1.Cistanoside A mediates p38/MAPK pathway to inhibit osteoclast activity
Yueyao LI ; Min ZHANG ; Jiaju YANG
Chinese Journal of Tissue Engineering Research 2025;29(6):1144-1151
BACKGROUND:Cistanoside A has the effects of anti-inflammation,antioxidation,antioxidation,reducing renal damage and anti-osteoporosis,but its effect on osteoclast differentiation,function and its underlying molecular mechanisms remain unclear. OBJECTIVE:To investigate the effect of Cistanoside A on osteoclast differentiation and bone resorption induced by receptor activator of nuclear factor kappa-B ligand(RANKL)in vitro and its mechanism. METHODS:Bone marrow macrophages were obtained from the femur and tibia of 4-6-week-old C57BL/6 mice.The cytotoxic effect of Cistanoside A(5,10,20,40,80,and 160 μmol/L)on bone marrow macrophage viability was examined using the cell counting kit-8 assay kit.Tartrate-resistant acid phosphatase staining was performed to observe the effect of different concentrations of Cistanoside A on osteoblast differentiation and its effective intervention concentration was determined.There was positive control group,Cistanoside A low,medium,and high dose groups(40,80,and 160 μmol/L).After cell attachment,50 ng/mL RANKL was added to induce osteoblast differentiation,and the corresponding dose of Cistanoside A was added to the Cistanoside A low,medium,and high dose groups,respectively.F-actin ring and 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride staining were performed to detect the effects of Cistanoside A on the formation of osteoclasts.Toluidine blue staining of bone abrasion slices was used to observe the effects of Cistanoside A on bone resorption function of osteoclasts.The expression of upstream and downstream proteins of the JNK/MAPK pathway was detected by Western blot.The expression of genes related to osteoclast differentiation and bone resorption function such as tartrate-resistant acid phosphatase,DC-STAMP,Nfatc-1,Ctsk and c-Fos was detected by RT-qPCR. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining,F-actin ring staining and resorption pit assay showed that Cistanoside A significantly inhibited RANKL-induced osteoclast differentiation and bone resorption in a dose-dependent manner compared with the positive control group.The results of RT-qPCR showed that compared with the positive control group,both high and low dose groups of Cistanoside A could significantly downregulate the mRNA expression of tartrate-resistant acid phosphatase,DC-STAMP,Nfatc-1,Ctsk and c-Fos in a dose-dependent manner.The results of western blot assay showed that the high dose group of Cistanoside A significantly inhibited the expression of p-JNK protein at 10,20,30 and 60 minutes of intervention;compared with the positive control group,Cistanoside A significantly inhibited the expression of Nfatc1 and c-Fos proteins in a dose-dependent manner.To conclude,Cistanoside A could inhibit the formation and bone resorption of osteoclasts by reducing the level of p-JNK protein,inhibiting the activation of MAPK pathway and the expression of key genes in osteoclasts.
2.FGF18 induces differentiation of human gingival fibroblasts into osteoblasts by upregulating BMP2
Yali Hou ; Huijuan Liu ; Hao Zhang ; Jingyuan Sun ; Peng Song ; Yueyao Liu ; Hexiang Li
Acta Universitatis Medicinalis Anhui 2025;60(2):279-285
Objective:
To investigate whether fibroblast growth factor 18(FGF18) can induce human gingival fibroblasts(HGFs) isolatedin vitroto differentiate into osteoblast-like cells, and to explore the mechanism of osteogenesis.
Methods :
HGFs were isolated, cultured and identified by tissue block method. The third generation of HGFs were divided into experimental group and control group. FGF18 and L-DMEM was added to the experimental group while L-DMEM was added to the control group.The effects of different concentrations of FGF18(0, 0.01, 0.02, 0.04, 0.06 mg/L) on proliferation of HGFs were detected by Methylthiazolyldiphenyl-tetrazolium bromide(MTT) assay. Alkaline phosphatase(ALP) and alizarin red staining were used to detect the osteogenesis and mineralization ability of the cells after induction. RT-PCR, immunocytochemistry staining, and Western blot were used to detect the expression of genes and proteins related to osteogenesis and BMP2 in the BMP signaling pathway.
Results:
Compared with the control group, the experimental group could promote the proliferation of HGFs at 3, 5, 7, 9, and 11days(P<0.05),ALP activity and mineral salt deposition increased after induction at 14 and 21 days(P<0.05), and the expressions of ALP, OPN, OCN mRNA and BMP2 mRNA in BMP signaling pathway significantly increased(P<0.01). The expressions of OPN, OCN and BMP2 protein at 21 days were significantly higher than those at 14 days(P<0.01).
Conclusion
FGF18 can promote the proliferation of HGFs, and induce the differentiation of HGFs into functional osteoblasts. The osteogenic mechanism is related to the upregulation of BMP2.
