1.Pharmacovigilance Signal Mining and Analysis of Ustekinumab versus Upadacitinib for Inflammatory Bowel Disease Based on the FAERS Database
Dong XIE ; Yu WANG ; Haojia LIN ; Qiuyue TU ; Hetong ZHANG ; Huizhen LI ; Qinghua YI ; Zhengxiang LI ; Hengjie YUAN ; Xiaocang CAO
Medical Journal of Peking Union Medical College Hospital 2025;16(6):1376-1383
To analyze potential adverse drug events(ADEs) associated with ustekinumab and upadacitinib in the treatment of inflammatory bowel disease(IBD) based on an international authoritative database, thereby providing evidence for clinical medication safety. Data were extracted from the Food and Drug Administration Adverse Event Reporting System(FAERS) database using OpenVigil 2.1. ADE reports were collected for ustekinumab(from Q3 2017 to Q1 2025) and upadacitinib(from Q3 2019 to Q1 2025), where each drug was identified as the primary suspected medication for IBD. Signal detection and statistical analysis were performed using the reporting odds ratio(ROR) and proportional reporting ratio(PRR) methods. A total of 3648 ADE reports for ustekinumab and 3812 for upadacitinib, with each as the primary suspected drug in IBD treatment, were retrieved. Using the ROR-PRR combined detection method, relevant ADE signals were identified. High-frequency ADEs associated with ustekinumab included hypersensitivity reactions, various infections, and brain fog, while those associated with upadacitinib included acne, flatulence, and herpes zoster. System organ class(SOC) analysis of positive signals indicated that both drugs commonly caused ADEs in categories such as Infections and infestations, Gastrointestinal disorders, Nervous system disorders, Skin and subcutaneous tissue disorders, and Respiratory, thoracic, and mediastinal disorders. Among these, Infections and infestations were the most frequent SOC, involving preferred terms such as Escherichia sepsis and Pneumococcal pneumonia. Ustekinumab and upadacitinib exhibit distinct safety profiles in the treatment of IBD. In addition to known ADEs described in the prescribing information, ustekinumab requires close monitoring for hypersensitivity reactions, opportunistic infections, and potential neurological risks. For upadacitinib, attention should be paid to risks of acne, herpes zoster, hypercholesterolemia, and thrombotic events. These findings provide important safety information to support individualized clinical decision-making in IBD management.
2.Diffuse large B-cell lymphoma with pulmonary cryptococcosis: report of 1 case and review of literature
Caiqin LIN ; Suli WANG ; Shaoying PAN ; Dongsheng XIE ; Miaomiao TIAN ; Leina SONG ; Huijun LING ; Huizhen SHI ; Bin ZHU ; Zhiyong DING ; Wenli ZHAO
Journal of Leukemia & Lymphoma 2025;34(3):155-158
Objective:To improve the understanding of patients with diffuse large B-cell lymphoma (DLBCL) with pulmonary cryptococcosis.Methods:The clinical data of 1 DLBCL patient with pulmonary cryptococcosis in the Central Hospital of Fengxian District of Shanghai in May 2023 were retrospectively analyzed, and the relevant literatures were reviewed.Results:This 75-year-old female patient was asymptomatic after 2 cycles of R-CHOP chemotherapy. The high-resolution CT of lung showed that lung nodules were progressively enlarged. Antibacterial treatment was ineffective. Pulmonary cryptococcosis was confirmed by bronchoalveolar lavage fluid (BALF) targeted high-throughput sequencing (tNGS) and cryptococcus capsular antigen (CrAg) detection. The central nervous system was not involved. And the long-term adequate-dose fluconazole was prescribed for 6 months, and the treatment against lymphoma was given synchronously. The lung nodule lesions reduced after antifungal therapy for 1 month. The lung nodules disappeared after the follow-up of 6 months after completion of final chemotherapy. The evaluation of lymphoma indicated complete remission.Conclusions:Pulmonary cryptococcosis occurs insidiously and shows no specific symptoms; its imaging manifestations are variable and routine anti-infection is ineffective. Immunochemotherapy for lymphoma patients is a high-risk factor for cryptococcal infection. tNGS and CrAg testing for BALF are effective methods of the confirmed diagnosis. The early and long-term adequate-dose antifungal treatment is the key to preventing the recurrence or progression.
