1.Advances in application of EEG-fNIRS technology in researches on neuropsychiatric disorders
Chenyang GAO ; Kai WU ; Wenhao LI ; Yi LI ; Zhile JIANG ; Yuxin WANG ; Wenrui CHEN ; Jing ZHOU
Chinese Journal of Medical Physics 2024;41(3):348-355
Currently,electroencephalogram(EEG),functional near-infrared spectroscopy(fNIRS),and functional magnetic resonance imaging have been widely studied and applied to neuropsychiatric disorders.In recent years,the devices which can realize the simultaneous acquisition of EEG and fNIRS has been developed and gradually applied in the studies on neuropsychiatric disorders.The review provides an introduction of the techniques of synchronized detection and data analysis for EEG-fNIRS,summarizes the analysis methods and new findings of the recent studies of stroke,epilepsy,and other neuropsychiatric disorders using EEG-fNIRS,and also discusses the future research directions.
2.Background, design, and preliminary implementation of China prospective multicenter birth cohort
Si ZHOU ; Liping GUAN ; Hanbo ZHANG ; Wenzhi YANG ; Qiaoling GENG ; Niya ZHOU ; Wenrui ZHAO ; Jia LI ; Zhiguang ZHAO ; Xi PU ; Dan ZHENG ; Hua JIN ; Fei HOU ; Jie GAO ; Wendi WANG ; Xiaohua WANG ; Aiju LIU ; Luming SUN ; Jing YI ; Zhang MAO ; Zhixu QIU ; Shuzhen WU ; Dongqun HUANG ; Xiaohang CHEN ; Fengxiang WEI ; Lianshuai ZHENG ; Xiao YANG ; Jianguo ZHANG ; Zhongjun LI ; Qingsong LIU ; Leilei WANG ; Lijian ZHAO ; Hongbo QI
Chinese Journal of Perinatal Medicine 2024;27(9):750-755
China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.
3.Clinical characteristics of aplastic anemia patients with abnormal autoantibodies and the impact of autoantibodies on immunosuppressive therapy response
Weiru LIANG ; Rui KANG ; Xin ZHAO ; Li ZHANG ; Liping JING ; Wenrui YANG ; Yuan LI ; Lei YE ; Kang ZHOU ; Jianping LI ; Huihui FAN ; Yang YANG ; Youzhen XIONG ; Fengkui ZHANG
Chinese Journal of Internal Medicine 2023;62(10):1200-1208
Objective:To investigate the clinical characteristics of patients with acquired aplastic anemia (AA) accompanied by abnormal antinuclear antibody (ANA) and autoantibodies and their effects on the efficacy of immunosuppressive therapy (IST).Method:A retrospective case-control study was conducted, analyzing the clinical data of 291 patients with AA who underwent IST and were screened for autoantibodies at initial diagnosis between January 2018 and December 2019 at Blood Diseases Hospital, Chinese Academy of Medical Sciences. According to the titer of ANA at the initial diagnosis, extracted nuclear antigen antibodies (ENAs) abnormality and the change of ANA titer after treatment, the treatment responses of 3 months and 6 months after IST were compared. The correlation between clinical features and ANA abnormality was analyzed by univariate and multivariate logistic regression analysis. The parameters of univariate analysis P<0.1 were included in multivariate analysis, stepwise regression analysis and subgroup analysis. Results:A total of 291 patients were included in the study, of which 145 (49.83%) were male. Among all patients, 147 (50.52%) tested positive for ANA at initial diagnosis, with titers of 1∶100, 1∶320, and 1∶1 000 observed in 94, 47, and 6 cases, respectively. Female gender, older age, presence of paroxysmal nocturnal hemoglobinuria (PNH) clone, and higher levels of IgG, IgA, and thyroid hormone were significantly associated with ANA positivity at initial diagnosis, while white cell counts, reticulocytes, and free triiodothyronine were significantly lower than that of ANA-negatively patients (all P<0.05). Furthermore, logistic regression analyses revealed that female gender ( OR=1.980, 95% CI 1.206-3.277), older age ( OR=1.017, 95% CI 1.003-1.032), and presence of PNH clone ( OR=1.875, 95% CI 1.049-3.408) were independent risk factors for ANA positivity at initial diagnosis. Subgroup analysis indicated that the risk of ANA positivity at initial diagnosis was even higher in PNH clone-positive patients in the subgroups of females ( OR=1.24, 95% CI 1.02-1.51), severe AA ( OR=1.26, 95% CI 1.07-1.47), and age≥40 years ( OR=1.26, 95% CI 1.05-1.52) (all P<0.05). However, ANA titers at initial diagnosis, presence of other abnormal ENAs, and changes in ANA titers after treatment with IST were not correlated with treatment response (all P>0.05). Conclusions:Approximately 50% of patients with AA had abnormal ANA, and their presence was significantly associated with female gender, older age, and presence of PNH clone at initial diagnosis. However, the presence of abnormal ANA and changes in ANA titers after treatment did not affect the efficacy of IST in patients with AA.
