Publications by authors named "Jingwen Zhang"

337 Publications

Identifying the Weaker Function Links in the Hazardous Chemicals Road Transportation System in China.

Int J Environ Res Public Health 2021 Jul 1;18(13). Epub 2021 Jul 1.

Public Administration and Humanities College, Dalian Maritime University, Dalian 116026, China.

Safety of the hazardous chemicals road transportation system (HCRTS) is an important, complex, social, and environmental sensitive problem. The complexity, dynamics, and multi-link features of HCRTS have made it necessary to think beyond traditional risk analysis methods. Based on the relevant literature, Functional Resonance Analysis Method (FRAM) is a relatively new systemic method for modeling and analyzing complex socio-technical systems. In this study, a methodology that integrates FRAM, fuzzy sets, and risk matrix is presented to quantitatively assess the risks factors representing failure function links in HCRTS. As the strength of function links can be illustrated by the RI (risk index) of risk factors identified in failure function links, 32 risk factors representing 12 failure function links were first identified by accident causes analysis and the framework of FRAM. Fuzzy sets were then utilized to calculate the weight of the likelihood and consequence of the risk factors. Finally, according to the assessment results of the identified risk factors by a two-dimensional risk matrix, the weaker function links in the whole HCRTS chain were identified. HCs road companies, regulatory authorities, relevant practitioners, and other stakeholders should pay more attention to these links.
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http://dx.doi.org/10.3390/ijerph18137039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297264PMC
July 2021

Solitary Fibrous Tumors of the Chest: An Analysis of Fifty Patients.

Front Oncol 2021 1;11:697156. Epub 2021 Jul 1.

Department of Geriatric Respiratory and Sleep, Henan Institute of Respiratory Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: A solitary fibrous tumor of the chest (SFTC) is a subtype of solitary fibrous tumor (SFT) with a low incidence rate. The purpose of this study is to analyze the diagnosis and treatment of SFTC and the difference between benign and malignant solitary fibrous tumor of the pleura (SFTP) to improve the understanding of this rare disease.

Methods: A retrospective analysis of fifty patients with SFTC (33 cases in the pleura and 17 in the lung) was performed. Clinical and imaging characteristics, pathological features, and treatment follow-up outcomes were analyzed.

Results: The common symptoms of the 50 patients included a cough, expectoration, chest tightness, fever, and chest pain. Space occupying lesions were found plain computed tomography (CT) and enhanced CT was used for enhancement of the tumors. It was also found that 18 cases had necrosis, and 5 cases had calcification. The histopathology results showed that frequent nuclear division, obvious morphological variation, necrosis, and the high expression of Ki-67 cells are markers of malignant SFTC. There were significant differences in age, chest tightness, necrotic foci in CT, and expression of Ki-67 between the benign and malignant SFTP cases. All the patients who received treatment were given an excellent prognosis.

Conclusion: A combination of enhanced CT, histopathology, and immunohistochemistry can be used for the accurate diagnosis of SFTC. Advanced age, chest tightness, necrotic foci in CT, and a high Ki-67 index were more likely to be malignant SFTP. Operation and radiofrequency ablation can provide favorable outcomes for both benign and malignant SFTC.
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http://dx.doi.org/10.3389/fonc.2021.697156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280784PMC
July 2021

Enhancing the thermoelectric properties of SnTe introducing [email protected] core-shell nanostructures.

Dalton Trans 2021 Jul 14. Epub 2021 Jul 14.

School of Materials Science and Engineering, Hefei University of Technology, Hefei 230009, China.

SnTe is an emerging IV-VI metal chalcogenide, but its low Seebeck coefficient and high thermal conductivity mainly originating from the high hole concentration limit its thermoelectric performance. In this work, an amorphous carbon core-shell-coated PbTe nanostructure prepared by a "bottom-up" method is first incorporated into the Sn1-ySbyTe matrix to enhance the thermoelectric performance of SnTe. The square-like PbTe nanoparticles maintain their original cubic morphology and do not grow up obviously after the SPS process due to the coating of the C layer, bringing about the formation of nanopores locally, while Sb alloying induces Sb point defects and Sb-rich precipitates. All these unique hierarchical microstructures finally lead to an ultralow lattice thermal conductivity (∼0.48 W-1 m-1 K-1) approaching amorphous limits (∼0.40 W-1 m-1 K-1). In addition, the incorporation of [email protected] core-shell nanostructures decreases the carrier mobility obviously with a slight loss in carrier concentration, resulting in the deterioration of electrical properties to a certain extent. As a result, a peak thermoelectric figure of merit (ZT) of 1.07 is achieved for Sn0.89Sb0.11Te-5%[email protected] at 873 K, which is approximately 154.76% higher than that of pristine SnTe. This work provides a new strategy to enhance the thermoelectric performance of SnTe and also offers a new insight into other related thermoelectric systems.
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http://dx.doi.org/10.1039/d1dt01725jDOI Listing
July 2021

