1.The establishment of head and neck squamous cell carcinoma PDX models and humanized immune reconstruction
Bixue HUANG ; Kexing LYU ; Ruihua FANG ; Changlin LIU ; Jinhong ZHANG ; Shiyun LUO ; Jing YANG ; Qiao SU ; Wenbin LEI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(10):1243-1251
Objective:To construct patient-derived xenograft (PDX) models from head and neck squamous cell carcinoma (HNSCC) patients, to explore the effect of immune reconstitution timing on the PDX modeling and immune microenvironment in humanized immune system mice (huHSC-NCG-hIL15), and to provide a reliable animal model for research on the mechanisms of head and neck squamous carcinoma and for studies on immune therapy drug interventions.Methods:This study enrolled 28 HNSCC patients (25 laryngeal carcinomas, 3 hypopharyngeal carcinomas). PDX models were established in Balb/c nude (nu) mice, NSG mice, and humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Fresh HNSCC samples were transplanted into Balb/c nu and NSG mice to generate PDX models, with subsequent analysis of success-associated factors. One successfully established PDX tumor was subsequently implanted into humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Tumor transplantation was performed at distinct immune reconstruction timepoints (2 vs. 7 weeks post-reconstitution), and tumor growth patterns were monitored. Flow cytometry and multiplex immunohistochemical staining were utilized to characterize immunological profiles in peripheral lymphoid organs and tumor microenvironments. Hematoxylin-eosin (HE) staining was employed to assess histomorphological concordance between primary patient tumors and PDX model tissues. Results:HNSCC PDX models were successfully established. NSG mice exhibited a higher and more stable tumor take rate compared to Balb/c nu mice (pilot study: 4/10 vs. 3/10 cases; mean take rate 60%-80% vs. 20%-60 %). The PDX success rate in NSG mice was 46.4% (13/28). In the huHSC-NCG-hIL15 mice model with immune reconstitution at 7 weeks, tumors grew significantly faster, and the PDX modeling process was shorter (617 mm3 at day 70 in 7-week cohort vs.280 mm3 in 2-week cohort). Flow cytometry analysis of the immune microenvironment showed that at 7 weeks of immune reconstitution, the proportions of B cells in the spleen and tumor tissues(2-week vs. 7-week: spleen 16.2% vs. 61.7%, tumor 26.0% vs. 38.8%) and myeloid cells in the spleen (2-week vs. 7-week: spleen 47.2% vs. 88.1 %) were significantly higher, while mice at 2 weeks post-reconstitution showed a higher proportion of T cells (2-week vs. 7-week: spleen 13.2% vs. 9.3%, tumor 4.8% vs. 2.5%). HE results demonstrated that the tumor tissues in PDX models maintained a high degree of morphological similarity to the primary tumors in both NSG and huHSC-NCG-hIL15 mouse models. Conclusion:The HNSCC PDX modeling protocol demonstrates operational feasibility and high reproducibility, establishing this model as a robust platform for mechanistic and immunotherapeutic studies.
2.Relationship Between Semi-Quantitative Parameters SUVmax and TBR of 18F-FDG PET/CT and Disease Activity of Takayasu Arteritis
Jingjing ZHANG ; Xin WEN ; Qiao RUAN ; Xingmin HAN ; Ruihua WANG
Chinese Journal of Medical Imaging 2025;33(5):562-566
Purpose To explore the relationship between semi-quantitative parameters maximum standard uptake value(SUVmax)and target-background ratio(TBR)of 18F-FDG PET/CT imaging and the activity of Takayasu arteritis.Materials and Methods A total of 110 patients with Takayasu arteritis from February 2016 to December 2022 in the First Affiliated Hospital of Zhengzhou University who underwent 18F-FDG PET/CT images were retrospectively reviewed.All Takayasu arteritis patients were divided into active(92 cases)and inactive groups(18 cases)according to Kerr score.The region of interest technique was used to measure the SUVmax of the arterial wall,and compares the SUVmax with the average SUV in the center of the inferior vena cava and the maximum SUV measured in the right lobe of the liver to obtain TBRblood pool and TBRliver.The diagnostic efficacy of SUVmax,TBRblood pool and TBRliver in Takayasu arteritis activity was compared using the receiver operating characteristic curve.The relationship between PET/CT parameters and Kerr score,erythrocyte sedimentation rate and C-reactive protein was evaluated.Results SUVmax,TBRblood pool and TBRliver in the active group were higher than those in the inactive group[3.70(3.03,5.18)vs.1.45(1.38,1.53),2.50(1.93,3.88)vs.0.91(0.79,1.16)and 1.37(1.00,1.96)vs.0.44(0.39,0.63);Z=5.510-5.900,all P<0.001],respectively.A SUVmax level of 2.65 was shown to be the best predictive cut-off value for Takayasu arteritis disease activity(sensitivity 83.7%,specificity 100%and area under the curve 0.91).A TBRblood pool level of 1.63 was shown to be the best predictive cut-off value for Takayasu arteritis disease activity(sensitivity 83.7%,specificity 94.4%and area under the curve 0.93).A TBRliver level of 0.81 was shown to be the best predictive cut-off value for Takayasu arteritis disease activity(sensitivity 87.0%,specificity 100%and area under the curve 0.94).SUVmax,TBRblood pool,TBRliver were all positively correlated with the Kerr score(r=0.88,0.89.0.90,all P<0.001),among which the correlation coefficient between TBRliver and the Kerr score was the highest.Conclusion SUVmax,TBRblood pool and TBRliver can evaluate disease activity in Takayasu arteritis patients,with TBRliver being the best.
