1.Effect of Wenpi tongluo kaiqiao formula against neuronal necroptosis in mice with Alzheimer’s disease and its mechanism
Xiaomin ZHU ; Wei CHEN ; Yulan FU ; Guifeng ZHUO ; Yingrui HUANG ; Ying ZHANG ; Lin WU
China Pharmacy 2025;36(9):1046-1051
OBJECTIVE To investigate the effects and mechanism of Wenpi tongluo kaiqiao formula (WPTL) against neuronal necroptosis in Alzheimer’s disease (AD) mice based on the Z-DNA binding protein 1 (ZBP1)/mixed lineage kinase domain-like protein (MLKL) signaling pathway. METHODS Forty APP/PS1 transgenic AD mice were randomly divided into model group, WPTL low-dose (WPTL-L) group (10.4 g/kg, calculated by the raw medicine), WPTL high-dose (WPTL-H) group (20.8 g/kg, calculated by the raw medicine) and donepezil hydrochloride group (3 mg/kg), with 10 mice in each group; another 10 C57BL/6J mice were selected as normal control group. Intragastric administration, once a day, for 30 consecutive days. Twenty-four hours after the last administration, Morris water maze test was performed to evaluate learning and memory abilities; the pathological morphology of hippocampal tissues was observed; the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4) were determined; the expressions of amyloid precursor protein (APP), Tau protein, and ZBP1/MLKL signaling pathway-related proteins in hippocampal tissues were detected; the positive expression of phosphorylated receptor-interacting protein kinase 3 (p-RIPK3) in the neurons of hippocampal tissues and mRNA expression of ZBP1 were measured in hippocampal tissues. RESULTS Compared with normal control group, the escape latency of mice in model group was prolonged significantly on day 3 to 5 (P<0.05), the times of crossing platform reduced significantly (P<0.05), and obvious pathological changes were observed in the hippocampal tissue. The level of TNF- α, the expressions of APP, p-Tau and ZBP1, the phosphorylation levels of RIPK1, RIPK3 and MLKL, the fluorescence intensity of p-RIPK3 as well as the mRNA expression of ZBP1 were significantly increased (P<0.05), while the serum level of IL-4 was decreased significantly (P<0.05). Compared with model group, above indexes were reversed significantly in administration groups (P<0.05), and pathological damage of hippocampal tissue was alleviated. CONCLUSIONS WPTL can inhibit the ZBP1/MLKL signaling pathway, reduce neuronal necroptosis in AD mice, and inhibit inflammatory responses, thereby improving learning and spatial memory abilities in AD mice.
2.Accuracy and consistency of predicting vault using NK and KS formulas before implantable collamer lens implantation
Xunshan ZU ; Li JIAO ; Yulan SUN ; Li LI
International Eye Science 2025;25(6):1014-1019
AIM: To explore the accuracy and consistency of predicting postoperative vault in implantable collamer lens(ICL)surgery based on the NK and KS formulas of CASIA2 OCT.METHODS: Retrospective case study. The study included 85 patients(170 eyes)who underwent ICL implantation for the correction of moderate to high myopia at the Refractive Surgery Center of Lunan Eye Hospital from October 2022 to October 2023. Routine examinations including ultrasound biomicroscopy(UBM), corneal endothelium assessment, optometry, intraocular pressure measurement, fundus examination, and corneal topography were performed. Patients who met the indications for ICL surgery were selected, and the recommended lens size was determined based on parameters such as corneal diameter and anterior chamber depth using standard methods. A CASIA2 OCT examination was used to obtain the corresponding lens size and predicted vault using the NK and KS formulas. The differences and consistency between the predicted vault by NK and KS formulas and the actual vault at 1 wk, 1, 3, and 6 mo postoperatively were analyzed. Paired t-tests were used to analyze the differences between the predicted vault by NK and KS formulas and the actual vault at each postoperative time point. The consistency between the predicted vault by NK and KS formulas and the actual vault at each time point was assessed using Bland-Altman analysis. Multivariate linear regression was used to analyze the correlation between actual vault and various anterior segment parameters.RESULTS: The NK formula showed statistically significant differences between the predicted values and the actual vault at 1, 3, and 6 mo postoperatively(all P<0.05), but no statistically significant difference was observed compared to the actual vault at 1 wk postoperatively(P=0.340). The KS formula demonstrated a statistically significant difference between the predicted values and the actual vault measured at 6 mo postoperatively(P<0.05). The lens vector height and lens model were influcing facotrs for the vault at 6 mo postoperatively(all P<0.05). Both the NK formula and KS formula had the highest consistency between their predicted vault and the actual vault at 6 mo postoperatively.CONCLUSION: The NK and KS formulas of CASIA2 OCT showed the highest consistency between the predicted postoperative vault and the actual vault at 6 mo postoperatively. Both formulas can serve as effective references for ICL model selection.
