1.18F-Florzolotau PET Imaging of Abnormal tau Protein Deposition in Alzheimer's Disease
Fangyang JIAO ; Jiaying LU ; Ming LI ; Qi HUANG ; Weiqi BAO ; Zhengwei ZHANG ; Zizhao JU ; Qianhua ZHAO ; Yihui GUAN ; Chuantao ZUO ; Huiwei ZHANG
Chinese Journal of Medical Imaging 2024;32(5):426-430,438
Purpose To explore the value of the new generation tau PET tracer 18F-Florzolotau in Alzheimer's disease(AD)at different stages.Materials and Methods Twenty-five MCI patients and sixty-one AD patients with positive β-amyloid status in Huashan Hospital,Fudan University from February 2020 to January 2022 were retrospectively enrolled with 18F-Florzolotau PET imaging and demographic and clinical data.The pre-processed PET images were analyzed by SPM two-sample t-test between MCI and AD groups,and the standardized uptake value ratios(SUVR)were extracted from the region of interest defined by SPM analysis(P<0.001);scaled subprofile model/principal component analysis was used to construct the different tau related patterns(MCItauRP,ADtauRP)and calculate the corresponding expression values.The classification efficiency of SUVR and MCItauRP,ADtauRP expression values was evaluated by receiver operating characteristic curve.Results Compared with MCI patients,tau protein deposition of AD patients was increased mainly in the bilateral temporal,occipital lobe(P<0.001),and the SUVR of these brain region in the AD group was higher than that in the MCI group(Z=-3.164,P<0.00l);the expression values of MCItauRP and ADtauRP were significantly different between the AD group and MCI group(t=3.72,Z=-3.51;both P<0.001),and these expression values of AD patients were higher than those in the MCI group;the accuracy of tauRP expression values and SUVR for the differentiation between the AD and MCI group were 61.63%,65.12%and 65.12%,respectively;the sensitivity was 88.00%,96.00%and 100.00%,respectively;the specificity was 50.82%,52.46%and 50.82%,respectively.Conclusion The new tau PET can identify and distinguish the differences in tau protein deposition between AD and MCI patients.However,the classification and diagnosis efficiency is not high.In the future,it is necessary to find a more ideal analysis method.
2.Pathogenesis of flunarizine-induced parkinsonism from gut-brain axis perspective
Nan DING ; Lixin PAN ; Changlin LIAN ; Zhifeng XU ; Yukai WANG ; Fen ZHANG ; Guanghua ZHAO ; Xiaojue LIANG ; Wenjie LAI ; Weiqi ZENG ; Jingjuan CHEN ; Guohua ZHANG
Chinese Journal of Neuromedicine 2024;23(4):333-339
Objective:To explore the pathogenesis of flunarizine-induced parkinsonism from gut-brain axis perspective.Methods:Thirty male C57BL/6 mice were randomly divided into control group and flunarizine group ( n=15). Mice in the control group were given 0.1 mL 50% polyethylene glycol 400+50% saline by gavage once/d for 2 weeks, while mice in the flunarizine group were given 6 mg/mL flunarizine+50% polyethylene glycol 400+50% saline by gavage at a daily dose of 30 mg/kg for 2 weeks. Body mass was recorded 1, 3, 5, 7, 10 and 14 d after drug administration, and motor function was assessed by rotarod test 14 d after drug administration; 16s RNA sequencing was performed in the feces to observe the intestinal flora; intestinal transit function was detected by Evans blue by gavage; and then, the mice were sacrificed and homogenate or frozen sections (brain and intestinal tissues) were prepared; dopamine-ergic neuron expression was detected by Western blotting; RT-qPCR was applied to detect the expressions of inflammatory factors in the substantia nigra, and immunofluorescent staining was used to detect the expressions of ZO-1 and Claudin-5 in the intestinal epithelial tissues. Results:Compared with the control group, the flunarizine group had lower body mass ratio 1, 3, 5, 7, 10 and 14 d after drug administration (ratio to body mass before drug administration). Compared with the control group, the flunarizine group had significantly shortened residence time in rod rotating and lower rotational speed when falling ( P<0.05). Compared with the control group, the flunarizine group had decreased tyrosine hydroxylase protein in the substantia nigra without significant difference ( P>0.05). Compared with the control group, the flunarizine group had significantly increased interleukin-6 and tumor necrosis factor-α in the substantia nigra (1.00±0.00 vs. 2.79±0.83; 