1.Exploring Therapeutic Effect of Yuejuwan on Depressed Mice Based on Lipidomics
Zhentao ZHANG ; Dan SU ; Huizhen LI ; Yonggui SONG ; Huanhua XU ; Meixizi LAI ; Zhifu AI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):85-94
ObjectiveTo investigate the effect of Yuejuwan on lipid metabolism in serum, prefrontal cortex and hippocampus of depressed mice based on lipidomics, and to explore the potential pathways for improving lipid metabolism to prevent depression. MethodsSeven-week-old C57BL/6 mice were randomly divided into blank group, model group, Yuejuwan group(3.6 g·kg-1) and fluoxetine group(10 mg·kg-1), and chronic unpredictable mild stress(CUMS) was used to establish the depression model. After 3 weeks of modeling, each administration group was gavaged with the corresponding drug solution according to the dose, and mice in the blank and model groups were given an equal volume of deionised water by gavage, one time/d for 2 weeks. After administration, the antidepressant effect of Yuejuwan was evaluated by neurobehavioral indices such as sucrose preference test, open field test, tail suspension test and forced swimming test. An automatic biochemical analyzer was used to measure contents of total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in mouse serum. Lipidomic analysis of mouse serum, prefrontal cortex and hippocampus was performed based on ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap mass spectrometry(UPLC-LTQ-Orbitrap-MS), and the expression of mammalian target of rapamycin(mTOR), ribosomal protein S6 kinase(S6K), phosphorylation(p)-mTOR, p-S6K in gastric tissues of mice was detected by Western blot. ResultsCompared with the blank group, mice in the model group exhibited significantly reduced sucrose preference rate and center movement time in the open field test(P<0.01), the immobility times in the tail suspension test and forced swimming test were significantly increased(P<0.01), and serum levels of TC, TG, LDL-C, HDL-C, AST and ALT were significantly elevated(P<0.05, P<0.01). Compared with the model group, the Yuejuwan group showed a significant increase in the sucrose preference rate and center movement time in the open field test(P<0.01), the immobility times in the tail suspension test and forced swimming test were significantly reduced(P<0.01), and the serum levels of TC, TG, LDL-C, AST and ALT were significantly decreased(P<0.05, P<0.01). Lipidomic analysis revealed that Yuejuwan had a significant effect on lipid metabolism in serum, prefrontal cortex and hippocampus of depressed mice, and The differential lipid metabolites were mainly enriched in the metabolic pathways of glycerophospholipid metabolism, sphingolipid signaling, and glycosylphosphatidylinositol-anchored protein biosynthesis, among which the glycerophospholipid metabolic pathway was the most significant. Western blot results showed that compared with the blank group, the relative expression levels of p-mTOR/mTOR and p-S6K/S6K in the gastric tissues of mice in the model group were significantly increased(P<0.01). In comparison with the model group, the relative expression levels of p-mTOR/mTOR and p-S6K/S6K in the gastric tissues of mice in the Yuejuwan group were significantly decreased(P<0.01). ConclusionThe intervention of Yuejuwan on lipid metabolism is one of the potential pathways for its antidepressant effect, which may be related to the regulation of mTOR/S6K signaling pathway upstream of lipid metabolism in the gastric tissues.
2.Textual Research of Key Information of Classic Formula Xieqingwan Based on Ancient and Modern Literature
Yujie CHANG ; Lyuyuan LIANG ; Jialei CAO ; Xinghang LYU ; Wenxi WEI ; Xiaofang WANG ; Huizhen ZHANG ; Sai REN ; Mengqi WANG ; Bingqi WEI ; Bingxiang MA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):226-234
ObjectiveThis paper aims to systematically collect and organize ancient and modern clauses and studies containing Xieqingwan, excavate and analyze the key information of Xieqingwan, and provide a reference for facilitating the development of the classic formula Xieqingwan. MethodsThe composition, dosage, decocting methods, usage, and other key information of Xieqingwan in ancient traditional Chinese medicine books were collected and analyzed by means of literature research and metrological methods. The modern clinical application of Xieqingwan was summarized. ResultsA total of 42 pieces of effective data involving 32 ancient traditional Chinese medicine books were collected. Xieqingwan was first recorded in Xiaoer Yaozheng Zhijue. The drug origin of this formula is basically clear in the ancient traditional Chinese medicine books. The modern drug usage and decocting method were as follows: Angelicae Sinensis Radix, Gentianae Radix et Rhizoma, Chuanxiong Rhizoma, Gardenia seeds, Radix et Rhizoma Rhei, Notopterygii Rhizoma et Radix, and Saposhnikoviae Radix were grounded to fine powder, decocted with honey, and finally formed into pills with the size of a chicken head (1.5 g). It was suggested that half a pill or one pill were taken for one dose with warm Lophatheri decoction and sugar. The indications and clinical application had developed from the recordings in Xiaoer Yaozheng Zhijue and evolved from pediatrics to ophthalmic otolaryngology, neurology, dermatology, digestion, and respiratory diseases. The main pathogenesis of these diseases is heat in the liver meridian and is treated. The effect of Xieqingwan is "clearing away heat and toxicity, removing fire and relaxing the bowels, and dispersing swelling and relieving pain". It is recommended to use the corresponding preparation methods in the 2020 Edition of Pharmacopoeia of the People's Republic of China. Modern clinical studies are centered around the clinical application of Xieqingwan, which is often modified and used in treating Tourette syndrome, herpes, febrile convulsion, sleepwalking, and insomnia. ConclusionThis paper conducts a thorough textual research of the key information of Xieqingwan, induces its historic evolution, and confirms its key information, so as to provide a reference for the future development of Xieqingwan.
