1.Tauroursodeoxycholic Acid Inhibits Neurogenic Heterotopic Ossification by Inducing Macrophage M2 Polarization and Upregulating IL-1β Secretion
Jiewen CHEN ; Hongxi LAI ; Yilong DENG ; Tianjun CHEN ; Shunying HUANG ; Feng YE ; Bingde ZHAO ; Shudong CHEN
Journal of Sun Yat-sen University(Medical Sciences) 2026;47(4):690-698
ObjectiveTo investigate the inhibitory effect of tauroursodeoxycholic acid (TUDCA) on neurogenic heterotopic ossification (NHO) after spinal cord injury and its potential mechanism. MethodsSPF-grade male C57BL/6 mice were used to establish an NHO model. The mice were randomly divided into three groups: sham operation group (laminectomy only), NHO model group (spinal cord injury + intramuscular injection of cardiotoxin), and TUDCA treatment group (NHO model + daily intragastric administration of TUDCA at 200 mg/kg for 4 consecutive weeks). The area and maturity of heterotopic ossification were quantitatively assessed by micro-computed tomography(micro-CT) and hematoxylin-eosin(H&E) staining. Flow cytometry was used to quantify the interleukin(IL)-1β secretion level of M2 macrophages. RAW264.7 macrophages were cultured in vitro and divided into control, tumor necrosis factor(TNF)α, and TNFα+TUDCA (200 μmol/L) groups to detect the expression level of the polarization marker CD206. Additionally, macrophages were divided into control, TUDCA 200 μmol/L, and TUDCA 400 μmol/L groups to assess the IL-1β secretion level. ResultsCompared with the NHO group, the bone volume in the TUDCA-treated group was significantly reduced (12.69±1.13 vs. 7.647±1.19, P=0.003). Compared with the TNFα group, qPCR results showed that the expression of the M2 macrophage marker CD206 was significantly upregulated in the TNFα+TUDCA group (0.55±0.019,1.11±0.023, P<0.001). Compared with the control group, ELISA results showed that TUDCA stimulation of macrophages significantly upregulated IL-1β secretion (404.7±24.38 vs. 652.8±32.61, P=0.003 7). TUDCA administration upregulated IL-1β secretion by local muscle macrophages and inhibited heterotopic ossification formation. ConclusionsTUDCA might participate in inhibiting NHO formation by inducing M2 macrophage polarization and upregulating IL-1β secretion, thereby alleviating the development and progression of neurogenic heterotopic ossification after spinal cord injury. This finding provides experimental evidence for expanding the application of TUDCA in the treatment of complications following spinal cord injury.
2.Hernia repair patch:recent advances in material design and application
Jingyu CHEN ; Ge HONG ; Ning GUO ; Tianjun LIU
Chinese Journal of Tissue Engineering Research 2025;29(16):3494-3502
BACKGROUND:Patch surgery by tension-free repair has become the first choice for treatment of abdominal hernias in recent years because of its effectiveness in reducing postoperative pain and recurrence rates compared to traditional suturing.OBJECTIVE:To summarize the advantages and disadvantages associated with the application of different hernia repair patch materials.METHODS:CNKI,Google Scholar,and PubMed databases were searched using Chinese and English search terms"abdominal wall defect,hernia patches,hernia treatment"for articles published from January 2018 to February 2024.A few classic early-onset articles were used to express the development of hernia repair.After preliminary screening by reading titles and abstracts,those with low relevance to hernia repair materials were excluded.Finally,90 articles were included for summarization.RESULTS AND CONCLUSION:Hernia repair patches can be divided into non-absorbable synthetic patches,absorbable synthetic patches,natural polymer patches,and composite patches based on different materials used.Non-absorbable patches have high mechanical strength and are beneficial for tissue healing in hernia areas,but long-term presence of patches in the body may trigger immune responses,leading to inflammation and pain.Absorbable synthetic patches and natural polymer patches have good tissue compatibility and degradability,but their mechanical strength is unstable.Composite material patches inherit the excellent mechanical properties of traditional non-absorbable patches and reduce the risk of complications through the design of absorbable parts.In subsequent studies of hernia repair patch materials,researchers should focus on how to combine novel technologies with composite patches to form multifunctionalized hernia repair materials.