3.Development of a stratified training program for operating room nurses in tertiary hospitals based on the Delphi method
Huizhen WANG ; Jie ZHANG ; Linjuan ZHANG ; Jingjing AN ; Li MU ; Lin ZHAO ; Yuhong SUN
Basic & Clinical Medicine 2025;45(8):1116-1120
Objective To develop a tiered training framework for operating room nurses in tertiary hospitals,provi-ding guidance for corresponding training curriculum development and clinical competency evaluation.Methods Delphi method was used to conduct two rounds of expert consultation on the preliminary training indicators,estab-lishing a comprehensive tiered training framework for operating room nurses.Results After two rounds of expert consultation,a tiered training framework for operating room nurses was constructed,which includes 6 primary indi-cators,19 secondary indicators and 62 tertiary indicators.The response rate of the two rounds of expert consultation for valid questionnaires were all over 99%and the expert authority coefficients were all over 0.87.Conclusions The consulted experts have good enthusiasm and authority;the developed framework comprehensively covers training content,laying a foundation for designing and implementing tiered training programs for operating room nurses.
4.Methodological Consideration on Combination Model of TCM Clinical Practice Guidelines and Real-world Study
Guozhen ZHAO ; Huizhen LI ; Ning LIANG ; Haili ZHANG ; Bin LIU ; Qianzi CHE ; Feng ZHOU ; He LI ; Xiaowen CHEN ; Long YE ; Jiahao LIN ; Xingyu ZONG ; Dingyi WANG ; Nannan SHI ; Yanping WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):87-93
The clinical practice guidelines of traditional Chinese medicine (TCM) have problems such as limited clinical application and unclear implementation effects, which may be related to the lack of clinical practice evidence. To provide reliable and precise evidence for clinical practice, this article proposes a model of combining TCM guidelines with real-world study, which includes 4 steps. Firstly, during the implementation process of the guidelines, a high-quality research database is established. Secondly, the recommendations in the guidelines are evaluated based on the established database in multiple dimensions, including applicability, effectiveness, safety, and cost-effectiveness, and thus their effectiveness in practical applications can be determined. Thirdly, based on the established database, core prescriptions are identified, and the targeted populations and medication plans are determined. That is, the best treatment regimen is established based on the analysis of abundant clinical data regarding the effects of different medication frequencies, dosages, and duration on efficacy. Fourthly, the guidelines are updated according to the real-world evidence. The research based on this model can provide real-world evidence for ancient and empirical prescriptions, improving their application in clinical practice. Moreover, this model can reduce research costs and improve research efficiency. When applying this model, researchers need to pay attention to the quality of real-world evidence, ensuring that it can truly reflect the situation in clinical practice. In addition, importance should be attached to the clinical application of guideline recommendations, ensuring that doctors can conduct standardized diagnosis and treatment according to the guidelines. Finally, full-process participation of multidisciplinary experts is encouraged to ensure the comprehensiveness and scientificity of the study. In conclusion, the application of this model will contribute to the development of TCM guidelines responsive to the needs of clinical practice and achieve the goal of promoting the homogenization of TCM clinical diagnosis and treatment.
