1.Mahoniae Caulis Alkaloids Ameliorate Depression by Regulating Synaptic Plasticity via cAMP Pathway
Junhui HE ; Chunlian JIA ; Kedao LAI ; Guili ZHOU ; Rongfei ZHOU ; Yi LI ; Dongmei LI ; Jiaxiu XIE ; Guining WEI ; Juying ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):132-140
ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids (MA) in ameliorating depression by network pharmacology, molecular docking, and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP, Genecards, HPO, DrugBank and OMIM database. The depression targets were collected through TCMIP, Genecards, HPO, DrugBank and OMIM database. Protein-protein interaction (PPI) network was constructed by protein interaction analysis (STRING) database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed through Bioinformatics (DAVID) database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone (CORT) once a day for 35 consecutive days. Sixty mice were randomly allocated into control (0.9% normal saline), model (CORT, 20 mg·kg-1), positive control (fluoxetine hydrochloride, 3.6 mg·kg-1), and MA (10, 5, and 2.5 mg·kg-1) groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling (TUNEL) was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor (BDNF), dopamine (DA), 5-hydroxytryptamine (5-HT), and norepinephrine (NE) in mice. The mRNA levels of cyclic adenosine monophosphate (cAMP) pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 (Cx43). ResultsA total of 434 component targets and 545 depression targets were obtained, including 84 common targets, among which 10 core targets were screened out. GO analysis predicted 34 biological processes, 15 cell components, and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group, CORT prolonged the immobility time of mice in forced swimming and tail suspension tests (P<0.01), lowered the serum levels of NE, BDNF, and 5-HT (P<0.05), up-regulated the mRNA levels of nuclear factor-κB (NF-κB) and interleukin-6 (IL-6) in the brain tissue (P<0.05), and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein (CREB) and BDNF (P<0.05) and the protein levels of protein kinase (PRKACA), phosphorylation (p)-CREB/CREB, BDNF, and Cx43 (P<0.05) in the brain tissue. Compared with the model group, high-dose MA reduced the immobility time of mice in forced swimming (P<0.05) and tail suspension (P<0.01) tests, raised the serum levels of NE, BDNF, and 5-HT (P<0.01), down-regulated the mRNA level of NF-κB (P<0.01), and up-regulated the mRNA level of BDNF (P<0.01) and protein levels of PRKACA, p-CREB/CREB, BDNF, and Cx43 (P<0.05). ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway, improving synaptic plasticity and gap junction function, and reducing neuroinflammation.
2.Mahoniae Caulis Alkaloids Ameliorate Depression by Regulating Synaptic Plasticity via cAMP Pathway
Junhui HE ; Chunlian JIA ; Kedao LAI ; Guili ZHOU ; Rongfei ZHOU ; Yi LI ; Dongmei LI ; Jiaxiu XIE ; Guining WEI ; Juying ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):132-140
ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids (MA) in ameliorating depression by network pharmacology, molecular docking, and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP, Genecards, HPO, DrugBank and OMIM database. The depression targets were collected through TCMIP, Genecards, HPO, DrugBank and OMIM database. Protein-protein interaction (PPI) network was constructed by protein interaction analysis (STRING) database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed through Bioinformatics (DAVID) database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone (CORT) once a day for 35 consecutive days. Sixty mice were randomly allocated into control (0.9% normal saline), model (CORT, 20 mg·kg-1), positive control (fluoxetine hydrochloride, 3.6 mg·kg-1), and MA (10, 5, and 2.5 mg·kg-1) groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling (TUNEL) was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor (BDNF), dopamine (DA), 5-hydroxytryptamine (5-HT), and norepinephrine (NE) in mice. The mRNA levels of cyclic adenosine monophosphate (cAMP) pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 (Cx43). ResultsA total of 434 component targets and 545 depression targets were obtained, including 84 common targets, among which 10 core targets were screened out. GO analysis predicted 34 biological processes, 15 cell components, and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group, CORT prolonged the immobility time of mice in forced swimming and tail suspension tests (P<0.01), lowered the serum levels of NE, BDNF, and 5-HT (P<0.05), up-regulated the mRNA levels of nuclear factor-κB (NF-κB) and interleukin-6 (IL-6) in the brain tissue (P<0.05), and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein (CREB) and BDNF (P<0.05) and the protein levels of protein kinase (PRKACA), phosphorylation (p)-CREB/CREB, BDNF, and Cx43 (P<0.05) in the brain tissue. Compared with the model group, high-dose MA reduced the immobility time of mice in forced swimming (P<0.05) and tail suspension (P<0.01) tests, raised the serum levels of NE, BDNF, and 5-HT (P<0.01), down-regulated the mRNA level of NF-κB (P<0.01), and up-regulated the mRNA level of BDNF (P<0.01) and protein levels of PRKACA, p-CREB/CREB, BDNF, and Cx43 (P<0.05). ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway, improving synaptic plasticity and gap junction function, and reducing neuroinflammation.