Fully redundant auxiliary system for gyrotron-based terahertz sources in long-term operation.

Rev Sci Instrum 2021 May;92(5):054711

Huazhong University of Science and Technology, Wuhan 430074, Hubei, China.

The Wuhan National High Magnetic Field Center is incorporating the flat-top pulsed magnetic field (FTPMF) into pulse gyrotrons. It will be the first chance to make a pulse-magnet gyrotron available for generating a long-pulse radiation of 100 ms or above without affecting its high operating frequency and high radiation power. However, unlike continuous wave gyrotrons, pulse gyrotrons in long-term operation have their own challenges, namely, misalignment caused by concussions, much stronger low-frequency electromagnetic interference from the pulse magnet, and inevitable explosion. This article will focus on the difficulties faced by pulse gyrotrons in years of operation, discuss the protection and restoration from failures, and, consequently, propose a fully redundant, explosion-proof, and quickly recoverable auxiliary system for long-term operation of pulse gyrotrons. This system integrates the control unit of traditional pulsed magnets and superconducting magnets so that it can be compatible with any form of gyrotron facilities. Therefore, once the FTPMF or the superconducting magnet is available, the long-pulse radiation will be obtained. Several experimental results, including the most recent explosion, show the reliability of the proposed system.
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http://dx.doi.org/10.1063/5.0050044DOI Listing
May 2021

Alterations in mitochondrial dynamics with age-related Sirtuin1/Sirtuin3 deficiency impair cardiomyocyte contractility.

Aging Cell 2021 Jul 3;20(7):e13419. Epub 2021 Jul 3.

Department of Surgery, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.

Sirtuin1 (SIRT1) and Sirtuin3 (SIRT3) protects cardiac function against ischemia/reperfusion (I/R) injury. Mitochondria are critical in response to myocardial I/R injury as disturbance of mitochondrial dynamics contributes to cardiac dysfunction. It is hypothesized that SIRT1 and SIRT3 are critical components to maintaining mitochondria homeostasis especially mitochondrial dynamics to exert cardioprotective actions under I/R stress. The results demonstrated that deficiency of SIRT1 and SIRT3 in aged (24-26 months) mice hearts led to the exacerbated cardiac dysfunction in terms of cardiac systolic dysfunction, cardiomyocytes contractile defection, and abnormal cardiomyocyte calcium flux during I/R stress. Moreover, the deletion of SIRT1 or SIRT3 in young (4-6 months) mice hearts impair cardiomyocyte contractility and shows aging-like cardiac dysfunction upon I/R stress, indicating the crucial role of SIRT1 and SIRT3 in protecting myocardial contractility from I/R injury. The biochemical and seahorse analysis showed that the deficiency of SIRT1/SIRT3 leads to the inactivation of AMPK and alterations in mitochondrial oxidative phosphorylation (OXPHOS) that causes impaired mitochondrial respiration in response to I/R stress. Furthermore, the remodeling of the mitochondria network goes together with hypoxic stress, and mitochondria undergo the processes of fusion with the increasing elongated branches during hypoxia. The transmission electron microscope data showed that cardiac SIRT1/SIRT3 deficiency in aging alters mitochondrial morphology characterized by the impairment of mitochondria fusion under I/R stress. Thus, the age-related deficiency of SIRT1/SIRT3 in the heart affects mitochondrial dynamics and respiration function that resulting in the impaired contractile function of cardiomyocytes in response to I/R.
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http://dx.doi.org/10.1111/acel.13419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282250PMC
July 2021

A Methodology for Dynamic Assessment of Laboratory Safety by SEM-SD.

