1.A novel feedback loop: CELF1/circ-CELF1/BRPF3/KAT7 in cardiac fibrosis.
Yuan JIANG ; Bowen ZHANG ; Bo ZHANG ; Xinhua SONG ; Xiangyu WANG ; Wei ZENG ; Liyang ZUO ; Xinqi LIU ; Zheng DONG ; Wenzheng CHENG ; Yang QIAO ; Saidi JIN ; Dongni JI ; Xiaofei GUO ; Rong ZHANG ; Xieyang GONG ; Lihua SUN ; Lina XUAN ; Berezhnova Tatjana ALEXANDROVNA ; Xiaoxiang GUAN ; Mingyu ZHANG ; Baofeng YANG ; Chaoqian XU
Acta Pharmaceutica Sinica B 2025;15(10):5192-5211
Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.
2.Comparison of potential profiles analysis of psychosocial adaptation and social alienation differences in nsoriasis natients
Junying QIAN ; Meng QIAO ; Shu WANG ; Lihua CHEN ; Mengqiu LIU ; Rong WEI ; Linlin XIN
Chongqing Medicine 2025;54(4):824-829
Objective To explore the potential categories of psychosocial adaptation in psoriasis patients and their differences in social alienation.Methods Using a cross-sectional survey design,convenience sam-pling was used to select 376 psoriasis patients from multiple hospitals in Shandong Province from September to December 2022.Participants completed the general information questionnaire,Psychosocial Adaptation to Illness Scale(PAIS-SR),Acceptance and Action Questionnaire-Ⅱ(AAQ-2),and General Alienation Scale(GAS).Latent profile analysis was performed using Mplus8.0 software to identify psychosocial adaptation patterns of psoriasis patients,and SPSS25.0 was used to compare social alienation differences among different adaptation groups.Results Psoriasis patients could be divided into two latent profiles:moderate psychosocial adaptation group(31.38%)and low psychosocial adaptation group(68.62%).Medical payment method,dis-ease recurrence,psoriasis subtype,disease duration,family history,skin lesion exposure,and AAQ-2 scores were identified as main influencing factors(P<0.05).Significant differences in total GAS scores were found between the two groups(P<0.05).Conclusion The psychosocial adaptation of psoriasis patients shows het-erogeneity and could be classified into two latent profiles.Targeted interventions should be implemented to improve psychosocial adaptation levels.
3.Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023 edition).
Qing ZHAO ; Tong WANG ; Hongbin WANG ; Peng CAO ; Chengyu JIANG ; Hongzhi QIAO ; Lihua PENG ; Xingdong LIN ; Yunyao JIANG ; Honglei JIN ; Huantian ZHANG ; Shengpeng WANG ; Yang WANG ; Ying WANG ; Xi CHEN ; Junbing FAN ; Bo LI ; Geng LI ; Bifeng LIU ; Zhiyang LI ; Suhua QI ; Mingzhen ZHANG ; Jianjian ZHENG ; Jiuyao ZHOU ; Lei ZHENG ; Kewei ZHAO
Chinese Herbal Medicines 2024;16(1):3-12
To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.
