1.Software-aided efficient identification of the components of compound formulae and their metabolites in rats by UHPLC/IM-QTOF-MS and an in-house high-definition MS2 library:Sishen formula as a case
Hong LILI ; Wang WEI ; Wang SHIYU ; Hu WANDI ; Sha YUYANG ; Xu XIAOYAN ; Wang XIAOYING ; Li KEFENG ; Wang HONGDA ; Gao XIUMEI ; Guo DE-AN ; Yang WENZHI
Journal of Pharmaceutical Analysis 2024;14(10):1484-1495
Identifying the compound formulae-related xenobiotics in bio-samples is full of challenges.Conventional strategies always exhibit the insufficiencies in overall coverage,analytical efficiency,and degree of automation,and the results highly rely on the personal knowledge and experience.The goal of this work was to establish a software-aided approach,by integrating ultra-high performance liquid chromatography/ion-mobility quadrupole time-of-flight mass spectrometry(UHPLC/IM-QTOF-MS)and in-house high-definition MS2 library,to enhance the identification of prototypes and metabolites of the compound formulae in vivo,taking Sishen formula(SSF)as a template.Seven different MS2 acquisition methods were compared,which demonstrated the potency of a hybrid scan approach(namely high-definition data-independent/data-dependent acquisition(HDDIDDA))in the identification precision,MS1 coverage,and MS2 spectra quality.The HDDIDDA data for 55 reference compounds,four component drugs,and SSF,together with the rat bio-samples(e.g.,plasma,urine,feces,liver,and kidney),were acquired.Based on the UNIFI? platform(Waters),the efficient data processing workflows were estab-lished by combining mass defect filtering(MDF)-induced classification,diagnostic product ions(DPIs),and neutral loss filtering(NLF)-dominated structural confirmation.The high-definition MS2 spectral li-braries,dubbed in vitro-SSF and in vivo-SSF,were elaborated,enabling the efficient and automatic identification of SSF-associated xenobiotics in diverse rat bio-samples.Consequently,118 prototypes and 206 metabolites of SSF were identified,with the identification rate reaching 80.51%and 79.61%,respectively.The metabolic pathways mainly involved the oxidation,reduction,hydrolysis,sulfation,methylation,demethylation,acetylation,glucuronidation,and the combined reactions.Conclusively,the proposed strategy can drive the identification of compound formulae-related xenobiotics in vivo in an intelligent manner.
2.Significance of 18F-PI-2620 PET imaging for diagnosing tau protein deposition in patients with different cognitive disorders alongside cognitive correlation analysis
Gan HUANG ; Yan ZHANG ; Cheng WANG ; Mei XIN ; Hongda SHAO ; Yue WANG ; Liangrong WAN ; Ju QIU ; Qun XU ; Jianjun LIU ; Xia LI ; Chenpeng ZHANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(5):273-278
Objective:To evaluate the values of 18F-PI-2620 PET/CT brain imaging with SUV ratio (SUVR) in the assessment of tau protein deposition in the brain of patients with different cognitive disorders and its correlation with cognition. Methods:This was a cross-sectional study. From December 2019 to November 2022, a total of 67 subjects including 54 patients with Alzheimer′s disease (AD; 21 males, 33 females, age (68.6±7.8) years), 7 patients with mild cognitive impairment (MCI; 1 male, 6 females, age (63.1±11.2) years) and 6 healthy controls (HC; 4 males, 2 females, age (69.0±5.8) years) were enrolled retrospectively in Renji Hospital. All participants were examined by 18F-PI-2620 PET/CT. SUVRs of brain regions were obtained, including frontal lobe, temporal lobe, occipital lobe, parietal lobe, insular lobe, whole brain, as well as 10 independent brain ROIs (amygdala, orbitofrontal cortex, cingulate gyrus, superior occipital gyrus, superior parietal gyrus, inferior angular gyrus, precuneus, inferior temporal gyrus, entorhinal cortex and parahippocampal gyrus), with inferior cerebellum cortex as the reference region. All participants were estimated by cognitive scales(mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA)). One-way analysis of variance and the least significant difference t test were used to