1.Drug delivery systems based on mesoporous silica nanoparticles for the management of hepatic diseases.
Boyan LIU ; Wenshi LIU ; Miao XU ; Tongyi ZHAO ; Bingxin ZHOU ; Ruilin ZHOU ; Ze ZHU ; Xuchun CHEN ; Zhiye BAO ; Keke WANG ; Heran LI
Acta Pharmaceutica Sinica B 2025;15(2):809-833
The liver performs multiple life-sustaining functions. Hepatic diseases, including hepatitis, cirrhosis, and hepatoma, pose significant health and economic burdens globally. Along with the advances in nanotechnology, mesoporous silica nanoparticles (MSNs) exhibiting diversiform size and shape, distinct morphological properties, and favorable physico-chemical features have become an ideal choice for drug delivery systems and inspire alternative thinking for the management of hepatic diseases. Initially, we introduce the physiological structure of the liver and highlight its intrinsic cell types and correlative functions. Next, we detail the synthesis methods and physicochemical properties of MSNs and their capacity for controlled drug loading and release. Particularly, we discuss the interactions between liver and MSNs with respect to the passive targeting mechanisms of MSNs within the liver by adjusting their particle size, pore diameter, surface charge, hydrophobicity/hydrophilicity, and surface functionalization. Subsequently, we emphasize the role of MSNs in regulating liver pathophysiology, exploring their value in addressing liver pathological states, such as tumors and inflammation, combined with multi-functional designs and intelligent modes to enhance drug targeting and minimize side effects. Lastly, we put forward the problems, challenges, opportunities, as well as clinical translational issues faced by MSNs in the management of liver diseases.
2.The clinical value of matrix metalloproteinase-3 combined with anti-mutant citrulline vimentin antibody and rheumatoid factor in the diagnosis of rheumatoid arthritis
Nan ZHANG ; Man LI ; Ting XIA ; Zhiye XU ; Zhiyang LI
Journal of Chinese Physician 2024;26(11):1681-1686
Objective:To investigate the diagnostic value of serum matrix metalloproteinase 3 (MMP-3) combined with anti-mutant citrulline vimentin antibody (anti-MCV) and rheumatoid factor (RF) in rheumatoid arthritis (RA).Methods:A retrospective study was conducted to select 78 patients diagnosed with RA, 30 with Sjogren′s syndrome (SS), 25 with connective tissue disease (CTD), and 38 with antiphospholipid syndrome (APS) from the Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University from August 2022 to April 2024. In the same period, 50 healthy controls were selected from the physical examination center of our hospital. Fasting peripheral blood RF, anti-streptolysin O (ASO), C-reactive protein (CRP), erythrocyte deposition rate (ESR), interleukin-6 (IL-6), procalcitonin (PCT), anti-keratin antibody (AKA), anti-MCV, MMP-3, anti-cyclic citrullinated peptide (anti-CCP) level. Fasting peripheral blood MMP-3 levels in SS, CTD, APS patients and healthy control group were compared, Spearman correlation analysis was used to evaluate the correlation between MMP-3 levels and various indicators, and logistic regression analysis was used to screen the related influencing factors of RA occurrence. The diagnostic value of serum MMP-3, anti-MCV, RF and combined detection for RA was evaluated by receiver operating characteristic (ROC) curve.Results:There were statistically significant differences in RF, CRP, ESR, IL6, AKA, antiMCV, MMP-3 and anti-CCP between RA group and healthy control group (all P<0.001), while there were no statistically significant differences in PCT and ASO between the RA group and the healthy control group (all P>0.05). Serum MMP-3 level in the RA group was significantly higher than that in SS, CTD, APS and healthy control group, and the difference was statistically significant (all P<0.05). MMP-3 was positively correlated with anti-CCP, CRP, ESR, anti-MCV, RF and AKA ( r=0.403, 0.532, 0.530, 0.431, 0.427, 0.391, all P<0.05). Multivariate logistic regression analysis showed that MMP-3 ( OR=1.082, P=0.02), anti-MCV ( OR=1.015, P=0.049) and RF ( OR=1.046, P=0.036) were independent risk factors for RA. ROC curve showed that when the cut-off value of MMP-3 was 53.10 ng/ml, the area under the curve for diagnosing RA was 0.889, the sensitivity was 74.5%, and the specificity was 96.0%. The area under ROC curve of MMP-3 combined with anti-MCV and RF for the diagnosis of RA was 0.975, the sensitivity was 88.2%, and the specificity was 99.7%. Conclusions:MMP-3 has a certain value in the differential diagnosis of RA, and MMP-3 combined with anti-MCV and RF is of great significance in the auxiliary diagnosis of RA.