4.Uyghur Medicine Yangxin Dawayimixike Honey Paste (养心达瓦依米西克蜜膏) in Treatment of 279 Cases Stable Angina Pectoris Patients with Qi Stagnation and Blood Stasis Syndrome:A Multi-center,Double-blind,Positive-controlled Randomized Clinical Trial
Binghua JIANG ; Lihua FAN ; Xiaofeng WANG ; Yingmin SONG ; Yanlai ZHANG ; Songyan QIAO ; Jing DONG ; Lihua JIN ; Yanping DING ; MAINISHA·MAIMAITI ; Jixian ZHAO ; Dongsheng GAO ; Qiuping ZHAO ; Lingxia GUAN ; Hongbin SUN ; Meise LIN ; Hengliang WANG ; Jun LI
Journal of Traditional Chinese Medicine 2024;65(21):2225-2233
ObjectiveTo observe the efficacy and safety of Uyghur medicine Yangxin Dawayimixike Honey Paste (养心达瓦依米西克蜜膏, YDMHP) in the treatment of stable angina pectoris (SAP) of qi stagnation and blood stasis syndrome. MethodsA randomized , double-blind, positive-controlled,multi-center clinical trial was conducted, in which 370 patients with SAP of qi stagnation and blood stasis syndrome were randomly divided into treatment group(279 cases)and control group(91cases)at a ratio of 3∶1. The treatment group was orally administered with YDMHP, 3 g each time, and placebo of Xuefu Zhuyu Capsule (血府逐瘀胶囊), 2.4 g each time, while the control group was treated with Xuefu Zhuyu Capsule, 2.4 g each time, and placebo of YDMHP, 3 g each time, both twice a day for a course of 12 weeks. The primary outcome was the effect of angina pectoris symptom. The secondary outcomes include single angina symptom scores such as number of attacks, duration of attacks, pain intensity and usae of nitroglycerin scores, the total angina symptom score before and after the treatment, the usage of nitroglycerin, the exercise duration in treadmill exercise test (TET) and the Duck treadmill score among patients,the scores of Seattle Angina Questionnaire (SAQ) on five dimensions including physical limitations, anginal stability, anginal frequency, treatment satisfaction, and disease perception, and efficacy of TCM syndrome and of each single TCM symptom after treatment. The safety were evaluated by examine blood routine, urine routine, liver and kidney function, fasting blood sugar, electrocardiogram, adverse events. ResultsThe total effective rate of angina symptom in the treatment group was 71.69% (200/279), significantly higher than 51.64% (47/91) in the control group (P<0.01). The curative and markedly effective rate of TCM syndrome in the treatment group was 53.05% (148/279), which was significantly higher than 25.27% (23/91) in the control group (P<0.01). After treatment, scores of the number as well as duration of angina attacks and pain severity, the total score of angina symptoms, and the usage of nitroglycerin significantly decreased in both groups, and more changes were seen in the treatment group than in the control group; the scores of physical limitations, anginal stability, anginal frequency, treatment satisfaction, and disease perception in both groups significantly increased, and more improvement were shown in the experimental group regarding the anginal stability, anginal frequency and treatment satisfaction (P<0.05 or P<0.01). The effects of chest pain, chest tightness, palpitation, shortness of breath and fatigue in experimental group were significantly higher than those in control group (P<0.05 or P<0.01). There was no significant difference in the exercise duration of treadmill test and Duke score among patients between the two groups either before or after treatment (P>0.05). Adverse events occurred in 66 cases (23.66%) of the experimental group and 16 cases (17.58%) of the control group, with no statistical significance between the two groups (P>0.05). ConclusionThe Uyghur medicine YDMHP can effectively improve symptoms of angina pectoris, reduce the number, duration, and intensity of attacks, decrease the dosage of nitrogly-cerin and improve the individual TCM symptoms and has good safety in the treatment of SAP patients of qi stagnation and blood stasis.
5.Effect of Tongdu Huoxue Decoction on Lumbar Spine Function and Serum Inflammatory Factor Levels in Patients with Acute Lumbar Disc Herniation
Yumo XIONG ; Zichen LI ; Ying LI ; Qiangbing XIAO ; Lihua WANG ; Hao HU ; Ruibing FENG ; Jie QIAO ; Yan HU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):135-141
ObjectiveTo observe the clinical efficacy of Tongdu Huoxue decoction in the treatment of acute lumbar disc herniation (LDH). MethodA total of 316 patients with acute LDH admitted to the orthopedic outpatient department of Hubei Provincial Hospital of Traditional Chinese Medicine and Honghu City Hospital of Traditional Chinese Medicine from January 2020 to June 2023 were randomly divided into two groups. 156 cases in the control group (two cases with stopped follow-up) were treated with meloxicam tablets, while 153 cases in the observation group (five cases with stopped follow-up) were treated with Tongdu Huoxue decoction. Both groups were treated for three months. The clinical efficacy, McGill Pain Score Scale (SF-MPQ), Oswestry Dysfunction Index (ODI) score, and the Japanese Orthopaedic Association (JOA) scores of the two groups before and after treatment were compared. The serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) of the patients before and after treatment were determined by using enzyme-linked immunosorbent assay (ELISA). The NDI-092 type electromyography-evoked potential instrument was adopted to measure the motor conduction velocity and clinical efficacy of the tibial and common peroneal nerves in patients of the two groups before and after treatment, and the clinical safety of the two groups of patients was compared. ResultAfter treatment, the total effective rate in the observation group was 95.4% (146/153), significantly higher than that in the control group of 76.3% (119/156) (χ2 =23.18, P<0.05). After treatment, both groups showed significant reductions in SF-MPQ and ODI scores, as well as the levels of IL-1β, IL-6, and TNF-α (P<0.05), with the observation group showing a more significant reduction (P<0.05). Both groups showed a significant increase in JOA scores and motor conduction velocities of the tibial and common peroneal nerves after treatment (P<0.05), with the observation group showing a more significant increase (P<0.05). ConclusionTongdu Huoxue decoction can alleviate lumbar and leg pain in acute LDH, improve lumbar spine function, and suppress inflammatory reactions. It is highly safe and is worthy of clinical promotion.
