1.Mechanism of 1,25(OH)2D3 improving liver inflammation in a rat model of nonalcoholic steatohepatitis induced by choline-deficient L-amino acid-defined diet
Haiyang ZHU ; Jingshu CUI ; Liu YANG ; Mengting ZHOU ; Jian TONG ; Hongmei HAN
Journal of Clinical Hepatology 2025;41(2):254-262
ObjectiveTo investigate the effect of 1,25(OH)2D3 on the level of peroxisome proliferator-activated receptor-γ (PPAR-γ) in the liver, the phenotype of hepatic macrophages, and liver inflammation in a rat model of nonalcoholic steatohepatitis (NASH), as well as the mechanism of 1,25(OH)2D3 improving liver inflammation. MethodsAfter 1 week of adaptive feeding, 24 specific pathogen-free Wistar rats were randomly divided into normal group [choline-supplemented L-amino acid-defined (CSAA) diet], normal+1,25(OH)2D3 group [CSAA diet+1,25(OH)2D3], model group [choline-deficient L-amino acid-defined diet (CDAA) diet], and model+1,25(OH)2D3 group [CDAA diet+1,25(OH)2D3], with 6 rats in each group. The dose of 1,25(OH)2D3 was 5 μg/kg for intraperitoneal injection twice a week for 12 weeks. The serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured, liver histopathology was observed, and SAF score was assessed. M1 hepatic macrophages and M2 hepatic macrophages were measured to analyze in the change in the phenotype of hepatic macrophages, and ELISA was used to measure the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-4 (IL-4), and interleukin-10 (IL-10) in liver tissue, and qPCR was used to measure the mRNA level of PPAR-γ. The two-factor analysis of variance was use for comparison between groups, and the least significant difference t-test was used for further comparison; the Pearson method was used for correlation analysis. ResultsCompared with the normal group, the model rats with CDAA diet-induced NASH had significant increases in the serum levels of AST and ALT (P=0.019 and P<0.001), the SAF score of liver histopathology (P<0.001), the level of M1 hepatic macrophages (P<0.001), and the ratio of M1 and M2 hepatic macrophages (P<0.001), as well as a significant increase in the level of TNF-α (P<0.001) and a significant reduction in the level of IL-4 in liver tissue (P=0.025). The 1,25(OH)2D3 group had significant reductions in the serum levels of ALT (P<0.001), the SAF score of liver histopathology (P<0.001), the level of M1 hepatic macrophages (P<0.001), and the ratio of M1 and M2 hepatic macrophages (P=0.001), the level of IL-1β (P<0.001) and a significant increase in the level of M2 hepatic macrophages (P=0.017), the level of IL-10 (P=0.039), the level of IL-4 (P<0.001), the level of PPAR-γ (P=0.016). There were significant interactions between CDAA diet-induced NASH model and 1,25(OH)2D3 in serum the levels of AST and ALT (P=0.007 and P=0.008), the SAF scores of liver histopathology (P<0.001), the level of M1 hepatic macrophages (P<0.001), the level of M2 hepatic macrophages (P=0.008), the ratio of M1 and M2 of hepatic macrophages (P=0.005), the level of TNF-α (P<0.001), the level of IL-10 (P=0.038), the level of IL-4 (P<0.001) and the level of PPAR-γ (P=0.009). The correlation analysis showed that PPAR-γ was negatively correlated with the ratio of M1 and M2 hepatic macrophages (r=-0.415, P=0.044) and was positively correlated with M2 hepatic macrophages (r=0.435, P=0.033), IL-10 (r=0.433, P=0.035), and IL-4 (r=0.532, P=0.007). ConclusionThis study shows that 1,25(OH)2D3 improves liver inflammation in NASH by activating PPAR-γ to regulate the phenotypic transformation of hepatic macrophages.
2.Enzyme-independent functions of HDAC3 in the adult heart.
Sichong QIAN ; Chen ZHANG ; Wenbo LI ; Shiyang SONG ; Guanqiao LIN ; Zixiu CHENG ; Wenjun ZHOU ; Huiqi YIN ; Yueli WANG ; Haiyang LI ; Ying H SHEN ; Zheng SUN
Acta Pharmaceutica Sinica B 2025;15(7):3561-3574
The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant (Δ33-70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2β (LAP2β). Tethering LAP2β to the HDAC3 Δ33-70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.
3.Expert consensus on digital restoration of complete dentures.
