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.Experience of Using Charcoal-Processed Traditional Chinese Medicine in the Treatment of Gynecological Hemorrhagic Disorders
Xiaolan WU ; Zhaoling YOU ; Guiyun WANG ; Kailing WANG ; Xiaojuan YE ; Lingyu LIAO ; Yueheng LI ; Huiping LIU
Journal of Traditional Chinese Medicine 2025;66(3):308-311
Charcoal-processed traditional Chinese herbal medicine has various therapeutic effects, including astringing, hemostasis, anti-diarrhea, clearing heat, tonifying, and warming the interior. This paper summarizes the clinical application features, compatible experiences, dosages, and precautions for over 20 types of charcoal-processed herbal medicine in the treatment of gynecological bleeding disorders caused by dysfunctions such as dysfunctional uterine bleeding, endometriosis, uterine incision pseudocavity, and vaginal bleeding resulting from threatened miscarriage. The charcoal-processed herbal medicine include Huangqin (Scutellaria Baicalensis) Charcoal, Dahuang (Rheum Palmatum) Charcoal, Cebai (Platycladus Orientalis) Charcoal, Diyu (Sanguisorba Officinalis) Charcoal, Daji (Cirsium Setosum) Charcoal, Xiaoji (Cirsium Japonicum) Charcoal, Shengdi (Rehmannia Glutinosa) Charcoal, Aiye (Artemisia Argyi) Charcoal, Paojiang (Zingiber Officinale) Charcoal, Xuduan (Dipsacus Asper) Charcoal, Duzhong (Eucommia Ulmoides) Charcoal, Qiancao (Rubia Cordifolia) Charcoal, Puhuang (Typha Angustifolia) Charcoal, Shanzha (Crataegus Pinnatifida) Charcoal, Jingjie (Schizonepeta Tenuifolia) Charcoal, Xueyu (Carthamus Tinctorius) Charcoal, Zonglyu (Areca Catechu) Charcoal, Wumei (Prunus Mume) Charcoal, Shudahuang (Rheum Officinale) Charcoal, Lianfang (Nymphaea Alba) Charcoal, Mianmaguanzhong (Clematis Armandii) Charcoal, and Oujie (Nelumbo Nucifera) Charcoal.
4.Changes and clinical significance of senescent cell proportion and senescence-associated cytokines in acute myeloid leukemia
Linlin LIU ; Qianshan TAO ; Huiping WANG ; Qing ZHANG ; Zhimin ZHAI
Chinese Journal of Immunology 2024;40(10):2141-2145
Objective:To investigate changes and clinical significance of senescent cell proportion and senescence-associated cytokines in peripheral blood of patients with acute myeloid leukemia(AML)in different states.Methods:AML patients who were diagnosed and treated in the Second Hospital of Anhui Medical University were selected as research subjects(17 cases in newly diag-nosed group,16 cases in remission group,and 12 cases in relapse group),morphology of leukemia blasts and proportion of senescent cells in peripheral blood of patients in each group were observed by Regis and senescence specific β-galactosidase(SA-β-gal)staining,levels of senescence-associated cytokines IL-8,IL-1β,IL-6,IL-10 in peripheral blood of each group were detected by cytometric bead array(CBA),and differences and clinical significance among groups were compared.Results:Relapse group peripheral blood smear Regis staining showed that morphology of leukemia blasts increased significantly and proportion of SA-β-gal positive cells was significantly increased(P<0.01);levels of serum senescence-associated cytokines IL-8,IL-1β,IL-6 and IL-10 in relapse group were significantly increased(P<0.05);there was no correlation between serum senescence-associated cytokine levels and proportion of peripheral blood leukemia blasts(P>0.05);relapsed patients with higher IL-8 levels trend to have lower re-induction remission rates and worse overall survival after relapse(P<0.05);multivariate Cox regression analysis showed that IL-8 level was an indepen-dent risk factor for prognosis of relapsed patients(P<0.05).Conclusion:Increased proportion of senescent cells and significantly increased levels of senescence-associated cytokines IL-8,IL-1β,IL-6,IL-10 in peripheral blood of AML patients are closely related to disease recurrence,and relapsed patients with higher IL-8 level had poor prognosis.
