1.Effect of Bushen Huoxue Prescription in Regulating PINK1/Parkin Pathway in Rat Model of Premature Ovarian Failure
Kailing WANG ; Yichen JING ; Guiyun WANG ; Yueheng LI ; Huiping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):150-158
ObjectiveTo investigate the mechanism of action of Bushen Huoxue prescription (BSHXP) in regulating premature ovarian failure in rats through the PTEN-induced kinase 1 (PINK1)/Parkinson's protein (Parkin) signaling pathway-mediated mitophagy. MethodsA total of 48 rats were randomly divided into a blank group consisting of eight rats, while the remaining 40 rats underwent modeling. The modeling group was intraperitoneally injected with 4 mg·kg-1 cisplatin solution, followed by a second injection one week later, for a total of two injections. The estrous cycle was observed through vaginal smears for 14 consecutive days to determine whether the modeling was successful. The successfully modeled rats were randomly divided into a model group, groups receiving low, medium, and high doses of BSHXP at 9.72, 19.44, and 38.88 g·kg-1·d-1 (BSHXP-L, BSHXP-M, and BSHXP-H groups), and a positive control group treated with estradiol valerate (0.09 mg·kg-1·d-1), for 21 consecutive days. The body weight of the rats was measured weekly. After the final administration, rats were anesthetized, and their blood and ovaries were collected. The ovarian weight was measured. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2). Assay kits were used to measure the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in the rat serum. Hematoxylin-eosin (HE) staining was used to observe the morphological changes in the ovaries. Immunohistochemistry (IHC) was performed to detect microtubule autophagy-related protein 1 light chain 3B(LC3B) protein expression in ovarian tissue, and electron microscopy was employed to examine the mitochondrial and autophagosome changes in the rat ovaries. Western blot was used to detect the protein expression of PINK1, Parkin, LC3B, and p62. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of PINK1, Parkin, LC3B, and p62 in ovarian tissue. ResultsCompared with the blank group, the model group showed significant reductions in body weight, weight gain, and ovarian weight (P<0.01), along with decreased serum AMH and E2 levels (P<0.01), while FSH and LH levels were increased (P<0.01). Serum MDA levels were significantly increased (P<0.01), and SOD levels were significantly reduced (P<0.01). The ovarian tissue structure was disordered, and the zona pellucida was wrinkled into an irregular acidophilic annular object, accompanied by an increased number of closed follicles. Electron microscopy showed mitochondrial swelling, unclear structure, and no obvious autophagosomes and autolysosome structures. The proteins and mRNA expression levels of PINK1, Parkin, LC3B, and p62 in the ovarian tissue were significantly reduced (P<0.01). Compared with the model group, all treatment groups showed varying degrees of increases in body weight and ovarian weight (P<0.05, P<0.01). Except for the BSHXP-L group, all treatment groups showed increased body weight gain (P<0.01). All treatment groups showed significantly increased serum AMH and decreased FSH levels (P<0.01). Except for the BSHXP group, all treatment groups showed varying degrees of increase and decrease in serum E2 and LH levels (P<0.05, P<0.01). All treatment groups showed reduced serum MDA levels (P<0.01), while the BSHXP-M, BSHXP-H, and the positive control groups demonstrated improved serum SOD levels (P<0.05, P<0.01). All treatment groups showed an increased number of follicles at all stages, visible mature follicles, and a decreased number of closed follicles. Electron microscopy showed relieved mitochondrial swelling, morphology close to normal, clear structure, and visible formation of autolysosomes in all treatment groups. Additionally, the protein and mRNA expression levels of PINK1, Parkin, LC3B, and p62 in ovarian tissue were significantly increased (P<0.05, P<0.01). ConclusionBSHXP may improve ovarian function in rats with premature ovarian failure by regulating the PINK1/Parkin signaling pathway, activating mitochondrial autophagy, and reducing oxidative damage.
