Publications by authors named "Wei Fan"

1,037 Publications

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microRNA-497-mediated Smurf2/YY1/HIF2α axis in tumor growth and metastasis of esophageal squamous cell carcinoma.

J Biochem Mol Toxicol 2022 Aug 8:e23182. Epub 2022 Aug 8.

Department of Thoracic Surgery, First Affiliated Hospital of Soochow University, Suzhou, China.

Aberrant expression of microRNA-497 (miR-497) is associated with tumor progression, but the molecular mechanisms in tumorigenesis remain largely unknown. Here, we report that miR-497 expression is downregulated in esophageal squamous cell carcinoma (ESCC) clinical samples. Consistently, upregulation of miR-497 inhibits ESCC cell malignant properties and tumor growth in vivo. Importantly, we uncovered that miR-497 upregulation suppressed ESCC cell growth and tumor growth by inhibiting Smurf2. Mechanistically, we showed that Smurf2 was a target of miR-497, and mediated YY1 expression to elevate HIF2α expression, thereby enhancing the malignancy of ESCC cells. Together, our study uncovered the role of the miR-497-mediated Smurf2/YY1/HIF2α axis in tumor growth and metastasis, which might provide potential therapeutic targets for human ESCC.
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http://dx.doi.org/10.1002/jbt.23182DOI Listing
August 2022

A New Prognostic Indicator of Immune Microenvironment and Therapeutic Response in Lung Adenocarcinoma Based on Peroxisome-Related Genes.

J Immunol Res 2022 26;2022:6084589. Epub 2022 Jul 26.

Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Army Medical University, Chongqing, China.

Lung adenocarcinoma (LUAD) has been the major cause of tumor-associated mortality in recent years and exhibits a poor outcome. New data revealed that peroxisomes have a function in the regulation of the development and progression of several tumors. However, the prognostic values of peroxisome-related genes (PRGs) were rarely reported. Genomic sequence, mutation, and clinical data of 535 LUAD tissues were obtained from TCGA data sets. Within the TCGA cohort, a multigene signature was constructed with the assistance of the LASSO Cox regression model. Three GEO data sets, including GSE3141, GSE31210, and GSE72094, were obtained as validation cohorts. ROC assays, Kaplan-Meier methods, and multivariate assays were applied to examine the prognostic capacities of the novel signature. Gene Set Enrichment Analysis (GSEA) was performed to further understand the underlying molecular mechanisms. In this study, we identified 47 differentially expressed peroxisome-related genes (PRGs), including 25 increased and 22 decreased PRGs. A prognostic model of six PRGs was established. The univariate and multivariate Cox analyses both showed that the value of risk score was less than 0.05. In LUAD patients, the strong connection between the risk score and overall survival was further verified in three other GEO data sets. TMB and cancer stem cell infiltration were shown to be significantly higher in the high-risk group in comparison to the low-risk group. The TIDE score of the group with the low risk was considerably greater than that of the group with the high risk. Several drugs, targeting PRG-related genes, were available for the treatments of LUAD. Overall, we developed a novel peroxisome-related prognostic signature for LUAD patients. This signature could successfully indicate LUAD patients' chances of survival as well as their immune system's responsiveness to treatments. In addition, it has the potential to serve as immunotherapeutic targets for LUAD patients.
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http://dx.doi.org/10.1155/2022/6084589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346542PMC
July 2022

Xanthorrhizol Ameliorates Oxidative Stress and Inflammation in Freund's Complete Adjuvant-Induced Rheumatoid Arthritis in Rats.

Appl Biochem Biotechnol 2022 Aug 6. Epub 2022 Aug 6.

Department of Sports Medicine, Nanchang Hongdu Hospital of TCM, Nanchang, 330008, Jiangxi, China.

Rheumatoid arthritis (RA) is an inflammatory disease and a common cause of disability. This study is aimed to ascertain the therapeutic potentials of the xanthorrhizol against Freund's complete adjuvant (FCA)-stimulated RA in rats. The RA was initiated in the rats via injecting FCA (0.1 ml) subcutaneously and then treated with xanthorrhizol (20 mg/kg) for 25 days. The hematological markers were investigated using the automated hematological analyzer. The organ index (spleen and thymus) and paw volume were inspected by standard methods. The ALP, SGOT, and SGPT activities were examined using kits. The levels of inflammatory biomarkers, i.e., IL-1β, IL-6, IL-10, and TNF-α, were inspected using assay kits. The status of MDA, SOD, CAT, GSH, COX-2, iNOS, and NF-κB was quantified using respective assay kits. The xanthorrhizol treatment appreciably improved the body weight and hematological parameters and reduced the arthritis score, organ index, and paw volume in the RA rats. The levels of RBCs and Hb were effectively improved, and activities of ALP, SGOT, and SGPT were decreased by the xanthorrhizol in the RA rats. The RA rats treated with 20 mg/kg of xanthorrhizol demonstrated the depleted IL-1β, IL-6, and TNF-α levels. The antioxidant markers SOD, CAT, and GSH were improved, and inflammatory biomarker levels such as COX-2, iNOS, and NF-κB were decreased by the xanthorrhizol in the RA rats. Overall, these outcomes witnessed that the xanthorrhizol effectively ameliorated the oxidative stress and inflammatory responses and attenuated the RA in rats. Hence, it could be a talented anti-arthritic medication to treat RA.
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http://dx.doi.org/10.1007/s12010-022-04091-4DOI Listing
August 2022

Enhanced Aromaticity and Open-shell Diradical Character in The Dianions of 9-Fluorenylidene Substituted Expanded Radialenes.

Angew Chem Int Ed Engl 2022 Aug 3. Epub 2022 Aug 3.

National University of Singapore, Chemistry, 3 Science Drive 3, 117543, Singapore, SINGAPORE.

Radialenes and expanded radialenes are cross-conjugated macrocycles displaying poor aromatic character. In this work, three 9-fluorenylidene substituted expanded [n]radialenes ( ER-n , n =3-5) with diacetylene spacer were synthesized and their structures were confirmed by X-ray crystallographic analysis and NMR spectroscopy. They all can be easily reduced into relatively stable dianions. Detailed experimental measurements and theoretical calculations suggest that their dianions ( ER-n 2- , n =3-5) are stabilized by both the aromatic fluorenyl anion substituents and the central aromatic rings with formally [4 n +2] delocalized π electrons. In addition, the dianions of the extended radialenes ( ER-4 2- and ER-5 2- ) show unique open-shell diradical character with a small singlet-triplet energy gap. For comparison, their linear counterparts ( L-3 and L-4 ) were also synthesized and their dianions exhibit very different redox and optical properties from their respective macrocycles.
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http://dx.doi.org/10.1002/anie.202209448DOI Listing
August 2022

In Vitro and In Vivo Evaluation of DTPA-HPMA Copolymers as Potential Decorporating Agents for Prophylactic Therapy of Actinide Contamination.