3.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.
4.Association between the transverse area of vertical spinal muscle at T 12 level and prognosis in elderly patients with acute coronary syndrome
Huizhen LIU ; Hongxia ZHANG ; Na SHANG ; Na WANG ; Junyu LI ; Guodong WANG
Chinese Journal of Emergency Medicine 2024;33(7):963-967
Objective:To analyze the association between the transverse area of erector spine muscle at T 12 level and prognosis in elderly patients with acute coronary syndrome (ACS). Methods:This was a prospective cohort study. Clinical data of elderly patients with ACS admitted to the coronary care unit or the emergency intensive care unit in Beijing Bo'Ai Hospital from January 2019 to June 2022. Blood routine and biochemical indicators were detected and echocardiography was performed within 24 hours after admission, chest CT examination was completed and the cross-sectional areas of the left and right vertical spinalis muscles were calculated at T 12 level, thrombolysis in myocardial infarction (TIMI) was performed within 24 hours after admission. The occurrence of major adverse cardiovascular and cerebral events (MACCE) within 12 months was followed up. The differences of clinical data and laboratory indexes between the MACCE group and the non-MACCE group were compared. Multivariable logistic regression model was used to analyze the association between the cross-sectional area of vertical spinal muscle at T 12 level and the occurrence of MACCE within 12 months after ACS. Results:A total of 406 patients were enrolled in the study, the incidence of MACCE within 12 months was 22.2%. The cross-sectional area of erector spine muscle at T 12 level [(20.43±3.51) cm 2vs. (24.36±3.66) cm 2, (Z=4.412, P<0.001)] in the MACCE group was lower than that in the non-MACCE group. Logistic regression analysis showed that after adjusting for sex, age, body mass index (BMI), TIMI score and revascularization, the cross-sectional area of erector spine muscle at T 12 level ( OR = 0.883, 95% CI: 0.803-0.971, P=0.010) was independently associated with MACCE within 12 months after ACS. Conclusion:The transverse area of vertical spinal muscle at T 12 level can be used as an independent predictor of MACCE within 12 months in elderly patients with ACS.
5.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.
6.Exploration of Value Variable Selection and Measurement for Chinese Patent Medicine Based on Hedonic Price Theory
Yijiu YANG ; Haili ZHANG ; He ZHU ; Wei LI ; Zhao CHEN ; Bin LIU ; Ning LIANG ; Huizhen LI ; Tian SONG ; Wenjie CAO ; Weili WANG ; Ziteng HU ; Yanping WANG ; Sheng HAN ; Nannan SHI
Chinese Health Economics 2024;43(5):68-71,78
To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.
7.Exploration of Value Variable Selection and Measurement for Chinese Patent Medicine Based on Hedonic Price Theory
Yijiu YANG ; Haili ZHANG ; He ZHU ; Wei LI ; Zhao CHEN ; Bin LIU ; Ning LIANG ; Huizhen LI ; Tian SONG ; Wenjie CAO ; Weili WANG ; Ziteng HU ; Yanping WANG ; Sheng HAN ; Nannan SHI
Chinese Health Economics 2024;43(5):68-71,78
To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.