compare the differences of SUVR in each brain region among HC, MCI and AD groups. ROC curve analysis was used to determine the optimal cut-off values of SUVR in each brain region for the differential diagnosis of AD-MCI and AD-HC. Pearson correlation analysis was employed to examine the correlations of SUVR with cognitive scale scores. Results:The SUVR of whole brain was 1.40±0.31 in AD group, 1.08±0.19 in MCI group, and 1.01±0.12 in HC group. SUVR analysis in the whole brain and each brain region could distinguish AD from HC, AD from MCI ( F values: 1.76-10.09, t values: 2.98-7.47, all P<0.05), but could not distinguish HC from MCI ( t values: 0.17-1.53, all P>0.05). ROC curve analysis showed that the best cut-off value of SUVR was 1.18 for whole brain (AUC=0.89), 1.13 for amygdala (AUC=0.94) and 1.26 for parahippocampal gyrus (AUC=0.94) for differential diagnosis of AD and HC, which was 1.06 for whole brain (AUC=0.82), 1.18 for amygdala (AUC=0.88) and 1.28 (AUC=0.88) for infratemporal gyrus to differential diagnosis of AD and MCI. SUVRs of the whole brain, frontal, occipital, parietal, temporal and insula were significantly negatively correlated with MMSE and MoCA cognitive scale scores ( r values: from -0.64 to -0.40, all P<0.05). Conclusions:SUVR quantitative analysis in 18F-PI-2620 PET imaging can assist the differential diagnosis of AD and HC, AD and MCI. The SUVRs of whole brain and five lobes show negative correlations with MMSE and MoCA scores.
3.Diagnostic efficiency of 18F-FDG PET for Alzheimer′s disease in patients with memory impairment
Yan ZHANG ; Chenpeng ZHANG ; Gan HUANG ; Cheng WANG ; Mei XIN ; Hongda SHAO ; Yue WANG ; Liangrong WAN ; Ju QIU ; Qun XU ; Xia LI ; Jianjun LIU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(12):712-717
Objective:To assess the diagnostic efficiency of 18F-FDG PET for Alzheimer′s disease (AD) in patients with memory impairment. Methods:A retrospective analysis was conducted on 96 patients (40 males, 56 females, age: 69.0(62.8, 74.0) years) initially diagnosed with memory impairment in Renji Hospital, School of Medicine, Shanghai Jiao Tong University between August 2019 and September 2023. The amyloid-tau-neurodegeneration (ATN) criteria, based on 18F-AV45+ 18F-PI-2620 PET/CT+ MRI imaging results, were used as the diagnostic standard for AD. Visual analysis (temporoparietal or posterior cingulate cortex (PCC) hypometabolism) and semi-quantitative analysis methods (PET-SCORE and NeuroQ software analysis (SUV ratio, SUVR)) were applied to evaluate the diagnostic efficiency of 18F-FDG PET imaging for AD. Diagnostic efficiencies of visual assessment and semi-quantitative parameters were compared by χ2 test. Additionally, Pearson correlation analysis was performed to examine the relationship between results of PET-SCORE and cognitive scales. Results:Of the 96 patients initially diagnosed with memory impairment, 61 were clinically diagnosed with AD, while 35 were non-AD patients. Visual assessment of temporoparietal hypometabolism showed the highest sensitivity (91.80%, 56/61), which was significantly different from the sensitivities of PET-SCORE (40.98%(25/61); χ2=29.03, P<0.001) and visual assessment of PCC hypometabolism (77.05%(47/61); χ2=5.82, P=0.016). While semi-quantitative assessment using PET-SCORE demonstrated the highest specificity (100%, 35/35), which was significantly different from the specificities of visual assessment methods (temporoparietal hypometabolism: 17.14%(6/35), χ2=27.03, P<0.001; PCC hypometabolism: 54.29%(19/35), χ2=14.06, P<0.001). PET-SCORE exhibited statistically significant correlations with Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Activities of Daily Living (ADL) scores ( r values: -0.38, -0.36, 0.31, all P<0.01). Conclusions:Among patients initially diagnosed with memory impairment, visual assessment in 18F-FDG PET imaging analysis demonstrates higher sensitivity, while semi-quantitative analysis using PET-SCORE exhibits higher specificity. PET-SCORE shows statistically significant correlation with the severity of cognitive decline.
