Publications by authors named "Lijun Fu"

108 Publications

A Multi-Centre Prospective Study of the Efficacy and Safety of Alglucosidase Alfa in Chinese Patients With Infantile-Onset Pompe Disease.

Front Pharmacol 2022 27;13:903488. Epub 2022 Jun 27.

Department of Cardiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

A high prevalence of infantile-onset Pompe disease (IOPD) in the Chinese population has been noted, but there are currently no reported clinical trials of enzyme replacement therapy (ERT) for IOPD in this population The purpose of this study was to evaluate the efficacy and safety of alglucosidase alfa in Chinese patients with IOPD. A multicentre, single-arm, prospective, open-label clinical trial was performed at 4 sites in China. Eligible Chinese subjects with IOPD received an infusion of alglucosidase alfa at a dose of 20 mg/kg every 2 weeks for up to 52 weeks. The primary endpoints of clinical efficacy were the survival rate and changes in the left ventricular mass index (LVMI). The safety assessment was based on the incidence of adverse events (AEs). A total of 10 eligible subjects were enrolled in the study. The mean age at the start of ERT was 5.36 ± 1.56 months. Nine subjects had survived after 52 weeks of treatment. One subject discontinued the study and died after mechanical ventilation was withdrawn. The intent-to-treat analysis demonstrated that the survival rate was 90.0% (95% confidence interval: 55.5-99.7%). The mean LVMI at week 52 was 70.59 ± 39.93 g/m compared to that of 298.02 ± 178.43 g/m at baseline, with a difference of -227.60 ± 155.99 g/m. All subjects had left ventricular mass (LVM) Z scores >10 at baseline, and eight subjects (80%) achieved Z scores <5 at week 52. No treatment-related AEs were observed, and no AEs led to the discontinuation of treatment. This clinical trial is the first study of ERT for IOPD in China, indicating that alglucosidase alfa has favourable efficacy and safety for the treatment of Chinese patients with IOPD (ClinicalTrials.gov number, NCT03687333).
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http://dx.doi.org/10.3389/fphar.2022.903488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271607PMC
June 2022

Strategies toward anode stabilization in nonaqueous alkali metal-oxygen batteries.

Chem Commun (Camb) 2022 Jul 19;58(58):8014-8024. Epub 2022 Jul 19.

School of Energy Sciences and Engineering, Nanjing Tech University, Nanjing 211816, Jiangsu Province, China.

Alkali metal-O batteries exhibit ultra-high theoretical energy density which is even on par with fossil energy and are expected to become the next generation energy storage devices. However, to maintain the advantages of high energy density of alkali metal-O batteries, the reversibility of alkali metal anodes with high capacity is of vital importance. But the alkali metal anode with high chemical activity often faces a variety of challenges, including various side reactions, dendrite formation and volume expansion. In this highlight, we focus on the challenges faced by alkali metal anodes in alkali metal-O batteries and introduce the latest strategies to effectively stabilize the metal anode. Future perspectives are pointed out, which are valuable for the further development of nonaqueous alkaline metal-O batteries.
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http://dx.doi.org/10.1039/d2cc02501aDOI Listing
July 2022

Spinal cord stimulation for treatment of neuropathic pain associated with syringomyelia.

Asian J Surg 2022 Jun 27. Epub 2022 Jun 27.

Department of Pain Management, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2022.06.111DOI Listing
June 2022

Versatile Asymmetric Separator with Dendrite-Free Alloy Anode Enables High-Performance Li-S Batteries.

Adv Sci (Weinh) 2022 Jun 24:e2202204. Epub 2022 Jun 24.

State Key Laboratory of Materials-oriented Chemical Engineering, Institute of Advanced Materials (IAM) and School of Energy Science and Engineering, Nanjing Tech University, Nanjing, 211816, P. R. China.

Lithium-sulfur batteries (LSBs) with extremely-high theoretical energy density (2600 Wh kg ) are deemed to be the most likely energy storage system to be commercialized. However, the polysulfides shuttling and lithium (Li) metal anode failure in LSBs limit its further commercialization. Herein, a versatile asymmetric separator and a Li-rich lithium-magnesium (Li-Mg) alloy anode are applied in LSBs. The asymmetric separator is consisted of lithiated-sulfonated porous organic polymer (SPOP-Li) and Li La Zr Nb O (LLZNO) layers toward the cathode and anode, respectively. SPOP-Li serves as a polysulfides barrier and Li-ion conductor, while the LLZNO functions as an "ion redistributor". Combining with a stable Li-Mg alloy anode, the symmetric cell achieves 5300 h of Li stripping/plating and the modified LSBs exhibit a long lifespan with an ultralow fading rate of 0.03% per cycle for over 1000 cycles at 5 C. Impressively, even under a high-sulfur-loading (6.1 mg cm ), an area capacity of 4.34 mAh cm after 100 cycles can still be maintained, demonstrating high potential for practical application.
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http://dx.doi.org/10.1002/advs.202202204DOI Listing
June 2022

Clinical characteristics and survival of children with hypertrophic cardiomyopathy in China: A multicentre retrospective cohort study.

EClinicalMedicine 2022 Jul 27;49:101466. Epub 2022 May 27.

Department of Cardiology, Shanghai Children's Medical Centre, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.

Background: Few data on paediatric hypertrophic cardiomyopathy (HCM) are available in developing countries. A multicentre, retrospective, cohort study was conducted to profile the clinical characteristics and survival of children with HCM in China.

Methods: We collected longitudinal data on children with HCM aged 0-18 years at three participating institutions between January 1, 2010 and December 31, 2019. Patients were identified by searching for the diagnosis using ICD-10 codes from the electronic medical records database. HCM was diagnosed morphologically with echocardiography or cardiovascular magnetic resonance imaging. The exclusion criteria were secondary aetiologies of myocardial hypertrophy. The primary outcomes were all-cause death or heart transplantation. The Kaplan-Meier method was used to estimate the survival rate of different groups.