3.Relationship Between Semi-Quantitative Parameters SUVmax and TBR of 18F-FDG PET/CT and Disease Activity of Takayasu Arteritis
Jingjing ZHANG ; Xin WEN ; Qiao RUAN ; Xingmin HAN ; Ruihua WANG
Chinese Journal of Medical Imaging 2025;33(5):562-566
Purpose To explore the relationship between semi-quantitative parameters maximum standard uptake value(SUVmax)and target-background ratio(TBR)of 18F-FDG PET/CT imaging and the activity of Takayasu arteritis.Materials and Methods A total of 110 patients with Takayasu arteritis from February 2016 to December 2022 in the First Affiliated Hospital of Zhengzhou University who underwent 18F-FDG PET/CT images were retrospectively reviewed.All Takayasu arteritis patients were divided into active(92 cases)and inactive groups(18 cases)according to Kerr score.The region of interest technique was used to measure the SUVmax of the arterial wall,and compares the SUVmax with the average SUV in the center of the inferior vena cava and the maximum SUV measured in the right lobe of the liver to obtain TBRblood pool and TBRliver.The diagnostic efficacy of SUVmax,TBRblood pool and TBRliver in Takayasu arteritis activity was compared using the receiver operating characteristic curve.The relationship between PET/CT parameters and Kerr score,erythrocyte sedimentation rate and C-reactive protein was evaluated.Results SUVmax,TBRblood pool and TBRliver in the active group were higher than those in the inactive group[3.70(3.03,5.18)vs.1.45(1.38,1.53),2.50(1.93,3.88)vs.0.91(0.79,1.16)and 1.37(1.00,1.96)vs.0.44(0.39,0.63);Z=5.510-5.900,all P<0.001],respectively.A SUVmax level of 2.65 was shown to be the best predictive cut-off value for Takayasu arteritis disease activity(sensitivity 83.7%,specificity 100%and area under the curve 0.91).A TBRblood pool level of 1.63 was shown to be the best predictive cut-off value for Takayasu arteritis disease activity(sensitivity 83.7%,specificity 94.4%and area under the curve 0.93).A TBRliver level of 0.81 was shown to be the best predictive cut-off value for Takayasu arteritis disease activity(sensitivity 87.0%,specificity 100%and area under the curve 0.94).SUVmax,TBRblood pool,TBRliver were all positively correlated with the Kerr score(r=0.88,0.89.0.90,all P<0.001),among which the correlation coefficient between TBRliver and the Kerr score was the highest.Conclusion SUVmax,TBRblood pool and TBRliver can evaluate disease activity in Takayasu arteritis patients,with TBRliver being the best.