3.Application of cross bar technique in repair of pectus excavatum
Tianjun ZHOU ; Dan TIAN ; Ruiqing SHI ; Zihao ZHOU ; Jiming TANG ; Dongkun ZHANG ; Xiaosong BEN ; Guibin QIAO ; Gang CHEN ; Liang XIE
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(11):1572-1578
Objective To explore the indication, surgical technique, and clinical efficacy of the cross bar based on the Nuss procedure in pectus excavatum. Methods The clinical data of patients who underwent cross bar based on the Nuss procedure from August 2023 to August 2024 in Guangdong Provincial People's Hospital were retrospectively analyzed. Results A total of 88 patients including 85 males and 3 females with a mean age of (17.56±5.20) years were enrolled. All operations were performed successfully without intraoperative cardiac injury, pericardial injury or diaphragmatic injury. The mean operation time was (147.65±47.75) min. The mean blood loss was (13.30±9.06) mL. The mean postoperative hospitalization stay was (4.81±1.55) days, without perioperative death. Six (6.82%) patients developed early postoperative complications, including 3 patients of pleural effusion, 1 patient of subcutaneous hematoma, 1 patient of suffocation and 1 patient of bar rotation. The postoperative outcomes were excellent in 71 (80.68%) patients, good in 16 (18.18%) patients and moderate in 1 (1.13%) patient. The excellent and good rate was 98.86%. Conclusion The cross bar technique is safe and convenient, with satisfactory results. It is worth promoting in clinical application.
4.Hernia repair patch:recent advances in material design and application
Jingyu CHEN ; Ge HONG ; Ning GUO ; Tianjun LIU
Chinese Journal of Tissue Engineering Research 2025;29(16):3494-3502
BACKGROUND:Patch surgery by tension-free repair has become the first choice for treatment of abdominal hernias in recent years because of its effectiveness in reducing postoperative pain and recurrence rates compared to traditional suturing.OBJECTIVE:To summarize the advantages and disadvantages associated with the application of different hernia repair patch materials.METHODS:CNKI,Google Scholar,and PubMed databases were searched using Chinese and English search terms"abdominal wall defect,hernia patches,hernia treatment"for articles published from January 2018 to February 2024.A few classic early-onset articles were used to express the development of hernia repair.After preliminary screening by reading titles and abstracts,those with low relevance to hernia repair materials were excluded.Finally,90 articles were included for summarization.RESULTS AND CONCLUSION:Hernia repair patches can be divided into non-absorbable synthetic patches,absorbable synthetic patches,natural polymer patches,and composite patches based on different materials used.Non-absorbable patches have high mechanical strength and are beneficial for tissue healing in hernia areas,but long-term presence of patches in the body may trigger immune responses,leading to inflammation and pain.Absorbable synthetic patches and natural polymer patches have good tissue compatibility and degradability,but their mechanical strength is unstable.Composite material patches inherit the excellent mechanical properties of traditional non-absorbable patches and reduce the risk of complications through the design of absorbable parts.In subsequent studies of hernia repair patch materials,researchers should focus on how to combine novel technologies with composite patches to form multifunctionalized hernia repair materials.
6.Bioinformatics analysis of ureaplasma urealyticum UP3-RS02445 and the preparation of monoclonal antibodies.
Hengxin CHEN ; Xiaohui JIA ; Yahui LI ; Yan ZHOU ; Tianjun JIA ; Ping LI
Chinese Journal of Cellular and Molecular Immunology 2024;40(11):1011-1017
Objective To make the bioinformatics analysis of Ureaplasma parvum UP3-RS02445 and prepare monoclonal antibody (mAb) against UP3-RS02445. Methods The biological characteristics of UP3-RS02445 protein were predicted by bioinformatics software. The UP3-RS02445 prokaryotic expression plasmid was constructed and the corresponding protein expression was induced by isopropyl-β-D-thiogalactoside (IPTG). Thus the expressed protein was used as immunogen to immunize female BALB/c mice. Hybridoma cell technology was used to prepare the monoclonal antibody against UP3-RS02445. The specificity and titer of monoclonal antibody were detected by Western blot and ELISA respectively. The subclass of heavy chain and subtype of light chain were identified by monoclonal antibody subtype identification test strip. Results Bioinformatics analysis showed that UP3-RS02445 protein was composed of 201 amino acids, without transmembrane domain and signal peptide, and belongs to non-secretory proteins. The recombinant prokaryotic plasmid of UP3-RS02445 was successfully constructed and the recombinant protein could be induced in large amount. After cell fusion, two hybridoma cells (A1H5 and A4E2) secreting UP3-RS02445 mAb were screened by ELISA and Western blot. The results of ELISA showed that the titers of monoclonal antibodies were 1:2560. Western blot and Immunofluorescence technique both indicated that the antibodies could bind specifically to the UP3-RS02445 protein. The heavy chain and light chain of the two mAbs were IgG1 and kappa subtypes respectively. Conclusion We prepared the UP3-RS02445 monoclonal antibodies with well specificity and high titer which might lay foundations for the subsequent development of UP diagnostic reagents and the functional study of protein.