Findings: A total of 564 children were recruited, with a median age at diagnosis of 1.0 year (interquartile range, IQR: 0.4-8.0 years), followed for a median of 2.6 years (1977 patient-years, IQR:0.5, 5.9 years). The underlying aetiology was sarcomeric (382, 67.7%), inborn errors of metabolism (IEMs) (108, 19.2%), and RASopathies (74, 13.1%). A total of 149 patients (26.4%) died and no patients underwent heart transplantation during follow-up. The survival probability was 71.1% (95% confidence interval [CI], 66.3%-75.3%) at 5 years. Patients with IEMs or those diagnosed during infancy had the poorest outcomes, with an estimated 5-year survival rate of 16.9% (95% CI, 7.7%-29.1%) and 56.0% (95% CI, 48.8%-62.5%), respectively. Heart failure was the leading cause of death in the cohort (90/149, 60.4%), while sudden cardiac death was the leading cause in patients with sarcomeric HCM (32/66, 48.5%).

Interpretation: There is a high proportion of patients with IEM and a low proportion of patients with neuromuscular disease in children with HCM in China. Overall, mortality remains high in China, especially in patients with IEMs and those diagnosed during infancy.

Funding: National Natural Science Fund of China (81770380, 81974029), China Project of Shanghai Municipal Science and Technology Commission (20MC1920400, 21Y31900301).
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http://dx.doi.org/10.1016/j.eclinm.2022.101466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157015PMC
July 2022

Comparison of Global and Regional Compliance-Guided Positive End-Expiratory Pressure Titration on Regional Lung Ventilation in Moderate-to-Severe Pediatric Acute Respiratory Distress Syndrome.

Front Med (Lausanne) 2022 23;9:805680. Epub 2022 May 23.

Department of Critical Care Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Purpose: To investigate the difference in the positive end-expiratory pressure (PEEP) selected with chest electrical impedance tomography (EIT) and with global dynamic respiratory system compliance (C) in moderate-to-severe pediatric acute respiratory distress syndrome (pARDS).

Methods: Patients with moderate-to-severe pARDS (PaO/FiO < 200 mmHg) were retrospectively included. On the day of pARDS diagnosis, two PEEP levels were determined during the decremental PEEP titration for each individual using the best compliance (PEEP) and EIT-based regional compliance (PEEP) methods. The differences of global and regional compliance (for both gravity-dependent and non-dependent regions) under the two PEEP conditions were compared. In addition, the EIT-based global inhomogeneity index (GI), the center of ventilation (CoV), and standard deviation of regional delayed ventilation (RVD) were also calculated and compared.

Results: A total of 12 children with pARDS (5 with severe and 7 with moderate pARDS) were included. PEEP and PEEP were identical in 6 patients. In others, the differences were only ± 2 cm HO (one PEEP step). There were no statistical differences in global compliance at PEEP and PEEP [28.7 (2.84-33.15) vs. 29.74 (2.84-33.47) ml/cm HO median (IQR), = 0.028 (the significant level after adjusted for multiple comparison was 0.017)]. Furthermore, no differences were found in regional compliances and other EIT-based parameters measuring spatial and temporal ventilation distributions.

Conclusion: Although EIT provided information on ventilation distribution, PEEP selected with the best C might be non-inferior to EIT-guided regional ventilation in moderate-to-severe pARDS. Further study with a large sample size is required to confirm the finding.
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http://dx.doi.org/10.3389/fmed.2022.805680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9167956PMC
May 2022

CircNRIP1 Exerts Oncogenic Functions in Papillary Thyroid Carcinoma by Sponging miR-653-5p and Regulating PBX3 Expression.

J Oncol 2022 19;2022:2081501. Epub 2022 May 19.

Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, No. l Construction of East Road, Erqi District, Zhengzhou, 450052 Henan, China.

Background: Circular RNA circ_0004771 (termed circNRIP1) was identified by RNA-Seq previously and was elevated in papillary thyroid carcinoma (PTC) tissues. A series of studies also showed that circNRIP1 was upregulated in some tumors and could promote the malignant progression of tumors. This research intended to focus on the role of circNRIP1 in PTC progression and explore the mechanisms underlying circNRIP1 functions.

Methods: RT-PCR or western blot determined circNRIP1, miR-653-5p, and pre-B-cell leukemia homeobox 3 (PBX3) expression. EdU, CCK-8, Tunel, and transwell assays determined cell proliferation, apoptosis, invasion, and migration, respectively. Luciferase reporter assay, RNA immunoprecipitation (RIP), and RNA pull down assays clarified the target relation between miR-653-5p and circNRIP1 or PBX3. Xenograft models were applied to explore the role of circNRIP1 .

Results: circNRIP1 significantly increased in PTC tissues and PTC cell lines than that in normal ones. Higher circNRIP1 expression was associated with the TNM stage and poorer overall survival. circNRIP1 knockdown attenuated the malignant progression of PTC, specifically by inhibiting proliferation and invasion/migration and promoting apoptosis. circNRIP1 was a miR-653-5p sponge; miR-653-5p knockdown reversed the suppressive role of circNRIP1 silence in PTC progression. PBX3, a target of miR-653-5p, was positively medicated through circNRIP1 via competitively sponging miR-653-5p. Knockdown of circNRIP1 attenuated the PTC tumor progression via miR-653-5p/PBX3 axis.

Conclusion: Silencing of circNRIP1 suppressed PTC development via miR-653-5p elevation and PBX3 reduction, providing a novel perspective for understanding PTC pathogenesis.
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http://dx.doi.org/10.1155/2022/2081501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9135513PMC
May 2022

Identification of Immune-Related Breast Cancer Chemotherapy Resistance Genes Bioinformatics Approaches.

