1.Self-therapeutic metal-based nanoparticles for treating inflammatory diseases.
Ruifang HAN ; Yu XIAO ; Qianqian BAI ; Chung Hang Jonathan CHOI
Acta Pharmaceutica Sinica B 2023;13(5):1847-1865
Inflammatory diseases are key contributors to high mortality globally and adversely affect the quality of life. Current treatments include corticosteroids or nonsteroidal anti-inflammatories that may cause systemic toxicity and biologics that may increase the risk of infection. Composite nanoparticles that bear not only the drug payload but also targeting ligands for delivery to inflammation sites at lowered systemic toxicity are established in the nanomedicine field, but their relatively large size often leads to systemic clearance. Metal-based nanoparticles with intrinsic anti-inflammatory properties represent attractive alternatives. They are not only designed to be compact for crossing biological barriers (with the nanoparticle serving as a dual carrier and drug), but also support label-free tracking of their interactions with cells. The review commences with an outline of the common inflammatory diseases, inflammatory pathways involved, and conventional drug-loaded nanoparticles for anti-inflammation. Next, the review features the emerging applications of self-therapeutic metal-based nanoparticles (e.g., gold, coper oxide, platinum, ceria, and zinc oxide) for managing inflammatory diseases in animals over the past three years, focusing on therapeutic outcomes and anti-inflammatory mechanisms. The review concludes with an outlook on the biodistribution, long-term toxicity, and clinical translation of self-therapeutic metal-based nanoparticles.
2.Effects of gibberellin priming on seedling emergence and transcripts involved in mesocotyl elongation in rice under deep direct-seeding conditions.
Ya WANG ; Yuetao WANG ; Ruifang YANG ; Fuhua WANG ; Jing FU ; Wenbo YANG ; Tao BAI ; Shengxuan WANG ; Haiqing YIN
Journal of Zhejiang University. Science. B 2021;22(12):1002-1021
Mesocotyl elongation is a key trait influencing seedling emergence and establishment in direct-seeding rice cultivation. The phytohormone gibberellin (GA) has positive effects on mesocotyl elongation in rice. However, the physiological and molecular basis underlying the regulation of mesocotyl elongation mediated by GA priming under deep-sowing conditions remains largely unclear. In the present study, we performed a physiological and comprehensive transcriptomic analysis of the function of GA priming in mesocotyl elongation and seedling emergence using a direct-seeding
3.Chromosomal abnormalities in spontaneous miscarriage specimens detected by combinatorial probe anchor synthesis?based high?throughput low coverage whole genome sequencing
Xiaohua WANG ; Ruifang BAI ; Yan ZHOU ; Hong DONG ; Yunpeng JI ; Dongxia HOU ; Wurigumula ; Xiaoling YANG ; Xiaoping JI
Chinese Journal of Obstetrics and Gynecology 2019;54(12):808-814
Objective To evaluate the application of combinatorial probe anchor synthesis (cPAS)?based high?throughput low coverage whole genome sequencing in chromosomal aberration detection in spontaneous miscarriage. Methods From September 2015 to May 2017, spontaneous miscarriage samples were collected from Inner Mongolia Maternal and Child Health Care Hospital. Those samples were further analyzed with two independent methods, fluorescence in situ hybridization (FISH) and low coverage whole genome sequencing on the BGISEQ?500 high?throughput platform. The performance of low coverage whole genome sequencing was assessed by comparing to FISH results. Results In 595 spontaneous miscarried specimens, low coverage whole genome sequencing revealed 144 cases (24.2%, 144/595) chromosomal abnormalities, of which a subset of 137 cases (23.0%, 137/595) were detected as aneuploidies, 2 cases (0.3%, 2/595) as mosaicisms and 5 cases (0.8%, 5/595) as copy number variation (≥5 Mb). Conclusion cPAS?based high?throughput low coverage whole genome sequencing is a reliable method in detecting chromosomal aberrations inspontaneous abortion tissues, including chromosome aneuploidies, mosaicisms and copy number variation (≥5 Mb).