4.The effect of on-demand glucocorticoid strategy on the occurrence and outcome of p-ALG-associated serum sickness in aplastic anemia
Xiawan YANG ; Kang ZHOU ; Jianping LI ; Huihui FAN ; Wenrui YANG ; Lei YE ; Yuan LI ; Yang LI ; Guangxin PENG ; Yang YANG ; Youzhen XIONG ; Xin ZHAO ; Liping JING ; Li ZHANG ; Fengkui ZHANG
Chinese Journal of Hematology 2023;44(3):211-215
Objective:To investigate the effect of on-demand glucocorticoid strategy on the occurrence and outcome of porcine anti-lymphocyte globulin (p-ALG) -associated serum sickness in aplastic anemia (AA) .Methods:The data of AA patients who received in the Anemia Diagnosis and Treatment Center of Haematology Hospital, CAMS & PUMC from January 2019 to January 2022 were collected. Among them, 35 patients were enrolled in the on-demand group, with the glucocorticoid strategy adjusted based on the occurrence and severity of serum sickness; 105 patients were recruited in the usual group by matching the age and disease diagnosis according to 1∶3 ratio in patients who received a conventional glucocorticoid strategy in the same period. The incidences, clinical manifestations, treatment outcomes of serum sickness, and glucocorticoid dosage between the two groups were analyzed.Results:The incidences of serum sickness in the on-demand group and the usual group were 65.7% and 54.3% ( P=0.237) , respectively. The median onset of serum sickness was the same [12 (9, 13) d vs the 12 (10, 13) d, P=0.552], and clinical symptoms and signs, primarily joint, and/or muscle pain, fever, and rash were similar. Severity grades were both dominated by Grades 1-2 (62.8% vs 51.4%) , with only a few Grade 3 (2.9% vs 2.9%) , and no Grades 4-5. No significant difference in the serum sickness distribution ( P=0.530) . The median duration of serum sickness was the same [5 (3, 7) d vs 5 (3, 6) d, P=0.529], and all patients were completely cured after glucocorticoid therapy. In patients without serum sickness, the average dosage of prophylactic glucocorticoid per patient in the usual group was (469.48 ±193.57) mg (0 in the on-demand group) . When compared to the usual group, the average therapeutic glucocorticoid dosage per patient in the on-demand group was significantly lower [ (125.91±77.70) mg vs (653.90±285.56) mg, P<0.001]. Conclusions:In comparison to the usual glucocorticoid strategy, the on-demand treatment strategy could significantly reduce glucocorticoid dosage without increasing the incidence of serum sickness; in addition, the duration of serum sickness and the incidence of above Grade 2-serum sickness were similar.