4.The establishment of head and neck squamous cell carcinoma PDX models and humanized immune reconstruction
Bixue HUANG ; Kexing LYU ; Ruihua FANG ; Changlin LIU ; Jinhong ZHANG ; Shiyun LUO ; Jing YANG ; Qiao SU ; Wenbin LEI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(10):1243-1251
Objective:To construct patient-derived xenograft (PDX) models from head and neck squamous cell carcinoma (HNSCC) patients, to explore the effect of immune reconstitution timing on the PDX modeling and immune microenvironment in humanized immune system mice (huHSC-NCG-hIL15), and to provide a reliable animal model for research on the mechanisms of head and neck squamous carcinoma and for studies on immune therapy drug interventions.Methods:This study enrolled 28 HNSCC patients (25 laryngeal carcinomas, 3 hypopharyngeal carcinomas). PDX models were established in Balb/c nude (nu) mice, NSG mice, and humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Fresh HNSCC samples were transplanted into Balb/c nu and NSG mice to generate PDX models, with subsequent analysis of success-associated factors. One successfully established PDX tumor was subsequently implanted into humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Tumor transplantation was performed at distinct immune reconstruction timepoints (2 vs. 7 weeks post-reconstitution), and tumor growth patterns were monitored. Flow cytometry and multiplex immunohistochemical staining were utilized to characterize immunological profiles in peripheral lymphoid organs and tumor microenvironments. Hematoxylin-eosin (HE) staining was employed to assess histomorphological concordance between primary patient tumors and PDX model tissues. Results:HNSCC PDX models were successfully established. NSG mice exhibited a higher and more stable tumor take rate compared to Balb/c nu mice (pilot study: 4/10 vs. 3/10 cases; mean take rate 60%-80% vs. 20%-60 %). The PDX success rate in NSG mice was 46.4% (13/28). In the huHSC-NCG-hIL15 mice model with immune reconstitution at 7 weeks, tumors grew significantly faster, and the PDX modeling process was shorter (617 mm3 at day 70 in 7-week cohort vs.280 mm3 in 2-week cohort). Flow cytometry analysis of the immune microenvironment showed that at 7 weeks of immune reconstitution, the proportions of B cells in the spleen and tumor tissues(2-week vs. 7-week: spleen 16.2% vs. 61.7%, tumor 26.0% vs. 38.8%) and myeloid cells in the spleen (2-week vs. 7-week: spleen 47.2% vs. 88.1 %) were significantly higher, while mice at 2 weeks post-reconstitution showed a higher proportion of T cells (2-week vs. 7-week: spleen 13.2% vs. 9.3%, tumor 4.8% vs. 2.5%). HE results demonstrated that the tumor tissues in PDX models maintained a high degree of morphological similarity to the primary tumors in both NSG and huHSC-NCG-hIL15 mouse models. Conclusion:The HNSCC PDX modeling protocol demonstrates operational feasibility and high reproducibility, establishing this model as a robust platform for mechanistic and immunotherapeutic studies.
5.Effects of G-CSF on proliferation and fibrosis of lens epithelial cells
Ruihua JING ; Yunqing WANG ; Xinli QIAO ; Fei XUE ; Bo MA
Journal of Xi'an Jiaotong University(Medical Sciences) 2022;43(6):840-844
【Objective】 In recent years, granulocyte colony stimulating growth factor (G-CSF) has been proved to be expressed in the posterior capsule of the lens of posterior capsular opacification (PCO), but its specific role remains unclear. The purpose of this study was to explore whether G-CSF plays a role in PCO. 【Methods】 First, human lens epithelial cells (HLEC-B3) were treated with different concentration of recombinant G-CSF protein and screened for effective appropriate concentration. Then, Western blotting was used to detect the effects of extracellular matrix (ECM) synthesis and epithelial mesenchymal transdifferentiation (EMT) marker genes after G-CSF treatment on HLEC-B3 cells. Finally, the effects of G-CSF treatment on the migration and invasion of HLEC-B3 cells were detected by scratch experiment and Transwell test. 【Results】 G-CSF at 80 μg/L could promote the proliferation of HLEC-B3 cells. After G-CSF was treated for 48 h, the expressions of EMT and ECM synthesis marker genes in HLEC-B3 cells were significantly upregulated with time. G-CSF could significantly promote HLEC-B3 cell invasion after 48 h induction. Similarly, G-CSF could also significantly induce cell migration compared to the CTRL group. 【Conclusion】 G-CSF can promote the proliferation, migration and invasion of HLEC-B3 cells, as well as EMT and ECM synthesis, which might be involved in the occurrence of PCO. Inhibiting the expression of G-CSF may be a new strategy for PCO prevention.