3.Establishment of a real-time quality control method for identifying random error in serum sodium ion based on artificial intel-ligence voting algorithm
Yuan LIU ; Hexiang ZHENG ; Zhiye XU ; Wenqin CHEN ; Hongyan SONG ; Yuxin CHEN
Chinese Journal of Clinical Laboratory Science 2024;42(10):772-777
Objective To establish a novel real-time quality control method for rapidly identifying the random error of sodium ion con-centration in serum using an artificial intelligence voting algorithm,and evaluate the relevant effectiveness of the model established on this basis.Methods A total of 144 754 test results of serum sodium ion rom the inpatients measured by Beckman AU5400 biochemis-try analyzer from January to May 2021 were obtained retrospectively from laboratory information system of the Department of Clinical La-boratory,Nanjing Drum Tower Hospital,and all the data were used as unbiased data for the current study.The random errors were arti-ficially introduced to generate the corresponding biased data set.Subsequently,the voting algorithm-based internal quality control model(ViQC)was established using the principles of the voting algorithm.The ViQC model and five classical PBRTQC(patient-based real-time quality control)algorithms were performed direct to each biased data.The analytical performance of the ViQC model was evaluated by using classification model criteria.The trimmed average number of patient samples until error detection(tANPed)was used to com-pare the clinical detection efficacy of the ViQC model with those of the five classical algorithms,and the error detection curves were plotted.Results Compare with all the classical algorithms,the ViQC model showed a false positive rate below 0.002 and achieved ac-curacy above 0.951 in detecting all the deviations.When the error factors were 1.5,2.5,and 3.0,the false positive rate of the ViQC model was zero.When the error factor was 2.5,its accuracy reached 0.979.Compared to the five classical PBRTQC algorithms,the ViQC model reduced the overall average tANPed by up to 34%and showed higher sensitivity for error detection.In addition,the ViQC model demonstrated the area under the ROC curve was as high as 0.989 at TEa on the test set,but the value of tANPed wasonly five.Conclusion We successfully established a real-time quality control model for the data of patients based on artificial intelligence algo-rithms,and its efficacy of clinical detection was superior to the traditional PBRTQC algorithms.
4.Experts consensus on standard items of the cohort construction and quality control of temporomandibular joint diseases (2024)
Min HU ; Chi YANG ; Huawei LIU ; Haixia LU ; Chen YAO ; Qiufei XIE ; Yongjin CHEN ; Kaiyuan FU ; Bing FANG ; Songsong ZHU ; Qing ZHOU ; Zhiye CHEN ; Yaomin ZHU ; Qingbin ZHANG ; Ying YAN ; Xing LONG ; Zhiyong LI ; Yehua GAN ; Shibin YU ; Yuxing BAI ; Yi ZHANG ; Yanyi WANG ; Jie LEI ; Yong CHENG ; Changkui LIU ; Ye CAO ; Dongmei HE ; Ning WEN ; Shanyong ZHANG ; Minjie CHEN ; Guoliang JIAO ; Xinhua LIU ; Hua JIANG ; Yang HE ; Pei SHEN ; Haitao HUANG ; Yongfeng LI ; Jisi ZHENG ; Jing GUO ; Lisheng ZHAO ; Laiqing XU
Chinese Journal of Stomatology 2024;59(10):977-987
Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.