3.Anti-vascular dementia effect of Yifei xuanfei jiangzhuo formula by inhibiting mitochondrial fission
Yulan FU ; Wei CHEN ; Guifeng ZHUO ; Xiaomin ZHU ; Yingrui HUANG ; Jinzhi ZHANG ; Fucai YANG ; Ying ZHANG ; Lin WU
China Pharmacy 2025;36(15):1859-1865
OBJECTIVE To investigate the intervention effect and its potential mechanism of Yifei xuanfei jiangzhuo formula by inhibiting mitochondrial fission in a vascular dementia (VaD) model rats. METHODS VaD rat model was established by bilateral common carotid artery ligation. The experimental animals were randomly divided into sham operation group (SHAM), model group (MOD),Yifei xuanfei jiangzhuo formula low-dose group (YFXF-L), Yifei xuanfei jiangzhuo formula high-dose group (YFXF-H), and Donepezil hydrochloride group (positive control), with 9 animals in each group. After 30 days of intervention, the spatial learning memory ability was assessed by Morris water maze experiment; HE staining was used to observe histopathological changes in CA1 area of hippocampus; ELISA was used to detect the levels of serum inflammatory factors [interleukin-1β (IL-1β) and IL-4]; Western blot was used to detect the expressions of heat shock protein 90 (HSP90)/mixed lineage kinase domain-like protein (MLKL)/dynamin-related protein 1 (Drp1) pathway-related proteins, mitochondrial fusion proteins (MFN1, MFN2), and adenosine triphosphate synthase 5A (ATP5A) in hippocampal tissues. The immunohistochemistry was used to detect the level of phosphorylated MLKL (p-MLKL); real-time fluorescence quantitative PCR was adopted to detect mRNA expressions ofHSP90, MFN1, MFN2 and ATP5A. RESULTS Compared with SHAM group, the escape latency of rats in the MOD group was significantly prolonged, the number of crossing the platform was significantly reduced, and the hippocampal tissues showed typical neuronal damage characteristics, the positive expression level of p-MLKL and the serum level of IL-1β significantly increased, while the serum level of IL-4 significantly decreased, the protein and mRNA expression of HSP90, as well as the protein expressions of p-MLKL/MLKL and p-Drp1(Ser616)/Drp1 were all significantly increased in hippocampal tissue, the protein and mRNA expressions of MFN1, MFN2 and ATP5A, and protein expression of p-Drp1(Ser637)/Drp1 were all significantly decreased (P<0.05). After the intervention of Yifei xuanfei jiangzhuo formula, above indicators in each treatment group were all significantly reversed (P<0.05). CONCLUSIONS Yifei xuanfei jiangzhuo formula may alleviate neuronal damage and neuroinflammatory responses in VaD rats by regulating the HSP90/MLKL/Drp1 signaling pathway, inhibiting mitochondrial fission, thereby maintaining mitochondrial dynamic balance and improving mitochondrial function.
