1.Preclinical study of a novel molecular probe 89Zr DFO-G4C2 for monitoring PD-1 expression levels
Yirong ZHU ; Weiwei KONG ; Jiaxi YOU ; Kairu NI ; Bing ZHANG ; Zengli LIU ; Yizhen SHI ; Zhihui HONG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(10):603-608
Objective:To design and synthesize 89Zr-deferoxamine(DFO)-G4C2, a novel molecular probe targeting programmed cell death receptor 1(PD-1), and evaluate its in vivo biodistribution and microPET/CT imaging characteristics in tumor-bearing mice. Methods:DFO-G4C2 was prepared by coupling DFO with G4C2, a monoclonal antibody targeting PD-1. The affinity and binding specificity of this amalgamation were subsequently assessed through the implementation of flow cytometry and surface plasmon resonance techniques. The molecular probe 89Zr-DFO-G4C2 was achieved by labeling DFO-G4C2 with the radioisotope 89Zr, and the labeling efficiency and in vitro stability of 89Zr-DFO-G4C2 were determined. Mouse models laden with CT26 colorectal cancer cells expressing PD-1 were established, followed by in vivo biodistribution and microPET/CT imaging studies, to explore the potential clinical value of 89Zr-DFO-G4C2. Additionally, the validity of this molecular probe was verified in 4T1 breast cancer models, affirming its efficacy as an imaging tool across different tumor models. Independent-sample t test was used to analyze the data. Results:DFO-G4C2 exhibited an affinity constant KD of (0.55±0.02) μmol/L, indicating a strong binding affinity. The binding rate to mouse PD-1 protein was determined to be (61.82±8.49)%. The labeling rate of 89Zr-DFO-G4C2 reached a high level of (98.76±0.51)%. Furthermore, the labeling rates in lysate and human serum after 144 h were measured to be (93.07±2.16)% and (83.42±3.21)%, respectively. MicroPET/CT imaging of CT26 tumor-bearing mice injected with 89Zr-DFO-G4C2 showcased pronounced radioactivity uptake in the tumor tissue. At 72 h post-injection, the tumor uptake value reached (10.47±0.34) percentage activity of injection dose per gram of tissue (%ID/g). The tumor uptake observed in the blocked experimental group, wherein an excess of unlabeled antibody was administered, was significantly lower at (6.26±1.03) %ID/g in comparison to the non-blocked group ( t=6.67, P=0.003). The in vivo biodistribution results were consistent with the observed microPET/CT imaging outcomes. MicroPET/CT imaging observations in the 4T1 breast cancer bearing mouse model were analogous to those obtained from the CT26 model. Conclusion:ImmunoPET based on the 89Zr-DFO-G4C2 molecular probe can non-invasively and visually assess the PD-1 expression level of tumors in vivo, and it is expected to be a new molecular imaging technique for immunotherapy monitoring of PD-1 inhibitors.
2.Correlation of Neutrophil-Lymphocyte and Albumin-Globulin Ratios With Outcomes in Patients With Breast Cancer Undergoing Neoadjuvant Chemotherapy or Upfront Surgery
Shi Hui YANG ; Min Li TEY ; Siqin ZHOU ; Phyu NITAR ; Hanis MARIYAH ; Yirong SIM ; Grace KUSUMAWIDJAJA ; Wen Yee CHAY ; Wong Fuh YONG ; Ru Xin WONG
Journal of Breast Cancer 2024;27(2):105-120
Purpose:
Higher neutrophil-lymphocyte ratio (NLRs) indicate a pro-inflammatory state and are associated with poor survival. Conversely, higher albumin-globulin ratio (AGRs) may be associated with improved prognosis. We aimed to investigate the association between NLR and AGR and prognosis and survival in patients with breast cancer.
Methods:
This retrospective study included all patients with stage I–III breast cancer between 2011 and 2017 in Singapore General Hospital and National Cancer Center Singapore.Multivariate logistic regression analysis of NLR, AGR, age, stage, grade, and subtype was performed. Survival data between groups were compared using Cox regression analysis and log-rank tests.
