1.Expert Consensus on Clinical Application of Pingxuan Capsules
Yuer HU ; Yanming XIE ; Yaming LIN ; Yuanqi ZHAO ; Yihuai ZOU ; Mingquan LI ; Xiaoming SHEN ; Wei PENG ; Changkuan FU ; Yuanyuan LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):201-210
As a patented characteristic medicine of Yi ethnic minority, Pingxuan capsules have the effects of nourishing the liver and kidney, pacifying the liver, and subduing Yang. With the main indications of dizziness, headache, palpitations, tinnitus, insomnia, dreaminess, waist and knee soreness caused by liver-kidney deficiency and liver Yang upward disturbance, Pingxuan capsules are widely used in the treatment of posterior circulation ischemic vertigo, vestibular migraine, benign paroxysmal positional vertigo. However, the current knowledge is limited regarding the efficacy, syndrome differentiation, and safety of this medicine. On the basis of summarizing the experience of clinicians and the existing evidence, this study invites clinical experts of traditional Chinese and Western medicine, pharmaceutical experts, and methodological experts from relevant fields across China to conduct evidence-based evaluation of Pingxuan capsules. The evaluation follows the Specifications for the Development of Clinical Expert Consensus on Chinese Patent Medicines issued by the Standardization Office of the China Association of Chinese Medicine, and reaches 5 recommendations and 16 consensus suggestions. The consensus clarifies the clinical applications, efficacy, dose, course of treatment, combination of medicines, precautions, and contraindications of Pingxuan capsules in the treatment of vertigo and explains the safety of clinical application. This consensus is applicable to clinicians (traditional Chinese medicine, Western medicine, and integrated traditional Chinese and Western medicine) and pharmacists in tertiary hospitals, secondary hospitals, and community-level medical and health institutions across China, providing a reference for the rational use of Pingxuan capsules in the treatment of vertigo. It is hoped that the promotion of this consensus can facilitate the rational use of drugs in clinical practice, reduce the risk of drug use, and give full play to the advantages of Pingxuan capsules in the treatment of vertigo diseases. This consensus has been reviewed and published by the China Association of Chinese Medicine, with the number GS/CACM330-2023.
2.Systematic review of pharmacoeconomic evaluation on PCSK9 inhibitors for the prevention of cardiovascular disease in patients with hypercholesterolemia
Yuanyuan FU ; Jiancheng ZHOU ; Ying ZOU ; Luying WANG ; Pingyu CHEN ; Yongqing WANG
China Pharmacy 2024;35(8):972-979
OBJECTIVE To systematically review the pharmacoeconomic evaluation literature about proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors for the prevention of cardiovascular disease in patients with hypercholesterolemia, and to provide a reference for clinical treatment, health decision-making and future follow-up research. METHODS Retrieved from English and Chinese databases such as PubMed and CNKI, the pharmacoeconomic literature about PCSK9 inhibitors (evolocumab and alirocumab) for the prevention of cardiovascular disease in patients with hypercholesterolemia was collected from the establishment of the database to October 8, 2023. The quality of the included literature was assessed with Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) scale. The descriptive analysis was performed for basic information, model structure, related parameters, sensitivity analysis and the results of included studies. RESULTS & CONCLUSIONS A total of 29 literature were included, with overall good quality. The evaluation mainly adopted the Markov model from the healthcare system, payer and societal perspective. The effectiveness and utility data mainly came from the previous studies; the direct cost was mainly considered with a discount rate of 1.5%-5.0% per year, while the willingness-to-pay threshold was often set at 1-3 times the gross domestic product per capita. Most health output indicators were measured in life years and quality-adjusted life years. The sensitivity analysis of most studies demonstrated the robustness and the main influential factor was the drug cost. Most Chinese studies showed that PCSK9 inhibitor was not cost-effective for the prevention of cardiovascular disease in patients with acute coronary syndrome, myocardial infarction and atherosclerotic cardiovascular disease. It was cost-effective to use PCSK9 inhibitors for the prevention of cardiovascular disease only in specific groups, such as patients with triple vessel disease, patients with newly diagnosed acute coronary syndrome and low-density lipoprotein cholesterol≥100 mg/dL. Future research should refer to the CHEERS 2022 scale to improve the design, and strive to select large-scale, high-quality data to enhance the quality of reports and the transparency of health decisions, so as to more accurately assess the cost-effectiveness of PCSK9 inhibitors.
