1.ATG5 counteracts nutritional stress in human hepatoblastoma HepG2 cells by regulating autophagic flux
Lian ZHAO ; Dongyun XIANG ; Huiyi WU ; Hao SUN ; Jinghuan DENG
Journal of Army Medical University 2025;47(13):1454-1462
Objective To investigate the effect of nutritional deficiency on autophagic flux in human hepatoblastoma HepG2 cells and the autophagy-dependent molecular pathway mediated by ATG5 against nutritional stress.Methods Lentiviral siRNA knockdown of ATG5 was performed to knock down the expression in HepG2 cells,and the transfection was verified by Western blotting and qRT-PCR.HBSS was used to treat HepG2 cells for 0,1,2,3,4,5,6 and 7 h for starvation-induced autophagy.Monodansylcadaverine(MDC)fluorescence staining was employed to detect the formation of intracellular autophagic vesicles.Western blotting was performed to measure the expression changes in microtubule-associated protein 1A/1B-light chain 3(LC3),autophagy receptor protein(sequestosome 1,P62),autophagy-related gene 5(ATG5)and nutrient stress pathway(AMPK/mTOR pathway)related proteins.CCK-8 assay was utilized to test cell proliferation.Results Compared with the HepG2 cells under conventional culture medium,starvation induction resulted in more autophagic vacuoles(accumulation of autofluorescent marker,MDC),which peaked at 6 h of starvation(P<0.000 1),up-regulated protein levels of LC3B-Ⅱ and ATG5(P<0.05),decreased protein expression of P62(P<0.05),gradual activation of the AMPK/mTOR pathway with elapse of starvation time,and increase in the intensity of autophagic flux.However,in the HepG2 cells with ATG5 knockdown,starvation treatment led to decreased ATG5 expression,no significant difference in LC3B-II and P62 changes,inhibited autophagic flux,and suppressed cell proliferation(P<0.000 1).Conclusion Human hepatoblastoma HepG2 cells can regulate autophagic flux to against nutritional stress by inducing ATG5 expression.
2.Clinical and genetic characteristics of young patients with myeloproliferative neoplasms
Mengyu ZHANG ; Mei BAO ; Dayu SHI ; Hongxia SHI ; Xiaoli LIU ; Na XU ; Minghui DUAN ; Junling ZHUANG ; Xin DU ; Ling QIN ; Wuhan HUI ; Rong LIANG ; Meifang WANG ; Ye CHEN ; Dongyun LI ; Wei YANG ; Gusheng TANG ; Weihua ZHANG ; Xia KUANG ; Wei SU ; Yanqiu HAN ; Limei CHEN ; Jihong XU ; Zhuogang LIU ; Jian HUANG ; Chunting ZHAO ; Hongyan TONG ; Jianda HU ; Chunyan CHEN ; Xiequn CHEN ; Zhijian XIAO ; Qian JIANG
Chinese Journal of Hematology 2023;44(3):193-201
Objectives:To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients.Results:1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion:Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.
3.Establishment of fingerprints of Coptidis Rhizoma-Magnoliae Officmalis Cortex for formula granule and determination of index components
Dongyun ZHAO ; Xudong CHENG ; Yifei WU ; Yuyu HUANG
International Journal of Traditional Chinese Medicine 2022;44(12):1402-1407
Objective:To study the HPLC fingerprints of Coptidis Rhizoma- Magnoliae Officmalis Cortex formula granules and the differences of active ingredients in different proportions; To explore the content changes of key components in different proportions of Coptidis Rhizoma- Magnoliae Officmalis Cortex. Methods:HPLC was used to determine the contents of several alkaloids and total phenol of Magnolia officinalis in Coptidis Rhizoma- Magnoliae Officmalis Cortex formula granules and their fingerprints, and the similarity evaluation, cluster analysis and principal component analysis were performed. Results:The similarity of fingerprint of 10 batches of Coptidis Rhizoma- Magnoliae Officmalis Cortex was > 0.950. 17 common peaks were identified, and 6 components were identified. Compared with single medicine, the contents of alkaloids and total phenols in the Coptidis Rhizoma- Magnoliae Officmalis Cortex formula granules were significantly reduced. The contents of multiple alkaloids and total phenols in the Coptidis Rhizoma- Magnoliae Officmalis Cortex formula granules in different proportions were different, and the contents of alkaloids and total phenols were the highest when the proportion of Coptidis Rhizoma- Magnoliae Officmalis Cortex was 2∶1. Conclusion:The contents of main components of Coptidis Rhizoma- Magnoliae Officmalis Cortex formula granules with different proportions are different, which can provide a certain basis for studying the compatibility mechanism of TCM couplet medicines.