3.Survey on ERAS implementation situation in Chongqing
Yiwei SHEN ; Su MIN ; Feng LYU ; Xiaonan LIU ; Juying JIN ; Li REN
Chongqing Medicine 2025;54(11):2649-2655
Objective To investigate the executive condition of Enhanced Recovery After Surgery(ERAS)measures among the hospitalized surgical patients in secondary and tertiary medical institutions of Chongqing City.Methods Using a multicenter cross-sectional survey approach,patients undergoing elective surgeries admitted and treated in 40 member units under the Chongqing Anesthesiology and Perioperative Medicine Specialized Alliance from July 11 to 30,2024 were selected as the survey subjects.Adherence to and completion of ERAS measures were calculated.Factors influencing measures with low completion rates were analyzed.Results A total of 2 100 questionnaires were issued,1 708 effective questionnaires were recovered with an effective recovery rate of 81.33%.Among them,there were 1 017 questionnaires in the tertiary medi-cal institutions and 691 questionnaires in the secondary medical institutions.The age of 1 708 patients ranged from 19-78 years old with a median age of 52 years old.Females were dominant.The proportion of patients from gastrointestinal surgery and those with secondary school education or above was high.Hypertension and diabetes were the main complication types.The surgical grade was concentrated at grades Ⅲ and Ⅳ.The ASA grading was concentrated at the grade Ⅰ/Ⅱ.The NYHA heart function grade was mainly the grade Ⅰ/Ⅱ.The ERAS measures compliance rate ranged from 36.36%to 95.45%,averaged 73.47%.The compliance rate of ERAS measures in the tertiary hospitals was higher than that in the secondary hospitals(75.82%vs.70.01%),and the difference was statistically significant(P<0.05).The average completion rate of ERAS measures was 74.08%.The top three in the completion rate were preoperative education(95.78%),preven-tive antibiotics and skin preparation(92.62%),and preoperative interview and evaluation(88.58%).The completion rates of Prehabilitation(55.27%)and preoperative fasting(57.67%)urgently needed to be in-creased.The completion rate of other measures was lower than 60%.Conclusion The compliance rate of ERAS measures needs to be increased,moreover there are significant differences among various hospitals.Fu-ture practices should focus on two measures:preoperative pre-rehabilitation exercises and preoperative oral intake of carbohydrates.