3.Immediate Effects of Acupuncture at Yanglingquan on Functional Connectivity of Brain Network in Patients with Stroke and Hemiplegia
Chen CHEN ; Kuangshi LI ; Xin YU ; Linlu WU ; Tianzhu CHEN ; Kang WU ; Yuanyuan LI ; Xinyue SHI ; Yihuai ZOU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(3):149-154
Objective To compare the immediate effects of acupuncture at the true and false acupoints of Yanglingquan on functional connectivity in sensorimotor network(SMN)and dorsal attentional network(DAN)of stroke patients based on functional magnetic resonance imaging(fMRI)technology;To explore the central regulatory mechanism and acupoint specificity of acupuncture in stroke patients with hemiplegia.Methods Totally 20 patients with stroke and hemiplegia were included in the study.fMRI scans of acupuncture at the true and false acupoints of Yanglingquan were performed once every 2 weeks,and motion-related SMN and DAN were extracted by independent component analysis to compare the differences in functional connectivity.Results In SMN,after acupuncture at the Yanglingquan true acupoint,the functional connectivity was enhanced compared with before acupuncture.The enhanced brain areas included the right anterior central gyrus,superior temporal gyrus,inferior frontal gyrus,cuneiform lobe,and anterior cuneiform lobe,as well as the left middle temporal gyrus,occipital gyrus,superior temporal gyrus,parahippocampal gyrus,inferior frontal gyrus,and superior temporal gyrus.After acupuncture at the Yanglingquan false acupoint,the functional connectivity was enhanced compared with before acupuncture.The enhanced brain areas included the right anterior central gyrus,superior frontal gyrus,middle frontal gyrus,and cingulate gyrus,as well as the left medial frontal gyrus,anterior cingulate gyrus,lentiform nucleus,and caudate nucleus.In DAN,after acupuncture at the Yanglingquan true acupoint,the functional connectivity was enhanced compared with before acupuncture.The enhanced brain areas included the right anterior cingulate lobe,superior temporal gyrus,middle temporal gyrus,and occipital gyrus,as well as the left cingulate gyrus,posterior cingulate gyrus,and anterior cingulate lobe.After acupuncture at the Yanglingquan false acupoint,the functional connectivity was enhanced compared with before acupuncture,and the enhanced brain areas included the right anterior cingulate gyrus,left anterior cingulate gyrus,and medial frontal gyrus.Conclusion Acupuncture at Yanglingquan can activate SMN and DAN bilateral related brain regions in patients with hemiplegia,which may promote the recovery of motor function by regulating the initiation and execution of motor activities,and has more acupoint specificity compared with false acupoint.
4.Effect of hyodeoxycholic acid on the activity of steatosis hepatocytes and its mechanism
Yuanyuan WANG ; Yan ZOU ; Zhaoxia LIU ; Xuefeng YANG
Journal of Clinical Hepatology 2024;40(2):292-297
ObjectiveTo investigate the role and mechanism of hyodeoxycholic acid (HDCA) in the progression of metabolic associated fatty liver disease (MAFLD), and to provide a new theoretical basis for further clarifying the pathogenesis of MAFLD. MethodsL02 hepatocytes were used as experimental cells, and palmitic acid was used to induce steatosis in L02 cells. The farnesoid X receptor (FXR) siRNA interference chain technique was used to construct a hepatocyte cell line with low FXR expression. CCK8 assay was used to observe the effect of HDCA on L02 steatosis hepatocytes at different concentrations (0, 100, 200, 300, and 400 μmol/L) and time points (12, 24, 36, and 48 hours). The method of qRT-PCR was used to measure the mRNA expression levels of FXR, proliferating cell nuclear antigen (PCNA), Cyclin D1, phosphatidylinositol 3-kinase (PI3K), and protein kinase-B (AKT), and Western blot was used to measure the protein expression levels of FXR, Cyclin D1, PCNA, PI3K, phosphorylated PI3K (p-PI3K), AKT, and phosphorylated (p-AKT). A one-way analysis of variance was used for comparison of normally distributed continuous data with homogeneity of variance between multiple groups, and the Tukey HSD test was used for further comparison between two groups; the Welch analysis of variance was used for comparison of normally distributed continuous data with heterogeneity of variance between multiple groups, and the Games-Howell test was used for further comparison between two groups. The independent-samples t test was used for comparison between two groups. ResultsCCK8 assay showed a significant reduction in the viability of L02 cells and steatosis hepatocytes treated by 300 μmol/L HDCA (P<0.05), and qRT-PCR showed a significant increase in the mRNA expression level of FXR and significant reductions in the mRNA expression levels of PCNA, Cyclin D1, PI3K, and AKT (all P<0.05). Western blot showed a significant increase in the protein expression level of FRX (P<0.05), and after interference of FXR expression in L02 cells, there were significant increases in the protein expression levels of PCNA, PI3K, p-PI3K, AKT, and p-AKT (all P<0.05). ConclusionHDCA inhibits the PI3K/AKT signaling pathway by upregulating FXR expression, thereby inducing a reduction in the viability of steatosis hepatocytes.
