Publications by authors named "Xiaohui Wang"

1,084 Publications

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Clinical analysis of gene mutations in pediatric patients with epilepsy.

Pediatr Investig 2022 Jun 26;6(2):93-99. Epub 2022 Apr 26.

Department of Neurology Beijing Children's Hospital, Capital Medical University, National Center for Children's Health Beijing China.

Importance: CHD2 is a member of the chromodomain helicase DNA-binding (CHD) family of proteins, which have important roles in the regulation of gene expression. Dysregulation of this protein may lead to various disorders.

Objective: To delineate the genotypes and phenotypes of CHD2-related epilepsy.

Methods: We analyzed the medical history, magnetic resonance imaging findings, and video-electroencephalogram recordings of 17 patients with mutations in the Neurology Department of Beijing Children's Hospital from June 2016 to June 2021.

Results: Age at seizure onset ranged from 6 months to 10 years; the median age at onset was 4 years. Generalized tonic-clonic, myoclonic, eyelid myoclonic, atonic, atypical absence, myoclonic-atonic, and spasm seizures were observed. Ten of the 17 patients had multiple types of seizures. One patient exhibited photosensitivity epilepsy and one patient exhibited grid image-induced visual reflex epilepsy. Developmental disability was present in 14 patients, while autism features were present in five patients. Sixteen patients had mutations of ; one patient had an inherited variant. Eleven mutations were novel. One patient had two mutations; that patient exhibited development delay and refractory epilepsy. Seizures were controlled in eight patients, improved in seven patients, and resistant to treatment in two patients.

Interpretation: Phenotype severity in patients with variants ranged from drug-responsive seizures to severe epileptic encephalopathy. Most patients exhibited developmental disorders.
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http://dx.doi.org/10.1002/ped4.12321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218986PMC
June 2022

More is simpler: Decomposition of ligand-binding affinity for proteins being disordered.

Protein Sci 2022 Jul;31(7):e4375

College of Chemistry and Molecular Engineering, and Beijing National Laboratory for Molecular Sciences (BNLMS), Peking University, Beijing, China.

In statistical mechanics, it is well known that the huge number of degrees of freedom does not complicate the problem as it seems, but actually greatly simplifies the analysis (e.g., to give a Boltzmann distribution). Here, we reveal that the ensemble averaging from the vast conformations of intrinsically disordered proteins (IDPs) greatly simplifies the nature of binding affinity, which can be reliably decomposed into a sum of the ligandability of IDP and the capacity of ligand. Such an unexpected regularity is applied to facilitate the virtual screening upon IDPs. It also provides essential insight in understanding the specificity difference between IDPs and conventional ordered proteins since the specificity is caused by deviation from the baseline behavior of protein-ligand binding.
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http://dx.doi.org/10.1002/pro.4375DOI Listing
July 2022

ACT001 Inhibits TLR4 Signaling by Targeting Co-Receptor MD2 and Attenuates Neuropathic Pain.

Front Immunol 2022 9;13:873054. Epub 2022 Jun 9.

Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China.

Neuropathic pain is a common and challenging neurological disease, which renders an unmet need for safe and effective new therapies. Toll-like receptor 4 (TLR4) expressed on immune cells in the central nervous system arises as a novel target for treating neuropathic pain. In this study, ACT001, an orphan drug currently in clinical trials for the treatment of glioblastoma, was identified as a TLR4 antagonist. quenching titrations of intrinsic protein fluorescence and saturation transfer difference (STD)-NMR showed the direct binding of ACT001 to TLR4 co-receptor MD2. Cellular thermal shift assay (CETSA) showed that ACT001 binding affected the MD2 stability, which implies that MD2 is the endogenous target of ACT001. simulations showed that ACT001 binding decreased the percentage of hydrophobic area in the buried solvent-accessible surface areas (SASA) of MD2 and rendered most regions of MD2 to be more flexible, which is consistent with experimental data that ACT001 binding decreased MD2 stability. In keeping with targeting MD2, ACT001 was found to restrain the formation of TLR4/MD2/MyD88 complex and the activation of TLR4 signaling axes of NF-κB and MAPKs, therefore blocking LPS-induced TLR4 signaling downstream pro-inflammatory factors NO, IL-6, TNF-α, and IL-1β. Furthermore, systemic administration of ACT001 attenuated allodynia induced by peripheral nerve injury and activation of microglia and astrocyte . Given the well-established role of neuroinflammation in neuropathic pain, these data imply that ACT001 could be a potential drug candidate for the treatment of chronic neuropathic pain.
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http://dx.doi.org/10.3389/fimmu.2022.873054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218074PMC
June 2022

A point-of-care microfluidic channel-based device for rapid and direct detection of fibrinogen in whole blood.

Lab Chip 2022 Jun 24. Epub 2022 Jun 24.

Institute of Health Service and Transfusion Medicine, Beijing 100850, P. R. China.

Hemorrhage is the leading cause of preventable death in civilian and battlefield traumatic injuries. Patients with severe traumatic hemorrhagic shock are more likely to be deficient in fibrinogen than those with other coagulation factors, and hypofibrinogenemia is an independent risk factor for mortality. Thus, rapid detection of fibrinogen levels is of great importance in these patients during damage control resuscitation. Plasma is used as an analyte in fibrinogen detection, which restricts the use of existing devices in emergencies. To meet the needs of on-site detection, we developed a point-of-care microfluidic channel-based device for direct measurement of fibrinogen concentration in whole blood. In our method, thrombin is dispersed on a reaction strip to initiate conversion of fibrinogen to fibrin. The permeability of the resulting blood clots depends on the fibrinogen level. A hydrophobic plastic protection flake between the reaction strip and a wicking strip is then removed to allow flow of unclotted blood. The rate of blood flow along the wicking strip was inversely related to the fibrinogen concentration. The whole process could be completed in as fast as 5 minutes for a whole blood sample size of 150 μL, and yielded accurate results ranging from 0 to 4 g L, which were unaffected by Ca, blood lipids, hematocrit, warfarin and tissue plasminogen activators (tPAs). Results using clinical whole blood samples were also highly consistent with those using an automatic coagulation analyzer, yielding a Pearson correlation coefficient of up to 0.919. This approach has potential for allowing rapid diagnosis of fibrinogen concentration in critically ill bleeding patients in different settings, thus helping to judge the suitability of fibrinogen replacement therapy (FRT) in cases of emergency bleeding and in patients at risk of thrombosis due to hyperfibrinogenemia.
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http://dx.doi.org/10.1039/d2lc00437bDOI Listing
June 2022

IgG Antibody Responses and Immune Persistence of Two Doses of BBIBP-CorV Vaccine or CoronaVac Vaccine in People Living with HIV (PLWH) in Shenzhen, China.