Results:
A total of 1,188 patients were included, of whom 323 received neoadjuvant chemotherapy (NACT) and 865 underwent upfront surgery. In patients who underwent NACT, a higher AGR was significantly associated with a higher pCR rate (cut-off > 1.28; odds ratio [OR], 2.03; 95% confidence interval [CI], 1.13–3.74; p = 0.020), better DFS (cut off > 1.55; hazard ratio [HR], 0.37; 95% CI, 0.16–0.85; p = 0.019), and better CSS (cut off > 1.46; HR, 0.39; 95% CI, 0.17–0.92; p = 0.031). Higher NLR was significantly associated with worse DFS (cut off > 4.09; HR, 1.77; 95% CI, 1.07–2.91; p = 0.026) and worse CSS (cut off > 4.09; HR, 1.98; 95% CI, 1.11–3.53; p = 0.021). In patients who underwent upfront surgery, higher AGR correlated with significantly better OS (cut off > 1.17; HR, 0.54; 95% CI, 0.36–0.82; p = 0.004) and higher NLR correlated with worse OS (cut off > 2.38; HR, 1.63; 95% CI, 1.09–2.44; p = 0.018).
Conclusion
NLR and AGR are useful in predicting the response to NACT as well as prognosis of patients with breast cancer. Further studies are needed to explore their value in clinical decision making.
3.Construction of an intervention program for diabetic retinopathy patients undergoing surgery based on the theory of'Timing It Right'
Mengyue ZHANG ; Yinghui SHI ; Xiaoxian ZHANG ; Chen CHEN ; Yirong HONG ; Weidan XIA ; Yanyan CHEN
Chinese Journal of Nursing 2023;58(24):2957-2963
Objective To construct an intervention program for diabetic retinopathy(DR)patients undergoing surgery based on the theory of'Timing It Right'.Methods Guided by the theory of'Timing It Right',based on literature review and semi-structured interview,the first draft of the intervention program was formulated.From December 2022 to February 2023,15 medical and nursing experts in ophthalmology and endocrinology from 5 provinces(cities)in Zhejiang,Sichuan,Shanxi,Chongqing and Shanghai were interviewed by Delphi expert for 2 rounds to seek their advice and revision,and the final draft was formed.Results The effective recovery rate of 2 rounds of expert consultations was 93.75%and 100%.The authority coefficients were 0.87.The importance and feasibility of Kendall'W coordination coefficients were 0.325,0.138 and 0.193,0.141 in 2 rounds,respectively(P<0.001).The finalized intervention program consisted of 6 months,which included 5 first-level items,18 second-level items and 43 third-level items.Conclusion The intervention program for DR patients undergoing surgery based on the theory of'Timing It Right'is reliable,scientific,feasible and practical,and it can meet the needs of such patients,providing a reference for improving their self-management ability,improving their negative emotions and delaying disease progression.
4.Accuracy of progress assessment with clear aligners.
Bo LI ; Yimeng XU ; Ruiying SHI ; Yirong HU ; Siying LIU ; Zexu GU
West China Journal of Stomatology 2022;40(6):698-703
OBJECTIVES:
This study aimed to investigate the accuracy of model superimposition and automatic analysis for upper and lower dentition widths in iTero Progress Assessment during the clear aligner process.
METHODS:
Nineteen cases were included in this retrospective case control study. Pretreatment dental cast (T0) and post treatment dental cast after staged treatment (T1) were available for three-dimensional (3D) model superimposition. The movements of maxillary teeth in the horizontal plane (cross section) after staged treatment and the widths of upper and lower dentitions were measured by 3D model superimposition in real world and iTero Progress Assessment. The data collected from the two methods were compared.