6.Feature analysis of the tissue methylation profile in adenocarcinoma patients with pulmonary nodules on CT scan
Qiaomei GUO ; Lihua QIAO ; Lin WANG ; Xueqing WANG ; Fei WU ; Xiaohui LIANG ; Yuteng SUN ; Jiatao LOU
Chinese Journal of Laboratory Medicine 2024;47(11):1277-1285
Objective:To investigate the tissue methylation features of adenocarcinoma patients presenting as pulmonary nodules on CT scans.Methods:A retrospective analysis was conducted on 70 adenocarcinoma patients with pulmonary nodules diagnosed at the Shanghai General Hospital from June 1, 2022 to January 20, 2024. Participants were assigned to two groups using the random number table, with 40 in the discovery group and 30 in the validation group. In the discovery group, tissue samples were analyzed using reduced representation bisulfite sequencing (RRBS) technology to compare the average methylation levels between cancer tissues and paired adjacent non-cancerous tissues. Differentially methylated regions (DMRs) were screened for analysis of their distribution across various genomic functional elements, and hierarchical clustering was plotted. GO and KEGG pathway enrichment analyses were further conducted on the DMRs. Subsequently, candidate DMRs associated with lung adenocarcinoma were validated using TCGA lung adenocarcinoma cohort and targeted bisulfite sequencing technology in the validation group. The comparison of methylation levels between groups was conducted using t-tests or non-parametric tests, while rates and composition ratios were analyzed using chi-square tests or Fisher′s exact test.Results:In discovery cohort, the average methylation level in cancer tissues was lower compared to adjacent normal tissues [(42.369±4.627) vs (44.370±4.046), t=?2.059, P=0.043]. A total of 37 995 DMRs were identified, including 16 889 upregulated regions and 21 106 downregulated regions, predominantly locating in promoter regions (48.917%), introns (36.457%), and exons (10.812%). The DMR clustering heatmap revealed two distinct clusters corresponding to cancer tissues and adjacent non-cancerous tissues. GO analysis showed that DMRs associated genes were mainly located in the cell membrane and nuclear chromatin, and were primarily involved in RNA polymerase Ⅱ-related transcription and regulation. KEGG pathway enrichment analysis indicated that DMRs associated genes were mainly involved in neuroactive ligand-receptor interaction, cancer pathways, calcium signaling pathway, cAMP signaling pathway, and MAPK signaling pathway. Validation in the TCGA cohort confirmed 11 potential characteristic DMRs. In the validation group, TBS confirmed that the methylation levels of DMRs associated with MIR10B, DMRTA2, HOPX, TFAP2B and MARCH11 in cancer tissues were significantly higher than those in adjacent non-cancerous tissues [11.200(4.305, 27.088) vs 2.650(1.298, 4.645), Z=?4.539, P<0.05; 18.610(13.600, 33.025) vs 8.675(5.488, 13.085), Z=?4.554, P<0.05; 17.600(2.183, 76.015) vs 1.085(0.898, 1.835), Z=?5.131, P<0.05; 5.250(3.220, 7.693) vs 3.495(2.165, 4.383), Z=?2.861, P<0.05; 11.515(7.525, 21.033) vs 7.830(5.518, 11.488), Z=?2.440, P<0.05 ], and the differences were statistically significant. Conclusions:Lung adenocarcinoma tissue exhibits different methylation patterns compared with adjacent normal lung tissue. The identified DMRs are involved in the regulation of several key pathways. Results from the TCGA cohort and an independent validation group support the potential diagnostic value of DMRs such as MIR10B, DMRTA2, HOPX, TFAP2B, and MARCH11 in lung adenocarcinoma, though their clinical application requires further validation.