Int J Environ Res Public Health 2021 06 17;18(12). Epub 2021 Jun 17.

School of Public Administration and Humanities, Dalian Maritime University, Dalian 116026, China.

Lab safety problems have become an impeding factor that cannot be ignored in normal teaching and scientific research activities at colleges and universities. As the risk factors of lab accidents can be conceptualized as occurring at multiple levels, systematically improving and optimizing lab safety is the crucial route to accident prevention in labs. In this paper, a novel method that integrates a structural equation model (SEM) and system dynamics (SD) is presented to dynamically assess lab safety with the characteristics of insufficient data and uncertainty. On the basis of a questionnaire investigation, the SEM was utilized to determine the influencing factors on lab safety and acquire the path coefficients among these factors, which were embedded into the SD model as the weight of the influencing factors. An illustration was carried out to test and validate the proposed method, and a sensitivity analysis was also conducted to recognize variables contributing the most to the improvement of lab safety. The results demonstrated that the safety input of human and management subsystems is the most effective to improve the lab safety; meanwhile, "safety awareness", "emergency ability", "operation skills", "safety culture" and "safety training" are the top five contributing factors, which can promote lab safety in the shortest time.
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http://dx.doi.org/10.3390/ijerph18126545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296441PMC
June 2021

Is Associated With Glioma Malignancy and Serves as a Potential Immunotherapy Biomarker.

Front Oncol 2021 10;11:665360. Epub 2021 Jun 10.

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.

, an interferon (IFN)-inducible gene, plays a promotional role in many tumors. However, its function in glioma remains unknown. In this study, bioinformatic analysis (TCGA, CGGA, Rembrandt) illustrated the upregulation and prognostic value of in gliomas. Immunohistochemical staining of clinical samples (n = 49) validated the DDX60 expression is higher in gliomas than in normal tissue (n = 20, < 0.0001). It also could be included in nomogram as a parameter to predict the 3- and 5-year survival risk (C-index = 0.86). The biological process of in glioma was mainly enriched in the inflammatory and immune response by GSEA and GO analysis. expression had a positive association with most inflammatory-related functions, such as hematopoietic cell kinase (HCK) (R = 0.31), interferon (R = 0.72), STAT1 (R = 54), and a negative correlation with IgG (R = -0.24). Furthermore, expression tends to be positively related to multiple infiltrating immune cells, while negatively related to CD56 dim nature killer cell in glioma. Some important immune checkpoints, like , , , , and , were all positively related with (all Pearson correlation R > 0.26). The expression and correlation between DDX60, EGF, and PD-L1 were confirmed by western blot in clinical samples (n = 14, < 0.0001) and GBM cells. These results indicated that might have important clinical significance in glioma and could serve as a potential immune therapeutic target.
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http://dx.doi.org/10.3389/fonc.2021.665360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222729PMC
June 2021

Recent advancements of nanomaterial-based therapeutic strategies toward sepsis: bacterial eradication, anti-inflammation, and immunomodulation.

Nanoscale 2021 Jun;13(24):10726-10747

Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, Ocean University of China, China.

Sepsis is a life threatening disease that is caused by a dysregulated host immune response to infection, resulting in tissue damage and organ dysfunction, which account for a high in-hospital mortality (approximately 20%). However, there are still no effective and specific therapeutics for clinical sepsis management. Nanomaterial-based strategies have emerged as promising tools for improving the therapeutic efficacy of sepsis by combating lethal bacterial infection, modulating systemic inflammatory response, preventing multiple organ failure, etc. This review has comprehensively summarized the recent advancements in nanomaterial-based strategies for the management of sepsis and severe complications, in which those nanosystems act either as inherent therapeutics or as nanocarriers for the precise delivery of agents. These formulations mechanically possess antibacterial, anti-inflammatory, immunomodulatory, and anti-oxidative effects, achieving multifunctional synergistic treatment efficacy against sepsis. Furthermore, several cell membrane-derived biomimetic nanoplatforms have been used as decoys to trap and neutralize the pathogenic toxins. The critical role of other adjuvant therapies in sepsis management, including the combination of nanotechnology and stem cell therapy, is also highlighted. Overall, this review provides insights into innovative nanotechnology-based strategies applied in sepsis treatment.
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http://dx.doi.org/10.1039/d1nr02706aDOI Listing
June 2021

Patient Demographics and Clinic Type Are Associated With Patient Engagement Within a Remote Monitoring Program.