3.Erratum: Author correction to "Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy" Acta Pharm Sin B (2022) 4224-4234.
Zekun LI ; Yongchun PAN ; Shiyu DU ; Yayao LI ; Chao CHEN ; Hongxiu SONG ; Yueyao WU ; Xiaowei LUAN ; Qin XU ; Xiaoxiang GUAN ; Yujun SONG ; Xin HAN
Acta Pharmaceutica Sinica B 2024;14(2):897-899
[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].
4.Monitoring of wearable long-range ambulatory electrocardiographic monitor for a community-based homebound elderly population
Zhiquan YUAN ; Na WU ; Huiyan JIAO ; Chengying LI ; Long WU ; Meng NIE ; Yueyao XU ; Lei YANG ; Yu WANG ; Yonghong WU ; Li ZHONG ; Yafei LI
Journal of Army Medical University 2024;46(11):1316-1322
Objective To investigate the results of ambulatory electrocardiographic(ECG)monitoring in a community-based homebound elderly population and to explore the applicability of wearable long-range ambulatory ECG monitor for them.Methods Elderly volunteers were recruited in Shuangbei Community,Shapingba District,Chongqing,from November 2021 to June 2023.A single-lead wearable ambulatory ECG recorder was applied to them to obtain ECG for 7 consecutive days.The adverse reactions,acceptability,monitoring duration,and arrhythmia detection rate during the wearing were described and recorded.Serious arrhythmic events included frequent atrial premature,atrial flutter,atrial fibrillation(AF),frequent ventricular premature,and RR intervals ≥5 s.Results There were 416 individuals enrolled,with a mean age of 71.2±6.6 years,and a male percentage of 36.1%(150 men).Finally,384(92.3%)participants completed the wearing of the ECG monitor for 7 d,with an average time of 159.2±29.4 h.There were 179 participants(48.5%)reporting no discomfort during wearing,and 175 ones(47.4%)feeling itchy at the wearing site.The monitoring results showed that the common arrhythmias were atrial premature contractions(97.1%),premature ventricular contractions(93.3%),atrial tachycardia(84.6%),bradycardia(46.6%),frequent atrial premature contractions(15.1%),ventricular tachycardia(13.2%),and long RR interval(11.8%).Among them,29.1%of the participants experienced serious arrhythmic events,and the detection rate of certain serious arrhythmic events was comparatively higher in the individuals≥70 years of age and those with history of previous cardiac disease.Conclusion The detection rate of common arrhythmias is quite high in the community-based homebound elderly population.A 7-day long-range ambulatory ECG monitoring may be appropriate.
5.Trajectory of systolic blood pressure fluctuation and its influencing factors in community-dwelling patients with hypertension
Meng NIE ; Na WU ; Huiyan JIAO ; Zhiquan YUAN ; Chengying LI ; Long WU ; Yueyao XU ; Lei YANG ; Yu WANG ; Yonghong WU ; Li ZHONG ; Yafei LI ; Jingyuan YANG
Journal of Army Medical University 2024;46(12):1457-1466,封3
Objective To analyze and construct systolic blood pressure(SBP)fluctuation trajectory in a community population with hypertension and to analyze the factors influencing different trajectories.Methods This is a community-based retrospective cohort study.A latent class trajectory model was used to identify and construct longitudinal trajectories of blood pressure change.Multinomial logistic regression analysis was performed to identify the associated factors of blood pressure trajectories by adjusting for different confounders.Potential confounding factors were identified using a directed acyclic graph based on a priori knowledge.Results A total of 793 patients with hypertension were enrolled in the analysis.They were divided into 3 groups by LCTM-fitted systolic blood pressure trajectories,namely stable low-level group(n=561,70.74%),declining group(n=170,21.44%)and rising group(n=62,7.82%).Significant differences were observed among the 3 trajectories groups in terms of age,frequency of exercise,ways of follow-up,salt intake,compliance behavior,and referral(P<0.05).Compared to the stable low-level group and adjusting for corresponding confounding factors,the male patients and the patients with"outpatient follow-up"were more likely to be classified into"declining group",with OR and 95%CI of 1.436(1.016~2.030)and 1.702(1.202~2.410),respectively.The participants aged ≥ 65 years,who did not exercise or occasionally exercised,and had moderate and severe salt intake,were more likely to be classified into the"rising group"(OR=1.949,2.284,2.433,4.540,95%CI:1.145~3.317,1.305~3.998,1.272~4.654,1.291~15.963).Conclusion SBP trajectories in community-dwelling hypertensive population can be divided into stable low-level,declining and rising groups.Gender,age,salt intake,exercise frequency,and follow-up methods may be influencing factors for SBP blood pressure trajectory.
