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.Real-world efficacy and safety of azvudine in hospitalized older patients with COVID-19 during the omicron wave in China: A retrospective cohort study.
Yuanchao ZHU ; Fei ZHAO ; Yubing ZHU ; Xingang LI ; Deshi DONG ; Bolin ZHU ; Jianchun LI ; Xin HU ; Zinan ZHAO ; Wenfeng XU ; Yang JV ; Dandan WANG ; Yingming ZHENG ; Yiwen DONG ; Lu LI ; Shilei YANG ; Zhiyuan TENG ; Ling LU ; Jingwei ZHU ; Linzhe DU ; Yunxin LIU ; Lechuan JIA ; Qiujv ZHANG ; Hui MA ; Ana ZHAO ; Hongliu JIANG ; Xin XU ; Jinli WANG ; Xuping QIAN ; Wei ZHANG ; Tingting ZHENG ; Chunxia YANG ; Xuguang CHEN ; Kun LIU ; Huanhuan JIANG ; Dongxiang QU ; Jia SONG ; Hua CHENG ; Wenfang SUN ; Hanqiu ZHAN ; Xiao LI ; Yafeng WANG ; Aixia WANG ; Li LIU ; Lihua YANG ; Nan ZHANG ; Shumin CHEN ; Jingjing MA ; Wei LIU ; Xiaoxiang DU ; Meiqin ZHENG ; Liyan WAN ; Guangqing DU ; Hangmei LIU ; Pengfei JIN
Acta Pharmaceutica Sinica B 2025;15(1):123-132
Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T NANC), time to symptom improvement (T SI), and time of hospital stay (T HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.
3.Palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis: A new target for anti-myocardial fibrosis.
Xuewen YANG ; Yanwei ZHANG ; Xiaoping LENG ; Yanying WANG ; Manyu GONG ; Dongping LIU ; Haodong LI ; Zhiyuan DU ; Zhuo WANG ; Lina XUAN ; Ting ZHANG ; Han SUN ; Xiyang ZHANG ; Jie LIU ; Tong LIU ; Tiantian GONG ; Zhengyang LI ; Shengqi LIANG ; Lihua SUN ; Lei JIAO ; Baofeng YANG ; Ying ZHANG
Acta Pharmaceutica Sinica B 2025;15(9):4789-4806
Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.
4.Introduction and implications of the pharmacy academic,professional and continuing education system in the Netherlands
Di LI ; Tianwen LI ; Qinglian ZHAI ; Zhiyuan TAN ; Yan QIAN
China Pharmacy 2025;36(23):2899-2905
OBJECTIVE To introduce the Dutch system of pharmacy academic education, professional practice and continuing education, and provide new ideas for constructing a “demand-driven, industry-education integrated, and sustainably developing” Chinese-style pharmacy education system. METHODS Through literature and public data retrieval, as well as collection of field visit materials, the study systematically combed the stage characteristics, institutional design, and innovative practices of Dutch pharmacy education, extracted its features and advantages, and proposed suggestions for pharmacy education reform in China. RESULTS & CONCLUSIONS The Dutch pharmacy academic education system is characterized by stepped competency-based training, integrating basic theory with early clinical practice at the undergraduate level, emphasizing specialized division of labor and strengthening clinical competence at the master’s level, and promoting industry-university-research collaborative innovation at the doctoral level. The practice qualification certification and continuing education exhibit multi-dimensional synergy. Specifically, the practice qualification certification process adheres to the guiding principle of “evidence-based competency”, implementing an access system centered on competency assessment, which requires passing national examinations and registration. The continuing education for hospital pharmacists is guided by patient safety, while continuing education for community pharmacists and other pharmacists (such as industrial pharmacists, regulatory science pharmacists, etc.) is guided by the frameworks of “digital situational learning” and a “triple tracks encompassing industry, regulation, and emerging fields”, respectively. China may draw on the five-dimensional path of Dutch pharmacy education in “early integration, vertical coherence, unified standards, industry-university-research collaboration, and intelligent empowerment” to reform its pharmacy education in aspects such as curriculum design, credit systems, evaluation criteria, training models, and training methods, aiming to cultivate pharmacy professionals aligned with China’s practical E-mail:cqqianyan@hospital.cqmu.edu.cn requirements.