4.Analysis on registration schemes for domestic clinical studies combining TCM with targeted drug therapy for lung cancer treatment
Jingyi ZENG ; Bo LIN ; Tiancheng ZHAO ; Juying JIAO ; Hegen LI ; Weijie XU
International Journal of Traditional Chinese Medicine 2025;47(1):108-113
Objective:To systematically review the current registered clinical study schemes in China regarding the combination of TCM and targeted drug therapy for lung cancer; To analyze their strengths and weaknesses; To provide reference for future study.Methods:Chinese Clinical Trial Registry for clinical study schemes combining TCM with targeted drug therapy for lung cancer treatment was retrieved from the inception to July 10, 2024. The general characteristics, study types, intervention measures, and outcome indicators of existing schemes were systematically summarized and analyzed.Results:A total of 15 studies were included, with the earliest study registered in 2013. Registration locations were concentrated in Shanghai, Guangdong, Tianjin, and Zhejiang. Among them, 9 studies received funding from local, national finance, or hospitals; 13 studies passed ethical review, and 12 included informed consent. The design schemes included 10 randomized controlled studies, 1 cohort study, 1 interventional single-arm study, and 3 observational studies. 6 studies had a sample size smaller than 100 cases, and most were single-center trials. Intervention measures primarily involved the combination of Chinese patent medicine or TCM with targeted drugs, with evaluation indicators mainly focusing on clinical symptoms and laboratory indicators. The setting of outcome indicators lacked a unified standard.Conclusions:Since 2013, clinical studies combining TCM with targeted drug therapy for lung cancer have been relatively methodologically sound but face challenges such as small sample sizes and a certain degree of regional concentration, leading to relatively insufficient representativeness. The future direction for improvement lies in multi-center, large-sample, and well-designed clinical trials. It is also necessary to establish a standardized and normalized system for evaluating outcomes. Integrating basic research to clarify the mechanisms of TCM can provide a theoretical basis for the combination of TCM and targeted drugs, which is conducive to enhancing the rigor and scientific nature of clinical trial design and promoting the formation of high-level evidence-based medicine.
5.Different Types of Obesity Play a Modifying Role in the Association Between Physical Activity and Metabolic Dysfunction-Associated Fatty Liver Disease
Yang CHANG ; Jiawei LI ; Gonghua WU ; Juying ZHANG ; Bing GUO ; Xing ZHAO
Journal of Sichuan University (Medical Sciences) 2025;56(1):149-155
Objective To explore the association between physical activity levels and metabolic dysfunction-associated fatty liver disease(MAFLD)and the modifying effects of different types of obesity.Methods A cross-sectional study was conducted on 19925 participants recruited from the Chengdu sub-cohort of the Southwest China Natural Population Cohort.The participants were recruited between 2018 and 2019.The association between physical activity and MAFLD prevalence was examined using the inverse probability weighting(IPW)method based on the generalized propensity score(GPS).The odds ratios(OR)and the 95%confidence interval(CI)for moderate and vigorous physical activity were calculated using the mild physical activity group as a reference.A restricted cubic spline function was used to model the exposure-response relationship between physical activity and MAFLD risk.The potential modifying effects of obesity types on the association between physical activity and MAFLD were evaluated in male and female populations.Results The prevalence of MAFLD was 17.30%.Compared to those engaging in mild physical activity,individuals participating in vigorous and moderate physical activities had a lower risk of MAFLD,with OR(95%CI)being 0.76(0.67,0.86)and 0.85(0.76,0.94),respectively.The exposure-response relationship showed a nonlinear association between physical activity and MAFLD risks(Pnonlinearity=0.005).The protective effect of physical activity against MAFLD was observed when physical activity reached approximately 20 METs-h/d.However,when physical activity exceeded 70 METs-h/d,no significant effect on MAFLD risk was observed.Among the female population,obesity type significantly modified the association between physical activity and MAFLD(P<0.05).In females with central obesity,the protective effect of physical activity on MAFLD showed a threshold effect,with the lowest disease risk observed at approximately 25 METs-h/d.However,physical activity exceeding 37.5 METs-h/d showed no statistically significant association with MAFLD risk.In contrast,for females with peripheral obesity,high levels of physical activity had limited effects on reducing MAFLD risks.Conclusion Moderate physical activity can significantly reduce the risk of MAFLD,and the obesity types can modify this association.It is recommended that individuals engage in approximately 20-70 METs-h/d of physical activity.For females with central obesity,physical activity should not exceed 37.5 METs-h/d,while for females with peripheral obesity,it should not exceed 30 METs-h/d.
