1.A Single-Arm Phase II Clinical Trial of Fulvestrant Combined with Neoadjuvant Chemotherapy of ER+/HER2– Locally Advanced Breast Cancer: Integrated Analysis of 18F-FES PET-CT and Metabolites with Treatment Response
Qing SHAO ; Ningning ZHANG ; Xianjun PAN ; Wenqi ZHOU ; Yali WANG ; Xiaoliang CHEN ; Jing WU ; Xiaohua ZENG
Cancer Research and Treatment 2025;57(1):126-139
Purpose:
This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy.
Materials and Methods:
Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety.
Results:
Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways.
Conclusion
This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.
2.A Single-Arm Phase II Clinical Trial of Fulvestrant Combined with Neoadjuvant Chemotherapy of ER+/HER2– Locally Advanced Breast Cancer: Integrated Analysis of 18F-FES PET-CT and Metabolites with Treatment Response
Qing SHAO ; Ningning ZHANG ; Xianjun PAN ; Wenqi ZHOU ; Yali WANG ; Xiaoliang CHEN ; Jing WU ; Xiaohua ZENG
Cancer Research and Treatment 2025;57(1):126-139
Purpose:
This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy.
Materials and Methods:
Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety.
Results:
Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways.
Conclusion
This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.
3.A Single-Arm Phase II Clinical Trial of Fulvestrant Combined with Neoadjuvant Chemotherapy of ER+/HER2– Locally Advanced Breast Cancer: Integrated Analysis of 18F-FES PET-CT and Metabolites with Treatment Response
Qing SHAO ; Ningning ZHANG ; Xianjun PAN ; Wenqi ZHOU ; Yali WANG ; Xiaoliang CHEN ; Jing WU ; Xiaohua ZENG
Cancer Research and Treatment 2025;57(1):126-139
Purpose:
This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy.
Materials and Methods:
Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety.
Results:
Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways.
Conclusion
This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.
4.Influencing factor of acute multivessel occlusion and its impact on prognosis of acute large vessel occlusion stroke patients after successful recanalization of endovascular treatment
Yuepei GAO ; Chenglei WANG ; Yapeng GUO ; Junfeng XU ; Xianhui DING ; Xiangjun XU ; Ke YANG ; Qian YANG ; Xianjun HUANG ; Zhiming ZHOU
Chinese Journal of Cerebrovascular Diseases 2024;21(11):767-777
Objective To investigate the influencing factors for acute multiple vessels occlusion(MVO)and its impact on the prognosis of patients with anterior circulation acute large vessel occlusion stroke(ALVOS)who achieved successful recanalization after endovascular treatment(EVT).Methods Patients with anterior circulation ALVOS who received successful EVT at the Yijishan Hospital of Wannan Medical College between July 2015 and April 2023 were retrospectively analyzed.Baseline data,including age,sex,onset-to-puncture time(OTP),onset-to-recanalization time(OTR),medical history(including atrial fibrillation,diabetes,hypertension),alcohol and smoking history,admission blood pressure(systolic and diastolic),Alberta stroke program early CT score(ASPECTS),National Institutes of Health stroke scale(NIHSS)score,trial of Org 10172 in acute stroke treatment(TOAST)classification(atherosclerotic type,cardioembolic type,and other etiology types),and 90-day modified Rankin scale(mRS)score were collected.Collateral circulation was assessed based on the degree of contrast agent reflux observed in the occluded arterial supply area during delayed DSA,and patients were classified into poor and good collateral circulation groups.Malignant cerebral edema was defined as a midline shift of ≥5 mm on the follow-up CT scan performed on day 3 post-surgery.The primary endpoint(efficacy indicator)was the 90-day mRS score,with mRS score≤ 2 considered as a good prognosis and mRS score>2 considered as a poor prognosis.The secondary endpoint(safety indicator)was the 90-day mortality rate.All patients were divided into MVO and non-MVO groups based on whether they had single or multiple intracranial vessel occlusions.Acute MVO was defined as the detection of acute occlusion of other large or medium vessels,in addition to the main vessels(internal carotid artery or M1/M2 segments of the middle crebral artery[MCA]),in CT angiography,MR angiography,or DSA,resulting in ischemia in brain regions distinct from the main occlusion area.Factors that showed statistically significant differences in univariate analysis were further analyzed using multivariate Logistic regression to identify the risk factors for the occurrence of acute MVO and the factors associated with the prognosis of ALVOS patients.Results A total of 846 patients with ALVOS were included,with ages ranging from 26 to 94 years(mean age[69±11]years).The proportion of male patients was 57.2%(484/846).The median admission ASPECTS was 8(7,9)and the median admission NIHSS score was 14(12,18).The incidence of malignant cerebral edema at 3 days post-surgery was 13.4%(112/835),and the 90-day mortality rate was 19.1%(162/846).