1.Mechanism of Action of Kaixinsan in Ameliorating Alzheimer's Disease
Xiaoming HE ; Xiaotong WANG ; Dongyu MIN ; Xinxin WANG ; Meijia CHENG ; Yongming LIU ; Yetao JU ; Yali YANG ; Changbin YUAN ; Changyang YU ; Li ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):20-29
ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease (AD) based on network pharmacology, molecular docking, and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and the Encyclopedia of Traditional Chinese Medicine(ETCM) databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards, Online Mendelian Inheritance in Man(OMIM), TTD, PharmGKB, and DrugBank databases were used to obtain the relevant targets of AD. The intersection (common targets) of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken, and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction(PPI) network. The CytoNCA plugin within Cytoscape was used to screen out the core targets, and the Metascape platform was used to perform gene ontology(GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2, and AutoDock Vina was used for molecular docking. Scopolamine (SCOP) was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control (CON) group (0.9% NaCl, n=8), model (SCOP) group (3 mg·kg-1·d-1, n=8), positive control group (3 mg·kg-1·d-1 of SCOP+3 mg·kg-1·d-1 of Donepezil, n=8), and Kaixinsan group (3 mg·kg-1·d-1 of SCOP+6.5 g·kg-1·d-1 of Kaixinsan, n=8). Mice in each group were administered with 0.9% NaCl, Kaixinsan, or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin (HE) staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay(ELISA) was used to determine the serum acetylcholine (ACh) and acetylcholinesterase (AChE) contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3(STAT3) and nuclear transcription factor(NF)-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained, and 578 potential targets (common targets) of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol, gijugliflozin, etc.. Potential core targets were STAT3, NF-κB p65, et al. GO functional enrichment analysis obtained 3 124 biological functions, 254 cellular building blocks, and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways, mainly involving cancer-related pathways, TRP pathway, cyclic adenosine monophosphate(cAMP) pathway, and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65, STAT3, and other targets involved in the NF-κB signaling pathway.
2.Discussion on the syndrome of toxin and blood stasis in myelodysplastic syndrome from Xuanfu theory
Jing HAO ; Jiaxin LYU ; Yanbo CHANG ; Zihan PENG ; Ziran HU ; Dongyu GUO ; Tianfeng QI ; Dandi HE ; Mingjie GAO ; Jinhuan WANG
International Journal of Traditional Chinese Medicine 2024;46(4):415-419
Myelodysplastic syndrome (MDS) is a malignant hematologic tumor, which is currently difficult to cure. The theory of Xuanfu was proposed by Liu Wansu, which is unique in the clinical evidence of Chinese medicine and is less frequently applied to hematological diseases. The application of Xuanfu theory in myelodysplastic syndrome provides new ideas for the treatment of the disease. The abnormal flow of Qi, blood and fluids caused by the occlusion of the Xuanfu is the cause of toxic stasis obstruction, which is the pathogenesis of toxic stasis obstruction. Thus, the method of dispersion of Bone from Xuanfu, the external treatment of Xuanfu, and regulation of liver qi and Xuanfu help to return to normal of opening and closing function of Xuanfu, and release toxic stasis. In this paper, we analyzed the evidence of toxin-stasis obstruction in myelodysplastic syndrome from the theory of Xuanfu, aiming to provide a feasible theoretical basis for clinical treatment of the disease.
