1.Ethical issues and reflections on clinical research of radiopharmaceuticals
Yonglan HU ; Li WANG ; Feng JIANG ; Jiyin ZHOU ; Zhengjun CHEN ; Jie ZHANG ; Zengrui ZHANG
Chinese Medical Ethics 2025;38(2):254-260
Radiopharmaceuticals play an important role in the diagnosis and treatment of cardiovascular and cerebrovascular diseases, malignant tumors, central nervous system diseases, and other diseases. Under the urgent need for clinical diagnosis and treatment as well as medical development, the clinical research of radiopharmaceuticals has become a hotspot in international research. By analyzing the current situation of clinical research on radiopharmaceuticals in Europe, America, and China, the ethical issues of clinical research on radiopharmaceuticals were elaborated from four aspects, including lack of relevant laws and regulations, a higher risk of radiopharmaceuticals, dilemmas in ethical review, and insufficient radiation protection. Response principles and measures were proposed from four aspects, including improving regulations and policies, enhancing radiological protection for all parties involved in the research, strengthening ethical review, and reinforcing the training of relevant personnel, to enhance the quality and level of clinical research on radiopharmaceuticals.
2.Screening of high risk children for lysosomal storage diseases and analysis of disease spectrum
Xueying SU ; Xiaoyuan ZHAO ; Yonglan HUANG ; Xi YIN ; Yanna CAI ; Li LIU ; Wen ZHANG
Chinese Journal of Pediatrics 2025;63(6):620-624
Objective:To screen high risk children for lysosomal storage diseases (LSD) in southern China and analyze the spectrum characteristics of LSD in this region.Methods:A cross-sectional study was conducted. A total of 7 435 children at high risk of LSD were screened at Guangzhou Women and Children′s Medical Center, Guangzhou Medical University from January 2009 to December 2024. The activities of 22 lysosomal enzymes from peripheral blood leukocytes or plasma were measured by fluorescence or colorimetric assays with synthetic substrates to screen for 24 LSD subtypes.Results:Among the 7 435 high risk children, 759 children were diagnosed with LSD (10.2%). The diagnosed cases included 506 males and 253 females, with an age at diagnosis of 3.0 (2.5, 5.5) years. The common disease types were mucopolysaccharidosis (MPS) (390 cases (51.4%)), sphingolipidoses (269 cases (35.4%)), glycogen storage disease (62 cases (8.2%)), and mucolipidosis types Ⅱ and Ⅲ (29 cases (3.8%)). Among the positive cases, 21 disease subtypes were identified. The 5 frequent subtypes, in descending order, were MPS type Ⅱ (197 cases (26.0%)), Gaucher disease (111 cases (14.6%)), MPS type ⅣA (87 cases (11.5%)), glycogen storage disease type Ⅱ (62 cases (8.2%)), and metachromatic leukodystrophy (MLD) (49 cases (6.5%)). The rarest subtypes were mannosidosis, multiple sulfatase deficiency and Wolman disease, each with 1 case (0.1%).Conclusions:Enzyme activity screening is essential for diagnosing high risk children with LSD. In Southern China, the most common LSD subtypes are MPS Ⅱ, Gaucher disease, MPS ⅣA, glycogen storage disease type Ⅱ, and MLD, while mannosidosis, multiple sulfatase deficiency and Wolman disease are the rarest.
