1.Exploring the Mechanism of Action of Guhuaisi Kangfu Pill for Treating Steroid-induced Osteonecrosis of the Femoral Head Based on WGCNA and Animal Experiment Validation
Wenxi LI ; Liangyu TIAN ; Jin ZHANG ; Caihong SHEN ; Zhimin YANG ; Jiaqiao GUO ; Yuju CAO
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(9):1306-1318
Objective To investigate the main pharmacological basis and mechanism of action of Guhuaisi Kangfu Pill(GHSKF)in the treatment of steroid-induced osteonecrosis of the femoral head(SONFH).Methods The active constituents and targets of GHSKF were screened by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and other databases.The speculative targets of SONFH were screened out based on GeneCards and Online Mendelian Inheritance in Man(OMIM)databases.The gene modules and hub genes of SONFH were identified using a weighted gene co-expression network analysis(WGCNA).The intersection of the two targets and the result of WGCNA was taken to obtain the potential targets of GHSKF for the treatment of SONFH.The key active constituents were screened with the"active constituent-target"network,which was constructed by the Cytoscape software.Then,the STRING database was used to construct the protein interaction network to screen the key targets.The Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of key targets was performed,and the relationship between key active constituent,key targets and key signaling pathways was explored.Finally,the molecular docking between key active constituents and key targets was verified.In addition,the SONFH rat model was used for experimental verification.Results A total of 146 compounds and the corresponding 346 targets were identified based on the TCMSP database.A total of 4 187 targets of SONFH were obtained based on GeneCards and OMIM databases.In addition,twelve gene modules and 2 556 hub genes of SONFH were screened out based on WGCNA.Quercetin,luteolin and kaempferol were key active ingredients for the treatment of SONFH.Various signaling pathways such as PI3K/AKT were involved.Molecular docking showed the key active ingredients had good binding activity with the key targets.The results of animal experiments demonstrated that GHSKF could improve bone biological alterations by up-regulating AKT1,PI3K,RUNX2,and down-regulating the expression of Caspase-3 and IL-6(P<0.01),which verified some results of the network pharmacology prediction.Conclusion We analyzed the potential mechanism of action of GHSKF for the treatment of SONFH using network pharmacology and animal experiments,which may provide a reference for further research on its pharmacological basis and targets.
2.Association Between Dietary Diversity and Caregiver Self-Efficacy for Complementary Feeding Among Infants and Young Children Aged 6-23 Months in Rural Nanchong City,Sichuan Province
Runxue GUO ; Xinying JI ; Linhua LI ; Fangqun LENG ; Qinxin LIU ; Yuju WU ; Huan ZHOU
Acta Academiae Medicinae Sinicae 2024;46(1):19-24
Objective To analyze the current situation of dietary diversity and caregiver self-efficacy for complementary feeding among infants and young children aged 6 to 23 months in rural Nanchong city,Sichuan province,and to explore the relationship between dietary diversity and caregiver self-efficacy.Methods Multi-stage randomized cluster sampling method was used to select infants and young children aged 6 to 23 months and their caregivers in rural areas of Nanchong city,Sichuan province as the subjects.A structured questionnaire was designed to collect the basic information of the subjects,dietary diversity,and caregiver self-efficacy for comple-mentary feeding.Multivariate Logistic regression was adopted to analyze the relationship between the dietary diver-sity and caregiver self-efficacy for complementary feeding of infants and young children.Results A total of 770 pairs of infants and young children and their caregivers were included.The minimum pass rate of dietary diversity was 61.56% (474/770)for all the infants and young children and 45.00% (108/240),69.16% (287/415),and 68.70% (79/115)for the infants and young children aged 6 to 11,12 to 17,and 18 to 23 months,respective-ly.The results of regression analysis showed that the caregiver self-efficacy of complementary feeding was a contributing fac-tor for qualified dietary diversity of infants and young children in the case of other confounders being controlled(OR = 1.42,95% CI=1.17-1.73,P<0.001).Conclusion The dietary diversity for infants and young children in rural Nan-chong city,Sichuan province needs to be improved,and caregivers with higher self-efficacy of complementary feeding are more likely to provide diversified complementary feeding for infants and young children.