4. Chromosomal abnormalities in spontaneous miscarriage specimens detected by combinatorial probe anchor synthesis-based high-throughput low coverage whole genome sequencing
Xiaohua WANG ; Ruifang BAI ; Yan ZHOU ; Hong DONG ; Yunpeng JI ; Dongxia HOU ; Rigumula WU ; Xiaoling YANG ; Xiaoping JI
Chinese Journal of Obstetrics and Gynecology 2019;54(12):808-814
Objective:
To evaluate the application of combinatorial probe anchor synthesis (cPAS)-based high-throughput low coverage whole genome sequencing in chromosomal aberration detection in spontaneous miscarriage.
Methods:
From September 2015 to May 2017, spontaneous miscarriage samples were collected from Inner Mongolia Maternal and Child Health Care Hospital. Those samples were further analyzed with two independent methods, fluorescence in situ hybridization (FISH) and low coverage whole genome sequencing on the BGISEQ-500 high-throughput platform. The performance of low coverage whole genome sequencing was assessed by comparing to FISH results.
Results:
In 595 spontaneous miscarried specimens, low coverage whole genome sequencing revealed 144 cases (24.2%, 144/595) chromosomal abnormalities, of which a subset of 137 cases (23.0%, 137/595) were detected as aneuploidies, 2 cases (0.3%, 2/595) as mosaicisms and 5 cases (0.8%, 5/595) as copy number variation (≥5 Mb).
Conclusion
cPAS-based high-throughput low coverage whole genome sequencing is a reliable method in detecting chromosomal aberrations inspontaneous abortion tissues, including chromosome aneuploidies, mosaicisms and copy number variation (≥5 Mb).
5.Technical operation criteria and clinical application guidelines for pediatric nuclear medicine
Yue CHEN ; Jigang YANG ; Fuqiang SHAO ; Ruifang ZHAO ; Xuemei WANG ; Peng XIE ; Bin LIU ; Hua PANG ; Ha WU ; Yaming XIA ; LI BAI
Chinese Journal of Medical Imaging Technology 2017;33(10):1591-1595
The technical operation criteria and clinical application guidelines for pediatric nuclear medicine include information related to the preparations,precautions,responsibilities of nuclear personnel,dosage of radiopharmaceutical,history-taking,imaging protocol,as well as indication and safety,focusing primarily on the usual pediatric nuclear medicine examinations.The purpose of the criteria and guidelines is to offer nuclear medicine physicians a framework that could prove practical and helpful in daily clinical practice.
6.Clinical significance of HER-2 protien overexpression and HER-2 gene dysregulation in non-small cell lung cancer
Xiaogang WANG ; Zhenwen CHEN ; Yanfeng XI ; Fei CHAI ; Yirong XU ; Jing LI ; Ruifang SUN ; Wei BAI
Cancer Research and Clinic 2016;28(1):21-27
Objective To investigate the dysregulation of HER-2 protein and gene in non-small cell lung cancer (NSCLC), and to identify the association between clinicopathological features,prognosis and HER-2 aberrations amongst protein and gene. Methods 140 NSCLC tissues (89 squamous cell carcinoma, 51 adenocarcinoma) with operative section and detailed case were taken from pathology department of Shanxi Cancer Hospital from Jan 2006 to Feb 2007, while 70 normal tissues were set as control group. Immunohistochemistry was applied to detect the state of HER-2 protein expression,and fluorescence in situ hybridization (FISH) was applied to test the status of gene amplification. Results In normal and NSCLC tissues, over-expression of HER-2 was detected in 0 case and 17 (12.14 %) cases (P < 0.05), respectively. The over-expression of HER-2 was associated with the pathological type of NSCLC, which was detected more frequently in adenocarcinoma (χ2 = 4.19, P = 0.04), rather than the gender, age, smoke history, clinical stages, and lymphatic metastasis of patients. 40 (28.57 %) cases presented HER-2 gene copy number ≥3, including 6 (4.29 %) patients with HER-2 gene amplification, 34 (24.29 %) patients with HER-2 gene multicopy. HER-2 gene amplification was associated with the pathological type (P = 0.024), smoke history (P = 0.048) and age (P = 0.015), rather than lymphatic, gender, clinical stages. None clinicopathological features were presented correlation with HER-2 gene multicopy (P > 0.05). There was no significantly difference in survival between patients with and without HER-2 protein over-expression and HER-2 gene dysregulation (P > 0.05). HER-2 protein over-expression was associated with HER-2 gene amplification (P > 0.05), while no relationship between HER-2 protein overexpression and HER-2 gene multicopy (P < 0.01). Conclusions The over-expression of HER-2 is related to pathological type of NSCLC with more frequent expression in adenocarcinoma. The incidence rate of HER-2 gene amplification in patients with adenocarcinoma histology, never-smokers, and young age is high. The HER-2 protein over-expression and gene dysregulation show no relation with the prognosis of NSCLC.