4.Association of CD19+CD24hiCD27+regulatory B cells with ankylosing spondylitis
Wei DAI ; Yulan LIU ; Yanmei ZENG ; Shiyun LI
Chinese Journal of Immunology 2024;40(9):1940-1943
Objective:To analyze the association of CD19+CD24hiCD27+regulatory B cells(Bregs)with ankylosing spondylitis(AS).Methods:Eighty patients with AS in Ganzhou People's Hospital from January 2019 to December 2021 were enrolled as observa-tion group,meantime,another 60 healthy individuals were set as control group.Observation group was further divided into subgroups according to clinical stages and disease activity,advanced stage,ankylosis stage,active stage and non-active stage.Percentage of CD19+CD24hiCD27+Bregs in CD19+cells in peripheral blood of observation group and control group,and observation group patients with different stages were detected and compared,thereafter,relationship between percentage of CD19+CD24hiCD27+Bregs and clini-cal characteristics of AS patients were discussed,such as course of disease,duration of morning stiffness,the Bath Ankylosing Spon-dylitis Disease Activity Index(BASDAI),IL-10,erythrocyte sedimentation rate(ESR),C-reactive protein(CRP)and X-ray classifi-cation of sacroiliitis.Results:Percentage of CD19+CD24hiCD27+Bregs in peripheral blood in observation group was higher than that in control group.Percentage of CD19+CD24hiCD27+Bregs in CD19+cells in AS patients at ankylosis stage was higher than that in patients at advanced stage,and percentage of CD19+CD24hiCD27+Bregs in peripheral blood of patients with bony ankylosis stage was higher than that in patients with fibrous ankylosis stage.Percentage of CD19+CD24hiCD27+Breg in CD19+B cells in active AS patients was sig-nificantly higher than that of patients with stable AS(P<0.05).Serum IL-10 level in observation group was lower than that in control group,while ESR and CRP levels were higher than those in control group,with statistical significance(P<0.05).Percentage of CD19+CD24hiCD27+Breg in CD19+B cells in peripheral blood of AS patients was positively correlated with BASDAI score and serum IL-10 level,while negatively correlated with ESR and CRP levels,and had no correlation with morning stiffness time and X-ray classi-fication of sacroiliitis.Conclusion:Percentage of CD19+CD24hiCD27+Bregs in peripheral blood is reduced in AS patients,moreover,percentage is closely related to disease stage,activity and laboratory indicators IL-10,ESR and CRP,which may be involved in the occurrence and development of AS.
5.Effects of calcitriol on PI3K/AKT signaling pathway and wound healing in diabetic foot ulcer rats
Yanhong LUO ; Yu TIAN ; Yunfeng WU ; Jiaojiao LI ; Shuxiang YANG ; Lingrui WANG ; Tingting XIE ; Yan YANG ; Yulan CAI
Chinese Journal of Diabetes 2024;32(7):532-539
Objective To investigate the effects of calcitriol intervention on PI3K/AKT signaling pathway and wound healing in rats with diabetic foot ulcer(DFU).Methods Thirty-two male SD rats were divided into normal control(Con)group,DFU group,calcitriol low dose(L)group and calcitriol high dose(H)group.A circular wound of 5 mm in diameter and deep to the fascia was made on the dorsum of the left foot of rats in each group.HE staining was used to evaluate the histopathological changes of the wounds.Immunohistochemical method was selected to compare the distribution of CD34-positive cells and the expression of p-PI3K and p-AKT in traumatic tissues of each group.ELISA was adopted in the detection of serum IL-6,IFN-γ,TNF-α and IL-7.RT-PCR was used to detect the mRNA expression of PI3K and AKT in each group,and western blot was used to detect the protein expression of PI3K,p-PI3K,AKT,p-AKT and VEGF.Results Compared with Con group,the expressions of IL-6,IFN-γ,TNF-α,IL-7,CD34,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K,p-AKT/AKT increased,while PI3K protein expression decreased in DFU,L and H groups(P<0.05),VEGF and AKT protein expression decreased in DFV and L groups(P<0.05).Compared with DFU group,the expressions of VEGF,AKT and PI3K protein increased(P<0.05),while the expressions of p-PI3K/PI3K,p-AKT/AKT decreased in L and H groups(P<0.05),IL-6 decreased in L group(P<0.05),and CD34 expression increased in H group(P<0.05),while IL-6,IFN-γ,TNF-α and IL-7,PI3K mRNA,AKT mRNA,p-AKT protein and p-PI3K protein expression decreased(P<0.05).Compared with L group,the expressions of CD34,VEGF,AKT and PI3K protein increased(P<0.05),while IL-6,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K and p-AKT/AKT decreased in H group(P<0.05).Conclusions Calcitriol intervention may reduce the activity of the PI3K/AKT signaling pathway,inhibit inflammation,promote neovascularization,and facilitate wound healing in rats with DFU.
