1.Research progress in functional polarization of tumor-associated macrophages and targeting strategies
Bei WANG ; Wenbo LI ; Xuran ZHANG ; Weihong REN
Chinese Journal of Microbiology and Immunology 2024;44(3):265-273
Tumor-associated macrophages (TAMs) are the predominant immune cells in the tumor microenvironment (TME). They have been shown to play an important immunosuppressive role in the development of TME and promote tumor immune escape, growth and metastasis. It is a current research hotspot to regulate the functional polarization of TAMs through trained immunity (metabolic reprogramming, epigenetic remodeling) to affect the occurrence and development of tumors. Therefore, in-depth research in this field not only presents a more comprehensive perspective on the pathogenesis of immune-mediated diseases, but also can provide new strategies for clinical anti-tumor immunotherapy. This paper outlines the origin of TAMs and the phenotypes and mechanisms of TAMs polarization, discusses the mechanisms by which metabolic reprogramming and epigenetic remodeling regulate TAMs, summarizes the regulation of TAMs activation and polarization by them, and provides an overview of the progress in TAMs at the current stage of clinical practice, hoping to provide reference for the development of new immunoprevention and treatment strategies.
2.Research progress of related factors affecting poor response to wet age-related macular degeneration
Haitao PAN ; Ruizhuang LI ; Qiuli ZHANG ; Xuran CHEN
International Eye Science 2024;24(4):567-571
Wet age-related macular degeneration(wARMD)emerges as a primary contributor to irreversible vision impairment in the aging demographic. In clinical practice, anti-vascular endothelial growth factor(VEGF)therapies exhibit pronounced success in managing wARMD. However, in the actual clinical application, there are significant individual differences in the prognosis of anti-VEGF drug therapy, and some patients show poor response to the treatment, which may be related to the morphological differences of retinal layers in macular area, genetics, systemic conditions and other factors. It will help develop a more rational and individualized treatment plan to judge the prognosis of patients according to their different clinical manifestations in advance, so as to reduce overtreatment and the risk of retinal damage. In recent years, most studies on treatment response mainly focus on fundus morphology, genetics and so on. In this study, the relevant factors affecting adverse response to wARMD were reviewed, aiming to provide with more accurate treatment and prognostic monitoring programs for clinicians.
3.Effect of LAG3 deficiency on natural killer cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis
Rousu ZIBIGU ; Ainiwaer ABIDAN ; Duolikun ADILAI ; Yinshi LI ; Xuejiao KANG ; Qian YU ; Bingqing DENG ; Xuran ZHENG ; Maolin WANG ; Jing LI ; Hui WANG ; Chuanshan ZHANG
Chinese Journal of Schistosomiasis Control 2024;36(1):59-66
Objective To investigate the effect of LAG-3 deficiency (LAG3-/-) on natural killer (NK) cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis. Methods C57BL/6 mice, each weighing (20 ± 2) g, were divided into the LAG3-/- and wild type (WT) groups, and each mouse in both groups was inoculated with 3 000 E. multilocularis protoscoleces via the hepatic portal vein. Mouse liver and spleen specimens were collected 12 weeks post-infection, sectioned and stained with sirius red, and the hepatic lesions and fibrosis were observed. Mouse hepatic and splenic lymphocytes were isolated, and flow cytometry was performed to detect the proportions of hepatic and splenic NK cells, the expression of CD44, CD25 and CD69 molecules on NK cell surface, and the secretion of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin (IL)-4, IL-10 and IL-17A. Results Sirius red staining showed widening of inflammatory cell bands and hyperplasia of fibrotic connective tissues around mouse hepatic lesions, as well as increased deposition of collagen fibers in the LAG3-/-group relative to the WT group. Flow cytometry revealed lower proportions of mouse hepatic (6.29% ± 1.06% vs. 11.91% ± 1.85%, P < 0.000 1) and splenic NK cells (4.44% ± 1.22% vs. 5.85% ± 1.10%, P > 0.05) in the LAG3-/- group than in the WT group, and the mean fluorescence intensity of CD44 was higher on the surface of mouse hepatic NK cells in the LAG3-/- group than in the WT group (t = −3.234, P < 0.01), while no significant differences were found in the mean fluorescence intensity of CD25 or CD69 on the surface of mouse hepaticNK cells between the LAG3-/- and WT groups (both P values > 0.05). There were significant differences