(1)Among the 846 ALVOS patients,810(95.7%)were in the non-MVO group and 36(4.3%)were in the MVO group.Univariate analysis showed significant differences between the MVO and non-MVO groups in terms of atrial fibrillation,malignant cerebral edema,admission ASPECTS,admission NIHSS scores,TOAST classification,collateral circulation,rate of complete recanalization,and 90-day poor prognosis rate(all P<0.05).However,there was no statistically significant difference in 90-day mortality between the two groups(P=0.193).Multivariate Logistic regression analysis showed that TOAST classification of cardioembolic type(OR,16.089,95%CI 1.835-141.061,P=0.012)and other etiology types(OR,9.768,95%CI 1.078-88.540,P=0.043)were associated with the occurrence of MVO.(2)Among the 846 ALVOS patients,445 had a good prognosis at 90days,and 401 had a poor prognosis.Univariate analysis showed that,compared to the good prognosis group,the poor prognosis group had a lower proportion of males and smokers,and a higher proportion of patients with older age,higher baseline systolic blood pressure,hypertension,diabetes,and atrial fibrillation(all P<0.01).Additionally,the poor prognosis group had higher admission NIHSS scores(P<0.01),lower admission ASPECTS,lower rates of good collateral circulation and complete recanalization,higher rates of malignant cerebral edema and MVO,and statistically significant differences in TOAST classification distribution(all P<0.01).Multivariate Logistic regression analysis showed that MVO was associated with poor 90-day prognosis in ALVOS patients after EVT(OR,3.368,95%CI 1.149-9.878,P=0.027).Furthermore,older age(OR,1.045,95%CI 1.025-1.066),diabetes(OR,1.719,95%CI 1.080-2.734),higher baseline systolic blood pressure(OR,1.012,95%CI 1.004-1.019),lower admission ASPECTS(OR,0.746,95%CI 0.674-0.826),higher admission NIHSS score(OR,1.115,95%CI 1.070-1.162),without immediate postoperative complete recanalization(OR,0.413,95%CI 0.290-0.592),poor collateral circulation(OR,0.594,95%CI 0.415-0.851),and malignant cerebral edema(OR,6.191,95%CI 3.026-12.670)were all associated with poor 90-day prognosis after EVT in ALVOS patients(all P<0.05).Conclusions The TOAST classification of cardioembolic type and other etiology types is associated with MVO.MVO is a risk factor for poor outcomes after successful EVT in ALVOS patients.
5.Molecular evolutionary of hemagglutinin gene of influenza A (H1N1) pdm09 virus in Shandong Province from 2009 to 2024
Zhihong ZHAO ; Yujie HE ; Julong WU ; Shaoxia SONG ; Lin SUN ; Zhong LI ; Xianjun WANG ; Zengqiang KOU ; Hongling WEN ; Ti LIU
Chinese Journal of Microbiology and Immunology 2024;44(7):580-587
Objective:To characterize and analyze the genetic variation of hemagglutinin (HA) of influenza A (H1N1) pdm09 subtype virus in Shandong Province, and explore the genetic variation patterns for providing reference for influenza monitoring, epidemic prevention and control, and vaccine strain selection.Methods:HA gene sequences of the recommended strains of influenza vaccine from 2009 to 2024 and the representative strains of each branch were downloaded from the GISAID Influenza Data Platform, and were phylogenetically analyzed and characterized in terms of amino acid site variation with the HA gene sequences of 298 influenza A (H1N1) virus strains isolated from Shandong Province. A phylogenetic tree was constructed using the maximum likelihood (ML) method of the IQ-TREE online tool, and the amino acid site variants were viewed using MegAlign software. The potential glycosylation sites of the HA gene were predicted using the NetNGlyc 1.0 online software.Results:The HA gene homology of the 298 influenza A (H1N1) viruses isolated in Shandong Province ranged from 91.2% to 100.0%. The evolutionary branches were gradually distantly related over time, but the direction of evolution was roughly the same as that in other provinces. Amino acid mutations in the HA occurred every year and most were found in the antigenic determinants.Conclusions:The HA genes of influenza viruses isolated in Shandong Province from 2009 to 2024 are still in the process of continuous evolution, and continuous monitoring of the epidemiological trends and the evolutionary directions of influenza viruses is essential for early warning of influenza virus pandemics.