3.Therapeutic effect of pachymic acid on Helicobacter pylori-associated gastritis in rats by regulating the PI3K/AKT/NF-κB signaling pathway
Lu XU ; Dongyu ZHANG ; Ruifeng WANG
Basic & Clinical Medicine 2024;44(4):489-495
Objective To explore the therapeutic effect and mechanism of pachymic acid(PA)on Helicobacter py-lori(Hp)-associated gastritis in rats.Methods A rat model of Hp-associated gastritis was established;all rats were separated into control group(CT group),model group(group M),PA low-dose group(PA L group),PA high-dose group(PA H group),and PA H+phosphatidylinositol 3-kinase(PI3K)activator(740 Y-P)group;the gastric mucosal injury index(UI)of rats in each group was evaluated,transmission electron microscopy was applied to observe the morphology of gastric mucosal cells.HE staining was applied to evaluate the pathological characteristics of gastric mucosa.ELISA was applied to detect the levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),IL-10,induc-ible nitric oxide synthase(iNOS),and superoxide dismutase(SOD)in gastric tissue.Western blot method was applied to detect the expression of PI3K,phosphorylated PI3K(p-PI3K),protein kinase B(AKT),p-AKT,nuclear factor(NF)-κB p65,and p-NF-κB p65 proteins.Results Compared with the CT group,the gastric mucosa erosion,epithelial ede-ma,congestion,and severe ulcers were observed in the group M,with epithelial cell pyknosis and inflammatory cell in-filtration,the UI,IL-6,TNF-α,iNOS,and the expression levels of p-PI3K/PI3K,p-AKT/AKT,p-NF-κB p65/NF-κB p65 proteins increased,the levels of IL-10 and SOD decreased(P<0.05);compared with group M,the gastric mucosal damage and inflammatory cell infiltration in the PA L and PA H groups were improved,the UI,IL-6,TNF-α,iNOS by the host animal and the expression of p-PI3K/PI3K,p-AKT/AKT,p-NF-κB p65/NF-κB p65 proteins all decreased,the level of IL-10 and SOD was increased(P<0.05);compared with the PA H group,the pathological damage of the gastric mucosa in the PA H+740 Y-P group was aggravated,with epithelial cell pyknosis.The UI,IL-6,TNF-α,iNOS,and the expression of p-PI3K/PI3K,p-AKT/AKT,p-NF-κB p65/NF-κB p65 proteins increased,the levels of IL-10 and SOD decreased(P<0.05).Conclusions PA might facilitate the treatment of Hp-associated gastritis in rats by inhibiting the PI3K/AKT/NF-κB signaling pathway.
4.Effect of transcutaneous electrical acupoint stimulation bracelet at Neiguan acupoint on post-operative nausea and vomiting after thyroidectomy under general anesthesia
Ming GONG ; Hongwei ZHU ; Dongyu ZHENG ; Na WANG ; Yonghua LI ; Hongbin YUAN
The Journal of Clinical Anesthesiology 2024;40(2):124-127
Objective To explore the effect of transcutaneous electrical acupoint stimulation bracelet at Neiguan acupoint on the postoperative nausea and vomiting after thyroidectomy under general an-esthesia.Methods Seventy-two female patients underwent thyroidectomy,aged 18-50 years,ASA physical status Ⅰ or Ⅱ,were enrolled.The patients were assigned 1 ∶ 1 to two groups by permuted block randomization:the electrical stimulation group and the control group,36 patients in each group.Before an-esthesia induction,patients in both groups wore domestic transcutaneous electrical acupoint stimulation bracelets,and the electrodes were aimed at Neiguan acupoint.The electrical stimulation group started to stimulate Neiguan acupoint,and adjusted the proper intensity to make the patient feel tingling in the related area of the hand.When the bracelet was fixed firmly,turned it off.At the end of the operation,the bracelet was turned on with the stimulation intensity set before induction for 24 hours.Patients in the control group also wore the bracelet for 24 hours,but it was never turned on.The number of cases of postoperative nausea and vomiting(PONV)and the number of remedial cases of antiemetic drugs were recorded.Results Compared with the control group,the incidence of PONV and postoperative vomiting in the electrical stimula-tion group were significantly reduced within 24 hours after surgery(P<0.05),and the differences were mainly in 1-6 hours after surgery(P<0.05).There was no significant difference in the rate of remedial ca-ses of antiemetic drugs between the two groups at different time periods.Conclusion Transcutaneous electri-cal stimulation bracelet at Neiguan acupoint can effectively reduce the incidence of PONV within 24 hours after thyroidectomy.
