1.Screening and characterization of anti-SARS-CoV-2 receptor binding domain antibodies with broad-spectrum neutralizing activity
NI Wanqi ; REN Li ; JIN Changzhong ; YANG Furong ; SHEN Yumin ; WANG Shuo ; HU Caiqin ; HAO Yanling ; LIU Ying ; ZHU Biao ; SHAO Yiming ; LI Dan ; WANG Zheng
China Tropical Medicine 2024;24(3):258-
convalescents, and to screen for broad-spectrum neutralizing antibodies against the SARS-CoV-2 RBD. Methods Using biotinylated RBD as a molecular probe, flow cytometry was employed to perform single-cell sorting of B cells from peripheral blood mononuclear cells (PBMCs) of convalescents. The obtained B cells were lysed and subjected to reverse transcription, followed by nested PCR amplification of the heavy and light chains of antibodies was conducted using random primers. The amplified products were cloned into corresponding expression vectors, and the respective matched heavy-light chain plasmids were co-transfected into 293F cells for expression. Monoclonal antibodies were then purified using Protein A column chromatography. Neutralization experiments were conducted with the wild-type (WT) pseudovirus, and antibodies with IC50<0.1 μg/mL were selected for further testing of neutralizing breadth and potency against the wild-type (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and currently prevalent pseudovirus strains (XBB, BA.5, BF.7). Results A total of 21 RBD-specific monoclonal B cells were obtained from two recovered patients, resulting in the isolation of 13 pairs of antibody light/heavy chains. Nine antibodies were successfully expressed, with P1-A1, P1-B6, and P1-B9 exhibiting IC50 values below 0.1 μg/mL against the pseudovirus of the wild-type strain (WT). Specifically, P1-B6 effectively neutralized the wild-type strain (WT), Beta variant (B.1.351), and Delta variant (B.1.617.2), with IC50 values reaching 0.01 μg/mL. P1-B9 demonstrated effective neutralization against the wild-type strain (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and Gamma variant (P.1) pseudoviruses, with IC50 values of 0.42 μg/mL, 0.63 μg/mL, 0.28 μg/mL, and 2.50 μg/mL, respectively. Additionally, P1-B6 exhibited good neutralization against BA.5 and BF.7 pseudoviruses, with IC50 values of 0.06 μg/mL and 0.09 μg/mL, respectively. Conclusions Infection with the SARS-CoV-2 WT strain can induce the generation of neutralizing antibodies with broad-spectrum activity. Generating these broadly neutralizing antibodies does not require an excessively high somatic hypermutation. The obtained antibodies can be used as candidates for SARS-CoV-2 diagnosis and prevention.
2.Automatic surgical classification of knee X-ray images using machine deep learning
Qianli MA ; Ming ZHENG ; Qiang CHEN ; Yuyun ZHENG ; Jiongjiong GUO ; Yumin CHEN ; Yi ZHAO
Chinese Journal of Orthopaedic Trauma 2024;26(10):834-841
Objective:To evaluate the performance of our self-developed deep learning (DL) model which was designed to automatically classify the knee X-ray images into one non-surgical category and 4 surgical categories, including non-surgical knees (NSK), high tibial osteotomy (HTO), total knee arthroplasty (TKA), unicompartmental knee arthroplasty (UKA), and tibial plateau fracture fixation with an internal fixation plate (TPFF).Methods:The knee X-ray images were collected of the patients who had undergone knee joint surgery at Department of Orthopaedics, Fuzhou Second General Hospital from January 2017 to December 2022. On the Baidu EasyDL AI platform, a multi-class object recognition DL model was built using the You Only Look Once (YOLO) algorithm. The model was trained on a dataset of 1,281 knee anteroposterior X-ray images (including NSK, HTO, TKA, UKA, and TPFF) to generate a DL model which was able to automatically recognize and classify the knee X-ray images. The reliability of the model classification performance was evaluated by analyzing the 5 indicators [accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)] using a test set of 450 knee anteroposterior X-ray images with the above 5 categories. The receiver operating characteristic curve was plotted and the area under the curve (AUC) was calculated to further quantify the classification performance of the model.Results:In the test set, on the whole, the model achieved an accuracy of 97.0%, a sensitivity of 92.4%, a specificity of 98.1%, a PPV of 92.4%, and a NPV of 98.1%, an AUC of 0.947, indicating a high reliability in classifying various categories. The model showed a best performance for TKA, with the 5 indicators being 99.1%, 99.0%, 99.1%, 97.1% and 99.7%. The model showed a slightly lower sensitivity for TPFF and HTO (87.0% and 86.0%, respectively).Conclusion:A successful DL model has been developed which can automatically classify the knee X-ray images into non-surgical and surgical categories due to its satisfactory performance, particularly in accuracy and AUC.