5.Metagenomic next-generation sequencing of plasma for the identification of bloodstream infectious pathogens in severe aplastic anemia
Yuan LI ; Youzhen XIONG ; Huihui FAN ; Liping JING ; Jianping LI ; Qingsong LIN ; Chunhui XU ; Ying LI ; Lei YE ; Meng JIAO ; Yang YANG ; Yang LI ; Wenrui YANG ; Guangxin PENG ; Kang ZHOU ; Xin ZHAO ; Li ZHANG ; Fengkui ZHANG
Chinese Journal of Hematology 2023;44(3):236-241
Objective:To analyze the diagnostic value of cell-free plasma metagenomic next-generation sequencing (mNGS) pathogen identification for severe aplastic anemia (SAA) bloodstream infection.Methods:From February 2021 to February 2022, mNGS and conventional detection methods (blood culture, etc.) were used to detect 33 samples from 29 consecutive AA patients admitted to the Anemia Diagnosis and Treatment Center of the Hematology Hospital of the Chinese Academy of Medical Sciences to assess the diagnostic consistency of mNGS and conventional detection, as well as the impact on clinical treatment benefits and clinical accuracy.Results:①Among the 33 samples evaluated by mNGS and conventional detection methods, 25 cases (75.76%) carried potential pathogenic microorganisms. A total of 72 pathogenic microorganisms were identified from all cases, of which 65 (90.28%) were detected only by mNGS. ②All 33 cases were evaluated for diagnostic consistency, of which 2 cases (6.06%) were Composite, 18 cases (54.55%) were mNGS only, 2 cases (6.06%) were Conventional method only, 1 case (3.03%) was both common compliances (mNGS/Conventional testing) , and 10 cases (30.3%) were completely non-conforming (None) . ③All 33 cases were evaluated for clinical treatment benefit. Among them, 8 cases (24.24%) received Initiation of targeted treatment, 1 case (3.03%) received Treatment de-escalation, 13 cases (39.39%) received Confirmation, and the remaining 11 cases (33.33%) received No clinical benefit. ④ The sensitivity of 80.77%, specificity of 70.00%, positive predictive value of 63.64%, negative predictive value of 84.85%, positive likelihood ratio of 2.692, and negative likelihood ratio of 0.275 distinguished mNGS from conventional detection methods (21/12 vs 5/28, P<0.001) . Conclusion:mNGS can not only contribute to accurately diagnosing bloodstream infection in patients with aplastic anemia, but can also help to guide accurate anti-infection treatment, and the clinical accuracy is high.
6.Automatic synthesis and myocardial imaging of 11C-meta-hydroxyephedrine
Yulin HE ; Guojian ZHANG ; Xia BAI ; Weina ZHOU ; Wenrui WANG ; Xiangcheng WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2022;42(11):672-675
Objective:To realize a fully automated synthesis of 11C-meta-hydroxyephedrine (mHED) and to perform imaging studies with it. Methods:11C-mHED was prepared by the 11CH 3-triflate method. The crude product was purified by semi-preparative high performance liquid chromatograph (HPLC) to obtain the final product. The radiochemical purity and specific activity were determined by radio-HPLC. The myocardial uptake and excretion process of the agent were monitored by microPET/CT imaging on 5 normal SD rats. The clinical imaging value was evaluated using PET/CT imaging in a patient (male, 42 years old) with myocardial infarction. Results:The automated synthesis of 11C-mHED was realized by a commercial synthesizer. The total synthesis time was about 30 min. The radiochemical yield was (15±2)% (non-decay corrected, n=10) and the radiochemical purity was greater than 98%. The specific activity was about 65 GBq/mmol. MicroPET/CT imaging in normal SD rats showed the myocardial uptake was highest at 10 min after the injection of imaging agent, and then the imaging agent was gradually excreted from the myocardium through the liver and gallbladder. PET/CT imaging of a patient with myocardial infarction showed an imaging agent defect near the apex in the inferior wall of the left ventricle, which was matched with results of ultrasound and electrocardiogram examination. Conclusions:11C-mHED can be successfully prepared automatically, with high radiochemical yield and specific activity. It can also highly concentrate in the myocardium, and the imaging effect with this agent is good in a patient with myocardial infarction.