1.00±0.00 vs. 3.39±1.37), significantly lower intestinal Evans blue propulsion rate (80.67%±4.51% vs. 50.67%±6.03%), and statistically decreased ZO-1 and Claudin-5 expressions in the colonic epithelial tissues (27.01±1.41 vs. 16.32±2.83; 37.00±2.80 vs. 24.52±2.12, P<0.05). Totally, 576 microorganisms were noted in both control group and flunarizine group, 744 in the control group alone, and 634 in the flunarizine group alone. The intestinal flora β diversity indices in the 2 groups were significantly different based on weighted Unifrac-principle coordinates analysis (PCoA, PCoA1: 39.88%; PCoA2: 30.69%). Compared with the control group, the microbial colony structure of mice in flunarizine group was dominated by phylum thick-walled bacteria and phylum warty microbacteria, and by families Muribaculaceae, Lachnospiraceae and Akkermansiaceae. Compared with the control group, the flunarizine group had significantly decreased relative abundance of Ackermannia spp. and Lactobacillus spp. in the intestinal flora ( P<0.05). Conclusion:Flunarizine may contribute to the pathogenesis of DIP by causing structural disturbances in the intestinal flora and inducing neuroinflammation based on the gut-brain axis.
3.Establishment and validation of a laboratory-based multiparameter model for predicting bone marrow metastasis in malignant tumors
Haocheng LI ; Wei XU ; Zhonghua DU ; Lin SONG ; Dan LIU ; Huihui SHAO ; Chunhe ZHAO ; Weiqi CUI ; Linlin QU
Chinese Journal of Laboratory Medicine 2024;47(11):1248-1255
Objective:To establish and validate the prediction model for bone marrow metastasis (BMM) in malignant tumors by screening out laboratory multiparameters.Methods:This case-control study collected 444 cases of malignant tumor patients who were hospitalized in the First Hospital of Jilin University from March 2018 to March 2024, including 243 cases for model establishment set and 201 cases for model validation set. The model establishment set was divided into BMM positive group (81 cases) and BMM negative group (162 cases), and the model validation set was divided into positive group (67 cases) and a negative group (134 cases). We collected patients′ clinical information such as gender, age, clinical diagnosis, and results of 47 laboratory tests including routine blood analysis, coagulation, liver function, tumor markers, potassium, sodium, chloride, and calcium ion tests, bone marrow morphology, and bone marrow biopsy. BMM was taken as the outcome event, differencial variables were analyzed using inter group comparisons, the correlation among parameters was analyzed using Pearson correlation analysis, the risk factors for BMM were analyzed using multivariate conditional logistic regression analysis, to establish logistic model, followed by efficiency evaluation on BMM predictive model using receiver operating characteristic (ROC) curves.Results:In the model establishment set, Pearson correlation analysis of 28 parameters that differed between the BMM positive and negative groups revealed that the correlation coefficients of 17 parameters, including mean platelet volume (MPV), hematocrit (HCT), hemoglobin (HGB), and prothrombin time (PT), were no more than 0.6 ( P<0.05). Further multivariate conditional logistic regression analysis demonstrated that MPV, HGB, HCT, PT, red cell distribution width (RDW), platelet count (PLT), alkaline phosphatase (ALP), chloride (Cl -), and mean erythrocyte hemoglobin concentration (MCHC) were the risk factors of BMM occurence in malignancy [MPV ( OR=9.929, 95% CI 2.688-71.335), HCT ( OR=8.232, 95% CI 6.223-9.841), HGB ( OR=4.300, 95% CI 1.947-16.577), PT ( OR=3.738, 95% CI 1.359-11.666), RDW ( OR=1.995, 95% CI 1.275-3.807), ALP ( OR=1.025, 95% CI 1.012-1.045), PLT ( OR=1.014, 95% CI 1.002-1.031), MCHC ( OR=0.724, 95% CI 0.523-0.880) and Cl -( OR=0.703, 95% CI 0.472-0.967)]. In the model establishment set, combiation of risk factors provided an AUC of 0.943 (95% CI 0.898-0.987, P<0.001), a sensitivity of 86.3%, and a specificity of 89.2% for BMM prediction. In the model validation set, the AUC was 0.924 (95% CI 0.854-0.960, P<0.001), with a sensitivity and specificity of 86.7% and 83.8%, respectively. Conclusion:This study built and validated a multiple-parameter model for BMM, which may facilitate the timely detection of BMM and provide reference for decision making of bone marrow aspiration.