3.Relationship Between Physical Activity and Depressive Symptoms Among Middle-Aged and Older Adults in Chengdu,Sichuan,China
Tianxin XU ; Yadi HE ; Zhengjie CAI ; Linhua LI ; Yuju WU ; Huan ZHOU
Acta Academiae Medicinae Sinicae 2024;46(4):497-506
Objective To investigate the current status of physical activity and depressive symptoms a-mong middle-aged and older adults in Chengdu,Sichuan and explore the relationship between physical activity and depressive symptoms.Methods Multi-stage proportional stratified random sampling was employed to select middle-aged and older adults aged ≥45 years as the participants,and face-to-face interviews were carried out to collect data.Logistic regression was adopted to explore the relationship between physical activity and depressive symptoms in middle-aged and older adults.The trend test was performed for the relationship between different lev-els of physical activity and depressive symptoms.The subgroup analysis and the test for multiplicative interactions were conducted for the relationship between physical activity and depressive symptoms.Results A total of 4376 middle-aged and older adults were included.Among them,14.58%(638/4376),25.98%(1137/4376),and 27.83%(1218/4376)had depressive symptoms,failed to reach the guideline-recommended standards of physical activity,and were at low levels of physical activity,respectively.There was a negative association be-tween reaching guideline-recommended physical activity standard and depressive symptoms in middle-aged and ol-der adults(OR=0.713,95%CI=0.589-0.861,P<0.001).In addition,moderate levels(OR=0.714,95%CI=0.586-0.871,P=0.001)and high levels of physical activity(OR=0.705,95%CI=0.548-0.906,P=0.006)had negative associations with the presence of depressive symptoms.The trend test revealed that the negative association between physical activity and depressive symptoms in middle-aged and older adults enhanced as the level of physical activity increased(Pfor trend=0.001).The subgroup analysis and the test for multiplicative interactions revealed that neither reaching guideline-recommended physical activity standards or not nor the physi-cal activity level had an interaction with each of the subgroups(all Pfor interaction>0.05).Conclusions The current status of depressive symptoms among middle-aged and older adults in Chengdu,Sichuan needs to be ameliora-ted.A negative association existed between reaching the guideline-recommended physical activity standard and pres-ence of depressive symptoms,and the negative association enhanced as the physical activity level elevated.
4.Bushen Huoxue Prescription Regulates PINP and β-CTX in Treatment of Femoral Head Necrosis with Syndrome of Liver and Kidney Deficiency
Zijia LIU ; Ying LI ; Pengtao CUI ; Bowen WANG ; Peigang ZHANG ; Wuyue TONG ; Zhihui ZHANG ; Yuju CAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):81-89
ObjectiveTo explore the therapeutic mechanism of Bushen Huoxue prescription from the perspective of bone metabolism by observing the clinical efficacy of this prescription in treating femoral head necrosis (ONFH, syndrome of liver and kidney deficiency) and its influences on bone metabolism indexes: N-terminal propeptide (PINP) and β-collagen degradation product (β-CTX). MethodSixty-six ONFH patients with the syndrome of liver and kidney deficiency in Zhengzhou Traditional Chinese Medicine Hospital of Orthopedics from December 2021 to September 2022 were selected. The patients were randomized into an experimental group and a control group by the parallel control method, with 33 patients in each group. The experimental group received Bushen Huoxue prescription orally, while the control group received Xianlinggubao Capsules orally, with a treatment cycle of 6 months. The visual analogue scale (VAS) score, Harris score, Association Research Circulation Osseous (ARCO) staging, imaging changes, quantitative scores of TCM symptoms, and serum levels of PINP and β-CTX were determined before and after treatment. The occurrence of adverse events and reactions was recorded. ResultThe total response rate in the experimental group was 83.87% (26/31), which was higher than that (68.75%, 22/32) in the control group (Z=-2.096, P<0.05). After treatment, the single and total scores of TCM symptoms, VAS score, and β-CTX level decreased in the two groups (P<0.05). Moreover, the decreases in the scores of hip pain, lower limb mobility, soreness of waist and knees, and lower limb flaccidity, total score of TCM symptoms, VAS score, and β-CTX level in the experimental were larger than those in the control group (P<0.05). After treatment, the imaging results showed no significant improvement in the two groups. The Harris score and PINP level in both groups increased after treatment (P<0.05), and the increases were more obvious in the experimental group than in the control group (P<0.05). No serious adverse event or adverse reaction appeared during the observation period. ConclusionBushen Huoxue prescription can relieve pain and TCM symptoms and improve the hip joint function in treating ONFH patients with the syndrome of liver and kidney deficiency. It can inhibit the development of ONFH, increase PINP, and decrease β-CTX. No obvious side effect appears during the clinical observation period, which shows that Bushen Huoxue prescription has good safety.