Telemed J E Health 2021 Jun 11. Epub 2021 Jun 11.

Center for Health Disparities Research, Medical University of South Carolina, Charleston, South Carolina, USA.

Remote physiological monitoring (RPM) is accessible, convenient, relatively inexpensive, and can improve clinical outcomes. Yet, it is unclear in which clinical setting or target population RPM is maximally effective. To determine whether patients' demographic characteristics or clinical settings are associated with data transmission and engagement. This is a prospective cohort study of adults enrolled in a diabetes RPM program for a minimum of 12 months as of April 2020. We developed a multivariable logistic regression model for engagement with age, gender, race, income, and primary care clinic type as variables and a second model to include first-order interactions for all demographic variables by time. The participants included 549 adults (mean age 53 years, 63% female, 54% Black, and 75% very low income) with baseline hemoglobin A1c ≥8.0% and enrolled in a statewide diabetes RPM program. The main measure was the transmission engagement over time, where engagement is defined as a minimum of three distinct days per week in which remote data are transmitted. Significant predictors of transmission engagement included increasing age, academic clinic type, higher annual household income, and shorter time-in-program ( < 0.001 for each). Self-identified race and gender were not significantly associated with transmission engagement ( = 0.729 and 0.237, respectively). RPM appears to be an accessible tool for minority racial groups and for the aging population, yet engagement is impacted by primary care location setting and socioeconomic status. These results should inform implementation of future RPM studies, guide advocacy efforts, and highlight the need to focus efforts on maintaining engagement over time.
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http://dx.doi.org/10.1089/tmj.2020.0535DOI Listing
June 2021

Damage to the blood‑brain barrier and activation of neuroinflammation by focal cerebral ischemia under hyperglycemic condition.

Int J Mol Med 2021 07 3;48(1). Epub 2021 Jun 3.

Department of Pathology, School of Basic Medical Science, Ningxia Medical University, Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of National Key Laboratory, Yinchuan, Ningxia 750004, P.R. China.

Hyperglycemia aggravates brain damage caused by cerebral ischemia/reperfusion (I/R) and increases the permeability of the blood‑brain barrier (BBB). However, there are relatively few studies on morphological changes of the BBB. The present study aimed to investigate the effect of hyperglycemia on BBB morphological changes following cerebral I/R injury. Streptozotocin‑induced hyperglycemic and citrate‑buffered saline‑injected normoglycemic rats were subjected to 30 min middle cerebral artery occlusion. Neurological deficits were evaluated. Brain infarct volume was assessed by 2,3,5‑triphenyltetrazolium chloride staining and BBB integrity was evaluated by Evans blue and IgG extravasation following 24 h reperfusion. Changes in tight junctions (TJ) and basement membrane (BM) proteins (claudin, occludin and zonula occludens‑1) were examined using immunohistochemistry and western blotting. Astrocytes, microglial cells and neutrophils were labeled with specific antibodies for immunohistochemistry after 1, 3 and 7 days of reperfusion. Hyperglycemia increased extravasations of Evan's blue and IgG and aggravated damage to TJ and BM proteins following I/R injury. Furthermore, hyperglycemia suppressed astrocyte activation and damaged astrocytic endfeet surrounding cerebral blood vessels following I/R. Hyperglycemia inhibited microglia activation and proliferation and increased neutrophil infiltration in the brain. It was concluded that hyperglycemia‑induced BBB leakage following I/R might be caused by damage to TJ and BM proteins and astrocytic endfeet. Furthermore, suppression of microglial cells and increased neutrophil infiltration to the brain may contribute to the detrimental effects of pre‑ischemic hyperglycemia on the outcome of cerebral ischemic stroke.
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http://dx.doi.org/10.3892/ijmm.2021.4975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175066PMC
July 2021

The Inhibition of B7H3 by 2-HG Accumulation Is Associated With Downregulation of VEGFA in IDH Mutated Gliomas.

Front Cell Dev Biol 2021 17;9:670145. Epub 2021 May 17.

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.