Radiat Res 2022 Aug 1. Epub 2022 Aug 1.

Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, 985830 Nebraska Medical Center, Omaha, Nebraska 68198.

The release of actinides into the environment represents a significant potential public health concern. Chelation therapy utilizing diethylenetriamine pentaacetate (DTPA) is a U.S. Food and Drug Administration (FDA)-approved therapy capable of mitigating the deposition of some absorbed actinides in the body. However, the pharmacokinetic profile of DTPA is not ideal for prophylactic applications. In this study, we examine the incorporation of DTPA into a HPMA copolymer (P-DTPA) to investigate if the enhanced blood circulation time can offer superior prophylactic protection and of improving in vivo radiometal decorporation. Utilizing lutetium-177 (177Lu) as an actinide model, the performance of P-DTPA and DTPA (control) were evaluated using selectivity studies in the presence of competing biological metals, chelation and stability assays in human serum and cytotoxicity studies using human umbilical vein endothelial cells (HUVEC). The in vivo decorporation efficiency of P-DTPA relative to DTPA and untreated controls was also evaluated over two weeks in CF-1 mice. In the experimental groups, the mice were prophylactically treated with P-DTPA or DTPA (30 μmol/kg) 6 or 24 h prior to 177LuCl3 administration. The in vitro results reveal that P-DTPA gives efficient complexation yields relative to DTPA with a tolerable cytotoxicity profile and good serum stability. The in vivo decorporation studies demonstrated enhanced total excretion of the 177Lu using P-DTPA compared to DTPA in both the 6 and 24 h prophylactic treatment study arms. This enhanced decorporation effect is certainly attributable to the expected prolonged biological half-life of DTPA when grafted to the HPMA polymer.
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http://dx.doi.org/10.1667/RADE-21-00244.1DOI Listing
August 2022

Identification of early invisible acute ischemic stroke in non-contrast computed tomography using two-stage deep-learning model.

Theranostics 2022 18;12(12):5564-5573. Epub 2022 Jul 18.

Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Although non-contrast computed tomography (NCCT) is the recommended examination for the suspected acute ischemic stroke (AIS), it cannot detect significant changes in the early infarction. We aimed to develop a deep-learning model to identify early invisible AIS in NCCT and evaluate its diagnostic performance and capacity for assisting radiologists in decision making. : In this multi-center, multi-manufacturer retrospective study, 1136 patients with suspected AIS but invisible lesions in NCCT were collected from two geographically distant institutions between May 2012 to May 2021. The AIS lesions were confirmed based on the follow-up diffusion-weighted imaging and clinical diagnosis. The deep-learning model was comprised of two deep convolutional neural networks to locate and classify. The performance of the model and radiologists was evaluated by the area under the receiver operator characteristic curve (AUC), sensitivity, specificity, and accuracy values with 95% confidence intervals. Delong's test was used to compare the AUC values, and a chi-squared test was used to evaluate the rate differences. 986 patients (728 AIS, median age, 55 years, interquartile range [IQR]: 47-65 years; 664 males) were assigned to the training and internal validation cohorts. 150 patients (74 AIS, median age, 63 years, IQR: 53-75 years; 100 males) were included as an external validation cohort. The AUCs of the model were 83.61% (sensitivity, 68.99%; specificity, 98.22%; and accuracy, 89.87%) and 76.32% (sensitivity, 62.99%; specificity, 89.65%; and accuracy, 88.61%) for the internal and external validation cohorts based on the slices. The AUC of the model was much higher than that of two experienced radiologists (65.52% and 59.48% in the internal validation cohort; 64.01% and 64.39% in external validation cohort; all < 0.001). The accuracy of two radiologists increased from 62.00% and 58.67% to 92.00% and 84.67% when assisted by the model for patients in the external validation cohort. : This deep-learning model represents a breakthrough in solving the challenge that early invisible AIS lesions cannot be detected by NCCT. The model we developed in this study can screen early AIS and save more time. The radiologists assisted with the model can provide more effective guidance in making patients' treatment plan in clinic.
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http://dx.doi.org/10.7150/thno.74125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330528PMC
August 2022

TG-Net: Combining transformer and GAN for nasopharyngeal carcinoma tumor segmentation based on total-body uEXPLORER PET/CT scanner.

Comput Biol Med 2022 Jul 21;148:105869. Epub 2022 Jul 21.

Lauterbur Research Center for Biomedical Imaging, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. Electronic address:

Nasopharyngeal carcinoma (NPC) is a malignant tumor, and the main treatment is radiotherapy. Accurate delineation of the target tumor is essential for radiotherapy of NPC. NPC tumors are small in size and vary widely in shape and structure, making it a time-consuming and laborious task for even experienced radiologists to manually outline tumors. However, the segmentation performance of current deep learning models is not satisfactory, mainly manifested by poor segmentation boundaries. To solve this problem, this paper proposes a segmentation method for nasopharyngeal carcinoma based on dynamic PET-CT image data, whose input data include CT, PET, and parametric images (Ki images). This method uses a generative adversarial network with a modified UNet integrated with a Transformer as the generator (TG-Net) to achieve automatic segmentation of NPC on combined CT-PET-Ki images. In the coding stage, TG-Net uses moving windows to replace traditional pooling operations to obtain patches of different sizes, which can reduce information loss in the coding process. Moreover, the introduction of Transformer can make the network learn more representative features and improve the discriminant ability of the model, especially for tumor boundaries. Finally, the results of fivefold cross validation with an average Dice similarity coefficient score of 0.9135 show that our method has good segmentation performance. Comparative experiments also show that our network structure is superior to the most advanced methods in the segmentation of NPC. In addition, this work is the first to use Ki images to assist tumor segmentation. We also demonstrated the usefulness of adding Ki images to aid in tumor segmentation.
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http://dx.doi.org/10.1016/j.compbiomed.2022.105869DOI Listing
July 2022

A chromosome-level reference genome of a Convolvulaceae species Ipomoea cairica.

G3 (Bethesda) 2022 Jul 27. Epub 2022 Jul 27.

Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture; Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs; Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, Guangdong, 518120, China.