5.Effects of different concentrations of morphine in combination with ropivacaine on proliferation,migration,invasion and cell cycle in MDA-MB-231 breast cancer cells
Xinyu ZHANG ; Gang CHEN ; Yuju TAN ; Yanru LIU ; Yunyun LI ; Aiqhua JIANG
China Modern Doctor 2024;62(2):62-66
Objective To investigate the effects of different concentrations of morphine in combination with ropivacaine on proliferation,migration,invasion and cell cycle in MDA-MB-231 breast cancer cells.Methods MDA-MB-231 breast cancer cells were inoculated on the culture plate for 24h and randomly divided into 8 groups:Control group(C),ropivacaine 400μg/ml group(R),morphine 3μg/ml group(LM),morphine 30μg/ml group(MM),morphine 300μg/ml group(HM),ropivacaine 400μg/ml group+ morphine 3μg/ml group(R+LM),ropivacaine 400μg/ml+ morphine 30μg/ml group(R+MM),and ropivacaine 400μg/ml+ morphine 300μg/ml group(R+HM).After treaments of MDA-MB-231 breast cancer cells for 24h,these proliferation,migration,invasion and cell cycle were evaluated.Results When using morphine alone,the proliferation inhibitive effect was positively correlated with the concentration of morphine.The proliferation was significantly inhibited by morphine of LM,MM,HM group(P<0.05).When using ropivacaine alone,the proliferation was significantly inhibited(P<0.05).When using morphine combined with ropivacaine,the high concentration morphine group has a synergistic effect with ropivacaine group on proliferation inhibition(P<0.05).When using morphine alone,the migration rate decreases sequentially with the increase of morphine concentration.The migration rate was significantly inhibited by morphine of LM,MM,HM group(P<0.05).When using ropivacaine alone,the migration rate was inhibited(P<0.05).When using morphine combined with ropivacaine,the low and medium concentration morphine group have a synergistic effect with ropivacaine group on migration rate(P<0.05).When using morphine alone,the number of cell invasion was decreased with the concentration of morphine increasing(P<0.05).The MM and HM groups inhibited cell invasion ability.When using ropivacaine alone,the invasiveness of cells was also inhibited(P<0.05).When using morphine combined with ropivacaine,the medium and high concentration morphine groups have a synergistic effect with ropivacaine group on inhibiting cell invasion ability(P<0.05).When using morphine alone,the cell cycle progression was inhibited into G2/M Phase(P<0.05).When using ropivacaine alone,the cell cycle progression was inhibited into G2/M phase(P<0.05).The combination of low concentration morphine and ropivacaine has synergistic effect on arresting at G0/G1 and S phase(P<0.05).Conclusion Morphine combined with ropivacaine inhibits the Proliferation,migration and invasion of MDA-MB-231 breast cancer cells in a dose-dependent manner.
6.Efficacy,metabolic characteristics,safety and immunogenicity of AK-HER2 compared with reference trastuzumab in patients with metastatic HER2-positive breast cancer:a multicenter,randomized,double-blind phase Ⅲ equivalence trial
Yang LUO ; Tao SUN ; Zhimin SHAO ; Jiuwei CUI ; Yueyin PAN ; Qingyuan ZHANG ; Ying CHENG ; Huiping LI ; Yan YANG ; Changsheng YE ; Guohua YU ; Jingfen WANG ; Yunjiang LIU ; Xinlan LIU ; Yuhong ZHOU ; Yuju BAI ; Yuanting GU ; Xiaojia WANG ; Binghe XU ; Lihua SONG
China Oncology 2024;34(2):161-175
Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.
7.Advances in studies on the effect of epithelial-mesenchymal transformation on radiotherapy sensitivity of tumors
Chinese Journal of Radiation Oncology 2023;32(4):384-388
Radiotherapy is one of the most important methods in the treatment of malignant tumors. However, the decrease of radiosensitivity of tumor cells is the main reason affecting the efficacy of radiotherapy. Epithelial-mesenchymal transition (EMT) is a complex biological process that confers several characteristics necessary for the progression of malignant tumors, such as tumor initiation, aggressiveness, transmissibility, and tolerance to chemotherapy and radiotherapy. In addition, EMT can also be induced by radiation, which endows tumor cells with radiation resistance. Previous studies have shown that inhibition of EMT could enhance the radiosensitivity of tumor cells, but the overall understanding of the molecular mechanisms, key targets and pathways involved are still lacking. In this article, recent studies on the role of EMT in tumor radiation therapy were reviewed, focusing on the signaling pathway, EMT-induced transcription factors, aiming to deepen the understanding of the effect of EMT on the sensitivity of radiotherapy and provide ideas for improving the clinical therapeutic effect of radiotherapy.