B7H3 (also known as CD276) is a co-stimulator checkpoint protein of the cell surface B7 superfamily. Recently, the function beyond immune regulation of B7H3 has been widely studied. However, the expression preference and the regulation mechanism underlying B7H3 in different subtypes of gliomas is rarely understood. We show here that B7H3 expression is significantly decreased in IDH-mutated gliomas and in cultured IDH1-R132H glioma cells. Accumulation of 2-HG leads to a remarkable downregulation of B7H3 protein and the activity of IDH1-R132H mutant is responsible for B7H3 reduction in glioma cells. Inhibition of autophagy by inhibitors like leupeptin, chloroquine (CQ), and Bafilomycin A1 (Baf-A1) blocks the degradation of B7H3 in glioma cells. In the meantime, the autophagy flux is more active with higher LC3B-II and lower p62 in IDH1-R132H glioma cells than in IDH1-WT cells. Furthermore, sequence alignment analysis reveals potential LC3-interacting region (LIR) motifs "F-V-S/N-I/V" in B7H3. Moreover, B7H3 interacts with p62 and CQ treatment significantly enhances this interaction. Additionally, we find that is positively correlated with and by bioinformatics analysis in gliomas. B7H3 and VEGFA are decreased in IDH-mutated gliomas and further reduced in 2-HG gliomas compared to 2-HG glioma sections by IHC staining. Our study demonstrates that B7H3 is preferentially overexpressed in IDH wild-type gliomas and could serve as a potential theranostic target for the precise treatment of glioma patients with wild-type IDH.
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http://dx.doi.org/10.3389/fcell.2021.670145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165280PMC
May 2021

South African Fathers Involvement and Their Adolescents' Sexual Risk Behavior and Alcohol Consumption.

AIDS Behav 2021 Jun 2. Epub 2021 Jun 2.

College of Nursing and Health Professions, Drexel University, Philadelphia, PA, USA.

Although considerable research has examined the influence of parent-adolescent relationships on the sexual health of adolescents, there is a great need for research to understand the influence of fathers on their children's HIV sexual risk behavior, particularly in sub-Saharan Africa. We examined how the residence and the involvement of fathers are related to their children's HIV sexual risk and alcohol consumption behaviors. A cross-sectional survey was completed by 175 sixth-grade adolescents in the Eastern Cape Province, South Africa. Analyses showed that adolescents living with their fathers had fewer sexual partners (B = - 0.606, SE = 0.299, p = .043) and consumed alcohol less frequently (B = - 0.642, SE = 0.294, p = .029). Adolescents who spent more quality days with their fathers in the past 30 days had fewer sexual partners (B = - 0.103, SE = 0.039, p = .008) and had condomless sex less frequently (B = - 0.097, SE = 0.047, p = 0.041). It was also found that there were significant father-residence × child-gender interactions on sexual debut (B = 1.132, SE = 0.564, p = .045) and on frequency of condomless sex (B = - 2.140, SE = 0.924, p = .021). These interactions indicate that boys living with their fathers were less likely to have had vaginal intercourse than girls and that girls living with their fathers were less likely to have unprotected sex than boys. This study highlights the importance of South African fathers' roles in their adolescent children's HIV sexual risk and alcohol drinking behaviors and the need to promote father-child relationships for adolescent health. The results suggest that health programs aiming to reduce South African adolescents' HIV sexual risk behaviors and alcohol consumption consider strategies that target their fathers.
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http://dx.doi.org/10.1007/s10461-021-03323-8DOI Listing
June 2021

Effect of Cryptorchidism on the Histomorphometry, Proliferation, Apoptosis, and Autophagy in Boar Testes.

Animals (Basel) 2021 May 12;11(5). Epub 2021 May 12.

Institute of Animal Biotechnology, College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Jinzhong 030801, China.

