1.Effect of fibrinogen on the progression of coronary plaque stenosis rate in patients with type 2 diabetes mellitus
Zhijie JIAN ; Xiangrui QIAO ; Haibo LI ; Guolin YAO ; Huafeng GUO ; Hui LIU ; Yue WU ; Jian YANG ; Lele CHENG
Chinese Journal of Arteriosclerosis 2024;32(5):410-414
Aim To investigate the relationship between fibrinogen(FIB)and the progression of coronary plaque stenosis rate in patients with type 2 diabetes mellitus(T2DM).Methods Hospitalized T2DM patients who underwent two or more coronary CT angiography(CCTA)examinations in the First Affiliated Hospital of Xi'an Jiaotong U-niversity from January 2015 to December 2020 were included.The subjects were divided into high FIB and low FIB groups according to the median of FIB.The differences in the progression of coronary plaque stenosis rate and other clini-cal characteristics were compared between the two groups,and the relationship between FIB level and the progression of coronary plaque stenosis rate was analyzed by Spearman's correlation analysis and Logistic regression.Results A total of 145 patients were included,73 in the high FIB group and 72 in the low FIB group at baseline,with a median follow-up time of 25(18,40)months between CCTA.The age,proportion of women,and the progression of coronary plaque ste-nosis rate were higher in the high FIB group than those in the low FIB group,and the differences were statistically signifi-cant(P<0.05).FIB level was positively correlated with the change in coronary plaque stenosis rate(r2=0.308,P<0.001).Multivariate Logistic regression analysis showed that FIB level was a risk factor for the progression of coronary plaque stenosis rate in patients with T2DM(OR=5.25,95%CI:1.97~14.02,P<0.001),after adjusting for age,sex and other clinical risk factors.Conclusion High baseline FIB level is an independent risk factor for the progression of coronary plaque stenosis rate in patients with T2DM,and monitoring FIB level is beneficial to cardiovascular risk stratifica-tion in patients with T2DM.
2.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.
3.Exploration on "Symptom-Syndrome-Drug" Regularity of Traditional Chinese Medicine for Coronary Microvascular Disease Based on Latent Structure Combined with Association Rules
Yilin ZHANG ; Jingjing WEI ; Hongxin GUO ; Lele HUO ; Mingjie ZHANG ; Jianfeng LU ; Aolong WANG ; Mingjun ZHU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(5):730-740
Objective To systematically explore the traditional Chinese medicine(TCM)common symptoms,syndrome elements,clinical syndrome differentiation,and medication rules of coronary microvascular disease(CMVD),and to provide a reference for quantitative criteria of clinical differentiation of CMVD,specification of the diagnosis and efficacy evaluation of TCM clinical syndrome,and guidance of clinical medication.Methods The databases including CNKI,Wanfang,VIP,and SinoMed were searched for research papers on the treatment of CMVD by TCM published from database inception to May 16,2023.Relevant information of the included literature was extracted and the database was established.Then,the frequency statistics of symptoms,syndrome elements,syndrome types and Chinese medicinals were carried out.Latent structural models were constructed using Latern 5.0 and Rstudio softwares respectively for comprehensive clustering and association rule analysis,so as to explore the symptom characteristics,syndrome elements distribution,common syndromes and medication rules for TCM treatment of CMVD.Results A total of 107 literature were included,involving 36 syndromes,17 syndrome elements,121 symptoms and 143 Chinese medicinals.It was speculated that the main syndrome element of CMVD was blood stasis,followed by qi deficiency,qi stagnation,phlegm turbidity,yin deficiency and yang deficiency.The main type of syndrome was qi deficiency and blood stasis,followed by heart blood stasis obstruction,qi stagnation and blood stasis,phlegm blended with stasis,qi-yin deficiency,etc..The main medicinals were Chuanxiong Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,Angelica Sinensis Radix and Astragali Radix.The medicinals used in the treatment of CMVD were classified as blood-activating and stasis-resolving drugs,deficiency-tonifying drugs,qi-regulating drugs in terms of their efficacy.Conclusion The location of CMVD is in heart,and related to liver and kidney.The syndrome of CMVD is deficiency in origin and excess in superficiality.Blood stasis runs through the development of the disease.The treatment is mainly to activate blood circulation and remove stasis,activate meridians and relieve pain,which should be supplemented with the therapies of tonifying and invigorating qi,soothing the liver and regulating qi,dispelling phlegm and dissipating masses according to the patients'syndromes.