Front Oncol 2022 21;12:772723. Epub 2022 Mar 21.

Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Chemotherapy resistance in breast cancer is an important factor affecting the prognosis of breast cancer patients. We computationally analyzed the differences in gene expression before and after chemotherapy in breast cancer patients, drug-sensitive groups, and drug-resistant groups. Through functional enrichment analysis, immune microenvironment analysis, and other computational analysis methods, we identified PRC1, GGTLC1, and IRS1 as genes that may mediate breast cancer chemoresistance through the immune pathway. After validation of certain other clinical datasets and cellular assays, we found that the above three genes influenced drug resistance in breast cancer patients and were closely related to the tumor immune microenvironment. Our finding that chemoresistance in breast cancer could be influenced by the mediation of tumor immunity expanded our knowledge of how to address this problem and could guide future research involving chemoresistance.
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http://dx.doi.org/10.3389/fonc.2022.772723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8978268PMC
March 2022

SRAS-net: Low-resolution chromosome image classification based on deep learning.

IET Syst Biol 2022 May 4;16(3-4):85-97. Epub 2022 Apr 4.

Hunan Provincial Key Laboratory of Intelligent Computing and Language Information Processing, Hunan Normal University, Changsha, China.

Prenatal karyotype diagnosis is important to determine if the foetus has genetic diseases and some congenital diseases. Chromosome classification is an important part of karyotype analysis, and the task is tedious and lengthy. Chromosome classification methods based on deep learning have achieved good results, but if the quality of the chromosome image is not high, these methods cannot learn image features well, resulting in unsatisfactory classification results. Moreover, the existing methods generally have a poor effect on sex chromosome classification. Therefore, in this work, the authors propose to use a super-resolution network, Self-Attention Negative Feedback Network, and combine it with traditional neural networks to obtain an efficient chromosome classification method called SRAS-net. The method first inputs the low-resolution chromosome images into the super-resolution network to generate high-resolution chromosome images and then uses the traditional deep learning model to classify the chromosomes. To solve the problem of inaccurate sex chromosome classification, the authors also propose to use the SMOTE algorithm to generate a small number of sex chromosome samples to ensure a balanced number of samples while allowing the model to learn more sex chromosome features. Experimental results show that our method achieves 97.55% accuracy and is better than state-of-the-art methods.
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http://dx.doi.org/10.1049/syb2.12042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290780PMC
May 2022

IL-10 contributes to gemcitabine resistance in extranodal NK/T-cell lymphoma cells via ABCC4.

Invest New Drugs 2022 06 28;40(3):537-545. Epub 2022 Feb 28.

Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Zhengzhou, Henan, 450000, China.

Background Chemotherapy resistance is a main reason for treatment failure in extranodal NK/T-cell lymphoma (ENKTL). Interleukin-10 (IL-10) is closely related to the occurrence and prognosis of ENKTL. We intended to study the role and molecular mechanism of IL-10 in ENKTL resistance. Methods Fifty serum samples were collected from patients with a histologically proven diagnosis of ENKTL. Fifty healthy volunteers were enrolled as a control group. The level of serum IL-10 was detected by ELISA. The NK/T-cell lymphoma cell lines YT and NK-92 were divided into the control group (untreated), IL-10 group (treated with IL-10), IL-10 + GEM group (treated with IL-10 and gemcitabine simultaneously) and GEM group (treated with gemcitabine). A CCK8 assay and flow cytometry were employed to detect the effects of IL-10 on each group. Western blotting was applied to detect the expression of ABC membrane transporter family proteins and signaling pathway proteins in each group. Results Serum IL-10 levels were higher in ENKTL patients as well asin patients with ineffective treatment. The IC50 value for gemcitabine in YT and NK-92 cells increased significantly in the presence of IL-10. The effects of gemcitabine resulting in cell killing, cell cycle arrest, and apoptosis promotion were also weakened by IL-10. The expression of ABCC4, STAT1, p-STAT1, Tyk2 and p-Tyk2 was significantly increased by IL-10. Conclusion Our results indicate that IL-10 contributes to the resistance of ENKTL cells via ABCC4 and that IL-10 regulates the JAK/STAT signaling pathway in YT and NK-92 cells.
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http://dx.doi.org/10.1007/s10637-022-01224-8DOI Listing
June 2022

Molecular and Phenotypic Expansion of Alström Syndrome in Chinese Patients.

Front Genet 2022 8;13:808919. Epub 2022 Feb 8.

Department of Endocrinology and Metabolism, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Alström syndrome (ALMS) is a rare inherited metabolic disease and ciliopathy. Large cohorts of ALMS are lacking around the world. Detailed genetic and phenotypic data were obtained from all affected individuals. Olfactory function was evaluated by the Chinese Smell Identification Test and facial pattern was analyzed with Face2gene. Fifty ALMS patients were included in this study, aged from 0.3 to 21.7 years old. Sixty-one variants in 50 patients from 47 different families were confirmed, including 59 truncating and two exon deletions. Twenty-four of those variants were novel. We also summarized all previously reported cases of Chinese ALMS patients (69 patients) and identified specific and common variants within the Chinese population. Besides, the Chinese Smell Identification Test scores in patients was lower than that in controls (11.97 Vs. 10.44, < .05), indicating olfactory identification impairments in ALMS patients. The facial pattern in ALMS patients was also distinctive from that of the controls ( < .05). In conclusion, this is the largest cohort of Chinese ALMS patients. We have successfully identified both specific and common variants in our cohort. We found a new phenotype of olfactory impairments in ALMS patients through a case-control study.
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http://dx.doi.org/10.3389/fgene.2022.808919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8861322PMC
February 2022

Boosting Polysulfide Catalytic Conversion and Facilitating Li Transportation by Ion-Selective COFs Composite Nanowire for LiS Batteries.