Ipomoea cairica is a perennial creeper that has been widely introduced as a garden ornamental across tropical, subtropical and temperate regions. Because it grows extremely fast and spreads easily, it has been listed as an invasive species in many countries. Here, we constructed the chromosome-level reference genome of Ipomoea cairica by PacBio HiFi and Hi-C sequencing, with assembly size of 733.0 Mb, contig N50 of 43.8 Mb and scaffold N50 of 45.7 Mb, and BUSCO complete rate of 98.0%. Hi-C scaffolding assigned 97.9% of the contigs to 15 pseudo-chromosomes. Telomeric repeat analysis reveals that 7 of the 15 pseudo-chromosomes are gapless and telomere-to-telomere. The transposable element content of I. cairica is 73.4%, obviously higher than that of other Ipomoea species. A total of 38,115 protein-coding genes were predicted, with the BUSCO complete rate of 98.5%, comparable to that of the genome assembly, and 92.6% of genes were functional annotated. In addition, we identified 3,039 tRNA genes and 2,403 rRNA genes in the assembled genome. Phylogenetic analysis showed that I. cairica formed a clade with I. aquatica, and they diverged from each other 8.1 million years ago. Through comparative genome analysis, we reconfirmed that a whole genome triplication event occurred specific to Convolvulaceae family and in the ancestor of the genus Ipomoea and Cuscuta. This high-quality reference genome of I. cairica will greatly facilitate the studies on the molecular mechanisms of its rapid growth and invasiveness.
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http://dx.doi.org/10.1093/g3journal/jkac187DOI Listing
July 2022

Tomato Oxalyl-CoA Synthetase Degrades Oxalate and Affects Fruit Quality.

Front Plant Sci 2022 7;13:951386. Epub 2022 Jul 7.

State Key Laboratory of Plant Physiology and Biochemistry, College of Life Science, Zhejiang University, Hangzhou, China.

Acyl activating enzyme 3 (AAE3) encodes oxalyl-CoA synthetase involved in oxalate degradation. In this study, we investigated the role of AAE3 (SlAAE3) in the fruit quality of tomato (). The purified recombinant SlAAE3 protein from exhibited a high activity toward oxalate, with a K of 223.8 ± 20.03 μm and V of 7.908 ± 0.606 μmol mg protein min. Transient expression of SlAAE3-green fluorescent protein (GFP) fusion proteins suggests that SlAAE3 is a soluble protein without specific subcellular localization. The expression of SlAAE3 is both tissue- and development-dependent, and increased during fruit ripping. The knockout mutants had improved fruit quality as evidenced by the increased sugar-acid ratio and mineral nutrient content. To find the mechanism by which SlAAE3 affects fruit quality, transcriptome, and metabolome were employed on SlAAE3 over-expressed line and wide type fruits. The transcriptomic and metabolic profiles indicated that SlAAE3 in fruits mainly functions at 20 days post-anthesis (20 DPA) and mature green (MG) stages, resulting in up-regulation of amino acid derivatives, nucleotides, and derivatives, but down-regulation of lipid compounds. However, differentially expressed genes (DEGs) were mainly enriched at redox pathways. Taken together, both and results suggest that SlAAE3-encoded protein acts as an oxalyl-CoA synthetase, which also participates in redox metabolism. These data provide a further understanding of the mechanism by which SlAAE3 participates in tomato fruit quality.
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http://dx.doi.org/10.3389/fpls.2022.951386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301600PMC
July 2022

A Universal Spinning-Coordinating Strategy to Construct Continuous Metal-Nitrogen-Carbon Heterointerface with Boosted Lithium Polysulfides Immobilization for 3D-Printed LiS Batteries.

Adv Sci (Weinh) 2022 Jul 21:e2203181. Epub 2022 Jul 21.

Hefei National Research Center for Physical Sciences at the Microscale, Department of Materials Science and Engineering, National Synchrotron Radiation Laboratory, CAS Key Laboratory of Materials for Energy Conversion, University of Science and Technology of China, Hefei, Anhui, 230026, P. R. China.

Constructing intimate coupling between transition metal and carbon nanomaterials is an effective means to achieve strong immobilization of lithium polysulfides (LiPSs) in the applications of lithium-sulfur (LiS) batteries. Herein, a universal spinning-coordinating strategy of constructing continuous metal-nitrogen-carbon (MNC, M = Co, Fe, Ni) heterointerface is reported to covalently bond metal nanoparticles with nitrogen-doped porous carbon fibers (denoted as M/M[email protected]). Guided by theoretical simulations, the Co/Co[email protected] hybrid is synthesized as a proof of concept and used as an efficient sulfur host material. The polarized CoNC bridging bonds can induce rapid electron transfer from Co nanoparticles to the NPCF skeleton, promoting the chemical anchoring of LiPSs to improve sulfur utilization. Hence, the as-assembled LiS battery presents a remarkable capacity of 781 mAh g at 2.0 C and a prominent cycling lifespan with a low decay rate of only 0.032% per cycle. Additionally, a well-designed Co/Co[email protected] electrode with a high sulfur loading of 7.1 mg cm is further achieved by 3D printing technique, which demonstrates an excellent areal capacity of 6.4 mAh cm at 0.2 C under a lean-electrolyte condition. The acquired insights into strongly coupled continuous heterointerface in this work pave the way for rational designs of host materials in LiS systems.
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http://dx.doi.org/10.1002/advs.202203181DOI Listing
July 2022

Advances, challenge and prospects in cell-mediated nanodrug delivery for cancer therapy: a review.

J Drug Target 2022 Jul 29:1-13. Epub 2022 Jul 29.

Department of Pharmacy, Fujian University of Traditional Chinese Medicine Fuzhou, Fujian, China.

Nanomedicine offers considerable opportunities to improve drugability and reduce toxicity for tumour therapy. However, the application of nanomedicine has achieved little success in clinical trials due to multiple physiological barriers to drug delivery. Circulating cells are expected to improve the physical distribution of drugs and enhance the therapeutic effect by overcoming various biological barriers in collaboration with nano-drug delivery systems owing to excellent biocompatibility, low immunogenicity and a long-circulation time and strong binding specificity. Nonetheless, we have noticed some limitations in implementing tthe strategy. In this article, we intend to introduce the latest progress in research and application of circulating cell-mediated nano-drug delivery systems, describe the main cell-related drug delivery modes, sum up the relevant points of the transport systems in the process of loading, transport and release, and lastly discuss the advantages, challenges and future development trends in cell-mediated nano-drug delivery.
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http://dx.doi.org/10.1080/1061186X.2022.2104299DOI Listing
July 2022

Protective effects of salavianolic acid A on clozapine-induced cardiotoxicity in zebrafish.

J Appl Toxicol 2022 Jul 20. Epub 2022 Jul 20.

Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China.