5.Osteosarcoma with bone metastasis or pulmonary metastasis show distinct genomic manifestations
Zhenyu CAI ; Yanchun SHE ; Lu XIE ; Han WANG ; Zhiye DU ; Yuan LI ; Tingting REN ; Jie XU ; Xin SUN ; Kunkun SUN ; Danhua SHEN ; Xiaodong TANG ; Wei GUO
Chinese Journal of Orthopaedics 2023;43(9):581-590
Objective:To investigate the genomic manifestation and pathogenesis of osteosarcoma with different relapse pattens, which were respectively initially presented with bone metastasis or pulmonary metastasis.Methods:From May 1, 2021 to October 1, 2021, 38 fresh tumor specimens and some paraffin-embedded specimens of high-grade osteosarcoma were collected in Peking University People's Hospital, including 29 males and 9 females, aged 19.6±2.2 years (range, 6-61 years). Among the 38 cases, 12 cases had initial bone metastasis (group A) and 26 cases had initial lung metastasis (group B), of which 15 cases (40%, 15/38) had paired specimens of primary and metastatic lesions. Based on Illumina NovaSeq 6000, we analyzed whole-exome sequencing (WES) as well as transcriptome for osteosarcoma with paired samples in different relapse patterns. During all their treatment courses, we also collected their paired samples to reveal these tumors' evolution. We sought to redefine disease subclassifications for osteosarcoma based on genetic alterations and correlate these genetic profiles with clinical treatment courses to elucidate potential evolving cladograms.Results:We found that osteosarcoma in group A mainly carried single-nucleotide variations (83%, 10/12), displaying higher tumor mutation burden [4.9 (2.8, 12.0) & 2.4 (1.4, 4.5), P=0.010] and neoantigen load [743.0 (316.5, 1,034.5) & 128.5 (49.0, 200.5), P=0.003], while those in group B mainly exhibit structural variants (58%, 15/26). The mutation spectrum showed that there was a significant difference in age-related gene imprinting 1 between the bone metastasis group and the lung metastasis group ( P=0.005). Samples were randomly selected from group A (3 patients) to investigate immunologic landscape by multiplex immunohistochemistry, from which we noticed tertiary lymphatic structure from one patient from group A. High conservation of reported genetic sequencing over time was found in their evolving cladograms. Conclusion:Osteosarcoma with mainly single-nucleotide variations other than structural variants might exhibit biological behavior predisposing toward bone metastases with older in age as well as better immunogenicity in tumor microenvironment.
6.Performance evaluation of some domestically produced biochemical reagents
Zhiye XU ; Sen WANG ; Hongyan SONG ; Hai DING ; Han SHEN ; Hong YAN
Chinese Journal of Laboratory Medicine 2022;45(11):1115-1122
Objective:To evaluation the performance of a total of 40 clinical biochemical reagents from three domestic manufacturers and two foreign manufacturers, and evaluate their clinical application value.Methods:The Beckman AU5400 automatic biochemical analyzer was used to verify the performance of 40 kinds of commonly used clinical biochemical reagents from three domestic manufacturers of Sichuan Maccura, Ningbo Medical System, and Shanghai Fosun Long March, and two foreign imported manufacturers of Roche and Japan′s Hitachi. The analysis samples were selected from the serum of patients who underwent clinical testing in Nanjing Drum Tower Hospital hospital from December 2021 to June 2022. Refer to China′s national health industry standards, China′s national pharmaceutical industry standards, the US Clinical Laboratory Standards Institute (CLSI) for the performance evaluation standards of in vitro diagnostic reagents, and the methods recommended in the relevant regulations of China′s State Food and Drug Administration on the management of in vitro diagnostic reagents. The precision, linear range, open bottle stability, interchangeability of calibrators and accuracy from different batches of 40 reagents were evaluated and validated. Simple linear regression analysis was used for linear regression, and P<0.05 indicated that the regression was statistically significant. Results:The overall precisions of 40 reagents were fine, except for one domestic reagent with low-level intra-batch coefficient of variation ( CV) exceeding the range declared in the specification. The intra-and inter-batch CVs of the remaining reagents were all smaller than those declared in their respective specifications. The linear ranges of domestic reagents and imported ones have achieved the linear ranges declared by each manufacturer. There were no statistical differences on the measurements between the reagents from open bottle of 30 days and the corresponding new ones for 40 reagents( P>0.05). The test values of domestic reagents and imported reagents after exchange of different batches of calibrators were within the ranges declared by each manufacturer. Both domestic reagents and imported reagents have passed the accuracy verification. Conclusions:The performance index of 27 biochemical detection indicators of the three domestic manufacturers are basically consistent with those of imported reagents, meeting the requirements of clinical biochemical laboratories. However, the bottle opening stability and anti-interference performance of some detection reagents needs to be improved.