Small 2022 Mar 21;18(11):e2106679. Epub 2022 Jan 21.

State Key Laboratory of Materials-oriented Chemical Engineering, Institute of Advanced Materials (IAM) and School of Energy Science and Engineering, Nanjing Tech University, Nanjing, 211816, P. R. China.

The large-scale application of lithium-sulfur batteries (LSBs) has been impeded by the shuttle effect of lithium-polysulfides (LiPSs) and sluggish redox kinetics since which lead to irreversible capacity decay and low sulfur utilization. Herein, a hierarchical interlayer constructed by boroxine covalent organic frameworks (COFs) with high Li conductivity is fabricated via an in situ polymerization method on carbon nanotubes (CNTs) ([email protected]). The as-prepared interlayer delivers a high Li ionic conductivity (1.85 mS cm ) and Li transference number (0.78), which not only acts as a physical barrier, but also a bidirectional catalyst for LiPSs redox process owing to the abundant heterointerfaces between the inner conductive CNTs and the outer COFs. After coupling such a catalytic interlayer with sulfur cathode, the LSBs exhibit a low decay rate of 0.07% per cycle over 500 cycles at 1 C, and long cycle life at 3 C (over 1000 cycles). More importantly, a remarkable areal capacity of around 4.69 mAh cm can still be maintained after 50 cycles even under a high sulfur loading condition (6.8 mg cm ). This work paves a new way for the design of the interlayer with bidirectional catalytic behavior in LSBs.
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http://dx.doi.org/10.1002/smll.202106679DOI Listing
March 2022

First Report of Rhizome Rot Caused by on Ginger in China.

Plant Dis 2022 Jun 16:PDIS10212324PDN. Epub 2022 Jun 16.

Tangshan Academy of Agricultural Sciences, Tangshan 063001, China.

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http://dx.doi.org/10.1094/PDIS-10-21-2324-PDNDOI Listing
June 2022

A Frequent Observation of Wolff-Parkinson-White Syndrome and Fasciculoventricular Pathways in Patients With Danon Disease.

Circ J 2022 01 23;86(2):309-318. Epub 2021 Dec 23.

Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Provincial People's Hospital.

Background: Danon disease is typically associated with cardiomyopathy and ventricular pre-excitation. The study aimed to characterize the clinical profile of Danon disease, analyze electrocardiographic (ECG) and electrophysiologic features, and investigate their association with Wolff-Parkinson-White (WPW) syndrome and fasciculoventricular pathways (FVPs).Methods and Results:Clinical course, family history, ECG and electrophysiological data were collected from 16 patients with Danon disease. Over 0.4-8 years of follow up, 1 female patient died suddenly, and 5 male patients died of progressive heart failure by age 13-20 years. Family history analysis revealed that 3 mothers experienced hospitalization or death for heart failure at age 28-41 years. There was 100% penetrance for ECG abnormalities in 13 patients with original ECGs. Short PR intervals and delta waves were present in 9 and 8 patients, respectively. There were significant age-associated increases in the QRS complex width (r=0.556, P=0.048) and the number of leads with notched QRS (r=0.575, P=0.04). Four patients who underwent electrophysiological studies all had FVPs, and 2 of them still had left-side atrioventricular pathways.

Conclusions: Danon disease causes a malignant clinical course characterized by early death caused by heart failure in both genders and progressive ECG changes as patients age. The pre-excited ECG pattern is related to FVPs and WPW, which is suggestive of extensive cardiac involvement.
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http://dx.doi.org/10.1253/circj.CJ-21-0572DOI Listing
January 2022

Left ventricular epicardial pacing achieved hyper-responsiveness in young children with dilated cardiomyopathy with left bundle branch block.

ESC Heart Fail 2021 12 2;8(6):4772-4779. Epub 2021 Nov 2.

Department of Cardiology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.

Aims: The management of heart failure (HF) in young children is challenging. The present study aimed to clarify the effect of left univentricular epicardial pacing on dilated cardiomyopathy with left bundle branch block (LBBB) in children.

Methods And Results: A total of five cases (30.86 ± 16.39 months, three female) of children weighing 5.8-15 kg with dilated cardiomyopathy and LBBB were included in this study. LBBB in one child occurred after device closure of peri-membranous ventricular septal defects, and the remaining four were idiopathically discovered early after birth. Before implantation, all children suffered from refractory HF and cardiac dilatation; the left ventricular ejection fraction was 33.48 ± 5.84% with Ross Heart Failure Classification III-IV. Electrical and mechanical dyssynchrony were observed in all children with QRS duration >140 ms and prolonged septal-to-left posterior wall motion delay. Left univentricular epicardial pacing was successfully implanted via left axillary minithoracotomy in the five children. Sensed atrioventricular delays (83 ± 15 ms) were optimized by velocity time integral of aortic blood flow before discharge. During the follow-up period (10.8 ± 2.68 months), the dilated failing heart was reversed significantly in terms of decreased left ventricular dimension (55.62 ± 3.46 vs. 38.94 ± 3.69 mm, P = 0.005), while the left ventricular ejection fraction improved to 60.18 ± 8.78% (P = 0.006).

Conclusions: In young children with low body weight, if HF is caused by or related to LBBB, left ventricular epicardial pacing still has an excellent effect.
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http://dx.doi.org/10.1002/ehf2.13657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712794PMC
December 2021

CircRNA NRIP1 promotes papillary thyroid carcinoma progression by sponging mir-195-5p and modulating the P38 MAPK and JAK/STAT pathways.