2.Effect of Bushen Huoxue Prescription in Regulating PINK1/Parkin Pathway in Rat Model of Premature Ovarian Failure
Kailing WANG ; Yichen JING ; Guiyun WANG ; Yueheng LI ; Huiping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):150-158
ObjectiveTo investigate the mechanism of action of Bushen Huoxue prescription (BSHXP) in regulating premature ovarian failure in rats through the PTEN-induced kinase 1 (PINK1)/Parkinson's protein (Parkin) signaling pathway-mediated mitophagy. MethodsA total of 48 rats were randomly divided into a blank group consisting of eight rats, while the remaining 40 rats underwent modeling. The modeling group was intraperitoneally injected with 4 mg·kg-1 cisplatin solution, followed by a second injection one week later, for a total of two injections. The estrous cycle was observed through vaginal smears for 14 consecutive days to determine whether the modeling was successful. The successfully modeled rats were randomly divided into a model group, groups receiving low, medium, and high doses of BSHXP at 9.72, 19.44, and 38.88 g·kg-1·d-1 (BSHXP-L, BSHXP-M, and BSHXP-H groups), and a positive control group treated with estradiol valerate (0.09 mg·kg-1·d-1), for 21 consecutive days. The body weight of the rats was measured weekly. After the final administration, rats were anesthetized, and their blood and ovaries were collected. The ovarian weight was measured. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2). Assay kits were used to measure the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in the rat serum. Hematoxylin-eosin (HE) staining was used to observe the morphological changes in the ovaries. Immunohistochemistry (IHC) was performed to detect microtubule autophagy-related protein 1 light chain 3B(LC3B) protein expression in ovarian tissue, and electron microscopy was employed to examine the mitochondrial and autophagosome changes in the rat ovaries. Western blot was used to detect the protein expression of PINK1, Parkin, LC3B, and p62. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of PINK1, Parkin, LC3B, and p62 in ovarian tissue. ResultsCompared with the blank group, the model group showed significant reductions in body weight, weight gain, and ovarian weight (P<0.01), along with decreased serum AMH and E2 levels (P<0.01), while FSH and LH levels were increased (P<0.01). Serum MDA levels were significantly increased (P<0.01), and SOD levels were significantly reduced (P<0.01). The ovarian tissue structure was disordered, and the zona pellucida was wrinkled into an irregular acidophilic annular object, accompanied by an increased number of closed follicles. Electron microscopy showed mitochondrial swelling, unclear structure, and no obvious autophagosomes and autolysosome structures. The proteins and mRNA expression levels of PINK1, Parkin, LC3B, and p62 in the ovarian tissue were significantly reduced (P<0.01). Compared with the model group, all treatment groups showed varying degrees of increases in body weight and ovarian weight (P<0.05, P<0.01). Except for the BSHXP-L group, all treatment groups showed increased body weight gain (P<0.01). All treatment groups showed significantly increased serum AMH and decreased FSH levels (P<0.01). Except for the BSHXP group, all treatment groups showed varying degrees of increase and decrease in serum E2 and LH levels (P<0.05, P<0.01). All treatment groups showed reduced serum MDA levels (P<0.01), while the BSHXP-M, BSHXP-H, and the positive control groups demonstrated improved serum SOD levels (P<0.05, P<0.01). All treatment groups showed an increased number of follicles at all stages, visible mature follicles, and a decreased number of closed follicles. Electron microscopy showed relieved mitochondrial swelling, morphology close to normal, clear structure, and visible formation of autolysosomes in all treatment groups. Additionally, the protein and mRNA expression levels of PINK1, Parkin, LC3B, and p62 in ovarian tissue were significantly increased (P<0.05, P<0.01). ConclusionBSHXP may improve ovarian function in rats with premature ovarian failure by regulating the PINK1/Parkin signaling pathway, activating mitochondrial autophagy, and reducing oxidative damage.
3.Impact of palliative care on medication use and medical utilization in patients with advanced cancer.