RESULTS:
The movements [Median (upper and lower quartiles)] of maxillary teeth in the horizontal plane after staged treatment were 2.31 (1.59, 3.22) and 1.79 (1.21, 3.03) mm in iTero Progress Assessment and 3D model analysis, respectively. Significant difference was observed between the two groups (P<0.05). In the measurement of upper and lower dentition width, four indicators were measured, including intercanine width upper, intermolar width upper, intercanine width lower, and intermolar width lower. Before treatment, the measurement of iTero Progress Assessment were (35.78±2.49), (56.21±2.51), (27.43±1.38), (52.26±2.91) mm, respectively, and actual measurement were (35.77±2.53), (56.17±2.47), (27.40±1.41), (52.30±2.86) mm, respectively, without significant difference (P>0.05). After stage treatment, the measurement of iTero Progress Assessment were (37.37±2.86), (57.76±2.56), (28.89±2.00), (54.16±2.19) mm, respectively, and actual measurement were (37.29±2.94), (57.71±2.63), (28.88±2.05), (54.01±2.15) mm, respectively, and there was no significant difference (P>0.05).
CONCLUSIONS
The data from iTero Progress Assessment did not coincide with the model superimposition results with palate as reference. The accuracy of model superimposition in iTero Progress Assessment needs further investigation, whereas the arch width analysis is accurate. Therefore, iTero Progress Assessment results should be interpreted with caution by orthodontists in clinical applications.
Case-Control Studies
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Cuspid
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Dental Arch
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Orthodontic Appliances, Removable
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Retrospective Studies
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Humans
5.Analysis of the trend of medication use in patients with ulcerative colitis in a single center from 2010 to 2019
Xianmin XUE ; Song SU ; He ZHOU ; Yujie ZHANG ; Jiayao WANG ; Yirong JIN ; Yongquan SHI ; Kaichun WU ; Jie LIANG
Chinese Journal of Digestion 2021;41(9):624-628
Objective:To analyze the trend of medication use in patients with ulcerative colitis (UC) in recent ten years in at Xijing Hospital, Air Force Military Medical University.Methods:From 2010 to 2019, the clinical data of 1 425 patients diagnosed with UC in the Department of Gastroenterology at Xijing Hospital, Air Force Medical University, were retrospectively collected. According to the period of medication, the UC patients were divided into year 2010 to 2014 group and year 2015 to 2019 group. The general information and the medication trend of year 2010 to 2014 group and year 2015 to 2019 group were analyzed. And then according to gender and age (<40 years old and ≥40 years old), patients were divided into subgroups and analyzed. Independent sample t test and chi-square test were used for statistical analysis. Results:The number of UC patients of year 2010 to 2014 group and year 2015 to 2019 group was 369 and 1 056, respectively. The percentages of patients in remission of the two groups were 9.5% (35/369) and 12.0% (127/1 056), respectively; the percentages of mild patients were 40.4% (149/369) and 41.6% (439/1 056), respectively; the percentages of moderate patients were 37.4% (138/369) and 28.9% (305/1 056), respectively; the percentages of severe patients were 12.7% (47/369) and 17.5% (185/1 056), respectively. There was no significant difference in the proportion of UC patients with different degrees between year 2010 to 2014 group and year 2015 to 2019 group ( P>0.05). There were no significant differences in the age and proportion of female between the year 2010 to 2014 group and year 2015 to 2019 group ((46.2±15.3) years old vs. (44.6±30.6) years old; 45.8%, 169/369 vs. 44.8%, 473/1 056; both P>0.05). The utilization rates of 5-aminosalicylic acid (5-ASA), glucocorticoid, immunosuppressants, and biological agents of the year 2015 to 2019 group were all higher than those of the year 2010 to 2014 group (96.8%, 1 022/1 056 vs. 90.0%, 332/369; 29.9%, 316/1 056 vs. 14.6%, 54/369; 8.4%, 89/1 056 vs. 2.4%, 9/369; 4.8%, 51/1 056 vs. 0.5%, 2/369, respectively), and the differences