6.Comparison of psychological anxiety between HBV-carrying pregnant women and healthy pregnant women and analysis of its influencing factors
Yuzhen ZHANG ; Kun QIAO ; Jiajun TU ; Ruihua TIAN ; Qiuyun LI ; Lili ZHANG ; Xingming LI
Chinese Journal of Modern Nursing 2020;26(22):3085-3089
Objective:To analyze the psychological anxiety and social support of HBV-carrying pregnant women and healthy pregnant women, and provide a reference for improving nursing interventions for hepatitis B virus (HBV) -carrying pregnant women.Methods:In this cross-sectional study, totally 314 pregnant women with HBV who attended outpatient services, established health files and had clear test results in a Beijing infectious disease specialist hospital from March to April 2019, and in two other ClassⅢ Grade A hospitals in the same period 420 healthy pregnant women were selected by convenient sampling. The Sociodemographic questionnaire, Self-Anxiety Scale (SAS) and Social Support Rating Scale (SSRS) were used to investigate the pregnant women.Results:There were statistically significant differences between HBV-carrying pregnant women and healthy pregnant women in education level, household registration status, family monthly income per capita, type of medical insurance, duration of pregnancy, status of pregnancy and subjective support scores ( P<0.05) . Multiple linear regression analysis controlling related factors found that whether the pregnant women carried the HBV had no effect on their psychological anxiety ( P>0.05) , and support utilization score, age, pregnancy days and education level affected the psychological anxiety of pregnant women ( P<0.05) .There was no statistically significant difference in SAS scores between the two groups of pregnant women ( t=-0.965, P>0.05) . Conclusions:The status of HBV carrying will not affect pregnant women's psychological anxiety, and factors such as social support utilization, education level, pregnancy days and age will have effect on pregnant women's psychological anxiety. It is recommended to take corresponding intervention measures to improve the utilization of social support, thereby alleviating the psychological anxiety of pregnant women.
7.A Novel Effect of Lipids Extracted from Vernix Caseosa on Regulation of Filaggrin Expression in Human Epidermal Keratinocytes
Wu QIAO ; Tinghan JIA ; Hongjian GU ; Ruihua GUO ; Ken KAKU ; Wenhui WU
Annals of Dermatology 2019;31(6):611-620
BACKGROUND: Vernix caseosa (VC), which is known as a unique human substance, is a biofilm that covers the skin of most human newborns. VC has many biological functions including anti-infective, skin cleansing and skin barrier repair. OBJECTIVE: In the study, we purpose to investigate the novel effect of lipids extracted from VC on the regulation of filaggrin (FLG) expression and anti-inflammation in normal human epidermal keratinocyte (NHEK) cells. METHODS: The lipids were extracted by chloroform/methanol (Folch method) and the major properties of fatty acid methyl esters were determined with gas chromatography-mass spectrometer. The relative viability of NHEK cells was evaluated by Cell Counting Kit 8 assay. The related expression of skin barrier protein was accessed with real-time quantitative polymerase chain reaction, Western blot and Immunofluorescence in NHEK cells with or without poly (I:C). Meanwhile, the changes of thymic stromal lymphopoietin (TSLP) and tumor necrosis factor alpha (TNF-α) are analyzed by enzyme-linked immunosorbent assay. RESULTS: VC lipids mostly contained saturated and branched chains fatty acids. The expression of mRNA and protein of FLG were significantly increased after the supplement with lipid in NHEK cells. Meanwhile, lipids reversed the inhibition of poly (I:C) on FLG. Moreover, lipids suppressed the over secretion of TSLP and TNF-α induced by poly (I:C). CONCLUSION: These results indicate that lipids extracted from VC has positive effects on the expression of FLG and anti-inflammation, suggesting that lipids of VC may be used for a reference for novel therapeutic method in reducing and remedying skin disease like atopic disease.
