1.Mechanisms of ribosomopathy and phase separation-related ribosomopathy.
Zhiyuan PAN ; Guofen LIN ; Hao LIU ; Guozhi LI ; Xiaoyi ZHANG ; Jiewen DAI
Journal of Zhejiang University. Science. B 2025;26(6):503-526
Ribosome is an intracellular ribonucleoprotein particle that serves as the site of protein biosynthesis. Ribosomal dysfunction caused by mutations in genes encoding ribosomal proteins (RPs) and ribosome biogenesis factors (RBFs) can lead to a spectrum of diseases, collectively known as ribosomopathy. Phase separation is a thermodynamic process that produces multiple phases from a homogeneous mixture. The formation of membraneless organelles and intracellular structures, including ribosomes and nucleoli, cannot occur without the involvement of phase separation. Here, ribosome structure, biogenesis, and their relationship with ribosomopathy are systematically reviewed. The tissue specificity of ribosomopathy and the role of phase separation in ribosomopathy are particularly discussed, which may offer some clues for understanding the mechanisms of ribosomopathy. Then, some new ideas for the prevention, diagnosis, and treatment of ribosomopathy are provided.
Humans
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Ribosomes/physiology*
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Ribosomal Proteins/metabolism*
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Mutation
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Animals
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Cell Nucleolus/metabolism*
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Protein Biosynthesis
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Phase Separation
2.AI-integrated IQPD framework of quality prediction and diagnostics in small-sample multi-unit pharmaceutical manufacturing: Advancing from experience-driven to data-driven manufacturing.
Kaiyi WANG ; Xinhai CHEN ; Nan LI ; Huimin FENG ; Xiaoyi LIU ; Yifei WANG ; Yanfei WU ; Yufeng GUO ; Shuoshuo XU ; Lu YAO ; Zhaohua ZHANG ; Jun JIA ; Zhishu TANG ; Zhisheng WU
Acta Pharmaceutica Sinica B 2025;15(8):4193-4209
The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.
3.Quercetin ameliorates myocardial injury in diabetic rats by regulating L-type calcium channels.
Hongyan SUN ; Guoqing LU ; Chengwen FU ; Mengwen XU ; Xiaoyi ZHU ; Guoquan XING ; Leqiang LIU ; Yufei KE ; Lemei CUI ; Ruiyang CHEN ; Lei WANG ; Pinfang KANG ; Bi TANG
Journal of Southern Medical University 2025;45(3):531-541
OBJECTIVES:
To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats.
METHODS:
Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique.
RESULTS:
The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin.
CONCLUSIONS
Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals
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Quercetin/pharmacology*
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Calcium Channels, L-Type/metabolism*
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Diabetes Mellitus, Experimental/metabolism*
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Rats, Sprague-Dawley
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Rats
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Myocytes, Cardiac/drug effects*
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Myocardium/pathology*
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Male
4.Activation of Centromedial Amygdala GABAergic Neurons Produces Hypotension in Mice.
Xiaoyi WANG ; Ziteng YUE ; Luo SHI ; Wei HE ; Liuqi SHAO ; Yuhang LIU ; Jinye ZHANG ; Shangyu BI ; Tianjiao DENG ; Fang YUAN ; Sheng WANG
Neuroscience Bulletin 2025;41(5):759-774
The central amygdala (CeA) is a crucial modulator of emotional, behavioral, and autonomic functions, including cardiovascular responses. Despite its importance, the specific circuit by which the CeA modulates blood pressure remains insufficiently explored. Our investigations demonstrate that photostimulation of GABAergic neurons in the centromedial amygdala (CeMGABA), as opposed to those in the centrolateral amygdala (CeL), produces a depressor response in both anesthetized and freely-moving mice. In addition, activation of CeMGABA axonal terminals projecting to the nucleus tractus solitarius (NTS) significantly reduces blood pressure. These CeMGABA neurons form synaptic connections with NTS neurons, allowing for the modulation of cardiovascular responses by influencing the caudal or rostral ventrolateral medulla. Furthermore, CeMGABA neurons targeting the NTS receive dense inputs from the CeL. Consequently, stimulation of CeMGABA neurons elicits hypotension through the CeM-NTS circuit, offering deeper insights into the cardiovascular responses associated with emotions and behaviors.