were all statistically significant ( χ2=26.766, 33.256, 15.315 and 14.038, all P<0.01). Within each of the year 2010 to 2014 group and the year 2015 to 2019 group, there were no significant differences between the female and male in the age, utilization rates of 5-ASA, glucocorticoid, immunosuppressants and biological agents ((47.2±13.6) years old vs. (45.3±16.5) years old, (43.1±12.9) years old vs. (45.8±39.5) years old, 88.8%, 150/169 vs. 91.0%, 182/200; 96.8%, 458/473 vs. 96.7%, 564/583; 13.6%, 23/169 vs. 15.5%, 31/200; 28.3%, 134/473 vs. 31.2%, 182/583; 2.4%, 4/169 vs. 2.5%, 5/200; 7.0%, 33/473 vs. 9.6%, 56/583; 0 vs. 1.0%, 2/200; 5.3%, 25/473 vs. 4.5%, 26/583; all P>0.05). In the patients aged≥40 years old of the year 2010 to 2014 group, the proportion of females was higher than that of the patients aged <40 years old (50.2%, 121/241 vs. 37.5%, 48/128), and the utilization rate of 5-ASA in patients aged ≥40 years old was lower than that of patients aged <40 years old (85.9%, 207/241 vs. 97.7%, 125/128), and the differences were statistically significant ( χ2=5.438 and 12.824, P=0.020 and P<0.01). In the year 2010 to 2014 group, there were no statistically significant differences in the utilization rates of glucocorticoid, immunosuppressants and biological agents between patients aged ≥40 years old and patients aged <40 years old (13.7%, 33/241 vs. 16.4%, 21/128; 2.1%, 5/241 vs. 3.1%, 4/128; 0 vs. 1.6%, 2/128; all P>0.05). In the year 2015 to 2019 group, the utilization rate of biological agents in patients aged≥40 years old was lower than that in patients aged<40 years old (3.7%, 23/630 vs. 46.5%, 198/426), and the difference was statistically significant ( χ2=4.721, P=0.030). In the year 2015 to 2019 group, there were no statistically significant differences in female proportion, utilization rates of 5-ASA, glucocorticoid, immunosuppressants and biological agents between patients aged≥40 years old and patients aged <40 years old (43.7%, 275/630 vs. 46.5%, 198/426; 96.0%, 605/630 vs. 97.9%, 417/426; 29.7%, 187/630 vs. 30.3%, 129/426; 8.6%, 54/630 vs. 8.2%, 35/426; all P>0.05). Conclusions:Compared with year 2010 to 2014, the number of UC patients remarkably increased in the year 2015 to 2019 in the Department of Gastroenterology, Xijing Hospiatal, Air Force Medical University. The utilization rates of 5-ASA, glucocorticoid, immunosuppressants and biological agents all increased in UC patients. The medication trends of UC patients with different gender were almost the same. The medication trends of UC patients with different age were different.
6.Confirmatory factor analysis of the Montreal Cognitive Assessment in evaluating elderly mild cognitive impairment
Xinxiu DONG ; Hui HU ; Ling WANG ; Yating AI ; Chongming YANG ; Kaili SUN ; Yirong SHI ; Mengying LI
Chinese Journal of Neurology 2018;51(12):966-971
Objective To assess the psychometric potential of the Montreal Cognitive Assessment Scale-Beijing (MoCA-BJ) as a screening instrument for mild cognitive impairment (MCI) in older adults in Wuhan communities of central China. Methods MoCA-BJ and Mini-Mental State Examination (MMSE) were adopted to assess the MCI of 381 older adults from 13 communities in Wuhan in 2015. Confirmatory factor analysis was conducted to evaluate the construct validity of MoCA-BJ, and the relationship between all aspects of cognitive function and MoCA different dimensions. Results MoCA-BJ had acceptable reliability (w=0.76), and MoCA-BJ and MMSE estimation results were highly correlated (r=0.73, P<0.01). By comparing three measurement models through confirmatory factor analysis, we found that the MoCA-BJ scale had two factors (F1: visual space executive function, F2: memory-based other cognitive functions) in model 3, fit degree of which was higher than model 1 by one factor, and there was a statistically significant difference in the number of factors between model 1 and model 3 (χ2dif=8.73,P<0.01). Conclusions The MoCA-BJ has two underlying factors that respectively represent two highly correlated but distinct factors, cognition and visual-spatial. Uninformative items should be revised with culturally sensitive items and the cut-off point for mild impairment should also be altered.