6.Blood hypercoagulation state lower limb deep vein thrombosis construction and validation of an early warning model based on random forest algorithm in diabetic peripheral neuropathy
Huan LUO ; Shiqin ZHU ; Yulan SHEN ; Hui YIN ; Shufang ZOU
Chinese Journal of Diabetes 2024;32(8):591-594
Objective To explore the influencing factors of type 2 diabetes mellitus(T2DM)merging with diabetic peripheral neuropathy(DPN),and to construct and verify a prediction model based on random forest algorithm.Methods 512 T2DM patients who were hospitalized in our hospital from January 2019 to December 2021 were divided into simple T2DM group(n=292)and T2DM combined with DPN group(DPN,n=220)based on whether or not DPN was present.The general data and biochemical indicators of the two groups were compared.Logistic regression analysis was conducted to identify the influencing factors of DPN in T2DM patients.A random forest model was constructed.Results Compared with the T2DM group,the DPN group showed an increase in weight loss rate,incidence of diabetic retinopathy(DR),WBC and HbA1c(P<0.05),with decrease in DM duration≥10 years,TG and HDL-C(P<0.05).Logistic regression analysis showed that age≥60 years,HbA1c,TG,HDL-C,rate of weight loss,DR were influencing factor for T2DM combined with DPN.The random forest model showed that when the number of trees was 387,the error rate was the lowest.The importance ranking of the influencing factors of T2DM combined with DPN were the rate of weight loss,TG,DR,HDL-C,HbA1c and age≥60 years.Conclusions Age≥60 years,HbA1c,TG,HDL-C,rate of weight loss and DR are influencing factors for T2DM combined with DPN,that can be used for early clinical diagnosis and treatment.
7.Effect of intervention therapy strategies on prognosis in elderly patients with acute ST-segment elevation myocardial infarction
Yafang WANG ; Yeran ZHU ; Suran RONG ; Xiangxin SHI ; Xiao'ou YANG ; Yulan LI
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(6):610-613
Objective To analyze the effects of immediate multi-vessel percutaneous coronary inter-vention(MV-PCI)and staged vascular intervention(Staged-PCI,immediate PCI for culprit-only followed by a delayed treatment of all other lesions)on the prognosis in elderly patients with acute ST-segment elevation myocardial infarction(STEMI).Methods A total of 417 elderly acute STEMI patients who underwent PCI in Baoding First Central hospital from January 2021 to June 2023 were enrolled,and according to different treatment strategies,they were divided into MV-PCI group(87 cases)and Staged-PCI group(330 cases).A propensity score matching(PSM)model was established based on baseline data of the two groups,there were 84 cases in each group.During a mean follow-up period of 13.5 months,with the occurrence of main adverse cardi-ovascular and cerebrovascular events(MACCE)as endpoint,the incidence of MACCE was com-pared between the two groups after PSM.Cox proportional hazard regression model was used to analyze the risk factors of MACCE.Results Before PSM,there were significant differences be-tween the two groups in terms of age,proportions of hypertension,diabetes and hyperlipidemia,family history,stroke history,peripheral artery disease,preoperative SBP,lesion vessels(such as left anterior descending branch and left circumflex branch),and number of non-diseased vessels(P<0.05).Kaplan-Meier survival curve showed that the incidences of MACCE and all-cause mor-tality were significantly lower in the MV-PCI group than the Staged PCI group(Plog rank<0.05).Multivariate Cox proportional hazard regression model showed that MV-PCI was a protective prognostic factor for MACCE(HR=0.263,95%CI:0.105-0.659,P=0.004)and all-cause death(HR=0.236,95%CI:0.007-0.722,P=0.016).Conclusion MV-PCI can significantly improve the prognosis of elderly patients with acute STEMI with multivessel disease.