5.Key Techniques and Methodological Considerations for Formation of Traditional Chinese Medicine Syndrome Classification Standards
Guozhen ZHAO ; Xingyu ZONG ; Xueyao ZHAO ; Huizhen LI ; Feng ZHOU ; Xuanling ZENG ; Jiahao LIN ; Ning LIANG ; Haili ZHANG ; Qianzi CHE ; Bin LIU ; Nannan SHI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):257-261
The classification of traditional Chinese medicine (TCM) syndromes is one of the core technical elements in the industry standard of Specification of Diagnosis and Therapeutic Effect Evaluation of Diseases and Syndromes in TCM. In the past,when clinical standards for TCM were formulated,the determination of TCM syndrome classification relied heavily on textbooks and expert experience,lacking systematic research. This approach thus failed to reflect the advancement and scientificity of the standards,thereby affecting their implementation and application. This article reviewed the presentation forms and technical methods of TCM syndrome classification,including the two-tier syndrome classification model with primary and secondary symptoms,as well as the application of modern literature research,ancient literature research,Delphi method,in-depth expert interviews,consensus conferences,and real-world research. When syndrome classification standards are developed,it is necessary to build upon modern literature research,adopt a mixed approach combining qualitative research and quantitative analysis results,and reach expert consensus through consensus conferences. Through systematic research,the scientificity,applicability,and coordination of TCM syndrome classification standards can be enhanced,providing guidance for the standardization of TCM.
6.Expert consensus on limb management of patients with transvenous temporary cardiac pacing
Radioactive Interventional Nursing Professional Committee of Chinese Nursing Association ; Huafen LIU ; Jiali ZHOU ; Zheng HUANG ; Zhixia ZHANG ; Jingyu LIANG ; Zhongxiang CAI ; Fuhong CHEN ; Yunying ZHOU ; Yunyan XIANYU ; Lin YAN ; Huidan YU ; Huizhen PENG ; Jian ZHU ; Yuan TIAN ; Yan ZHANG ; Hejun JIANG ; Su ZHANG
Chinese Journal of Nursing 2024;59(13):1581-1583
Objective To form the expert consensus on the limb management of patients with transvenous temporary cardiac pacing,standardize the limb management of patients with transvenous temporary cardiac pacing,and reduce complications related to the limb.Methods Using evidence-based methods,the evidence in this field was searched,evaluated and summarized,and relevant recommendations and research conclusions were extracted and classified by the level of evidence quality,and then the first draft of the consensus was formed.From December 2023 to January 2024,through 2 rounds of expert consultation and 4 rounds of expert meetings,the content was adjusted and the consensus was reached.Results Totally 16 experts participated in the consultation.The positive coefficient is 100%;the authoritative coefficient is 0.847 and 0.836;the average value of each index is more than>3.8;the coefficient of variation is less than 0.21.The Kendall's harmony coefficient of the 2 rounds of expert consultation is 0.372 and 0.314,respectively,which were statistically significant.The consensus covers the preoperative,intraoperative and postoperative on limb management of patients with transvenous temporary cardiac pacing.Totally 11 themes were involved,including the preoperative preparation,position and catheter fixation in operation,position and catheter fixation in postoperative,activity,turn and transfer,duty shift on limb,nursing care after withdrawal of the catheter,prevention of deep vein thrombosis of the operative limb and prevent infection.Conclusion The consensus is highly scientific,and it is helpful to standardize the limb management of patients with transvenous temporary cardiac pacing.
7.Postoperative Patient-controlled Analgesia: Thirty Years of Clinical Experience in Peking Union Medical College Hospital
Lin ZHAO ; Liying REN ; Weihua NIE ; Yaqi CHEN ; Jie ZHANG ; Shengjie ZHANG ; Yingli WANG ; Cuicui DIAO ; Huiying MA ; Zheng ZHANG ; Li ZHOU ; Le SHEN ; Huizhen WANG ; Yuguang HUANG
Medical Journal of Peking Union Medical College Hospital 2024;15(2):239-245
Postoperative pain seriously affects the recovery process of patients, resulting in prolonged hospital stay and increased care costs. Appropriate application of patient-controlled analgesia devices can effectively relieve perioperative acute pain. In 1994 patient-controlled analgesia began to be used in Peking Union Medical College Hospital, and the Acute Pain Service Working Group was established in 2004. With the cooperation of anesthesiologists and specialist nurses, the group jointly has implemented the whole process and standardized management based on patient-controlled analgesia, and constantly improved and innovated working methods, laying a solid foundation for the development of postoperative pain management. This paper systematically reviews and summarizes the work from the aspects of clinical focus, nursing management experience, promotion and dissemination of pain treatment concepts, and development of acute pain service model under the new situation, with the hope of providing valuable reference for comprehensively strengthening pain management in the process of diagnosis and treatment, and enhancing patients' satisfaction with perioperative analgesia services.