5.Expert consensus on the rational use of psychotropic drugs related to intensive care medicine
Shenglin SHE ; Zhen SONG ; Tongwen SUN ; Jingguo ZHAI ; Yan YU ; Ningbo YANG ; Maosheng FANG ; Wenbin GUO ; Man WANG ; Guanglei XUN ; Lulu ZHANG ; Xijia XU ; Xiaoli WU ; Qinling WEI ; Fang LIU ; Huiping LI ; Xingrong SONG ; Youping WANG ; Yingjun ZHENG ; Xueqin SONG
Chinese Journal of Nervous and Mental Diseases 2024;50(9):513-524
Critical care medicine-related treatment is an interdisciplinary and multi-professional process,often leading to secondary or concomitant mental disorders in clinical practice.Currently,there is no consensus on the pharmacological treatment of related mental illnesses in China.The Chinese Society of Psychosomatic Medicine collaborated with the Critical Care Medicine expert group to form a consensus writing expert group.After a systematic review of relevant literature,summarizing published domestic and foreign literature,and extensive discussions,the consensus was developed.The consensus elaborates on the principles and processes of the standardized use of psychotropic drugs in critical care medicine,as well as the clinical indications,precautions,and specific drug selection of various psychiatric medications,providing feasible suggestions and guidance for the clinical application of psychiatric medications in the intensive care unit.
6.Research Progress on Permanent Pacemaker Implantation After Transcatheter Aortic Valve Replacement
Nan CHEN ; Xi PENG ; Junpeng LIU ; Huiping ZHANG
Chinese Circulation Journal 2024;39(9):924-930
Indications of transcatheter aortic valve replacement(TAVR)are extending to lower risk population.High atrioventricular block is one of the common complication of TAVR,permanent pacemaker implantation is receiving high recognition now.This review summarizes research progress on the anatomy,indicators,predictors and prognosis of permanent pacemaker implantation after TAVR.
7.The Role of Cells and Cytokines in Male Infertility Induced by Orchitis
Ying XU ; Wanyi CHEN ; Xiaoyu WU ; Kai ZHAO ; Chunyan LIU ; Huiping ZHANG
The World Journal of Men's Health 2024;42(4):681-693
Recent studies on male infertility reveal a growing worry: more infertile men are dealing with inflammation in the testis. Analyzing testicular biopsies from infertile men highlights a significant presence of inflammation. This connection, supported by clinical and pathological evidence, emphasizes that testicular inflammation hampers sperm production, leading to lasting declines in sperm count and quality. However, the exact reasons behind male infertility due to orchitis, a type of testicular inflammation, are still uncertain. Understanding these fundamental aspects of molecular signals and cellular mechanisms in testicular inflammation is crucial. Our review delves into recent literature with a dual objective: elucidating potential mechanisms involving immune cells, non-immune cells, and cytokines that link orchitis to male infertility, while also paving the way for precise interventions and solutions to address the challenges of male infertility.
8.Study on influencing factors for falls risks score in the elderly
Sihang FANG ; Dizhi LIU ; Chunyuan JIA ; Danni GAO ; Liang SUN ; Xiaoquan ZHU ; Qi ZHOU ; Ze YANG ; Wei XU ; Yuan LYU ; Guofang PANG ; Caiyou HU ; Huiping YUAN
Chinese Journal of Geriatrics 2024;43(11):1481-1485
Objective:To investigate the factors influencing fall risk scores in elderly individuals.Methods:A total of 4 419 individuals were randomly selected using the cluster sampling method from Beijing, Nanning(Guangxi), and Yinchuan(Ningxia).Data on demographic characteristics and fall-related incidents were gathered and analyzed for their correlation with fall risk scores.Results:The fall risk score showed significant associations with various factors, such as the history of falls within one year( β=-3.607, 95% CI: -3.881 to -3.332), care methods( β=2.442, 95% CI: 2.226 to 2.658), exercise( β=0.714, 95% CI: 0.443 to 0.986), retirement( β=-0.585, 95% CI: -0.819 to -0.351), age( β=0.173, 95% CI: 0.159 to 0.187), and use of walking aids( β=-3.737, 95% CI: -4.054 to -3.421). Conclusions:Fall risk scores in older adults are influenced by a variety of factors.Factors such as no history of falls within the past year, living independently, engaging in physical activity, and being employed may contribute to lower fall risk scores in older adults.
