5.Efficacy and safety of vericiguat added to GDMT regimen in the treatment of heart failure with reduced ejection fraction
Xingyuan ZHAO ; Xiangyan CHEN ; Nan HU ; Liying WANG ; Hui XUE ; Zongling XIA
China Pharmacy 2025;36(17):2165-2169
OBJECTIVE To evaluate the efficacy and safety of guideline-directed medical therapy (GDMT) combined with vericiguat in treating heart failure with reduced ejection fraction (HFrEF). METHODS A retrospective study was conducted on 346 patients with HFrEF who received standardized diagnosis and treatment at the First People’s Hospital of Changzhou from January 2023 to May 2024. They were divided into standard treatment group (n=215) and vericiguat group (n=131). Patients in the standard treatment group received GDMT, while patients in the vericiguat group received GDMT combined with vericiguat. Propensity score matching (PSM) was used to balance confounding factors between two groups, and the effectiveness (including outcome and prognostic indicators) and safety (occurrence of adverse events) of both groups were evaluated. Kaplan-Meier survival curves for primary and secondary outcome events were drawn, and the influential factors of primary outcome events were screened through univariate and multivariate Cox regression analysis. RESULTS After PSM, there were 100 patients in the standard treatment group and 100 patients in the vericiguat group, and there was no statistically significant differences in baseline data between two groups (P>0.05). During a 1-year follow-up, there were statistically significant differences in the cumulative incidence of major outcome events between the standard treatment group and the vericiguat group, cumulative incidence of hospitalization events due to heart failure, changes in N-terminal pro-B-type natriuretic peptide levels before and after treatment between the standard treatment group and the vericiguat group (P<0.05). There was no statistically significant difference in the incidence of adverse events between the two groups (P>0.05). Multivariate Cox regression analysis results showed that left ventricular ejection fraction ≤35% was a risk factor for the occurrence of major outcome events within 1 year [hazard ratio (HR)= 2.090, 95% confidence interval (CI): 1.175-3.718, P=0.012], while the use of vericiguat was a protective factor for the occurrence of major outcome events within 1 year (HR=0.505, 95%CI: 0.284-0.899, P=0.020). CONCLUSIONS Compared with GDMT, GDMT combined with vericiguat can improve the clinical symptoms and prognosis of HFrEF patients, and has good safety.
6.Study on the Mechanism of Guanyuan Mingmen Sequential Acupuncture Activating FSHR/cAMP/PKA Pathway to Promote Granulosa Cell Proliferation in POI Model Rats
Jiang-Hong XU ; Yue-Lai CHEN ; Ping YIN ; Xue-Dan ZHAO ; Hui-Min ZHENG ; Jun-Wei HU ; Lu-Min LIU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(4):965-972
Objective To observe the therapeutic effects and mechanisms of Guanyuan Mingmen Sequential Acupuncture on rats with premature ovarian insufficiency(POI)model.Methods Female SD rats were divided into the blank group,the model group,the protein kinase A(PKA)inhibitor(H89)+acupuncture group,and the acupuncture group,with 12 rats in each group.Except for the blank group,the POI model was prepared by gavage with Tripterygium Glycosides Tablets in the other three groups of rats.After the model was successfully established,the blank group and the model group were bundled once a day;in the acupuncture group,Guanyuan(RN4)point was taken during the intermotility period,and in the pre-motility period,Mingmen(DU4)point was taken;in the H89+acupuncture group,the intervention was performed in accordance with the acupuncture protocol of the acupuncture group,and H89 was injected intraperitoneally for 30 minutes prior to each acupuncture session.Continuous intervention was performed for 20 days.Samples were taken from each group of rats in the first estrus period and in proestrus period after intervention.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of follicle stimulating hormone(FSH)and estradiol(E2)during the estrous phase,Western Blot was used to measure the protein expressions of follicle stimulating hormone receptor(FSHR)and aromatase P450(P450arom)during the estrous phase,and the activity of granulocytes during the estrous phase and the proestrus phase were measured using the cell-counting kit 8(CCK-8)method.The immunohistochemistry method was used to detect the protein expression of pre-motility proliferating cell nuclear antigen(PCNA).Results(1)Compared with the blank group,the serum FSH level of the model group and H89+acupuncture group was significantly increased(P<0.01),and the E2 level was significantly decreased(P<0.001);there was no difference between the FSH level of the H89+acupuncture group and that of the model group(P>0.05),and the E2 level of the H89+acupuncture group was lower than that of the model group(P<0.05);the FSH level of the acupuncture group was lower than that of the model group and that of the H89+acupuncture group(P<0.05),had no difference with the blank group(P>0.05),E2 level was significantly higher than the model group and H89+ acupuncture group(P<0.01),still being lower than the blank group(P<0.05).(2)The protein expressions of FSHR and P450arom in the model group and H89 + acupuncture group was lower than those in the blank group;the protein expression of FSHR in the H89 + acupuncture group was not different from that in the model group(P>0.05),while the protein expression level of P450arom was lower than that in the model group(P<0.05);the protein expression levels of FSHR and P450arom in the acupuncture group were higher than those in the model group and H89 + acupuncture group,but still lower than those in the blank group(P<0.05).(3)Both GCs activity and average optical density value of PCNA in the model group and H89+acupuncture group were lower than the blank group(P<0.05);both GCs activity and average optical density value of PCNA in the H89+acupuncture group were lower than the model group(P<0.05);the activity of GCs and average optical density value of PCNA of the acupuncture group were significantly higher than that of the model group and H89+acupuncture group(P<0.05 or P<0.01).Conclusion Guanyuan Mingmen Sequential Acupuncture can regulate sex hormone levels,increase GCs activity and promote GCs cell proliferation by up-regulating protein expressions of follicle stimulating hormone receptor(FSHR)/cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)pathway FSHR,P450arom,thus improving POI.
