1.Role of Kupffer cells in hepatitis B virus infection
Lele SHI ; Tao WANG ; Sunzedong GU ; Xiaofei YANG ; Ye ZHANG ; Jianqi LIAN
Chinese Journal of Clinical Infectious Diseases 2017;10(6):473-477
Hepatitis B virus(HBV)infection is the main cause of chronic liver diseases in China. The clearance of HBV is important for patients with chronic hepatitis B.Current antiviral therapy includes interferon and nucleotide analogues.The adverse reactions of interferon are common which restrict its application.Nucleotide analogues need long-term maintenance treatment.Kupffer cells (KCs) are the main innate immune cells in the liver.Studies have shown that KCs play an important role in hepatitis B virus infection.It can inhibit virus replication effectively , but may also result in immune dysfunction , causing HBV persistence.Understanding the mechanism related to the role of KCs in hepatitis B virus infection may lead to a new approach of antiviral therapy.
2.Immune response mechanism of human adenovirus infection
Tao WANG ; Sunzedong GU ; Hongyu YI ; Lele SHI ; Xiaofei YANG ; Jian-Qi LIAN
Chinese Journal of Clinical Infectious Diseases 2018;11(5):394-400
Human adenovirus ( HAdV ) is the most widely used vector of gene drugs . Its applications range from oncolytic therapy to vaccination , besides , HAdV is one of the most important pathogen causing acute respiratory infections in infants and young children .How the human innate immune system protects against HAdV has always been the focus of its application as a vaccine carrier .In patients with immunodeficient and hematopoietic stem cell transplant , specific T cell immunotherapy is also one of the hotspots in recent years .Although some HAdV vector vaccines have entered clinical trials , the immune mechanism remains controversial .This article describes how the human innate immune system and the adaptive immune system defend against HAdV and the escape mechanism of HAdV for human immune responses ,in order to indicate directions for vaccine research and deepen clinicians 'understanding of HAdV severe infections .
3.CT findings and clinical value analysis of ovarian torsion in children
Jiaojing LIU ; Pange WANG ; Lele KANG ; Shengli SHI
Journal of Practical Radiology 2024;40(2):275-277,296
Objective To investigate the characteristics of CT findings in pediatric ovarian torsion and improve the understanding of pediatric ovarian torsion.Methods The clinical and CT data of 20 cases of ovarian torsion confirmed by pathology and/or surgery were analyzed retrospectively,based on the timing of ovarian torsion,they were divided into fetal and non-fetal groups.All 20 cases underwent plain CT scan and 11 cases underwent CT enhancement.Results All of the 20 cases were unilateral duplication,including 12 cases right and 8 cases left.There were 8 cases of ovarian torsion in the fetal group,all of them were visited with the finding of abdominal mass.The eggshell calcification on CT manifestations was found in 8 cases,and 2 cases of pelvic effusion.There were 12 cases of ovarian torsion in the non-fetal group,all of them presented with abdominal pain,CT showed the disc sign in 7 cases,peduncular protrusion sign in 6 cases,adnexal bleeding sign in 2 cases,subcapsular effusion sign in 2 cases,the uterus displaced to the ipsilateral ovary in 6 cases and pelvic effusion in 10 cases.The disc sign and peduncular protrusion sign were direct signs for the diagnosis of ovarian torsion,and the adnexal bleeding sign and subcapsular effusion sign suggested the possibility of necrosis.Conclusion Pediatric ovarian torsion CT findings with typical signs such as disc sign,peduncular protrusion sign,adnexal bleeding sign and subcapsular effusion sign,combined with clinical history,a more accurate diagnosis can be given,providing assistance in clinical treatment.