8.Therapeutic effect of resistance exercise in elderly patients with chronic heart failure combined with sarcopenia
Zengshuai WANG ; Yanan LIU ; Yulan LI ; Caixia FENG
Chinese Journal of Geriatrics 2024;43(9):1107-1113
Objective:To explore the efficacy and safety of low-and medium-intensity resistance exercise in patients with chronic heart failure(CHF)combined with sarcopenia.Methods:In the randomized controlled study, 100 elderly patients with CHF combined with sarcopenia who were hospitalized in the Department of Cardiology of the Second Affiliated Hospital of Baotou Medical College from October 2020 to August 2022 were selected and divided into the control group and the intervention group according to the randomized numerical scale method.In the control group, angiotensin-converting enzyme inhibitors/angiotensin receptor inhibitors, β receptor antagonists, diuretics and other standard heart failure medications were routinely given, as well as nutritional support, health education and guidance; in the intervention group, low-intensity resistance exercise was given in addition to the treatment of the control group, and the two groups were evaluated for the NYHA cardiac function classification, grip strength, 5 times sitting time, 6-meter walking time, serum B-type natriuretic peptide level before and after 12 weeks of treatment; limb skeletal muscle mass index(ASMI), visceral fat area, extracellular water ratio were measured by body composition analyzer; right ventricular internal diameter, left atrial internal diameter, left ventricular end-diastolic internal diameter, left ventricular ejection fraction(LVEF) were measured by echocardiography.Changes in each index before and after treatment were compared between the 2 groups.Serious adverse cardiovascular events related to training were followed up by outpatient clinic visits or telephone at 4-week interval over 12 weeks.Results:30 cases were dislodged because they could not adhere to the exercise or could not follow up on time, and finally 70 patients were included, 27 in the control group and 43 in the intervention group.Compared with pre-treatment, grip strength[(17.73±4.54)kg vs.(17.00±4.32)kg, t=8.969], limb skeletal muscle mass[(17.57±3.41)kg vs.(17.24±3.34)kg, t=7.170], and ASMI[(6.02±0.72)kg/m 2vs.(5.85±0.67)kg/m 2, t=6.866]were elevated in the intervention group after 12 weeks(all P<0.05); 5 times sitting up time[(16.17±3.25)s vs.(14.54±3.21)s, t=12.808, ]and 6-meter walking time[(12.30±3.24)s vs.(10.76±3.14)s, t=9.391]shortened(all P<0.05).Compared with pre-treatment, the intervention group showed reduced left ventricular end-diastolic internal diameter[(59.62±9.07)mm vs.(58.48±9.71)mm, t=4.552], increased LVEF[(34.69±7.93)% vs.(35.88±7.92)%, t=4.752], and increased extracellular water ratio[(39.27±7.74)% vs.(38.92±7.41)%, t=6.058]after 12 weeks(all P<0.05).At 12 weeks of follow-up, no training-related serious adverse events occurred in the intervention group.The difference in the incidence of serious adverse cardiovascular events between the two groups(3.70% vs.2.33%, P>0.05)was not statistically significant. Conclusions:Treatment combined with low-and moderate-intensity resistance exercise improves muscle mass, muscle strength, physical function, and cardiac function in elderly patients with CHF combined with sarcopenia without increasing the incidence of adverse events.