Vaccines (Basel) 2022 May 31;10(6). Epub 2022 May 31.

School of Public Health, University of South China, Hengyang 421001, China.

The purpose of this study was to preliminarily evaluate the immunogenicity and immune persistence of inactivated SARS-CoV-2 vaccines in PLWH in the real world. We collected blood samples from 132 PLWH aged 18-59 years who were vaccinated with two doses of BBIBP-CorV vaccine (Sinopharm) or CoronaVac vaccine (SinoVac) at 28 ± 7 days and 180 ± 20 days the after second dose, to detect the level of Spike receptor binding domain-protein specific IgG (S-RBD-IgG) by using chemiluminescence. We found that the BBIBP-CorV vaccine or the CoronaVac vaccine induced lower S-RBD-IgG antibody seropositivity rates and levels in PLWH than in healthy controls (HCs). The BBIBP-CorV vaccine or the CoronaVac vaccine induced lower humoral immune responses in PLWH, having lower CD4T cell counts (<350 cells/μL) compared to PLWH, and having higher CD4T cell counts (≥350 cells/μL) after a second dose of vaccination. The BBIBP-CorV vaccine or the CoronaVac vaccine induced lower S-RBD-IgG antibody levels in PLWH, having CD4T cell counts ≥350 cells/μL compared to HCs. No negative effects were observed in terms of the CD4T cell counts and HIV RNA viral load (VL) of PLWH after vaccination. Ninety-nine PLWH and eighty-three HCs completed a second blood collection for testing; we found a statistically significant decrease in the humoral immune response both in PLWH and HCs from 28 days to 180 days after a second dose of BBIBP-CorV vaccine or CoronaVac vaccine. The S-RBD-IgG antibody induced by the BBIBP-CorV vaccine or the CoronaVac vaccine declined faster in the PLWH population than in the healthy population, and two doses of the BBIBP-CorV vaccine or the CoronaVac vaccine may not be enough to provide PLWH with persistent immunity against SARS-CoV-2. It is necessary for PLWH to be prioritized for a third dose over the healthy population, but the immunogenicity of the third dose of the homologous or heterologous vaccine requires further study.
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http://dx.doi.org/10.3390/vaccines10060880DOI Listing
May 2022

Elevated CO Altered Rice VOCs Aggravate Population Occurrence of Brown Planthoppers by Improving Host Selection Ability.

Biology (Basel) 2022 Jun 8;11(6). Epub 2022 Jun 8.

Department of Entomology, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, China.

It is predicted that plant volatile organic compounds (VOCs) are affected by the atmospheric CO levels rising globally, which further affects the interaction between plants and herbivorous insects, especially the host selection behavior of herbivorous insects. In this study, the effects of elevated CO on the host-selection behavior of the brown planthopper (BPH) , and the emission of VOCs from the healthy and BPH-damaged rice plants were studied simultaneously to make clear the population occurrence of BPH under global climate change. Compared with ambient CO, elevated CO significantly increased the host selection percent of BPH for the healthy (CK) and BPH-damaged rice plants, and the host selection percent of BPH for the BPH-damaged rice plants was significantly higher than that for the healthy rice plants under elevated CO, which might be regulated by the transcription levels of , and in BPH due to the upregulated transcriptional levels of these three genes of BPH under elevated CO. In addition, we analyzed and quantified the emission of VOCs in rice plants grown under ambient CO and elevated CO by GS-MS. A total of 36 VOCs from rice plants were identified into eight categories, including alkanes, alkenes, alcohols, aldehydes, ketones, esters, phenols and aromatic hydrocarbons. Elevated CO significantly decreased the contents of heptadecane, linalool and limonene from rice plants compared with ambient CO. Besides, the contents of linalool, phytol, decanal, 1-methyldecalin and 2,6-diphenylphenol from BPH-damaged rice plants under ambient CO, and undecane, hexadecane, nonanal and 2,6-diphenylphenol from BPH-damaged rice plants under elevated CO were all significantly higher than those from healthy rice plants. The percentage composition of phenols was positively correlated with the host selection rate of BPH. Our study indicates that elevated CO is beneficial to promote the host selection ability of BPH for rice plants damaged by BPHs due to the changed plant VOCs.
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http://dx.doi.org/10.3390/biology11060882DOI Listing
June 2022

Clinical, radiologic, and physiologic features of idiopathic pulmonary fibrosis (IPF) with and without emphysema.

Expert Rev Respir Med 2022 Jun 29:1-9. Epub 2022 Jun 29.

Department of Pulmonary and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, P.R.China.

Background: Idiopathic pulmonary fibrosis (IPF) can combine with emphysema, a condition termed as IPF with emphysema (IPFE). We compared the clinical, radiologic, and physiologic features of IPF and IPFE.

Research Design And Methods: Newly diagnosed IPF    and IPFE    patients were recruited between January 2018 and September 2020. Symptoms, high resolution computed tomography (HRCT), pulmonary function test (PFT) data, composite physiologic index (CPI), gender-age-physiology (GAP) scores, and follow-up data were obtained.

Results: The IPFE group had greater proportion of male smokers, and of lung cancer cases. The IPFE group had higher VC, FVC FEV, and lower FEV/FVC and DL and lower percent fibrosis on HRCT. Both groups had similar symptoms and mortality. Mortality rate was associated with inability to perform PFT, CPI, GAP scores, percent fibrosis, VC, FVC, FEV and DL, serum SCC-Ag and CA125, and anti-fibrotic therapy (≥12 months) in IPF, while it was associated with inability to perform PFT, CPI, percent fibrosis, DL, serum CEA, CYFRA21-1 and CA125, and anti-fibrotic therapy (≥12 months) in IPFE.

Conclusion: IPF and IPFE patients are different in smoking history, physiologic indices, HRCT patterns and prognostic factors, however, they have similar mortality. Anti-fibrotic therapy could improve the survival rate in both IPF and IPFE.
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http://dx.doi.org/10.1080/17476348.2022.2093717DOI Listing
June 2022

Intermolecular Hydrogen-Bond-Assisted Solid-State Dual-Emission Molecules with Mechanical Force-Induced Enhanced Emission.

J Org Chem 2022 Jul 21;87(13):8503-8514. Epub 2022 Jun 21.