3.A case report of renal foreign-body
Xianshen SHA ; Zheng CHEN ; Zhichao LIN ; Zexiong GUO ; Yumin ZHUO
Chinese Journal of Urology 2024;45(9):709-710
Renal foreign-body is rare in clinical practice. This article reports a case of 12-year-old male patient who presented with intermittent right lumbar stabbing pain for one year. Physical and laboratory examinations showed no significant abnormalities. Enhanced CT and three-dimensional angiography indicated a metal object in the anterior superior pole of the right kidney. The patient had a history of consuming vermicelli frequently over the past year. Considering the medical history and clinical examinations, it was hypothesized that a foreign body had penetrated the duodenum and lodged into the kidney. A foreign body extraction was performed via 3D laparoscopy, confirming the object to be a 25 mm long metallic needle. The patient was discharged on the third postoperative day. Follow-up at six months showed the patient to be in good condition.
4.A novel biodegradable polymer-coated sirolimus-eluting stent: 1-year results of the HELIOS registry.
Bo ZHENG ; Yi LIU ; Ruining ZHANG ; Wangwei YANG ; Fangju SU ; Rutao WANG ; Dapeng CHEN ; Guidong SHEN ; Yumin QIU ; Lianmin WANG ; Chang CHEN ; Zhongwei WU ; Fei LI ; Jiayi LI ; Chengxiang LI ; Chao GAO ; Ling TAO
Chinese Medical Journal 2023;136(15):1848-1854
BACKGROUND:
The HELIOS stent is a sirolimus-eluting stent with a biodegradable polymer and titanium oxide film as the tie-layer. The study aimed to evaluate the safety and efficacy of HELIOS stent in a real-world setting.
METHODS:
The HELIOS registry is a prospective, multicenter, cohort study conducted at 38 centers across China between November 2018 and December 2019. A total of 3060 consecutive patients were enrolled after application of minimal inclusion and exclusion criteria. The primary endpoint was target lesion failure (TLF), defined as a composite of cardiac death, non-fatal target vessel myocardial infarction (MI), and clinically indicated target lesion revascularization (TLR) at 1-year follow-up. Kaplan-Meier methods were used to estimate the cumulative incidence of clinical events and construct survival curves.
RESULTS:
A total of 2998 (98.0%) patients completed the 1-year follow-up. The 1-year incidence of TLF was 3.10% (94/2998, 95% closed interval: 2.54-3.78%). The rates of cardiac death, non-fatal target vessel MI and clinically indicated TLR were 2.33% (70/2998), 0.20% (6/2998), and 0.70% (21/2998), respectively. The rate of stent thrombosis was 0.33% (10/2998). Age ≥60 years, diabetes mellitus, family history of coronary artery disease, acute myocardial infarction at admission, and device success were independent predictors of TLF at 1 year.
CONCLUSION:
The 1-year incidence rates of TLF and stent thrombosis were 3.10% and 0.33%, respectively, in patients treated with HELIOS stents. Our results provide clinical evidence for interventional cardiologists and policymakers to evaluate HELIOS stent.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, NCT03916432.