6.Correlation study between cerebral microbleeds and cognitive dysfunction in patients with cerebral small vessel disease
Jianguo ZHOU ; Dayong FU ; Yundan WANG ; Xianjun MA
China Modern Doctor 2024;62(15):51-53,66
Objective To explore correlation between cerebral microbleeds(CMBs)and cognitive dysfunction in patients with cerebral small vessel disease.Methods A total of 80 patients with cerebral small vessel disease admitted to Department of Encephalopathy in Nanjing University of Chinese Medicine Affiliated Lianyungang Hospital from January 2020 to December 2022 were selected as research objects.They were divided into CMBs positive group(50 cases)and CMBs negative group(30 cases)based on the presence or absence of CMBs in the cerebral hemisphere.General clinical data of two groups were compared.Cognitive function was assessed by using Montreal cognitive assessment scale(MoCA).Results Age and incidence rate of hypertension in CMBs positive group were significantly higher than those in CMBs negative group(P<0.05).Total score of MoCA,scores of visuospatial and executive function,abstract thinking and delayed recall in CMBs positive group were significantly lower than those in CMBs negative group(P<0.05).Conclusion CMBs are closely related to the potential mechanism,clinical diagnosis and degree assessment of cognitive dysfunction in patients with cerebral small vessel disease.
7.Application of multimodal magnetic resonance imaging in the research on depression in Parkinson disease
Hui WANG ; Xianjun MA ; Jianxia XU
Journal of Apoplexy and Nervous Diseases 2024;41(11):993-998
Depression is one of the most common and earliest non-motor symptoms of Parkinson disease(PD)and can significantly increase the burden on PD patients,caregivers,and society.Due to the neglect of non-motor symptoms in clinical diagnosis and treatment and the overlaps between depression and other symptoms of PD,there are serious defi-ciencies in the diagnosis or treatment of depression in PD,and therefore,it is of great significance to identify objective bio-markers for depression in PD and investigate their application value.The development of multimodal magnetic resonance imaging makes it possible to achieve this goal.Multimodal MRI has revealed a wide range of brain lesions in PD with de-pression,with similar pathological changes as primary depression,as well as specific abnormalities in brain structure and function.At present,there is still no exact pathological model for PD with depression,and multimodal MRI has promising application prospects in exploring the pathophysiological mechanisms of PD with depression and identifying the biomarkers for early diagnosis and monitoring.
8.Prevalence and influencing factors of thyroid nodules among different occupational groups in Shijiazhuang City
Haihong ZHANG ; Wei WANG ; Zhenguo MU ; Sujuan ZHENG ; Zhihui MA ; Xianjun LIU
Chinese Journal of Endemiology 2024;43(9):726-731
Objective:To investigate the prevalence and related influencing factors of thyroid nodules in different occupational groups in Shijiazhuang City.Methods:Different occupational groups who underwent physical examination at the Second Hospital of Shijiazhuang City from May to December 2015 and had lived there for more than 10 years were selected as the investigation subjects, including workers, farmers, science and technology education personnel, medical and health personnel, civil servants and individual businessmen. Questionnaire survey and thyroid examination were conducted, blood lipid, blood glucose and thyroid hormone levels were tested, and related influencing factors of thyroid nodules were analyzed.Results:A total of 1 440 different occupational subjects were surveyed, and the prevalence of thyroid nodules was 20.35% (293/1 440). The prevalence of thyroid nodules in females (22.59%, 159/704) was significantly higher than that in males (18.21%, 134/736), and the difference was statistically significant (χ 2 = 4.26, P = 0.039). There was a statistically significant difference in the prevalence of thyroid nodules in different age groups (χ 2 = 73.87, P < 0.001), with the highest prevalence in the 70 - 80 age group (43.75%, 21/48). There was a statistically significant difference in the prevalence of thyroid nodules among different occupational groups (χ 2 = 36.56, P < 0.001), with the highest prevalence in individual businessmen (31.84%, 78/245). By univariate analysis, the prevalence of thyroid nodules in people with good economic status [27.45% (42/153) vs 19.48% (248/1 273)], radiation exposure history [26.39% (109/413) vs 17.92% (184/1 027)], and diabetes history [33.71% (30/89) vs 19.47% (263/1 351)] was higher (χ 2 = 5.35, 13.06, 10.45, P < 0.05). Conclusions:The prevalence of thyroid nodules in occupational group in Shijiazhuang City is relatively high, and the prevalence of thyroid nodules in females is significantly higher than that in males. Economic status, radiation exposure history and diabetes history are the main influencing factors.