5.Efficacy and safety of obturator urethral suspension for the treatment of male stress urinary incontinence
Dongyu SU ; Qi WANG ; Xiaopeng ZHANG ; Kexin XU
Chinese Journal of Urology 2024;45(9):676-680
Objective:To evaluate the safety and efficacy of transtobturator urethral sling operation in the treatment of male stress urinary incontinence.Methods:A retrospective analysis was conducted on the clinical data of 13 male patients with stress urinary incontinence who underwent transvaginal sling procedure at Peking University People's Hospital from June 2011 to July 2024. The patients' average age was (71.6±5.4) years. Among them, 9 patients had undergone radical prostatectomy, and 4 had undergone transurethral resection of the prostate (TURP). Of the 13 patients, 7 had moderate urinary incontinence, and 6 had severe urinary incontinence. The median daily number of urine pads used by the 13 patients before surgery was 5 (3, 8), and the median score of the Incontinence Quality of Life Questionnaire (I-QOL) was 16 (12, 28). The median score of the Male Stress Urinary Incontinence Grading Scale (MSIGS) was 2 (2, 3). All the 13 patients underwent transvaginal sling procedure. The patients were placed in the lithotomy position, and the urethral bulb was dissected anatomically beneath the scrotum. The sling was guided by a needle and pulled out through the obturator foramen, and placed over the urethral bulb. The sling was tightened and the tension adjusted to fully suspend the urethra. A urinary catheter was left in place for 1-7 days after surgery. The patients' postoperative daily use of urine pads, scores of the I-QOL and MSIGS, and postoperative complications were followed up.Results:Postoperative follow-up ranged from 2 to 139 months, with a median follow-up time of 12 months. Of the 13 patients, 2 were cured, 9 had improved and 2 had no significant improvement. The number of diapers used per day by patients postoperatively was 1 (1, 4) pieces, the I-QOL score was 75 (46, 82), and the MSIGS score was 1 (0, 2), which were all significantly improved compared to preoperative values ( P<0.01). Among the 6 severe stress urinary incontinence patients who were followed up, the number of diapers used per day was significantly reduced compared to preoperative values[ 2(1, 5) vs. 8(7, 8) pieces], and the I-QOL score was significantly improved [ 60(35, 70) vs. 12(10, 16) ], while the MSIGS score was significantly lower [ 2(1, 3) vs. 3(2, 4) ]. Among the 7 moderate stress urinary incontinence patients, the number of diapers used per day was significantly reduced compared to preoperative values [1 (0, 1) vs. 4 (4, 5) pieces], and the I-QOL score was significantly improved [ 80(75, 82) vs. 21(18, 30) ], while the MSIGS score was significantly lower [ 0 (0, 1) vs. 2 (2, 3) ]. The symptoms of 1 patient were not significantly improved after the surgery, and were improved after Virtue sling suspension 3 years later. Conclusions:The use of transtobturator urethral sling operation for the treatment of moderate to severe male stress urinary incontinence has shown clear efficacy, with a low incidence of postoperative complications.
