distribution across various drug combinations. In clinical practice, particular attention should be paid to the concomitant use of apixaban or rivaroxaban with strong cytochrome P450 3A4 or P-glycoprotein inhibitors such as posaconazole and itraconazole. For other DOAC-triazole antifungal combinations, close monitoring for bleeding-related manifestations and timely adjustment of anticoagulation or antifungal regimens are also warranted.
2.Culture and identification of rat corpus cavernosum smooth muscle cells by modified tissue block adherence method
Tao ZHANG ; Maobin YU ; Meijun LIU ; Ziyang MA ; Peihai ZHANG
Acta Universitatis Medicinalis Anhui 2026;61(1):113-117
ObjectiveTo establish an in vitro culture model of rat corpora cavernous smooth muscle cells (CCSMCs) using a modified tissue block adherence method. MethodsCorpus cavernosum smooth muscle tissue was digested with collagenase type I and subsequently cultured using an adherent method. Cells were purified via differential adhesion and identified through immunofluorescence and Western blotting. ResultsCCSMCs began to emerge from the tissue block after 3 days, increased significantly by day 7, and converged by day 12. Post-passage, CCSMCs exhibited strong proliferation and a “peak-to-valley” phenomenon. After purification, the cells tested positive for α-smooth muscle actin (α-SMA), confirming the successful establishment of the in vitro culture model. ConclusionThe modified tissue block adherence method is a cost-effective and efficient way to obtain high-purity CCSMCs.
3.Construction of whole-process management system for smart pharmacy based on the integration of traceability codes and drug batch numbers
Ziyang ZHANG ; Danyan SHAO ; Junjuan FAN ; Jian’an BAO ; Jingjing MA
China Pharmacy 2026;37(5):565-570
OBJECTIVE To construct a whole-process management system for the smart pharmacy based on the integration of drug batch numbers and traceability codes, aiming to solve the problems of low upload rates and traceability difficulties of drug traceability codes in the central pharmacy, and to enhance its level of refined management and medication safety. METHODS Following the FOCUS-PDCA framework(find,organize,clarify,understand,select-plan,do,check,act), a drug batch number and traceability code management system was established by optimizing batch number management processes, introducing “pre-scan registration” technology, and establishing a dynamic “code pool” mechanism. Based on medical insurance upload data and operational performance indicators in our hospital from June to August 2025, the differences in management efficacy before and after the implementation of the system were compared and analyzed. RESULTS The drug batch number and traceability code management system was successfully established, achieving “one-object, one-code” whole-process association with batch numbers for inpatient drugs, especially split drugs. After the application of this system, the upload rate of inpatient drug traceability codes reached 100%, significantly higher than the average upload rate of inpatient drugs in other tertiary hospitals in our city (with the highest rate being only 23.22%, P <0.001). The inventory stocktaking error rate dropped from 0.9% to 0.3% (a decrease of 66.7%); the number of daily dispensing errors decreased from 1.43 to 0.37; the dispensing time (14.75 min) for temporary medical orders recovered to the routine level (14.42 min) prior to the system implementation. CONCLUSIONS By adopting the “pre-scan registration-code pool management-closed-loop traceability” model, this system enables traceability for individual drug products in their smallest packaging units, improves the upload rate of traceability codes, significantly reduces the medication dispensing error rate, and does not increase the time cost for temporary medical order dispensing, thereby balancing efficiency with closed-loop traceability.