7.Hematologic responses to avatrombopag switch in TPO-RA refractory aplastic anemia
Liping JING ; Huihui FAN ; Wenrui YANG ; Yuan LI ; Jianping LI ; Li ZHANG ; Yang LI ; Kang ZHOU ; Youzhen XIONG ; Lei YE ; Guangxin PENG ; Yang YANG ; Xin ZHAO ; Fengkui ZHANG
Chinese Journal of Hematology 2022;43(11):921-927
Objective:Short-term efficacy and safety of afatrombopag conversion therapy in patients with aplastic anemia (AA) who were previously ineffectively treated with intense immunosuppressive therapy (IST) combined with TPO receptor Agonist (TPO-RA) or who were unable to tolerate the side effects of TPO-RA.Methods:Analysis of patients with severe aplastic anemia (SAA) treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from January 2021 to December 2021 who received IST combined with TPO-RA (eltrombopag/hatrombopag) for at least 6 months, but was ineffective for at least 3 months or patients who cannot continue to use TPO-RA due to side effects, and switched from TPO-RA to avatrombopag (APAG) , and treated for at least 6 months. This study analyzed its short-term efficacy and evaluated its safety.Results:The median age was 54 (14-68) years old among the 16 patients with AA (8 male and eight female) . A total of ten patients (refractory group) who did not respond to IST combined with TPO-RA were converted to APAG median therapy for 6 (6-10) months. Only seven patients (70% ) obtained trilineage HR [four cases of complete treatment response (CTR) , one case of good treatment response (GPR) , and two cases of partial treatment response (PR) ], all of which began to take effect at 3 months of APAG treatment. There were six patients with TPO-RA intolerance, and APAG was treated for 6 (2 to 8) months. About four patients (67% ) received HR (three GPR cases and one PR case) , of which two patients received PR at 3 months and four patients received HR at 6 months of APAG treatment. No APAG-related grade 2 or more adverse events occurred during the APAG therapy, no thrombotic events occurred, no fibrologic tissue hyperplasia was found in the bone marrow pathology reexamination at 6 months of treatment, and none of the patients discontinued the drug due to adverse events.Conclusion:APAG may be a better switching treatment option for patients with AA who are refractory or are intolerant to TPO-RA.
8.Experimental study of SPECT myocardial blood flow quantitative analysis in animals with coronary microvascular disease
Wenrui WANG ; Bowen HAO ; Guojian ZHANG ; Hong QU ; Weina ZHOU ; Yulin HE ; Xiangcheng WANG ; Xuemei WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2021;41(9):544-549
Objective:To compare the quantitative parameters of myocardial blood flow based on SPECT imaging and those determined by PET imaging in coronary microvascular disease (CMVD) animal models, in order to clarify the accuracy and feasibility of SPECT quantitative analysis in CMVD.Methods:Seven Saanen milk goats (either male or female; (20±5) kg), were selected for establishing CMVD animal models by microsphere embolization. Dynamic myocardial perfusion imaging (DMPI) with one-day method of resting + ATP stress 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT was performed before and after the modeling, respectively. One-day method of resting + ATP stress 13N-ammonia PET DMPI was performed after the modeling. The quantitative parameters determined by SPECT and PET after the modeling, including stress myocardial blood flow (SMBF), resting myocardial blood flow (RMBF) and myocardial flow reserve (MFR), were compared by paired t test. Parameters based on SPECT after modeling were compared with those of baseline levels. Bland-Altman analysis was applied to access the agreement between SPECT and PET. Results:Four of the seven experimental goats were fully imaged. The RMBF(ml·g -1·min -1; 1.52±0.27 vs 1.29±0.20), SMBF(ml·g -1·min -1; 0.74±0.19 vs 0.99±0.26), and MFR (0.53±0.16 vs 0.76±0.10) of the left ventricle (global) obtained by SPECT and PET in CMVD models were not significantly different ( t values: 3.121, 1.195, 1.930, all P>0.05). Among left anterior descending branch (LAD), left circumflex (LCX) and right coronary artery (RCA), the RMBF, SMBF and MFR values quantified by SPECT and PET were neither statistically significant ( t values: 0.182-2.734, all P>0.05). Bland-Altman analysis showed the quantitative parameters measured by SPECT and PET DMPI in left ventricle, LAD, LCX, RCA had a good consistency. The difference between the two methods for determining RMBF was up to 0.63 ml·g -1·min -1, and that of SMBF was up to 0.66 ml·g -1·min -1. All points are within the 95% confidence limit; MFR differs at most by 0.56, and 14/16 points were within 95% confidence limit. The RMBF (ml·g -1·min -1) of left ventricle measured by SPECT after modeling was not significantly different from that before modeling (1.52±0.27 vs 1.57±0.36; t=0.166, P>0.05); the SMBF (ml·g -1·min -1) and MFR after modeling were significantly lower than those before modeling (0.74±0.19 vs 2.34±0.89, 0.53±0.16 vs 1.39±0.31, t values: 3.836, 6.309, both P<0.05). Similar results were found when comparing the parameters of LAD/LCX/RCA after modeling with those before modeling (RMBF t values: 0.191, 0.235, 0.195, all P>0.05; SMBF/MFR t values: 0.411-19.911, all P<0.05). Conclusion:The blood flow quantitative parameters measured by SPECT imaging have a good consistency with those based on PET imaging, and the myocardial blood flow quantitative analysis of SPECT can evaluate the blood flow perfusion of CMVD.