4.The high-resolution chest CT findings and clinical features of dermatomyositis with anti-melanoma differentiation-associated gene 5 antibody
Wang CHEN ; Xiaofei SHI ; Diansen CHEN ; Zhan SHI ; Lele SONG
Chinese Journal of Rheumatology 2022;26(1):22-26
Objective:To investigate the high resolution computed tomography (HRCT) findings, laboratory test results and clinical manifestations of anti-melanoma differentiation-associated gene 5 (MDA5) antibody positive dermatomyositis complicated with lung interstitial lesions, and to analyze the correlation between the HRCT findings and clinical course of disease.Methods:Twenty-seven patients with anti-MDA5 antibody positive associated dermatomyositis (DM) were included and divided into two groups: acute/subacute group ( n=15) and chronic group ( n=12). HRCT images of lung were analyzed. Clinical data including gender, age, clinical manifestations and course of disease, anti-Ro52 antibody, creatine kinase (CK), antinuclear antibody (ANA), anti-Jo-1 antibody and erythrocyte sedimentation rate (ESR) were also collected. χ2 test was adopted for statistical analysis. Results:① Interstitial changes were 100%(27/27). The proportion of unilateral localized distribution was the most [48%(13/27)], followed by bilateral localized distribution [30%(8/27)], and bilateral diffuse distribution [22%(6/27)). ② Among the HRCT findings of lung interstitial changes, ground glass shadow was the most common presentations [59%(16/27)], followed by subpleural curve sign [63%(17/27)] and interlobular septal thickening [56%(15/27)], while honeycomb sign [0(0/27)] had the lowest rate of presentation. ③ Compared with the chronic progressive group, the acute/subacute progressive group presented as chest tightness (80% vs 8%, χ2=13.715, P<0.05) and dyspnea (47% vs 0, χ2=7.560, P<0.05). Acute/subacute HRCT showed ground glass opacity (87% vs 25%, χ2=10.501, P<0.05). The prominent HRCT showed interlobular septal thickening in the chronic course group (83% vs 33%, χ2=6.750, P<0.05). ④ The anti-MDA5 antibody (+++) index was significantly different (88% vs 25%, χ2=8.168, P<0.05). There was no significant difference in anti-Ro52 antibody (+), ANA(+), anti-Jo-1 antibody(+), CK elevation and ESR elevation between the two groups ( P>0.05). Conclusion:Most dermatomyositis patients with positive anti-MDA5 antibody are complicated with interstitial lung lesions, the HRCT manifestations of lung are diverse. In order to confirm the diagnosis of this disease, clinical manifestations, laboratory and pathological examinations are required.
5.Application of FOCUS-PDCA Cycle Management in Reducing the Incidence of Irrational Medical Orders of Parenteral Nutrition
Yinli HE ; Qinying LUO ; Lele DONG ; Chengsen PANG ; Huixia LU ; Yating ZHANG ; Xiaoxia ZHANG ; Weihua DONG ; Shufeng WANG ; Bingyin WEIYI ; SHI FENG
China Pharmacy 2017;28(34):4842-4845
OBJECTIVE:To reduce the incidence of irrational medical orders for parenteral nutrition,and promote the rational use of parenteral nutrition. METHODS:The medical orders for parenteral nutrition of the first quarter of 2016 in general surgery de-partment of our hospital were collected,and the number and types of its irrational medical orders were summed up. Then FO-CUS-PDCA(Find-organize-clarify-understand-select-plan-do-check-act)cycle management was adopted to analyze and improve the existing problems in issuing medical orders for parenteral nutrition. The improved(the third quarter of 2016)medical orders for par-enteral nutrition were collected,the number and types of its irrational medical orders were summed up,and management effect was evaluated. RESULTS:Establishing nutrition support group,strengthening the training and communication of medical staff,adding prescription evaluation module for parenteral nutrition in hospital information system and a number of measures had made the inci-dence of irrational medical orders for parenteral nutrition in general surgery department declined from 48.25%(1433/2970)before improvement to 5.67%(120/2118)after improvement. The incidences of cation excess,inappropriate selection of drugs and inap-propriate compatibility in irrational types were 0. CONCLUSIONS:FOCUS-PDCA cycle management can reduce the irrational rate of medical orders for parenteral nutrition and promote the rational use of parenteral nutrition in hospital.
6.Association analysis of PPP1R3A gene polymorphism with schizophrenia in Uygur Chinese population.