4.APOE-mediated suppression of the lncRNA MEG3 protects human cardiovascular cells from chronic inflammation.
Hongkai ZHAO ; Kuan YANG ; Yiyuan ZHANG ; Hongyu LI ; Qianzhao JI ; Zeming WU ; Shuai MA ; Si WANG ; Moshi SONG ; Guang-Hui LIU ; Qiang LIU ; Weiqi ZHANG ; Jing QU
Protein & Cell 2023;14(12):908-913
5.Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging.
Ying JING ; Yuesheng ZUO ; Yang YU ; Liang SUN ; Zhengrong YU ; Shuai MA ; Qian ZHAO ; Guoqiang SUN ; Huifang HU ; Jingyi LI ; Daoyuan HUANG ; Lixiao LIU ; Jiaming LI ; Zijuan XIN ; Haoyan HUANG ; Juan Carlos Izpisua BELMONTE ; Weiqi ZHANG ; Si WANG ; Jing QU ; Guang-Hui LIU
Protein & Cell 2023;14(7):497-512
Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.
Animals
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Humans
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Sarcopenia/metabolism*
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Forkhead Box Protein O3/metabolism*
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Muscle, Skeletal/metabolism*
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Aging/metabolism*
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Primates/metabolism*
6.Single-cell profiling reveals a potent role of quercetin in promoting hair regeneration.
Qian ZHAO ; Yandong ZHENG ; Dongxin ZHAO ; Liyun ZHAO ; Lingling GENG ; Shuai MA ; Yusheng CAI ; Chengyu LIU ; Yupeng YAN ; Juan Carlos Izpisua BELMONTE ; Si WANG ; Weiqi ZHANG ; Guang-Hui LIU ; Jing QU
Protein & Cell 2023;14(6):398-415
Hair loss affects millions of people at some time in their life, and safe and efficient treatments for hair loss are a significant unmet medical need. We report that topical delivery of quercetin (Que) stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice. We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1α in endothelial cells. Skin administration of a HIF-1α agonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que. Together, these findings provide a molecular understanding for the efficacy of Que in hair regrowth, which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine, and suggest a route of pharmacological intervention that may promote hair regrowth.
Mice
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Animals
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Quercetin/pharmacology*
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Endothelial Cells
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Hair
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Hair Follicle
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Alopecia
7.Interpretation of Detection and identification standard of hookworm—Hook-worm larvae coproculture techniques (WS/T 791—2021)
Yan DENG ; Tiantian JIANG ; Weiqi CHEN ; Yalan ZHANG ; Hongwei ZHANG ; Dongyang ZHAO
Chinese Journal of Schistosomiasis Control 2023;35(3):279-281
Detection and identification standard of hookworm—Hookworm larvae coproculture techniques (WS/T 791—2021) is the first recommended technical standard for hookworm detection and species identification using the hookworm larvae coproculture technique in China. This standard was issued on November 23, 2021, and had been in effect since May 1, 2022. This article provides a detailed interpretation pertaining to the background, drafting process, main contents, and dos and don’ts for better understanding and application of this standard among professionals working in disease control and prevention institutions and medical institutions.