4.The application and correlation study of γ rule and DVH evaluation for VMAT dose verification evaluation of cervical cancer patients
YangGuang MA ; Rizhen MAI ; Yuntong PEI ; Fangna WANG ; Lele LIU ; Yuexin GUO
Chinese Journal of Radiation Oncology 2022;31(5):450-455
Objective:To evaluate the volumetric modulated arc therapy (VMAT) dose verification of cervical cancer based on γ rule and dose volume histogram (DVH) and to perform correlation analysis between the evaluation results and the dose differences.Methods:Twenty cervical cancer VMAT plans were selected and performed on TrueBeam Linac. The delivered point and surface dose was measured by FC-65 G and ArcCheck and the results were compared to those calculated by Eclipse. The dose of patients was reconstructed by 3DVH. Then, differences between the reconstructed and plan value of D mean, D 95%, D 98% and D 2% of PTV, V 20Gy of left and right femoral head, V 40Gy of rectum, D 1cm 3 of cord, D 98%, D 2% and D 50% of the 50% prescription iso-dose volume (IDV), were evaluated and 3-dimensional (3D) γ was assessed for each organ. Lastly, Pearson’s correlation coefficient was used to analyze the relationship between point dose difference, 2D γ pass-rate (γ%), γ mean and 3D γ% of each organ and the dose difference. Results:Small differences were found between the point dose measured, reconstructed and the plan value. Differences between D mean of PTV, all dose parameters of IDV and plan values were all within 3% and V 40Gy of rectum showed the largest difference. As for the 3D γ%, the maximum pass rate was found for the left and right femoral head and the maximum variance for cord D 1cm 3. There was a moderate correlation between measured and reconstructed point dose deviation and dose difference of each organ, while no significant correlation was found for 2D γ%. Strong correlation was found between 3D γ% of target and D 50% of PTV/IDV and no correlation was found for other organs. Conclusion:The performance of both γ-and DVH-based evaluation can reveal dose error for dose verification, but both of them have some limitations and should be combined in clinical practice.
5.The impact factors of longitudinal dose fall-off outside the target with helical tomotherapy
Haiyang WANG ; Yifei PI ; Bin HAN ; Fei JIA ; Lele LIU ; Fangna WANG ; Fanyang KONG ; Yuntong PEI ; Jinyan HU ; Yuexin GUO
Chinese Journal of Radiological Medicine and Protection 2021;41(3):183-187
Objective:To study the changing characteristics and impact factors of helical tomotherapy (HT)for longitudinal dose fall-off outside the target, in order to guide the plan junction or pretreatment target and implementation efficiency in clinical.Methods:Eight patients with head and neck tumors admitted to the Department of Oncology Radiotherapy of the First Affiliated Hospital of Zhengzhou University in December 2019 were retrospectively selected as the research objects. The planning target area and dose drop structure were outlined in the head and neck images with a thickness of 1 mm obtained by Siemens SOMATOM Definition AS positioning computerized tomography (CT). Different field widths (FW, 5.0 cm/2.5 cm/1.0 cm) and pitches (0.430/0.287/0.215) were assembled for planning with the same modulation factor (1.8), finest does calculation grid (0.195 cm ×0.195 cm) and other planning parameters were consistent. The plans were designed by different parameters, and the result was analyzed by univariate analysis.Results:The that different pitch curves coincided under the same field width by comparative analyzing, so pitchs had no effect on dose drop. The different field width curves were independent of each other, indicating that the field width had an effect on dose drop in the head and foot direction. The relationship between the longitudinal dose drop speed outside the target and the change of the field width was inversely correlated: the larger field widths meant the slower dose fall-off and the larger penumbra, while the smaller field widths meant the faster fall-off and the smaller penumbra. When the dose fall-off to 50% of the prescribed dose, the distance from the target was approximately equal to half the field widths, and the pitchs had not affect the rate of dose-drop, while the dose at different distances from the target boundary could be calculated by the fitting formulas. The field widths and pitchs had little effect on the CI and HI index of the target, relatively, the target area was best when the field width was 2.5 cm. The total beam-on time gradually decreased with the increase of the field widths and pitches.Conclusions:When segment target therapy needs to consider planning junction, execution efficiency, and controlling longitudinal dose fall-off and considered the execution, the optimal planned parameters such as field widths and pitches could be selected or the target at the junction regions could be adducted according to the longitudinal dose drop formula, so as to achieve the ideal dose distribution.