8.Mechanism of Stemona tuberosa Alkaloids in Inhibiting Proliferation and Inducing Apoptosis of Non-small Cell Lung Cancer NCI-H460 Cells
Si LIN ; Huizhen QIN ; Liba XU ; Li LONG ; Hua ZHU ; Xiaoxun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(22):71-78
ObjectiveTo study the effect and underlying mechanism of Stemona tuberosa alkaloids on the proliferation and apoptosis of human non-small cell lung cancer NCI-H460 cells. MethodNon-small cell lung cancer NCI-H460 cells were divided into a blank group and S. tuberosa alkaloids groups (50, 100, 150, 200, and 250 mg·L-1). The effect of S. tuberosa alkaloids on the proliferation of human NCI-H460 cells was observed by thiazolyl blue tetrazolium bromide (MTT) assay and colony formation assay. Cell apoptosis was observed by Hoechst 33258 staining and flow cytometry. Real-time fluorescence-based polymerase chain reaction (Real-time PCR) was used to detect the effect of S. tuberosa alkaloids on the mRNA expression of cysteinyl aspartate-specific protease 3 (Caspase-3), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and epidermal growth factor receptor (EGFR). The protein expression levels of Caspase-3, Bax, Bcl-2, protein kinase B (Akt), phosphorylated (p-)Akt, EGFR, c-Jun N-terminal kinase (JNK), p-JNK, p38 mitogen-activated protein kinase (p38 MAPK), and p-p38 MAPK were measured by Western blot. ResultCompared with the blank group, the S. tuberosa alkaloids groups showed increased inhibition rate on cell proliferation (P<0.01), reduced number of cell clones formed and the rate of cell clonal formation (P<0.05, P<0.01), and increased karyopyknosis, cytoplasmic aggregation, and cell apoptosis rate (P<0.01). The S. tuberosa alkaloids groups at 100, 150, 200, and 250 mg·L-1 showed increased Caspase-3 mRNA expression (P<0.05), decreased EGFR mRNA expression (P<0.05, P<0.01), up-regulated protein expression of Caspase-3 and p-JNK (P<0.01), and down-regulated protein expression of EGFR and p-Akt (P<0.05, P<0.01). Additionally, compared with the blank group, the S. tuberosa alkaloids groups showed increased expression of Bax mRNA (P<0.01), decreased expression of Bcl-2 mRNA (P<0.01), up-regulated protein expression of Bax and p-p38 MAPK (P<0.01), and down-regulated protein expression of Bcl-2 (P<0.01). ConclusionsS. tuberosa alkaloids can inhibit proliferation and induce apoptosis of human non-small cell lung cancer NCI-H460 cells, and the mechanism may be related to the inhibition of EGFR protein expression and phosphorylation of Akt protein, as well as the activation of the JNK/p38 MAPK signaling pathway.