6.Effects of Questionnaire-Based Psychological Survey Methods on the Evaluation Results in a Patient Cohort
Yueyao XU ; Wenwen CHEN ; Ling LI ; Li YUAN ; Mengxian HUANG ; Yuanyuan QU ; Huan SONG ; Jianwei ZHU
Acta Academiae Medicinae Sinicae 2024;46(3):324-328
Objective To assess the influences of self-and interviewer-administered methods on the scores of anxiety and depression questionnaires among the patients with sports injuries.Methods A total of 532 participants with sports injuries treated in the Sports Medicine Center of West China Hospital,Sichuan University from November 2022 to May 2023 were included.They were randomly assigned to either the interviewer-administered group(n=270)or the self-administered group(n=262)to complete the generalized anxiety disorder(GAD-7)and the patient health questionnaire(PHQ-9)scales.The total scores and prevalence rates of anxiety and depres-sion were compared between the two groups.Results There was no statistically significant difference in gender,occupation,or surgical site between the two groups(all P>0.05).The self-administered group had higher scores of GAD-7 and PHQ-9 scales than the interviewer-administered group(P<0.001,P<0.001).A greater proportion of participants in the self-administered group than in the interview-administered group met the criteria for mild to moderate anxiety and depression(P<0.001,P=0.002).The prevalence rates of moderate to se-vere anxiety(GAD-7 ≥10)and depression(PHQ-9 ≥10)showed no statistically significant difference between the two groups(P=0.761,P=0.086).Conclusion This study demonstrates that the participants in the self-administered group are more likely to report mild to moderate symptoms of anxiety and depression than those in the interviewer-administered group.
7.Implicit, But Not Explicit, Emotion Regulation Relieves Unpleasant Neural Responses Evoked by High-Intensity Negative Images.
Yueyao ZHANG ; Sijin LI ; Kexiang GAO ; Yiwei LI ; Jiajin YUAN ; Dandan ZHANG
Neuroscience Bulletin 2023;39(8):1278-1288
Evidence suggests that explicit reappraisal has limited regulatory effects on high-intensity emotions, mainly due to the depletion of cognitive resources occupied by the high-intensity emotional stimulus itself. The implicit form of reappraisal has proved to be resource-saving and therefore might be an ideal strategy to achieve the desired regulatory effect in high-intensity situations. In this study, we explored the regulatory effect of explicit and implicit reappraisal when participants encountered low- and high-intensity negative images. The subjective emotional rating indicated that both explicit and implicit reappraisal down-regulated negative experiences, irrespective of intensity. However, the amplitude of the parietal late positive potential (LPP; a neural index of experienced emotional intensity) showed that only implicit reappraisal had significant regulatory effects in the high-intensity context, though both explicit and implicit reappraisal successfully reduced the emotional neural responses elicited by low-intensity negative images. Meanwhile, implicit reappraisal led to a smaller frontal LPP amplitude (an index of cognitive cost) compared to explicit reappraisal, indicating that the implementation of implicit reappraisal consumes limited cognitive control resources. Furthermore, we found a prolonged effect of implicit emotion regulation introduced by training procedures. Taken together, these findings not only reveal that implicit reappraisal is suitable to relieve high-intensity negative experiences as well as neural responses, but also highlight the potential benefit of trained implicit regulation in clinical populations whose frontal control resources are limited.
Humans
;
Emotional Regulation
;
Electroencephalography
;
Evoked Potentials/physiology*
;
Cognition/physiology*
;
Emotions/physiology*
8.Clinical efficacy of laparoscopic surgery for infected pancreatic necrosis in subgastric approach
Feng FENG ; Chen XU ; Zhikai YANG ; Weihong ZHAO ; Ang LI ; Jingpo ZHANG ; Wei WANG ; Yueyao SUN ; Yong LI ; Fengshan LI ; Jianhua LIU
Chinese Journal of Pancreatology 2022;22(6):426-431
Objective:To investigate the technical key points and clinical effects of laparoscopic surgery using the subgastric approach for infected pancreatic necrosis (IPN).Methods:From October 2020 to October 2021, The clinical data of 6 patients with IPN after severe acute pancreatitis (SAP) undergoing laparoscopic surgery using the subgastric approach at First Hospital and Second Hospital of Hebei Medical University was retrospectively analyzed. Parameters in this report included the operation time, estimated blood loss, and the patient's vital signs, inflammatory marker CRP, and WBC before operation and postoperative 24 h, 3 d, and 1 w, and postoperative complications including pancreatic leakage, organ failure, bleeding, and abdominal infection and incision infection. Follow-up after surgery was completed in outpatient checkups and long-term complications were recorded.Results:There were 4 male and 2 female patients. The median age of the 6 patients was 50 (43.5, 56.5) years. Laparoscopic debridement surgery using the subgastric approach was successfully completed in all the patients and no reoperation was needed. The median operation time was 65 (52.5, 85) min; the median estimated blood loss was 20 (25, 37.5) ml. Median APACHEⅡ score one day before surgery was 11.5 (10.25, 12.75) and the median MCTSI score at initial admission was 8 (7, 8). The inflammatory parameters including CRP, WBC, and neutrophil count on postoperative day 3 and 1w were significantly lower than those before surgery, and all the differences were statistically significant (all P value <0.05). One patient had a postoperative pancreatic fistula and was alleviated after ERCP with pancreatic stent implantation. Another patient had a incision infection after surgery and recovered after complete surgical drainage of the abdominal wall incision. No patients had complications such as heart, lung, and kidney failure, abdominal hemorrhage and infection. During the follow-up, 5 of 6 patients had no newly-occurred diabetes, except one patient who had diabetes before the operation. None of the 6 patients had recurrent IPN. Conclusions:Laparoscopic surgery using the subgastric approach for infected IPN in lesser omental sac is safe and feasible.