The clinical use of clozapine (CLZ), an atypical antipsychotic drug, was affected by side effects, such as cardiotoxicity. We selected normally-developing zebrafish embryos to explore the antagonism of salvianolic acid A (SAA) against clozapine-induced cardiotoxicity. Embryos were treated with CLZ and SAA, and zebrafish phenotypes were observed at 24 h, 48 h, 72 h, and 96 h after treatment. The observed phenotypes included heart shape, heart rate, and venous sinus-arterial bulb (SV-BA) interval. Real-time quantitative PCR was used to detect changes in the expression of genes involved in heart inflammation, oxidative stress and apoptosis. The results showed that SAA relieved pericardial edema, increased heart rate, and reduced the SV-BA interval. The PCR results also showed that when the zebrafish embryos were incubated with SAA and CLZ for 96 h, the expression of il-1b and nfkb2 were significantly down-regulated, the expression of sod1 and cat were significantly up-regulated, the expressions of mcl1a and mcl1b were significantly down-regulated. In summary, SAA can antagonized clozapine-induced cardiotoxicity.
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http://dx.doi.org/10.1002/jat.4368DOI Listing
July 2022

Risk Factors for Benign Convulsions With Mild Gastroenteritis.

Front Pediatr 2022 29;10:925896. Epub 2022 Jun 29.

Department of Pediatrics, Liyang People's Hospital, Liyang, China.

Objective: To investigate the risk factors for benign convulsions with mild gastroenteritis (CwG) and provide a basis for the early identification and diagnosis.

Method: We selected children with CwG and acute gastroenteritis in the same period who attended the pediatric department of the Liyang People's Hospital from June 2018 to June 2021. A retrospective analysis of the general data, clinical characteristics, and laboratory test results of the two groups was performed. Finally, we conducted a multifactorial logistic regression analysis to derive the risk factors for CwG.

Results: A total of 82 children were included in the CwG and 93 children were included in the acute gastroenteritis group. Univariate analysis showed no significant differences in gender, age, vomiting, diarrhea, neutrophil, lymphocyte, hemoglobin, platelets, and serum calcium. Statistically significant differences were found in onset season, rotavirus, white blood cells, aspartate aminotransferase, alanine transaminase, serum sodium, and uric acid. Finally, multifactorial logistic regression analysis showed rotavirus (OR, 3.042, 95% CI, 1.116-8.289, = 0.030), serum sodium (OR, 0.811, 95% CI, 0.684-0.962, = 0.016) and uric acid (OR, 1.018, 95% CI, 1.012-1.024, = 0.000) to be independent risk factors.

Conclusion: Characteristics of gastroenteritis symptoms such as vomiting and diarrhea cannot be used to predict the onset of CwG. Rotavirus is an independent risk factor for CwG, and decreased serum sodium and increased uric acid can be used as early warning indicators for CwG.
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http://dx.doi.org/10.3389/fped.2022.925896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277103PMC
June 2022

The role of preserved bowel and mesentery fixation in apple-peel intestinal atresia.

BMC Pediatr 2022 07 11;22(1):407. Epub 2022 Jul 11.

Department of Pediatric Surgery, The First Affiliated Hospital of Harbin Medical University, No.23 Youzheng Street, Nangang District, Harbin, 150007, China.

Objective: This study explored the feasibility of mesoplasty with end-to-side anastomosis in the treatment of different apple-peel mesenteric defects with high jejunal atresia.

Methods: A retrospective analysis was performed on 42 premature infants admitted to the hospital between 2014 and 2021. Prenatal ultrasound scans revealed bowel dilatation. The patients experienced vomiting after birth and produced white or no meconium. Plain radiography showed double or triple bubble signs and the patients underwent emergency laparotomy. High jejunal atresia with different apple-peel atresia appearance was discovered intraoperatively, involving mobilization of the ileocecal region. Patients received end-to-side anastomosis between the enlarged blind pouch and atretic bowel, as well as mesoplasty. A jejunal feeding tube was placed trans-nasally. Patients were discharged after achieving full enteral feeding. We also reviewed the literature on the subject.

Results: Three patients died and 39 survived. The discharged patients were followed up for 12 months, and none showed post-operative complications such as intestinal obstruction, malnutrition, or chronic diarrhea. All surviving patients reached the expected height and weight for children of the same age.

Conclusion: For cases of high jejunal atresia with apple-peel intestinal atresia, mesoplasty may be a good option to avoid postoperative volvulus.
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http://dx.doi.org/10.1186/s12887-022-03475-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275155PMC
July 2022

Nomograms predicting recurrence in patients with triple negative breast cancer based on ultrasound and clinicopathological features.

Br J Radiol 2022 Aug 2:20220305. Epub 2022 Aug 2.

Department of Ultrasound Medicine, the Second Affiliated Hospital of Harbin Medical University, Heilongjiang, China.

Objectives: The clinicopathological and ultrasound features associated with recurrence in patients with triple negative breast cancer (TNBC) were used to develop a nomogram to predict the prognosis of TNBC.

Methods: Clinicopathological data of 300 patients with TNBC treated between July 2012 and September 2014 were retrospectively reviewed. The endpoint was progression-free survival (PFS). Prognostic factors were screened by multivariate COX regression to develop nomograms. The C-index and calibration curves were used to evaluate the predictive accuracy and discriminatory ability of nomograms.

Results: Of 300 patients with TNBC followed-up for 5 years, 80 (26.7%) had PFS events. Five informative prognostic factors (large size, vertical orientation, posterior acoustic enhancement, lymph node involvement, and high pathological stage) were screened and used to construct a nomogram for PFS. The C-index of the PFS nomogram was 0.88 ( < 0.01, 95% confidence interval, 0.85-0.90), indicating good predictive accuracy.

Conclusions: We developed and validated a nomogram for predicting PFS in TNBC. Vertical orientation and posterior acoustic enhancement in ultrasound images of TNBC were associated with worse outcomes.

Advances In Knowledge: Patients with TNBC have a very poor prognosis and patients have a high risk of recurrence, and our study developed a nomogram based on ultrasound and clinicopathological features for TNBC patients to improve the accuracy of individualized prediction of recurrence and provide help for clinical treatment.
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http://dx.doi.org/10.1259/bjr.20220305DOI Listing
August 2022

Assessing dynamic metabolic heterogeneity in non-small cell lung cancer patients via ultra-high sensitivity total-body [F]FDG PET/CT imaging: quantitative analysis of [F]FDG uptake in primary tumors and metastatic lymph nodes.

Eur J Nucl Med Mol Imaging 2022 Jul 11. Epub 2022 Jul 11.

Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.

Purpose: This study aimed to quantitatively assess [F]FDG uptake in primary tumor (PT) and metastatic lymph node (mLN) in newly diagnosed non-small cell lung cancer (NSCLC) using the total-body [F]FDG PET/CT and to characterize the dynamic metabolic heterogeneity of NSCLC.

