1.Regulatory effect of autophagy on the resistance of human liver cancer cell Huh7 to lenvatinib
Dahong CHEN ; Yafei WU ; Wenjing DIAO ; Huihua YANG ; Pengjuan MAO ; Qin LI
China Pharmacy 2024;35(8):961-966
OBJECTIVE To investigate the regulatory effect of autophagy on the resistance of human liver cancer cell Huh7 to lenvatinib. METHODS Using human liver cancer cell Huh7 as subject, the lenvatinib-resist cell model (Huh7-LR) was generated by the low-dose gradient method combined with long-term administration. The sensitivity of parental cell Huh7 and drug-resistant cell Huh7-LR to lenvatinib was detected by using CCK-8 assay and flow cytometry. Western blot assay and GFP-mCherry-LC3 plasmid transfection were performed to detect the expression levels of autophagic protein Beclin-1, autophagic adapter protein sequestosome 1 (p62), microtubule-associated protein 1 light chain 3 (LC3) and autophagic level. Furthermore, an autophagy activation model was constructed by cell starvation, the protein expression of p62 and autophagy level were detected by using Western blot assay and GFP-mCherry-LC3 plasmid transfection, and the effect of autophagy activation on the sensitivity of Huh7-LR cells to lenvatinib was detected by flow cytometry. RESULTS Compared with parental cells, the drug resistance index of Huh7-LR cells was 6.2; protein expression of p62 was increased significantly, while apoptotic rate, protein expression of Beclin-1 and LC3Ⅱ/ LC3Ⅰ ratio were all reduced significantly (P<0.05 or P<0.01); the level of autophagy was decreased to some extent. Autophagy activation could significantly increase the protein expression of p62 in Huh7-LR cells (P<0.05) and autophagy level, and significantly increase its apoptotic rate (P<0.05). CONCLUSIONS Autophagy is involved in lenvatinib resistance, and activating autophagy can reverse the resistance of liver cancer cells to lenvatinib to some extent.
2.Improvement of Depression-like Behavior of Depression Model Mice by Sinisan via Regulating GSK-3β/A20/C/EBPβ to Inhibit Activation of Microglia
Hongyun CHEN ; Dongying YANG ; Huiqing LIAO ; Yanyan ZENG ; Linke PAN ; Shasha BAI ; Di DENG ; Yafei SHI ; Rong ZHANG ; Lei YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(12):16-23
ObjectiveTo investigate the antidepressant effect of Sinisan (SNS) by regulating glycogen aynthase kinase-3β (GSK-3β)/tumor necrosis factor alpha-induced protein 3(A20)/CCAAT enhancer binding protein β(C/EBPβ) to inhibit the activation of microglia. MethodA total of 72 male C57/6J mice were randomly divided into the normal group, model group, fluoxetine group (5.0 mg·kg-1), low-dose Sinisan group (4.9 g·kg-1), medium-dose Sinisan group (9.8 g·kg-1), and high-dose Sinisan group (19.6 g·kg-1), with 12 mice in each group. After one week of adaptive feeding, chronic unpredictable mild stress (CUMS) was performed to establish the depression model. In the fifth week, drug treatment was conducted for four weeks. In the ninth week, behavioral tests were performed, including sucrose preference test (SPT), open field test (OPT), elevated plus maze (EPM) test, and forced swimming test (FST). Western blot was used to detect the expression levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), nitric oxide synthase (iNOS), GSK-3β, A20, and C/EBPβ in the cortex. The expression of M1-polarized ionized calcium-binding adapter molecule 1 (Iba1) and cluster of differentiation 68 (CD68) in microglia was detected by immunofluorescence. ResultAfter eight weeks of CUMS, compared with the normal group, the mice in the model group had a significantly reduced sucrose preference rate (P<0.01), and the activity in the central area of the OPT was significantly reduced (P<0.01). The activity in the open arm area of the EPM test was significantly reduced (P<0.05), and the immobility time of FST was increased (P<0.01). The expression levels of inflammatory proteins IL-1β, IL-6, and iNOS were increased (P<0.01), and the fluorescence co-localization index of Iba1 and CD68 was increased (P<0.05). The protein expression levels of GSK-3β and C/EBPβ were significantly increased (P<0.05, P<0.01). After four weeks of SNS intervention, compared with the model group, the mice in the SNS group had significantly increased sucrose preference rate (P<0.01), significantly increased activities in the central area and the open arm area in the OPT and the EPM test (P<0.05), and significantly reduced immobility time in the FST (P< 0.01). The protein expression levels of IL-1β, IL-6, and iNOS were significantly decreased (P<0.05), and the fluorescence co-localization index of Iba1 and CD68 was decreased in the high-dose SNS group (P<0.05). The protein expression levels of GSK-3β and C/EBPβ in the medium-dose and high-dose SNS groups were significantly decreased (P<0.01), and that of A20 was significantly increased (P<0.01). ConclusionThe antidepressant effect of SNS is related to the regulation of GSK-3β/A20/C/EBPβ protein expression and the inhibition of M1-type activation of microglia.