7.Evaluation of the application value of BALF-EGFR gene mutation in targeted therapy for lung cancer patients based on droplet digital PCR
Xiaohui LIANG ; Fei WU ; Wanxing XU ; Lihua QIAO
International Journal of Laboratory Medicine 2024;45(23):2918-2921
Objective To evaluate the clinical application value of bronchoalveolar lavage fluid(BALF)as a specimen for epidermal growth factor receptor(EGFR)gene mutation detection.Methods Droplet digital polymerase chain reaction(ddPCR)was used to detect the mutation situation of relevant sites(L858R and E746_A750del)in EGFR gene in BALF of totally 52 lung cancer patients,and the corresponding molecular pathological results were compared.Results With molecular pathological as a gold standard,the sensitivity of BALF for the detection of E746_A750del was 58.3%(14/24),specificity was 100.0%(14/14)and concord-ance was 73.7%(28/38,Kappa=0.508,P<0.01),while the sensitivity of BALF for the detection of L858R was 64.3%(9/14),specificity was 100.0%(14/14)and concordance was 82.1%(23/28,Kappa=0.643,P<0.01).Compared with the molecular pathological results,it showed high concordance in determining mu-tations of E746_A750del and L858R in EGFR gene in BALF(0.40<Kappa<0.75).The detection rate of EGFR gene mutation in BALF was related with tumor stage(P<0.05).The abundance of mutations could predict to some extent the distant metastasis of lung cancer.Conclusion BALF specimens have important clinical application value in detecting EGFR gene mutations in lung cancer patients and could serve as a sup-plement to molecular pathology detection.
8.Research and implementation of ideological and political elements into the medical physics curriculum
Lihua QIAO ; Jing ZHANG ; Lei LIU ; Ruibin ZHAO
Chinese Journal of Medical Education Research 2023;22(2):185-187
In order to improve the students' initiative and values in knowledge seeking, this study integrates ideological and political elements into the medical physics curriculum. On the basis of the standard curriculum, 11 ideological and political elements corresponding to 6 knowledge points are added to the courseware and teaching plan and implemented in the classroom. The changes of students' ideological and moral level and values before and after teaching were statistically analyzed by questionnaire. The results show that through the integration of ideological and political elements, 98.15% (106/108) think it is necessary to integrate the ideological and political elements into the curriculum. The proportion of students who study for the purpose of working skills, national medical care and world medical care has increased, while the proportion of students who earn credits has decreased, which shows that students' learning initiative and values have been improved.
9.The creation and application of entity teaching model of medical physics—taking hemodynamics as example
Haobo KANG ; Lihua QIAO ; Hui TIAN ; Yarui HU ; Jingzhe LI ; Chenru HAO
Chinese Journal of Medical Education Research 2021;20(5):529-532
Hemodynamics is a branch of fluid mechanics, which mainly studies the physiological process of circulatory system from the perspective of mechanics, and has a wide range of applications in medicine. The entity teaching model is made to help medical students master the knowledge of hemodynamics more easily and intuitively by showing them the phenomenon of laminar flow, turbulence and axial concentration of red blood cells. And then we check their learning effect by questionnaires. Students are interested in the entity teaching model that the teacher has used in the class. Thus, the entity teaching model can play an important role in the teaching process.
10.Research on the construction and application of digital question databaseof medical physics
Lihua QIAO ; Ruibin ZHAO ; Chenru HAO ; Yanjun MENG ; Hui TIAN ; Jingjing ZHANG ; Jing LI ; Ziqiang CHI ; Li CHENG
Chinese Journal of Medical Education Research 2020;19(4):410-414
Objective:Through constructing an online question database of medical physics, teachers and students can make use of the Internet to realize interaction in or after class, so students' ability of independent learning and the quality of teaching can be improved.Methods:Based on teaching outlines, the type, quantity and difficulty of the test questions were discussed and determined by teachers in the teaching and research office, and the online question database of medical physics was constructed with the help of Internet platform to realize self-testing and teacher-student interaction.Results:Through the construction and application of online question database, students' learning initiative was mobilized, the effectiveness of teacher-student interaction was improved, and empirical materials for teaching formation evaluation were obtained. Self-examination and teacher-student interaction help improve students independent learning and problem solving ability. And data generated on the platform enable teachers to know students' learning situation and their teaching quality.Conclusion:The construction and application of Internet + digital online question database of medical physics can greatly promote the teaching effect.

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