Diagn Pathol 2021 Oct 25;16(1):93. Epub 2021 Oct 25.

Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Νo. 1 Jianshe East Road, 450052, Zhengzhou, China.

Background: Circular RNAs (circRNAs) have become a hot topic in the area of tumor biology due to its closed structure and the post-transcriptional regulatory effect. This study aims to clarify the roles of circRNA nuclear receptor-interacting protein 1 (NRIP1; circNRIP1) and the possible mechanisms in papillary thyroid carcinoma (PTC).

Methods: The real-time PCR was used to detect the expression level of CircRNA NRIP1 in PTC specimens and cell lines. The effects of CircRNA NRIP1 and miR-195-5p on the PTC cell functions were detected by MTT, transwell, and flow cytometry assays. Dual-luciferase reporter assays and pull down assays were used to verify the association between circRNA NRIP1 and miR-195-5p. The murine xenograft models were constructed to detect the roles of CircRNA NRIP1 and miR-195-5p. Western blot was applied to detect the effects of CircRNA NRIP1 and miR-195-5p on the P38 MAPK and JAK/STAT singling pathways.

Results: CircRNA NRIP1 was over-expressed in PTC tissues and cells and the high levels of CircRNA NRIP1 were correlated with advanced PTC stage. Depletion of CircRNA NRIP1 inhibited PTC cell proliferation, invasion, while accelerated apoptosis. miR-195-5p upregulation repressed proliferation and invasion capabilities, and accelerated apoptosis of PTC cell lines and restraining the growth of tumor xenografts, while the functions were reversed following CircRNA NRIP1 overexpression in PTC cells and tumor xenografts. Besides, the protein levels of p-p38, p-JAK2 and p-STAT1 were remarkably down-regulated in miR-195-5p overexpressed PTC cells and tumor xenografts, whereas CircRNA NRIP1 up-regulation overturned the impacts.

Conclusions: In conclusion, CircRNA NRIP1 promoted PTC progression by accelerating PTC cells proliferation, invasion and tumor growth, while impeding apoptosis by way of sponging miR-195-5p and regulating the P38 MAPK and JAK/STAT pathways.
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http://dx.doi.org/10.1186/s13000-021-01153-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8543861PMC
October 2021

Atypical TNF-TNFR superfamily binding interface in the GITR-GITRL complex for T cell activation.

Cell Rep 2021 09;36(12):109734

Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address:

Glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) is a critical regulatory molecule in modulation of T cell immune responses. Here we report the mouse GITR (mGITR) and mGITR ligand (mGITRL) complex structure and find that the binding interface of mGITR and mGITRL is distinct from the typical tumor necrosis factor superfamily (TNFSF)/TNF receptor superfamily (TNFRSF) members. mGITR binds to its ligand with a single domain, whereas the binding interface on mGITRL is located on the side, which is distal from conserved binding sites of TNFSF molecules. Mutational analysis reveals that the binding interface of GITR/GITRL in humans is conserved with that in the mouse. Substitution of key interacting D93-I94-V95 (DIV) in mGITR with the corresponding K93-F94-S95 (KFS) in human GITR enables cross-recognition with human GITRL and cross-activation of receptor signaling. The findings of this study substantially expand our understanding of the interaction of TNFSF/TNFRSF superfamily molecules and can benefit the future design of biologics by targeting GITR/GITRL.
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http://dx.doi.org/10.1016/j.celrep.2021.109734DOI Listing
September 2021

A sensor of liquid methanol for direct methanol fuel cells.

Anal Chim Acta 2021 Sep 18;1177:338785. Epub 2021 Jun 18.

School of Energy Science and Engineering, Nanjing Tech University, Nanjing, 211816, Jiangsu, PR China. Electronic address:

The methanol sensors are of significance to maintain the efficient and stable operation of direct methanol fuel cells (DMFCs). The issues, including stability, the relationship between temperature, current density and concentration need, however, urgent attention. A novel electrochemical methanol sensor which is based on current output limited by methanol diffusion is developed. The stability of sensors was lifted steeply through introducing a reference electrode, narrowing the methanol flow channel, and adding a water container. The relationship between the temperature, response current and methanol concentration was determined with the help of theoretical derivation and the validity was verified by the fitting result. Other sensors can avail of this relationship to correct the temperature effect. Application test indicated that the sensor may be of great potential for the accurate monitoring of methanol concentration at the levels of DMFCs application.
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http://dx.doi.org/10.1016/j.aca.2021.338785DOI Listing
September 2021

Pharmacophore-Based Design of Phenyl-[hydroxycyclohexyl] Cycloalkyl-Carboxamide Mitofusin Activators with Improved Neuronal Activity.

J Med Chem 2021 09 20;64(17):12506-12524. Epub 2021 Aug 20.

Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, United States.

Mitochondrial fragmentation from defective fusion or unopposed fission contributes to many neurodegenerative diseases. Small molecule mitofusin activators reverse mitochondrial fragmentation , promising a novel therapeutic approach. The first-in-class mitofusin activator, , has a short plasma and limited neurological system bioavailability, conferring "burst activation". Here, pharmacophore-based rational redesign generated analogues of incorporating cycloalkyl linker groups. A cyclopropyl-containing linker, , improved plasma and brain , increased nervous system bioavailability, and prolonged neuron pharmacodynamic effects. Functional and single-crystal X-ray diffraction studies of stereoisomeric analogues of containing sulfur as a "heavy atom", and , showed that biological activity resides in the R/R configuration, . Structural analysis revealed stereoselective interactions of associated with its mimicry of MFN2 Val372, Met376, and His380 side chains. Modification of murine ALS phenotypes and supports advancement of for neurological conditions that may benefit from sustained mitofusin activation.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632069PMC
September 2021

Clinical value of pediatric sepsis-induced coagulopathy score in diagnosis of sepsis-induced coagulopathy and prognosis in children.