3.Nomogram model of recurrence after RFCA for patients with atrial fibrillation complicated with heart failure
Yanru LI ; Weidong JIN ; Hao GUO ; Minglei HAN ; Zhen LIU ; Yonglan HOU
The Journal of Practical Medicine 2025;41(17):2637-2645
Objective To develop and validate a nomogram model for predicting recurrence after radiofre-quency catheter ablation(RFCA)in patients with atrial fibrillation and heart failure using body surface electrocar-diogram indicators and clinical indicators.Methods We retrospectively analyzed 305 patients with atrial fibrilla-tion complicated with heart failure who underwent RFCA from January 2019 to January 2024.Patients were random-ized into training set(213 cases)and validation set(92 cases)at a ratio of 7:3 and followed up for at least 1 year.Based on the recurrence status,the patients were divided into recurrence group and non-recurrence group,with body surface electrocardiogram indicators and clinical indicators collected.Multivariate logistic regression analysis identified for risk factors for post RFCA recurrence,which were used to construct a nomogram.Model performance was assessed using the area under the receiver operating characteristic curve(AUC),Hosmer-Lemeshow test,calibration curves,and decision curve analysis(DCA).Results Among the 305 patients,84(27.54%)experi-enced recurrence after treatment.In the training set,61 patients had recurrence and 152 did not.No statistical differences were observed between the training set and the validation set(all P>0.05).In the training set,the recurrence group exhibited a higher proportion of persistent atrial fibrillation and significantly higher CHA2DS2-VASc scores,larger left atrial diameter,longer PR interval,and higher levels of NLR and NT-proBNP compared to the non-recurrence group(all P<0.05).Multivariate stepwise regression analysis revealed that high CHA2DS2-VASc score,long left atrial diameter,prolonged PR interval,and high NLR were independent risk factors of recurrence after RFCA(P<0.05)A four-factor prediction model was established as:Ln(P/1-P)=-12.87+0.84*CHA2DS2-VASc score+0.11* left atrial diameter+0.03*PR interval+0.31*NLR.The training and validation models showed AUCs of 0.85(95%CI:0.80~0.91)and 0.85(95%CI:0.76~0.94),respectively,suggesting that the model had good predictive efficiency.Hosmer-Lemeshow test results(χ2=2.43,P=0.965 for the training set;χ2=5.30,P=0.725 for the validation set)confirmed model fit,indicating that the fitted probability value was consistent with the actual probability value.Calibration curves after 1 000 times of Bootstrap repeated sampling showed the bias calibration curves of the training set and the validation set had good consistency with the actual curves,both close to the ideal curve.DCA revealed clinical utility across a wide threshold probability range(0.02~1.0 for the training set;0.04~1.0 for the validation set).Conclusion This nomogram,based on body surface electrocardiogram indicators and clinical indicators,effectively predicts post-RFCA recurrence in atrial fibrillation and heart failure patients,offering a useful tool for early assessment of recurrence risk.
4.Nomogram model of recurrence after RFCA for patients with atrial fibrillation complicated with heart failure
Yanru LI ; Weidong JIN ; Hao GUO ; Minglei HAN ; Zhen LIU ; Yonglan HOU
The Journal of Practical Medicine 2025;41(17):2637-2645
Objective To develop and validate a nomogram model for predicting recurrence after radiofre-quency catheter ablation(RFCA)in patients with atrial fibrillation and heart failure using body surface electrocar-diogram indicators and clinical indicators.Methods We retrospectively analyzed 305 patients with atrial fibrilla-tion complicated with heart failure who underwent RFCA from January 2019 to January 2024.Patients were random-ized into training set(213 cases)and validation set(92 cases)at a ratio of 7:3 and followed up for at least 1 year.Based on the recurrence status,the patients were divided into recurrence group and non-recurrence group,with body surface electrocardiogram indicators and clinical indicators collected.Multivariate logistic regression analysis identified for risk factors for post RFCA recurrence,which were used to construct a nomogram.Model performance was assessed using the area under the receiver operating characteristic curve(AUC),Hosmer-Lemeshow test,calibration curves,and decision curve analysis(DCA).Results Among the 305 patients,84(27.54%)experi-enced recurrence after treatment.In the training set,61 patients had recurrence and 152 did not.No statistical differences were observed between the training set and the validation set(all P>0.05).In the training set,the recurrence group exhibited a higher proportion of persistent atrial fibrillation and significantly higher CHA2DS2-VASc scores,larger left atrial diameter,longer PR interval,and higher levels of NLR and NT-proBNP compared to the non-recurrence group(all P<0.05).Multivariate stepwise regression analysis revealed that high CHA2DS2-VASc score,long left atrial diameter,prolonged PR interval,and high NLR were independent risk factors of recurrence after RFCA(P<0.05)A four-factor prediction model was established as:Ln(P/1-P)=-12.87+0.84*CHA2DS2-VASc score+0.11* left atrial diameter+0.03*PR interval+0.31*NLR.The training and validation models showed AUCs of 0.85(95%CI:0.80~0.91)and 0.85(95%CI:0.76~0.94),respectively,suggesting that the model had good predictive efficiency.Hosmer-Lemeshow test results(χ2=2.43,P=0.965 for the training set;χ2=5.30,P=0.725 for the validation set)confirmed model fit,indicating that the fitted probability value was consistent with the actual probability value.Calibration curves after 1 000 times of Bootstrap repeated sampling showed the bias calibration curves of the training set and the validation set had good consistency with the actual curves,both close to the ideal curve.DCA revealed clinical utility across a wide threshold probability range(0.02~1.0 for the training set;0.04~1.0 for the validation set).Conclusion This nomogram,based on body surface electrocardiogram indicators and clinical indicators,effectively predicts post-RFCA recurrence in atrial fibrillation and heart failure patients,offering a useful tool for early assessment of recurrence risk.