5.Infiltration and immunosuppressive function of tumor-associated B cells in gastric cancer patients
Yuxian LI ; Zhenquan DUAN ; Ying WANG ; Xueling TAN ; Xiaohong YU ; Yuanyuan ZHANG ; Baohang ZHU ; Yuan QIU ; Liusheng PENG ; Quanming ZOU
Journal of Army Medical University 2024;46(9):1034-1040
Objective To investigate the distribution of B cells in both tumor and non-tumor tissues of gastric cancer patients,analyze their phenotypic characteristics and explore the impact on T cell proliferation.Methods Immunohistochemical staining was utilized to detect the expression of B cell surface marker CD 19 in tumor and non-tumor tissues from 33 gastric cancer patients.The expression levels of chemokine receptors and immunoglobulin molecules on B cells in both tumor and non-tumor tissues were measured using flow cytometry.Chemotaxis experiments were conducted to examine the role of the CXCL12-CXCR4 axis in B cell chemotaxis.B cells isolated and purified from both tissue types were co-cultured with autologous peripheral T cells to assess their effect on T cell proliferation.Results There were significantly more B cells infiltrated in tumor tissues than those infitrated in the non-tumor tissues of gastric cancer patients(P<0.01),and CXCR4 was highly expressed on tumor-infiltrating B cells compared with B cells derived from non-tumor tissues(P<0.05).The Cancer Genome Atlas(TCGA)analysis indicated that the expression level of CXCL12 in tumor tissues was positively correlated with the expression level of CD19 in gastric cancer patients(r=0.15,P<0.01).And the expression level of CXCL12 in tumor tissues of the gastric cancer patients was also positively correlated with the number of B cells infiltrated in tumor tissues.Chemotaxis experiments confirmed that the CXCL12-CXCR4 axis was involved in promoting B cell chemotaxis(P<0.05).Although B cells in tumor and non-tumor tissues had similar levels of IgM,IgG,and IgA expression,tumor-infiltrating B cells significantly inhibited the proliferation of T cells when compared with B cells derived from non-tumor tissues(P<0.01).Conclusion There are more B cells infiltrated in gastric cancer tissues,which may be recruited to tumor tissues through the CXCL12-CXCR4 axis,and then inhibit T cell proliferation to promote the progression of gastric cancer.
6.Effects of Tai Chi Chuan on Voxel-mirrored Homotopic Connectivity in Patients with Chronic Fatigue Syndrome
Yuanyuan LI ; Kuangshi LI ; Kang WU ; Xiaojie HU ; Tianjiao XU ; Renzhao MA ; Tianzhu CHEN ; Yi REN ; Yihuai ZOU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(9):139-144
Objective To compare the changes of brain voxel-mirrored homotopic connectivity(VMHC)of patients before and after Tai Chi Chuan training based on functional magnetic resonance imaging(fMRI)technology;To discuss the central effect mechanism of Tai Chi Chuan in treating chronic fatigue syndrome(CFS).Methods A total of 25 CFS patients(experiment group)and 27 healthy individuals(control group)were recruited to undergo a 1-month Tai Chi Chuan intervention.All receive one month of Tai Chi Chuan training.Differences in SF-36 scores and VMHC between CFS patients and HCs were compared.Results Before training,the SF-36 scores in the experimental group were significantly lower than those in the control group(P<0.001),and the VMHC in the bilateral inferior occipital gyrus,paracentral lobule,lingual gyrus,insula and superior temporal gyrus brain areas were weakened.After training,the scores of SF-36 in the experimental group significantly increased(P<0.001),and the VMHC in bilateral inferior occipital gyrus,superior temporal gyrus,anterior cuneiform lobe and paracentral lobule were significantly enhanced.The difference in whole brain VMHC was positively correlated with the difference in energy scores in SF-36(r=0.456,P=0.025);some scores of SF-36 in the control group significantly increased(P<0.05),and no significant changes in VMHC were observed in brain regions.Conclusion Tai Chi Chuan can effectively improve the quality of life of patients with CFS.This change may be related to the enhancement of functional connections in brain regions such as inferior occipital gyrus,superior temporal gyrus,precuneus,paracentral lobule,et al.