4.Health-related quality of life and its associated variables in Chinese patients with Philadelphia-negative myeloproliferative neoplasms
Mei BAO ; Dayu SHI ; Hongxia SHI ; Xiaoli LIU ; Minghui DUAN ; Junling ZHUANG ; Xin DU ; Ling QIN ; Wuhan HUI ; Rong LIANG ; Meifang WANG ; Ye CHEN ; Dongyun LI ; Wei YANG ; Gusheng TANG ; Weihua ZHANG ; Xia KUANG ; Wei SU ; Yanqiu HAN ; Limei CHEN ; Jihong XU ; Zhuogang LIU ; Jian HUANG ; Chunting ZHAO ; Hongyan TONG ; Jianda HU ; Chunyan CHEN ; Xiequn CHEN ; Zhijian XIAO ; Qian JIANG
Chinese Journal of Hematology 2021;42(12):985-992
Objectives:To explore health-related quality of life (HRQoL) and identify its associated variables in Chinese patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to adult patients with MPNs to assess symptom burden measured by MPN-10 and HRQoL measured by Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) .Results:The data from 1405 respondents with MPNs, including 645 (45.9%) with essential thrombocythemia (ET) , 297 (21.1%) with polycythemia vera (PV) , and 463 (33.0%) with myelofibrosis (MF) , were analyzed. 646 (46.0%) respondents were male. The median age was 56 (range, 18-99) years. The mean MPN-10 scores were 13.0±12.7, 15.0±14.7, and 21.0±16.6 ( P<0.001) , and the physical component summary (PCS) and mental component summary (MCS) scores were 48.0±8.5, 47.0±9.0, and 42.0±10.0 ( P<0.001) and 51.0±11.0, 50.0±10.8, and 49.0±11.1 ( P=0.002) for respondents with ET, PV, and MF, respectively. Respondents with MF reported the lowest score of physical functioning, role functioning, emotional functioning, cognitive functioning, social function, and global health status (all P<0.01) and the highest score of fatigue, pain, dyspnea, appetite loss, diarrhea, and financial problems (all P<0.05) in EORTC QLQ-C30. Multivariate analyses revealed that higher MPN-10 scores were significantly associated with lower PCS (-0.220 to -0.277, P<0.001) and MCS (-0.244 to -0.329, P<0.001) scores; increasing age (-1.923 to -4.869; all P<0.05) , lower PCS score. Additionally, comorbidity (ies) , symptom at diagnosis, splenomegaly, anemia, unknown driver gene, and higher annual out-of-pocket cost were significantly associated with lower PCS and/or MCS scores. However, age ≥ 60 years, urban household registration, concomitant medication, and receiving ruxolitinib therapy in respondents with MF were associated with higher MCS scores. Weak correlations were found between MPN-10 score (except the subscale of appetite loss and constipation) and EORTC QLQ-C30 score in majority of subscales in respondents with ET (| r| = 0.193-0.457, all P<0.001) , PV (| r| = 0.192-0.529, all P<0.01) , and MF (| r| = 0.180-0.488, all P<0.001) , respectively. Conclusions:HRQoL in patients with MPN was significantly reduced, especially in patients with MF. Sociodemographic and clinical variables were significantly associated with the HRQoL in patients with MPNs.
5.Design and verification of microelectrode twisting machine.
Xinyu LIU ; Dongyun WANG ; Enhui ZHAO ; Meifang MA ; Li SHI
Journal of Biomedical Engineering 2020;37(2):317-323
As an interface between external electronic devices and internal neural nuclei, microelectrodes play an important role in many fields, such as animal robots, deep brain stimulation and neural prostheses. Aiming at the problem of high price and complicated fabrication process of microelectrode, a microelectrode twisting machine based on open source electronic prototyping platform (Arduino) and three-dimensional printing technology was proposed, and its microelectrode fabrication performance and neural stimulation performance were verified. The results show that during the fabrication of microelectrodes, the number of positive twisting turns of the electrode wire should generally be set to about 1.8 times of its length, and the number of reverse twisting rings is independent of the length, generally about 5. Moreover, compared with the traditional instrument, the device is not only inexpensive and simple to manufacture, but also has good expandability. It has a positive significance for both the personalization and popularization of microelectrode fabrication and the reduction of experimental cost.