8.Effect of CIPP evaluation model in the specialist training of junior nurses in the Department of Otolaryngology
Yuju ZHANG ; Wei CHEN ; Haixue WU ; Na LI ; Jiangtao LIU ; Haiqing YU ; Wenhong LU ; Na XIONG
Chinese Journal of Modern Nursing 2021;27(8):1071-1074
Objective:To explore effects of the specialist nurse training program of based on the context, input, process, product (CIPP) evaluation model in the training of junior nurses in the Department of Otolaryngology.Methods:From April 2018 to May 2020, convenience sampling method was used to select 80 specialist nurses who received training in the Shandong ENT Hospital as research objects. A total of 40 nurses who received traditional training from April 2018 to March 2019 were divided into a control group. From April 2019 to May 2020, 40 nurses who were trained in a specialist nurse training program based on the CIPP evaluation model were divided into observation groups. This study compared nurses' core competence and training qualification rate.Results:After training, the core competence score of observation group was higher than that of control group, and the difference was statistically significant ( P<0.05) . The training qualification rate of observation group and control group was 92.50% (37/40) and 70.00% (28/40) respectively, also with a statistical difference ( P<0.05) . Conclusions:The training program for specialist nurses based on the CIPP evaluation model can improve the theoretical knowledge and practical ability of nurses, and then improve the quality of clinical care, and promote the long-term development of the hospital, which is worthy of promotion.
9.Effectiveness of self-health management in high-risk individuals for diabetes
Chinese Journal of Geriatrics 2018;37(10):1134-1136
Objective To explore the effectiveness of health risk assessment-based self-health management in individuals at high risk for diabetes.Methods From January 2016 to December 2017,we selected 1200 individuals at high risk for diabetes and divided them into a regular group(n=600)and a management group(n =600)using random number table sampling.The regular group was given regular health education and management,while the management group received intervention targeting high-risk factors.Both groups were under observation for six months and intervention effects in the two groups were compared.Results After intervention,fasting blood glucose,postprandial blood glucose,and glycosylated hemoglobin in the management group were significantly lower than in the regular group (P <0.05);Patients in the management group had better self-management than those in the regular group at strict diet control (90.0% vs.76.3%),strict medication compliance (86.7% vs.71.7%),weekly exercise time > 1 h (92.5% vs.70.0%),and weekly blood glucose measurements >3 (89.5% vs.76.7%) (P <0.05);scores on patient satisfaction with intervention were higher in the management group than in the regular group(94.77±4.26 vs.84.65±t7.77,P< 0.05).Conclusions Health risk assessment-based self-health management proves to be effective for individuals at high risk for diabetes,with effective control over blood sugar levels as well as improvement in self-management efficacy and patient satisfaction.
10.Impact of the neglected Cysticercus cellulose infection on mental health among school-aged children in Tibetan agricultural areas.
Ruixue YE ; Yuju WU ; Qingzhi WANG ; Min CAO ; Tiaoying LI ; Xingwang CHEN ; Huan ZHOU
Journal of Central South University(Medical Sciences) 2018;43(10):1137-1144
To determine the impact of Cysticercus cellulose (C. cellulose) infection on mental health among school-aged children in Tibetan agricultural areas of Sichuan Province.
Methods: In October 2015, all primary schools located in Tibetan agricultural areas in Yajiang, Ruoergai, and Muli county of Sichuan Province were selected as the research sites. All school-aged children at five- and six-grade were enrolled for the study by a multistage stratified cluster sampling method. Antibodies against C. cellulose were detected. Mental Health Test and questionnaire survey were conducted for school-aged children to collect data. The impact of C. cellulose infection on mental health among school-aged children was analyzed with the multilevel linear regression.
Results: A total of 2 453 school-aged children were investigated. The C. cellulose seropositive rate was 6.03% (148/2 453). There were 0.16% (4/2 453) patients with seropositive accompanied by seizure, 2.28% (56/2 453) with seropositive accompanied by headache, 2.08% (51/2 453) with seropositive accompanied by frequent weak, and 0.41% (10/2 453) were seropositive accompanied by frequent nausea. The rate of C. cellulose infection was 4.53% (111/2 453). The mean score of the mental health test was 6.59±2.61. There were significant difference in score of mental health test in children whose demographic characteristics were different. The mental health scores of school-aged children were clustered at the school level. After controlling the factors of demographic characteristics, the result of multilevel model demonstrated that the factor of school-aged children with C. cellulose seropositive accompanied by headache was statistically significant (β=1.14, P=0.017).
Conclusion: The status of C. cellulose infection among school-aged children in Tibetan agricultural areas is not optimistic. C. cellulose infection has impacted on mental health of local school-aged children. It is necessary to strengthen the prevention and control of C. cellulose infection in epidemic area.
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Cysticercosis
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complications
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epidemiology
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Humans
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Mental Health
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Neurodevelopmental Disorders
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epidemiology
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etiology
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Seroepidemiologic Studies
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Tibet
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epidemiology

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