J Thromb Haemost 2021 12 22;19(12):2930-2937. Epub 2021 Sep 22.

Department of Cardiology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: In adults, sepsis-induced coagulopathy (SIC) is diagnosed by the SIC score, known as sepsis-3. There is no pediatric SIC (pSIC) score at present.

Objectives: We proposed a pSIC scoring method and evaluated the diagnostic efficacy of the score in the diagnosis of SIC in children.

Patients/methods: Patient data were retrospectively analyzed from Shanghai Children's Medical Center between February 2014 and January 2015. The pSIC score was modified from the SIC score. The area under ROC curve (AU-ROC) was used to compare the prognostic values of pSIC with other scores for pediatric sepsis-induced disseminated intravascular coagulation (DIC) to arrive at a 28-day outcome.

Results And Conclusions: There were 54 patients in the pSIC group and 37 in the non-pSIC group. The Kaplan-Meier survival curve analysis showed that the 28-day prognosis was better in the non-pSIC than in the pSIC group (p < .001). The AU-ROC of the pSIC score in predicting 28-day mortality in sepsis was 0.716, with the optimal cutoff value of >3 inferior to that of pediatric sequential organ failure (0.716 vs. 0.921, p < .001). The AU-ROC of pSIC in predicting nonovert DIC was 0.845 and the optimal cutoff value was >3. The AU-ROC of pSIC in predicting overt DIC was 0.901, with the best optimal cutoff value of >4. The pSIC score can be used to diagnose SIC in children, screen potential nonovert DIC, and assess the severity of sepsis, organ dysfunction, and 28-day outcome in children.
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http://dx.doi.org/10.1111/jth.15500DOI Listing
December 2021

Editorial: Acquired Heart Disease in Children: Pathogenesis, Diagnosis and Management.

Front Pediatr 2021 15;9:725670. Epub 2021 Jul 15.

Department of Cardiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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http://dx.doi.org/10.3389/fped.2021.725670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319598PMC
July 2021

Machine Learning for Early Warning of Septic Shock in Children With Hematological Malignancies Accompanied by Fever or Neutropenia: A Single Center Retrospective Study.

Front Oncol 2021 15;11:678743. Epub 2021 Jun 15.

Pediatric Artificial Intelligence Clinical Application and Research Center, Shanghai, China.

Objectives: The purpose of this article was to establish and validate clinically applicable septic shock early warning model (SSEW model) that can identify septic shock in hospitalized children with onco-hematological malignancies accompanied with fever or neutropenia.

Methods: Data from EMRs were collected from hospitalized pediatric patients with hematological and oncological disease at Shanghai Children's Medical Center. Medical records of patients (>30 days and <19 years old) with fever (≥38°C) or absolute neutrophil count (ANC) below 1.0 × 10/L hospitalized with hematological or oncological disease between January 1, 2017 and August 1, 2019 were considered. Patients in whom septic shock was diagnosed during the observation period formed the septic shock group, whereas non-septic-shock group was the control group. In the septic shock group, the time points at 4, 8, 12, and 24 hours prior to septic shock were taken as observation points, and corresponding observation points were obtained in the control group after matching. We employed machine learning artificial intelligence (AI) to filter features and used XGBoost algorithm to build SSEW model. Area under the ROC curve (AU-ROC) was used to compare the effectiveness among the SSEW Model, logistic regression model, and pediatric sequential organ failure score (pSOFA) for early warning of septic shock.

Main Results: A total of 64 observation periods in the septic shock group and 2191 in the control group were included. AU-ROC of the SSEW model had higher predictive value for septic shock compared with the pSOFA score (0.93 vs. 0.76, Z = -2.73, P = 0.006). Further analysis showed that the AU-ROC of the SSEW model was superior to the pSOFA score at the observation points 4, 8, 12, and 24 h before septic shock. At the 24 h observation point, the SSEW model incorporated 14 module root features and 23 derived features.

Conclusion: The SSEW model for hematological or oncological pediatric patients could help clinicians to predict the risk of septic shock in patients with fever or neutropenia 24 h in advance. Further prospective studies on clinical application scenarios are needed to determine the clinical utility of this AI model.
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http://dx.doi.org/10.3389/fonc.2021.678743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240637PMC
June 2021

An Artificial Polyacrylonitrile Coating Layer Confining Zinc Dendrite Growth for Highly Reversible Aqueous Zinc-Based Batteries.

Adv Sci (Weinh) 2021 Jun 30;8(11):e2100309. Epub 2021 Mar 30.

Department of Chemistry, University of Venda, Thohoyandou, 0950, South Africa.

Aqueous rechargeable zinc-metal-based batteries are an attractive alternative to lithium-ion batteries for grid-scale energy-storage systems because of their high specific capacity, low cost, eco-friendliness, and nonflammability. However, uncontrollable zinc dendrite growth limits the cycle life by piercing the separator, resulting in low zinc utilization in both alkaline and mild/neutral electrolytes. Herein, a polyacrylonitrile coating layer on a zinc anode produced by a simple drop coating approach to address the dendrite issue is reported. The coating layer not only improves the hydrophilicity of the zinc anode but also regulates zinc-ion transport, consequently facilitating the uniform deposition of zinc ions to avoid dendrite formation. A symmetrical cell with the polymer-coating-layer-modified Zn anode displays dendrite-free plating/stripping with a long cycle lifespan (>1100 h), much better than that of the bare Zn anode. The modified zinc anode coupled with a Mn-doped V O cathode forms a stable rechargeable full battery. This method is a facile and feasible way to solve the zinc dendrite problem for rechargeable aqueous zinc-metal batteries, providing a solid basis for application of aqueous rechargeable Zn batteries.
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http://dx.doi.org/10.1002/advs.202100309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188195PMC
June 2021

Nonporous Gel Electrolytes Enable Long Cycling at High Current Density for Lithium-Metal Anodes.