6.Effects of pecking moxibustion on pattern characteristics and synovial cell ultrastructure of rats with rheumatoid arthritis due to damp heat affecting bones/joints
Ting YUE ; Dongyu YANG ; Huirong DENG ; Yu LIU ; Yu WANG ; Jibo YANG ; Zhongting ZHAO ; Xingke YAN ; Tiantian ZHU ; Yanping YANG
Journal of Acupuncture and Tuina Science 2024;22(4):280-288
Objective:To observe the effect of pecking moxibustion on the pattern characteristics of redness,swelling,heat,and pain in the affected joints,also the synovial cell ultrastructure in rats with rheumatoid arthritis(RA)due to damp heat affecting bones/joints,and to explore the anti-inflammatory mechanism of pecking moxibustion in treating the early stage of RA. Methods:Eighteen rats were randomly selected from 78 female ones as the blank group,and all the other rats were subjected to preparing the"differentiation of disease and pattern"RA model due to damp heat affecting bones/joints by using the method of"collagen-induced arthritis plus windy,damp,and hot environment stimulation".Fifty-four rats with successful modeling were randomly divided into a model group,a drug group,and a pecking moxibustion group,with 18 rats in each group.Rats in the drug group were given methotrexate at a dose of 1 mg/(kg·bw)on the 1st,8th,and 15th days.Rats in the pecking moxibustion group were treated with pecking moxibustion at Quchi(LI11),Dazhui(GV14),and Ashi points,and each point was treated with moxibustion for 15 min every day and a total of 3 courses of treatment,with 6 d as a course of treatment.After treatment,the capillary permeability,joint swelling,joint surface temperature,and plantar thermal pain threshold of the diseased joints in rats were observed,and the ultrastructural changes of synovial cells were observed by transmission electron microscopy. Results:The local swelling,surface temperature,and Evans blue(EB)leakage volume were significantly higher(P<0.05),the thermal pain threshold was significantly lower(P<0.05),and the synovial cell ultrastructure was obviously damaged in the affected joints in the model group compared with the blank group.The swelling degree,surface temperature,and EB leakage volume were significantly reduced(P<0.05),the thermal pain threshold was significantly increased(P<0.05),and the ultrastructural abnormalities of synovial cells were significantly improved in the diseased joints in the drug group and the pecking moxibustion group compared with the model group.The thermal pain threshold of rats in the pecking moxibustion group was significantly improved compared with the drug group(P<0.05). Conclusion:Pecking moxibustion obviously improves the pattern characteristics of local redness,swelling,heat,and pain in the diseased joints of rats with RA due to damp heat affecting bones/joints and effectively repairs the ultrastructure of the damaged synovium.It suggests that the pecking moxibustion intervention has a significant anti-inflammatory effect on early RA.
7.Current status and prospect of pravastatin in pregnancy
Xiaohong LIN ; Dongyu WANG ; Lixia SHEN ; Zilian WANG
Chinese Journal of Perinatal Medicine 2023;26(8):696-700
Cholesterol-lowing statins such as pravastatin have been contraindicated in pregnant women for a long time, but recent clinical evidence has demonstrated its safety. Studies have found that pravastatin can correct the imbalance in angiogenesis, reduce vascular inflammation and improve the conditions in patients with placental and maternal vascular dysfunction-related diseases, such as preeclampsia, fetal growth restriction and antiphospholipid syndrome. However, universal administration of pravastatin in pregnancy still requires more evidence on its safety from human clinical trials with larger sample sizes. This article reviews the current situation and prospect of pravastatin in pregnancy.
8.Study on the Jianpi Huatan Formula Regulating VSMC Proliferation-related miRNA in ApoE-/-AS mice Based on High-throughput Sequencing Technology
Miao TIAN ; Lianqun JIA ; Xing JU ; Le GUAN ; Yang WANG ; Dongyu MIN ; Gaole DU ; Jingyu TONG ; Guanlin YANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(11):3646-3653
Objective This study used high-throughput sequencing technology to detect the regulation of JianPiHuaTan Prescription(JPHT)on the ApoE-/-mouse miRNA related to vascular smooth muscle cells proliferation and migration,verify the expression of related proteins,and explore the therapeutic effect of JPHT on atherosclerosis.Methods Ten of C57BL/6J mice were used as control group,and 30 ApoE-/-mice were randomly divided into model group,western medicine group and JPHT group.Sequencing technology was performed on aortic sample to select the differentially expressed miRNA.We screened out the tagetted miRNA related to VSMCs proliferation and migration.RT-qPCR and Western blot technology were used to test the differentially expressed miRNA and tagetted protein.Results Compared with model group,a total of 9 miRNAs were changed in JPHT group,among which 7 were up-regulated and 2 were down-regulated.The expression of miRNA-34a was up-regulated in JPHT group.The miRNA-34a and α-SMA protein expression in aorta of JPHT group were significantly different with model group by RT-qPCR and Western blot experiment(P<0.01).Conclusion Jianpi Huatan Prescription may improve ApoE-/-mice atherosclerosis through inhibitting the proliferation of vascular smooth muscle cells by regulating miRNA-34a.