Spontaneous unilateral cryptorchid boars have one testis in the abdomen or inguinal canal, causing its temperature to be at or near the body temperature, which impairs spermatogenesis, although the histomorphometry and molecular mechanisms underlying this process remain unclear. The aim of the present study was to determine the histomorphometry, proliferation, apoptosis, and autophagy alterations in spermatogonia and Sertoli cells in unilateral cryptorchid, scrotal (contrascrotal), and preweaning piglet (preweaning) testes. Histomorphometrical analysis of cryptorchid testes showed that the seminiferous tubules contained only Sertoli cells and a few spermatogonia, but did not contain post-meiotic germ cells. The number of spermatogonia markedly decreased, and the number of Sertoli cells did not change remarkably in cryptorchid testes. TUNEL assay results showed that apoptosis signals were predominantly observed in spermatogonia. In cryptorchid and contrascrotal testes, proliferating cell nuclear antigen (PCNA) and LC3 were located in spermatogonia. The number of PCNA-positive, TUNEL-positive, and LC3-positive germ cells was low, and the protein and mRNA levels of PCNA and LC3 were significantly decreased in cryptorchid testes. Taken together, the number of Sertoli cells did not change remarkably, whereas the number of germ cells decreased in the cryptorchid testes, compared with that in the contrascrotal testes. Insufficient proliferation, excessive apoptosis, and autophagy were involved in the regulation of the decrease in spermatogonia in cryptorchid boar testes.
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http://dx.doi.org/10.3390/ani11051379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152062PMC
May 2021

Comparison of different parathyroid autograft project after total parathyroidectomy in patients with secondary hyperparathyroidism.

Am J Otolaryngol 2021 May 19;42(6):103085. Epub 2021 May 19.

Department of Head and Neck Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No.145 Middle Shandong Road, Shanghai 200001, China. Electronic address:

Objective: To evaluate the feasibility and efficacy of total parathyroidectomy followed by modified needle-quantified injection of parathyroid autograft compared with classic incision and transplantation.

Methods: We conducted a retrospective study of 171 patients with secondary hyperparathyroidism treated by hemodialysis or peritoneal dialysis. These patients were included in our study from April 2006 to December 2016, who had undergone total parathyroidectomies with autotransplantation. Patients were divided into classic incision for transplantation of parathyroid autograft group and modified needle-quantified injection group. Clinical and biochemical characteristics, including preoperative and postoperative intact parathyroid hormone levels were recorded and compared between two group patients.

Results: To compare the techniques of modified needle-quantified injection and classic incision and transplantation, pre- and postoperative biochemistry and length of operation was recorded and analyzed. Preoperative biochemistry was similarly in both groups. However, autograft function achieved was significantly faster in the group with modified needle-quantified injection compared with classic incision and transplantation (P = 0.03). Median time to parathyroid function regain was 3 months for injection compared with 7 months for classic incision. There was no remarkable difference in the recurrence rates between the two groups.

Conclusion: The modified needle-quantified injection of parathyroid tissue is a feasible and simple alternative to the more commonly used method of classic incision and transplantation.
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http://dx.doi.org/10.1016/j.amjoto.2021.103085DOI Listing
May 2021

Sustained Release Systems for Delivery of Therapeutic Peptide/Protein.

Biomacromolecules 2021 06 6;22(6):2299-2324. Epub 2021 May 6.

Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, Ocean University of China, Qingdao 266100, China.

Peptide/protein therapeutics have been significantly applied in the clinical treatment of various diseases such as cancer, diabetes, . owing to their high biocompatibility, specificity, and therapeutic efficacy. However, due to their immunogenicity, instability stemming from its complex tertiary and quaternary structure, vulnerability to enzyme degradation, and rapid renal clearance, the clinical application of protein/peptide therapeutics is significantly confined. Though nanotechnology has been demonstrated to prevent enzyme degradation of the protein therapeutics and thus enhance the half-life, issues such as initial burst release and uncontrollable release kinetics are still unsolved. Moreover, the traditional administration method results in poor patient compliance, limiting the clinical application of protein/peptide therapeutics. Exploiting the sustained-release formulations for more controllable delivery of protein/peptide therapeutics to decrease the frequency of injection and enhance patient compliance is thus greatly meaningful. In this review, we comprehensively summarize the substantial advancements of protein/peptide sustained-release systems in the past decades. In addition, the advantages and disadvantages of all these sustained-release systems in clinical application together with their future challenges are also discussed in this review.
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http://dx.doi.org/10.1021/acs.biomac.1c00160DOI Listing
June 2021

Mutations in the sodium channel genes SCN1A, SCN3A, and SCN9A in children with epilepsy with febrile seizures plus(EFS+).

Seizure 2021 May 9;88:146-152. Epub 2021 Apr 9.

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, China; Department of Pediatrics, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, China. Electronic address:

Purpose: To explore disease-causing gene mutations of epilepsy with febrile seizures plus (EFS+) in Southern Chinese Han population.