5.Analysis and prediction of the disease burden of esophageal cancer by province in China from 1990 to 2019
Zhiyuan CHENG ; Tinglu WANG ; Yunfei JIAO ; Jinlei QI ; Maigeng ZHOU ; Rong WAN ; Zhaoshen LI ; Luowei WANG
Chinese Journal of Digestion 2025;45(3):156-161
Objective:To analyze the prevalence, trends in disease burden, and risk factors of esophageal cancer in various provinces of China from 1990 to 2019.Methods:Utilizing data from the 2019 global burden of disease study, the disease burden of esophageal cancer of 31 provinces, municipalities, and autonomous regions, as well as Hong Kong Special Administrative Region and Macao Special Administrative Region of China from 1990 to 2019 were analyzed. The disease burden of esophageal cancer in China was described with the number (and incidence) of cases, the number (and mortality) of death, and disability-adjusted life year (DALY) and their age-standardized rates. Joinpoint regression analysis and t-test were used to evaluate the annual percent change and the average annual percent change (AAPC). Scatter plots and Spearman correlation coefficients were performed to analyze the correlation between the disease burden of esophageal cancer and the socio-demographic index (SDI), as well as DALY in each province. Results:In 2019, there were 278 121 new cases of esophageal cancer and 257 316 deaths in China, increased by 60.13% and 45.70% respectively compared with 1990. The top 3 provinces with the highest age-standardized incidence of esophageal cancer were Sichuan Province (25.96/100 000), Jiangsu Province (23.80/100 000), and Fujian Province (21.98/100 000). From 1990 to 2019, except for Jiangsu Province and Sichuan Province, the age-standardized incidence in other provinces showed a declining trend. The age-standardized mortality and DALYs of esophageal cancer decreased in all provinces as well as in Hong Kong and Macao Special Administrative Regions of China. The attributable risk factors of esophageal cancer caused deaths in China mainly included smoking, alcohol consumption, high body mass index, and low fruit intake, accounting for 91.38% of all the cases. With the increase of the SDI, the age-standardized rates of DALY in high incidence areas of esophageal cancer (Sichuan Province, Jiangsu Province, Fujian Province, Henan Province, Chongqing City, Xinjiang Uygur Autonomous Region, Shanxi Province, and Anhui Province) demonstrated a trend of initially decline and then an upward. In contrast, the age-standardized rates of DALY of esophageal cancer in other provinces, as well as in Hong Kong and Macao Special Administrative Regions of China, showed a trend of initially upward and then decline. The age-standardized rate of DALY of esophageal cancer showed a negative correlation with SDI ( r=-0.315, P<0.001). From 1990 to 2019, the age-standardized incidence and mortality of esophageal cancer generally demonstrated a downward trend. The AAPC was -1.43% ( t=-19.16, P<0.001) for incidence and -1.83% ( t=-29.63, P<0.001) for mortality, respectively. It is projected that by 2044, the actual number of new esophageal cancer cases in China will increase from 278 121 in 2019 to 291 206 in 2044, and the actual number of deaths will increase from 257 316 to 275 856. Conclusions:In recent years, the disease burden of esophageal cancer in China remains a serious status, with significant differences in geography and gender. It is projected that by 2044, the number of new esophageal cancer cases and deaths in China will continue to increase. Effective strategies and policies are urgently needed to reduce the disease burden.
6.Investigation and management of a clustered incident of incision infection after microtia plastic surgery
Jian SUN ; Zhiyuan CHEN ; Hua XU ; Limei MA ; Weiguang LI
Chinese Journal of Nosocomiology 2025;35(16):2432-2436
OBJECTIVE To summarize the process of investigation,disposal and prevention of a cluster incident of post-operative incision infection following microtia plastic surgery in the otorhinolaryngology department of a terti-ary care hospital,in order to provide a basis for hospital-aquired infection prevention and control.METHODS An epidemiological survey was conducted on seven patients who underwent otorhinolaryngoplasty for microtia in the ENT department of a tertiary care hospital from 27 Jul.to 7 Sep.2023,and interventions were implemented.RESULTS The incidence rate of infection was 71.43%among post-otorhinolaryngoplasty patients.In 5 patients,area for electrocoagulation of haemostatic increased by approximately 50%compared to the previous period,and drainage tubes were left in the surgical area for 11 to 13 days.Patients changed dressings in a shared dressing room.Pseudomonas aeruginosa was detected in three of the infected patients,and their antibiotic sensitivity pat-terns were similar to that of a lower respiratory tract infection patient(case 0)in the same department.CONCLUSION Inadequate aseptic practice by medical staff,longer retention of drainage tubes,incomplete disin-fection of the environment of the dressing room,and changes in surgical procedures may be the primary factors contributing to the occurrence of this cluster of infections.