Animals
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GABAergic Neurons/physiology*
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Male
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Central Amygdaloid Nucleus/physiopathology*
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Hypotension/physiopathology*
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Mice
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Blood Pressure/physiology*
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Mice, Inbred C57BL
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Solitary Nucleus/physiology*
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Photic Stimulation
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Neural Pathways/physiology*
5.The prediction of MR angiography collateral circulation score on one-year outcome in acute vertebrobasilar artery occlusion patients
Shanshan HUANG ; Bofeng BAI ; Pan LIU ; Yongbin LI ; Xiaoyi DUAN
Journal of Practical Radiology 2025;41(4):554-559
Objective To investigate the relationship between pre-treatment collateral circulation and long-term clinical outcomes in patients with acute vertebrobasilar artery occlusion(VBAO)undergoing endovascular treatment(EVT).Methods A retrospective analysis was conducted on 129 VBAO patients who underwent EVT.Patients were categorized into short-term(90 d)and long-term(1 year)outcome groups based on follow-up duration.Clinical data were collected,and the posterior circulation collateral score(PC-CS)based on magnetic resonance angiography(MRA)was evaluated.Inter-rater reliability of the MRA PC-CS was evaluated using Cohen's Kappa coefficient.The predictive value of MRA PC-CS for outcomes was analyzed using receiver operating characteristic(ROC)curves.Multivariate logistic regression analysis was employed to identify independent predictors of long-term outcomes.Results A total of 109 patients were included in the long-term follow-up,with 78 survivors and 31 deaths.The MRA PC-CS demonstrated high diagnostic efficacy for predicting long-term outcomes,with an area under the curve(AUC)of 0.85[95%confidence interval(CI)0.78-0.92,P<0.000 1],with an optimal cutoff value of 5 points.Multivariate logistic regression analysis revealed that age[odds ratio(OR)1.07,95%CI 1.02-1.13,P=0.005],admission National Institutes of Health Stroke Scale(NIHSS)score(OR 1.08,95%CI 1.02-1.14,P=0.01),occipital lobe infarction(OR 3.96,95%CI 1.25-12.56,P=0.02),and MRA PC-CS≤5 points(OR 0.23,95%CI 0.06-0.84,P=0.03)were independent predictors of long-term outcomes.Conclusion The MRA PC-CS can independently predict adverse long-term functional outcomes in VBAO patients.
6.Formulation and Interpretation of the Measuring Method of Silicone Oil in Prefilled Syringe
Changshuai ZHAO ; Xueting LIU ; Aijuan LIU ; Xiaoyi MENG ; Yong SHEN ; Lei CHEN
Herald of Medicine 2025;44(7):1070-1073
Objective To formulate the 2025 edition of the Pharmacopoeia of the People's Republic of China of prefilled syringe silicone oil determination method,and to interpret the method content.Methods The prefilled syringe was added silicone solvent ethyl acetate to the roll edge of the sleeve and let it stand for extraction for 5 minutes,then put the silicon solvent in the evaporating dish dried at 105 ℃ to constant weight,then add 1mL ethyl acetate into the sleeve for rinsing and placing in the same evaporating dish,and then dry in a water bath at 105℃ to constant weight.The content of silicone oil in the sleeve of the prefilled syringe was calculated according to the quality difference.Results The reliability of the experimental method was verified by the ultimate extraction test,standard recovery test,and precision investigation.The results showed that the ultimate extraction could be achieved after 5 minutes of extraction with ethyl acetate.The recovery rate of the method was 100.0%-101.6%,and the precision was 3.5%.Conclusion The formulation of the determination method refers to the measurement method of silicone oil content in relevant standards at home and abroad,combined with the problems existing in the measurement of silicone oil content in daily tests,to further improve the operability of the detection method,the method is simple,efficient,feasible and reliable.