Yue FENG ; Zhihong FENG ; Jing LI ; Jihua CHEN ; Haiyang YU ; Xinquan JIANG ; Yongsheng ZHOU ; Yumei ZHANG ; Cui HUANG ; Baiping FU ; Yan WANG ; Hui CHENG ; Jianfeng MA ; Qingsong JIANG ; Hongbing LIAO ; Chufan MA ; Weicai LIU ; Guofeng WU ; Sheng YANG ; Zhe WU ; Shizhu BAI ; Ming FANG ; Yan DONG ; Jiang WU ; Lin NIU ; Ling ZHANG ; Fu WANG ; Lina NIU
International Journal of Oral Science 2025;17(1):58-58
Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans
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Denture, Complete
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Computer-Aided Design
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Denture Design/methods*
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Consensus
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Printing, Three-Dimensional
4.MolP-PC: a multi-view fusion and multi-task learning framework for drug ADMET property prediction.
Sishu LI ; Jing FAN ; Haiyang HE ; Ruifeng ZHOU ; Jun LIAO
Chinese Journal of Natural Medicines (English Ed.) 2025;23(11):1293-1300
The accurate prediction of drug absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties represents a crucial step in early drug development for reducing failure risk. Current deep learning approaches face challenges with data sparsity and information loss due to single-molecule representation limitations and isolated predictive tasks. This research proposes molecular properties prediction with parallel-view and collaborative learning (MolP-PC), a multi-view fusion and multi-task deep learning framework that integrates 1D molecular fingerprints (MFs), 2D molecular graphs, and 3D geometric representations, incorporating an attention-gated fusion mechanism and multi-task adaptive learning strategy for precise ADMET property predictions. Experimental results demonstrate that MolP-PC achieves optimal performance in 27 of 54 tasks, with its multi-task learning (MTL) mechanism significantly enhancing predictive performance on small-scale datasets and surpassing single-task models in 41 of 54 tasks. Additional ablation studies and interpretability analyses confirm the significance of multi-view fusion in capturing multi-dimensional molecular information and enhancing model generalization. A case study examining the anticancer compound Oroxylin A demonstrates MolP-PC's effective generalization in predicting key pharmacokinetic parameters such as half-life (T0.5) and clearance (CL), indicating its practical utility in drug modeling. However, the model exhibits a tendency to underestimate volume of distribution (VD), indicating potential for improvement in analyzing compounds with high tissue distribution. This study presents an efficient and interpretable approach for ADMET property prediction, establishing a novel framework for molecular optimization and risk assessment in drug development.
Deep Learning
5.External therapy of TCM for gastroesophageal reflux disease: an overview of systematic reviews
Wenwan PENG ; Yuxin WANG ; Zheng ZHOU ; Haiyang HUANG ; Mingguo DONG
International Journal of Traditional Chinese Medicine 2024;46(10):1363-1370
Objective:To overview the systematic reviews/meta analysis of the treatment of external therapy of TCM for gastroesophageal reflux disease (GERD).Methods:Systematic reviews/meta analysis of the treatment of external therapy of TCM for GERD were retrieved from CNKI, Wanfang Data, VIP, CBM, PubMed, Embase and Cochrane Library databases from the establishment of the databases to 31st, December 2022. The AMSTAR 2 tool, PRISMA 2020 reporting specifications, and GRADE guidelines were used to evaluate the methodological quality, reporting quality, and evidence quality of the included literature. A multiple evaluation was performed in six dimensions: year of publication, type of study design, methodological quality score, reporting quality score, degree of homogeneity, and risk of publication bias evaluation.Results:A total of 9 systematic reviews/meta analysis were included, of which 1 was of low quality methodological quality and 8 was of very low quality. GRADE guidelines evidence quality grading results showed 33 outcome indicators, 9 of which were with moderate evidence, 21 of which were with low evidence, and 3 of which were with very low evidence. 9 articles had reporting quality scores ranging from 16 to 24, of which 1 report was relatively complete and 8 had some deficiencies. The rank mean scores of multiple evaluations indicated that 2 articles were of high quality and 1 article was of poor quality.Conclusions:The quality of evidence for the treatment of external therapy of TCM for GERD is intermediate in terms of improving the cure rate and reducing adverse effects, and is recommended for clinical use. However, the methodological quality and reporting quality of the current systematic reviews/meta analysis of the treatment of external therapy of TCM for GERD need to be improved, and users of the evidence ought to use the above evidence with caution for decision making.