7.Effect of "four-staff co-management" follow-up mode on the control of risk factors and medium-term prognosis improvement in patients with coronary heart disease after PCI
Guoming ZHANG ; Cuilian DAI ; Jiajin CHEN ; Weimei OU ; Chengmin HUANG ; Zhixian LIU ; Zhiyuan JIN ; Jiyi LIN ; Bin WANG ; Xiaofeng GE ; Suiji LI ; Xiang CHEN ; Yan WANG
Chinese Journal of General Practitioners 2025;24(4):426-433
Objective:To investigate the effect of "four-staff co-management" follow-up mode on risk factor control and medium-term prognosis improvement in patients with coronary heart disease after percutaneous coronary intervention (PCI).Methods:This was a intervention study. Patients with coronary heart disease who were admitted to the Xiamen Cardiovascular Hospital of Xiamen University from June 2021 to January 2022 and successfully discharged after PCI were included. According to the different types of follow-up after discharge, patients were divided into the traditional follow-up group and the "four-staff co-management" follow-up group. The "four-staff co-management" follow-up mode means that specialists, specialist managers in third-level A hospitals and general practitioners and health managers in basic hospitals were jointly responsible for post-discharge follow-up of PCI patients. Baseline clinical data were collected. The primary endpoints were the rate of compliance of coronary heart disease risk factor control at 12 months after surgery, the rate of secondary surgery, and the incidence of mid-term major adverse cardiovascular and cerebrovascular events (MACCE). Unplanned secondary PCI included symptom-driven secondary PCI and asymptomatic secondary PCI. MACCE includes myocardial infarction, hospitalization for heart failure, stroke, major bleeding, all-cause death, and composite endpoints including these events.Results:A total of 2 181 patients were enrolled, including 1 097 patients in the traditional follow-up group and 1 084 patients in the "four-staff co-management" follow-up group. At baseline, there were no statistically significant differences in gender, age, discharge diagnosis, co-existing diseases, echocardiographic indexes, and coronary artery lesions between the two groups (all P>0.05). There were no significant differences between the two groups in total PCI stent length, maximum internal diameter of stent, proportion of patients using drug balloon, proportion of patients with a planned second surgery during hospitalization, and discharge with drugs (all P>0.05). Twelve months after PCI, the reduction in HbA1c and low-density lipoprotein cholesterol was greater in the "four-staff co-management " follow-up group than that in the traditional follow-up group (all P<0.05), and the rate of reaching the standard for low-density lipoprotein cholesterol was higher than that in the traditional follow-up group ( P=0.001), but there was no statistical significance between the two groups for blood pressure and blood glucose (all P>0.05). During the follow-up period, the proportion of symptom-driven second operation patients was lower in the "four-staff co-management" follow-up group than that in the traditional follow-up group ( P<0.001), and there was no significant difference in the proportion of asymptomatic second operation patients between the two groups ( P=0.191). The proportion of hospitalized patients with heart failure in the "four-staff co-management" follow-up group was lower than that in the traditional follow-up group ( P=0.029), and there was no significant difference in the proportion of myocardial infarction, cerebral infarction, cerebral hemorrhage, massive hemorrhage, death and complex endpoint events between the two groups (all P>0.05). Conclusion:The "four-staff co-management" follow-up mode can effectively improve the control of risk factors and medium-term prognosis in patients with coronary heart disease after PCI.
8.Filter's retraction hook capture technique of pull-assisted method for endovascular retrieval of conical inferior vena cava filter whose hook attached to the wall
Xuan TIAN ; Jianlong LIU ; Han ZHENG ; Jinyong LI ; Xiao LIU ; Mi ZHOU ; Wei JIA ; Peng JIANG ; Zhiyuan CHENG ; Yunxin ZHANG ; Chengjia QU ; Run HUA ; Chenyang TIAN
Chinese Journal of General Surgery 2025;40(11):856-862
Objective:To investigate the clinical application value of a novel filter's retraction hook capture technique of pull-assisted method for the endovascular retrieval of conical inferior vena cava (IVC) filters whose hook attached to the wall.Methods:From January 2020 to December 2024, patients with conical filters whose hook attached to the wall admitted at Beijing Jishuitan Hospital were enrolled consecutively.Results:A total of 46 patients underwent filter retrieval using filter's retraction hook capture technique of pull-assisted method. Among these patients, 39 cases (84.8%) were successful in filter retrieval, with the penetration distance of cranial anchor vertex of 3.3(2.5, 4.4) mm, and 13 (33.3%) filters were deformed. The other 7 cases were unsuccessful, with a penetration distance of cranial anchor vertex of 5.0 (4.3, 5.0) mm, and 6 (85.7%) filters were deformed. There was a statistically significant difference between the two groups ( P<0.05). One case (2.2%) had IVC injury, one case (2.2%) experienced filter fracture, and no symptomatic pulmonary embolism occurred. Logistic regression analysis showed that filter deformation was an independent dangerous factor for filter's retraction. Conclusions:Filter's retraction hook capture technique of pull-assisted method is effective in removing conical filters whose hook attached to the wall, with no symptomatic PE occurring. This method can be considered as a new adjuvant technique for filter retrieval.