7.Recent technical research hot spots and development progresses in medical whole-body positron emission tomography.
Han SHI ; Dong DU ; Zhihong SU ; Jianfeng XU ; Yirong ZOU ; Qiyu PENG
Journal of Biomedical Engineering 2015;32(1):218-224
Medical whole-body positron emission tomography (PET), one of the most successful molecular imaging technologies, has been widely used in the fields of cancer diagnosis, cardiovascular disease diagnosis and cranial nerve study. But, on the other hand, the sensitivity, spatial resolution and signal-noise-ratio of the commercial medical whole-body PET systems still have some shortcomings and a great room for improvement. The sensitivity, spatial resolution and signal-noise-ratio of PET system are largely affected by the performances of the scintillators and the photo detectors. The design of a PET system is usually a trade-off in cost and performance. A better image quality can be achieved by optimizing and balancing the key components which affect the system performance the most without dramatically increases in cost. With the development of the scintillator, photo-detector and high speed electronic system, the performance of medical whole-body PET system would be dramatically improved. In this paper, we report current progresses and discuss future directions of the developments of technologies in medical whole-body PET system.
Humans
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Positron-Emission Tomography
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trends
8.Analysis of the risk factors of hepatocellular carcinoma in cirrhotic patients with chronic hepatitis B.
Yuanqing ZHANG ; Lijun PENG ; Yirong CAO ; Zhiping ZENG ; Yujing WU ; Hong SHI ; Shiyao CHEN ; Jinsheng GUO
Chinese Journal of Hepatology 2015;23(7):512-516
OBJECTIVETo identify risk factors of hepatocellular carcinoma (HCC) in cirrhotic patients with chronic hepatitis B (CHB).
METHODSA total of 715 cirrhotic patients with CHB were recruited from the Zhongshan Hospital Affiliated to Fudan University and enrolled in this case-control study between January 2009 and September 2014. All participants were Chinese Han residing in Shanghai and the surrounding areas. The patients were divided into a cirrhosis group (n =281) and a HCC group (n=434). History of hepatitis B infection and HCC, as well as clinical data from serological, imaging and pathological examinations were collected for analysis.SPSS software, version 19.0, was used for all statistical comparisons.
RESULTSSingle factor analysis indicated that development of HCC in cirrhotic patients with CHB was significantly associated with male sex, age of 50 years or more, family history of HCC, alcohol consumption,fatty liver, detectable levels of hepatitis B virus (HBV) DNA, and history of HBV infection without effective antiviral treatment. Multivariate logistic regression analysis indicated that age of 50 years or more (P =0.005, odds ratio [OR] =1.766), history of alcohol consumption (P =0.002, Or = 2.570), family history of HCC (P =0.014, Or = 2.268), fatty liver (P =0.023, Or = 3.390), and history of HBV infection without effective antiviral treatment (P < 0.001,Or = 5.389) were risk factors of HCC.The risk factors for development of HCC in cirrhotic patients with hepatitis B after achieving sustained virologic suppression (SVS) were family history of HBV infection (P =0.014, Or = 2.537), family history of HCC (P =0.037,Or = 3.339) and fatty liver (P =0.018, Or = 11.646).
CONCLUSIONRisk factors of HCC in cirrhotic patients with CHB include age,drinking history,family history of HCC, fatty liver, and ineffective antiviral treatment of CHB.Family history of HBV infection or HCC, and fatty liver disease, were significantly associated with HCC development after SVS in patients with hepatitis B-related cirrhosis.