9.Effect of Stemona tuberosa Alkaloids on Apoptosis and PI3K/Akt and JNK/MAPK Signaling Pathways of Human Lung Cancer A549 Cells
Si LIN ; Huizhen QIN ; Zeyu LI ; Liba XU ; Lingyu DENG ; Jing LUO ; Fengfeng XIE ; Miao ZHANG ; Hua ZHU ; Xiaoxun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(4):69-76
ObjectiveTo investigate the effect of Stemona tuberosa alkaloids (STA) on apoptosis and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and c-Jun N-terminal kinase/p38 mitogen-activated protein kinase (JNK/p38 MAPK) signaling pathways in human lung cancer A549 cells. MethodA549 cells were classified into blank group and STA groups (100, 150, 200, 250, 300 mg⋅L-1). Thiazole blue (MTT) assay and colony formation assay were used to evaluate the proliferation of A549 cells. Apoptosis was observed based on Hoechst 33258 staining, flow cytometry, and Annexin V-FITC/PI staining. Western blot was employed to detect the expression of apoptosis-related proteins cysteine-aspartic acid protease-3 (Caspase-3), B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax), and Bcl-2, and the expression of PI3K, phosphorylated (p)-PI3K, Akt, p-Akt, JNK, p-JNK, p38 MAPK, and p-p38 MAPK. ResultCompared with the blank group, STA groups (150, 200, 250, 300 mg⋅L-1) demonstrated the increase in inhibition rate of cell proliferation (P<0.01) and cell clone inhibition rate, and decrease in cell clone formation rate (P<0.01). In comparison with the blank group, STA groups showed typical characteristics of apoptosis, such as chromatin condensation and enhanced fluorescence reaction. The apoptosis rate of STA groups was significantly higher than that of the blank group (P<0.01). Compared with the blank group, STA (150, 200, 250, 300 mg⋅L-1) significantly up-regulated the protein expression of Caspase-3 and Bax (P<0.05, P<0.01) and down-regulated the expression of Bcl-2 protein (P<0.01). Compared with the blank group, STA had no significant influence on the total protein expression of PI3K, Akt, JNK, and p38 MAPK. However, STA (150, 200, 250, 300 mg⋅L-1) significantly decreased the levels of p-PI3K and p-Akt (P<0.05, P<0.01) and increased the level of p-p38 MAPK (P<0.05, P<0.01). Compared with the blank group, STA (200, 250, 300 mg⋅L-1) significantly raised the level of p-JNK (P<0.05, P<0.01). ConclusionSTA can inhibit the proliferation and induce the apoptosis of A549 cells by inhibiting PI3K/Akt signaling pathway and activating JNK/p38 MAPK signaling pathway.
10.Research progress of pharmacological action and mechanism of piperine
Si LIN ; Huizhen QIN ; Lingyu DENG ; Miao ZHANG ; Fengfeng XIE ; Zeyu LI ; Hua ZHU
China Pharmacy 2022;33(13):1653-1659
Piperine is a kind of amide alkaloids presenting in Piper nigrum L.,which has the pharmacological action such as protecting cardiovascular system ,regulating glucose and lipid metabolism ,anti-tumor,improving nervous system diseases , anti-inflammation and so on. This paper summarized the pharmacological action and mechanisms of piperine in recent years and found that piperine ,as the main active ingredient of P. nigrum ,could protect the cardiovascular system by reducing inflammation and oxidative stress ;improve mitochondrial function through anti-inflammatory and antioxidant effects ,thereby regulate glucose and lipid metabolism ;play an anti-tumor role by mediating the signaling pathways of Wnt/β-catenin,NF-κB/Nrf-2/KeAP-1/HO-1, PI3K/Akt,TGF-β1/Smad2/ERK1/2;improve neurological diseases by inhibiting autophagy ,relieving inflammation ,improving antioxidant,inhibiting neuronal apoptosis and regulating the expression of related proteins in neurons ;play an anti-inflammatory effect by inhibiting the activity of NF-κB and other signaling pathways and reducing the expression of inflammation-related proteins. However,the mechanism of action of piperine is not perfect ,and most of the studies have been confined to the pharmacological level or a certain signaling pathway and a certain target ,without being able to elucidate the interconnection between the relevant signaling pathway and the specific target from a holistic perspective. In the follow-up ,the specific targets of piperine can be identified and clinical trials can be carried out to provide support for the clinical application of piperine.

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