7.Study on artificial intelligence-based ultrasonic-assisted diagnosis for developmental dysplasia of the hip
Xiwei SUN ; Qingjie WU ; Zhiye GUAN ; Xiaogang HE ; Jun SUN ; Jihong FANG ; Fang YANG ; Yudong LIN ; Liang YUAN ; Kang XIE ; Jianyi JIANG ; Chuanbin LIU ; Hongtao XIE ; Jingyuan XU ; Sicheng ZHANG
Chinese Journal of Orthopaedics 2022;42(16):1084-1092
Methods:Two thousand standard sections images werre collected from 2 000 clinical retrospective pediatric hip ultrasound videos from January 2019 to January 2021. All standard sections were annotated by the annotation team through the self-designed software based on Python 3.6 environment for image cross-media data annotation and manual review standardization process with unified standards. Among them, 1 753 were randomly selected for training the deep learning system, and the remaining 247 were used for testing the system. Further, 200 standard sections were randomly selected from the test set, and 8 clinicians independently completed the film reading annotation. The 8 independent results were then compared with the AI results.Results:The testing set consists of 247 patients. Compared with the clinician's measurements, the area under the receiver operating characteristic curve (AUC) of diagnosing hip joint maturity was 0.865, the sensitivity was 76.19%, and the specificity was 96.9%. The AUC of AI system interpretation under Graf detailed typing was 0.575, the sensitivity was 25.90%, the specificity was 89.10%. The 95% LoA of α-angle determined by Bland-Altman method, of -4.7051° to 6.5948° ( Bias -0.94, P<0.001), compared with clinicians' measurements. The 95% LoA of β-angle, of -7.7191 to 6.8777 ( Bias -0.42, P=0.077). Compared with those from 8 clinicians, the results of AI system interpretation were more stable, and the β-angle effect was more prominent. Conclusion:The AI system can quickly and accurately measure the Graf correlation index of standard DDH ultrasonic standard diagnosis plane.
8.Reproducibility analysis of quantitative susceptibility mapping of cerebral subcortical nuclei in healthy adults.
Huan XU ; Qinglin MENG ; Wenping FAN ; Xue WANG ; Mengqi LIU ; Zhiye CHEN
Journal of Southern Medical University 2020;40(12):1810-1815
OBJECTIVE:
To investigate the intra- and inter-scanner reproducibility of quantitative susceptibility mapping (QSM) of cerebral subcortical nuclei in healthy adults.
METHODS:
QSM was performed in 21 healthy adults on two different 3.0T MR scanners, and the region of interest (ROI) method was used to measure the magnetic susceptibility value of the left subcortical nuclei (the head of the caudate, putamen, globus pallidus, thalamus, substantia nigra and red nucleus). The intraclass correlation coefficient (ICC) and Bland-Altman method were used to evaluate the inter-scanner and intra-scanner reliability.