3.Application status of risk assessment models for periodontal disease
NIE Min ; XU Hongdan ; WU Yafei ; YANG Jingmei
Journal of Prevention and Treatment for Stomatological Diseases 2024;32(3):235-240
Risk assessment models for periodontal disease provide dentists with a precise and consolidated evaluation of the prognosis of periodontitis, enabling the formulation of personalized treatment plans. Periodontal risk assessment systems have been widely applied in clinical practice and research. The application fields of periodontal risk assessment systems vary based on the distinctions between clinical periodontal parameters and risk factors. The assessment models listed below are commonly used in clinical practice, including the periodontal risk calculator (PRC), which is an individual-based periodontal risk assessment tool that collects both periodontal and systemic information for prediction; the periodontal assessment tool (PAT), which allows for quantitative differentiation of stages of periodontal disease; the periodontal risk assessment (PRA) and modified periodontal risk assessment (mPRA), which are easy to use; and the classification and regression trees (CART), which assess the periodontal prognosis based on a single affected tooth. Additionally, there are orthodontic-periodontal combined risk assessment systems and implant periapical risk assessment systems tailored for patients needing multidisciplinary treatment. This review focuses on the current application status of periodontal risk assessment systems.
4.Effects of marathon exercise on knee cartilage volume and T2 relaxation time
Lingbin XU ; Feng FU ; Xiaofeng YANG ; Qiqian SANG ; Yafei XU ; Mingjie WU ; Lu XUE
Chinese Journal of Orthopaedics 2024;44(5):294-301
Objective:To investigate the effects of marathon exercise on knee cartilage volume and T2 relaxation time (T2 value) based on MRI.Methods:From December 2018 to December 2021, 25 healthy volunteers without long-distance running habits and 32 non-professional marathon runners with long-term long-distance running were recruited to undergo knee MRI 3D water-selective excitation (three dimensional water-selective excitation, 3D-WATS) and T2 mapping imaging were performed, and the cartilage volumes in 5 knee areas and T2 values in 42 subareas were extracted for analysis. To compare the cartilage volume and its ratio to body surface area of knee joint of healthy volunteers and non-professional marathon runners, the T2 value of cartilage in each subregion, and the correlation between marathon exercise intensity and the volume and T2 value of cartilage in different regions.Results:Compared with healthy volunteers, there was no significant difference in cartilage volume or the ratio of body surface area to body volume of non-professional marathon runners ( P>0.05). There were significant differences between healthy volunteers and non-professional marathon runners in cartilage T2 values of the median layer of medial condyle of femur (47.61±5.65 ms and 44.29±6.10 ms) and the deep layer of medial condyle of femur (36.82±9.05 ms and 31.67±7.59 ms), deep precondylar area of medial femur (38.37±4.68 ms and 34.09±4.19 ms), shallow area of medial condylar area of femur (52.17±11.11 ms and 45.51±7.76 ms), middle layer of medial condylar area of femur (49.09±5.08 ms and 45.63±5.04 ms), medial layer of anterior condylar region of lateral femur (45.69±4.68 ms and 42.57±5.77 ms), superficial layer of posterior condylar region of lateral femur (55.42±18.41 ms and 47.99±8.39 ms), deep layer of anterior tibial medial plateau (33.40±7.76 ms and 29.03±5.69 ms), deep layer of posterior tibial medial plateau (31.28±5.02 ms and 27.92±5.99 ms), deep layer of patellofemoral