9.The value of 3D and 2D radiomics features models of MRI in predicting Ki-67 expression in Luminal breast cancer
Yang YIN ; Wenlu LI ; Jitao GUO ; Jian ZHANG ; Na LI ; Yan ZHAO ; Zhiyuan YANG
Journal of Practical Radiology 2025;41(1):52-57
Objective To explore the value of 3D and 2D radiomics features models based on multiparameter MRI in predicting Ki-67 expression(with 14%and 20%as the critical values,respectively)in breast cancer.Methods The MRI images of 147 patients with pathologically confirmed Luminal breast cancer were analyzed retrospectively.The patients were randomly divided into training set and test set according to the ratio of 7︰3.The 3D and 2D radiomics features of intratumor and peritumor were extracted from diffusion weighted imaging(DWI),dynamic contrast enhancement(DCE)mask(S0)and DCE phase 3(S3)images.Then the models were constructed by multiple pipeline combinations of three feature normalization methods,two feature dimensionality reduction methods,four feature selection methods,and ten classifiers.The receiver operating characteristic(ROC)curve and the area under the curve(AUC)were used to evaluate the prediction performance of the models in order to select the best 3D and 2D single parame-ter(DWI,S0,S3)and multiparameter combination(S0+S3,S0+DWI,S3+DWI,S0+S3+DWI)models.Finally,the differ-ences between the models were compared by De Long test.Results With 14%as the critical value,the AUC of 3D and 2D models in the training set were 0.726-0.824 and 0.707-0.835,respectively,and those in the test set were 0.724-0.82 and 0.701-0.805.With 20%as the critical value,the AUC of 3D and 2D models in the training set were 0.743-0.868 and 0.793-0.881,respectively,and those in the test set were 0.738-0.853 and 0.743-0.814.There was no significant statistical difference between 3D and 2D models with the same parameter in the two critical values standards.Conclusion The multiparameter MRI-based radiomics models can bet-ter predict the expression of Ki-67 in breast cancer,and the models based on intratumor and peritumor 3D and 2D features have the same prediction efficiency.
10.Characteristics of cardiac lesions in 17 patients with Fabry disease
Junlan YANG ; Zhiyuan WEI ; Bin WANG ; Zuolin LI ; Jingyuan CAO ; Li SUN ; Weiwei YU ; Shijun ZHANG ; Weiming HE ; Aihua ZHANG ; Xiaoliang ZHANG
Chinese Journal of Cardiology 2025;53(5):529-536
Objectives:To summarize the characteristics of Fabry′s disease with cardiac involvement.Methods:This was a single-center, cross-sectional, retrospective study. Patients with Fabry disease who were admitted to Zhongda Hospital Affiliated to Southeast University from January 2022 to March 2023 were included. Clinical data, laboratory results, electrocardiogram, echocardiography and cardiac magnetic resonance findings of enrolled patients were collected. Clinical presentations and imaging features of patients with Fabry′s disease with cardiac involvement were summarized and analyzed.Results:A total of 17 patients from 8 families were included, with 9 males and diagnosis age of (44.35±13.72) years. Cardiac involvement and other organ involvement were presented in all patients and the heart was the most vulnerable organ (17/17). 24 h electrocardiogram showed frequent sinus arrhythmia in 3 patients. Echocardiography showed reduced left ventricular ejection fraction in 1 patient, myocardial hypertrophy in 13 patients, and left ventricular wall thickness ≥13 mm in 10 patients. Mitral regurgitation was observed in 11 patients and tricuspid regurgitation in 12 patients. Two patients underwent two-dimensional speckle tracking echocardiography, both revealing reduced regional longitudinal strain of the left ventricle, primarily in the basal segments. Cardiac magnetic resonance showed reduced left ventricular ejection fraction in 2 patients, myocardial hypertrophy in 16 patients, and left ventricular wall thickness≥13 mm in 14 patients. T1 value was reduced in 16 patients, with late gadolinium enhancement observed in 9 patients and “pseudo-normalization” of T1 values in 1 patient. The most susceptible target organ besides the heart was the kidneys (14/17), followed by the central nervous system (9/17). Additional findings inclucling cutaneous angiokeratoma in 4 patients, peripheral neuropathy with burning pain and hypohidrosis or hyperhidrosis in 6 patients, and corneal vortex opacities in 2 patients.Conclusion:The main manifestations of cardiac involvement in Fabry′s disease are decreased cardiac function, left ventricular hypertrophy and myocardial fibrosis. Advanced imaging techniques such as two-dimensional speckle tracking, T1 Mapping, and late gadolinium enhancement are useful in detecting myocardial pathological changes of Fabry′s disease.

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