RESULTS:
The ICCs of the susceptibility value ranged from 0.90 to 0.99 for all the subcortical gray nuclei except for the head of the caudate nucleus measured on the same MR scanner by the same observer. Bland-Altman analysis revealed that the points with susceptibility differences for all the subcortical gray nuclei except for substantia nigra located in the 95% CI of limits of agreement for the same MR scanner. The ICCs of the susceptibility value for the inter-scanner was 0.49 (0.08-0.75) for the head of the caudate nuleus, 0.80 (0.57-0.91) for the putamen, 0.77 (0.51-0.90) for the globus pallidus, 0.78 (0.54-0.91) for the thalamus, 0.80 (0.56-0.91) for the substantia nigra and 0.93 (0.83-0.97) for the red nucleus. The points with susceptibility difference (95.2%, 20/21) located in the 95% CI of limits of agreement for the putamen and the thalamus measured on two different MR scanners.
CONCLUSIONS
The intra-scanner reproducibility of QSM of the subcortical gray nuclei is superior to the inter-scanner reproducibility in healthy adults.
Adult
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Brain/diagnostic imaging*
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Gray Matter
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Humans
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Iron
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Magnetic Resonance Imaging
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Reproducibility of Results
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Substantia Nigra/diagnostic imaging*
9.Multicystic Encephalomalacia:Report of One Case.
Huan XU ; You LIU ; Xue WANG ; Wenping FAN ; Zhiye CHEN
Acta Academiae Medicinae Sinicae 2019;41(6):866-870
The magnetic resonance imaging findings of multicystic encephalomalacia are featured by bilateral frontal large cystic lesion with corpus callosum involvement,evident heterogeneous enhancement of the lesion margin,ring hyperintensity on diffusion weighted imaging,and high choline peak and low N-acetylaspartate peak of the enhanced lesion margin on magnetic resonance spectroscopy.This article reports a case of multicystic encephalomalacia.
Corpus Callosum
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Encephalomalacia
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Humans
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Magnetic Resonance Imaging
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Magnetic Resonance Spectroscopy
10.Long-term protection of infants against hepatitis B by neonatal immunoprophylaxis born from mothers infected with hepatitis B virus
Yanjing RUI ; Yimin DAI ; Yaning ZHENG ; Mingzhe NING ; Zhiye XU ; Zhiqun WANG ; Yali HU ; Yihua ZHOU
Chinese Journal of Applied Clinical Pediatrics 2018;33(22):1724-1726
Objective To evaluate the long-term efficacy of neonatal immunoprophylaxis in children born from mothers infected with hepatitis B virus (HBV),and to clarify whether a booster vaccination is required.Methods Totally 252 children of HBV infected mothers,who were negative for hepatitis B surface antigen (HBsAg) tested in Nanjing Drum Tower Hospital in 2012,were enrolled to participate in this study from July to September,2017.Revaccination of hepatitis B vaccine was recorded and other relevant informations were collected.HBV serologic markers were detected in each child.Results Totally 198 children (78.6%) were followed up.They were (8.4 ± 2.2) years old and 112 cases were boys.All 198 children were negative for both HBsAg and hepatitis B core antibody (anti-HBc).The overall positive rate of hepatitis B surface antibody (anti-HBs) (≥ 10 IU/L) was 65.7%.During period of 2012 to 2017,53 children were boosted with hepatitis B vaccine.Their median anti-HBs titer in 2017 was higher than that in 2012 (327.95 IU/L vs.158.01 IU/L),and the difference was significant (Z =-4.480,P <0.05).The other 145 children were not revaccinated,their median anti-HBs titer was decreased from 214.19 IU/L in 2012 to 70.49 IU/L in 2017,and the difference was significant (Z =-6.575,P < 0.05).Of 145 children who were not revaccinated,25 cases had anti-HBs levels < 10 IU/L and 120 cases ≥ 10 IU/L in 2012,and the other 47 cases also showed the antibody < 10 IU/L in 2017,but none of them was infected with HBV.Conclusions Neonatal immunoprophylaxis in infants from HBV-infected can provide long-term protection against hepatitis B.The children with anti-HBs < 10 IU/L are still immune to HBV and booster vaccination for them seems unnecessary.

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