surface (35.65±6.99 ms and 32.30±5.28 ms), respectively ( P<0.05). In non-professional marathon runners, the medial tibial plateau cartilage volume was negatively correlated with step frequency ( r=-0.371, P=0.035), the lateral femoral condylar cartilage volume was negatively correlated with step frequency ( r=-0.365, P=0.043), and the lateral tibial plateau cartilage volume was negatively correlated with step frequency ( r=-0.550, P=0.001). The T2 value of the medial layer cartilage in the anterior tibial medial plateau region was negatively correlated with body weight ( r=-0.277, P=0.039) and body mass index ( r=-0.290, P=0.030). The T2 value of the superficial layer of patellofemoral surface was negatively correlated with the amount of running in 3 months ( r=-0.457, P=0.010). The superficial T2 value in the posterior lateral plateau of the tibia was negatively correlated with stride length ( r=-0.437, P=0.014), and the medial layer cartilage T2 value in the anterior condylar area of the lateral femur was negatively correlated with stride frequency ( r=-0.380, P=0.035). Conclusion:Marathon exercise had little effect on the knee cartilage volume, but had a certain effect on the cartilage T2 value, resulting in changes in cartilage structure. The higher the step frequency, the smaller the cartilage volume. The greater the body weight or body mass index, the greater the amount of running in 3 months, and the greater the stride length, the lower the cartilage T2 value.
5.Trends in age-, period- and cohort-specific incidence of hepatitis C in Chifeng City from 2008 to 2022
LI Wenjun ; LI Hui ; YANG Jingyuan ; YANG Hong ; GAO Ya ; GAO Baicheng ; LI Yao ; ZHANG Qiyue ; QIU Yafei
Journal of Preventive Medicine 2024;36(6):514-517,522
Objective:
To explore incidence trend of hepatitis C in Chifeng City, Inner Mongolia Autonomous Region from 2008 to 2022, so as to provide the basis for formulating prevention and control measures for hepatitis C.
Methods:
Data of reported hepatitis C cases in Chifeng City from 2008 to 2022 was collected through the Infectious Disease Information Reporting Management System. Trends in incidence of hepatitis C were analyzed using annual percent change (APC) and average annual percent change (AAPC). Impact of age, period and birth cohort on the risk of developing hepatitis C were analyzed by an age-period-cohort model.
Results:
The annual average reported incidence rate of hepatitis C in Chifeng City was 59.13/105 from 2008 to 2022. The incidence showed an upward trend from 2008 to 2018 (APC=9.405%, P<0.05) and a downward trend from 2018 to 2022 (APC=-17.475%, P<0.05), but the overall trend was not statistically significant (AAPC=0.937%, P>0.05). The age-period-cohort model analysis showed that the incidence risks of hepatitis C in the residents aged 0 to 4 years and 45 to 84 years were higher than those in the residents aged 40 to 44 years (the control group). The incidence risk of hepatitis C increased with age from 40 to 79 years. Compared with 2008-2012, the incidence risk of hepatitis C showed an increasing trend followed by a decline in 2008-2022. The incidence risk was higher in 2013-2017 and lower in 2018-2022 than in 2008-2012. The incidence risk of hepatitis C showed an increasing trend followed by a decreasing trend by using the birth cohort from 1968 to 1972 as the control. The birth cohort from 1953 to 1977 had a higher incidence risk of hepatitis C than other birth cohorts.
Conclusions
The overall incidence of hepatitis C in Chifeng City from 2008 to 2022 appeared a tendency towards a decline, and the incidence risk increased with age. Screening and health education for the elderly and high-risk birth cohorts should be strengthened.