7.Research progress on rehabilitation motivation in cancer patients
Yiru WANG ; Hong WANG ; Xiao AN ; Zhicong ZHOU ; Xu SUN ; Xiaoyi LIU ; Ziwei TONG
Chinese Journal of Nursing 2025;60(12):1512-1517
Rehabilitation is an effective measure to improve the quality of life for cancer patients,and strong rehabilitation motivation is an important influencing factor for patients' compliance with rehabilitation.This paper mainly reviews the concepts,assessment tools,influencing factors,and intervention strategies of rehabilitation motivation in cancer patients,with the aim of providing references for medical staff to improve the level of rehabilitation compliance in cancer patients and develop targeted rehabilitation management strategies.
8.Rehabilitation effects based on immersive virtual reality as a treatment for peripheral vestibular dysfunction:a Meta-analysis
Xiaoyi LIU ; Hong WANG ; Zhicong ZHOU ; Xu SUN ; Yiru WANG ; Ziwei TONG ; Xiaoying LIU
Chinese Journal of Nursing 2025;60(9):1140-1146
Objective To systematically evaluate the rehabilitation effect of immersive virtual reality technology for patients with peripheral vestibular dysfunction,and to provide theoretical basis and practical guidance for the design of efficient rehabilitation training programs.Methods PubMed,Embase,Cochrane Library,Web of Science,CINAHL,CNKI,Wanfang Database,VIP Database,and China Biomedical Literature Database were searched for randomized controlled trials on the intervention effect of immersive virtual reality technology in patients with peripheral vestibular dysfunction from inception to February 2025.RevMan5.4 software was used to perform meta-analysis of the literature that met the quality standards.Results A total of 10 papers with 491 patients with peripheral vestibular dysfunction were included.Meta-analysis showed that immersive virtual reality technology improved vertigo symptoms in patients with peripheral vestibular dysfunction compared with conventional vestibular rehabilitation care[SMD=-1.41,95%CI(-1.58,-0.70),P<0.001],and subgroup analysis showed that the frequency of intervention was<5 times/week[SMD=-1.31,95%CI=(-1.96,-0.66),P<0.001],single intervention duration<30 min[SMD=-1.45,95%CI=(-2.21,-0.70),P<0.001],and intervention period≤7 weeks[SMD=-1.49,95%CI(-2.04,-0.94),P<0.001]were more significant.Immersive virtual reality technology reduced the risk of falls[MD=4.66,95%CI(3.84,5.48),P<0.001],and improved anxiety and depression[SMD=2.65,95%CI(1.98,3.33),P<0.001].Conclusion Immer-sive virtual reality technology improves vertigo symptoms,reduces the risk of falls,and improves anxiety and depres-sion symptoms in patients with peripheral vestibular dysfunction,in which the intervention period of ≤7 weeks,<5 training sessions per week,and each training session of<30 min are better for improving vertigo symptoms in patients with peripheral vestibular dysfunction.