between the LAG3-/- and WT groups in terms of the percentages of IFN-γ (t = −0.723, P > 0.05), TNF-α (t = −0.659, P > 0.05), IL-4 (t = −0.263, P > 0.05), IL-10 (t = −0.455, P > 0.05) or IL-17A secreted by mouse hepatic NK cells (t = 0.091, P > 0.05), and the percentage of IFN-γ secreted by mouse splenic NK cells was higher in the LAG3-/- group than in the WT group (58.40% ± 1.64% vs. 50.40% ± 4.13%; t = −4.042, P < 0.01); however, there were no significant differences between the two groups in terms of the proportions of TNF-α (t = −1.902, P > 0.05), IL-4 (t = −1.333, P > 0.05), IL-10 (t = −1.356, P > 0.05) or IL-17A secreted by mouse splenic NK cells (t = 0.529, P > 0.05). Conclusions During the course of E. multilocularis infections, LAG3-/- promotes high-level secretion of IFN-γ by splenic NK cells, which may participate in the reversal the immune function of NK cells, resulting in aggravation of hepatic fibrosis.
4.The application of high resolution vascular wall imaging in the diagnosis and treatment of children's central nervous system vasculitis
Yimin CAO ; Mingfeng ZHANG ; Chengye ZHANG ; Xuran FENG ; Pingyong FENG ; Lixia ZHOU
Journal of Practical Radiology 2024;40(9):1499-1502
Objective To investigate the clinical value of high resolution vascular wall imaging(HRVWI)in the diagnosis and treatment of central nervous system vasculitis(CNSV)in children.Methods A total of 36 children with CNSV underwent HRVWI examination were selected.The HRVWI imaging features,involved vessel types and stenosis degree were analyzed retrospectively and compared with magnetic resonance angiography(MRA).Combined with some patients'follow-up and reviewed imaging after treatment.Results HRVWI showed that all of the 36 children with CNSV had cerebral arteritis,and the affected inflammatory ves-sels showed varying degrees of focal arterial wall thickening and enhancement,mainly uniform thickening and centripetal enhance-ment of the affected arterial wall.Most were mid-enhanced,and the stenosis degree was mostly at level 1(21/36).According to the type of involvement cerebrovascular,there were 26 cases of large-medium vessel type,6 cases of small vessel type and 4 cases of mixed type.Compared with MRA,HRVWI had a higher sensitivity in diagnosing CNSV(P<0.05).13 cases were followed up after treat-ment,and HRVWI showed cerebral vasculitis relief in 8 cases and progression in 5 cases,consistent with changes in clinical symp-toms and laboratory indicators.Conclusion The imaging features of CNSV in children with different causes are different.HRVWI has a high sensitivity in the diagnosis of CNSV in children.HRVWI plays an important role in the diagnosis and treatment of CNSV in children.
5.Analysis of individual monitoring results of occupational external exposure in a steel enterprise in Baotou city from 2018 to 2022
Jing WANG ; Shuchao SUN ; Xuran REN ; Xiaogang LU ; Jie ZHANG ; Shiyu PANG ; Rong JIN
Chinese Journal of Radiological Medicine and Protection 2024;44(8):675-680
Objective:To study the levels of individual dose of radiation workers in a steel enterprise in Baotou City from 2018 to 2022, and analyze the main factors affecting the annual dose, and provide basic data for revising relevant standards.Methods:According to the requirements of occupational external exposure personal monitoring standards (GBZ 128-2019), the personal dose monitoring of workers working in a steel enterprise in Baotou City from 2018 to 2022 was carried out, three months for a period, continuous monitoring 4 periods, and the results were analyzed.Results:A total of 1 360 workers from 10 employers within the enterprise were surveyed. The annual doses were in the range of 0.500 - 0.844 mSv, with an average annual individual dose of 0.676 mSv. Especially, the average annual individulal effective dose to workers for safety management and inspection was 0.986 mSv, hiher than 0.698 mSv to rolling workers, pump operators, and continuous casters ( Z = 56.89, P < 0.001). Additionally, female worders working with the radiation generators had a higher average annual individual effective dose of 0.821 mSv, than 0.691 mSv to the male workers who were exposed to sealed sources possibly in many cases as needed, with a statistically significant difference ( Z =-5.53, P < 0.001). Conclusions:The average annual individual effective dose to radiation workers in an iron and steel enterprise in Baotou City meets the requirements of the relevent national standard. The annual dose of women and some workers is relatively high, so the management of radiation workers should be strengthened and the radiation protection measures in the workplace should be improved.