9.Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy.
Zekun LI ; Yongchun PAN ; Shiyu DU ; Yayao LI ; Chao CHEN ; Hongxiu SONG ; Yueyao WU ; Xiaowei LUAN ; Qin XU ; Xiaoxiang GUAN ; Yujun SONG ; Xin HAN
Acta Pharmaceutica Sinica B 2022;12(11):4224-4234
Near-infrared (NIR)-light-triggered nanomedicine, including photodynamic therapy (PDT) and photothermal therapy (PTT), is growing an attractive approach for cancer therapy due to its high spatiotemporal controllability and minimal invasion, but the tumor eradication is limited by the intrinsic anti-stress response of tumor cells. Herein, we fabricate a tumor-microenvironment responsive CRISPR nanoplatform based on oxygen-deficient titania (TiO2-x ) for mild NIR-phototherapy. In tumor microenvironment, the overexpressed hyaluronidase (HAase) and glutathione (GSH) can readily destroy hyaluronic acid (HA) and disulfide bond and releases the Cas9/sgRNA from TiO2-x to target the stress alleviating regulators, i.e., nuclear factor E2-related factor 2 (NRF2) and heat shock protein 90α (HSP90α), thereby reducing the stress tolerance of tumor cells. Under subsequent NIR light illumination, the TiO2-x demonstrates a higher anticancer effect both in vitro and in vivo. This strategy not only provides a promising modality to kills cancer cells in a minimal side-effects manner by interrupting anti-stress pathways but also proposes a general approach to achieve controllable gene editing in tumor region without unwanted genetic mutation in normal environments.
10.Meta-analysis of Therapeutic Efficacy of Yixinshu Preparation Combined with Conventional Therapy in the Trea- tment of Angina Pectoris of Coronary Heart Disease
Yingjie HUANG ; Lei HUANG ; Yuxuan TAO ; Haiyi LI ; Yueyao ZHANG ; Junmao WEN ; Wei WU
China Pharmacy 2021;32(3):339-345
OBJECTIVE:To systematically evaluate therape utic efficacy of Yixinshu preparation combined with conventional treatment plan for angina pectoris of coronary heart disease (CHD)vs. conventional treatment plan ,and to provide evidence-based reference for clinical drug use. METHODS :Retrieved from Cochrane library ,PubMed,Embase,CBM,CNKI,Wanfang database and VIP ,randomized controlled trials (RCTs)about Yixinshu preparation combined with conventional treatment plan (trial group ) versus conventional treatment plan (control group )for angina pectoris of coronary heart disease were collected during Jan. 1st in 2012 to Oct. 1st in 2020. After extracting the data ,the quality of included studies were evaluated with Cochrane System Evaluator Handbook 5.3;Meta-analysis was performed by using Stata 15.0 software. RESULTS :A total of 23 RCTs involving 2 853 subjects were included. The results of Meta-analysis showed that the efficacy of angina pectoris [RR =0.92,95%CI(0.87,0.97),P<0.05], the times of angina pectoris attack [SMD =-0.98,95%CI(-1.09,-0.87),P<0.05],the duration of angina pectoris [SMD = -0.77,95%CI(-0.88,-0.67),P<0.05],ECG curative effect [RR =0.91,95%CI(0.84,0.98),P<0.05] and the improve rate of TCM syndromes [RR =0.89,95%CI(0.85,0.94),P<0.05] in trial group were all better than control group ,with statistical significance. CONCLUSIONS :Yixinshu preparation combined with conventional treatment plan is better than conventional treatment plan in terms of improving therapeutic efficacy of angina pectoris and ECG ,TCM syndrome improvement rate ,as well as reducing the frequency of angina pectoris attack ,angina pectoris attack duration.


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