Methods: The 60-min dynamic total-body [F]FDG PET/CT was performed before treatment. The PTs and mLNs were manually delineated. An unsupervised K-means classification method was used to cluster patients based on the imaging features of PTs. The metabolic features, including Patlak-Ki, Patlak-Intercept, SUV, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and textural features, were extracted from PTs and mLNs. The targeted next-generation sequencing of tumor-associated genes was performed. The expression of Ki67, CD3, CD8, CD34, CD68, and CD163 in PTs was determined by immunohistochemistry.

Results: A total of 30 patients with stage IIIA-IV NSCLC were enrolled. Patients were divided into fast dynamic FDG metabolic group (F-DFM) and slow dynamic FDG metabolic group (S-DFM) by the unsupervised K-means classification of PTs. The F-DFM group showed significantly higher Patlak-Ki (P < 0.001) and SUV (P < 0.001) of PTs compared with the S-DFM group, while no significant difference was observed in Patlak-Ki and SUV of mLNs between the two groups. The texture analysis indicated that PTs in the S-DFM group were more heterogeneous in FDG uptake than those in the F-DFM group. Higher T cells (CD3/CD8) and macrophages (CD68/CD163) infiltration in the PTs were observed in the F-DFM group. No significant difference was observed in tumor mutational burden between the two groups.

Conclusion: The dynamic total-body [F]FDG PET/CT stratified NSCLC patients into the F-DFM and S-DFM groups, based on Patlak-Ki and SUV of PTs. PTs in the F-DFM group seemed to be more homogenous in terms of [F]FDG uptake than those in the S-DFM group. The higher infiltrations of T cells and macrophages were observed in the F-DFM group, which suggested a potential benefit from immunotherapy.
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http://dx.doi.org/10.1007/s00259-022-05904-8DOI Listing
July 2022

Structured clay minerals-based nanomaterials for sustainable photo/thermal carbon dioxide conversion to cleaner fuels: A critical review.

Sci Total Environ 2022 Jul 8;845:157206. Epub 2022 Jul 8.

Chemical and Petroleum Engineering Department, UAE University, P.O. Box 15551, Al Ain, United Arab Emirates. Electronic address:

In efforts to achieve a sustainable development goal, the utilization of CO to generate renewable fuels is promising, as it is a sustainable technology that provides affordable and clean energy. To realize the production of renewable green fuels, a proficient and low-cost technology is required. Using photo/thermal catalytic process, the goal of sustainable CO hydrogenation can be achieved. There have been several types of catalysts under exploration, however, they are expensive with limited availability. In the current development, green materials such as mineral clays are emerging as cocatalyst/supports for CO hydrogenation. Clays are bestowed with various beneficial properties such as a large surface area, high porosity, abundant basic sites, excellent thermal stability and chemical corrosion resistance. Clays are promising materials that can drastically reduce the cost in catalyst preparation, partially fulfil the energy demand and reduce greenhouse gas emission. This review aims to focus on the various types of clays and their applications in the field of photo/thermal CO hydrogenation to renewable fuels. Firstly, the classifications of clays are provided, whereby they can be differentiated based on their silicate layers, namely 1:1 and 2:1 type clay and their properties are thoroughly discussed to provide advantages and applications. The applications of various clays such as kaolinite, halloysite, montmorillonite, attapulgite, saponite and volkonskoite for CO hydrogenation reactions are systematically discoursed. In addition, various approaches to improve the capability of raw clays as catalyst support are critically discussed, which include thermal treatment, exfoliation, acid-leaching and pillaring approaches. A critical discussion regarding the engineering aspects to further enhance clay-based catalyst for CO hydrogenation are further disclosed. In short, clays are freely available materials that can be found in abundance. However, there are many more different types of natural green clays that have not been studied and explored in various energy applications.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157206DOI Listing
July 2022

Full-Length Transcriptome Sequencing Reveals Alternative Splicing and lncRNA Regulation during Nodule Development in .

Int J Mol Sci 2022 Jul 1;23(13). Epub 2022 Jul 1.

State Key Laboratory of Crop Stress Adaptation and Improvement, School of Life Sciences, Henan University, Kaifeng 475001, China.

Alternative splicing (AS) is a ubiquitous phenomenon among eukaryotic intron-containing genes, which greatly contributes to transcriptome and proteome diversity. Here we performed the isoform sequencing (Iso-Seq) of soybean underground tissues inoculated and uninoculated with Rhizobium and obtained 200,681 full-length transcripts covering 26,183 gene loci. It was found that 80.78% of the multi-exon loci produced more than one splicing variant. Comprehensive analysis of these identified 7874 differentially splicing events with highly diverse splicing patterns during nodule development, especially in defense and transport-related processes. We further profiled genes with differential isoform usage and revealed that 2008 multi-isoform loci underwent stage-specific or simultaneous major isoform switches after Rhizobium inoculation, indicating that AS is a vital way to regulate nodule development. Moreover, we took the lead in identifying 1563 high-confidence long non-coding RNAs (lncRNAs) in soybean, and 157 of them are differentially expressed during nodule development. Therefore, our study uncovers the landscape of AS during the soybean- interaction and provides systematic transcriptomic data for future study of multiple novel directions in soybean.
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http://dx.doi.org/10.3390/ijms23137371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266934PMC
July 2022

Effective suppression of triple negative breast cancer by paclitaxel nanoparticles conjugated with transmembrane TNF-α monoclonal antibody.

Int J Pharm 2022 Jul 5;624:121969. Epub 2022 Jul 5.

Department of Clinical Laboratory & Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China. Electronic address:

Transmembrane TNF-α (tmTNF), a transmembrane form of TNF-α, was reported overexpressed in approximately 84% of triple-negative breast cancer (TNBC) patients and has emerged as a valid candidate biomarker for targeting TNBC. Paclitaxel is a first-line chemotherapeutic agent for the treatment of triple-negative breast cancer, but suffers from low water solubility, resulting in its low bioavailability. To achieve site-specific delivery of the anticancer chemotherapeutic drug (paclitaxel) on TNBC, we developed tmTNF-α monoclonal antibody (mAb)-conjugated paclitaxel (PTX) nanoparticles (NPs) (tmTNF-α mAb-PTX NPs) as potential nanocarriers. This targeted delivery-therapy nanocarriers was conducted by using an emulsification-evaporation method. tmTNF-α mAb-PTX NPs displayed favorable physicochemical properties. Compared with the control groups, tumor growth in human MDA-MB-231 xenograft mice was suppressed significantly by tmTNF-α mAb-PTX NPs. TmTNF-α mAb-PTX NPs exerts anti-tumor effects via promoting apoptosis and regulating mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K) / protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) cascade, as well as AMP-activated protein kinase (AMPK) and nuclear factor Kappa-B (NF-κB) pathways. Moreover, tmTNF-α mAb-PTX NPs can inhibit the process of epithelial-mesenchymal transition (EMT) in TNBC to suppress tumor progression and metastasis. Together, the novel tmTNF-α mAb-PTX NPs based targeted drug delivery system is a potentially highly effective approach for treating TNBC.
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http://dx.doi.org/10.1016/j.ijpharm.2022.121969DOI Listing
July 2022

Intraocular lens power calculation after radical keratotomy and photorefractive keratectomy: A case report.