7.Exploration of the Mechanism of Huoxiang Zhengqi Dropping Pills Based on GC-TOF/MS Metabolo-mics Technology in Rats with Dampness Encumbering the Spleen and Stomach Type
Lixi LI ; Hailong LU ; Zhongjie ZOU ; Yuanyuan XIE ; Mengjuan GONG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(6):771-777
Objective To explore the mechanism of Huoxiang Zhengqi Dropping Pills in treating dampness encumbering the spleen and stomach type rats by metabolomics method based on gas chromatography-time of flight mass spectrometry(GC-TOF/MS).Methods Male SD rats were randomly divided into normal group,model group and Huoxiang Zhengqi Dropping Pills group(1 g·kg-1).The rat model of dampness encumbering the spleen and stomach was prepared by comprehensive physical modeling method combined with improper diet.Intragastric administration was performed once a day for 10 consecutive days.The macroscopic signs and behavioral indexes(body mass,body length,tail length,abdominal circumference index and spontaneous activities frequency)of rats were observed.GC-TOF/MS method was used to analyze the serum and urine metabolome of rats,identify potential biomarkers related to dampness encumbering the spleen and stomach,and analyze the metabolic pathway of Huoxiang Zhengqi Dropping Pills in rats with dampness encumbering the spleen and stomach.Results Compared with the normal group,the body mass,body length,tail length and spontaneous activities frequency of the rats in the model group were significantly reduced(P<0.05),and the abdominal circumference index was significantly increased(P<0.05).Compared with the model group,the body mass,body length and spontaneous activities frequency of the rats in the Huoxiang Zhengqi Dropping Pills group were significantly increased(P<0.05),and the abdominal circumference index was significantly decreased(P<0.05).A total of 38 and 44 potential biomarkers related to dampness encumbering the spleen and stomach were identified in rat serum and urine,respectively.Huoxiang Zhengqi Dropping Pills can effectively interfere with the serum and urine metabolic phenotypes of model rats,and can significantly reverse 17 and 13 potential biomarkers in serum and urine,involving a total of 7 metabolic pathways.Conclusion The intervention mechanism of Huoxiang Zhengqi Dropping Pills on rats with dampness encumbering the spleen and stomach syndrome may be related to the regulation of tryptophan metabolism,histidine metabolism,glutamate-glutamine metabolism,energy metabolism and intestinal flora.
8.Effect of aortic smooth muscle BK channels on mediating chronic intermittent hypoxia-induced vascular dysfunction
Ping ZHANG ; Pengtao ZOU ; Xiao HUANG ; Xianghui ZENG ; Songtao LIU ; Yuanyuan LIU ; Liang SHAO
The Korean Journal of Physiology and Pharmacology 2024;28(5):469-478
Chronic intermittent hypoxia (CIH) can lead to vascular dysfunction and increase the risk of cardiovascular diseases, cerebrovascular diseases, and arterial diseases. Nevertheless, mechanisms underlying CIH-induced vascular dysfunction remain unclear. Herein, this study analyzed the role of aortic smooth muscle calciumactivated potassium (BK) channels in CIH-induced vascular dysfunction. CIH models were established in rats and rat aortic smooth muscle cells (RASMCs). Hemodynamic parameters such as mean blood pressure (MBP), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were measured in rats, along with an assessment of vascular tone. NO and ET-1 levels were detected in rat serum, and the levels of ET-1, NO, eNOS, p-eNOS, oxidative stress markers (ROS and MDA), and inflammatory factors (IL-6 and TNF-α) were tested in aortic tissues. The Ca2+ concentration in RASMCs was investigated. The activity of BK channels (BKα and BKβ) was evaluated in aortic tissues and RASMCs. SBP, DBP, and MBP were elevated in CIH-treated rats, along with endothelial dysfunction, cellular edema and partial detachment of endothelial cells. BK channel activity was decreased in CIH-treated rats and RASMCs. BK channel activation increased eNOS, p-eNOS, and NO levels while lowering ET-1, ROS, MDA, IL-6, and TNF-α levels in CIH-treated rats. Ca2+ concentration increased in RASMCs following CIH modeling, which was reversed by BK channel activation. BK channel inhibitor (Iberiotoxin) exacerbated CIH-induced vascular disorders and endothelial dysfunction. BK channel activation promoted vasorelaxation while suppressing vascular endothelial dysfunction, inflammation, and oxidative stress, thereby indirectly improving CIH-induced vascular dysfunction.