9.Postnatal age-related change of brain volume and its association with neurobehavior outcome in term neonates
Yuying FENG ; Linlin ZHU ; Pengxuan BAI ; Yao GE ; Miaomiao WANG ; Congcong LIU ; Xianjun LI ; Jian YANG ; Chao JIN
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(1):133-138
Objective To analyze the relationship of the volume of 87 brain regions with postnatal age and neurobehavior in full-term neonates.Methods A total of 75 full-term newborns[gestational age(39.38±1.22)weeks;male/female(51/24);postnatal age(11.11±6.67)days]without abnormalities on brain MRI(three-dimensional T1-weighted imaging,3D T1WI)at our hospital between November 2010 and September 2017 were retrospectively included.Based on the template of 87 brain regions,the neonatal brains were divided into 87 brain regions and their volumes were calculated by using V-shape Bottleneck network(VB-Net)deep learning segmentation technique,Pearson partial correlation and regression analysis were used to explore the relationship of the volume of each brain region with postnatal age and neurobehavioral scores.Results After adjusting for gestational age,birth weight,head circumference,body length and sex,66.7%of the regional brain volumes(58/87 brain regions)significantly increased with the postnatal age(correlation coefficient r:0.2-0.7,P<0.05).The volumes of gray matter in bilateral lentiform nucleus,left caudate nucleus,right occipital lobe,right inferior temporal lobe,and bilateral anterior temporal lobe strongly correlated with the postnatal age(r>0.50,P<0.05).The gray matter volume of the right occipital lobe linearly increased with age(slope:100.67),and was positively correlated with behavioral scores(r=0.324,P<0.01).Conclusion Most of regional brain volumes increase with the postnatal age during the neonatal period,and the fastest growth occurs in primary sensorimotor-related brain regions,presenting the spatial heterogeneity.Partial brain region grows with the development of behavioral ability.
10.Effects of 3.0T magnetic resonance noise on the hearing of children aged 0-12 years with routine hearing protection
Huifang ZHAO ; Chao JIN ; Fangyao CHEN ; Cong TIAN ; Peiyao CHEN ; Xiaoyu WANG ; Miaomiao WANG ; Congcong LIU ; Xianjun LI ; Jian YANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(1):145-149
Objective To explore the effect of exposure to noise of 3.0T magnetic resonance imaging(MRI)on children's cochlear function.Methods We prospectively recruited 72 children who underwent cranial MRI examination at our hospital from May to November 2018;3M earplugs and sponge mats were used for hearing protection during MRI scanning.Noise level(dBA)of each MRI sequence was detected with a nonmagnetic microphone and a sound level meter.Distortion product otoacoustic emissions(DPOAE)test at 2-7 kHz was performed 24 hours before and 30 minutes after the MRI examination.Paired t-test or Wilcoxon signed-rank test was used to analyze differences in DPOAE amplitude before and after the MRI examination.Results The average noise level of MRI measured in the study was(107.7±3.92)dBA.Compared with that before the MRI examination,the DPOAE amplitude(dB)changed little after the MRI examination;the range of amplitude differences in each age group was as follows:left ear(-0.24-1.10)and right ear(-0.24-0.74)in the 0-1 year-old group;left ear(-0.07-0.59)and right ear(-0.57-0.75)in the 2-5 year-old group;left ear(-0.36-0.44)and right ear(-0.30-0.57)in the 6-12 year-old group.No statistically significant difference was found(correction P>0.05).Conclusion No potential impact of 3.0T MRI noise on children's cochlear function was observed under routine hearing protection.

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