6.Association Between Surrogate Markers of Insulin Resistance and Incident Cardiovascular Disease in a Population With Stages 0-3 Cardiovascular-Kidney-Metabolic Syndrome:A Prospective Cohort Study
Yajie ZHAO ; Lele WANG ; Jiawei LI ; Bing GUO ; Juying ZHANG ; Xiaolin GUO ; Yuying LUO ; Gonghua WU ; Xing ZHAO
Journal of Sichuan University (Medical Sciences) 2025;56(2):495-505
Objective To investigate the association between 8 insulin resistance(IR)surrogate markers and incident atherosclerotic cardiovascular disease(ASCVD)in population with cardiovascular-kidney-metabolic syndrome(CKM)of stages 0-3,and to identify the surrogate marker with the best predictive performance.Methods A study was conducted on 20121 community residents classified as CKM stages 0-3 from the Chengdu cohort of the China Multi-Ethic Cohort.A Cox proportional hazards model was used to calculate hazard ratios(HRs)between each IR surrogate marker and incident ASCVD.Cubic spline regression was employed to explore the dose-response relationships between these markers and incident ASCVD.The relative relationships between different markers and incident ASCVD were examined through the ratio of HRs(RHRs).Time-dependent area under the receiver operating characteristic curve(TDAUC)and Uno's C-statistic were calculated to compare the predictive performance of each marker for incident ASCVD.Based on the PREVENT equation components and the 8 surrogate markers under analysis,random forest feature selection was used to determine the contribution of each marker to accurate prediction.Results During a follow-up period of82 741.93 person-years,1447 incident cases of ASCVD were recorded,with an incidence density of 17.49 per 1000 person-years.Association analyses indicated that the triglyceride to high-density lipoprotein cholesterol ratio(TG/HDL)and the TyG/(TG/HDL)index were not associated with incident ASCVD(P>0.05).The TyG index combined with obesity measurement parameters emerged as a reliable predictor of ASCVD incidence.The most promising indicator,TyG index with waist-to-height ratio(TyG_WHtR),exhibited an inverted J-shaped association with incident ASCVD(P for nonlinearity=0.045;TDAUC=0.640;C=0.634),while the TyG index with body mass index(TyG_BMI),waist circumference(TyG_WC),and waist-to-hip ratio(TyG_WHR)showed positive linear associations(all P for trend<0.05),with relatively lower predictive performance(C=0.564,0.588,and 0.598,respectively).Although both the TyG index and the metabolic score for insulin resistance(METS-IR)were associated with increased ASCVD risk(TyG:Q2 vs.Q1,HR=1.23 and Q4 vs.Q1,HR=1.24;METS-IR:P for non-linearity=0.045),they exhibited poor predictive performance for incident ASCVD.Conclusion The TyG index combined with obesity measurement parameters is an ideal IR surrogate marker for predicting incident ASCVD in populations with stages 0-3 CKM.Monitoring these markers will facilitate the prevention and control of cardiovascular diseases in CKM populations.
7.Progress of radiotherapy in oligometastatic non-small cell lung cancer
Shuyue LI ; Chenying MA ; Juying ZHOU ; Xiaoting XU ; Songbing QIN
Journal of International Oncology 2024;51(3):170-174
The effective local management of oligometastatic non-small cell lung cancer (NSCLC) has the potential to prolong patients' survival. The role of radiotherapy as a local treatment modality in patients with oligometastatic NSCLC, whether as first-line therapy or consolidation therapy, remains uncertain. Several studies have demonstrated that stereotactic ablative radiotherapy can offer clinical benefits for patients with oligometastatic NSCLC without increasing adverse reactions. Furthermore, the exploration of the potential synergistic effects of combining radiotherapy and immunotherapy on extending progression-free survival and overall survival in patients with oligometastatic NSCLC is also a topic worthy of attention.