8.Effects of body mass index on lung function in patients with chronic obstructive pulmonary disease
Yu FENG ; Xiaoli ZENG ; Li DONG ; Weiqi ZHAO ; Yong CHENG ; Xiaoju LIU
Chinese Journal of Health Management 2022;16(4):229-235
Objective:To investigate the effects of body mass index (BMI) on lung function in patients with chronic obstructive pulmonary disease (COPD).Methods:A total of 3 312 patients with COPD were selected from outpatients and inpatients in Department of Gerontal Respiratory Medicine of the First Hospital of Lanzhou University from August 2016 to August 2020, including 1 103 patients in stable period and 2 209 patients in acute exacerbation period. According to body mass index (BMI), these COPD patients were divided into four groups: low weight (56 cases, 131 cases), normal weight (448 cases, 945 cases), overweight (424 cases, 773 cases) and obesity groups (175 cases, 360 cases) respectively in stable stage and in acute exacerbation stage. The lung function of inspiratory capacity (IC), vital capacity (VC), residual volume (RV)/total lung capacity (TLC), forced expiratory volume in 1 second (FEV 1), forced vital capacity (FVC), FEV 1/FVC, maximal mid-expiratory flow (MMEF), diffusing capacity of the lung for carbon monoxide (DLCO), DLCO normalized per liter alveolar volume (DLCO/VA), respiratory impedance (Zrs), respiratory resistance at 5 Hz (R5), respiratory resistance at 20 Hz (R20) and respiratory reactance at 5 Hz (X5) were measured using MasterScreen PFT in all patients, and the influence of BMI on lung function was analyzed respectively. The risk factors of impaired lung function were analyzed by ordered logistic regression with lung function grade as dependent variable and age, gender, smoking history, smoking index and BMI as independent variables (“%pred”represents the percentage of predicted value). Results:The proportion of patients with lung function grade Ⅲ/Ⅳ in acute exacerbation period (64.9%, 37%, 27.4%, 24.4%) was higher than that in stable stage (42.9%, 25.9%, 13.7%, 9.1%), while the proportion of patients with lung function grade Ⅰ in stable stage (21.4%, 34.2%, 38.2%, 40.0%) was higher than that in acute exacerbation period (7.6%, 20.0%, 25.4%, 22.8%) (all P<0.05). The IC%pred, VC%pred, FEV 1%pred, FVC%pred, FEV 1/FVC, MMEF%pred, DLCO%pred, DLCO/VA%pred and R20 in low weight group were significantly lower than other groups both in stable period and acute exacerbation period (all P<0.05). The RV/TLC was higher in low weight group than that of normal weight and overweight groups in both periods (all P<0.05). The IC%pred, FEV 1%pred, FEV 1/FVC, DLCO%pred, DLCO/VA%pred, R5 and R20 in overweight and obesity groups were higher than those of normal weight group (all P<0.05). The RV/TLC, FEV 1/FVC, DLCO%pred, DLCO/VA%pred, Zrs, R5 and R20 in obesity group were higher than those of overweight group (all P<0.05). The ordered logistic regression analysis showed that low weight was independent risk factor for impaired lung function of COPD both in stable period [ OR (95% CI) 2.316 (1.206-3.554)] and acute exacerbation period [ OR (95% CI): 2.457 (1.647-3.669)]. Conclusion:Lower BMI has an adverse effect on lung function, and it is an independent risk factor for impaired lung function in COPD patients.