Methods: Blood samples and clinical data were collected from 49 Southern Han Chinese patients with EFS+. Gene screening was performed using whole-exome sequencing and panel sequencing for 485 epilepsy-related genes. The pathogenicity of variants was evaluated based on ACMG scoring and assessment of clinical concordance.

Results: We identified 10 putatively causative sodium channel gene variants in 49 patients with EFS+, including 8 variants in SCN1A (R500Q appeared twice), one in SCN3A and one in SCN9A. All these missense mutations were inherited from maternal or paternal and were evaluated to be of uncertain significance according to ACMG. The clinical features of patients were in concordance with the EFS+ phenotype of the mutated SCN1A, SCN3A and SCN9A gene. The clinical phenotypes of 11 probands with these gene variants included febrile seizures plus (FS+, n=7), Dravet Syndrome (n=3), FS+ with focal seizures (n=1). Three probands with SCN1A variants (R500Q located in the non-voltage areas, or G1711D in the pore-forming domain) developed severe Dravet syndrome. The affected individuals with the other 6 SCN1A variants located outside the pore-forming domain showed mild phenotypes. Novel SCN3A variant ((D1688Y) and SCN9A variant (R185H) were identified in two probands respectively and both of the probands had FS+.

Conclusion: The SCN1A, SCN3A, and SCN9A gene mutations might be a pathogenic cause of EFS+ in Southern Chinese Han population.
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http://dx.doi.org/10.1016/j.seizure.2021.04.006DOI Listing
May 2021

Ferroportin 3 is a dual-targeted mitochondrial/chloroplast iron exporter necessary for iron homeostasis in Arabidopsis.

Plant J 2021 Apr 22. Epub 2021 Apr 22.

Department of Biology, Amherst College, Amherst, MA, 01002, USA.

Mitochondria and chloroplasts are organelles with high iron demand that are particularly susceptible to iron-induced oxidative stress. Despite the necessity of strict iron regulation in these organelles, much remains unknown about mitochondrial and chloroplast iron transport in plants. Here, we propose that Arabidopsis ferroportin 3 (FPN3) is an iron exporter that is dual-targeted to mitochondria and chloroplasts. FPN3 is expressed in shoots, regardless of iron conditions, but its transcripts accumulate under iron deficiency in roots. fpn3 mutants cannot grow as well as the wild type under iron-deficient conditions and their shoot iron levels are lower compared with the wild type. Analyses of iron homeostasis gene expression in fpn3 mutants and inductively coupled plasma mass spectrometry (ICP-MS) measurements show that iron levels in the mitochondria and chloroplasts are increased relative to the wild type, consistent with the proposed role of FPN3 as a mitochondrial/plastid iron exporter. In iron-deficient fpn3 mutants, abnormal mitochondrial ultrastructure was observed, whereas chloroplast ultrastructure was not affected, implying that FPN3 plays a critical role in the mitochondria. Overall, our study suggests that FPN3 is essential for optimal iron homeostasis.
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http://dx.doi.org/10.1111/tpj.15286DOI Listing
April 2021

CASB: a concanavalin A-based sample barcoding strategy for single-cell sequencing.

Mol Syst Biol 2021 04;17(4):e10060

Shenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.

Sample multiplexing facilitates single-cell sequencing by reducing costs, revealing subtle difference between similar samples, and identifying artifacts such as cell doublets. However, universal and cost-effective strategies are rather limited. Here, we reported a concanavalin A-based sample barcoding strategy (CASB), which could be followed by both single-cell mRNA and ATAC (assay for transposase-accessible chromatin) sequencing techniques. The method involves minimal sample processing, thereby preserving intact transcriptomic or epigenomic patterns. We demonstrated its high labeling efficiency, high accuracy in assigning cells/nuclei to samples regardless of cell type and genetic background, and high sensitivity in detecting doublets by three applications: 1) CASB followed by scRNA-seq to track the transcriptomic dynamics of a cancer cell line perturbed by multiple drugs, which revealed compound-specific heterogeneous response; 2) CASB together with both snATAC-seq and scRNA-seq to illustrate the IFN-γ-mediated dynamic changes on epigenome and transcriptome profile, which identified the transcription factor underlying heterogeneous IFN-γ response; and 3) combinatorial indexing by CASB, which demonstrated its high scalability.
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http://dx.doi.org/10.15252/msb.202010060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022202PMC
April 2021

Academic detailing increases prescription drug monitoring program use among primary care practices.