Shenzhen Institute of Aggregate Science and Technology, School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen 518172, China.

Hydrogen bonds not only play a crucial role in the life sciences but also endow molecules with fantastic physical and chemical properties, which help in the realization of their high-tech applications. This work presents an efficient strategy for achieving highly efficient solid-state dual-emission blue emitters with mechanical force-induced enhanced emission properties via intermolecular hydrogen bonds via novel pyrene-based intermediates, namely, 1,3,6,8-tetrabromo-2,7-dihydroxypyrene () and 1,3,6,8-tetrabromo-2-hydroxypyrene (), prepared via hydroxylation and bromination of pyrene in high yields. Moreover, further use of a classical Pd-catalyzed coupling reaction affords new pyrene-based luminescent materials , which display high thermal stability (in range of 336-447 °C), blue emission (<463 nm), and high quantum yields in solution. Interestingly, with the monosubstituted hydroxyl (OH) or methoxy (OMe) group located at position 2 of pyrene, compounds and display exciting dual emission with mechanical force-induced enhanced emission properties, due to the presence of several hydrogen-bond interactions. Moreover, this series of compounds exhibits numerous advantages, for example, deeper blue emission with a narrower full width at half-maximum, a stronger steric effect, and higher hydrophilicity. Thus, these novel bromopyrene intermediates and related pyrene-based luminescent materials will pave the way for further exploration of novel organic solid-state luminescent materials for potential application in organic electronics, bioimaging, chemosensors, etc.
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http://dx.doi.org/10.1021/acs.joc.2c00617DOI Listing
July 2022

Recombinant EGFL7 Mitigated Pressure Overload-Induced Cardiac Remodeling by Blocking PI3K /AKT/ Signaling in Macrophages.

Front Pharmacol 2022 26;13:858118. Epub 2022 May 26.

Department of Geriatrics, 960 Hospital of PLA(The General Hospital of Jinan Command), Jinan, China.

Inflammation and endothelial dysfunction play an essential role in heart failure (HF). Epidermal growth factor-like protein 7 (EGFL7) is upregulated during pathological hypoxia and exerts a protective role. However, it is unclear whether there is a link between abnormal EGFL7 expression and inflammation in overload stress-induced heart failure. Our results showed that EGFL7 transiently increased during the early 4 weeks of TAC and in hypertensive patients without heart failure. However, it decreased to the basal line in the heart tissue 8 weeks post-transverse aortic constriction (TAC) or hypertensive patients with heart failure. Knockdown of EGFL7 with siRNA accelerated cardiac dysfunction, fibrosis, and macrophage infiltration 4 weeks after TAC. Deletion of macrophages in siRNA-EGFL7-TAC mice rescued that pathological phenotype. research revealed the mechanism. PI3K /AKT/N signaling in macrophages was activated by the supernatant from endothelial cells stimulated by siRNA-EGFL7+phenylephrine. More macrophages adhered to endothelial cells, but pretreatment of macrophages with PI3Kγ inhibitors decreased the adhesion of macrophages to endothelial cells. Ultimately, treatment with recombinant rmEGFL7 rescued cardiac dysfunction and macrophage infiltration in siRNA-EGFL7-TAC mice. In conclusion, EGFL7 is a potential inhibitor of macrophage adhesion to mouse aortic endothelial cells. The downregulation of EGFL7 combined with increased macrophage infiltration further promoted cardiac dysfunction under pressure overload stress. Mechanistically, EGFL7 reduced endothelial cell adhesion molecule expression and inhibited the PI3K /AKT/NF B signaling pathway in macrophages.
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http://dx.doi.org/10.3389/fphar.2022.858118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200063PMC
May 2022

Adipocyte-derived kynurenine promotes obesity and insulin resistance by activating the AhR/STAT3/IL-6 signaling.

Nat Commun 2022 Jun 17;13(1):3489. Epub 2022 Jun 17.

Department of Respiratory and Critical Care Medicine, the Center for Biomedical Research, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Aberrant amino acid metabolism is a common event in obesity. Particularly, subjects with obesity are characterized by the excessive plasma kynurenine (Kyn). However, the primary source of Kyn and its impact on metabolic syndrome are yet to be fully addressed. Herein, we show that the overexpressed indoleamine 2,3-dioxygenase 1 (IDO1) in adipocytes predominantly contributes to the excessive Kyn, indicating a central role of adipocytes in Kyn metabolism. Depletion of Ido1 in adipocytes abrogates Kyn accumulation, protecting mice against obesity. Mechanistically, Kyn impairs lipid homeostasis in adipocytes via activating the aryl hydrocarbon receptor (AhR)/Signal transducer and activator of transcription 3 /interleukin-6 signaling. Genetic ablation of AhR in adipocytes abolishes the effect of Kyn. Moreover, supplementation of vitamin B6 ameliorated Kyn accumulation, protecting mice from obesity. Collectively, our data support that adipocytes are the primary source of increased circulating Kyn, while elimination of accumulated Kyn could be a viable strategy against obesity.
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http://dx.doi.org/10.1038/s41467-022-31126-5DOI Listing
June 2022

Value of Quantitative SPECT/CT Lymphoscintigraphy in Improving Sentinel Lymph Node Biopsy in Breast Cancer.

Breast J 2022 28;2022:6483318. Epub 2022 Mar 28.

Department of Nuclear Medicine, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong, China.

Methods: We retrospectively enrolled breast cancer patients who underwent SPECT/CT prior to sentinel lymph node biopsy. Quantification of radiotracer uptake from SPECT/CT data was performed. A radioactivity count threshold ( ) using SPECT/CT was calculated for detecting metastatic sentinel lymph nodes. To localize sentinel lymph nodes exactly, we compared the positions of sentinel lymph nodes localized using SPECT/CT with positions localized surgically using an intraoperative -probe.

Results: 491 patients were included, with a median of 3 sentinel lymph nodes/patient detected by the -probe and 2 sentinel lymph nodes/patient detected by SPECT/CT. As the number of sentinel lymph nodes visualized on SPECT/CT images, the metastasis incidence of lymph nodes in the ≤2 SLNs group was significantly higher than that in the >2 SLNs group (35% vs. 15%, < 0.001). No metastasis was found in lymph nodes with  ≤ 30% in the >2 SLNs group, and thus, 30% (157/526) of SPECT/CT-identified nodes would avoid unnecessary removal. The positions of sentinel lymph nodes localized by SPECT/CT and -probe were identical in 42% (39/93) of patients.