Dingyi CHEN ; Haoxin DU ; Yichen ZHANG ; Yanfei WANG ; Wei LIU ; Yuanyuan JIAO ; Luwen SHI ; Xiaodong GUAN ; Xinpu LU
Journal of Peking University(Health Sciences) 2025;57(5):996-1001
OBJECTIVE:
To evaluate the effect of palliative care on drug use, medical service utilization and medical expenditure of patients with advanced cancer.
METHODS:
A cohort of patients including pal-liative care and standard care was constructed using the medical records of the patients in Peking University Cancer Hospital from 2018 to 2020, and coarsened exact matching was used to match the two groups of patients. The average monthly opioid consumption, hospitalization rate, intensive care unit (ICU) rate and operation rate, and the average monthly total cost were selected to evaluate drug use, medical service utilization and medical expenditure. Chi-square test and Wilcoxon signed rank test were used to compare the differences between the two groups before and after exposure and the change in the palliative care group. The net impact of palliative care on the patients was calculated using the difference-in-differences analysis.
RESULTS:
In this study, 180 patients in the palliative care group and 3 101 patients in the stan-dard care group were finally included in the matching, and the matching effect of the two groups was good (L1 < 0.1). Before and after exposure, the average monthly opioid consumption in the palliative care group was significantly higher than that in the standard care group (Before exposure: 0.3 DDD/person-month vs. 0.1 DDD/person-month, P < 0.01; After exposure: 0.7 DDD/person-month vs. 0.1 DDD/person-month, P < 0.01; DDD refers to defined daily dose), palliative care significantly increased the average monthly opioid consumption in the patients (0.3 DDD/person-month, P < 0.01). The hospitalization rate (48.9% vs. 74.3%, P < 0.01) and operation rate (3.9% vs. 8.8%, P < 0.01) of the patients in palliative care group were significantly lower than those in standard care group, and the ICU rate became similar between the two groups (1.1% vs. 1.6%, P=0.634). Palliative care significantly reduced the patients ' hospitalization rate (-25.6%, P < 0.01), ICU rate (-4.9%, P < 0.01) and operation rate (-14.5%, P < 0.01). Before and after exposure, the average monthly total costs of pal-liative care group were slightly higher than those of standard care group (Before exposure: 20 092.3 yuan vs. 19 132.8 yuan, P=0.725; After exposure: 9 719.8 yuan vs. 8 818.8 yuan, P=0.165). Palliative care increased the average monthly total cost by 2 208.8 yuan, but it was not statistically significant (P=0.316).
CONCLUSION
Palliative care can increase the opioid consumption in advanced cancer patients, reduce the rates of hospitalization, ICU and surgery, but has no significant effect on medical expenditure.
Humans
;
Palliative Care/economics*
;
Neoplasms/drug therapy*
;
Analgesics, Opioid/economics*
;
Male
;
Female
;
Middle Aged
;
Aged
;
Hospitalization/economics*
;
Intensive Care Units/statistics & numerical data*
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Health Expenditures/statistics & numerical data*
;
Adult
;
Drug Utilization/statistics & numerical data*
;
Patient Acceptance of Health Care/statistics & numerical data*
5.Natural product virtual-interact-phenotypic target characterization: A novel approach demonstrated with Salvia miltiorrhiza extract.
Rui XU ; Hengyuan YU ; Yichen WANG ; Boyu LI ; Yong CHEN ; Xuesong LIU ; Tengfei XU
Journal of Pharmaceutical Analysis 2025;15(2):101101-101101
Natural products (NPs) have historically been a fundamental source for drug discovery. Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents, and corresponding targets. In the present study, an innovative natural product virtual screening-interaction-phenotype (NP-VIP) strategy that integrates virtual screening, chemical proteomics, and metabolomics to identify and validate the bioactive targets of NPs. This approach reduces false positive results and enhances the efficiency of target identification. Salvia miltiorrhiza (SM), a herb with recognized therapeutic potential against ischemic stroke (IS), was used to illustrate the workflow. Utilizing virtual screening, chemical proteomics, and metabolomics, potential therapeutic targets for SM in the IS treatment were identified, totaling 29, 100, and 78, respectively. Further analysis via the NP-VIP strategy highlighted five high-confidence targets, including poly [ADP-ribose] polymerase 1 (PARP1), signal transducer and activator of transcription 3 (STAT3), amyloid precursor protein (APP), glutamate-ammonia ligase (GLUL), and glutamate decarboxylase 67 (GAD67). These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM. The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research, proposing a comprehensive approach that could be adapted for broader pharmacological explorations.