7.Identification of Scolopendra Dispensing Granules by Allele-specific PCR
Yuansheng XU ; Li HU ; Chao JIANG ; Yuyang ZHAO ; Tianyun CHEN ; Hui ZHANG ; Hui TIAN ; Yuan YUAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(4):48-54
ObjectiveTo establish an allele-specific polymerase chain reaction (PCR) method for identifying Scolopendra dispensing granules, so as to ensure the quality and therapeutic effects of Scolopendra and its preparations. MethodThe primer interval suitable for the PCR was selected based on the cytochrome c oxidase subunit 3(COX-3) gene sequence of Scolopendra, and the single nucleotide polymorphism (SNP) loci of Scolopendra and its adulterants were mined from the interval for the design of specific primers. The samples of Scolopendra and its adulterants were collected. The PCR system was established and optimized regarding the annealing temperature, cycles, Taq enzymes, DNA template amount, PCR instruments, and primer concentrations, and the specificity and applicability of this method were evaluated. ResultThe PCR system was composed of 12.5 μL 2×M5 PCR Mix, 0.4 μL forward primer (10 μmol·L-1), 0.4 μL reverse primer (10 μmol·L-1), 2.5 μL DNA template, and 9.2 μL sterile double distilled water. PCR parameters: Pre-denaturation at 94 ℃ for 3 min, 30 cycles (94 ℃ for 20 s, 62 ℃ for 20 s, 72 ℃ for 45 s), and extension at 72 ℃ for 5 min. After PCR amplification with the system and parameters above, the electrophoresis revealed a bright band at about 135 bp for Scolopendra and no band for the adulterants. ConclusionThe established allele-specific PCR method can accurately identify the medicinal materials, decoction pieces, and standard decoction freeze-dried powder of Scolopendra, as well as the intermediates and final products of Scolopendra dispensing granules, which is of great significance for ensuring the quality and clinical efficacy of Scolopendra and its preparations.
8.Current Situation of Health Technology Assessment in Traditional Chinese Medicine Hospitals
Simin XU ; Hui ZHAO ; Jing HU ; Zhaolan LIU ; Weiwei SUN ; Xing LIAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(4):190-197
ObjectiveThis study aims to understand the recognition of practitioners in traditional Chinese medicine (TCM) hospitals on hospital-based health technology assessment (HB-HTA), assessment needs, challenges, and suggestions, so as to provide references for the future work. MethodThe convenient sampling method was adopted to survey the relevant practitioners in TCM hospitals. The questionnaire included 39 questions in 4 dimensions and was distributed through the online platform Weijuanxing. ResultA total of 244 questionnaires were recovered, and the obtained data were analyzed in SPSS. The results showed that 137 practitioners were very familiar with HB-HTA and there was no significant difference in the recognition of practitioners in different occupations (F=0.251; P=0.778). The practitioners in Hong Kong, Macao, and Taiwan had lower recognition than those in other regions. In terms of the assessment needs, 127 practitioners believed that it was very necessary to carry out HB-HTA in TCM hospitals in the future. Chinese patent medicines/Chinese herbal medicine decoction pieces (5.91) and TCM appropriate technology (5.57) had higher assessment priority scores. The assessment needs were high for the effectiveness (235 practitioners) and safety (224 practitioners) of health technology. The lack of specialized organization and standardized evaluation process system and the shortage of talents were considered to be the major challenges for the future development in this field. ConclusionThe stakeholders carrying out the health technology assessment in TCM hospitals had certain awareness of HB-HTA. Most practitioners believed that it was necessary to carry out HB-HTA in TCM hospitals in the future, while the work might face challenges such as the lack of organizations and system and the shortage of talents, which requires policy support.