ACS Appl Mater Interfaces 2021 Mar 21;13(12):14258-14266. Epub 2021 Mar 21.

State Key Laboratory of Materials-Oriented Chemical Engineering, Institute of Advanced Materials (IAM) and School of Energy Science and Engineering, Nanjing Tech University, Nanjing 211816, China.

Lithium-metal anodes with high theoretical capacity and ultralow redox potential are regarded as a "holy grail" of the next-generation energy-storage industry. Nevertheless, Li inevitably reacts with conventional liquid electrolytes, resulting in uneven electrodeposition, unstable solid electrolyte interphase, and Li dendrite formation that all together lead to a decrease in active lithium, poor battery performance, and catastrophic safety hazards. Here, we report a unique nonporous gel polymer electrolyte (NP-GPE) with a uniform and dense structure, exhibiting an excellent combination of mechanical strength, thermal stability, and high ionic conductivity. The nonporous structure contributed to a uniform distribution of lithium ions for dendrite-free lithium deposition, and Li/NP-GPE/Li symmetric cells can maintain an extremely low and stable polarization after cycling at a high current density of 10 mA cm. This work provides an insight that the NP-GPE can be considered as a candidate for practical applications for lithium-metal anodes.
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http://dx.doi.org/10.1021/acsami.1c00182DOI Listing
March 2021

[Analysis of ALMS1 gene variants in seven patients with Alström syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Feb;38(2):112-116

Department of Endocrinology and Metabolism, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China.

Objective: To explore the genetic basis for 7 patients with Alström syndrome.

Methods: DNA was extracted from peripheral blood samples of the patients and their parents. Whole exome sequencing was carried out for the patients. Suspected variant was verified by Sanger sequencing and bioinformatic analysis.

Results: Genetic testing revealed 12 variants of the ALMS1 gene among the 7 patients, including 7 nonsense and 5 frameshift variants, which included c.5418delC (p.Tyr1807Thrfs*23), c.10549C>T (p.Gln3517*), c.9145dupC (p.Thr3049Asnfs*12), c.10819C>T (p.Arg3607*), c.5701_5704delGAGA (p.Glu1901Argfs*18), c.9154_9155delCT (p.Cys3053Serfs*9), c.9460delG (p.Val3154*), c.9379C>T (p.Gln3127*), c.12115C>T (p.Gln4039*), c.1468dupA (p.Thr490Asnfs*15), c.10825C>T (p.Arg3609*) and c.3902C>A (p.Ser1301*). Among these, c.9154_ 9155delCT, c.9460delG, c.9379C>T, and c.1468dupA were unreported previously. Based on the standards and guidelines of American College of Medical Genetics and Genomics, the c.9379C>T and c.12115C>T variants of the ALMS1 gene were predicted to be likely pathogenic (PVS1+PM2), whilst the other 10 variants were predicted to be pathogenic (PVS1+ PM2+ PP3+PP4).

Conclusion: ALMS1 variants probably underlay the Alström syndrome in the 7 patients, and genetic testing can provide a basis for the clinical diagnosis of this syndrome. The discovery of four novel variants has expanded the mutational spectrum of Alström syndrome.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200115-00033DOI Listing
February 2021

Higher Levels of Triglyceride, Fatty Acid Translocase, and Toll-Like Receptor 4 and Lower Level of HDL-C in Pregnant Women with GDM and Their Close Correlation with Neonatal Weight.

Gynecol Obstet Invest 2021 22;86(1-2):48-54. Epub 2021 Jan 22.

Department of Obstetrics and Gynecology, North China University of Science and Technology Affiliated Hospital, Tangshan, China,

Objectives: In this study, we aimed to compare the levels of maternal blood lipids, placental and venous blood lipid transporters, and inflammatory factor receptors in pregnant women with and without gestational diabetes mellitus (GDM). We also aimed to figure out the relationship between these values and neonatal weight.

Methods: Fifty pregnant women with GDM under blood glucose control belong to the case group, and 50 pregnant women with normal glucose tolerance in concurrent delivery belong to the control group. Fasting venous blood of these pregnant women was taken 2 weeks before delivery, and umbilical cord blood was collected after delivery. The levels of triglyceride (TG), serum total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) in maternal blood and umbilical cord blood were tested in the laboratory department of our hospital. The level of toll-like receptor 4 (TLR4) in serum of umbilical veins was detected by the double-antibody sandwich ELISA. Western blot and RT-PCR were used to detect the protein and mRNA expressions of TLR4, LPL, and FAT/CD36 in the placenta.

Results: The level of TG in maternal blood in the case group was remarkably higher than that in the control group, which was opposite to the level of HDL-C. In the umbilical cord blood of women with GDM, the expression of TLR4 increased and was closely correlated with neonatal weight. In the placenta of women with GDM, the expressions of FAT/CD36 and TLR4 increased, and both of them were closely correlated with neonatal weight. Besides, TLR4 in umbilical cord blood increased and was closely correlated with neonatal weight. Although the expression of LPL in the placenta decreased, it had no obvious correlation with neonatal weight.

Conclusions: TG in maternal blood, TLR4 in the placenta and umbilical cord blood, and FAT/CD36 in the placenta were positively correlated with neonatal weight. However, HDL-C in maternal blood was negatively correlated with neonatal weight. Although the expression of LPL in the placenta reduced due to GDM, it had no correlation with neonatal weight.
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http://dx.doi.org/10.1159/000510032DOI Listing
May 2021

Optimal utilization of fluoroethylene carbonate in potassium ion batteries.