5.Screening of high risk children for lysosomal storage diseases and analysis of disease spectrum
Xueying SU ; Xiaoyuan ZHAO ; Yonglan HUANG ; Xi YIN ; Yanna CAI ; Li LIU ; Wen ZHANG
Chinese Journal of Pediatrics 2025;63(6):620-624
Objective:To screen high risk children for lysosomal storage diseases (LSD) in southern China and analyze the spectrum characteristics of LSD in this region.Methods:A cross-sectional study was conducted. A total of 7 435 children at high risk of LSD were screened at Guangzhou Women and Children′s Medical Center, Guangzhou Medical University from January 2009 to December 2024. The activities of 22 lysosomal enzymes from peripheral blood leukocytes or plasma were measured by fluorescence or colorimetric assays with synthetic substrates to screen for 24 LSD subtypes.Results:Among the 7 435 high risk children, 759 children were diagnosed with LSD (10.2%). The diagnosed cases included 506 males and 253 females, with an age at diagnosis of 3.0 (2.5, 5.5) years. The common disease types were mucopolysaccharidosis (MPS) (390 cases (51.4%)), sphingolipidoses (269 cases (35.4%)), glycogen storage disease (62 cases (8.2%)), and mucolipidosis types Ⅱ and Ⅲ (29 cases (3.8%)). Among the positive cases, 21 disease subtypes were identified. The 5 frequent subtypes, in descending order, were MPS type Ⅱ (197 cases (26.0%)), Gaucher disease (111 cases (14.6%)), MPS type ⅣA (87 cases (11.5%)), glycogen storage disease type Ⅱ (62 cases (8.2%)), and metachromatic leukodystrophy (MLD) (49 cases (6.5%)). The rarest subtypes were mannosidosis, multiple sulfatase deficiency and Wolman disease, each with 1 case (0.1%).Conclusions:Enzyme activity screening is essential for diagnosing high risk children with LSD. In Southern China, the most common LSD subtypes are MPS Ⅱ, Gaucher disease, MPS ⅣA, glycogen storage disease type Ⅱ, and MLD, while mannosidosis, multiple sulfatase deficiency and Wolman disease are the rarest.
6.Protective Effect and Mechanism of miR-328-3p on Coronary Artery Endothelial Cell Injury Induced by Oxidized Low-density Lipoprotein
Yonglan HOU ; Xia LI ; Jianmei WANG ; Zhen LIU ; Minglei HAN ; Zhenghao LIU ; Weidong JIN
Journal of Sichuan University (Medical Sciences) 2024;55(5):1210-1216
Objective To investigate the protective effect of miR-328-3p on oxidized low-density lipoprotein(ox-LDL)-induced coronary artery endothelial cell injury and the potentially relevant mechanisms.Methods Human coronary artery endothelial cells(HCAECs)were induced with ox-LDL,and the cells were divided into a control group consisting of normal cells,an ox-LDL group receiving ox-LDL treatment,an ox-LDL+miR-NC group transfected with miR-NC and treated with ox-LDL,an ox-LDL+miR-328-3p group transfected with miR-328-3p and treated with ox-LDL,and ox-LDL+miR-328-3p+pcDNA group co-transfected miR-328-3p and pcDNA and treated with ox-LDL,and an ox-LDL+miR-328-3p+insulin-like growth factor 2(IGF2)group co-transfected miR-328-3p and IGF2 and treated with ox-LDL.The expression level of miR-328-3p was determined with RT-qPCR.Cell proliferation was determined by MTT.Cell apoptosis was measured by flow cytometry.Western blot was conducted to examine the protein expression levels of cleaved cas-3 and IGF2.ELISA was performed to determine the levels of tumor necrosis factor α(TNF-α),interleukin(IL)-6,and IL-1β.Dual luciferase reporter experiment was performed to verify the targeting relationship between miR-328-3p and IGF2.Results Compared with those of the control group,miR-328-3p expression level and cell activity were significantly reduced in the ox-LDL group(P<0.05),while the apoptotic rate,the protein expression levels of cleaved cas-3,IGF2,Bax,and Bcl-2,and the levels of TNF-α,IL-6,and IL-1β were significantly increased(P<0.05).Compared with those of the ox-LDL+miR-NC group,miR-328-3p expression level and cell activity significantly increased in the ox-LDL+miR-328-3p group(P<0.05),while the apoptosis rate,the protein expression levels of cleaved cas-3 and IGF2,and the levels of TNF-α,IL-6,and IL-1β were significantly reduced.IGF2 was a functional target of miR-328-3p.Compared with those of the ox-LDL+miR-328-3p+pcDNA co-transfection group,the IGF2 protein level was significantly increased(P<0.05)and cell activity was significantly decreased(P<0.05)in the ox-LDL+miR-328-3p+IGF2 co-transfection group,while the apoptosis rate,cleaved cas-3 protein level,and the levels of TNF-α,IL-6,and IL-1β were significantly elevated(P<0.05).Conclusion miR-328-3p inhibits ox-LDL-induced apoptosis and inflammatory in coronary artery endothelial cell injury through targeted negative regulation of IGF2.