Humans
;
Middle Aged
;
Sirolimus/therapeutic use*
;
Drug-Eluting Stents/adverse effects*
;
Prospective Studies
;
Cohort Studies
;
Treatment Outcome
;
Risk Factors
;
Time Factors
;
Percutaneous Coronary Intervention/adverse effects*
;
Cardiovascular Agents/therapeutic use*
;
Coronary Artery Disease/therapy*
;
Myocardial Infarction/etiology*
;
Thrombosis/complications*
;
Polymers
;
Registries
5.Analysis of coronary angiographic findings in 117 children with Kawasaki disease and coronary artery lesion
Meng ZHANG ; Qing CUI ; Diqi ZHU ; Jie SHEN ; Lijun FU ; Fen LI ; Wei GAO ; Tingliang LIU ; Ying GUO ; Jinghao ZHENG ; Yumin ZHONG
Chinese Journal of Applied Clinical Pediatrics 2023;38(7):491-496
Objective:To analyze the coronary angiographic (CAG) characteristics of coronary artery lesion (CAL) in children with Kawasaki disease (KD), and to clarify the necessity of CAG in the diagnosis and treatment of KD combined with CAL in children.Methods:It was a retrospective study to analyze the clinical data, electrocardiogram, echocardiography, time and findings of CAG in children with KD and CAL who underwent CAG in Shanghai Children′s Medical Center of Shanghai Jiao Tong University School of Medicine from January 2013 to August 2022.The distribution, type, severity, and prognosis of CAL were analyzed.Results:A total of 117 children with KD and CAL were included in the analysis.The onset age of KD was from 2 months to 12.8 years old, and the age of performing CAG was from 8 months to 18.1 years old.A total of 234 coronary artery lesions were detected in 117 cases.Among them, CAL in the right coronary artery (RCA), left anterior descending branch (LAD), left main coronary artery and left circumflex artery were detected in 96 branches(41.1%), 78 branches(33.3%), 44 branches(18.8%), and 16 branches(6.8%), respectively.Unilateral coronary artery involvement was detected in 43 cases (36.8%), of which LAD was the dominant; while bilateral involvement was detected in 74 cases (63.2%), among which, LAD and RCA were the most involved arteries.Stratified by the degree of coronary involvement, large coronary aneurysms and severe coronary stenosis were most frequently occurred in the RCA and LAD.In contrast, 10 cases (13.6%), 20 cases (24.3%), 55 cases (45.8%) and 37 cases (67.3%) of intraluminal lesions were found in small, medium and large coronary aneurysms, and stenosis or occlusion, respectively.The incidence of intraluminal lesions tended to be higher in the site of severe lesions.CAG showed stenosis or occlusion in a total of 55 cases, and collateral circulation at varying degrees was found in cases of severe stenosis or occlusion.Conclusions:CAL in children with KD are complex and varied.Although clinical symptoms, routine electrocardiogram and cardiac ultrasound may indicate severe CAL.Their applications are limited by the diagnosis of the type (especially stenosis), degree, and extent of CAL, as well as the detection of extracoronary lesions.CAG is of great significance to identify vascular lesions and guide clinical management of KD combined with CAL in children.
6.Application of 99Tc m-MIBI SPECT/CT imaging in patients with primary cervical dystonia
Honglei LI ; Li WANG ; Chaoling JIN ; Xiaohui DUAN ; Mingrui DONG ; Xiaojian LIU ; Yumin ZHENG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(5):277-280
Objective:To evaluate the value of 99Tc m-methoxyisobutylisonitrile(MIBI) SPECT/CT imaging for the identification of dystonic muscles in patients with primary cervical dystonia (PCD). Methods:A total of 10 patients with PCD (3 males, 7 females, age (47.3±9.9) years) and 10 healthy subjects (4 males, 6 females, age (43.5±9.4) years; control group) between August 2019 and October 2021 in China-Japan Friendship Hospital were enrolled prospectively. All subjects underwent 99Tc m-MIBI SPECT/CT scan. The SUV max of 8 bilateral representative muscles, including rectus capitis posterior major, obliquus capitis inferior, splenius capitis, semispinalis, sternocleidomastoid, trapezius, musculus scalenus muscle and levator scapulae were evaluated in control group. In PCD group, muscles with abnormal uptake were determined. ROI was drawn and SUV max was measured. Independent-sample t test was used to analyze the differences of SUV max between normal and abnormal muscles. The detecting rates of neck MRI and SPECT/CT for abnormal muscles were analyzed by χ2 test. Results:Normal muscles of healthy subjects showed mild symmetrical radioactivity distribution, with the SUV max of 1.10±0.19. A total of 60 muscles with abnormal uptake in 10 patients were found, including 7 rectus capitis posterior major, 10 obliquus capitis inferior, 8 splenius capitis, 8 semispinalis, 10 sternocleidomastoid, 5 trapezius, 3 musculus scalenus muscle and 9 levator scapulae. The SUV max of muscles with abnormal uptake was 1.81±0.43, which was higher than that of normal muscles ( t=17.05, P<0.001). Only 30 pieces abnormal hypertrophy muscle were found by neck MRI, and the detecting rate was much lower than that of SPECT/CT (18.75%(30/160) vs 37.50%(60/160); χ2=28.03, P<0.001). Conclusion:99Tc m-MIBI SPECT/CT may be a useful method for identifying dystonic muscles and a guide to precision therapy in patients with PCD.