4.Clinical and Mechanistic Research Progress on Classical Traditional Chinese Medicine Formulas in Treatment of Chronic Heart Failure
Guo YANG ; Yan ZHANG ; Ziyang YUAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):256-265
Chronic heart failure (CHF) is a clinical syndrome characterized by impaired ventricular ejection function due to cardiac abnormalities, representing the terminal stage of most cardiovascular diseases. With its rising prevalence and significant impact on patients' quality of life, CHF has emerged as a major global public health concern. Current Western medicine treatments mainly involve the oral administration of the "new quadruple therapy" drugs and diuretics. Despite substantial progress in pathological research and clinical treatment, challenges persist, including considerable side effects, drug resistance, and marked interindividual variability in therapeutic response. Therefore, exploring and leveraging the advantages of traditional Chinese medicine (TCM) in treating CHF has become an urgent research priority. TCM has a millennia-long history in the prevention and treatment of heart failure, accumulating extensive clinical experience. Characterized by its multi-component and multi-target properties, TCM enables holistic regulation of multiple systemic functions and intervention in the progression of heart failure, demonstrating significant clinical relevance in its management. By employing therapeutic strategies such as warming Yang, promoting diuresis, replenishing Qi, nourishing Yin, and activating blood circulation, TCM effectively improves myocardial fibrosis, inhibits oxidative stress responses, enhances myocardial contractility, and ameliorates ventricular remodeling. Modern proprietary Chinese medicines derived from classic formulas, based on the theoretical foundation of traditional prescriptions, not only exhibit favorable clinical efficacy but also offer notable advantages in convenience, stability, and safety. This review systematically examined the significant therapeutic effects and underlying mechanisms of classical TCM formulas in the treatment of CHF, and provided an overview of the clinical application of modern proprietary Chinese medicines. It aims to provide new strategies for the clinical diagnosis and treatment of CHF.
5.Mechanism of Action of Main Active Components of Epimedii Folium in Treatment of Common Andrological Diseases: A Review
Tao ZHANG ; Maobin YU ; Jinkun QI ; Bailong JIANG ; Meijun LIU ; Ziyang MA ; Peihai ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):337-346
Andrological diseases have become an important public health problem threatening men's health worldwide, which significantly affects the quality of life of patients and brings a heavy disease burden. Western medicine often faces the dilemma of obvious side effects and limited efficacy. Traditional Chinese medicine has unique advantages in the prevention and treatment of andrological diseases and has accumulated rich clinical experience. Epimedii Folium, as a traditional Chinese medicine for strengthening kidney and Yang, exerts a key therapeutic effect on andrology diseases through multi-component synergy, multi-target regulation, and multi-pathway intervention. Recent studies have found that the main active components of Epimedii Folium, such as icariin, icariside, and icaritin, are the key material basis for the treatment of andrological diseases. The active components of Epimedii Folium can play a role in common andrological diseases such as erectile dysfunction, male infertility, and prostate cancer by regulating the activity of the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway, participating in oxidative stress response, regulating the secretion of hypothalamic-pituitary-gonadal axis hormones, improving spermatogenic dysfunction, and inhibiting the proliferation of cancer cells. However, the systematic action network and molecular mechanisms of the active components of Epimedii Folium have not been fully elucidated, thereby limiting its potential for clinical translation and application. In the future, it is necessary to combine cutting-edge technologies such as metabolomics, single-cell sequencing, and targeted nanoscale drug delivery systems, strengthening the research on the compatibility rules of active components and organ-specific delivery, providing a scientific basis for the development of innovative andrology traditional Chinese medicine formulas with international competitiveness, and promoting the innovation and breakthrough of andrology disease treatment modes.