Medicine (Baltimore) 2022 Jul 8;101(27):e29465. Epub 2022 Jul 8.

Department of Ophthalmology, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.

Rationale: To report a rare case of calculating the IOL power in a cataract patient who underwent both radial keratotomy (RK) and photorefractive keratectomy (PRK).

Patient Concerns: A 48-year-old woman underwent bilateral RK at age 22 and bilateral PRK at age 46. She developed bilateral corneal haze and corneal endothelial inflammation and received steroids therapy for long time after PRK. Then she was referred to our hospital due to decreased vision in the both eyes.

Diagnoses: The patient was diagnosed with binocular complicated cataract, corneal haze, high myopia and post corneal refractive surgery (RK and PRK).

Interventions: The patient underwent bilateral phacoemulsification. The IOL power was calculated using SRK/T formula for RK and Haigis-L formula for PRK, respectively. We finally selected the Haigis-L formula and the intraocular lens (SN60WF) was implanted within the capsular bag.

Outcomes: After the surgery, both eyes showed myopia drift, and the right eye continuously fluctuated in refractive results. However, by nearly 1 year later, refractive results in both eyes had stabilized, and no other complications had occurred.

Lessons: IOL power in patients who undergo both RK and PRK can be reliably calculated using the Shammas-PL, Average of multiple formulas, or Barret True-K No History formulas. Haigis-L formula is not suitable. Such patients require at least three months after surgery to attain refractive stability in both eyes.
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http://dx.doi.org/10.1097/MD.0000000000029465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259111PMC
July 2022

Respiratory Motion and Airflow Estimation During Sleep Using Tracheal Movement and Sound.

Nat Sci Sleep 2022 1;14:1213-1223. Epub 2022 Jul 1.

Sleep Research Laboratory of the University Health Network Toronto Rehabilitation Institute, Toronto, Ontario, Canada.

Purpose: Due to lack of access and high cost of polysomnography, portable sleep apnea testing has been developed to diagnose sleep apnea. Despite being less expensive, and having fewer sensors and reasonable accuracy in identifying sleep apnea, such devices can be less accurate than polysomnography in detecting apneas/hypopneas. To increase the accuracy of apnea/hypopnea detection, an accurate airflow estimation is required. However, current airflow measurement techniques employed in portable devices are inconvenient and subject to displacement during sleep. In this study, algorithms were developed to estimate respiratory motion and airflow using tracheo-sternal motion and tracheal sounds.

Patients And Methods: Adults referred for polysomnography were included. Simultaneous to polysomnography, a patch device with an embedded 3-dimensional accelerometer and microphone was affixed to the suprasternal notch to record tracheo-sternal motion and tracheal sounds, respectively. Tracheo-sternal motion was used to train two mathematical models for estimating changes in respiratory motion and airflow compared to simultaneously measured thoracoabdominal motion and nasal pressure from polysomnography. The amplitude of the estimated airflow was then adjusted by the tracheal sound envelope in segments with unstable breathing.

Results: Two hundred and fifty-two subjects participated in this study. Overall, the algorithms provided highly accurate estimates of changes in respiratory motion and airflow with mean square errors (MSE) of 3.58 ± 0.82% and 2.82 ± 0.71%, respectively, compared to polysomnographic signals. The estimated motion and airflow from the patch signals detected apneas and hypopneas scored on polysomnography in 63.9% and 88.3% of cases, respectively.

Conclusion: This study presents algorithms to accurately estimate changes in respiratory motion and airflow, which provides the ability to detect respiratory events during sleep. Our study suggests that such a simple and convenient method could be used for portable monitoring to detect sleep apnea. Further studies will be required to test this possibility.
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http://dx.doi.org/10.2147/NSS.S360970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255718PMC
July 2022

Examination of Charge Modifications of an Endolysosomal Trapping Inhibitor in an Antagonistic NTSR1-Targeted Construct for Colon Cancer.

Bioconjug Chem 2022 07 6;33(7):1363-1376. Epub 2022 Jul 6.

Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska 68198-6120, United States.

Many low-molecular weight targeted radiotherapeutics (TRTs) are capable of rapidly achieving exceptional tumor to non-target ratios shortly after administration. However, the low tumor residence time of many TRTs limits therapeutic dose delivery and has become the Achilles heel to their clinical translation. To combat the tumor efflux of these otherwise promising agents, we have previously presented a strategy of equipping low-molecular weight TRTs with irreversible cysteine cathepsin inhibitors (e.g., E-64 analogues). These inhibitors are capable of forming irreversible adducts with cysteine proteases within the endolysosomal compartments of cells. Using these endolysosomal trapping agents (ETs), the receptor-targeted constructs are able to increase tumor retention and, thus, deliverable therapeutic doses. In this study, we examine this approach in the development of agents targeting the neurotensin receptor subtype 1 (NTSR1), a receptor overexpressed in numerous cancers. Using an antagonistic NTSR1-targeting vector, we explore the impact of charge modification of the ETs on the in vitro and in vivo biological performance of the constructs using HT-29 colon cancer models. Four ETs (based on the epoxysuccinyl peptide E-64) with various charge states were synthesized and incorporated into the structures of the NTSR1-targeted antagonist. These four Lu-labeled, ET-enhanced, NTSR1-targeted agents (Lu-NA-ET1-4), along with the structurally analogous Lu-3BP-227, currently in clinical trials, underwent a battery of in vitro assays using HT-29 xenograft colon cancer cells to examine their NTSR1 binding, internalization and efflux, inhibition, and adduct formation properties. The biodistribution profile of these constructs was studied in an HT-29 mouse model. Charge modification of the terminal carboxylic acid and arginine of the ETs had deleterious effects on inhibition kinetics and in vitro adduct formation. Contrastingly, deletion of the arginine resulted in a modest increase in inhibition kinetics. Incorporation of ETs into the NTSR1-targeted agents was well-tolerated with minimal impact on the in vivo NTSR1 targeting but resulted in increased renal uptake. This study demonstrates that the ETs can be successfully incorporated into antagonistic NTSR1-targeted constructs without compromising their adduct formation capabilities. Based on these results, further exploration of the endolysosomal trapping approach is warranted in NTSR1- and other receptor-targeted antagonistic constructs.
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http://dx.doi.org/10.1021/acs.bioconjchem.2c00214DOI Listing
July 2022

Evaluation of pediatric malignancies using total-body PET/CT with half-dose [F]-FDG.