4.Effectiveness of antiretroviral therapy for the first time on HIV/AIDS patients in Jiangyin
Jianmei TANG ; Hongda LU ; Yin XU ; Liang ZOU
Journal of Public Health and Preventive Medicine 2022;33(3):109-112
Objective To analyze the effect of HIV/AIDS patients receiving antiretroviral therapy (ART) for the first time in Jiangyin, and to provide a reference for further improvement of Jiangyin's AIDS antiretroviral treatment. Methods The historical cards and related information in the treatment management database of Jiangyin City's cases who received ART for the first time from 2005 to 2019 were collected and statistically analyzed. The changes in viral load and CD4+ T lymphocytes (CD4 cells) before and after treatment were compared. Results Among 652 patients receiving ART, 507 cases (77.76%) were successful in virological treatment. The median natural change rate of annual average CD4 cell count was 90.8 cells/μL/year (χ2=37.915, P<0.05; H=9.781, P<0.05). There were statistically significant differences in virological treatment and immune recovery between different age groups (χ2=10.713, P<0.05; H =10.394, P<0.05) and different baseline CD4 count layers. The results showed that age and baseline CD4 value were the influencing factors of treatment effect. Conclusion Age and baseline CD4 value can affect the effect of ART treatment. The older the age and the lower the baseline CD4 value, the worse the virological efficacy and the recovery effect of CD4 cells. It is suggested that the infected patients should be involved in ART in time, which is conducive to shorten the time of initial treatment and further improve the effect of antiviral treatment.
5.Sex disparity of lung cancer risk in non-smokers: a multicenter population-based prospective study based on China National Lung Cancer Screening Program
Zheng WU ; Fengwei TAN ; Zhuoyu YANG ; Fei WANG ; Wei CAO ; Chao QIN ; Xuesi DONG ; Yadi ZHENG ; Zilin LUO ; Liang ZHAO ; Yiwen YU ; Yongjie XU ; Jiansong REN ; Jufang SHI ; Hongda CHEN ; Jiang LI ; Wei TANG ; Sipeng SHEN ; Ning WU ; Wanqing CHEN ; Ni LI ; Jie HE
Chinese Medical Journal 2022;135(11):1331-1339
Background::Non-smokers account for a large proportion of lung cancer patients, especially in Asia, but the attention paid to them is limited compared with smokers. In non-smokers, males display a risk for lung cancer incidence distinct from the females—even after excluding the influence of smoking; but the knowledge regarding the factors causing the difference is sparse. Based on a large multicenter prospective cancer screening cohort in China, we aimed to elucidate the interpretable sex differences caused by known factors and provide clues for primary and secondary prevention.Methods::Risk factors including demographic characteristics, lifestyle factors, family history of cancer, and baseline comorbidity were obtained from 796,283 Chinese non-smoking participants by the baseline risk assessment completed in 2013 to 2018. Cox regression analysis was performed to assess the sex difference in the risk of lung cancer, and the hazard ratios (HRs) that were adjusted for different known factors were calculated and compared to determine the proportion of excess risk and to explain the existing risk factors.Results::With a median follow-up of 4.80 years, 3351 subjects who were diagnosed with lung cancer were selected in the analysis. The lung cancer risk of males was significantly higher than that of females; the HRs in all male non-smokers were 1.29 (95% confidence interval [CI]: 1.20-1.38) after adjusting for the age and 1.38 (95% CI: 1.28-1.50) after adjusting for all factors, which suggested that known factors could not explain the sex difference in the risk of lung cancer in non-smokers. Known factors were 7% (|1.29-1.38|/1.29) more harmful in women than in men. For adenocarcinoma, women showed excess risk higher than men, contrary to squamous cell carcinoma; after adjusting for all factors, 47% ([1.30-1.16]/[1.30-1]) and 4% ([7.02-6.75]/[7.02-1])) of the excess risk was explainable in adenocarcinoma and squamous cell carcinoma. The main causes of gender differences in lung cancer risk were lifestyle factors, baseline comorbidity, and family history.Conclusions::Significant gender differences in the risk of lung cancer were discovered in China non-smokers. Existing risk factors did not explain the excess lung cancer risk of all non-smoking men, and the internal causes for the excess risk still need to be explored; most known risk factors were more harmful to non-smoking women; further exploring the causes of the sex difference would help to improve the prevention and screening programs and protect the non-smoking males from lung cancers.