6.Construction of CRISPR/Cas9 knock-in system for tardigrade damage suppressor gene Dsup and its effect on HEK 293T cell proliferation
Yuting GAO ; Biao ZHANG ; Yali JIA ; Haiyang WANG ; Tao FAN ; Jiafei XI ; Wen YUE ; Quan ZENG ; Junnian ZHOU
Military Medical Sciences 2024;48(8):586-593
Objective To construct HEK 293T cells that express tardigrade Dsup protein fused with green fluorescent protein copGFP in order to study the effect of Dsup protein on proliferation of HEK 293T cells.Methods The CRISPR/Cas9 gene knock-in system was constructed.The target gene fragments of Dsup,copGFP,EF1α and puromycin were amplified by PCR and inserted into pAAVS1-SFFV to construct the fusion vector of Dsup and copGFP,which was known as pAAVS1-SFFV-Dsup-copGFP-EF1α-Puro.pAAVS1-SFFV-Dsup-copGFP-EF1 α-Puro and pAAVS1-CRISPR-Cas9 vector were co-transfected into HEK 293T cells before Dsup gene was inserted into the AAVS1 region of HEK 293T cells via homologous recombination.The HEK 293T cells expressing Dsup gene were obtained following puromycin selection,flow cytometry sorting and genome identification.The expression of Dsup at mRNA and protein levels and proliferation-related genes(MCM2,MCM4,PCNA,Ki-67)were examined to investigate the effects of Dsup gene on the proliferation of HEK 293T-Dsup-copGFP cells.Results The pAAVS1-SFFV-Dsup-copGFP-EF1α-Puro recombinant vector was constructed,and the HEK 293T-Dsup-copGFP cells with Dsup gene inserted in the AAVS1 region were obtained,where both Dsup mRNA and protein were expressed.The cell proliferation rate of HEK 293T-Dsup-copGFP was higher than that of HEK 293T-Control-copGFP(P<0.001).Further investigation revealed that the expressions of Ki-67 and MCM4 protein in HEK 293T-Dsup-copGFP were significantly higher than in the control group,indicating that the knock in of Dsup gene might enhance the proliferation ability of human cells by promoting the expression of Ki-67 and MCM4 protein.Conclusion A gene editing vector is constructed,and stable cell line HEK 293T-Dsup-copGFP for Dsup fusion expression with copGFP is established.The expression of Dsup gene in HEK 293T cells can promote cell proliferation,possibly by upregulating the expressions of Ki-67 and MCM4 protein.
7.Exploration on the acupuncture treatment of psychosomatic disorders based on the theory of "holism of body and spirit"
Chuntong ZHOU ; Lu REN ; Qin LYU ; Haiyang CHEN ; Xin ZHOU ; Junjing MIAO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(9):1306-1311
The concept of "holism of body and spirit" originated in the pre-Qin period as a philosophical idea to understand the world,and later became an important theory adopted in traditional Chinese medicine (TCM). Acupuncture,as a traditional TCM treatment modality,can be guided by the theory of "holism of body and spirit" in the clinical treatment of psychosomatic disorders. However,there is no clear and standardized operational model based on this theory currently. The combination of theory and practice is essential for the effective application and development of TCM. Currently,there are numerous schools and methods of acupuncture treatment for psychosomatic disorders,and the analytical perspectives on psychosomatic disorders vary,which leads to the complexity of integrating theory and practice and makes it difficult to conclude and summarize the standardized process. Given that TCM is a classical and time-honored medical science,tracing its historical origins and summarizing the diagnostic and treatment plans of different representative physicians might help in advancing acupuncture treatment for psychosomatic disorders. This paper analyzes and discusses the connection between philosophical ideas and medical theories,the application of theories into practice,and the analysis and summary of medical case literature,and puts forward the specific mode of acupuncture treatment of psychosomatic disorders,so as to provide new ideas and references for clinical practice.
8.The value of POSSUM score system in predicting postoperative complications in elderly patients and its correlation with Clavien-Dindo classification
Qianhua ZHOU ; Liang ZHANG ; Yiming SHI ; Haiyang WANG
Chongqing Medicine 2024;53(4):542-546,554
Objective To explore the value of the Physiology and Surgical Severity Score(POSSUM)scoring system in predicting postoperative complications in elderly patients with thoracic surgery,and to ana-lyze its correlation with Clavien-Dindo classification.Methods The data of 182 elderly patients who under-went thoracic surgery in this hospital from October 2019 to March 2023 were retrospectively analyzed.They were divided into the complication group and the non-complication group according to whether there were complications after surgery.The baseline data and POSSUM score of the two groups were analyzed,and the receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of POSSUM for post-operative complications in elderly patients.POSSUM of patients with different Clavien-Dindo classification was compared,and the correlation between POSSUM and Clavien-Dindo classification analyzed.Results The incidence of pulmonary infection was the highest in the complication group,followed by hypoproteinemia.POSSUM in the complication group was higher than that in non-complication group before operation,and the difference was statistically significant(P<0.05).The ROC curve showed that the area under curve(AUC)value of POSSUM was 0.829;In the complication group,according to Clavien-Dindo classification,there were 5 cases of grade Ⅰ,47 cases of grade Ⅱ,8 cases of grade Ⅱ Ⅲ,7 cases of grade Ⅳ and 8 cases of grade V,the difference was statistically significant(P<0.05).The correlation analysis showed that POSSUM score was positively correlated with Clavien-Dindo classification(r>0.513,P<0.05).Conclusion The POSSUM scoring system has a high value in predicting postoperative complications in elderly patients with thoracic surgery.