7.Application of 68Ga-NOTA-3P-TATE-RGD PET/CT in the evaluation of neuroendocrine neoplasms
Yuanyuan JIANG ; Yumin ZHENG ; Zhaohui ZHU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2023;43(11):649-654
Objective:To investigate the value of PET/CT imaging with 68Ga-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid-3 polyethylene glycol- D-Phe1-Tyr3-Thr8-octreotide Arg-Gly-Asp (NOTA-3P-TATE-RGD), a dual somatostatin receptor 2- and integrin α vβ 3- targeting tracer, in the evaluation of neuroendocrine neoplasms (NEN). Methods:From April 2021 to February 2022, 35 patients (19 males, 16 females; median age 54(41, 61) years) with histologically confirmed NEN in Peking Union Medical College Hospital were prospectively enrolled. All patients were scanned with both 68Ga-NOTA-3P-TATE-RGD and 68Ga-1, 4, 7, 1 0-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid- D-Phe1-Tyr3-Thr8-octreotide (DOTATATE) PET/CT imaging within one week. The differences of the numbers of detected lesions, SUV max and tumor-to-background ratio (TBR) between the two imaging methods were compared by Wilcoxon signed-rank test. Results:Of the 35 patients, the total numbers of lesions detected by 68Ga-NOTA-3P-TATE-RGD and 68Ga-DOTATATE were 1 190 and 1 106, respectively. 68Ga-NOTA-3P-TATE-RGD and 68Ga-DOTATATE both detected 35 primary tumors and performed comparably in detecting lymph node metastases (4(1, 8) vs 4(1, 8); z=-0.45, P=0.655) and bone metastases (5(2, 60) vs 5(2, 66); z=-1.11, P=0.244). However, the number of liver lesions detected by 68Ga-NOTA-3P-TATE-RGD was significantly higher than that by 68Ga-DOTATATE (17(6, 27) vs 8(3, 26); z=-2.31, P=0.021). 68Ga-DOTATATE demonstrated higher SUV max than 68Ga-NOTA-3P-TATE-RGD (15.6(9.9, 24.9) vs 12.7(8.0, 18.4); z=-7.19, P<0.001), while the TBR of liver metastases was significantly lower (3.4(1.8, 5.5) vs 6.1(3.8, 10.8); z=-7.56, P<0.001). Conclusion:68Ga-NOTA-3P-TATE-RGD performs better than 68Ga-DOTATATE in the detection of liver metastases, while is comparable to 68Ga-DOTATATE in detecting lesions of other sites.
8.Cerebral blood flow perfusion imaging in patients with laughing gas abuse
Lijie YIN ; Liping FU ; Chaoling JIN ; Renbin WANG ; Changle TIE ; Li WANG ; Yumin ZHENG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2021;41(3):136-139
Objective:To explore the changes of cerebral blood flow (CBF) perfusion caused by N 2O (laughing gas) abuse. Methods:From December 2017 to October 2018, the CBF perfusion images of 24 patients with laughing gas abuse (9 males, 15 females; age: 18-32(24.0±8.9) years) from China-Japan Friendship Hospital were analyzed retrospectively. The region uptake statistics of different brain regions of interest (ROI) (basal ganglia, central region, cerebellum, cingulate gyrus, frontal lobe, medial temporal lobe, occipital lobe, parietal lobe, temporal lobe) between patients with laughing gas abuse and normal people of the same age group from background software database were calculated automatically. Statistic>1.68 indicated the increase of local CBF perfusion, while statistic < -1.68 indicated the decrease of local CBF perfusion. The correlation between the statistics of bilateral brain regions and the correlation between statistical values and clinical indicators were analyzed by Pearson and Spearman correlation analyses.Results:The correlation of the statistics between bilateral regions of each brain area was significant( r values: 0.503-0.892, all P<0.05). The decreased CBF proportions of frontal and temporal lobes were 62.5%(15/24) and 70.8%(17/24), respectively. The highest proportion of increased CBF was cingulate gyrus (33.3%, 8/24). There were significant correlations between frontal lobe, central brain area and duration of laughing gas abuse ( rs values: 0.375, 0.305, both P<0.05). Conclusion:CBF perfusion imaging is helpful for understanding the changes of CBF in patients with laughing gas abuse.