6.Gout in thoracic spinal canal: a case report and systematic review
Bingshan YAN ; Yancheng LIU ; Hong ZHANG ; Duo SHAN ; Guoyun BU ; Peijia LIU ; Hongda XU ; Yongcheng HU
Chinese Journal of Orthopaedics 2021;41(12):790-799
Objective:To summarize the clinical manifestations, epidemiological features and progress of diagnosis and treatment of gout in the spinal canal.Methods:A 59-year-old male patient was admitted to the hospital due to back pain, weakness in both lower limbs, hypoaesthesia and feeling of walking and stepping on cotton for more than one month. The preoperative imaging examination showed there were space-occupying lesions in the spinal canal at the T 8, 9 level with severe canal stenosis. The patient underwent posterior T 8, 9 laminectomy decompression, debridement and T 7-T 10 pedicle screw internal fixation under general anesthesia. The thoracic spinal gout was diagnosed by postoperative pathology. Further, the following keywords, "gout", "gout of spinal canal", "gout of spine" and "intraspinal gout", were used to search in the Chinese and English databases. A total of 62 patients with intraspinal gout were retrieved. The age, gender, involved disease, history of gout or hyperuricemia, laboratory indicators and imaging data of 63 patients were collected. Results:A total of 63 patients with intraspinal gout were retrieved. The gender of one patient was unknown. The remaining patients included 54 males (87.1%, 54/62) and 8 females (12.9%, 8/62) with the ratio of male to female 6.75∶1. The average age was 52(35, 67) years (range 20-82 years) and the peak onset period was 60-79 years. Fifty-six cases (88.9%, 56/63) of all patients suffered the disease from one single site of the spine, including 26 cases in the lumbar-sacral (46.4%), 22 cases (39.3%) in the thoracic spine and 8 cases (14.3%) in the cervical spine. However, only 7 patients had the disease at more than two sites at the same time accounting for 11.1% of all patients (7/63). Fifty-three patients (91.4%, 53/58) had a history of hyperuricemia with an average duration of 8.6 years (range 3 months to 28 years). The clinical symptoms of intraspinal gout were not specific. There were 70.5% (43/61) patients had local pain and up to 98.4% (60/61) patients had varying degrees of neurological dysfunction. X-ray examinations often showed no positive results due to technical limitations. Among 41 patients with CT imaging data, 31 cases showed mid-to-high density elliptical or irregular calcifications in the spinal canal and the remaining 10 patients showed medium-low density soft tissue masses. There were 96.2% (51/53) of patients with intraspinal gout showed medium or low signal on T1WI MRI examination but without high signal or low signal on T2WI (40 cases of high signal, 13 cases of high signal or mixed signal). All 63 patients were finally diagnosed by pathological examination and 5 of them with histological features. The main pathological features included foreign body granuloma, red-stained crystal-like deposits in the cytoplasm of foreign body giant cells, birefringent spindle or needle-like crystals under polarized light microscope.Conclusion:Gout in the spinal canal is a rare condition. Dual-energy CT has high sensitivity and specificity in identifying gout and it can provide a more accurate method in diagnosis of spinal gout. However, the final diagnosis depends on postoperative pathology. If case of spinal instability or neurological dysfunction, surgery had to be performed. Hyperuricemia should be treated in order to reduce the risk of acute attacks.