Antibodies, Monoclonal/immunology*
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Animals
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Mice, Inbred BALB C
;
Female
;
Computational Biology/methods*
;
Mice
;
Ureaplasma urealyticum/genetics*
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Bacterial Proteins/genetics*
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Antibody Specificity
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Enzyme-Linked Immunosorbent Assay
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Hybridomas/immunology*
7.H19 recruited N 6 -methyladenosine (m 6 A) reader YTHDF1 to promote SCARB1 translation and facilitate angiogenesis in gastric cancer.
Rumeng BAI ; Miaomiao SUN ; Yuanyuan CHEN ; Shuaishuai ZHUO ; Guoxin SONG ; Tianjun WANG ; Zhihong ZHANG
Chinese Medical Journal 2023;136(14):1719-1731
BACKGROUND:
Angiogenesis is described as a complex process in which new microvessels sprout from endothelial cells of existing vasculature. This study aimed to determine whether long non-coding RNA (lncRNA) H19 induced the angiogenesis of gastric cancer (GC) and its possible mechanism.
METHODS:
Gene expression level was determined by quantitative real-time polymerase chain reaction and western blotting. Cell counting kit-8, transwell, 5-Ethynyl-2'-deoxyuridine (EdU), colony formation assay, and human umbilical vein endothelial cells (HUVECs) angiogenesis assay as well as Matrigel plug assay were conducted to study the proliferation, migration, and angiogenesis of GC in vitro and in vivo . The binding protein of H19 was found by RNA pull-down and RNA Immunoprecipitation (RIP). High-throughput sequencing was performed and next Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted to analyze the genes that are under H19 regulation. Methylated RIP (me-RIP) assay was used to investigate the sites and abundance among target mRNA. The transcription factor acted as upstream of H19 was determined through chromatin immunoprecipitation (ChIP) and luciferase assay.
RESULTS:
In this study, we found that hypoxia-induced factor (HIF)-1α could bind to the promoter region of H19, leading to H19 overexpression. High expression of H19 was correlated with angiogenesis in GC, and H19 knocking down could inhibit cell proliferation, migration and angiogenesis. Mechanistically, the oncogenic role of H19 was achieved by binding with the N 6 -methyladenosine (m 6 A) reader YTH domain-containing family protein 1 (YTHDF1), which could recognize the m 6 A site on the 3'-untransated regions (3'-UTR) of scavenger receptor class B member 1 (SCARB1) mRNA, resulting in over-translation of SCARB1 and thus promoting the proliferation, migration, and angiogenesis of GC cells.
CONCLUSION
HIF-1α induced overexpression of H19 via binding with the promoter of H19, and H19 promoted GC cells proliferation, migration and angiogenesis through YTHDF1/SCARB1, which might be a beneficial target for antiangiogenic therapy for GC.