6.Construction and Testing of Health LifeStyle Evidence (HLSE)
Chen TIAN ; Yong WANG ; Yilong YAN ; Yafei LIU ; Yao LU ; Mingyao SUN ; Jianing LIU ; Yan MA ; Jinling NING ; Ziying YE ; Qianji CHENG ; Ying LI ; Jiajie HUANG ; Shuihua YANG ; Yiyun WANG ; Bo TONG ; Jiale LU ; Long GE
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1413-1421
Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (
7.The Effect and Mechanism of Estrogen and Estrogen Receptors in the Pathogenesis of Non-Invasive Fungal Rhinosinusitis
Chuanmei YANG ; Yafei SU ; Luhua SHEN ; Hong ZHANG ; Teng WANG ; Siyu JI ; Zhiyong XIAO
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(6):1017-1025
[Objective]To explore the role of estrogen and estrogen receptor (ER) in the pathogenesis and regulation of non-invasive fungal rhinosinusitis (NIFR).[Methods]Totally 60 patients with NIFS who met the inclusion criteria in Fuzhou Second General Hospital from November 2020 to November 2023 were selected as the NIFS group,while 30 healthy volunteers were recruited as the blank control group. Samples of each group were collected. The number of eosinophils and mast cells in each group were detected by HE staining;ER expression was detected by immunohistochemistry and immunofluorescence;mRNA expression levels of NF-κB,IKK and MASPIN were detected by qPCR;and protein expression levels of NF-κB,IKK and MASPIN were detected by immunohistochemistry and Western blot.[Results]In the NIFS group,the counts of eosinophils and mast cells were significantly increased respectively,compared with those in the control group,and the inter-group differences are statistically significant (P<0.01 and P<0.05,respectively). The Estrogen Receptor (ER) score in the NIFS group was significantly increased compared with that in the control group,and the inter-group differences are statistically significant (P<0.05). Additionally,the average high-density value in the NIFS group was significantly increased compared with that in the control group,and the inter-group differences are statistically significant (P<0.01). The expression levels of NF-κB,IKK,and MASPIN in the NIFS group were significantly increased respectively,compared with those in the control group,and the inter-group differences are statistically significant (P<0.01,P<0.05,and P<0.01,respectively). The mRNA expression levels of NF-κB,IKK,and MASPIN in the NIFS group were significantly increased,respectively,compared with those in the control group (P<0.01). Furthermore,the protein expression levels of NF-κB,IKK,and MASPIN in the NIFS group were increased,respectively,and the inter-group differences are statistically significant (P<0.01,P<0.01,and P<0.05,respectively).[Conclusion]Our results show that the significant increase in the number of eosinophils and mast cells,and in the expression levels of ER,NF-κB,IKK and MASPIN may indicate a significant increase in eosinophil and mast cell infiltration in ER positive patients,and suggest the involvement of estrogen and its receptors in the pathogenesis of NIFS.
8.Treatment of Pulmonary Inflammatory Diseases by Traditional Chinese Medicine Through Regulating Mitochondrial Oxidative Stress: A Review
Mengdi SHI ; Chao WANG ; Yafei YOU ; Lisha LU ; Yang YANG ; Weichao JING ; Lujia LIU ; Youpeng WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):249-258
Pulmonary fibrosis, chronic obstructive pulmonary disease, acute lung injury, asthma, and infectious pneumonia are common pulmonary inflammatory diseases worldwide. There is evidence that mitochondria produce a large amount of reactive oxygen species (ROS) when stimulated by inflammation, leading to oxidative stress that affects the onset and progression of pulmonary inflammatory diseases. With in-depth research, traditional Chinese medicine (TCM) has made significant progress in the treatment of pulmonary inflammatory diseases. An increasing amount of evidence indicates that single TCM and their active components, as well as TCM compound formulas, can improve mitochondrial oxidative stress status through multi-target and multi-pathway mechanisms, thereby effectively treating pulmonary inflammatory diseases. Currently, there is a lack of systematic review and summary of TCM research in this field both domestically and internationally. Therefore, this article aims to summarize and conclude the mechanisms by which TCM regulates mitochondrial oxidative stress to intervene in pulmonary inflammatory diseases, providing a scientific basis for its clinical application and offering new ideas and references for in-depth research on the prevention and treatment of pulmonary inflammatory diseases with TCM.