Eur J Nucl Med Mol Imaging 2022 Jul 5. Epub 2022 Jul 5.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfengdong Road, Guangzhou, 510060, Guangdong, China.

Purpose: To explore the impact of a true half dose of [F]-FDG on image quality in pediatric oncological patients undergoing total-body PET/CT and investigate short acquisition times with half-dose injected activity.

Methods: One hundred pediatric oncological patients who underwent total-body PET/CT using the uEXPLORER scanner after receiving a true half dose of [F]-FDG (1.85 MBq/kg) were retrospectively enrolled. The PET images were first reconstructed using complete 600-s data and then split into 300-s, 180-s, 60-s, 40-s, and 20-s duration groups (G600 to G20). The subjective analysis was performed using 5-point Likert scales. Objective quantitative metrics included the maximum standard uptake value (SUV), SUV, standard deviation (SD), signal-to-noise ratio (SNR), and SNR of the background. The variabilities in lesion SUV, SUV, and tumor-to-background ratio (TBR) were also calculated.

Results: The overall image quality scores in the G600, G300, G180, and G60 groups were 4.9 ± 0.2, 4.9 ± 0.3, 4.4 ± 0.5, and 3.5 ± 0.5 points, respectively. All the lesions identified in the half-dose images were localized in the G60 images, while 56% of the lesions could be clearly identified in the G20 images. With reduced acquisition time, the SUV and SD of the backgrounds were gradually increased, while the TBR values showed no statistically significant differences among the groups (all p > 0.1). Using the half-dose images as a reference, the variability in the lesion SUV gradually increased from the G180 to G20 images, while the lesion SUV remained stable across all age groups. SNR was highly negatively correlated with age.

Conclusion: Total-body PET/CT with a half dose of [F]-FDG (1.85 MBq/kg, estimated whole-body effective dose: 1.76-2.57 mSv) achieved good performance in pediatric patients, with sufficient image quality and good lesion conspicuity. Sufficient image quality and lesion conspicuity could be maintained at a fast scanning time of 60 s with half-dose activity.
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http://dx.doi.org/10.1007/s00259-022-05893-8DOI Listing
July 2022

Development and validation of novel prognostic models based on RNA-binding proteins in breast cancer.

J Int Med Res 2022 Jun;50(6):3000605221106285

Department of Breast Cancer, Hubei Cancer Hospital; Tongji Medical College, Huazhong University of Science and Technology and Hubei Provincial Clinical Research Center for Breast Cancer, Wuhan, Hubei, China.

Objectives: We aimed to construct novel prognostic models based on RNA-binding proteins (RBPs) in breast cancer (BRCA) and explore their roles in this disease and their effects on tumor-infiltrating immune cells (TIICs).

Methods: Datasets were downloaded from the Gene Expression Omnibus (GEO) database. Functions and prognostic values of RBPs were systematically investigated using a series of bioinformatics analysis methods. TIICs were assessed using CIBERSORT.

Results: Overall, 138 differentially expressed RBPs were identified, of which 86 were upregulated and 52 were downregulated. Of these, 13 RBPs were identified as prognosis-related and adopted to construct an overall survival (OS) model, while 12 RBPs were used for the relapse-free survival (RFS) model. High-risk patients had poorer OS and RFS rates than low-risk patients. The results indicate that the OS and RFS models are good prognostic models with reliable predictive abilities. In addition, the proportions of CD8, CD4 naïve, and CD4 memory resting T cells, as well as resting dendritic cells, were significantly different between the low-risk and high-risk groups in the OS model.

Conclusions: OS and RFS signatures can be used as reliable BRCA prognostic biomarkers. This work will help understand the prognostic roles and functions of RBPs in BRCA.
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http://dx.doi.org/10.1177/03000605221106285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9252011PMC
June 2022

Simultaneous Presentation of Multiple Myeloma and Lung Cancer: Case Report and Gene Bioinformatics Analysis.

Front Oncol 2022 13;12:859735. Epub 2022 Jun 13.

Department of Hematology and Rheumatology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, China.

Patients diagnosed with more than one cancer generally develop the individual tumors sequentially. There are a few cases of co-occurring multiple myeloma and lung cancer reported in the literature. Here, we report two cases of co-occurring multiple myeloma and lung cancer in patients who presented with the chief complaint of pain. The diagnoses of multiple myeloma and lung cancer were supported by hematologic and biochemical investigations, as well as bone marrow and lung histopathologic examination. We provided suitable interventions for both two patients. The patients are still currently undergoing treatment and followed up closely. We first performed a bioinformatic analysis to determine commonly shared genes and pathways in the two types of cancer types. Fortunately, we identified the hub gene mitochondrial trans-2-enoyl-CoA reductase (MECR), which was overexpressed in both tumors. Survival analysis correlated higher MECR expression with poorer overall survival. Signaling pathway analysis suggested possible transduction pathways implicated in the co-occurrence of both tumors. The clinical cases combined with bioinformatic analysis may provide insight for the pathogenesis of synchronous tumors.
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http://dx.doi.org/10.3389/fonc.2022.859735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235397PMC
June 2022

Effects of rhythmic auditory stimulation on upper-limb movements in patients with Parkinson's disease.

Parkinsonism Relat Disord 2022 Jun 23;101:27-30. Epub 2022 Jun 23.

Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.

Introduction: Rhythmic auditory stimulation (RAS) is an effective technique extensively used to alleviate lower-limb bradykinesia in patients with Parkinson's disease (PD). However, RAS effects on upper-limb bradykinesia have not been well studied. This study investigated immediate effects of RAS on upper-limb movements in PD patients and healthy people.

Methods: PD patients (n = 23) and age- and gender-matched healthy controls (n = 23) executed left-hand, right-hand, and both-hand movement tasks of the Purdue Pegboard Test when listening to the beats of RAS, including 100%, 110%, and 120% of the baseline tempo, which was fastest movement performance of each participant without the aid of RAS. Sequence of RAS and tasks was randomized for each participant.

Results: PD patients had slower upper-limb movements than did health controls. An interaction was found between RAS and tasks. In both patients and controls and for all task conditions, 120%RAS induced higher scores than did 110% RAS, and the latter induced higher scores than did 100%RAS. In both patients and controls and for all RAS conditions, the right-hand condition induced higher scores than did the left-hand condition, and the latter induced higher scores than did the both-hand condition.

Conclusions: RAS was effective in regulating upper-limb movements in PD patients, which may be explained by rich neural connections between auditory and motor cortical areas in humans. Clinical practitioners should consider using RAS in clinical therapy. Future neuroimaging studies are needed to explore neural mechanisms of RAS in PD patients.
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http://dx.doi.org/10.1016/j.parkreldis.2022.06.020DOI Listing
June 2022

A prognostic risk model for ovarian cancer based on gene expression profiles from gene expression omnibus database.