9.Study on Zhou Meisheng's moxibustion treatment for epidemic hemorrhagic fever based on data mining and knowledge map
Bingyuan ZHOU ; Caifeng ZHU ; Haiyang ZHAO ; Xiaofeng QIN ; Fei DAI ; Na ZHANG ; Yumei JIA ; Anqi WU
International Journal of Traditional Chinese Medicine 2024;46(3):369-376
Objective:To explore the therapeutic law of moxibustion in Professor Zhou Meisheng's medical manuscripts for epidemic hemorrhagic fever (EHF) based on data mining and knowledge map technology.Methods:The manuscript data of Professor Zhou Meisheng's moxibustion treatment of EHFwere collected from Infectious Diseases Department of Dangshan County People's Hospital from December 16, 1985 to December 25, 1987. Graphpad Grism 8.0 software was used for descriptive analysis. PHP 5.4 program code was used for association rule analysis. SPSS Statistics 26.0 was used for clustering analysis. Neo4j Community 3.5.25 database was used to analyze the syndrome-weight graph.Results:205 prescriptions were included. There were 21 symptoms with frequency>40, in which the frequency of aversion to cold, fever, rash and irritability was 100%. The main types of moxibustion methods used in the treatment included moxibustion frame fumigation moxibustion, Wanying acupoint moxibustion pen moxibustion, and fire needle instead of moxibustion. There were 29 acupoints with a frequency of >25, including Zhongwan (CV12), Shenshu (BL23) and Mingmen (DU4), etc. Association rules showed that Sanyinjiao (SP6)-Zhongwan (CV12)-Feishu (BL13)-Shenshu (BL23)-Zhiyang (DU9) had the highest correlation. Six effective clustering combinations of moxibustion for EHF were summarized by clustering analysis. The weight graph can obtained the first 30 relationships with high correlation of target syndromes.Conclusions:Professor Zhou applied the idea of "moxibustion for heat syndrome" to the treatment of EHF, and took the method of "acupoint selection according to symptoms" as the main acupoint selection idea for moxibustion treatment of EHF. In clinical practice, moxibustion combined with auxiliary operation of TCM is often used to treat EHF, which can achieve good results.
10.Perioperative results of cardiac valve surgery in patients with asymptomatic SARS-CoV-2 infection
Xiaochen WANG ; Hailei SUN ; Chaoyu ZHANG ; Zhengchun ZHOU ; Yu WEI ; Haiyang XUAN ; Guangcun CHENG ; Jianjun GE
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(07):962-966
Objective To analyze the perioperative outcomes of cardiac valve surgery in patients with asymptomatic SARS-CoV-2 infection. Methods The perioperative clinical data of patients receiving heart valve replacement in the Department of Cardiovascular Surgery, the First Affiliated Hospital of University of Science and Technology of China from November 2022 to February 2023 were retrospectively analyzed. According to whether the patients were infected with SARS-CoV-2, they were divided into a non-infected group and an asymptomatic group. The perioperative data of the patients were compared between the two groups, and the effect of asymptomatic infection on the result of heart valve replacement surgery was analyzed. Results A total of 66 patients were enrolled including 36 males and 30 females with a mean age of 58.0±11.1 years. There were 51 patients in the non-infected group and 15 patients in the asymtomatic group. There were 2 patients of mitral valve replacement, 20 patients of aortic valve replacement, 1 patient of double valve replacement, 3 patients of aortic valve replacement with tricuspid valvoplasty, 22 patients of mitral valve replacement and tricuspid valvoplasty, 18 patients of double valve replacement and tricuspid valvoplasty. Asymptomatic infected patients received more emergency surgery than uninfected patients (26.7% vs. 0.0%, P<0.01). There was no statistical difference in the duration of extracorporeal circulation, aortic occlusion, mechanical ventilation time after the surgery, ICU stay, postoperative drainage volume, or postoperative complications between the two groups. Conclusion Perioperative results of cardiac valve surgery in patients with asymptomatic SARS-CoV-2 infection and non-infection are almost the same.

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