6.Effect of evolocumab early use after PCI on blood lipids and inflammatory factors in patients with ultra-high-risk ASCVD
Weijian ZHANG ; Bingkun LIU ; Yichen LIU ; Yao YAN ; Chuanyan ZHAO
Chongqing Medicine 2025;54(2):446-451
Objective To investigate the effects of evolocumab in the early postoperative period after percutaneous coronary intervention(PCI)on blood lipids and inflammatory cytokines in the patients with ul-tra-high-risk atherosclerotic cardiovascular disease(ASCVD).Methods A total of 65 patients with ultra-high-risk ASCVD treated by PCI in this hospital from October 2022 to March 2023 were selected as the study subjects and divided into the observation group(n=33)and control group(n=32)according to the used drugs.The patients in the control group received the treatment of oral rosuvastatin 10 mg;on the basis of the treatment in the control group,the observation group was treated with subcutaneous injection of evolocumab 140 mg immediately after PCI.The fasting blood samples were collected before surgery,on postoperative 3 d,1,3,6 months,and the levels of inflammation and blood lipid indexes were detected and recorded.The occur-rences of cardiovascular adverse events(MACE)and other complications in postoperative 6 months were re-corded.Results The levels of LDL-C,Lp-PLA2 and lipoprotein a on postoperative 3 d,1,3,6 months in the observation group were gradually decreased,moreover were lower than those in the control group,and the differences were statistically significant(P<0.05).The levels of IL-6,homocysteine and hs-CRP on postoper-ative 3 d,1,3,6 months in the two groups were decreased,moreover the levels of various indexes in the obser-vation group were lower than those in the control group,and the differences were statistically significant(P<0.05).The incidence rate of MACE in the observation group was lower than that in the control group,and the difference was statistically significant(P<0.05);the difference in the incidence rates of other complications between the two groups was not statistically significant(P>0.05).According to the Log Rank test,the sur-vival rate of the observation group was higher than that of the control group,and the difference was statistical-ly significant(P<0.05).Conclusion The early application of evolocumab after PCI could reduce the blood lipid level and inflammatory cytokines levels of the patients with ultra-high-risk ASCVD,and increase their survival rate.
7.Tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device in anterior mediastinal masses
Junmin ZHU ; Junjie WANG ; Jianming YUE ; Yixin SUN ; Yichen LIU ; Lei WANG ; Lin LIN ; Jie LI ; Jinlan ZHAO ; Xuehua TU ; Ningying DING ; Jianrong HU ; Chunmei HE ; Leilei TIAN ; Hongtao TANG ; Jiasheng ZHAO ; Cheng CHEN ; Yongxiang SONG ; Yunwei TIAN ; Yong XIAO ; Kaidi LI ; Lin MA ; Yun WANG ; Longqi CHEN ; Dong TIAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(11):1603-1609
Objective To assess the clinical value of a novel surgical technique—Tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device in the resection of anterior mediastinal masses. Methods Patients who underwent tubeless subxiphoid uniportal video-assisted thoracoscopic surgery via balance-shaped sternal elevation device in anterior mediastinal masses process at the Department of Thoracic Surgery, West China Hospital, Sichuan University from March to April 2025 were included, and their clinical data were analyzed. Results A total of 4 patients were included, with 2 males and 2 females, aged 58-75 years. The diameter of the tumor was 2.5-3.0 cm. The operation time was 60.0-150.0 min, intraoperative blood loss was 5-10 mL, pain score on the 3rd day after surgery was 0 points, and postoperative hospital stay was 2-3 days. All patients achieved complete resection of the masses and thymus without perioperative complications. Conclusion The tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device technique optimizes surgical visualization and instrument maneuverability while avoiding complications related to conventional anesthesia and tubing, thereby markedly enhancing the minimally invasive profile of anterior mediastinal masses resections. In addition to maintaining procedural safety, this approach effectively reduces postoperative pain and accelerates patient recovery, highlighting its potential for widespread clinical adoption.