Conclusions: Quantitative Tc-99 m SC SPECT/CT imaging has the potential to preoperatively locate sentinel lymph nodes and intraoperatively avoid unnecessary sentinel lymph node biopsy.
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http://dx.doi.org/10.1155/2022/6483318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9187279PMC
June 2022

Thermo-processable chitosan-based plastic substitute with self-adaptiveness and closed-loop recyclability.

Carbohydr Polym 2022 Sep 26;291:119479. Epub 2022 Apr 26.

State Key Laboratory of Pulp and Paper Engineering, South China University of Technology, Guangzhou 510640, China. Electronic address:

The increasing environmental burden generated by disposable plastic wastes makes the development of sustainable substitute materials an emergent task. As one of the most abundant bioresources, chitosan (CS) has been considered as a potential candidate for plastic substitution. Conventionally, CS-based materials are fabricated through a solution-processing procedure due to the high crystallinity of CS. Herein, we designed a CS-based material via integrating CS into the network of polyimine (PI), which shows thermomechanical processability similar to plastics. Strong interactions were achieved through dynamic imine bond and hydrogen bond and thus formed a thermo-processable dynamic composite network. These CS-based plastic substitutes exhibit exceptional mechanical performances, excellent thermal/chemical stability, and a series of self-adaptiveness, including re-healing, reprocessing and multi-layer laminating. Notably, CPs can be easily degraded and 100% recycled for the production of next-generation materials. This work provides an alternative route to produce green and sustainable biomass materials as a plastic substitute.
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http://dx.doi.org/10.1016/j.carbpol.2022.119479DOI Listing
September 2022

Endovascular Treatments for Coarctation of the Aorta with Concurrent Poststenotic Aneurysms in Adults.

Ann Vasc Surg 2022 Jun 7. Epub 2022 Jun 7.

Department of Vascular Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address:

Background: Coarctation of the aorta with poststenotic aneurysms is rare and complex. Here we report a relatively large group of endovascular treatments for the disease.

Materials And Methods: Fifteen patients from two centers between 2006 and 2019 were included in the study. The patients were retrospectively divided into two groups. Patients in the complex group had insufficient proximal landing zone (<2 cm) or the zigzag shape of aorta. Their demographics, clinical manifestations, endovascular procedures, and follow-up results were analyzed.

Results: There were 7 patients in the simple group and 8 patients in the complex group. Eleven patients were symptomatic. Despite the unfavorable anatomy in the complex group, technical success reached 100%. The diameter of coarctation increased from 8.6 mm to 16.7 mm with poststenotic aneurysms successfully excluded at the same time. In patients without sufficient proximal landing zone, left subclavian artery was covered by the stent grafts and then sacrificed (three patients) or revascularized (four patients). Other than one patient who suffered iliac artery rupture and received open repair, there was no other perioperative complications. Computed tomography angiography repeated at mean 42 months postoperation confirmed patency of stents and the exclusion of aneurysms with no aortic wall injury. Mild endoleaks occurred in two patients in the complex group and were left to observation. During 55.0 months follow-up, except for one patient who received secondary left subclavian artery fenestration, all other patients remained asymptomatic.

Conclusions: Endovascular treatments for coarctation of the aorta with poststenotic aneurysm showed a high technical success and could be an alternative solution for such disease.
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http://dx.doi.org/10.1016/j.avsg.2022.05.023DOI Listing
June 2022

The Immunological Roles of Olfactory Ensheathing Cells in the Treatment of Spinal Cord Injury.

Front Immunol 2022 20;13:881162. Epub 2022 May 20.

Translational Medicine Center, Hong Hui Hospital, Xi'an Jiaotong University, Xi'an, China.

Spinal cord injury (SCI) is a devastating type of neurological disorder of the central nervous system (CNS) with high mortality and disability. The pathological processes of SCI can usually be described as two stages, namely, primary and acute secondary injuries. Secondary injury produces more significant exacerbations of the initial injury. Among all the mechanisms of secondary damage, infection and inflammatory responses, as the principle culprits in initiating the second phase of SCI, can greatly contribute to the severity of SCI and numerous sequelae after SCI. Therefore, effectively antagonizing pro-inflammatory responses may be a promising treatment strategy to facilitate functional recovery after SCI. Olfactory ensheathing cells (OECs), a unique type of glial cells, have increasingly become potential candidates for cell-based therapy in the injured CNS. Strikingly, there is growing evidence that the mechanisms underlying the anti-inflammatory role of OECs are associated with the immune properties and secretory functions of these cells responsible for anti-neuroinflammation and immunoregulatory effects, leading to maintenance of the internal microenvironment. Accordingly, a more profound understanding of the mechanism of OEC immunological functions in the treatment of SCI would be beneficial to improve the therapeutic clinical applications of OECs for SCI. In this review, we mainly summarize recent research on the cellular and molecular immune attributes of OECs. The unique biological functions of these cells in promoting neural regeneration are discussed in relation of the development of novel therapies for CNS injury.
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http://dx.doi.org/10.3389/fimmu.2022.881162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9163387PMC
June 2022

Corrigendum: Celastrol Downmodulates Alpha-Synuclein-Specific T Cell Responses by Mediating Antigen Trafficking in Dendritic Cells.

Front Immunol 2022 20;13:907993. Epub 2022 May 20.

Department of Biology, Faculty of Science, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China.

[This corrects the article DOI: 10.3389/fimmu.2022.833515.].
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http://dx.doi.org/10.3389/fimmu.2022.907993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164218PMC
May 2022

Novel Loss-of-Function Variants in Cause Childhood-Onset Epileptic Encephalopathy in Chinese Patients.

Genes (Basel) 2022 May 19;13(5). Epub 2022 May 19.

Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Centre for Children's Health, Beijing 100045, China.

Developmental and epileptic encephalopathy-94 (DEE94) is a severe form of epilepsy characterized by a broad spectrum of neurodevelopmental disorders. It is caused by pathogenic variants. While only a few pathogenic variants have been reported with detailed clinical phenotypes, most of which lack molecular analysis. In this study, next-generation sequencing (NGS) was performed to identify likely pathogenic variants in patients with epilepsy. Three likely pathogenic variants were finally identified in different patients. The seizure onset ages were from two years to six years. Patients 1 and 2 had developmental delays before epilepsy, while patient 3 had intellectual regression after the first seizure onset. The observed seizures were myoclonic, febrile, and generalized tonic-clonic, which had been controlled by different combinations of antiepileptic drugs. Two (c.1809_1809+1delGGinsTT, p.? and c.3455+2_3455+3insTG, p.?) and one maternal (c.3783G>A, p.W1261*) variant were identified, which were all predicted to be pathogenic/likely pathogenic. Molecular analysis was performed in patient 1, and we detected aberrantly spliced products, proving the pathogenicity of this variant. New cases with novel variants, along with a detailed clinical and molecular analysis, are important for a better understanding of -related epileptic encephalopathy.
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http://dx.doi.org/10.3390/genes13050908DOI Listing
May 2022

Effect of early mobilization combined with early nutrition on acquired weakness in critically ill patients (EMAS): A dual-center, randomized controlled trial.