9.Effect of aortic smooth muscle BK channels on mediating chronic intermittent hypoxia-induced vascular dysfunction
Ping ZHANG ; Pengtao ZOU ; Xiao HUANG ; Xianghui ZENG ; Songtao LIU ; Yuanyuan LIU ; Liang SHAO
The Korean Journal of Physiology and Pharmacology 2024;28(5):469-478
Chronic intermittent hypoxia (CIH) can lead to vascular dysfunction and increase the risk of cardiovascular diseases, cerebrovascular diseases, and arterial diseases. Nevertheless, mechanisms underlying CIH-induced vascular dysfunction remain unclear. Herein, this study analyzed the role of aortic smooth muscle calciumactivated potassium (BK) channels in CIH-induced vascular dysfunction. CIH models were established in rats and rat aortic smooth muscle cells (RASMCs). Hemodynamic parameters such as mean blood pressure (MBP), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were measured in rats, along with an assessment of vascular tone. NO and ET-1 levels were detected in rat serum, and the levels of ET-1, NO, eNOS, p-eNOS, oxidative stress markers (ROS and MDA), and inflammatory factors (IL-6 and TNF-α) were tested in aortic tissues. The Ca2+ concentration in RASMCs was investigated. The activity of BK channels (BKα and BKβ) was evaluated in aortic tissues and RASMCs. SBP, DBP, and MBP were elevated in CIH-treated rats, along with endothelial dysfunction, cellular edema and partial detachment of endothelial cells. BK channel activity was decreased in CIH-treated rats and RASMCs. BK channel activation increased eNOS, p-eNOS, and NO levels while lowering ET-1, ROS, MDA, IL-6, and TNF-α levels in CIH-treated rats. Ca2+ concentration increased in RASMCs following CIH modeling, which was reversed by BK channel activation. BK channel inhibitor (Iberiotoxin) exacerbated CIH-induced vascular disorders and endothelial dysfunction. BK channel activation promoted vasorelaxation while suppressing vascular endothelial dysfunction, inflammation, and oxidative stress, thereby indirectly improving CIH-induced vascular dysfunction.
10.Effect of aortic smooth muscle BK channels on mediating chronic intermittent hypoxia-induced vascular dysfunction
Ping ZHANG ; Pengtao ZOU ; Xiao HUANG ; Xianghui ZENG ; Songtao LIU ; Yuanyuan LIU ; Liang SHAO
The Korean Journal of Physiology and Pharmacology 2024;28(5):469-478
Chronic intermittent hypoxia (CIH) can lead to vascular dysfunction and increase the risk of cardiovascular diseases, cerebrovascular diseases, and arterial diseases. Nevertheless, mechanisms underlying CIH-induced vascular dysfunction remain unclear. Herein, this study analyzed the role of aortic smooth muscle calciumactivated potassium (BK) channels in CIH-induced vascular dysfunction. CIH models were established in rats and rat aortic smooth muscle cells (RASMCs). Hemodynamic parameters such as mean blood pressure (MBP), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were measured in rats, along with an assessment of vascular tone. NO and ET-1 levels were detected in rat serum, and the levels of ET-1, NO, eNOS, p-eNOS, oxidative stress markers (ROS and MDA), and inflammatory factors (IL-6 and TNF-α) were tested in aortic tissues. The Ca2+ concentration in RASMCs was investigated. The activity of BK channels (BKα and BKβ) was evaluated in aortic tissues and RASMCs. SBP, DBP, and MBP were elevated in CIH-treated rats, along with endothelial dysfunction, cellular edema and partial detachment of endothelial cells. BK channel activity was decreased in CIH-treated rats and RASMCs. BK channel activation increased eNOS, p-eNOS, and NO levels while lowering ET-1, ROS, MDA, IL-6, and TNF-α levels in CIH-treated rats. Ca2+ concentration increased in RASMCs following CIH modeling, which was reversed by BK channel activation. BK channel inhibitor (Iberiotoxin) exacerbated CIH-induced vascular disorders and endothelial dysfunction. BK channel activation promoted vasorelaxation while suppressing vascular endothelial dysfunction, inflammation, and oxidative stress, thereby indirectly improving CIH-induced vascular dysfunction.

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