Alcohol Drinking ; Antiviral Agents ; Carcinoma, Hepatocellular ; Case-Control Studies ; China ; Fatty Liver ; Hepatitis B virus ; Hepatitis B, Chronic ; Humans ; Liver Cirrhosis ; Liver Neoplasms ; Male ; Odds Ratio ; Risk Factors
9.Mechanisms of hyperglycemia induced by immunosuppressant FK506
Ling ZHANG ; Meng SUN ; Bo SHI ; Lili TANG ; Cunzao WU ; Yong CAI ; Peng XIA ; Shaoling ZHENG ; Yirong YANG ; Bicheng CHEN
Chinese Journal of Pathophysiology 2014;(8):1363-1367
[ABSTRACT]AIM:ToinvestigatetheeffectofimmunosuppressantFK506onserumglucoseinratsandtoex-plore its mechanism .METHODS: Sprague-Dawley rats ( n =12 ) were randomly divided into drug group and normal group.The rats in drug group were intraperitoneally injected with FK 506 at dose of 1 mg· kg-1 · d-1 and the rats in nor-mal group received saline (1 mL· kg-1 · d-1 , ip) for 14 d.The fasting weight and fasting glucose were regularly meas-ured every 2 d.Visceral fat was isolated from the rats at the end of experiment .The mRNA expression of adiponectin , lep-tin, visfatin, resistin, retinol-binding protein 4 ( RBP4) and peroxisome proliferator-activated receptors γ( PPAR-γ) was determined by real-time fluorescence quantitative PCR .The protein expression of PPAR-γand adiponectin was measured by Western blotting .RESULTS:Compared with normal group , the concentration of fasting blood glucose in model group was significantly increased from the 10th day (P<0.05).At day 14, the fasting blood glucose of the model group increased from (5.10 ±0.62) mmol/L to (7.73 ±0.73) mmol/L.No significant change of blood glucose in normal group between the 10th day and the 14th day [from (4.66 ±0.32) mmol/L to (5.80 ±0.10) mmol/L] was observed.Compared with normal group , the mRNA expression of PPAR-γ, adiponectin and leptin in the adipose tissue of model group was signifi-cantly decreased ( P <0.01 ) , whereas the expression of visfatin , resistin and RBP4 was significantly increased ( P <0.05).Compared with normal group, the expression of PPAR-γand adiponectin in model group was decreased (P <0.01).CONCLUSION:FK506 may decrease the expression of PPAR-γto change the expression of adipocytokines and induce hyperglycemia in rats .
10.Predictive value of spiral CT in composition changes of pediatric urinary stones
Yuan LI ; Xinsheng XI ; Xiaorui RU ; Gang HUANG ; Baoguang SHI ; Weihua LI ; Li DONG ; Yirong CHEN
Chinese Journal of Urology 2011;32(12):843-845
Objective To investigate the predictive value of spiral CT in composition changes of pediatric urinary.Methods A total of 25 pediatric patients with urinary stones were investigated.Eighteen patients with renal stones were stratified into two groups:an alkalization therapy alone group ( n =9 ) and a comprehensive therapy group (n =9).Flame atomic absorption spectrum (AAS) was employed to measure calcium level of the pediatric urinary stones.Spiral CT was employed to measure the peak CT number in vitro of all the pediatric urinary stones and 61 adult urinary stones,which served as controls.Results All pediatric urinary stones contained calcium ( 0.11% - 26.30% ).A positive correlation was observed between the CT number of pediatric urinary stone and its stone calcium level ( r =0.855,P < 0.01 ).Compared to the alkalization therapy alone group,the CT number and stone calcium level of pediatricrenal stones in the comprehensive therapy group were significant higher (stone CT number:162 ± 60 HU VS.783 ±476 HU,P < 0.01 ; stone calcium level:1.30 ± 1.52% VS 19.83 ± 7.48%,P < 0.01 ).Compared to ≤400 HU pediatric renal stones,> 400 HU renal stones contained more calcium (21.71 ± 5.27%,1.65 ±1.82%,P < 0.01 ) and failed to dissolve by alkalization therapy alone ( x2 =11.455,P < 0.01 ).Conclusions CT could be a predictive tool for composition changes of pediatric urinary stones.In clinical CT scanning setting,>400 HU pediatric urinary stones probably will contain more calcium and not be suitable for alkalization therapy alone.

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