1.Efficient strategies for microglia replacement in spinal cord injury models
Fanzhuo ZENG ; Yuxin LI ; Jiachen SUN ; Xinyang GU ; Shan WEN ; He TIAN ; Xifan MEI
Chinese Journal of Tissue Engineering Research 2024;28(7):1007-1014
BACKGROUND:As the incidence of spinal cord injury increases with the years and axon regeneration after spinal cord injury was very difficult.How to promote the recovery from spinal cord injury and improve the transplantation efficiency of stem cells and other therapeutic cells after spinal cord injury has been the focus of clinical and scientific research. OBJECTIVE:To establish the efficient transplantation and replacement of mouse spinal cord microglia in the spinal cord injury model. METHODS:CX3CR1 creER-/+::LSL-BDNF-/+-tdTomato mice,CX3CR1+/GFP mice,β-actin GFP mice and C57 BL/6J wild-type mice at 8-10 weeks of age were selected.According to the requirements of the experiment,they were randomly divided into six groups.(1)Sham operation group:eight C57 BL/6J wild-type mice were used when only the lamina was removed without injury.(2)Spinal cord contusion injury group:eight C57 BL/6J wild-type mice were used.(3)Spinal cord crush injury group:eight C57 BL/6J wild-type mice were used.(4)Conjoined symbiotic spinal cord strike injury group:β-actin GFP mice with green fluorescent blood were surgically stitched together with C57 BL/6J wild-type mice,using eight β-actin GFP mice and eight C57 BL/6J wild-type mice.(5)Mr BMT-X Ray group(using PLX5622 to eliminate the spinal microglia and bone marrow transplantation with X-ray radiation):Bone marrow cells from four CX3CR1 creER-/+::LSL-BDNF-/+-tdTomato mice were extracted and transplanted into eight C57 BL/6J wild-type mice for spinal cord injury modeling.(6)Mr BMT-Busulfan group(using PLX5622 to eliminate the spinal microglia and bone marrow transplantation with Busulfan):Bone marrow cells from four CX3CR1+/GFP mice were transplanted into eight C57 BL/6J wild-type mice.The percentage of cell transplantation replacement in this group was observed,and the spinal cord injury model was not established in this group.The sham operation group,spinal cord contusion injury group and spinal cord crush injury group were sampled by perfusion on day 14 after spinal cord injury.The conjoined symbiotic spinal cord strike injury group was sampled by perfusion on day 7 after spinal cord injury.Mr BMT-X Ray group was sampled by perfusion on day 28 after spinal cord injury.Mr BMT-Busulfan group was sampled by perfusion on day 28 after transplantation.The sampling site was a 1.2 cm long spinal cord with the T10 segment as the center.In the Mr BMT-X Ray group and Mr BMT-Busulfan group,additional mouse brain tissue was retained to see if it would lead to brain transplantation and replacement.The number and proportion of transplanted and replaced cells in the damaged area were measured using transgenic mice,symbiosis and immunofluorescence. RESULTS AND CONCLUSION:Compared with the traditional peripheral blood transplantation(9.8%)of mice in the conjoined symbiotic spinal cord strike injury group,the new transplantation methods,Mr BMT-X Ray and Mr BMT-Busulfan,could greatly improve the proportion of spinal microglia transplantation and replacement,which could reach 84.8%and 95.6%,respectively.The difference was significant(P<0.05).The results showed that Mr BMT-X Ray and Mr BMT-Busulfan could achieve efficient replacement of spinal microglia cells,and could improve the problems of low cell transplantation efficiency,few survival numbers and unclear differentiation of the traditional cell transplantation methods.In addition,Mr BMT-X Ray can only replace the microglia in the spinal cord,while Mr BMT-Busulfan could avoid brain inflammation and injury caused by X-ray radiation transplantation.