PLoS One 2022 26;17(5):e0268599. Epub 2022 May 26.

Department of Intensive Care Unit, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

Aim: The study aimed to investigate the effect of early mobilization combined with early nutrition (EMN) on intensive care unit-acquired weakness (ICU-AW) in intensive care unit (ICU) settings compared with early mobilization (EM) or routine care.

Methods: A prospective, dual-center, randomized controlled trial was conducted. The control group underwent standard care without a pre-established routine for mobilization and nutrition. The EM group underwent early, individualized, progressive mobilization within 24 h of ICU admission. The EMN group underwent early mobilization, similar to the EM group plus guideline-based early nutrition (within 48 h of ICU admission). The primary outcome was the occurrence of ICU-AW at discharge from the ICU. Secondary outcomes included muscle strength, functional independence, organ failure, nutritional status, duration of mechanical ventilation (MV), length of ICU stay, and ICU mortality at ICU discharge.

Results: A total of 150 patients were enrolled and equally distributed into the three groups. Patients undergoing routine care only were more susceptible to ICU-AW upon ICU discharge than those in the EM or EMN groups (16% vs. 2%; p = 0.014 for both), and had a lower Barthel Index than others (control vs. EM/EMN: 57.5 vs 70.0; p = 0.022). The EMN group had improved muscle strength (p = 0.028) and better nutritional status than the control group (p = 0.031). Both interventions were associated with a lower ICU-AW (EM vs. control: p = 0.027, OR [95% CI] = 0.066 [0.006-0.739]; EMN vs. control: p = 0.016, OR [95% CI] = 0.065 [0.007-0.607]).

Conclusion: EM and EMN had positive effects. There was little difference between the effects of EM and EMN, except for muscle strength improvement. Both EM and EMN may lead to a lower occurrence of ICU-AW and better functional independence than standard care. EMN might benefit nutritional status more than usual care and promote improvement in muscle strength.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0268599PLOS
May 2022

NCAPG Promotes the Proliferation of Renal Clear Cell Carcinoma via Mediating with CDK1.

Dis Markers 2022 13;2022:6758595. Epub 2022 May 13.

Department of Urologic Surgery, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003 Henan, China.

Objective: Currently, lots of scholars have proved that the expression of NCAPG is associated with the prognosis of several cancers, while the relationship between NCAPG and renal clear cell carcinoma remains unclear, so the main aim of this research is to explore the effects of NCAPG on the progression of renal clear cell carcinoma.

Methods: We observed the differential expression of NCAPG in several cancers from GEPIA online database, and the expression of NCAPG in renal clear cell carcinoma and normal tissue was compared and further verified by IHC assay. CCK-8 assay and clone formation experiment were conducted to observe the change of NCAPG on the proliferation. GraphPad was used for data analysis, and -test and analysis were used to analyze the correlation between NCAPG/CDK1 and renal clear cell carcinoma.

Results: NCAPG was upregulated in renal clear cell carcinoma compared with the normal tissue, and the expression of NCAPG was associated with the clinical prognosis of pancreatic cancer especially with tumor size ( = 0.010). Knockdown NCAPG could restrain the proliferation of renal clear cell carcinoma. CDK1 was found to be tightly related with NCAPG, and the expression of CDK1 was also associated with the prognosis.

Conclusions: NCAPG was upregulated in renal clear cell carcinoma, which was related with tumor size and overall survival. NCAPG might promote the proliferation of renal clear cell carcinoma via mediating CDK1. NCAPG/CDK1 complex might provide a new treatment strategy for lots of patients with renal clear cell carcinoma.
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http://dx.doi.org/10.1155/2022/6758595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9122706PMC
May 2022

A Facile Fabrication of CdSe/ZnS QDs-Block Copolymer Brushes-Modified Graphene Oxide Nanohybrid with Temperature-Responsive Behavior.

Materials (Basel) 2022 May 7;15(9). Epub 2022 May 7.

College of Chemistry and Materials Science, Inner Mongolia Minzu University, Tongliao 028000, China.

In this paper, we described a straightforward one-step chemical method for the synthesis of semiconductor quantum dots(QDs)-block copolymer brushes functionalized graphene oxide(GO) fluorescence nanohybrids. The azobenzene-terminated block copolymer poly(N-isopropylacrylamid)-b-poly(styrene-co-5-(2-methacryoylethyloxymethyl)-8-quinolinol)(PNIPAM--P(St--MQ)) was modified on the surface of GO sheets via host-guest interactions between β-cyclodextrin-modified GO and azobenzene moieties, and simultaneously CdSe/ZnS QDs were integrated on the block copolymer brushes through the coordination between 8-hydroxyquinoline units in the polymer brushes and CdSe/ZnS QDs. The resulting fluorescence nanohybrid exhibited dual photoluminescence at 620 nm and 526 nm, respectively, upon excitation at 380 nm and LCST-type thermo-responsive behavior which originated from the change in the PNIPAM conformation in the block copolymer brushes of GO sheets.
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http://dx.doi.org/10.3390/ma15093356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100873PMC
May 2022

HG-15, a Halotolerant Rhizoplane Bacterium, Promotes Growth and Salinity Tolerance in Wheat ().

Biomed Res Int 2022 7;2022:9506227. Epub 2022 May 7.

College of Forestry, Shandong Agriculture University, Taian, China.