6.Effect of self-efficacy on depression in patients with hematologic malignancy: the mediating role of social support and the moderating effect of resilience
Xuran CAO ; Kuo ZHANG ; Yaxin DU ; Chuanxin LIU
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(5):420-425
Objective:To explore the correlation between self-efficacy and depression in patients with hematologic malignancy, and analyze the mediating role of social support and the moderating effect of resilience.Methods:From February to June 2017, a total of 284 patients with hematologic malignancy in Jining Medical University Affiliated Hospital completed Connor-Davidson resilience scale (CD-RISC), social support rate scale (SSRS), general self-efficacy scale (GSES), self-rating depression scale (SDS). SPSS 21.0 software was used for statistical analysis, and the correlation was obtained by Pearson correlation analysis, and PROCESS v3.4 macro program was used to test the mediating and moderating effects.Results:Self-efficacy played a significant negatively predictive effect on depression in patients with hematologic malignancy( β=-0.35, t=-6.16, P<0.01). Social support partially mediated the correlation between self-efficacy and depression(the mediating effect was -0.05, accounted for 14.29%(-0.05/-0.35) of the total effect). Resilience moderated the mediating effect of social support on the correlation between self-efficacy and depression.The self-efficacy had no predictive effect on social support when the level of resilience was low and it had a significant negatively predictive effect on social support when the level of resilience was high (simple slope=-0.28, P<0.01, 95% CI=-0.39- -0.18). Conclusion:Self-efficacy has a moderating effect on depression in patients with hematologic malignancy.Self-efficacy affects depression through social support, and resilience regulates the mediating role of social support in the relationship between self-efficacy and depression.
7.Robot-assisted Posterior Laparoscopic Modified "Single-position" Treatment for Upper Tract Urothelial Carcinoma:Report of 7 Cases
Hua LIU ; Guang JIA ; Jiuliang WANG ; Guoling ZHANG ; Baiju TAO ; Bowen WANG ; Le MENG ; Xiangyu ZHU ; Xuran JI ; Chunyang WANG
Chinese Journal of Minimally Invasive Surgery 2023;23(12):944-949
Objective To evaluate the feasibitity of robot-assisted posterior laparoscopic modified"single-position"radical nephroureterectomy.Methods A retrospective analysis was made on 7 patients receiving robot-assisted posterior laparoscopic single-position radical nephroureterectomy between April 2022 and April 2023.The patients were in a fully healthy lateral position,and an artificial pneumoperitoneum was established.Trocars were placed at the right costal margin of the posterior axillary line,3-4 cm above the iliac crest of the midaxillary line,6-8 cm below the anterior axillary line,and 3-4 cm above the iliac crest of the midaxillary line near the outer edge of the musculus rectus abdominis,respectively.After the kidney was removed,the ureter was freed down to the iliac vessels,and then the main joint of the robot was reversed 180° for redocking.The ureter was continuously freed downwards to the bladder wall and the catheter was clamped.The bladder was opened after filling with indocyanine green and distilled water mixture.Then the fluid in the bladder was washed,the contralateral ureteral orifice was observed,the affected side of the ureter was resected,and the bladder incision was sutured by two layers with V-LOCK 2-0 sutures.The incision was extended under the right costal margin of the posterior axillary line and 3-4 cm above the iliac crest of the midaxillary line to remove the specimen.Results The operation was successfully completed in all the 7 cases.The surgical operation time was 155-263 min(mean,247.0 min)and the blood loss was 20-100 ml(mean,42.9 ml).The postoperative anal exhaust time was 14-24 h(mean,22.6 h).There were 1 case of postoperative absorption fever,2 cases of moderate anemia,and 2 cases of postoperative incision fat liquefaction.In the 2 patients with moderate anemia,one patient developed postoperative intramuscular artery rupture leading to massive bleeding and the formation of hematoma in the surgical area,with the amount of bleeding being approximately 1000 ml,and the other had moderate anemia before and after surgery.The hospital stay ranged 8-16 d(mean,11.6 d).Pathologic examinations showed high-grade uroepithelial carcer in all the patients.Postoperative follow-ups lasted 3-9 months,with a mean of 6.2 months.None had bladder tumor recurrence or distant metastasis.Conclusion Robot-assisted posterior laparoscopic modified"single-position"radical nephroureterectomy is safe and feasible.