6.Research progress in treatment of tuberculous meningitis
Lele WANG ; Jianqiong GUO ; Jungang LI ; Song YANG ; Shenjie TANG
Chinese Journal of Clinical Infectious Diseases 2021;14(5):392-398
Tuberculous meningitis is the most common and serious type of central nervous system tuberculosis, with high mortality and disability rate, which has attracted extensive attention of global public health. The high mortality rate and disability rate of tuberculosis meningitis may be related to its lack of specific clinical and imaging characteristics, insufficient attention from clinicians, lack of early sensitive and specific diagnostic testing techniques, delay in treatment, and restricted penetration of anti-TB drugs into the blood-brain barrier or/and MDR-TB, etc. This article reviews the disease burden of TBM, chemotherapy drugs and regimens, anti-inflammatory agents, aspirin, interventional and surgical treatment to provide reference for clinical management of this disease.
7.Preliminary study on the protective effect of glycosyltransferase Colgalt2 gene deletion on acetaminophen-induced liver injury
Xiaohui ZHANG ; Lele GUO ; Hongshan WEI ; Feng REN ; Jing ZHANG
Chinese Journal of Hepatology 2021;29(1):67-71
Objective:To investigate the protective effect of Colgalt2 gene deletion on acute liver injury induced by acetaminophen (APAP) in mice.Methods:Colgalt2 +/+ wild-type control mice and Colgalt2 -/- mice (all C57BL/6J strains) were selected as the research subject. APAP solution was injected intraperitoneally to establish a mouse model of acute liver injury. The mouse were divided into four groups: Colgalt2 +/+ wild-type control group, Colgalt2 +/+ wild-type drug group (APAP 500 mg/kg), Colgalt2 -/- control group, and Colgalt2 -/- drug group (APAP 500 mg/kg). The survival rate was measured to plot survival curve. Liver function was evaluated by detecting serum ALT and AST levels. Liver histopathological changes were observed by HE staining to evaluate the condition of liver injury. Western blot was used to detect protein c-Jun N-terminal kinase (JNK)-related liver injury. Results:Compared with Colgalt2 +/+ mice, the survival rate was significantly increased after giving APAP to Colgalt2 -/- mice (86.7% vs. 40%), and liver cell necrosis and inflammatory cell infiltrates of Colgalt2 +/+ mice were milder. Serum ALT, and AST level was significantly decreased [ALT: (5 291.9 ± 1 016.34) U/L vs. (1 616.9 ± 330.65) U/L, P = 0.000; AST: (4 978.0 ± 1 028.43) U/L vs. (1 851.0 ± 437.55) U/L, P = 0.000]. The expression level of JNK was significantly decreased in liver tissue. Conclusion:Colgalt2 gene deletion has a protective effect on acute liver injury induced by acetaminophen (APAP) in mice. Therefore, Colgalt2 may be a potential therapeutic option for acetaminophen-induced hepatotoxicity.
8.Clinicopathological features and prognosis of immunoglobulin A nephropathy after renal transplantation
Tianjing ZHANG ; Pingfan LU ; Yuanjun DENG ; Yang CAI ; Lele LIU ; Chunjiang ZHANG ; Yiyan GUO ; Qian LI ; Na ZHU ; Beichen TIAN ; Min HAN
Chinese Journal of Organ Transplantation 2020;41(2):84-88
Objective:To summarize the relationship between the clinicopathological features and prognosis of immunoglobulin A nephropathy (IgAN) after renal transplantation.Methods:A total of 34 patients with IgAN after renal transplantation confirmed by renal biopsy were enrolled. And another 34 patients with primary IgAN confirmed by initial renal biopsy were adopted as controls. Clinical and pathological features of two groups were compared to explore the relationship between clinicopathological features and prognosis of allograft IgAN.Results:As compared with primary IgAN group, renal function in allograft IgAN group included serum creatinine [(158.5±75.9) vs (84.8±26.8) umol/L], urea nitrogen [(9.7±6.1) vs (5.2±1.4) mmol/L], uric acid [(406.7±87.8) vs (359.0±92.6) umol/L], estimated glomerular filtration rate {(57.4±25.4) vs (91.2±28.6) [ml/(min·1.73m 2)]}. All were statistically significantly higher ( P<0.05) while other parameters showed no differences. Pathologically, the proportion of T1 type (50.0% vs 17.6%) of renal tubular atrophy/interstitial fibrosis was significantly higher in allograft IgAN group than control group ( P<0.05). Furthermore, univariate and multivariate Logistic regression analyses were performed between various pathological parameters and prognosis in allograft IgAN patients. It indicated that the degree of mesangial hyperplasia of patients with transplanted IgAN had a significantly negative impact on the prognosis. Conclusions:The clinicopathological features of patients with allograft IgAN show no difference from those of patients with primary IgAN. And among patients with allograft IgAN, those with severe mesangial hyperplasia often have a worse prognosis.