7.Advances in Imaging-Based Evaluation of Solid Tumors Treated With Immune Checkpoint Inhibitors
Shangying YANG ; Xinyu LIU ; Huadan XUE ; Zhengyu JIN ; Yonglan HE ; Yuan LI
Acta Academiae Medicinae Sinicae 2024;46(4):610-618
Immune checkpoint inhibitors have shown remarkable benefits in the treatment of solid tumors,while the occurrence of atypical response patterns and immune-related adverse events during treatment challenges the accuracy of therapeutic evaluation.Medical imaging is crucial for the evaluation of immunotherapy.It enables the assessment of treatment efficacy via both morphological and functional ways and offers unique a predictive val-ue when being combined with artificial intelligence.Here we review the recent research progress in imaging-based evaluation of solid tumors treated with immune checkpoint inhibitors.
8.Effects of hydrogen sulfide on autophagy and angiogenesis of skin wound in diabetic rats
Yuanyuan LI ; Fusheng ZHAO ; Kexin ZHANG ; Yonglan CHEN ; Na ZHANG ; Xinyue JIANG ; Chunfu GU ; Geng WU
Chinese Journal of Pathophysiology 2023;39(12):2223-2233
AIM:To explore the effect and mechanism of hydrogen sulfide(H2S)on autophagy and angiogene-sis in skin wound of diabetic rats.METHODS:Among 36 healthy 8-week-old male Sprague-Dawley rats,12 rats were se-lected as control group,and the remaining rats were intraperitoneally injected with streptozotocin(STZ)to induce diabetic model and were randomly divided into diabetes mellitus(DM)group and NaHS(H2S donor)intervention(DM+NaHS)group,with 12 rats in each group.A skin trauma model was established by excising the skin of the back of rats in each group.The rats in DM+NaHS group were intraperitoneally injected with NaHS(56 μmol/kg),and the rats in control and DM groups were daily received the same volume of normal saline for 21 consecutive days.The healing of skin wound was measured on days 0,7,14 and 21 after operation.On the 21st day after surgery,the content of H2S in skin tissues was de-tected by C-7Az fluorescent probe,and the morphological changes and angiogenesis of wound tissues were observed by HE staining.The expression of CD31 was detected by immunofluorescence staining,and endothelial autophagy was detected by double staining of CD31 and beclin-1.The protein levels of cystathionine γ-lyase(CSE),CD31,microtubule-associated protein 1 light chain 3(LC3),beclin-1,P62,Bcl-2,Bax,phosphatidylinositol 3-kinase(PI3K),protein kinase B(PKB/Akt)and mammalian target of rapamycin(mTOR)in wound tissues were determined by Western blot.Caspase-3 and propidium iodide(PI)staining was used to detect cell apoptosis,and apoptosis of vascular endothelial cells was deter-mined with CD31 and TUNEL double immunofluorescence staining.RESULTS:Compared with DM group,the wound healing rate,H2S content and CSE protein expression were significantly increased in DM+NaHS group(P<0.01),but still lower than those in control group(P<0.01).HE staining showed that the wound surface in DM group was thin and wide,with few capillary,while that in DM+NaHS group was thicker with lots of capillary and wound width was reduced.Com-pared with DM group,CD31 expression was markedly increased(P<0.01),the fluorescence intensity of caspase-3 and PI was significantly decreased(P<0.01),and CD31+/beclin-1+ as well as CD31+/TUNEL+ cells were decreased(P<0.01)in DM+NaHS group.Western blot analysis showed that compared with DM group,the levels of beclin-1,Bax and LC3-Ⅱ/LC3-Ⅰ were significantly decreased(P<0.01),while the levels of P62 and Bcl-2,as well as ratios of p-PI3K/PI3K,p-Akt/Akt and p-mTOR/mTOR were significantly increased(P<0.01)in DM+NaHS group.CONCLUSION:H2S can promote skin wound healing,which may be related to activation of PI3K/Akt/mTOR signaling pathway,inhibition of endothelial au-tophagy and apoptosis,and promotion of angiogenesis in diabetic rats.