Equipment Design
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Microelectrodes
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Printing, Three-Dimensional
6.An evaluation study on the randomized controlled trial of preoperative skin preparation for emergency percutaneous coronary intervention based on GRADE system
Peipei QIN ; Xufei LUO ; Yunxia HAO ; Jie WU ; Zhouzhou LIU ; Yan ZHANG ; Yanjuan ZHANG ; Ran PANG ; Rui ZHAO ; Yan LIU ; Dongyun ZHAO ; Yu SUN ; Qingyin LI
Chinese Journal of Modern Nursing 2018;24(33):3975-3979
Objective To systematically evaluate and analyze the evidence level of randomized controlled trials (RCT) of preoperative skin preparation for emergency percutaneous coronary intervention (PCI), and to understand the current research status and evidence level of preoperative skin preparation randomized controlled trials for emergency PCI, and provide reference for skin preparation for emergency PCI. Methods PubMed, EMbase, The Cochrane Library, CINAHL, JBI, CBM, CNKI, Wanfang DATA were searched by computer from inception to March, 2018 for emergency PCI preoperative skin preparation randomized controlled trials. Two evidence panel members searched and selected articles independently and the quality was assessed in accordance with Cochrane Manual. The articles were analyzed with Review Manager 5.3, and the evidence quality was assessed with GRADE profiler 3.6.1 software. Results A total of 5 RCTs were included, of which the number of RCTs with grade A quality was 1 and the number of RCTs with grade B was 4. The results of the Meta analysis showed that there was no significant difference in the incidence of skin infections at the postoperative puncture site by conventional methods for routine removal of surgical wild hair and no removal of hair prior to emergency PCI (P<0.05). In addition, regular removal of hair before surgery may result in prolonged preoperative preparation and may cause psychological discomfort to the patient. After the GRADE system rating, the quality of the evidence body was of a lower level. Conclusions It is more beneficial to shorten the treatment time without routine removal of all the hair at the puncture site and the surrounding patients. The evidence included is not yet certain whether the incomplete removal of hair can reduce the infection rate. In the future, more large-scale, multi-center, high-quality research should be carried out to provide more credible evidence for this study.
7.Expression of tissue neuronal cell adhesion molecule 56, chromogranin A, and synapto-physin and its relationship with clinicopathological features and prognosis in 92 Chi-nese patients with primary esophageal small cell carcinoma
Dongyun ZHANG ; Xia LI ; Jianwei KU ; Song LIU ; Jianchao YAO ; Jing WANG ; Tangjuan ZHANG ; Xueke ZHAO ; Lidong WANG
Chinese Journal of Clinical Oncology 2017;44(5):204-209
Objective:To investigate the expression level of synaptophysin (Syn), tissue neuronal cell adhesion molecule 56 (CD56) and chromogranin A (CgA) in 92 primary esophageal small cell carcinoma (PESC) and to explore its repationship with clinicopathological features and clinical outcome. Methods:Immunohistochemical studies of CD56, CgA, and Syn were performed in 92 paraffin-embed-ded tissues with clinical-related information obtained from 500,000 esophageal and gastric cardia carcinoma databases established by Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital of Zhengzhou University in Henan, China. Binary logistic regression was used to analyze the correlations of CgA, Syn, and CD56 expression with clinicopathological features. Kaplan-Mei-er survival analysis and Cox proportional hazards regression models were performed for univariate and multivariate survival analyses. Log-rank test was used to compare the difference in survival rates. Results:The CgA-positive expression rate in PESC at lower segment of esophagus (72.2%) was higher than those at the middle and lower segments (41.1%, 10.0%) (P=0.001). The expression level of CD56, CgA, and Syn was not correlated with gender (P=0.262, 0.998, 0.931), age (P=0.250, 0.998, 0.703), tumor invasion (P=0.253, 0.997, 0.061), and lymph node metastasis (P=0.767, 0.998, 0.613). Univariate analysis showed no survival influence in patients with and without lymph node metastasis (P=0.563). Multivariate survival analysis showed that patients with PESC mixed squamous cell car-cinoma (HR=2.58;95%Cl, 1.11-5.98) and higher CgA protein expression (HR=1.87;95%Cl, 1.02-3.43) exhibited a longer survival time than those with pure PESC and without CgA expression. Conclusion:Tissue CgA level was associated with tumor location in PESC. His-tological type and tissue CgA expression were independent important prognostic factors, and lymph node metastasis exerted no influ-ence on survival in PESC.
8.Effects of simulated weightlessness on biomechanics of motion unit of rhesus monkey lumbar vertebra
Xiaoping WANG ; Ming LU ; Pei MA ; Zhiming CHEN ; Wei YUAN ; Fujiang ZHAO ; Hao ZHAO ; Dongyun REN ; Huasong MA ; Zhihong WU
Chinese Journal of Tissue Engineering Research 2016;20(26):3843-3848
BACKGROUND:It is generaly believed that the spine wil be extended, and vertebral muscle atrophy, bone loss of vertebral body, increased height and area of intervertebral disc, changes of composition of intervertebral disc wil occur in the condition of weightlessness. These are likely to be the cause of high incidence of low back pain. OBJECTIVE:To observe changes in lumbar spine bone microstructure analysis of simulated weightlessness on rhesus lumbar spine biomechanics. METHODS:Fourteen young rhesus monkeys were randomly divided into two groups: control group (n=7;free activities in the cage during the experiment), and experimental group (n=7; the use of head-down-10° on a special bed by bundle lying to simulate weightlessness). RESULTS AND CONCLUSION:(1) The results of Micro-CT examination: in the experimental group, structure model index in trabecular bone of increased. Trabecular bone changed from plate-like to the rod-like change. The intersection number of bone tissue in unit length to non-bone tissue declined. The average width of the canal between the trabecular bone increased, suggesting that there have been signs of osteoporosis in the experimental group. (2) Under an optical microscope, in the experimental group, bone hyperplasia line was disordered and irregular. Thick endplate trabecularbone became smal, shalow, and arranged substantialy perpendicular to the direction of trabecular bone and cartilage endplate. The closer the endplate surface, the smaler trabecular bone was. Compared with the control group, these smal trabecular bones were thin and curved. Bone marrow cavity was oval. The degree of the connection between the trabecular bones is poor, reflecting the structural characteristics of significant osteoporosis. (3) It is indicated that weightlessness affected the biomechanical properties of rhesus lumbar motion unit.