8.Impact of cold circulation liquid temperature on ablation focus morphology of microwave ablation for porcine liver in vitro
Xia LUO ; Ping HE ; Xin YANG ; Juying ZHANG ; Qiong JIANG ; Linli FENG ; Hanmei LI ; Xiaoqing TANG ; You YANG ; Jinhong YU
Chinese Journal of Interventional Imaging and Therapy 2024;21(5):294-297
Objective To observe the impact of cold circulation liquid temperature on ablation focus morphology of microwave ablation(MWA)for in vitro porcine liver tissue.Methods Twenty in vitro fresh porcine liver blocks were randomly divided into ice water circulation group(group A)and normal temperature circulation group(group B),respectively.Ten target ablations in each subgroups in group A and group B,i.e.A1 and B1(50 W,1 min),A2 and B2(50 W,5 min),A3 and B3(60 W,1 min),A4 and B4(60 W,5 min),A5 and B5(70 W,1 min)as well as A6 and B6(70 W,5 min)subgroups were performed using different ablation power(50,60,70 W)and ablation time(1,5 min),respectively.Then the morphology indexes of ablation foci,including longitudinal diameter(LD),transverse diameter(TD),roundness index(RI)and volume(V)were compared between subgroups in group A and B,also among subgroups within group A and B.Results Under the same ablation power and time,LD of ablation foci in subgroups of group A were all smaller than those of group B(all P<0.05).Significant differences of RI of ablation foci were found between A1 and B1,A2 and B2,A4 and B4,A5 and B5 as well as A6 and B6 subgroups(all P<0.05),but not between A3 and B3 subgroups(P>0.05).However,the main effect of cold circulation liquid temperature on ablation focus TD(F=1.125)nor V(F=3.332)was not significant(both P≥0.05).Under the same cold circulation liquid temperature,significant differences of the morphology indexes of ablation foci were detected between A1 and A2,A3 and A4 as well as A5 and A6 subgroups,also between corresponding subgroups in group B(all P<0.05).Conclusion During MWA for in vitro porcine liver tissue under constant ablation power and time,taken ice water as the cold circulation liquid was benefit to ablation focus shaped spherically.With the extension of ablation time,the larger the ablation focus,the higher the RI.
9.Reflection on Improving College Students’ Health Literacy from the Perspective of Health Ethics
Ge SONG ; Yao XIAN ; Xia LIAO ; Xueliang YANG ; Huifeng ZHANG ; Juying JIN ; Weimin LI
Chinese Medical Ethics 2023;36(6):641-645
Contemporary college students have low levels of health literacy, facing problems such as weak awareness of health care, unhealthy diet habits, insufficient physical activity, and inadequate emergency response to public health emergencies. The reasons may be related to weak personal awareness of health literacy, imperfect health education system, shortage of health literacy education talents, lack of family health literacy education, and the insufficient social investment in health literacy cultivation. Faced with this current situation, the government, universities, families, individuals, and society should respond to the call of "Healthy China 2030" Plan Outline, regard improving college students’ health literacy level as their own responsibility, help them eliminate or reduce the risk factors affecting health, improve their health literacy level and quality of life, and contribute to the Healthy China strategy.
10.Hippo pathway-manipulating neutrophil-mimic hybrid nanoparticles for cardiac ischemic injury via modulation of local immunity and cardiac regeneration.
Qiaozi WANG ; Yanan SONG ; Jinfeng GAO ; Qiyu LI ; Jing CHEN ; Yifang XIE ; Zhengmin WANG ; Haipeng TAN ; Hongbo YANG ; Ning ZHANG ; Juying QIAN ; Zhiqing PANG ; Zheyong HUANG ; Junbo GE
Acta Pharmaceutica Sinica B 2023;13(12):4999-5015
The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines. Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules. Here, we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR, fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles (MSNs) loaded with microRNA-10b. The hybrid membrane could endow nanoparticles with strong capacity to migrate into inflammatory sites and neutralize proinflammatory cytokines and increase the delivery efficiency of microRNA-10b into adult mammalian cardiomyocytes (CMs) by fusing with cell membranes and leading to the release of MSNs-miR into cytosol. Upon NM@miR administration, this nanoparticle could home to the injured myocardium, restore the local immunity, and efficiently deliver microRNA-10b to cardiomyocytes, which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-10b. This combination therapy could finally improve cardiac function and mitigate ventricular remodeling. Consequently, this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury.

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