9.Evaluation of the efficacy and safety of iron therapy in patients with paroxysmal nocturnal hemoglobinuria complicated with iron deficiency anemia
Guangxin PENG ; Li ZHANG ; Wenrui YANG ; Liping JING ; Kang ZHOU ; Yang LI ; Lei YE ; Yuan LI ; Jianping LI ; Huihui FAN ; Xin ZHAO ; Yang YANG ; Fengkui ZHANG
Chinese Journal of Hematology 2020;41(8):671-674
Objective:To evaluate the efficacy and safety of iron supplement in patients who have paroxysmal nocturnal hemoglobinuria (PNH) with iron deficiency.Methods:We performed analyses on the clinical data of 48 patients who accepted oral and/or intravenous iron treatment. Forty-eight consecutive PNH patients with iron deficiency who visited our hospital between November 2011 and August 2018 were enrolled in the study.Results:Total 30 patients received oral iron; 18 patients received intravenous iron supplements, including 6 who did not respond to oral iron. The median PNH clone size was 90.2% (38.5%-99.9%) in the granulocytes and 69.7% (27.6%-98.1%) in the red blood cells. The response rate was 56% (20/36) in patients who received oral iron, and the hemoglobin concentration increased 21 (10-52) g/L compared to that at baseline. Sixteen out of eighteen (89%) patients responded to intravenous iron; 6 patients who did not respond to oral iron received intravenous iron, and the hemoglobin level of 5 patients increased. Patients exhibited increased LDH levels and deepen urine after iron supplementation; however, no severe adverse events, such as thrombosis and iron-related adverse effects, were noted.Conclusion:Iron treatment is safe and effective in increasing the hemoglobin level in PNH patients with iron deficiency; those who did not respond to oral iron could benefit from intravenous iron supplement.
10.Retreatment with immunosuppression for 23 patients with refractory or relapsed severe aplastic anemia
Jianping LI ; Guangxin PENG ; Lei YE ; Yang LI ; Wenrui YANG ; Yuan LI ; Huihui FAN ; Xin ZHAO ; Kang ZHOU ; Liping JING ; Li ZHANG ; Fengkui ZHANG
Chinese Journal of Hematology 2020;41(8):661-665
Objective:This study aims to evaluate the efficacy and safety of secondary immunosuppressive therapy (IST) in refractory or relapsed severe aplastic anemia.Methods:The hematologic response and safety of 23 patients with refractory or relapsed SAA treated with secondary IST (including ATG/ALG + cyclosporine or HD-CTX) in our hospital were retrospectively analyzed.Results:A total of 23 patients were involved, including 11 males and 12 females, with a median age of 21 (11-62) years. In the refractory group, the interval of IST was 7 (6-12) months. In the relapsed group, on the other hand, the interval between two courses of IST was 39 (14-51) months. At 6 months after IST, the overall response rate was 69.5% (16/23) ; 60% (6/10) of the refractory group vs 77% (10/13) of the relapsed group; 64% (7/11) of the ATG/ALG group vs 75% (9/12) of the HD-CTX group. Among the patients who got the hematologic response, two patients relapsed again, all of them from the relapse group. After the third IST, they got the response again. Conclusion:The second IST is safe and effective for refractory and relapsed SAA patients; the early serologic reaction should be paid attention to when using the same ATG/ALG, and the risk can be reduced by changing the type of ATG/ALG or other IST programs. The third IST can still obtain the treatment response for the second relapse patients.

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