8.C/EBPβ mediates expressions of downstream inflammatory factors of the tumor necrosis factor-α signaling pathway in renal tubular epithelial cells with NPHP1 knockdown
Danmei HUANG ; Yaqing LIU ; Dantong LI ; Jinglan ZHANG ; Yichen YANG ; Liangzhong SUN
Journal of Southern Medical University 2024;44(1):156-165
Objective To explore the activation of tumor necrosis factor-α(TNF-α)signaling pathway and the expressions of the associated inflammatory factors in NPHP1-defective renal tubular epithelial cells.Methods A human proximal renal tubular cell(HK2)model of lentivirus-mediated NPHP1 knockdown(NPHP1KD)was constructed,and the expressions of TNF-α,p38,and C/EBPβ and the inflammatory factors CXCL5,CCL20,IL-1β,IL-6 and MCP-1 were detected using RT-qPCR,Western blotting or enzyme-linked immunosorbent assay.A small interfering RNA(siRNA)was transfected in wild-type and NPHP1KDHK2 cells,and the changes in the expressions of TNF-α,p38,and C/EBPβ and the inflammatory factors were examined.Results NPHP1KDHK2 cells showed significantly increased mRNA expressions of TNF-α,C/EBPβ,CXCL5,IL-1β,and IL-6(P<0.05),protein expressions of phospho-p38 and C/EBPβ(P<0.05),and IL-6 level in the culture supernatant(P<0.05),and these changes were significantly blocked by transfection of cells with siRNA-C/EBPβ(P<0.05).Conclusion TNF-α signaling pathway is activated and its associated inflammatory factors are upregulated in NPHP1KDHK2 cells,and C/EBPβ may serve as a key transcription factor to mediate these changes.
9.Analysis of causes and solutions for vacuum suction weakness of dental units
Xinya LI ; Yichen WANG ; Yansong LIU ; Anjia ZHENG ; Shubin WU ; Baolin FAN ; Jianxia WANG
China Medical Equipment 2024;21(2):193-195,199
An efficient vacuum suction system is a necessary prerequisite for the smooth operation of the oral diagnosis and treatment.During the use of the dental units,there is often a situation of vacuum suction weakness,resulting in the inability to discharge the mixture of blood,saliva,dental tissue and other mixtures in time,which affects the doctor's treatment field and increases the risk of aspiration pneumonia and cross-infection in patients.The working principle,pipeline system,filters and other aspects of the vacuum suction system that may affect the suction efficiency was analyzed.The causes and solutions of vacuum suction weakness were discussed,and operation suggestions were proposed to ensure the safe and effective use of equipment and ensure the safety of diagnosis and treatment.
10.Progress in research of tracing contacts exposed to high risk behaviors of HIV-infected patients
Huan LIU ; Yichen JIN ; Houlin TANG
Chinese Journal of Epidemiology 2024;45(5):755-760
Tracing the contacts exposed to high risk behaviors of HIV-infected patients can facilitate the diagnosis and discovery of HIV positive individuals for timely treatment and intervention to reduce secondary transmission, which is of great importance for the control of AIDS epidemic. With the development of HIV gene sequence detection and analysis technology, the application of HIV molecular transmission network in traditional contact tracing based on epidemiological investigation can contribute to the accurate reveal of HIV transmission mode, clarification of HIV transmission characteristics and identification of the population at high risk for HIV infection to provide evidence-based insights for the accurate prevention and control of AIDS. This paper summarized the progress in the research of tracing the contacts exposed to high risk behaviors of HIV-infected patients to provide reference for the AIDS prevention and control in the future.

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