9.Value of serum VEGF, PGR combined with magnifying chromoendoscopy in the diagnosis of Epstein-Barr virus associated gastric carcinoma and the pathogenesis analysis
Haifeng GAO ; Yulan ZHANG ; Lingge HE ; Dengfeng WANG ; Ning MA ; Ting XUE
Cancer Research and Clinic 2024;36(5):341-346
Objective:To investigate the value of serum vascular endothelial growth factors (VEGF), pepsinogen ratio (PGR) combined with magnifying chromoendoscopy in the diagnosis of Epstein-Barr virus associated gastric carcinoma (EBVaGC).Methods:A retrospective case control study was conducted. The clinical data of 314 patients with gastric cancer who were confirmed by pathological examination in Baoji Central Hospital from January 2018 to January 2023 were retrospectively collected. All patients were divided into EBVaGC group (34 cases) and EB virus negative gastric cancer (EBVnGC) group (280 cases) according to the result of EB virus quantitative real time polymerase chain reaction in serum before treatment, while 50 healthy volunteers who underwent the physical examination in the same period were selected as the control group. The level of VEGF was detected by using enzyme-linked immunosorbent assay (ELISA), and serum levels of pepsinogen (PG) Ⅰ and PGⅡ were detected by using fluorescence immunochromatography. PGR was calculated by PGⅠ-to-PGⅡ ratio. Electronic magnification gastroscopy was performed, suspicious lesions were stained and the pathological state of gastric tissues was observed. Taking the pathological results of living tissues as the gold standard, the diagnostic efficacy of each index alone and the combination detection for EBVaGC was calculated. Multivariate logistic regression model was used to analyze the independent risk factors of the incidence of EBVaGC.Results:The age of patients in EBVaGC group, EBVnGC group and the healthy control group was (61±10) years, (63±12) years and (61±12) years, respectively; and there were 28 males (82.4%), 228 males (81.4%) and 41 males (82.0%), respectively. There were no statistically significant differences in age and gender among the 3 groups (all P>0.05). The serum VEGF level and the proportion of positive patients detected by endochromatography in EBVaGC group were higher than those in the EBVnGC group and the healthy control group [VEGF: (253±48) pg/ml vs. (183±38) pg/ml, (92±25) pg/ml; positive proportion: 94.1% (32/34) vs. 77.9% (218/280), 2.0% (1/50)], and the PGR in EBVaGC group was lower than that in EBVnGC group and the healthy control group (2.1±1.0 vs. 3.1±1.1, 14.1±1.9), and the differences were statistically significant (all P<0.05). The sensitivity of serum VEGF in the diagnosis of EBVaGC was higher than that of PGR [73.5% (25/34) vs. 66.9% (22/34)]. The diagnostic specificity of PGR [78.2% (219/280) vs. 69.3% (194/280)] and accuracy [76.8% (241/314) vs. 69.8% (219/314)] were higher than those of VEGF. The sensitivity [85.3% (29/34)], specificity [82.9% (232/280)] and accuracy [83.1% (261/314)] of magnifying chromoendoscopy in the diagnosis of EBVaGC were higher than those of VEGF and PGR. The sensitivity [94.1% (32/34)], specificity [95.7% (268/280)] and accuracy [95.5% (300/314)] of the 3 combined detection were higher than those of single and pairwise detection. Multivariate logistic regression analysis showed that the independent risk factors for the incidence of EBVaGC included alcoholism ( OR = 2.310, 95% CI: 1.243-3.581, P = 0.007), spicy food preference ( OR = 1.516, 95% CI: 1.084-2.142, P = 0.026), irregular diet ( OR = 1.448, 95% CI: 1.013-2.104, P = 0.043), family history of gastric cancer ( OR = 2.732, 95% CI: 1.312-4.894, P = 0.001). Conclusions:Serum VEGF and PGR combined with magnifying chromoendoscopy can improve the diagnostic efficiency of EBVaGC, and developing good eating will be helpful to prevent or slow down the progression of stomach diseases.
10.Family resilience mechanisms in children with obstetrical brachial plexus palsy:a qualitative study
Xiaoju ZHANG ; Yulan ZHU ; Pengfei YAN
Modern Hospital 2024;24(11):1776-1779,1785
Objective To explore mechanisms of family resilience in children with obstetrical brachial plexus palsy(OBPP)and provide a basis for developing interventions to family resilience.Methods Semi-structured interviews were conduc-ted with 10 primary caregivers,and data were analyzed through content analysis.Results Three themes were distilled,namely,great impact of the injurious event on the family,positive response of the family to the injurious event,and hidden pain that the injurious event brought to the family.Conclusion The overall resilience of families of OBPP children is in a high level.It is es-sential to address the adverse impact of the injurious event on the families,consolidate the positive results of the family's re-sponse to the injury,and promote the restoration and enhancement of the family's function.

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