9.Triple fusion PET/MRI in location of epileptogenic focus in patients with focal cortical dysplasia
Yi JIN ; Chaoling JIN ; Yumin ZHENG ; Tian LIANG ; Sheng XIE ; Xiaoxuan LI ; Dantao PENG ; Pei RONG ; Dongyan WU
Chinese Journal of Neuromedicine 2021;20(9):915-920
Objective:To explore the value of triple fusion positron emission tomography (PET)/MRI in location of epileptogenic focus in patients with focal cortical dysplasia (FCD).Methods:Three patients with refractory partial epilepsy, admitted to our hospital from December 2016 to June 2017, were chosen in our study. The raw MRI and PET images of these patients were processed using Freesurfer and FSL image processing softwares. After extraction and coregistration, precise PET/MRI fusion images were obtained; and the grey-white matter dividing line was highlighted on this fusion image to form triple-fusion images to observe the hypometabolic area and clarify the location.Results:Triple-fusion images of these 3 patients were acquired. In patient 1, a marked decrease in metabolism was noted in the gyrus region delineated by the gray-white matter boundary in the right cingulate gyrus. In patient 2, the area with slightly increased local signal in the right superior frontal gyrus (MRI FLAIR sequence) was the area with reduced metabolism. In patient 3, an area of local decreased metabolism was noted in the right cingulate gyrus. The preoperative evaluation of all 3 patients showed that the above areas were epileptic foci; the patients were followed up for 2 years after surgical resection, no clinical seizures occurred in all patients, and antiepileptic drugs were gradually stopped. All 3 patients were diagnosed as having FCD by postoperative pathology.Conclusion:Triple fusion PET/MRI is a powerful way to assist FCD diagnosis, especially for those FCD cases which are difficult to be diagnosed by other imaging methods, and has a potential clinical application value in epilepsy patients.
10.Characteristics of cerebral blood flow in patients with psychiatric symptoms caused by nitrous oxide abuse
Li WANG ; Lijie YIN ; Renbin WANG ; Zunjing LIU ; Mingrui DONG ; Xiaohui DUAN ; Yumin ZHENG ; Wen HONG ; Changle TIE ; Fang LIU
Chinese Journal of Behavioral Medicine and Brain Science 2020;29(11):989-994
Objective:To investigate the clinical, neuropsychological and regional cerebral blood flow (rCBF) characteristics in patients with psychiatric symptoms caused by nitrous oxide abuse.Methods:Twelve patients with psychiatric symptoms caused by nitrous oxide abuse were enrolled from February 2018 to February 2020 in the Department of Neurology, China-Japan Friendship Hospital and the First Hospital of Tsinghua University.All patients were scored with the brief psychiatric rating scale (BPRS), Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA). The SPECT/CT images were collected with low-energy and high-resolution collimator.After the pictures were reconstructed, 18 brain regions were automatically sketched and calculated by Database Comparison software.The statistical value of the difference between the general mean value of each brain region and that of the corresponding region of interest in the same age group was estimated.Results:(1)The clinical manifestations of 12 patients were anxiety, depression, hallucination, delusion, and 7 patients were accompanied by cognitive decline.(2)Neuropsychological examination: BPRS score was 57.83±11.15 (anxiety depression factor was 3.94±0.47; lacking active factor was 3.25±0.85; thinking disturbance factor was 3.21±1.27; activity factor was 2.28±0.56; hostility factor was 3.14±1.24). The score of self-knowledge impairment was 2.92±1.08, the score of inability to work was 4.50±1.17, the score of HAMD was 32.75±10.13, the score of HAMA was 18.67±5.80, the score of MMSE was 27.67±2.50, and the score of MoCA was 24.58±3.78.(3)SPECT showed that compared with the general mean value of the corresponding regions of interest of normal people, the patients showed hypoperfusion in the frontal lobe (7 patients, 58.30%) and the temporal lobe (8 patients, 66.70%).Conclusion:Nitrous oxide abuse has an obvious effect on rCBF.The psychiatric symptoms include anxiety, depression, hallucination, delusion and so on, which affect the ability to work and learn.SPECT has important value in the diagnosis of nitrous oxide abuse, and indicates changes in local brain functional activity.

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