7.Significance of C-myc expression in T-lymphoblastic lymphoma/leukemia and its relation with prognosis.
Yanhua ZHANG ; Jing LI ; Yanfeng XI ; E-mail: XYF609@SOHU.COM. ; Wenqi BAI ; Wei BAI ; Ruifang SUN
Chinese Journal of Pathology 2015;44(8):571-577
OBJECTIVETo study the C-myc gene and protein in T lymphoblastic lymphoma/leukemia (T-LBL/ALL) and its relationship to prognosis.
METHODS60 cases of T-LBL/ALL with follow-up data were studied by using immunohistochemical EnVision method for CD1a, CD3, εCD3, CD7, CD10, CD34, CD43, CD45RO, CD99, TDT, CD20, CD23, MPO, Ki-67 and C-myc. 20 cases of reactive lymph nodes were selected as normal control group of C-myc gene and protein. Fluorescence in-situ hybridization (FISH) for C-myc gene (located on chromosome8q24) was performed to detect its breakage and gain.
RESULTSAmong the 60 cases of T-LBL/ALL, immunohistochemistry results showed:the percentages of tumor cells expression of CD1a, CD3, εCD3, CD7, CD10, CD34, CD43, CD45RO, CD99 and TDT were 38.3% (23/60), 75.0% (45/60), 45.0% (27/60), 95.0% (57/60), 36.7% (22/60), 23.3% (14/60), 60.0% (36/60), 41.7% (25/60), 96.7% (58/60) and 93.3% (56/60). Separately, while CD20, CD23 and MPO were all negative. A figure of Ki-67 expression ≤ 80% was found in 36 cases and > 80% was found in 24 cases. The positive rate of C-myc protein was 66.7% (40/60) in 60 cases of T-LBL/ALL, was 0% (0/20) in 20 cases of reactivated lymphoid tissue (χ² = 26.67, P < 0.05). C-myc protein expression was positively correlated with the mediatinal width and Ki-67 index (P < 0.05). Fluorescence in-situ hybridization results showed that among the 60 cases of T-LBL/ALL, C-myc gene with breakage of 8q24 was detected in 6 cases (10.0%), and gains in 11 cases (18.3%). 20 cases of reactive lymph nodes were not occurred breakage and gains of C-myc gene. It is not significant between C-myc gene and protein expression (P > 0.05). In addition, in 60 cases of T-LBL/ALL, 12(20.0%) cases of C-myc protein and genetic abnormalities coexist. Log-rank analysis results: The prognosis of C-myc protein positive group was worse than negative group (P < 0.05). The relationship of C-myc gene and prognosis was not significant (P > 0.05). C-myc protein and genetic abnormality coexist is related with worse prognosis (P < 0.05). COX analysis results show that the C-myc protein positive group may be a independent poor prognosis factors (P < 0.05).