Humans
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Cell Line, Tumor
;
Cell Proliferation/genetics*
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Endothelial Cells/metabolism*
;
Gene Expression Regulation
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Gene Expression Regulation, Neoplastic/genetics*
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Hypoxia
;
MicroRNAs/genetics*
;
RNA
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RNA, Long Noncoding/metabolism*
;
RNA-Binding Proteins/metabolism*
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Scavenger Receptors, Class B/metabolism*
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Stomach Neoplasms/genetics*
8.CD103 +CD8 +T cells combined with neutrophil-to-lymphocyte ratio predict response to neoadjuvant chemoimmunotherapy in advanced oral squamous cell carcinoma
Bowen LI ; Siqi REN ; Suling CHEN ; Tianjun LAN ; Fan WU ; Jinsong LI
Chinese Journal of Stomatology 2023;58(12):1257-1264
Objective:To investigate the relationship between the expression of CD103 +CD8 +T cells in locally advanced oral squamous cell carcinoma (LA-OSCC), and the response to neoadjuvant chemoimmunotherapy (NACI). Methods:Thirty LA-OSCC patients from the Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, who underwent NACI from June 2020 to December 2022 were analyzed, including 16 responders and 14 non-responders. Using multiple immunofluorescence technique to stain sections of patients to verify the correlation between the expression of CD103 +CD8 +T cells and the efficacy of NACI. CD103 +CD8 +T cell density was counted using Inform and HALO software. The Spearman correlation coefficient in rank correlation is used to describe the correlation between CD103 +CD8 +T cell and neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-lymphocyte ratio (PLR), systemic immune inflammation index (SII) It′s effectiveness as a predictive marker to NACI was analyzed by receiver operator characteristic (ROC) curve analysis and decision curve analysis (DCA). Two-tailed t-test or Mann-Whitney U-test was used to compare data between two groups, and one-way ANOVA was used to compare data between multiple groups. SPSS 22.0 and GraphPad prism 9.0 software were used for statistical analysis and plotting of relevant statistical graphs such as histograms. P<0.05 was considered a statistically significant difference. Results:The density of CD103 +CD8 +T cells has expanded in advanced OSCC patients who are responsive to NACI. The CD103 +CD8 +T cell densities in the responsive and nonresponsive groups were 118.30(41.92, 197.80) pcs/mm 2 and 21.63(4.91, 71.92) pcs/mm 2 respectively, with statistically significant differences( U=52.00, P=0.012). CD103 +CD8 +T cell abundance was negatively correlated with NLR, dNLR, PLR, and SII ( P<0.05). ROC curve analysis showed that the AUC for predicting efficacy of NLR, dNLR, PLR, and SII were 0.781 ( P=0.009, 95% CI: 0.5715-0.9910), 0.671 ( P=0.105, 95% CI: 0.467-0.881), 0.679 ( P=0.020 95% CI: 0.549-0.951), 0.750 ( P=0.096, 95% CI: 0.461-0.896), respectively. The AUC for CD103 +CD8 +T cells alone was 0.861 ( P=0.013, 95% CI: 0.585-0.950), and the AUC of combining CD103 +CD8 +T cells with NLR was 0.896 ( P=0.025, 95% CI: 0.454-0.938). Conclusions:The density of CD103 +CD8 +T cells is expanded in advanced OSCC patients who are responsive to NACI. CD103 +CD8 +T cells positively predict favorable responses as a strong indicator to NACI in advanced OSCC patients. Co-interpretation of CD103 +CD8 +T cells and NLR value enhances the predictive accuracy of NACI in advanced OSCC patients.
9.Advances in lipid metabolism during Chlamydia infection
Lifang CHEN ; Rongrong ZHANG ; Tianjun JIA
Chinese Journal of Microbiology and Immunology 2021;41(6):479-483
Chlamydia, a gram-negative obligate intracellular pathogen, is a major cause of human reproductive tract, eye and respiratory tract infections. It replicates in a special membrane-binding chamber called inclusion and survives in the host′s hostile intracellular environment through secreting effectors, but requires host-derived lipids to grow and develop in the cells. Emerging evidences suggest that Chlamydia has evolved a variety of strategies to meet its lipid needs by interacting with host cell compartments and redirecting the transport pathway to its intracellular niche. This paper briefly described the pathway for obtaining host lipids and the mechanism of lipid metabolic during Chlamydia infection.
10.Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter trial.
Dongsheng WANG ; Binqing FU ; Zhen PENG ; Dongliang YANG ; Mingfeng HAN ; Min LI ; Yun YANG ; Tianjun YANG ; Liangye SUN ; Wei LI ; Wei SHI ; Xin YAO ; Yan MA ; Fei XU ; Xiaojing WANG ; Jun CHEN ; Daqing XIA ; Yubei SUN ; Lin DONG ; Jumei WANG ; Xiaoyu ZHU ; Min ZHANG ; Yonggang ZHOU ; Aijun PAN ; Xiaowen HU ; Xiaodong MEI ; Haiming WEI ; Xiaoling XU
Frontiers of Medicine 2021;15(3):486-494
Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.
Antibodies, Monoclonal, Humanized
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COVID-19/drug therapy*
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Humans
;
SARS-CoV-2
;
Treatment Outcome

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