9.Risk factors for pulmonary infection in patients with lung cancer after chemotherapy:A Meta-analysis
Shuangyan XIE ; Sijin LI ; Zeyun LI ; Amin MA ; Yonglan YU ; Du XIE
China Modern Doctor 2023;61(34):14-18
Objective To systematically evaluate the risk factors for pulmonary infection in patients with lung cancer after chemotherapy.Methods CNKI,Wanfang Data,VIP,PubMed,Embase,and the Cochrane Library were searched from inception to October 2022 to collect case-control studies and cohort studies about risk factors for pulmonary infection in patients with lung cancer after chemotherapy.Two researchers independently conducted literature screening,data extraction,and quality assessment.Rev Man 5.3 software was used for Meta-analysis.Results A total of 15 literatures were included,including 3960 patients with lung cancer after chemotherapy.Meta analysis results showed that age≥60 years,smoking history,drinking history,hypertension,diabetes mellitus,atelectasis,hypoproteinaemia,TNM staging of stage Ⅲ-Ⅳ,central lung cancer,small cell lung cancer,invasive operation,Karnofsky performance status score<80 points before chemotherapy,combined chemotherapy drugs,duration of chemotherapeutic ?2 weeks,white blood cell count≤3.0×109/L after chemotherapy,albumin<30g/L after chemotherapy,and hospital stay>20 days were risk factors for pulmonary infection in patients with lung cancer after chemotherapy(P<0.05).Conclusion There were many risk factors for pulmonary infection in patients with lung cancer after chemotherapy.Prevention and control measures should be taken based on the related risk factors to reduce the incidence rate of pulmonary infection.
10.Clinical analysis of 3 cases of autoimmune encephalitis with antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
Huanhuan LI ; Chunhong LI ; Chao SUN ; Zhe RUAN ; Rongjing GUO ; Ting GAO ; Yonglan TANG ; Ting CHANG
Chinese Journal of Neurology 2022;55(4):319-328
Objective:To analyse the clinical features of encephalitis patients with antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR).Methods:Three anti-AMPAR encephalitis patients diagnosed in Tangdu Hospital, the Air Force Military Medical University between January 2020 and May 2021 were retrospectively reviewed. The clinical symptoms, supplementary examination, treatment options and outcomes with knowledge from literature were summarized in this study.Results:Three patients aging from 12 to 70 years presented with symptoms ranging from cognitive impairment, personality change to headache and paralysis. The lung occupying lesion was pathologically proved to be small cell lung cancer in case 1. Antibody to AMPAR (AMPAR-ab) was positive in both blood and cerebrospinal fluid of case 1, with coexisting antibodies against sex-determining region of Y chromosome-related high mobility group box 1 in blood, and the symptoms persisted but did not recur following therapy with corticosteroids. AMPAR-ab was detected only in serum in case 2, with the lesion located in both frontal and temporal lobes, centrum semiovale and lateral ventricle, combined with classic imaging features of intracranial hypotension, and the syndrome was partially improved following treatment with corticosteroids. The lesions were located in the pons and middle cerebellar peduncle, accompanied by cerebellar atrophy in case 3. Spinal cord magnetic resonance imaging showed long hyperintense lesions involving the cervical and thoracic cord, extending from C 2 to Th 10 level on T 2-weighted images. AMPAR-ab was positive in both serum and cerebrospinal fluid. And the symptoms improved significantly following treatment with corticosteroids and intravenous immunoglobulin. Conclusions:The clinical manifestations of anti-AMPAR encephalitis are highly heterogeneous, and brainstem and spinal cord can also be involved in addition to the limbic system, accompanied by brain atrophy. Combining with concurrent antibodies, especially the intracellular antibodies, malignancy needs to be closely monitored; the immunotherapy is effective and the presence of tumor superimposed with multiple antibodies may be associated with poor prognosis.

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