6.Mechanism of Ferroptosis in Regulating Chronic Heart Failure and Traditional Chinese Medicine Prevention and Treatment Based on Qi Deficiency and Stagnation: A Review
Ziyang YUAN ; Yan ZHANG ; Wei ZHANG ; Yaqin WANG ; Wenjun MAO ; Guo YANG ; Xuewei WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):248-255
Chronic heart failure (CHF) is the final stage of cardiovascular diseases. It is a complex syndrome, with dyspnea and edema as the main clinical manifestations, and it is characterized by complex disease conditions, difficult cure, and high mortality. Ferroptosis, a new type of programmed cell death, is different from other types of programmed cell death. Ferroptosis is iron-dependent, accompanied by lipid peroxide accumulation and mitochondrial shrinkage, becoming a hot research topic. Studies have confirmed that ferroptosis plays a key role in the occurrence and development of CHF. The regulation of ferroptosis may become a potential target for the treatment of CHF in the future. The theory of Qi deficiency and stagnation refers to the pathological state of original Qi deficiency and abnormal transportation and distribution of Qi, blood, and body fluid, which has guiding significance for revealing the pathogenesis evolution of some chronic diseases. We believe that Qi deficiency and stagnation is a summary of the pathogenesis of ferroptosis in CHF. Deficiency of Qi (heart Qi) is the root cause of CHF, and stagnation (phlegm turbidity and blood stasis) is the branch of this disease. The two influence each other in a vicious circle to promote the development of this disease. Traditional Chinese medicine (TCM) plays an important role in the treatment of CHF, improving the prognosis and quality of life of CHF patients. This paper explores the correlation between the theory of Qi deficiency and stagnation and the mechanism of ferroptosis in CHF. Furthermore, this paper reviews the mechanism of Chinese medicines and compound prescriptions in preventing and treating CHF by regulating ferroptosis according to the principles of replenishing Qi and dredging to remove stagnation, aiming to provide new ideas and methods for the treatment of CHF with TCM.
7.Discovery of selective HDAC6 inhibitors driven by artificial intelligence and molecular dynamics simulation approaches
Xingang LIU ; Hao YANG ; Xinyu LIU ; Minjie MOU ; Jie LIU ; Wenying YAN ; Tianle NIU ; Ziyang ZHANG ; He SHI ; Xiangdong SU ; Xuedong LI ; Yang ZHANG ; Qingzhong JIA
Journal of Pharmaceutical Analysis 2025;15(8):1860-1872
Increasing evidence showed that histone deacetylase 6(HDAC6)dysfunction is directly associated with the onset and progression of various diseases,especially cancers,making the development of HDAC6-targeted anti-tumor agents a research hotspot.In this study,artificial intelligence(AI)technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline,which combined Voting strategy based on compound-protein interaction(CPI)prediction models,cascade molecular docking,and molecular dynamic(MD)simulations.The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays.Among the identified compounds,Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity(IC50=5.41 nM)than that of tubastatin A(TubA)(IC50=15.11 nM),along with a favorable subtype selectivity profile(selectivity index ≈ 117.23 for HDAC1),which was further verified by the Western blot analysis.Additionally,Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells,exerting desirable antiproliferative activity(IC50=2.59 μM).Furthermore,based on long-term MD simulation trajectory,the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis,thereby elucidating its binding mechanism.Moreover,the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation,thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.
8.A randomized controlled trial of value orientation brief therapy combined with selective serotonin reuptake inhibitors in mild to moderate depression
Ziyang JI ; Lijing SHI ; Yifang FU ; Yixuan ZHANG ; Meiqi SHAO ; Manyu HE ; Jiao DONG ; Fengju YAO ; Huiying WANG ; Changhong WANG
Chinese Mental Health Journal 2025;39(3):193-199
Objective:To evaluate the effect of value orientation brief therapy(VBT)combined with selective serotonin reuptake inhibitors(SSRIs)on clinical symptoms,rumination,decision-making ability,and cognitive func-tion in patients with mild to moderate depression.Methods:Eighty patients meeting the DSM-5 diagnostic criteria for mild to moderate depression were randomly assigned to either a medication(SSRIs)group(36 completed)or a VBT combined group(38 completed)for a 6-week intervention.Baseline and post-intervention assessments includ-ed the Hamilton Depression Scale(HAMD),Hamilton Anxious Scale(HAMA),Ruminative Response Scale-Chi-nese Version(RRS-CV),Iowa Gambling Test(IGT),number of eye fixation(NEF),responsive search score(RSS)in exploratory eye trajectory movement were used to evaluate patients'anxiety and depression symptoms,ru-minative thinking,decision-making function,and cognitive function.Results:The VBT combined group showed sig-nificantly better therapeutic effects than the medication group(P<0.05).Compared to baseline and the medication group,the VBT combined group had significantly lower post-intervention scores in HAMD,HAMA,symptom rumi-nation,introspective reflection,compulsive meditation,and RRS-CV total scores after intervention(Ps<0.05),and significantly higher scores in IGT net profit scores,NEF,and RSS scores(Ps<0.05).Compared with the medica-tion group,the VBT combined group demonstrated a greater reduction in HAMD,HAMA,symptom rumination,in-trospective reflection,compulsive meditation,and RRS-CV total scores before and after intervention(Ps<0.05),and a larger increase in IGT net profit scores,NEF,and RSS scores(Ps<0.05).Conclusion:VBT combined with SSRIs effectively improves the symptoms of depression,anxiety,decision-making ability,rumination thinking,and cognitive function in patients with mild to moderate depression.