2.The distribution of biomarkers for Behcet syndrome and their clinical relevance in real-world studies
Jiachen LI ; Feng SUN ; Tian LIU
Chinese Journal of Preventive Medicine 2024;58(9):1341-1347
Objective:To explore the distribution of different biomarkers for Behcet′s syndrome (BS) and their correlation with distinct clinical phenotypes of BS patients in real-world studies.Methods:This study was a retrospective cross-sectional study. A total of 483 patients diagnosed with BS in the Department of Rheumatology and Immunology, Peking University People′s Hospital from 2019 to 2022 were enrolled. The baseline information and clinical features of the patients were recorded at their first diagnosis and tested the level of HLA-B51, several auto-antibodies, antistreptolysin-O(ASO), immune globulin, complement in blood serum and interleukin-6 (IL-6). Logistic regression was used to analyze the correlation of biomarkers and phenotypes.Results:Among BS patients, the number of positive cases for HLA-B51, anti-endothelial cell antibody (AECA), antinuclear antibodies (ANA) and ASO was 129, 115, 79 and 54, respectively. The positive rate of other biomarkers was less than 5.0%. About 12.6% of patients with BS had an increased level of IgA ( n=61), and 10.8% of patients had an increased level of IgG ( n=52). About 41.0% of patients had increased levels of IL-6 ( n=198), and 6.4% of patients had decreased levels of IgM ( n=31). About 11.2% of patients had decreased levels of C3 ( n=54), and 6.0% of patients had decreased levels of C4 ( n=29). Elevated IgA was a risk factor for the articular phenotype of BS ( OR=2.652, P=0.011). Decreased complement C4 was a risk factor for the neurological phenotype of BS ( OR=3.594, P=0.039). Positive ASO was a risk factor for the gastrointestinal phenotype of BS ( OR=2.578, P=0.041). Elevated IL-6 was a risk factor for the ocular phenotype of BS ( OR=7.560, P=0.016). Conclusion:HLA-B51 and AECA are common biomarkers in BS. Elevated IgA, decreased complement C4, positive ASO, and elevated IL-6 are risk factors for different phenotypes of BS.
3.Phylogenetic and antigenic analysis on hemagglutinin gene of influenza B virus (Victoria) in 2023-2024 surveillance season in Beijing
Guilan LU ; Jiachen ZHAO ; Weixian SHI ; Li ZHANG ; Yimeng LIU ; Zhaomin FENG ; Ying SUN ; Daitao ZHANG ; Xiaomin PENG
Chinese Journal of Experimental and Clinical Virology 2024;38(4):415-421
Objective:To disclose phylogenetic and antigenic characteristics of hemagglutinin (HA) gene of influenza B virus (Victoria) (BV) in the 2023-2024 influenza surveillance season in Beijing, and understand the matching with influenza vaccine component strain.Methods:Pharyngeal swab specimens from influenza like-illness (ILI) in the 2023-2024 influenza surveillance season were collected from surveillance network labs in Beijing and BV strains were isolated through MDCK or chicken embryo culture. After extracting nucleic acid, HA gene was amplified and sequenced. The nucleotide and amino acid sequence identity were conducted and the maximum likelihood method in Mega 5.0 software was used to construct the phylogenetic tree of HA gene. N-glycosylation sites of HA were performed online. Furthermore, three-dimensional structure of HA was available from SWISS-MODEL homologous modeling. Hemagglutination inhibition (HI) tests were performed to analyze antigenic characteristics of HA of BV strains.Results:Fifty-four BV strains were randomly selected to be analyzed further. Compared with the HA gene of this influenza season vaccine strain (B/Austria/1359417/2021), there are three amino acid mutations among all BV strains, two of which are located in two different antigenic determinants. Furthermore, the phylogenetic tree analysis revealed that only one subgroup of 1A.3a.2 was circulating simultaneously. All BV strains are located in Clade 1A.3a.2 subgroup, and in the same subgroup with that of the vaccine component BV strain in 2023-2024. All BV strains have the same glycosylation sites as that of the vaccine component BV strain in 2023-2024. Antigenic analysis showed that all BV strains were antigenically similar with its vaccine strain.Conclusions:In the 2023-2024 influenza surveillance season, the prevalent BV strains in the population in Beijing city are located in Clade 1A. 3a. 2 subgroup. The antigen matching between BV epidemic strains and vaccine BV components is relatively high during this surveillance season.