7.Analysis of low-dose computed tomography compliance and related factors among high-risk population of lung cancer in three provinces participating in the cancer screening program in urban China
Yan WEN ; Lianzheng YU ; Lingbin DU ; Donghua WEI ; Yunyong LIU ; Zhuoyu YANG ; Yadi ZHENG ; Zheng WU ; Xinyang YU ; Liang ZHAO ; Yiwen YU ; Hongda CHEN ; Jiansong REN ; Chao QIN ; Yongjie XU ; Wei CAO ; Fei WANG ; Jiang LI ; Fengwei TAN ; Min DAI ; Wanqing CHEN ; Ni LI ; Jie HE
Chinese Journal of Preventive Medicine 2021;55(5):633-639
Objective:To analyze the compliance and related factors of low-dose computed tomography (LDCT) screening among the high-risk population of lung cancer in three provinces participating in the cancer early diagnosis and early treatment program in urban areas of China.Methods:From October 2017 to October 2018, 17 983 people aged between 40 and 74 years old at high risk of lung cancer were recruited from Zhejiang, Anhui and Liaoning provinces. The basic demographic characteristics, living habits, history of the disease and family history of cancer were collected by using a cancer risk assessment questionnaire, and the data of participants examined by LDCT were obtained from the hospitals participating in the program. The screening compliance was quantified by the screening participation rate, and it was calculated as the proportion of participants completing LDCT scan among high-risk population. The related factors of LDCT screening compliance were analyzed by using a multivariate logistic regression model.Results:The age of 17 983 participants was (56.52±8.22) years old. Males accounted for 51.9% (N=9 332), and 69.5% (N=12 495) had ever smoked, including former smokers and current smokers. A total of 6 269 participants were screened by LDCT, and the screening participation rate was 34.86%. The results of multivariate logistic regression analysis showed that the age group of 50 to 69 years old, female, passive smokers, alcohol consumption, family history of lung cancer and history of chronic respiratory diseases were more likely to be screened by LDCT, while the compliance of LDCT screening in current smokers was low.Conclusions:The LDCT screening compliance of the high-risk population of lung cancer in urban areas of China still needs to be improved. Age, sex, smoking, drinking, family history of lung cancer and history of chronic respiratory disease are associated with screening compliance.