9.Effects of Huatan Quyu Decoction on Cognitive Function and Expressions of GABA and VILIP-1 in Brain Tissue in Rats with Cerebral Small Vessel Disease
Yuqian TIAN ; Yongjun FANG ; Yali HU ; Hui ZHANG ; Xiaofeng HUANG ; Pengfang WEI ; Xinya ZHAO ; Yongmei YAN
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(2):123-129
Objective To observe the effects of Huatan Quyu Decoction on cognitive function and the expressions of GABA and VILIP-1 in brain tissue of rats with cerebral small vessel disease;To discuss its mechanism for treatment on cerebral small vessel disease.Methods Totally 48 male SD rats were randomly divided into blank group,model group,Huatan Quyu Decoction low-and high-dosage groups,with 12 rats in each group.Except for the blank group,a rat model of cerebral small vessel disease was prepared by in vitro injection of homologous microemboli.Huatan Quyu Decoction low-and high-dosage groups were given Huatan Quyu Decoction 1.25 and 2.5 g/kg by gavage,the blank group and model group were gavage with equal amounts of distilled water for 28 consecutive days.Morris water maze experiment was conducted on day 1,7,14,and 28 after administration to evaluate the learning and memory abilities of rats,HE staining was used to observe pathological changes in hippocampal tissue,and immunohistochemical staining was used to detect the expressions of GABA and VILIP-1 proteins in brain tissue.Results Compared with the blank group,the escape latency of Morris water maze experiment in model group significantly prolonged(P<0.05),and the number of crossing platforms was significantly reduced(P<0.05);the arrangement of hippocampal tissue cells was disordered,gaps widen,and nuclei atrophy and necrosis,the GABA expression in brain tissue significantly decreased(P<0.05),while the VILIP-1 expression significantly increased(P<0.05).Compared with the model group,the escape latency of Morris water maze experiment in the Huatan Quyu Decoction low-and high-dosage groups significantly shortened(P<0.05)on day 7,14,and 28 of administration,and the number of crossing platforms significantly increased(P<0.05),GABA expression significantly increased(P<0.05),while VILIP-1 expression significantly decreased(P<0.05).Compared with the Huatan Quyu Decoction low-dosage group,the escape latency of Morris water maze experiment in Huatan Quyu Decoction high-dosage group decreased at various time points,and the number of crossing platforms increase,the pathological damage of hippocampal tissue was reduced,the expression of GABA in brain tissue increased,and the expression of VILIP-1 decreased,with statistical significance(P<0.05).Conclusion Huatan Quyu Decoction can increase the expression of GABA in brain tissue and inhibit the expression of VILIP-1,thereby improve the cognitive function of rats with cerebrovascular disease.
10. Berberine interferes with RSV infection of HEp-2 cells by inducing mitophagy autophagy
Yu-Juan CUI ; Yu-Juan CUI ; Hui ZHAO ; Dong-Xia SU ; Dan-Dong HU
Chinese Pharmacological Bulletin 2024;40(2):308-316
Aim To explore the effect of berberine (B E) on RSV infected HEp-2 cells and the related mechanism. Methods HEp-2 cells were infected with RSV and treated with BE. Cell viability was assessed using the CCK-8 assay. Protein expression levels of NLRP3, ASC, caspase-1, PINK1, Parkin, Beclinl, p62, LC3 I,LC3 II,and BNIP3 in HEp-2 cells were detected by Western blot. The secretion level of IL-1 p in HEp-2 cells was measured using ELISA. Apoptosis rate and mitochondrial membrane potential of HEp-2 cells were examined by flow cytometry. Mitochondrial ROS (mtROS) in HEp-2 cells was detected through MitoSOX staining. Colocalization of mitochondria and autophagosomes in HEp-2 cells was investigated using immunofluorescence staining. Cyclosporin A was used for validation experiments. Results BE could significantly improve the activity of RSV-infected HEp-2 cells,reduce the apoptosis rate (P < 0. 05), and decrease the activation level of NLRP3 inflammasomes and IL-lp level (P <0. 05); BE improved mitochondrial function by increasing mitochondrial membrane potential and ATP levels,and reduced mtROS. BE significantly promoted the colocalization of mitochondria-autophagosome in RSV infected cells, inducing PINK1/ Parkin and BNIP3 to mediate mitochondrial autophagy; cyclosporine A aggravated RSV infection. Conclusions BE has protective effects on HEp-2 cells infected by RSV. The mechanism may be related to the inhibitory effect of BE on the production of mtROS and the activation of NLRP3 inflammasomes by inducing PINK1/ Parkin and BNIP3-mediated mitochondrial autophagy.

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