4.The distribution of biomarkers for Behcet syndrome and their clinical relevance in real-world studies
Jiachen LI ; Feng SUN ; Tian LIU
Chinese Journal of Preventive Medicine 2024;58(9):1341-1347
Objective:To explore the distribution of different biomarkers for Behcet′s syndrome (BS) and their correlation with distinct clinical phenotypes of BS patients in real-world studies.Methods:This study was a retrospective cross-sectional study. A total of 483 patients diagnosed with BS in the Department of Rheumatology and Immunology, Peking University People′s Hospital from 2019 to 2022 were enrolled. The baseline information and clinical features of the patients were recorded at their first diagnosis and tested the level of HLA-B51, several auto-antibodies, antistreptolysin-O(ASO), immune globulin, complement in blood serum and interleukin-6 (IL-6). Logistic regression was used to analyze the correlation of biomarkers and phenotypes.Results:Among BS patients, the number of positive cases for HLA-B51, anti-endothelial cell antibody (AECA), antinuclear antibodies (ANA) and ASO was 129, 115, 79 and 54, respectively. The positive rate of other biomarkers was less than 5.0%. About 12.6% of patients with BS had an increased level of IgA ( n=61), and 10.8% of patients had an increased level of IgG ( n=52). About 41.0% of patients had increased levels of IL-6 ( n=198), and 6.4% of patients had decreased levels of IgM ( n=31). About 11.2% of patients had decreased levels of C3 ( n=54), and 6.0% of patients had decreased levels of C4 ( n=29). Elevated IgA was a risk factor for the articular phenotype of BS ( OR=2.652, P=0.011). Decreased complement C4 was a risk factor for the neurological phenotype of BS ( OR=3.594, P=0.039). Positive ASO was a risk factor for the gastrointestinal phenotype of BS ( OR=2.578, P=0.041). Elevated IL-6 was a risk factor for the ocular phenotype of BS ( OR=7.560, P=0.016). Conclusion:HLA-B51 and AECA are common biomarkers in BS. Elevated IgA, decreased complement C4, positive ASO, and elevated IL-6 are risk factors for different phenotypes of BS.
5.Pharmacovigilance for Radiopharmaceuticals
Yue SUN ; Yuxuan ZHENG ; Zhenjiang ZHANG ; Yuxian ZHANG ; Ran ZHANG ; Chang LU ; Li ZHANG ; Ding LI ; Jiachen TU ; Jing XIE ; Huan ZHOU ; Jian GONG
Herald of Medicine 2024;43(10):1615-1619
Radiopharmaceuticals play an important role in the medical field,but they also carry certion risks and potential safety concerns.Medical institutions implement pharmacovigilance to ensure the safety of patients'drug use,including the safety of Radiopharmaceuticals.The operation and management of the pharmacovigilance system in the United States and the European Union are relatively mature.China can learn from their advanced concepts and establish our own radiopharmaciligence system.
6.A case report of multidisciplinary diagnosis and treatment of severe acute pancreatitis with severe abdominal infection and biliary stricture
Jiawen WU ; Rui KONG ; Jisheng HU ; Yan LUO ; Jiachen SHI ; Yuncheng HAN ; Bei SUN
Chinese Journal of General Surgery 2024;33(9):1529-1535
Severe acute pancreatitis(SAP)is a critical condition in general surgery settings,characterized by high mortality and poor prognosis.On February 28,2024,the Department of Hepatobiliary Surgery at the First Affiliated Hospital of Harbin Medical University admitted a 36-year-old male patient.The patient presented with"upper abdominal pain accompanied by fever for three months and jaundice of the skin and sclera for one week."Physical examination revealed 11 puncture tubes,and a palpable mass measuring 3 cm × 5 cm in the upper abdomen.Enhanced CT and magnetic resonance cholangiopancreatography indicated acute pancreatitis.The patient was diagnosed with"SAP,infectious pancreatic necrosis,and biliary stenosis."He had severe abdominal infection and complex postoperative complications,making treatment challenging.Consequently,a multidisciplinary team(MDT)consultation was initiated.After three rounds of MDT consulfation and freating,the patient ultimately recovered successfully and was discharged.This article reviews the MDT treatment process for this patient and summarizes the characteristics of this condition based on relevant literature to provide insights and experience for clinical practice.