9.The effects of repetitive transcranial magnetic stimulation combined with divergent shock wave on the muscle spasm in patients with traumatic spinal cord injury
Lihua LUO ; Dongyu WU ; Yusheng WANG
Chinese Journal of Rehabilitation Medicine 2023;38(12):1663-1668
Objective:To observe the effects of repetitive transcranial magnetic stimulation combined with divergent shock wave on muscle spasm in patients with traumatic spinal cord injury,and to explore a new clinical treatment method for the disease. Method:Fifity-nine patients with traumatic spinal cord injury with muscle spasm from January 2017 to June 2021 were selected and randomly divided into the observation group(n=30)and the control group(n=29)with the method of random number table.The patients in the observation group received repeated transcranial magnet-ic stimulation combined with divergent shock wave therapy,while the patients in the control group received ba-clofen treatment.Both groups received conventional rehabilitation therapy,including exercise therapy,acupunc-ture and massage.The treatment time was 8 weeks.The modified Ashworth score,Barthel index and SF-36 score of the patients in the observation group and the control group were compared before and after treatment. Result:After treatment,the effective rate of the observation group was 86.67%,which was significantly high-er than that of the control group(P<0.05).The total score of Barthel index and SF-36 score of the two groups were significantly increased compared with those before treatment(P<0.05).The Barthel index and SF-36 score in the observation group were significantly higher than those in the control group(P<0.05). Conclusion:Repetitive transcranial magnetic stimulation combined with divergent shock wave can effectively im-prove the symptoms of muscle spasm in patients with traumatic spinal cord injury and can fully improve their ability of daily life and quality of life,which has achieved good clinical efficacy.
10.Content determination of 5-HMF in glucosamine hydrochloride tablets and formation kinetics study
Dongyu NI ; Qiongfen WANG ; Mengqi ZHANG ; Bin LI ; Jing SHI ; Hong XU ; Shuai ZHANG
China Pharmacy 2023;34(8):950-954
OBJECTIVE To establish the method for the content determination of 5-hydroxymethylfurfural (5-HMF) in glucosamine hydrochloride tablets, and to analyze its regularity and influential factors. METHODS Quantitative analysis of 5-HMF was performed using high-performance liquid chromatography. The analysis was conducted on Shim-pack GIST C18-AQ column with mobile phase consisted of 0.1% phosphoric acid solution-methanol (90∶10, V/V) at the flow rate of 1.0 mL/min. The column temperature was 30 ℃, and detection wavelength was 284 nm. The injection volume was 20 μL. Reaction kinetics test of different temperatures was adopted to analyze the relationship of 5-HMF content with reaction temperature and reaction time, and utilized to build its formation kinetic model. RESULTS The linger range of 5-HMF was 0.057-5.698 μg/mL (r=0.999 9). The limits of detection and quantitation were 5.70 and 17.09 ng/mL; RSDs of precision, repeatability and stability (24 h) tests were all lower than 1.0% (n=6). The average recoveries ranged from 99.38% to 99.73%(RSD=0.53%, n=9). The contents of the 5-HMF in 8 batches of samples ranged 4.10-35.13 μg/g. Results of data fitting in reaction kinetics test showed that the higher reaction temperature and the longer reaction time, the higher 5-HMF content in the sample. At 50, 60, 70 and 80 ℃ , the relationship between the content of 5-HMF and the reaction time was linear, in accordance with a zero-order kinetic model. The reaction rate constants were 6.789, 7.715, 8.815 and 11.430, respectively. CONCLUSIONS The established method has strong specificity, high sensitivity, and good accuracy; the reaction temperature and reaction time are important influential factors for the formation of 5-HMF in glucosamine hydrochloride tables. The change rule of its content conforms to the zero-order kinetic model.

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