9.The clinical feature of bone metastases in lung cancer patients with different pathological types
Yao XU ; Chao ZHANG ; Xu GUO ; Lele LIU ; Xiuxin HAN ; Guowen WANG
Chinese Journal of Orthopaedics 2019;39(6):329-335
Objective Based on lung cancer center database,we analyzed the clinical characteristics of lung patients with bone metastases.The relationship between bone metastases,skeletal-related events,survival time and different pathological subtypes of lung cancer were also evaluated in this study.Methods A total of 861 patients with lung cancer were studied from May 2010 to April 2012 at Tianjin Medical University Cancer Institute and Hospital.As to follow-up situation,patients' survival status and treatment information were collected by telephone follow-up and (or) examinationsin outpatient.The clinical characteristics,skeletal-related events and survival of bone metastaticpatients with different pathological types of lung cancer were analyzed.Logistic regression analysis was used to identify risk factors for bone metastases.The relationship between histological subtypes and the incidence of bone metastases was evaluated using Odds Ratios (ORs).The chi-square test was used to compare the proportion of bone metastases,synchronous bone metastases and SREs among different histological subtypes patients.The overall survivals was evaluated using the Kaplan Meier.Results A total of 861 patients with lung cancerwere enrolled in this study,including 293 cases with bone metastases.The average follow-up of our population was 14.2 months and the last follow-up time was September 2017.Among different pathological types of lung cancer,adenocarcinoma (39.14%,173/442) has the highest incidence of bone metastases,followed by other types (29.91%,35/117),squamous cell carcinoma (29.47%,56/190) and SCLC (25.89%,29/112).Spine (59.73%,175/293) was the most common location site of the bone metastases,followed by the ribs (49.15%,144/293),pelvis (20.48%,60/293),femur (16.38%,48/293) and sternal (16.38%,48/293).Lung adenocarcinoma was a risk factor for bonemetastases (P=0.002).In ORs analyze,adenocarcinoma patients were more likely to develop bone metastases [OR=1.60,95%CI (1.21~2.13)].In our cohort,58.36%of patients with lung cancer had skeletal related events.Among various types of skeletal related events of patients with bone metastases,the most common one was radiotherapy for bone metastases (51.88%,152/293),followed by pathological fractures (15.02%,44/293),spinal cord compression (6.48%,19/293),bone instability requiring surgery (4.78%,14/293) and hypercalcemia (1.71%,5/293).There was no significant difference between different types of skeletal related events.The median survival time of the patients with bone metastases was 11.5 months.There was no significant difference in survival between adenocarcinoma patients and non-adenocarcinoma patients (P=0.111).Conclusion This study suggested that the incidence of bone metastasis in lung adenocarcinoma was 39.14% and lung adenocarcinoma was a risk factor for bone metastases,which supported early screening and monitoring of bone metastasis in the patients.
10. A quantitative evaluation on the image-quality parameters and quality assurance thresholds setting of accelerator on-board imaging system
Jinyan HU ; Yuntong PEI ; Yangguang MA ; Haiyang WANG ; Lele LIU ; Yuexin GUO
Chinese Journal of Radiation Oncology 2019;28(12):919-923
Objective:
To achieve quantitative analysis of image quality parameters and establish warning and action thresholds for the on-board imaging (OBI) system of linear accelerator.
Methods:
The Catphan604 phantom was repeatedly scanned in the Full-Fan and Half-Fan CBCT scanning modes on a Varian EDGE linear accelerator, and the software based on Python language development in-house was utilized to analyze image quality parameters, such as CT number linearity, geometric consistency, slice thickness, spatial resolution, uniformity and low-contrast resolution. The quantitative analysis results of each image quality parameter obtained from 16 times of scanning within 16 months were normalized to the mean and the standard deviations were recorded. A run chart analysis was created to determine the warnings and action thresholds.
Results:
The software built in-house can quantitatively analyze the image parameters of the two scanning modes of OBI system. The low-contrast resolution of Half-Fan was better than that of Full-Fan, whereas the spatial resolution of Full-Fan was superior to that of Half-Fan. One standard deviation (1σ) was set as the warning threshold and 2 standard deviations (2σ) as the action threshold, respectively. The tolerance level of Half-Fan was smaller than that of Full-Fan.
Conclusion
Self-developed software enables quantitative analysis of accelerator image quality parameters, establishes warning and action tolerance of quality assurance and provides guidance for image quality assurance under image-guided radiotherapy specification.

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