9.Study on the neuroprotective effect of curculigoside on rats with spinal cord injury
Na LIU ; Peipei HUANG ; Jing YANG ; Yafei LI
China Pharmacy 2024;35(12):1469-1475
OBJECTIVE To investigate the neuroprotective effect of curculigoside (CUR) on rats with spinal cord injury (SCI) based on phosphatase and tensin homologue deleted on chromosome ten gene-induced putative kinase 1 (PINK1)/E3 ubiquitin ligase Parkin signaling pathway. METHODS Taking male SD rats as subjects, 15 rats were randomly selected as sham operation group; the rest rats were chosen to establish SCI model by spinal cord impact method, and then were divided into model group, CUR low-dose group (36 mg/kg CUR, gavage), CUR high-dose group (72 mg/kg CUR, gavage) and CUR high-dose+3- methyladenine (3-MA) group (72 mg/kg CUR, gavage+20 mg/kg autophagy inhibitor 3-MA, intraperitoneal injection), with 15 rats in each group. Rats in each group were given corresponding liquid/normal saline, once a day, for 28 consecutive days. Basso- Beattie-Bresnahan (BBB) score and Rivlin inclined plate experiment were performed on the 14th and 28th day after administration; the pathological changes of spinal cord tissue in rats were observed in each group; the apoptosis of spinal cord tissue, the levels of oxidative stress factors [malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH)], and the protein expressions of brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), PINK1, Parkin, p62 and microtubule- associated protein light chain 3 (LC3) were all determined. RESULTS Compared with the sham operation group, obvious edema and bleeding in the spinal cord tissue of rats were observed in the model group, accompanied by a large number of inflammatory cell infiltration; BBB score and inclined plate angle, SOD and GSH levels, the protein expressions of BDNF, PINK1 and Parkin, and LC3Ⅱ/Ⅰ ratio were significantly reduced; the apoptosis rate, MDA level, the protein expressions of GFAP and p62 in spinal cord tissue were significantly increased (P<0.05). Compared with the model group, the edema, bleeding and infiltration of inflammatory cells in the spinal cord tissue of rats were reduced in the administration groups, and the above quantitative indicators had been significantly improved (P<0.05); 3-MA could significantly reverse the improvement effects of the above indexes by CUR (P<0.05). CONCLUSIONS CUR can promote the recovery of neurological and motor functions in SCI rats, improve the pathological injury of the spinal cord and inhibit apoptosis, which may be related to mitochondrial autophagy mediated by activating the PINK1/Parkin signaling pathway.
10.Application status of risk assessment models for periodontal disease
Min NIE ; Hongdan XU ; Yafei WU ; Jingmei YANG
Journal of Prevention and Treatment for Stomatological Diseases 2024;(3):235-240
Risk assessment models for periodontal disease provide dentists with a precise and consolidated evalua-tion of the prognosis of periodontitis,enabling the formulation of personalized treatment plans.Periodontal risk assess-ment systems have been widely applied in clinical practice and research.The application fields of periodontal risk assessment systems vary based on the distinctions between clinical periodontal parameters and risk factors.The assess-ment models listed below are commonly used in clinical practice,including the periodontal risk calculator(PRC),which is an individual-based periodontal risk assessment tool that collects both periodontal and systemic information for pre-diction;the periodontal assessment tool(PAT),which allows for quantitative differentiation of stages of periodontal dis-ease;the periodontal risk assessment(PRA)and modified periodontal risk assessment(mPRA),which are easy to use;and the classification and regression trees(CART),which assess the periodontal prognosis based on a single affected tooth.Additionally,there are orthodontic-periodontal combined risk assessment systems and implant periapical risk as-sessment systems tailored for patients needing multidisciplinary treatment.This review focuses on the current applica-tion status of periodontal risk assessment systems.


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