Biochem Genet 2022 Jun 27. Epub 2022 Jun 27.

Department of Gynecology, Lanzhou University Second Hospital, No. 82 Cuiyingmen, Chengguan District, Lanzhou City, 730030, Gansu Province, China.

This study explored prognostic genes of ovarian cancer and built a prognostic model based on these genes to predict patient's survival, which is of great significance for improving treatment of ovarian cancer. GSE26712 dataset was downloaded from Gene Expression Omnibus database as training set, while OV-AU dataset was downloaded from ICGC website as validation set. All genes in GSE26712 were analyzed by univariate Cox regression, Lasso regression, and multivariate Cox regression analyses. Then prognosis-related feature genes were screened to construct a multivariate risk model. Meanwhile, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed on samples in the high/low-risk groups using Gene Set Enrichment Analysis (GSEA) software. Finally, survival curve and receiver operating characteristic curve were drawn to verify the validity of the model. Ten feature genes related to prognosis of ovarian cancer were obtained: CMTM6, COLGALT1, F2R, GPR39, IGFBP3, RNF121, MTMR9, ORAI2, SNAI2, ZBTB16. GSEA enrichment analysis showed that there were notable differences in biological pathways such as gap junctions and homologous recombination between the high/low-risk groups. Through further verification of training set and validation set, the 10-gene prognostic model was found to be effective for the prognosis of ovarian cancer patients. In this study, we constructed a 10-gene prognostic model which predicted the prognosis of ovarian cancer patients well by integrating clinical prognostic parameters. It may have certain reference value for subsequent clinical treatment research of ovarian cancer patients and help in clinical treatment decision-making.
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http://dx.doi.org/10.1007/s10528-022-10232-5DOI Listing
June 2022

AgRP neurons control feeding behaviour at cortical synapses via peripherally derived lysophospholipids.

Nat Metab 2022 06 27;4(6):683-692. Epub 2022 Jun 27.

Department of Molecular and Translational Neuroscience of Anatomy II, University of Cologne, Cologne, Germany.

Phospholipid levels are influenced by peripheral metabolism. Within the central nervous system, synaptic phospholipids regulate glutamatergic transmission and cortical excitability. Whether changes in peripheral metabolism affect brain lipid levels and cortical excitability remains unknown. Here, we show that levels of lysophosphatidic acid (LPA) species in the blood and cerebrospinal fluid are elevated after overnight fasting and lead to higher cortical excitability. LPA-related cortical excitability increases fasting-induced hyperphagia, and is decreased following inhibition of LPA synthesis. Mice expressing a human mutation (Prg-1) leading to higher synaptic lipid-mediated cortical excitability display increased fasting-induced hyperphagia. Accordingly, human subjects with this mutation have higher body mass index and prevalence of type 2 diabetes. We further show that the effects of LPA following fasting are under the control of hypothalamic agouti-related peptide (AgRP) neurons. Depletion of AgRP-expressing cells in adult mice decreases fasting-induced elevation of circulating LPAs, as well as cortical excitability, while blunting hyperphagia. These findings reveal a direct influence of circulating LPAs under the control of hypothalamic AgRP neurons on cortical excitability, unmasking an alternative non-neuronal route by which the hypothalamus can exert a robust impact on the cortex and thereby affect food intake.
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http://dx.doi.org/10.1038/s42255-022-00589-7DOI Listing
June 2022

Cerebrovascular intervention therapy worked positively in one patient with severe cerebral venous sinus thrombosis due to hyperthyroidism: a case report and review of the literature.

J Med Case Rep 2022 Jun 26;16(1):250. Epub 2022 Jun 26.

Department of Neurology, Shanghai Xuhui District Central Hospital, 966 Middle Huaihai Road, Xuhui District, Shanghai, China.

Background: With further understanding of cerebral venous sinus thrombosis, hyperthyroidism has gradually been revealed as a rare predisposing factor for cerebral venous sinus thrombosis, which may present as more compact clots and resistance to fibrinolysis, also known as a predictor of worse outcomes. For patients with severe cerebral venous sinus thrombosis, proper treatment method should be initiated as soon as possible since they may deteriorate rapidly.

Case Presentation: In this case report, we present a 32-year-old Mongoloid woman admitted with progressive headache, impaired consciousness, and right limb weakness, diagnosed with cerebral venous sinus thrombosis caused by hyperthyroidism. A cerebrovascular intervention with local thrombolytic infusion was performed at the site of thrombosis, followed by dilatation with balloon and thrombus aspiration in venous sinus, with partial recanalization observed and anticoagulation given as a next step. After cerebrovascular intervention, the patient's condition improved rapidly and she was discharged with her National Institute of Health Stroke Scale score being decreased from 17 to 2.

Conclusions: When patients with hyperthyroidism suffer from headache, progressive disturbance of consciousness, seizures, and other symptoms, the presence of cerebral venous sinus thrombosis should be considered and corresponding examinations should be performed as soon as possible. For patients with severe cerebral venous sinus thrombosis, cerebrovascular intervention might be a safe and effective approach if conventional management fails.
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http://dx.doi.org/10.1186/s13256-022-03463-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233794PMC
June 2022

Expert consensus on oncological [F]FDG total-body PET/CT imaging (version 1).

Eur Radiol 2022 Jun 25. Epub 2022 Jun 25.

Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.

Background: [F]FDG imaging on total-body PET/CT (TB PET/CT) scanners, with improved sensitivity, offers new potentials for cancer diagnosis, staging, and radiation treatment planning. This consensus provides the protocols for clinical practices with a goal of paving the way for future studies with the total-body scanners in oncological [F]FDG TB PET/CT imaging.

Methods: The consensus was summarized based on the published guidelines and peer-reviewed articles of TB PET/CT in the literature, along with the opinions of the experts from major research institutions with a total of 40,000 cases performed on the TB PET/CT scanners.

Results: This consensus describes the protocols for routine and dynamic [F]FDG TB PET/CT scanning focusing on the reduction of imaging acquisition time and FDG injected activity, which may serve as a reference for research and clinic oncological PET/CT studies.

Conclusion: This expert consensus focuses on the reduction of acquisition time and FDG injected activity with a TB PET/CT scanner, which may improve the patient throughput or reduce the radiation exposure in daily clinical oncologic imaging.

Key Points: • [F]FDG-imaging protocols for oncological total-body PET/CT with reduced acquisition time or with different FDG activity levels have been summarized from multicenter studies. • Total-body PET/CT provides better image quality and improved diagnostic insights. • Clinical workflow and patient management have been improved.
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http://dx.doi.org/10.1007/s00330-022-08960-8DOI Listing
June 2022
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