Certain plant growth-promoting bacteria (PGPB) reduce salt stress damage in plants. HG-15 is a halotolerant bacterium (able to withstand NaCl concentrations as high as 30%) isolated from the wheat rhizoplane in the Yellow River delta. A qualitative and quantitative investigation of the plant growth-promoting characteristics of this strain confirmed nitrogen fixation, potassium dissolution, ammonia, plant hormone, ACC deaminase, and proline production abilities. HG-15 colonization of wheat roots, stems, and leaves was examined via scanning electron microscopy, rep-PCR, and double antibiotic screening. After inoculation with the HG-15 strain, the pH (1.08-2.69%), electrical conductivity (3.17-11.48%), and Na (12.98-15.55%) concentrations of rhizosphere soil significantly decreased ( < 0.05). Under no-salt stress (0.15% NaCl), low-salt stress (0.25% NaCl), and high-salt stress (0.35% NaCl) conditions, this strain also significantly increased ( < 0.05) the dry weight (17.76%, 24.46%, and 9.31%), fresh weight (12.80%, 20.48%, and 7.43%), plant height (7.79%, 5.86%, and 13.13%), and root length (10.28%, 17.87%, and 48.95%). Our results indicated that HG-15 can effectively improve the growth of wheat and elicit induced systemic tolerance in these plants, thus showing its potential as a microbial inoculant that can protect wheat under salt stress conditions.
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http://dx.doi.org/10.1155/2022/9506227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9107367PMC
May 2022

Phenotypic and Genotypic Characteristics of Associated Seizure Diseases.

Front Mol Neurosci 2022 28;15:821012. Epub 2022 Apr 28.

Department of Neurology, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China.

Although variants result in a wide range of phenotypes, genotype-phenotype associations are not well established. We aimed to explore the phenotypic characteristics of associated seizure diseases and establish genotype-phenotype correlations. We retrospectively analyzed clinical data and results of genetic testing in 41 patients carrying variants. Patients were divided into two groups based on their clinical manifestations: the Dravet Syndrome (DS) and non-DS groups. In the DS group, the age of seizure onset was significantly earlier and ranged from 3 to 11 months, with a median age of 6 months, than in the non-DS group, where it ranged from 7 months to 2 years, with a median age of 10 and a half months. In DS group, onset of seizures in 11 patients was febrile, in seven was afebrile, in two was febrile/afebrile and one patient developed fever post seizure. In the non-DS group, onset in all patients was febrile. While in the DS group, three patients had unilateral clonic seizures at onset, and the rest had generalized or secondary generalized seizures at onset, while in the non-DS group, all patients had generalized or secondary generalized seizures without unilateral clonic seizures. The duration of seizure in the DS group was significantly longer and ranged from 2 to 70 min (median, 20 min), than in the non-DS group where it ranged from 1 to 30 min (median, 5 min). Thirty-one patients harbored variants, and nine patients had inherited variants. Localization of missense variants in the voltage sensor region (S4) or pore-forming region (S5-S6) was seen in seven of the 11 patients in the DS group and seven of the 17 patients in the non-DS group. The phenotypes of -related seizure disease were diverse and spread over a continuous spectrum from mild to severe. The phenotypes demonstrate commonalities and individualistic differences and are not solely determined by variant location or type, but also due to functional changes, genetic modifiers as well as other known and unknown factors.
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http://dx.doi.org/10.3389/fnmol.2022.821012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096348PMC
April 2022

Comparison of arithmetic mean and energy-weighted mean flood histogram generation methods for dual-ended readout positron emission tomography detectors.

Med Phys 2022 May 14. Epub 2022 May 14.

Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People's Republic of China.

Purpose: Dual-ended readout pixelated scintillator array detectors can provide a suitable crystal resolvability and satisfactory depth of interaction (DOI), energy, and timing resolutions. Usually, the flood histogram measured by one-sided readout is depth dependent, and the flood histogram quality degrades as the distance between the interaction site and photodetector increases. Information measured by two photodetectors must be combined to obtain an improved flood histogram yielding a better PET scanner spatial resolution.

Methods: Two flood histogram generation algorithms for dual-ended readout of pixelated scintillator array detectors were compared by theoretical calculations and experimental measurements. The first algorithm is the arithmetic mean (AM) algorithm, which assigns the same weight to the flood histograms measured by photodetectors 1 and 2. The second algorithm is the energy-weighted mean (EWM) algorithm, which assigns each flood histogram a certain weight proportional to the energy measured by the photodetector. Theoretical equations were derived to determine the quality of the flood histograms obtained with these two algorithms. Experimental measurements were performed with an 18 × 18 lutetium-yttrium oxyorthosilicate (LYSO) array with a crystal size of 0.62 × 0.62 × 20 mm read out by two multi-anode photomultiplier tubes at both ends. Flood histograms of the whole array and five specific depths were compared between the above two algorithms.

Results: The theoretical results indicated that the flood histograms obtained with the EWM method matched those obtained with the AM method at the middle detector depth and were better at other detector depths when the distance (S) between the locations of the same crystal in the flood histograms measured by photodetectors 1 and 2 reached 0. The advantage of the EWM method decreased with increasing S value since the crystal position in the flood histogram obtained with the EWM method varies with the depth when S does not equal 0. The advantage of the EWM method decreased with increasing S value. The experimental results generally agreed with the theoretical predictions. Compared to the AM method, the EWM method provided a similar flood histogram at a depth of 10 mm but generated a better flood histogram at depths of 2 and 18 mm. Although an inverse correlation between Q (a quality factor representing the advantage of the EWM method) and S was observed, the variation in Q given the same S value was high. The average Q value at the same S still agreed with the theoretical predictions.

Conclusions: Theoretical equations were derived, and experimental measurements were performed to compare two flood histogram generation algorithms for dual-ended readout PET detectors. The results indicated that the EWM method based on inverse variance weighting theory could provide better flood histograms than those provided by the AM method.
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http://dx.doi.org/10.1002/mp.15710DOI Listing
May 2022

Integrating circuit theory and landscape pattern index to identify and optimize ecological networks: a case study of the Sichuan Basin, China.

Environ Sci Pollut Res Int 2022 May 5. Epub 2022 May 5.

College of Geography and Resources, Sichuan Normal University, Chengdu, 610101, China.

The notion of ecological networks (EN) and their identification can support approaches to nature conservation strategies aiming at biodiversity, landscape connectivity, and people's well-being. Integrating ecosystem services (ESs), morphological spatial pattern analysis (MSPA), circuit theory, and landscape pattern index analysis, we proposed a new framework for mapping EN that was expected to promote economic development and ecological protection. Specifically, source areas were extracted through a combination of ESs and MSPA that integrated functional and morphological spatial attributes. Resistance surfaces were determined based on habitat quality. A network linking ecological source areas was then identified using circuit theory, and landscape pattern index analysis was used to identify ecological strategy nodes in view of the heterogeneity within ecological corridors. The results showed that the Sichuan Basin involved 553 ecological sources, 641 ecological corridors, and 33 ecological nodes that altogether included 20 ecological strategy nodes. Constructing regional EN can promote the transformation of multiple, chaotic, and scattered ecological elements to systematic and networked ecological elements and ultimately promote harmonious coexistence between humans and nature. This study provided a methodology for the extraction of ecological source areas and strategy nodes and can provide a significant reference for the management and optimization of EN.
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http://dx.doi.org/10.1007/s11356-022-20383-yDOI Listing
May 2022

Effects of Repetitive Transcranial Magnetic Stimulation on Cognitive Function in Patients With Stress-Related Depression: A Randomized Double-Blind fMRI and H-MRS Study.