Xinyu SHI ; Zhiguo AN ; Lele SUN ; Bin XU ; Daibin MU ; Songnian FU ; Hongxing HU ; Xiao LUO ; Wen DU ; Ping YAN ; Lu JIN ; Dan NIE ; Limu-Ershaer-Ai KAO ; Yongyong SHI ; Qingzhong. YI
Chinese Journal of Nervous and Mental Diseases 2019;45(6):356-360
Objective To explore the correlation between exon region polymorphism of PPP1R3A gene and schizophrenia in Uygur Chinese population. Methods PPP1R3A gene exon region DNA amplification was performed using multiple PCR targeted capture next-generation sequencing method in 528 patients with schizophrenia and 576 healthy controls of Uyghur descent, Illumina HiSeq X Ten was used for sequencing, the symptoms of schizophrenia were assessed by positive and negative symptoms scale (PANSS). Results The allelic and genotypic distributions in rs1800000 of PPP1R3A gene between patients with schizophrenia and healthy controls had significant difference (P<0.05), rs1799999 in genotype frequency between the female case and control groups showed significant difference (P<0.05). Furthermore, the allelic distributions of rs8192686 between male cases and controls had significant difference (P<0.05). Conclusion PPP1R3A gene rs1800000 may be associated with the development of schizophrenia in Uygur Chinese population; rs1799999 may be a risk factor for susceptibility of female Uygur Chinese schizophrenia; The C allele at rs8192686 may be associated with male Uygur Chinese schizophrenia.
7.Mechanism of glioma stem cells with high expression of PTPRZ1 inducing TAMs polarization to M2 immunosuppressive phenotype
Lele AN ; Ying YANG ; Qing LIU ; Feiyue DOU ; Lujing WANG ; Yue CHENG ; Chao WANG ; Qianying RUAN ; Lei ZHOU ; Haitao GUO ; Weikai KONG ; Xuegang LI ; Chuan LAN ; Fei LI ; Yu SHI
Journal of Army Medical University 2024;46(8):796-803
Objective To explore the effect of glioma stem cells with high expression of protein tyrosin phosphatase receptor type Z1 (PTPRZ1 )on the phenotypic polarization and phagocytosis of tumor-associated macrophages and its regulatory mechanism.Methods GSCs and non-stem tumor cells (NSTCs) were screened out from human glioblastoma (GBM) specimens using flow cytometry,and the PTPRZ1 expression in paired GSCs and NSTCs were detected.Human peripheral blood mononuclear cells (PBMC)-derived CD14+monocytes were exposed to the conditioned medium from glioma cells or recombinant chemokine C-C motif ligand 20 (CCL20)for TAM polarization.Stable PTPRZ1 knockout GSCs (PTPRZ1-KO GSCs) were constructed using CRISPR/Cas9. TAM phagocytosis to GSCs,NSTCs,PTPRZ1-Control GSCs (PTPRZ1-Ctrl GSCs)and PTPRZ1-KO GSCs and the expression of immunosuppressive phenotype (M2) polarization marker CD163 were examined using flow cytometry.Differentially expressed genes (DEGs ) between paired GSCs and NSTCs were determined using a bulk RNA-sequencing dataset (GSE54791 )from Gene Expression Omnibus (GEO).A gene set informing worse outcome of patients with GBM was generated using The Cancer Genome Atlas (TCGA)-GBM cohort.By intersecting the aforementioned gene set with the gene set that encodes for human membrance proteins,the PTPRZ1 gene is obtained.Gene set enrichment analysis (GSEA)was used for pathway enrichment analysis to compare the differentially regulated pathways between GBMs with high or low PTPRZ1 expression.Bulk RNA sequencing,qRT-PCR and Western blotting were used to identify the DEGs between PTPRZ1-KO GSCs and PTPRZ1-Ctrl GSCs.Results GSCs were more capable of escaping from TAM phagocytosis than NSTCs (P<0.05 )and had specifically up-regulated PTPRZ1 expression.PTPRZ1-KO significantly suppressed GSCs escaping from TAM phagocytosis (P<0.01 ). GBMs with high PTPRZ1 expression showed significant inhibition of pathways mediating phagocytosis (P<0.05).The expression of CCL20 as a M2 TAM polarization chemokine was significantly down-regulated in PTPRZ1-KO GSCs (P<0.05 ).Treatment with recombinant CCL20 up-regulated the expression of CD163 as a M2 TAM marker in TAM.Conclusion PTPRZ1+GSCs mediate M2 TAM polarization and inhibit TAM phagocytosis,which may be related to the up-regulation of CCL20 in PTPRZ1+GSCs.