9.Clinical study of iguratimod in the treatment of active rheumatoid arthritis
Wenmin ZHAO ; Dongyun YAO ; Heshui HUO ; Chenman QIN ; Qiujin WEI ; Kai SUN
Chinese Journal of Postgraduates of Medicine 2016;39(5):450-452
Objective To study the clinical efficacy and safety of iguratimod in the treatment of active rheumatoid arthritis. Methods Ninety patients with rheumatoid arthritis were randomly divided into three groups, with 30 cases in each group. Group A: oral administration of iguratimod, 25 mg two times a day, and oral administration of methotrexate, 10 mg once a week. Group B:oral administration of iguratimod, 25 mg two times a ady. Group C: oral administration of methotrexate, 15 mg once a week. According to the American College of Rheumatology criteria for judging 20%, 50%and 70%(ACR20, ACR 50 and ACR 70) improvement of swollen and tender joint was judged according to the American College Of Rheumatology criteria, and the adverse reactions were observed. Results After the treatment in group A and group B ACR20, ACR50 and ACR70 were higher than those in group C [76.67%(23/30) and 60.00% (18/30) than 40.00% (12/30), 50.00% (15/30) and 33.33% (10/30) than 20.00% (6/30), 23.33%(7/30) and 13.33%(4/30) than 6.67%(2/30)], and in group A was higher than that in group B. The differences were statistically significant (P<0.05). The adverse reaction rate in group A and group B was significantly lower than that in group C:16.67%(5/30) and 13.33%(4/30) than 30.00%(9/30), and the difference was statistically significant (P<0.05); the adverse reaction occurred rate in group A and group B, had no significant difference (P>0.05). Conclusions Monotherapy with iguratimod in the treatment of active rheumatoid arthritis is superior to methotrexate, and has fewer side effects. The combined application of the two drugs is more effective, and can reduce the dose of methotrexate and reduce the incidence of side effects, which is worthy of clinical application.
10.Effect of early rehabilitation nursing intervention on the patients with lumbar intervertebral fusion
Li ZHAO ; Dongyun DUAN ; Zhiyan WANG ; Jilu LIU ; Wei LIU
Journal of Navy Medicine 2016;37(4):348-351
Objective To explore the effect of early rehabilitation nursing intervention on the patients with lumbar interverte-bral fusion, so as to provide nursing experience for those patients with lumbar intervertebral fusion.Methods Seventy-six patients with lumbar degenerative disease implemented with lumbar intervertebral fusion were randomly divided into the observation group and the control group, each consisting of 38 patients.The control group received routine nursing, while the observation group received early re-habilitation nursing intervention, all having a consecutive intervention of 12 weeks.Total scores of low back pain oswestry disability in-dex ( ODI) and scores of main items, visual analog scores ( VAS) and scores of depression symptom ( SDS) both before and after inter-vention were closely observed and compared between the 2 groups.Results Total ODI scores and scores of 5 major items ( pain sensa-tion, self-care, sleep, sit-up, social activity) in the 2 groups after intervention were significantly decreased as compared with those be-fore intervention (P<0.05).Total ODI scores and scores of the above 5 major items in the observation group after intervention were significantly lower than those of the control group after intervention (P<0.05).Scores of waist and lower limb VASs in the two groups after intervention were significantly lower than those before intervention(P<0.05).SDS scores in the observation group after interven-tion were significantly lower than those before intervention(P>0.05),while no significant changes in them could be noted in the control group(P>0.05).Scores of waist and lower limb VAS, as well as SDS in the observation group after intervention were significantly low-er than those of the control group after intervention(P<0.05).Conclusion Early rehabilitation nursing intervention could significantly hasten the rehabilitation of the patients with lumbar intervertebral fusion, alleviate waist and leg pain, and improve symptoms of depres-sion, and was worthy further clinical popularization.

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