CONCLUSIONSC-myc may play an important role on the development of T-LBL/ALL. It may be a independent prognosis factors.
Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Leukocyte Common Antigens ; Lymph Nodes ; pathology ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; metabolism ; Prognosis ; Proto-Oncogene Proteins c-myc ; metabolism
8.Expression of CD68, cyclin D1 and rearrangement of bcl-6 gene are adverse prognostic factors in diffuse large B-cell lymphoma.
Xiaojie LIANG ; Jinfen WANG ; E-mail: JFENW@HOTMAIL.COM. ; Wei BAI ; Ruifang SUN
Chinese Journal of Pathology 2015;44(8):559-564
OBJECTIVETo study expression of CD68, cyclin D1 protein and rearrangement of bcl-6 gene impact on the prognosis of diffuse large B-cell lymphoma (DLBCL).
METHODSGets paraffin samples of the 105 cases DLBCL with the detailed follow-up information, and were studied by using immunohistochemical EnVision method for CD3, CD10, CD20, CD68, cyclin D1, bcl-6, MUM 1, SOX-11 immunolabeling. The DLBCL were classified into germinal center B cell-like (GCB) subtypes and non-germinal center B cell-like (non-GCB) subtypes according to Hans'algorithm. Application of fluorescence in situ hybridization (FISH) technique to detect the bcl-6 gene rearrangement. The relationship between CD68, cyclin D1 protein, the bcl-6 gene and the curative effect of chemotherapy and survival was analyzed using statistical software. Respectively by GCB type, non-GCB type immune phenotype and CHOP, R-CHOP chemotherapy group, compare the curative effects.
RESULTS105 patients had GCB 19 cases (18.1%), non-GCB 86 cases (81.9%), CD68 expression was 18 cases (17.1%), cyclin D1 high expression 36 cases (34.3%), bcl-6 gene rearrangement in 21 cases (21.9%), there is no correlation among the three (P > 0.05). One-way analysis of variance showed that age ≤ 60 years, clinical stage I-II, IPI score 0 to 2 points, LDH (U/L) < 245 IU/L,GCB subtypes, R-CHOP therapy, the prognosis of patients with better (P < 0.05), But gender, primary site no correlation with prognosis (P > 0.05). CD68, cyclin D1 high expression, bcl-6 rearrangement had poor prognosis (P < 0.05). Stratification analysis results show GCB-type or non-GCB type with high expression of CD68 contrast alloimmune phenotype groups had a poor prognosis, non-GCB type with high expression of cyclin D1 and rearrangement of bcl-6 gene had a poor prognosis (P < 0.001, P = 0.02). Treatment scheme of layered display, the CHOP treatment, significantly correlated with overall survival with high expression of CD68, cyclin D1 (P < 0.05), the R-CHOP treatment, there was no statistically significant difference between CD68, cyclin D1 high expression and overall survival (P = 0.428 and 0.168). Multivariate COX model analysis showed that high expression of CD68 (P = 0.026), high expression of cyclin D1 (P = 0.003) and high levels of LDH (P = 0.005) were adverse prognostic factors independent.
CONCLUSIONShigh expression of CD68, cyclin D1 and rearrangement of bcl-6 gene suggests poor prognosis, CD68, cyclin D1 protein and bcl-6 gene can be used as a prognostic indicator in patients with DLBCL.