9.Study on transmission mechanisms of resistance gene and virulence gene of Klebsiella pneumoniae
Ashao JIA ; Xiaoyi FAN ; Juzhen LIU ; Yunzu HUANG ; Jingxuan ZHAO ; Guangchao YU
Chinese Journal of Nosocomiology 2025;35(16):2441-2444
OBJECTIVE To investigate the horizontal transfer mechanisms and genetic evolutionary characteristics of virulence genes in hypervirulent Klebsiella pneumoniae(HvKP)and resistance genes in carbapenem-resistant K.pneumoniae(CRKP).METHODS The donor strain was a CRKP strain harboring both VIM and KPC resist-ance genes.The positive control was a CRKP strain containing blaIMP-4.The recipient strain was Escherichia coli J53.The horizontal transfer capability of the resistance genes was verified by plasmid conjugation assay.Fifty HvKP strains were collected from the First Affiliated Hospital of Jinan University from 2017 to 2021 and conjuga-ted with the plasmids of five CRKP strains which could mediate the transmission of drug resistance genes.The conjugants were screened by selective medium containing meropenem,and polymerase chain reaction(PCR)was used to detect the resistance and virulence genes in the conjugation-successful strains.The lethality of conjugants was verified by Galleria mellonella larval assays.RESULTS The donor CRKP strain had the ability to mediate re-sistance gene transmission.Its blaKPC gene was successfully transferred to E.coli J53,but the transference of the VIM gene failed.Five CRKP strains with the ability to mediate resistance gene transmission were screened,of which one strain carried both VIM and KPC resistance genes,and the other four strains carried the IMP-4 resist-ance gene.Only one CRKP strain with the blaIMP-4 resistance gene was successfully conjugated with HvKP,carry-ing both virulence genes(aerobactin and RmpA)and the blaIMP-4 resistance gene,with positive wire drawing test result.The Galleria mellonella larvae test showed that the conjugation-successful strain caused the death of all lar-vae within 24 hours.CONCLUSIONS In the hospital environment,CRKP and HvKP can form"superbugs"with both drug resistance and high virulence through plasmid conjugation,posing a severe challenge to clinical an-ti-infection treatment.It is necessary to strengthen the prevention and control of hospital-acquired infections.
10.Diagnostic value of 18F-PSMA-1007 PET/CT in patients with PI-RADS 1-3 prostate cancer lesions on multi-parametric MRI
Liang LUO ; Ruiyan WANG ; Jungang GAO ; Yang LI ; Xiang LIU ; Xiaoyi DUAN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(10):595-599
Objective:To evaluate the diagnostic efficacy of 18F-prostate specific membrane antigen (PSMA)-1007 PET/CT in patients with prostate imaging reporting and data system (PI-RADS) 1-3 lesions on multi-parametric MRI (mpMRI) and pathologically confirmed prostate cancer. Methods:Clinical, pathological, and imaging data of 59 patients (age (67.8±7.6) years) with PI-RADS 1-3 lesions on mpMRI in the First Affiliated Hospital of Xi′an Jiaotong University between December 2021 and March 2024 were retrospectively collected. Those patients also underwent 18F-PSMA-1007 PET/CT and prostate biopsy during the same period due to an elevated prostate specific antigen (PSA) level. The diagnostic performances of 18F-PSMA-1007 PET/CT for PI-RADS 1-3 prostate cancer and clinically significant prostate cancer were evaluated by using pathological results as the standard. Mann-Whitney U test was used to compare differences in clinical characteristics and PET parameters between PET-positive and PET-negative groups, and logistic regression analysis was performed to select independent influencing factors for the PET/CT diagnosis of prostate cancer. Results:Of the included 59 patients, 7, 27, and 25 had PI-RADS scores of 1, 2, and 3 respectively. Benign prostate hyperplasia was pathologically confirmed in 8 patients, and prostate cancer was confirmed in 51 patients, of which 37 had clinically significant prostate cancer. The sensitivity of 18F-PSMA-1007 PET/CT in diagnosing prostate cancer was 86.3%(44/51), the specificity was 2/8, the accuracy was 78.0%(46/59), the positive predictive value was 88.0%(44/50), and the negative predictive value was 2/9. For patients with clinically significant prostate cancer, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 91.9%(34/37), 27.3%(6/22), 67.8%(40/59), 68.0%(34/50), and 6/9, respectively. SUV max was significantly higher in the PET-positive group ( n=44) than that in the PET-negative group ( n=7; 12.8(9.1, 23.5) vs 5.1(5.0, 6.2); Z=-4.16, P=0.001). Logistic regression analysis showed that SUV max was an independent influencing factor for the diagnosis of prostate cancer by 18F-PSMA-1007 PET/CT (odds ratio ( OR)=6.01, 95% CI: 1.57-23.00, P=0.009). Conclusions:18F-PSMA-1007 PET/CT has a high sensitivity and positive predictive value in prostate cancer patients with PI-RADS 1-3 on mpMRI. It can be used as a supplementary modality to mpMRI to guide clinical decision for patients with PI-RADS 1-3 and clinically suspected prostate cancer lesions.

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