Front Neurol 2022 15;13:844606. Epub 2022 Apr 15.

Laboratory of Stress Medicine, Beijing Institute of Basic Medical Sciences, Beijing, China.

Objectives: To reveal the effects of repetitive transcranial magnetic stimulation (rTMS) on the improvement of cognitive function in patients with stress-related depression, and to enrich the neural mechanism(s) underlying rTMS so as to improve cognitive function in patients with stress-related depression.

Methods: We conducted a randomized, double-blind, placebo-controlled study of rTMS in patients with stress-related depression who were 18-40 years of age. Patients were randomly allocated to either a sham or experimental group in a 1:1 ratio. A 10-session rTMS protocol was used with 10-Hz stimulation over the left dorsolateral prefrontal cortex (DLPFC). Clinical assessments (HAMD, HAMA, DASS, MoCA), neuropsychologic (Stroop, WCST), and resting state fMRI and H-MRS assessments were executed at two time points-baseline and after the 10th rTMS session.

Results: rTMS relieved the mental symptoms of patients in both groups. The MoCA score of patients in the experimental group increased; the number of correct answers increased significantly in Stroop testing, and the number of errors and omissions decreased significantly; the number of persistent errors decreased significantly; and the time used to complete the test decreased to an even greater extent in the WCST experimental group. The ReHo value in the lingual gyrus of the right hemisphere and the cuneus of the left and right hemispheres in the experimental group decreased after treatment. The DC value in the left and right hemispheric cuneus and postcentral gyrus of the left hemisphere in the experimental group diminished after treatment. The functional connections of these brain regions also changed as the Cho and NAA/Cr of the left DLPFC changed, with alterations related to the improvement in cognitive function. The level of choline (Cho) in the left DLPFC of the experimental group was significantly lower than that of the control group, and the level of N-acetylaspartate/creatine (NAA/Cr) in the left DLPFC of the control group was significantly higher than that of the experimental group. These changes were related to the overall improvement in cognitive function.

Conclusions: Ten-Hz rTMS over the left DLPFC improved the cognitive function of patients with stress-related depression. The governing mechanism for this phenomenon may be via rTMS effects on multiple visual-related brain regions and their functional connections, and on the somatosensory cortex and its functional connection with visual and auditory cortex, reducing the level of Cho and stabilizing the level of NAA/Cr in the left DLPFC.
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http://dx.doi.org/10.3389/fneur.2022.844606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9051398PMC
April 2022

Improving Data Surveillance Resilience Beyond COVID-19: Experiences of Primary heAlth Care quAlity Cohort In ChinA (ACACIA) Using Unannounced Standardized Patients.

Am J Public Health 2022 06 28;112(6):913-922. Epub 2022 Apr 28.

Dong (Roman) Xu is with SMU Institute for Global Health (SIGHT), School of Health Management and Dermatology Hospital, Southern Medical University (SMU), Guangzhou, China. Yiyuan Cai is with the Department of Epidemiology and Health Statistics, School of Public Health, Guizhou Medical University, Guizhou, China. Xiaohui Wang is with the Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, China. Yaolong Chen is with the Institute of Health Data Science, Lanzhou University, Lanzhou, China. Wenjie Gong is with HER Team and the Department of Maternal and Child Health, Xiangya School of Public Health, Central South University, Changsha, China. Jing Liao and Jinghua Li are with the Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China. Jifang Zhou is with the School of International Business, China Pharmaceutical University, Nanjing, China. Zhongliang Zhou is with the School of Public Policy and Administration, Xi'an Jiaotong University, Xi'an, China. Nan Zhang and Huijuan Liang are with the School of Health Management, Inner Mongolia Medical University, Hohhot, China. Chengxiang Tang is with the Macquarie University Centre for the Health Economy, Macquarie Business School, Macquarie University, Sydney, Australia. Baibing Mi is with the Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China. Yun Lu is with the Department of Preventive Medicine, Maternal and Child Health, School of Public Health, Guizhou Medical University, Guizhou, China. Ruixin Wang is with the Department of Health Economics, School of Public Health, Fudan University, Shanghai, China. Jay Pan is with HEOA Group, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.

We analyzed COVID-19 influences on the design, implementation, and validity of assessing the quality of primary health care using unannounced standardized patients (USPs) in China. Because of the pandemic, we crowdsourced our funding, removed tuberculosis from the USP case roster, adjusted common cold and asthma cases, used hybrid online-offline training for USPs, shared USPs across provinces, and strengthened ethical considerations. With those changes, we were able to conduct fieldwork despite frequent COVID-19 interruptions. Furthermore, the USP assessment tool maintained high validity in the quality checklist (criteria), USP role fidelity, checklist completion, and physician detection of USPs. Our experiences suggest that the pandemic created not only barriers but also opportunities to innovate ways to build a resilient data collection system. To build data system reliance, we recommend harnessing the power of technology for a hybrid model of remote and in-person work, learning from the sharing economy to pool strengths and optimize resources, and dedicating individual and group leadership to problem-solving and results. (. 2022;112(6):913-922. https://doi.org/10.2105/AJPH.2022.306779).
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http://dx.doi.org/10.2105/AJPH.2022.306779DOI Listing
June 2022

Genomic Variations and Immune-Related Features of TMB, PD-L1 Expression and CD8 T Cell Infiltration in Chinese Pulmonary Sarcomatoid Carcinoma.

Int J Gen Med 2022 20;15:4209-4220. Epub 2022 Apr 20.

Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People's Republic of China.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare and distinct subtype of lung cancer characterized by its aggressiveness and dismal prognosis. However, genomic landscape and immune contexture have not been fully elucidated among PSC patients.