Antibodies, Monoclonal, Murine-Derived ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; B-Lymphocytes ; classification ; Cyclin D1 ; metabolism ; Cyclophosphamide ; DNA-Binding Proteins ; genetics ; Doxorubicin ; Gene Rearrangement ; Germinal Center ; cytology ; Humans ; In Situ Hybridization, Fluorescence ; Lymphoma, Large B-Cell, Diffuse ; diagnosis ; Prednisone ; Prognosis ; Proto-Oncogene Proteins c-bcl-6 ; Vincristine
9.Expression of c-myc in anaplastic large cell lymphoma and its significance
Fei CHAI ; Zhenwen CHEN ; Yanfeng XI ; Ruifang SUN ; Wei BAI ; Jing LI ; Yirong XU
Journal of Leukemia & Lymphoma 2015;24(4):238-244
Objective To investigate the protein expression and genetic alterations of c-myc in primary systemic anaplastic large cell lymphoma (ALCL) and discuss its relationship with clinicopathologic features and immunophenotypes.Methods 87 cases of ALCL were selected.Immunohistochemical method was used to detect the protein expression of c-myc,ALK,CD3,CD10,CD20,CD30 and EMA.c-myc and ALK genetic alterations were detected by using fluorescence in situ hybridization (FlSH).The interrelationships between protein expression,genetic alterations and clinicopathological parameters were analysed statistically.Results Immunohistochemical results:of 87 cases,ALK protein was expressed in 54 cases (62.1%).c-myc protein was expressed in 27 cases (31.0 %).ALK and c-myc were co-expressed in 20 cases (23.0 %).c-myc protein expression,ALK and c-myc co-expression increased with the upgrade of ALCL clinical stages,and the expression was higher in International Prognostic Index (IPI) high-risk groups than in low-risk groups (P < 0.05).FISH test results:of 87 ALCL cases,there were 50 cases (57.5 %) of ALK rearrangements and 19 cases (21.8 %) of ALK aneuploidy.c-myc rearrangement was detected in none of 87 ALCL cases,but there was aneuploidy in 19 cases (21.8 %).The differences of c-myc aneuploidy in ALK positive and negative groups were statistically insignificant (P > 0.05),while they were statistically significant in c-myc groups (P < 0.05) and in different IPI groups (P < 0.05).Conclusion c-myc protein expression and aneuploidy were related with ALCL clinical stages and IPI,which could be used as an indicator of estimating ALCL malignant degree and predicting prognosis.
10.The relationship between expression of Her-2 and human papillomavirus and clinicopathological features in esophageal and stomach multiple primary cancers
Xialin ZHANG ; Jianmin LI ; Ruifang SUN ; Wei BAI
Cancer Research and Clinic 2015;(9):597-601
Objective To analyze the relationship between expression of Her-2 protein and the infection of human papillomavirus (HPV) and clinicopathological features in upper gastrointestinal multiple primary cancers, and to explore the relationship between the different histological malignancies in a single-system. Methods 39 patients were primary esophageal squamous cell carcinoma and gastric/cardia adenocarcinoma. By using immunohistochemistry (IHC) methods, the expression of Her-2 protein in 39 cases of multiple primary cancers specimens were examined, and by using insitu hybridization (ISH) technology, the infection of HPV in the same ones were detected. Results The over-expression of Her-2 protein in esophageal squamous cell carcinoma was not significantly relative to the degree of differentiation, the depth of penetration, the lymph node metastasis and the patientsˊage and gender (P> 0.05). The over-expression of Her-2 protein in gastric adenocarcinoma was closely correlated to the invasion depth and lymph node metastasis (P<0.05), no obvious correlation with the factors of patientsˊage and gender and the degree of differentiation (P > 0.05). The infection of HPV in esophageal squamous cell carcinoma and gastric adenocarcinoma was not significantly relative to the degree of differentiation, the depth of penetration,the lymph node metastasis, and the age and gender of the patients (P> 0.05). In the upper gastrointestinal multiple primary cancers, the Her-2 protein over-expression had the consistency (κ= 0.56, P< 0.05). Meanwhile, the HPV-DNA expression also had the consistency (κ=0.80, P<0.05). Conclusion Both Her-2 protein and HPV expression show the consistency in upper gastrointestinal multiple primary cancers,which suggests that Her-2 protein and HPV may be the common oncogenic factors for both esophageal squamous cell carcinoma and gastric adenocarcinoma.

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