8.Analysis of low-dose computed tomography compliance and related factors among high-risk population of lung cancer in three provinces participating in the cancer screening program in urban China
Yan WEN ; Lianzheng YU ; Lingbin DU ; Donghua WEI ; Yunyong LIU ; Zhuoyu YANG ; Yadi ZHENG ; Zheng WU ; Xinyang YU ; Liang ZHAO ; Yiwen YU ; Hongda CHEN ; Jiansong REN ; Chao QIN ; Yongjie XU ; Wei CAO ; Fei WANG ; Jiang LI ; Fengwei TAN ; Min DAI ; Wanqing CHEN ; Ni LI ; Jie HE
Chinese Journal of Preventive Medicine 2021;55(5):633-639
Objective:To analyze the compliance and related factors of low-dose computed tomography (LDCT) screening among the high-risk population of lung cancer in three provinces participating in the cancer early diagnosis and early treatment program in urban areas of China.Methods:From October 2017 to October 2018, 17 983 people aged between 40 and 74 years old at high risk of lung cancer were recruited from Zhejiang, Anhui and Liaoning provinces. The basic demographic characteristics, living habits, history of the disease and family history of cancer were collected by using a cancer risk assessment questionnaire, and the data of participants examined by LDCT were obtained from the hospitals participating in the program. The screening compliance was quantified by the screening participation rate, and it was calculated as the proportion of participants completing LDCT scan among high-risk population. The related factors of LDCT screening compliance were analyzed by using a multivariate logistic regression model.Results:The age of 17 983 participants was (56.52±8.22) years old. Males accounted for 51.9% (N=9 332), and 69.5% (N=12 495) had ever smoked, including former smokers and current smokers. A total of 6 269 participants were screened by LDCT, and the screening participation rate was 34.86%. The results of multivariate logistic regression analysis showed that the age group of 50 to 69 years old, female, passive smokers, alcohol consumption, family history of lung cancer and history of chronic respiratory diseases were more likely to be screened by LDCT, while the compliance of LDCT screening in current smokers was low.Conclusions:The LDCT screening compliance of the high-risk population of lung cancer in urban areas of China still needs to be improved. Age, sex, smoking, drinking, family history of lung cancer and history of chronic respiratory disease are associated with screening compliance.
9.COVID-19 patient firstly visiting eye doctor due to tarsadenitis and subconjunctival hemorrhage: A case report
Man XU ; Hongda ZHANG ; Xiaoguang NIU
Chinese Journal of Experimental Ophthalmology 2020;38(4):374-376
A 35-year-old female patient with a history of significant epidemiological exposure firstly visited eye doctor due to acute tarsadenitis in the right eye.Subsequently, she developed subconjunctival hemorrhage, fever and cough and received topical administration of antibiotics and systemic treatment of antiviral drug.Shortly thereafter, both his mother and father, who denied COVID-19 associated epidemiological history, appeared fever, fatigue and other symptoms and diagnosed as COVID-19.This female patient was diagnosed as COVID-19 by CT image of lung and COVID-19 RNA detection 17 days and 24 days after firstly visited eye doctor, respectively, and received specialized isolation treatment.The symptoms of COVID-19 are very varied, eye doctors should keep alert and pay attention to personal protection.
10. The relationship between inflammatory markers and the risk of lung cancer: a prospective cohort study
Gang WANG ; Luopei WEI ; Ni LI ; Weiguo XU ; Kai SU ; Fang LI ; Fengwei TAN ; Zhangyan LYU ; Xiaoshuang FENG ; Xin LI ; Hongda CHEN ; Yuheng CHEN ; Lanwei GUO ; Hong CUI ; Pengfei JIAO ; Hexin LIU ; Jiansong REN ; Shouling WU ; Jufang SHI ; Min DAI ; Jie HE
Chinese Journal of Oncology 2019;41(8):633-637
Objective:
To investigate whether elevated levels of C-reactive protein (CRP) and neutrophil (NE) in the blood is associated with an increased risk of lung cancer incidence.
Methods:
From 2006 to 2007, all employees and retirees from Kailuan (Group) Limited liability Corporation were included in this Kailuan Cohort study. The last follow-up date was December 2015. Data on new cases of lung cancer were collected, and multivariable Cox proportional hazards regression models were used to the relationship between baseline CRP and NE at baseline and risk of lung cancer.
Results:
A total of 92 735 participants were enrolled in this study. During the follow-up, 850 new cases of lung cancer were identified. All subjects were divided into four groups according to the combination level of CRP and NE at baseline: CRP≤3 mg/L and NE≤4×109/L(Group A), CRP≤3 mg/L and NE>4×109/L(Group B), CRP>3 mg/L and NE≤4×109/L(Group C), CRP>3 mg/L and NE>4×109/L(Group D). The cumulative incidence of lung cancer were 950/100 000, 1 030/100 000, 1 081/100 000 and 1 596/100 000 in these four groups, respectively (


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