8.Allosteric inhibition reveals SHP2-mediated tumor immunosuppression in colon cancer by single-cell transcriptomics.
Jian GAO ; Zhigui WU ; Mingxia ZHAO ; Rui ZHANG ; Manru LI ; Dongdong SUN ; Haibo CHENG ; Xianjia QI ; Yuxian SHEN ; Qiang XU ; Hongqi CHEN ; Dijun CHEN ; Yang SUN
Acta Pharmaceutica Sinica B 2022;12(1):149-166
Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and stable (MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68+ macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively, our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.
9.Clinical Reference Strategy for the Selection of Treatment Materials for Maxillofacial Bone Transplantation: A Systematic Review and Network Meta-Analysis
Shuxin ZHANG ; Xinyi ZHANG ; Yanli LI ; Xuran MAO ; Rui LIU ; Yanxin QI ; Eui-Seok LEE ; Heng Bo JIANG
Tissue Engineering and Regenerative Medicine 2022;19(3):437-450
Bone graft materials have mixed effects of bone repair in the field of oral maxillofacial surgery. The qualitative analyses performed by previous studies imply that autogenous odontogenic materials and autogenous bone have similar effects on bone repair in clinical jaw bone transplantation. This retrospective systematic assessment and network metaanalysis aimed to analyze the best effect of clinical application of autogenous odontogenic materials and autogenous, allogeneic, and xenogeneic bone grafts in bone defect repair. A systematic review was performed by searching the PubMed, Cochrane Library, and other journal databases using selected keywords and Medical Subject Headings search terms. 10 Papers (n = 466) that met the inclusion criteria were selected. The assessment of heterogeneity did not reveal any overall statistical difference or heterogeneity (P = 0.051 [ 0.05), whereas the comparison between autogenous and allogeneic bone grafts revealed local heterogeneity (P = 0.071 0.1). Risk of bias revealed nine unclear studies and one high-risk study. The overall consistency was good (P = 0.065 [ 0.05), and the local inconsistency test did not reveal any inconsistency. The publication bias was good. The confidence regarding the ranking of bone graft materials after GRADE classification was moderate. The effects on bone repair in the descending order were as follows: autogenous odontogenic materials, xenogeneic bone, autogenous bone, and allogeneic bone. This result indicates that the autogenous odontogenic materials displayed stronger effects on bone repair compared to other bone graft materials. Autogenous odontogenic materials have broad development prospects in oral maxillofacial surgery.
10.Progress in application of alveolar exhaled nitric oxide in pediatric lung diseases
International Journal of Pediatrics 2022;49(4):274-278
As a biomarker of airway inflammation, alveolar exhaled nitric oxide(CaNO), which represents small airway inflammation, is increasingly used in respiratory diseases.CaNO not only can be applied to children bronchial asthma severity evaluation, the selection of treatment and treatment effect of the dynamic monitoring, can also be applied to the early diagnosis of interstitial lung disease and assessment of the severity of lung damage for other diseases such as tuberculosis, pulmonary hypertension diagnosis.This paper reviews the diagnostic and therapeutic value of CaNO in pediatric respiratory diseases, and discusses the role of CaNO in the diagnosis and therapeutic evaluation in pediatric lung diseases.

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