8.A real-world study of 176 cases with aplastic anemia treated in outpatient
Lele ZHANG ; Xiao YU ; Liwei FANG ; Hong PAN ; Qian LIANG ; Jingyu ZHAO ; Zhexiang KUANG ; Jun SHI
Chinese Journal of Hematology 2021;42(1):58-62
Objective:To explore the diagnostic process and outcomes of patients with aplastic anemia (AA) who received outpatient treatment in a real-world setting.Methods:The diagnostic processes, treatment regimens, and outcomes of 176 patients with AA treated in outpatient centers from January 2018 to December 2019 were reviewed.Results:The median interval from the onset of symptoms to the first visit was 7 (5-120) months. Complaints during the first visit included bleeding (52.3% ) , anemia (51.7% ) , and infection (6.8% ) . For diagnosis, 168 patients (95.5% ) underwent bone marrow aspiration; however, only 22 of them (17.1% ) consented aspiration in multiple sites (sternum) . The completion rate of bone marrow biopsy was 85.1% (143/168) ; flow immunophenotype and karyotype analyses were performed on 59.5% (100/168) and 58.9% (99/168) of AA patients, respectively, and the culture of clonal forming units by bone marrow mononuclear cells was performed on 26.8% (45/168) of AA patients. The most preferred regimen was cyclosporine combined with androgen and levamisole (43.8% , 77 patients) , followed by cyclosporine combined with androgen (25.6% , 45 patients) . Cyclosporine alone was administered in 24 patients (13.6% ) and androgen alone in 16 patients (9.1% ) . Furthermore, 14 patients (7.9% ) did not consent to any drugs or only chose traditional Chinese medicine. The patients were divided according to the frequencies of follow-up: regular follow-up group (≥4 times/year, n=130) and irregular group (<4 times/year, n=46) . The former had a higher 6-month remission rate (52.5% vs 28.0% , P=0.005) , a greater high-quality remission rate in 12 months (40.7% vs 16.7% , P=0.027) , and a lower relapse rate in 24 months (4.4% vs 36.4% , P=0.001) . Conclusion:In real-world settings, bone marrow aspiration in multiple sites should be addressed in outpatient treatment for AA diagnostic work-up, including PNH clone screening, flow immunophenotype, chromosome karyotype analysis, and culture of clonal forming units. Patients with AA who follow regular visits were more likely to achieve high-quality remission and a lower relapse rate. Visits at least four times per year are recommended for AA patients undergoing outpatient treatment.
9.Kinetics of immune activated T cells in aplastic anemia mouse model
Weiwang LI ; Ruonan LI ; Lele ZHANG ; Qiuyi MA ; Haoyuan LI ; Wenjun WANG ; Jin MAO ; Yajing CHU ; Weiping YUAN ; Jun SHI
Chinese Journal of Hematology 2022;43(7):581-586
Objective:To explore the dynamic changes of donor derived T cells at different time points in the aplastic anemia mouse model.Methods:The aplastic anemia mouse model was induced and then the proportion of infiltrated donor derived T cells in spleen and bone marrow, expression of activation molecular markers, cell cycle and functional subsets were measured by flow cytometry at different time points to evaluate the functional status of T cells in different periods.Results:①T cell immune-mediated aplastic anemia mouse model was successfully established by half lethal dose irradiation combined with major histocompatibility antigen (MHC) haploidentical lymph node cells infusion. ②The donor derived T cells began to infiltrate significantly in the spleen of aplastic anemia mouse from the 3rd day after transplantation and the ratio of CD4 +/CD8 + gradually inverted. After the 5th day, they gradually entered the bone marrow, predominated by CD8 + cells. ③The expression peak of CD69 in donor CD4 + cells was later than that in CD8 + cells. The trend of CD25 expression in CD4 + cells was the same as that in CD8 + cells, but the expression level in CD8 + cells was higher than CD4 + cells. ④The proportion of donor CD4 + cells in S/G 2/M phase reached the peak in spleen, about 12%, within 3 days after transplantation, while a higher level in CD8 + cells, which was about 20%. And the proportion of both CD4 + and CD8 + cells in S/G 2/M phase increased again after entering bone marrow, which was continued to be higher in CD8 + cells than that in CD4 + cells after 3 days of transplantation. ⑤Immune activated T cells in the spleen rapidly differentiated into effector memory T cells (T EM) after a short central memory T cell (T CM) stage. After entering the bone marrow, some T EM differentiated into effector cells to further function. Conclusion:In the aplastic anemia mouse model, donor derived T cells activated rapidly after entering the allogenic recipient, reached its proliferation booming period and differentiated into T EM cells within 5 days. After 5 days, they began to enter the bone marrow to continue proliferate and damage hematopoiesis.