9.Effects of mild intraventricular hemorrhage on early motor development in infants with high risk of brain injury
Jingyu BU ; Huiping ZHANG ; Ru JIAN ; Sa YUAN ; Tian LIU ; Yanni CHEN
Chinese Pediatric Emergency Medicine 2024;31(8):586-591
Objective:To assess the effect of mild intraventricular hemorrhage(IVH)on the early motor development of infants at high risk of brain injury,and to guide the intervention according to its characteristics.Methods:A retrospective cohort study was conducted to select neonates discharged from the Neonatal Unit of Xi 'an Children 's Hospital from February 1,2022 to March 31,2023,with one or more high-risk factors of brain injury.The patients were assigned to low-grade IVH group and no IVH group according to ultrasound diagnosis.The research subjects exclucled other brain injury diseases besides mild IVH.Motor development was assessed using test of infant motor performance(TIMP),reflecting performance in head control,auditory and visual responses,defensive movements,trunk movements,limb movements,and more.Both groups completed TIMP assessment between discharge and 16 weeks of the corrected age(CA).The differences of TIMP scores between two groups were compared . Results:A total of 329 neonates at high risk for brain injury were recruited,including 98 cases with grade Ⅰ-Ⅱ IVH(low-grade IVH group)diagnosed through brain ultrasonography and 231 controls(no IVH group).The Z scores of TIMP in the low-grade IVH group were lower than that in no IVH group(-0.25 ±0.87 vs.0.03 ±0.71, P=0.015).The risk factors of brain injury were matched for further comparison.At CA2-5 weeks,the scores in low-grade IVH group of TIMP total scores(74.10 ±12.28 vs.84.24 ±7.71),observation items(10.57 ±1.47 vs.11.24 ±1.29),elicitation(63.17 ±12.13 vs.73.00 ±7.36),sitting(9.14 ±2.90 vs.11.65 ±3.26),supine(22.07 ±4.73 vs.24.79 ±3.55),prone position(10.35 ±3.74 vs.12.82 ±3.15)and lateral position(4.00 ±2.85 vs.5.48 ±2.13)were significantly lower than those in no IVH group( P<0.05).At CA6-9 weeks,the scores in low-grade IVH group of sitting position(10.44 ±4.01 vs.12.96 ±3.02),supine position(24.04 ±4.60 vs.26.83 ±3.53),lateral position(4.83 ±2.53 vs.6.25 ±2.6)were significantly lower than those in no IVH group( P<0.05).At CA12-15 weeks,the low-grade IVH group showed significant differences in TIMP total score(104.00 ±12.98 vs.114.10 ±13.16),elicitation(92.00 ±12.64 vs.102.00 ±13.10),sitting(17.00 ±3.50 vs.19.13 ±3.55)and lateral position(7.35 ±2.14 vs.9.00 ±2.37)compared with those from no IVH group( P<0.05). Conclusion:Mild intraventricular hemorrhage affected the early motor development of high-risk infants with brain injury,mainly manifested as a lag in the ability of head control at CA2-5 weeks,and the trend continued until CA12-15 weeks.Early monitoring of motor ability and intervention of head control ability should be carried out in high-risk children with mild intraventricular hemorrhage.
10.Targeted delivery of rosuvastatin enhances treatment of hyperhomocysteinemia-induced atherosclerosis using macrophage membrane-coated nanoparticles
Liu DAYUE ; Yang ANNING ; Li YULIN ; Li ZHENXIAN ; You PEIDONG ; Zhang HONGWEN ; Quan SHANGKUN ; Sun YUE ; Zeng YALING ; Ma SHENGCHAO ; Xiong JIANTUAN ; Hao YINJU ; Li GUIZHONG ; Liu BIN ; Zhang HUIPING ; Jiang YIDENG
Journal of Pharmaceutical Analysis 2024;14(9):1301-1319
Rosuvastatin(RVS)is an excellent drug with anti-inflammatory and lipid-lowering properties in the aca-demic and medical fields.However,this drug faces a series of challenges when used to treat atherosclerosis caused by hyperhomocysteinemia(HHcy),including high oral dosage,poor targeting,and long-term toxic side effects.In this study,we applied nanotechnology to construct a biomimetic nano-delivery system,macrophage membrane(M?m)-coated RVS-loaded Prussian blue(PB)nanoparticles(MPR NPs),for improving the bioavailability and targeting capacity of RVS,specifically to the plaque lesions associated with HHcy-induced atherosclerosis.In vitro assays demonstrated that MPR NPs effectively inhibited the Toll-like receptor 4(TLR4)/hypoxia-inducible factor-1α(HIF-1α)/nucleotide-binding and oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathways,reducing pyroptosis and inflammatory response in macrophages.Additionally,MPR NPs reversed the abnormal distribution of adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1)/ATP binding cassette transporter G1(ABCA1)/ATP binding cassette transporter G1(ABCG1)caused by HIF-1α,promoting cholesterol efflux and reducing lipid deposition.In vivo studies using apolipoprotein E knockout(ApoE-/-)mice confirmed the strong efficacy of MPR NPs in treating atherosclerosis with favorable bio-security,and the mechanism behind this efficacy is believed to involve the regulation of serum metabolism and the remodeling of gut microbes.These findings suggest that the synthesis of MPR NPs provides a promising nanosystem for the targeted therapy of HHcy-induced atherosclerosis.

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