9.Association of school bullying and psychological resilience with suicide attempts in children and adolescents with major depressive disorder
Kewen YAN ; Caiying ZHANG ; Ziyang HUANG ; Li XU ; Rushuang ZENG ; Die ZHANG ; Chengxia TANG ; Tong LI ; Yiling XIE ; Yaru CAO ; Linling JIANG ; Runxu YANG ; Yusan CHE ; Jin LU ; Yuanyuan XIAO
Chinese Mental Health Journal 2025;39(5):416-422
Objective:To explore the relationship between suicide attempts,school bullying,and psychological resilience in children and adolescents with major depressive disorder(MDD)and school bullying and psychological resilience.Methods:A total of 784 patients with MDD aged 10 to 18 years were included.The Chinese version of the Olweus Bullying Victimization Questionnaire,Adolescent Psychological Resilience Scale,and a suicide attempt assessment were utilized to evaluate school bullying,psychological resilience,and suicide attempt.Stepwise logistic regression was applied to identify the associated factors of suicide attempts.Results:The occurrence of suicide at-tempts in children and adolescents with MDD was positively associated with physical bullying(OR=1.85,95%CI:1.14-3.02)and indirect bullying(OR=1.48,95%CI:1.06-2.04),and negatively associated with higher levels of goal focus(OR=0.62,95%CI:0.45-0.85)and positive cognition(OR=0.62,95%CI:0.45-0.85)at higher levels.Conclusion:Bullying significantly increases the risk of suicide attempts in children and adolescents with MDD,while higher psychological resilience could mitigate this risk.
10.Progress of researchs on drug resistance mechanisms and clinical antimicrobial treatment of carbapenem-resistant Enterobacteriaceae infections
Lijuan LI ; Ziyang YUAN ; Haixing MO ; Lu ZHANG ; Lisha LAI ; Wenjin FU
Chinese Journal of Nosocomiology 2025;35(14):2219-2224
The drug resistance of the carbapenem-resistant Enterobacteriaceae(CRE)strains was mainly induced by multiple approaches such as production of carbapenemases,increase of bacterial outer membrane permeability,activation of active efflux pump system,formation of biofilm and drug modifying mechanisms.Those mecha-nisms involve deletion,mutation,insertion and posttranscriptional modification of relevant encoding genes,which may affect the susceptibility of the CRE strains to antibiotics.At present,the conventional clinical thera-pies include the use of traditional antibiotics,either the one-drug use or combined use of drugs.The development of novel antibacterial therapy is under way.The epidemiological characteristics of CRE infections,drug resist-ance mechanisms,current and prospective treatment strategies for CRE infections(covering new application of the drugs in available,the novel drugs such as ceftazidime/avibactam,meropenem/vaborbactam and imipenem/rele-bactam)were deeply reviewed in this article,so as to provide reliable reference for clinical prevention,control and treatment of CRE infections.

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