8.Medium to low intensity exercise interferes with the expression of LncRNA HOTAIR in chondrocytes in high-fat-fed mice with knee joint damage
Huizhen ZHANG ; Wei WU ; Haitao LUO
Chinese Journal of Tissue Engineering Research 2024;28(11):1684-1689
BACKGROUND:Low to moderate intensity aerobic exercise can help protect knee cartilage.Long-chain non-coding RNAs are crucial for gene regulation.Among them,HOTAIR can activate numerous transcriptional co-repressors to repress the activation of certain genes. OBJECTIVE:To detect the expression levels of HOX transcript antisense RNA(HOTAIR)and other related factors in chondrocytes of high fat-fed mice and after low to moderate intensity exercise intervention,and to investigate their role in cartilage injury and sports rehabilitation. METHODS:Thirty C57BL/6 male mice were randomly divided into control group(normal feeding),high fat feeding group and high fat feeding plus treadmill exercise group,with 10 mice in each group.The mice in the high fat feeding plus treadmill exercise group were subjected to an 8-week low to middle intensity treadmill exercise,and the mice in the other two groups were caged.During this period,body mass was weighed every week on Sunday.After the 8-week exercise,both lower extremities of mice were taken,and the knee joint was scanned using Micro CT to make a 3D femoral condyle image to obtain relevant parameters.Hematoxylin-eosin and safranin O-fast green staining of the knee joint were performed for Mankin and Osteoarthritis Research Society International(OARSI)scoring.RT-PCR was performed to detect the mRNA levels of cartilage metabolic indicators and lipid metabolism indicators,including type II collagen,matrix metalloproteinase 13,interleukin 1,low-density lipoprotein receptor-related protein 5,HOTAIR and its downstream factor lysine specific demethylase 1. RESULTS AND CONCLUSION:The body mass of high fat-fed mice were higher than that of the control group(P<0.01),and the body mass of the high fat feeding plus treadmill exercise group was lower than that of the high fat feeding group(P<0.05).The connectivity density of high fat-fed mice was higher than that of the control group(P<0.01).Mankin and OARSI scores of the high fat feeding were higher than those of the control group(P<0.01)and high fat feeding plus treadmill exercise group(P<0.05).The mRNA level of type II collagen was higher in the control group than the high fat feeding plus treadmill exercise group(P<0.05)and high fat feeding group(P<0.01)as well as higher in the high fat feeding plus treadmill exercise group than the high fat feeding group(P<0.01).The mRNA levels of matrix metalloproteinase 13,interleukin 1,low-density lipoprotein receptor-related protein 5,HOTAIR and lysine specific demethylase 1 were higher in the high fat feed group than the control group and high fat feeding plus treadmill exercise group(P<0.01).To conclude,high fat feeding can increase the bone substance of the femoral condyle,lead to knee cartilage wear,and cause chondrocyte metabolism disorder.HOTAIR is highly expressed in this process.An 8-week low to middle intensity treadmill exercise can reduce body mass,alleviate knee cartilage wear,improve chondrocyte function and down-regulate HOTAIR expression in mice.
9.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.
10.Methods and Challenges for Identifying and Controlling Confounding Factors in Traditional Chinese Medicine Observational Studies
Guozhen ZHAO ; Ziheng GAO ; Chen ZHAO ; Huizhen LI ; Ning LIANG ; Bin LIU ; Qianzi CHE ; Haili ZHANG ; Yixiang LI ; Feng ZHOU ; He LI ; Bo LI ; Nannan SHI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):120-126
As a supplement to randomized controlled trials, observational studies can provide evidence for the effectiveness of traditional Chinese medicine (TCM) treatment measures. They can also study influencing factors of diseases, etiology, and prognosis. However, there is a confounding effect due to the lack of randomization, which seriously affects the causal inference between the study factors and the outcome, resulting in confounding bias. Therefore, identifying and controlling confounding factors are key issues to be addressed in TCM observational studies. According to the causal network and the characteristics of TCM theory, confounding factors can be categorized into measured and unmeasured confounding factors. In addition, attention must be paid to identifying confounding factors and intermediate variables, as well as the interaction between confounding factors and study factors. For methods of controlling confounding factors, measured confounding factors can be controlled by stratification, multifactor analysis, propensity scores, and disease risk scores. Unmeasured and unknown confounding factors can be corrected using instrumental variable methods, difference-in-difference methods, and correction for underlying event rate ratios. Correcting and controlling confounding factors can ensure a balance between groups, and confounding bias can be reduced. In addition, methods such as sensitivity analysis and determination of interactions make the control of confounding factors more comprehensive. Due to the unique characteristics of TCM, observational studies of TCM face unique challenges in identifying and controlling confounding factors, including the ever-changing TCM treatment measures received by patients, the often-overlooked confounding effects in the four diagnostic information of TCM, and the lack of objective criteria for TCM evidence-based diagnosis. Some scholars have already conducted innovative explorations to address these issues, providing a methodological basis for conducting higher-quality TCM observational studies, so as to obtain more rigorous real-world evidence of TCM and gradually develop quality evaluation criteria for OS that are consistent with the characteristics of TCM.

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