9.Exploration and practice of patient satisfaction evaluation management in multi-campus public hospitals
Weiqi ZHANG ; Rong ZHAO ; Haoning WANG ; Songxuan YU ; Jiayu MO ; Xiaorong WU ; Yang WEN ; Shulei FAN ; Yanli SHEN ; Huiyun YUAN
Chinese Journal of Hospital Administration 2022;38(4):280-284
Patient satisfaction is one of the core indicators to measure the service quality of medical institutions. To this end, a multi-campus public hospital in Shanghai constructed a management system of patient satisfaction evaluation. Since 2021, its call center has conducted a full coverage satisfaction assessment for discharged patients from its three campuses and collected dissatisfaction information feedback. The hospital organized relevant clinical departments and functional departments to fully communicate with the dissatisfied patients according to the feedback information, followed by a joint rectification. The hospital regularly conducts in-depth analysis of all complaints for timely discovery of common problems in different campuses for continuous improvement. This practice can provide reference for multi-campus hospitals to promote homogeneous management, to improve management efficiency, service quality and patient satisfaction.
10.Diabetes mellitus promoted lymph node metastasis in gastric cancer: a 15-year single-institution experience
Xinhua CHEN ; Yuehong CHEN ; Tao LI ; Weiqi LIANG ; Huilin HUANG ; Hongtao SU ; Chuyang SUI ; Yanfeng HU ; Hao CHEN ; Tian LIN ; Tao CHEN ; Liying ZHAO ; Hao LIU ; Guoxin LI ; Jiang YU
Chinese Medical Journal 2022;135(8):950-961
Background::Previous studies have revealed that diabetes mellitus (DM) promotes disease progress of gastric cancer (GC). This study aimed to further investigating whether DM advanced lymph nodes (LNs) metastasis in GC.Methods::The clinicopathologic data of GC patients with >15 examined LN (ELN) between October 2004 and December 2019 from a prospectively maintained database were included. The observational outcomes included the number (N3b status) and anatomical distribution (N3 stations) of metastatic LN (MLN).Results::A total of 2142 eligible patients were included in the study between October 2004 and December 2019. N3 stations metastasis (26.8% in DM vs. 19.3% in non-DM, P = 0.026) and N3b status (18.8% in DM vs. 12.8% in non-DM, P = 0.039) were more advanced in the DM group, and multivariate logistic regression analyses confirmed that DM was an independent factor of developing N3 stations metastasis (odds ratio [OR] = 1.771, P= 0.011) and N3b status (OR= 1.752, P= 0.028). Also, multivariate analyses determined DM was independently associated with more MLN (β = 1.424, P = 0.047). The preponderance of N3 stations metastasis (DM vs. non-DM, T1-2: 2.2% vs. 4.9%, T3: 29.0% vs. 20.3%, T4a: 38.9% vs. 25.8%, T4b: 50.0% vs. 36.6%; ELN16-29: 8.6% vs. 10.4%, ELN30-44: 27.9% vs. 20.5%, ELN ≥ 45: 37.7% vs. 25.3%), N3b status (DM vs. non-DM, T1-2: 0% vs. 1.7%, T3: 16.1% vs. 5.1%, T4a: 27.8% vs. 19.1%, T4b: 44.0% vs. 28.0%; ELN16-29: 8.6% vs. 7.9%, ELN30-44: 18.0% vs. 11.8%, ELN ≥ 45: 26.4% vs. 17.3%), and the number of MLN (DM vs. non-DM, T1-2: 0.4 vs. 1.1, T3: 8.6 vs. 5.2, T4a: 9.7 vs. 8.6, T4b: 17.0 vs. 12.8; ELN16-29: 3.6 vs. 4.6, ELN30-44: 5.8 vs. 5.5, ELN ≥ 45: 12.0 vs. 7.7) of DM group increased with the advancement of primary tumor depth stage and raising of ELN. Conclusions::DM was an independent risk factor for promoting LN metastasis. The preponderance of LN involvement in the DM group was aggravated with the advancement of tumor depth.

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