Biofilms
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Blotting, Western
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Cell Count
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Enzyme-Linked Immunosorbent Assay
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Esters
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Fatty Acids
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Fluorescent Antibody Technique
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Humans
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Infant, Newborn
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Inflammation
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Keratinocytes
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Methods
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Polymerase Chain Reaction
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RNA, Messenger
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Skin
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Skin Diseases
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Tumor Necrosis Factor-alpha
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Vernix Caseosa
8.Prognostic prediction value of pretreatment 18F-FDG PET/CT in pediatric neuroblastoma
Biao DU ; Baoping LIU ; Xingmin HAN ; Ruihua WANG ; Xinli XIE ; Qiao RUAN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2018;38(1):33-36
Objective To explore the prognostic value of pretreatment 18F-fluorodeoxyglucose (FDG) PET/CT in pediatric neuroblastoma (NB).Methods Twenty-seven NB patients (18 males,9 females;average age (4.6±2.4) years) confirmed by pathology from June 2012 to November 2015 were retrospectively included.All patients had detailed clinical and follow up data.They underwent 18F-FDG PET/CT scan before any treatment,and the largest diameter of primary tumors,maximum standardized uptake value (SUVmax) of primary tumor (Tmax),SUVmax of liver (Lmax),Tmax/Lmax ratio,clinical staging,serum ferritin,serum lactate dehydrogenase (LDH) and serum neuron-specific enolase (NSE) were recorded as prognostic factors.Patients were followed up after treatment for 3-32 months (median:24 months).KaplanMeier survival analysis was used to analyze the influence of Tmax and Tmax/Lmax ratio on 2-year progression free survival (PFS).Cox regression analysis was used to comprehensive analyze the influence of various factors on PFS.Results Of the 27 patients,12(44.4%) experienced disease progression during the follow-up period.Univariate analysis showed that N-myc gene amplification,serum LDH,serum NSE,serum ferritin,the largest diameter of primary tumors,Tmax and Tmax/Lmax ratio were significant prognostic factors for 2-year PFS.The multivariate analysis showed that only the Tmax and Tmax/Lmax,ratio were independent prognostic factors for 2-year PFS.Conclusion 18F-FDG PET/CT can provide effective information on the prognostic information for pediatric NB patients.
9.Quantitative analysis of human endogeneous retrovirus family W env1 in placentas of patients with preeclampsia in iodine deficiency areas
Liping ZHAI ; Lingxiao LIU ; Ruihua QIAO ; Shicun ZHENG
Chinese Journal of Endemiology 2015;34(12):866-869
Objective To detect the expression of human endogeneous retrovirus family W env1 (HERVWE1) in placentas of normal pregnant women and patients with preeclampsia and explore its role in the pathogenesis of preeclampsia.Methods Fifty-two cases of placental tissues provided by Shandong Maternity Hospital were from iodine deficiency areas (county or city:.Zhangqu, Changqing, Pingyin) of Shandong Province, including 30 cases of preeclampsia placentas as case group, 22 cases of normal term pregnancy placentas as control group.The mRNA expression of HERVWE1, human chorionic somator mammotropin (HCS), chorionic specific transcription factor (GCMa) and amino acyl carrier 2 (ASCT-2) in placentas of the two groups were determined by real-time PCR, and the protein expression of HERVWE1 was determined by Western blotting.Results The mRNA expression levels of HERVWE1 (0.149 ± 0.045 vs.0.409 ± 0.028) and HCS (336.600 ± 50.100 vs.815.600 ± 101.300) in placentas of patients with preeclampsia were significantly lower than those in the control group (t =25.60, 20.40,all P < 0.05).There were no significant difference in GCMa (0.022 ± 0.007 vs.0.024 ± 0.009) and ASCT-2 (0.423 ± 0.050 vs.0.438 ± 0.060) between the two groups (t =0.87, 0.95, all P > 0.05);Western blotting analysis showed that expression of HERVWE1 protein (0.340 ± 0.010 vs.0.580 ± 0.010) in placentas of the case group was lower than that in normal pregnant women (t =85.50, P < 0.05).Conclusion The expression of HERVWE1 is significantly decreased in placentas of the case group and is associated with pathogenesis of preeclampsia.
10.Comparison of two coils for MR angiography based on the SDNR method.
Longchen WANG ; Bin LI ; Yunfeng XIAO ; Ruihua QIAO
Chinese Journal of Medical Instrumentation 2011;35(4):256-259
In this paper, signal-to-noise ratio (SNR) and signal different-to-noise ratio (SDNR) methods were used to compare image quality using two different radiofrequency coils. The two coil types included an eight-element phased-array coil and a quadrature birdcage head coil with endcap and the comparison studies performed on a uniform cylindrical phantom and volunteer respectively. The results showed phased-array coil have advantages and proved effectiveness of the method in the evaluation and selection of coils.
Adult
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Cerebral Angiography
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methods
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Humans
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Magnetic Resonance Angiography
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methods
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Male
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Signal-To-Noise Ratio

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