Chem Commun (Camb) 2021 Feb 14;57(13):1607-1610. Epub 2021 Jan 14.

State Key Laboratory of Materials-oriented Chemical Engineering, College of Chemical Engineering, School of Energy Science and Engineering, Nanjing Tech University, Nanjing, Jiangsu 211816, China.

This work provides a novel strategy of optimal utilization of fluoroethylene carbonate to generate a uniform and compact solid electrolyte interface film, enhancing the cycle life of potassium ion batteries. With K foil being treated with fluoroethylene carbonate prior to use, enhanced cycling performance up to 1200 hours was achieved. Combining in situ electrochemical impedance spectroscopy with the distribution of relaxation time analysis and XPS analysis, the solubility of KF in the electrolyte is proposed as a crucial factor to determine the quality of a solid electrolyte interface. Our work contributes to understanding the role and manipulating the usage of the fluoroethylene carbonate additive in potassium ion batteries.
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http://dx.doi.org/10.1039/d0cc06467jDOI Listing
February 2021

Boosting Capacitive Sodium-Ion Storage in Electrochemically Exfoliated Graphite for Sodium-Ion Capacitors.

ACS Appl Mater Interfaces 2020 Nov 13;12(47):52635-52642. Epub 2020 Nov 13.

School of Energy Science and Engineering & Institute of Advanced Materials, Nanjing Tech University, Nanjing 211816, Jiangsu Province, China.

Sodium (Na)-ion capacitors possess higher energy density than supercapacitors and higher power density than Na-ion batteries. However, kinetic mismatches between fast capacitive charge storage on the cathode and sluggish battery-type reactions on the anode lead to a poor charge/discharge rate capability and insufficient power output of Na-ion capacitors. Thus, developing suitable anode materials for Na-ion capacitors is urgently desirable. This work demonstrates an electrochemically exfoliated graphite (EEG) anode with enhanced capacitive charge storage, greatly boosting the Na-ion reaction kinetics of co-intercalation. The EEG anode shows a high reversible capacity of 109 mAh g and maintains a good capacity retention of 90% after 1000 cycles. The assembled Na-ion capacitor using the EEG anode can finish the charge/discharge process in less than 10 s, which achieves an ultrahigh power density of 17,500 W kg with an energy density of 17 Wh kg. The high capacitive contributions at both the anode and cathode contribute to the fast rate capability and high power output of the fabricated Na-ion capacitors. This work will promote the development of ultrafast charging sodium-ion storage devices.
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http://dx.doi.org/10.1021/acsami.0c14611DOI Listing
November 2020

A defective g-CN/RGO/TiO composite from hydrogen treatment for enhanced visible-light photocatalytic H production.

Nanoscale 2020 Nov;12(43):22030-22035

School of Energy Science and Engineering, Nanjing Tech University, Nanjing, Jiangsu 211816, China.

Photocatalytic H2 evolution is a clean technology to alleviate energy and environmental issues. The limited light absorption and the separation efficiency of photogenerated charge carriers are the major hurdles constraining the application of numerous photocatalysts. Herein, we report a simple and effective strategy, a multistep heat-treatment method, to synthesise a defective g-C3N4/RGO/TiO2 composite to increase its rate of activity for H2 production. The defects, nitrogen and oxygen vacancies, are simultaneously introduced on the surface of the g-C3N4/RGO/TiO2 composite. The vacancy defects essentially endow g-C3N4/RGO/TiO2 with a boosted photocatalytic H2 evolution rate (4760 μmol h-1 g-1) under visible-light irradiation, which is higher than that of the most of g-C3N4/TiO2 composites. This is attributed to the improved visible-light absorption as well as the separation and transfer rate of photogenerated charge carriers arising from vacancy defects. This study may provide an avenue for preparing defective photocatalysts for efficient H2 evolution.
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http://dx.doi.org/10.1039/d0nr05141aDOI Listing
November 2020

Clinical characteristics and therapeutic outcomes of pulmonary arterial hypertension secondary to congenital portosystemic shunts.

Eur J Pediatr 2021 Mar 3;180(3):929-936. Epub 2020 Oct 3.

Department of Cardiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.

The aim of this retrospective study was to investigate the clinical characteristics and therapeutic outcomes of pulmonary arterial hypertension (PAH) secondary to congenital portosystemic shunts (CPSS). Thirty-three pediatric patients diagnosed in our institution with CPSS between 2012 and 2019 were enrolled in this study. The patients were divided into PAH and non-PAH groups. The PAH group included 15 patients who presented with unexplained PAH when CPSS was diagnosed. Two patients with microangiopathic hemolytic anemia died of right heart failure shortly after diagnosis. One patient received a liver transplant at the age of 4.3 years and showed a mild decrease in pulmonary artery pressure (PAP) 4 years after the operation. Seven patients underwent one-stage shunt closure at a median age of 2.8 years (1.4-13 years). Follow-up examinations, from 1.6 to 4.1 years after intervention, showed marked reduction of PAP in one patient and stabilization of PAH in six others. However, in one patient who underwent two-stage shunt closure, a marked increase in PAP was noted after partial ligation of the shunt. The remaining four patients received only pulmonary vasodilator therapy, and one of them died of right heart failure 12 years after the PAH diagnosis. The non-PAH group included 18 patients without evidence of PAH upon CPSS diagnosis. Shunt closure was carried out in eight of these patients, but one patient subsequently developed PAH after the resolution of hepatopulmonary syndrome.Conclusion: CPSS may be a more likely cause of unexplained PAH in pediatric patients than previously thought. Shunt closure or liver transplantation may prevent the progression of PAH, or even improve it for the majority of CPSS patients.
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http://dx.doi.org/10.1007/s00431-020-03817-yDOI Listing
March 2021
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