Methods: In the present study, whole-exome-sequencing (WES) analyses were performed to depict genomic landscape of 38 independent PSC samples. Tumor mutation burden (TMB) was calculated with the total number of non-synonymous SNVs and indel variants per megabase of coding regions. PD-L1 expression and CD8 T cell density were evaluated by immunohistochemistry in PSC samples. Their associations with genomic mutation were further assessed in genes with most frequent mutation. Overall survival (OS) of PSC patients with top mutated genes and high and low TMB, PD-L1 and CD8 TIL expressions were further compared. Subgroup analyses of OS stratified by morphology and pathological type were conducted. Their correlation with TMB, PD-L1 and CD8 T cell were further assessed.

Results: We identified a cohort of genomic and somatic mutation in PSC patients. Subgroup patients with distinct clinicopathological features were found to harbor different genomic mutations and immunologic features. Besides, genomic profiles influenced outcomes, with SARS mutation associated with worsened prognosis.

Conclusion: Through the mapping of genetic and immunologic landscape, we find the heterogeneity among the subgroups of PSC. Our findings may provide opportunities for therapeutic susceptibility among Chinese PSC patients.
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http://dx.doi.org/10.2147/IJGM.S357659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035462PMC
April 2022

Lactate induces vascular permeability via disruption of VE-cadherin in endothelial cells during sepsis.

Sci Adv 2022 04 27;8(17):eabm8965. Epub 2022 Apr 27.

Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.

Circulating lactate levels are a critical biomarker for sepsis and are positively correlated with sepsis-associated mortality. We investigated whether lactate plays a biological role in causing endothelial barrier dysfunction in sepsis. We showed that lactate causes vascular permeability and worsens organ dysfunction in CLP sepsis. Mechanistically, lactate induces ERK-dependent activation of calpain1/2 for VE-cadherin proteolytic cleavage, leading to the enhanced endocytosis of VE-cadherin in endothelial cells. In addition, we found that ERK2 interacts with VE-cadherin and stabilizes VE-cadherin complex in resting endothelial cells. Lactate-induced ERK2 phosphorylation promotes ERK2 disassociation from VE-cadherin. In vivo suppression of lactate production or genetic depletion of lactate receptor GPR81 mitigates vascular permeability and multiple organ injury and improves survival outcome in polymicrobial sepsis. Our study reveals that metabolic cross-talk between glycolysis-derived lactate and the endothelium plays a critical role in the pathophysiology of sepsis.
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http://dx.doi.org/10.1126/sciadv.abm8965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045716PMC
April 2022

Antiviral Treatments Eliminate the Adverse Impacts of High Baseline HBV Loads on the Survival of HBV-Related HCC Patients.

J Hepatocell Carcinoma 2022 19;9:315-325. Epub 2022 Apr 19.

Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.

Background: In consideration of no standard exclusion criteria for hepatitis B virus (HBV) loads in hepatocellular carcinoma (HCC)-related clinical trials, this study aimed to investigate the prevalence of HBV-related exclusion criteria among current clinical trials and evaluate whether antiviral treatments could eliminate the adverse effects from high HBV loads for HCC patients.

Methods: This is a retrospective study including 772 HCC clinical trials on ClinicalTrials.gov and 1784 HCC patients receiving antiviral treatment. The Kaplan-Meier (K-M) method was used to compare the progression-free survival (PFS) and overall survival (OS) between different groups, and Cox regression analyses were performed to validate possible risk factors on PFS and overall survival OS.

Results: Among 772 clinical trials, 58.3% did not adopt baseline HBV loads as exclusion criteria, 18.0% was 2000 IU/mL, and 10.5% was receiving antiviral therapy. We observed baseline HBV loads had no significant impact on PFS (p = 0.491, 0.155, 0.119, 0.788, 0.280, 0.683 respectively) and OS (p = 0.478, 0.741, 0.263, 0.039, 0.999, 0.581 respectively) in all patients or each treatment group including hepatectomy, radiofrequency ablation, interventional therapy, targeted drugs and anti-programmed cell death immunotherapy, except for the OS of interventional therapy group, where patients with high HBV loads had higher BCLC stage, serum AFP level and ALBI grade (p = 0.009, 0.015 and 0.003, respectively).

Conclusion: Antiviral treatments could eliminate the adverse impacts of high HBV loads on the survival of HCC patients. Simplified eligibility criteria can be adopted for HCC patients with HBV infection where regular antiviral therapy should be enough.
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http://dx.doi.org/10.2147/JHC.S363123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9034869PMC
April 2022

High resolution detectors for whole-body PET scanners by using dual-ended readout.

EJNMMI Phys 2022 Apr 21;9(1):29. Epub 2022 Apr 21.

Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.

Background: Most current whole-body positron emission tomography (PET) scanners use detectors with high timing resolution to measure the time-of-flight of two 511 keV photons, improving the signal-to-noise ratio of PET images. However, almost all current whole-body PET scanners use detectors without depth-encoding capability; therefore, their spatial resolution can be affected by the parallax effect.

Methods: In this work, four depth-encoding detectors consisting of LYSO arrays with crystals of 2.98 × 2.98 × 20 mm, 2.98 × 2.98 × 30 mm, 1.95 × 1.95 × 20 mm, and 1.95 × 1.95 × 30 mm, respectively, were read at both ends, with 6 × 6 mm silicon photomultiplier (SiPM) pixels in a 4 × 4 array being used. The timing signals of the detectors were processed individually using an ultrafast NINO application-specific integrated circuit (ASIC) to obtain good timing resolution. The 16 energy signals of the SiPM array were read using a row and column summing circuit to obtain four position-encoding energy signals.

Results: The four PET detectors provided good flood histograms in which all crystals could be clearly resolved, the crystal energy resolutions measured being 10.2, 12.1, 11.4 and 11.7% full width at half maximum (FWHM), at an average crystal depth of interaction (DOI) resolution of 3.5, 3.9, 2.7, and 3.0 mm, respectively. The depth dependence of the timing of each SiPM was measured and corrected, the timing of the two SiPMs being used as the timing of the dual-ended readout detector. The four detectors provided coincidence time resolutions of 180, 214, 239, and 263 ps, respectively.

Conclusions: The timing resolution of the dual-ended readout PET detector was approximately 20% better than that of the single-ended readout detector using the same LYSO array, SiPM array, and readout electronics. The detectors developed in this work used long crystals with small cross-sections and provided good flood histograms, DOI, energy, and timing resolutions, suggesting that they could be used to develop whole-body PET scanners with high sensitivity, uniform high spatial resolution, and high timing resolution.
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http://dx.doi.org/10.1186/s40658-022-00460-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023628PMC
April 2022
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