7.Review on functional CT imaging for pretreatment assessment in gastric cancer
Tiezhu REN ; Qianqian CHEN ; Wenjuan ZHANG ; Juan DENG ; Xin'an SU ; Min XU ; Yuan XU ; Jiachen SUN ; Yufeng LI ; Junlin ZHOU
Chinese Journal of Medical Physics 2024;41(7):836-841
Both morbidity and mortality of gastric cancer are in the front rank among malignant tumors.At present,enhanced CT is served as an important imaging method for preoperative diagnosis and assessment of gastric cancer,but it is mostly based on morphological evaluation and unable to perform quantitative analysis.The functional imaging technology represented by energy spectral CT and CT perfusion imaging has a variety of quantitative parameters,which is expected to make up for the shortcomings of conventional CT.The review introduces the basic principles of energy spectral CT and CT perfusion imaging,and summarizes their applications in the diagnosis,pathological classification,grading,staging and efficacy prediction of gastric cancer,aiming to improve the understanding of functional CT imaging for the pretreatment assessment in gastric cancer.
8.Advances in Imaging of Genotype and Targeted Therapy Efficacy of Gastrointestinal Stromal Tumors
Jiachen SUN ; Tiezhu REN ; Yuan XU ; Junlin ZHOU
Chinese Journal of Medical Imaging 2024;32(7):741-746
Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal tract,and they are also genetically heterogeneous tumors.c-KIT gene or PDGFRA gene mutation is the main driving factor leading to its occurrence,and it is also one of the key factors affecting the treatment and prognosis of patients with GISTs.Imaging examination is non-invasive and can display tumors from multiple angles and directions,making it the main method for preoperative evaluation of GISTs.With the continuous development of imaging technology,non-invasive and definite genotyping of GISTs by imaging methods before surgery plays a positive role in the selection of targeted drugs and doses for patients and the evaluation of targeted treatment efficacy.This article reviews the imaging progress on the genotype of GISTs and the efficacy of targeted therapy.
9.Antitumor effects and mechanisms of action of chidamide combined with curcumin in the treatment of cutaneous T-cell lymphoma
Guanyu WANG ; Jiachen SUN ; Tingting LI ; Yimeng WANG ; Chunlei ZHANG
Chinese Journal of Dermatology 2024;57(8):728-738
Objective:To evaluate the efficacy and safety of chidamide combined with curcumin in the treatment of cutaneous T-cell lymphoma (CTCL) .Methods:Human CTCL cell lines HH and HuT-78 were cultured in vitro and treated with gradient concentrations of chidamide (0.4, 0.8, 1.6, 3.2, and 6.4 μmol/L) and curcumin (1.25, 2.5, 5, 10, and 20 μmol/L) alone or in combination, and the combination index (CI) of chidamide and curcumin for HH and HuT-78 cells was evaluated. Cultured HH/HuT-78 cells were divided into chidamide group (treated with 0.4 μmol/L chidamide), curcumin group (treated with 10 μmol/L curcumin), combination group (treated with 0.4 μmol/L chidamide + 10 μmol/L curcumin), and solvent control group (treated with dimethyl sulfoxide) ; after 48-hour treatment, the MTS assay was performed to evaluate the cell viability, flow cytometry to detect cell apoptosis and analyze cell cycle, and real-time quantitative PCR (RT-PCR) and Western blot analysis were conducted to determine the mRNA and protein expression of apoptosis-related genes nuclear factor (NF) -κB p65, B-cell lymphoma 2 (Bcl-2), and caspase-3, respectively. A tumor-bearing mouse model was established with HH cells in immunodeficient mice. These tumor-bearing mice were randomly divided into 4 groups: chidamide group (gavaged with 10 mg/kg chidamide), curcumin group (gavaged with 100 mg/kg curcumin), combination group, and solvent control group. The treatment was administered daily for 12 days, and body weight and tumor size were measured. On day 13, these mice were sacrificed, and tumor tissues were collected. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to detect apoptosis of tumor cells, and RT-PCR and Western blot analysis were conducted to determine the expression of apoptosis-related genes and proteins. Differences among multiple groups were analyzed using one-way analysis of variance, and multiple comparisons were performed using least significant difference- t test. Results:The CI values of chidamide (0.4 - 6.4 μmol/L) combined with curcumin (1.25 - 20 μmol/L) were all < 1, indicating a synergistic effect. After 48-hour treatment, the proliferation rates of HH and HuT-78 cells were significantly lower in the combination groups than in the chidamide groups and curcumin groups (all P < 0.05) ; HH and HuT-78 cells both showed significantly increased apoptosis rates in the combination groups compared with the chidamide groups, curcumin groups and control groups (HH cells: 70.47% ± 7.87% vs. 31.95% ± 9.43%, 37.23% ± 10.74%, 11.76% ± 5.65%, all P < 0.001; HuT-78 cells: 28.31% ± 1.70% vs. 21.29% ± 3.61%, 18.74% ± 1.82%, 3.18% ± 1.00%, all P < 0.001) ; in both HH and HuT-78 cells, the combination groups exhibited significantly increased caspase-3 mRNA expression and cleaved protein levels (all P < 0.05), but significantly decreased mRNA and protein expression of NF-κB p65 and Bcl-2 compared with the control groups, chidamide groups, and curcumin groups (all P < 0.05). On day 13 in the in vivo experiment, the tumor volume was significantly lower in the combination group (107.00 ± 43.10 mm 3) than in the control group (1 833.00 ± 281.20 mm 3), chidamide group (453.30 ± 91.71 mm 3), and curcumin group (548.50 ± 90.72 mm 3, all P < 0.05) ; the apoptosis level of tumor cells detected by TUNEL staining was significantly higher in the combination group than in the chidamide group, curcumin group, and control group (all P < 0.05) ; compared with the chidamide group, curcumin group, and control group, the combination group showed significantly increased expression of caspase-3 mRNA and cleaved caspase-3 protein (all P < 0.05), but significantly decreased mRNA and protein expression of NF-κB p65 and Bcl-2 (all P < 0.05). During the treatment period, there was no significant difference in the body weight of mice among the 4 groups ( P < 0.05) ; after sacrifice of the mice, no abnormalities were found in histopathological manifestations of their resected visceral tissues, blood routine test results, or liver and kidney function indicators. Conclusion:The combination of chidamide and curcumin had a synergistic antitumor effect on CTCL, which may be related to the inhibition of cell proliferation and induction of tumor cell apoptosis.
10.Artificial Intelligence in the Prediction of Gastrointestinal Stromal Tumors on Endoscopic Ultrasonography Images: Development, Validation and Comparison with Endosonographers
Yi LU ; Jiachuan WU ; Minhui HU ; Qinghua ZHONG ; Limian ER ; Huihui SHI ; Weihui CHENG ; Ke CHEN ; Yuan LIU ; Bingfeng QIU ; Qiancheng XU ; Guangshun LAI ; Yufeng WANG ; Yuxuan LUO ; Jinbao MU ; Wenjie ZHANG ; Min ZHI ; Jiachen SUN
Gut and Liver 2023;17(6):874-883
Background/Aims:
The accuracy of endosonographers in diagnosing gastric subepithelial lesions (SELs) using endoscopic ultrasonography (EUS) is influenced by experience and subjectivity. Artificial intelligence (AI) has achieved remarkable development in this field. This study aimed to develop an AI-based EUS diagnostic model for the diagnosis of SELs, and evaluated its efficacy with external validation.
Methods:
We developed the EUS-AI model with ResNeSt50 using EUS images from two hospitals to predict the histopathology of the gastric SELs originating from muscularis propria. The diagnostic performance of the model was also validated using EUS images obtained from four other hospitals.
Results:
A total of 2,057 images from 367 patients (375 SELs) were chosen to build the models, and 914 images from 106 patients (108 SELs) were chosen for external validation. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the model for differentiating gastrointestinal stromal tumors (GISTs) and non-GISTs in the external validation sets by images were 82.01%, 68.22%, 86.77%, 59.86%, and 78.12%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the external validation set by tumors were 83.75%, 71.43%, 89.33%, 60.61%, and 80.56%, respectively. The EUS-AI model showed better performance (especially specificity) than some endosonographers.The model helped improve the sensitivity, specificity, and accuracy of certain endosonographers.
Conclusions
We developed an EUS-AI model to classify gastric SELs originating from muscularis propria into GISTs and non-GISTs with good accuracy. The model may help improve the diagnostic performance of endosonographers. Further work is required to develop a multi-modal EUS-AI system.

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