J Am Pharm Assoc (2003) 2021 Jul-Aug;61(4):418-424.e2. Epub 2021 Mar 3.

Objective: Clinical review of a prescription drug monitoring program (PDMP) is considered a valuable tool for opioid prescribing risk mitigation; however, PDMP use is often low, even in states with mandatory registration and use policies. The objective was to evaluate the impact of an academic detailing (AD) outreach intervention on PDMP use among primary care prescribers.

Methods: AD intervention was delivered to primary care based controlled substance prescribers (N = 87) and their associated PDMP delegates (n = 42) by a clinical pharmacist as 1 component of a large-scale, statewide initiative to improve opioid prescribing safety. Prescriber PDMP use behavior was assessed by prescriber self-report and analysis of objective 2016-2018 PDMP data regarding the number of monthly report requests. We compared means between pre- and postintervention using a paired t test and plotted the monthly average reports over time to assess the trend of mean reports over time. Generalized linear mixed model with a negative binomial distribution was used to assess the difference in the trend and magnitude of the combined count of reports for the entire sample and prescriber subsets that were segmented on the basis of the adoption status of PDMP.

Results: The monthly mean of reports by combined prescribers and delegates significantly increased after the AD intervention (mean 28.1 pre vs. 53.0 post; P < 0.001), with the increase in delegate reports (mean 17.1 pre vs. 60.0 post; P < 0.001) driving the overall increase. Reports were requested 40.4 times more often than in the preintervention period (P < 0.001). Patterns of pre- to postchanges in mean monthly report requests differed by baseline PDMP adoption status.

Conclusion: The AD intervention was transformative in facilitating practice change to use delegates to run reports. Visits with both prescribers and delegates, including hands-on PDMP training and registration assistance, can be viewed as beneficial for practice facilitation.
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http://dx.doi.org/10.1016/j.japh.2021.02.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273068PMC
March 2021

Corrigendum to "Effects of alternate-day fasting, time-restricted fasting and intermittent energy restriction DSS-induced on colitis and behavioral disorders" [Redox Biology 32, 2020, 101535].

Redox Biol 2021 Aug 31;44:101955. Epub 2021 Mar 31.

Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaan Xi, China; Department of Food Science, Cornell University, Ithaca, NY, 14853, United States. Electronic address:

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http://dx.doi.org/10.1016/j.redox.2021.101955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212148PMC
August 2021

Blocking DNA Damage Repair May Be Involved in Stattic (STAT3 Inhibitor)-Induced FLT3-ITD AML Cell Apoptosis.

Front Cell Dev Biol 2021 16;9:637064. Epub 2021 Mar 16.

Department of Hematology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

The FMS-like tyrosine kinase 3 (FLT3)- internal tandem duplication (ITD) mutation can be found in approximately 25% of all acute myeloid leukemia (AML) cases and is associated with a poor prognosis. The main treatment for FLT3-ITD-positive AML patients includes genotoxic therapy and FLT3 inhibitors, which are rarely curative. Inhibiting STAT3 activity can improve the sensitivity of solid tumor cells to radiotherapy and chemotherapy. This study aimed to explore whether Stattic (a STAT3 inhibitor) affects FLT3-ITD AML cells and the underlying mechanism. Stattic can inhibit the proliferation, promote apoptosis, arrest cell cycle at G0/G1, and suppress DNA damage repair in MV4-11cells. During the process, through mRNA sequencing, we found that DNA damage repair-related mRNA are also altered during the process. In summary, the mechanism by which Stattic induces apoptosis in MV4-11cells may involve blocking DNA damage repair machineries.
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http://dx.doi.org/10.3389/fcell.2021.637064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007876PMC
March 2021

Using Deep Neural Network to Diagnose Thyroid Nodules on Ultrasound in Patients With Hashimoto's Thyroiditis.

Front Oncol 2021 16;11:614172. Epub 2021 Mar 16.

Department of Ultrasound Diagnosis, Ruijin Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China.

Objective: The aim of this study is to develop a model using Deep Neural Network (DNN) to diagnose thyroid nodules in patients with Hashimoto's Thyroiditis.

Methods: In this retrospective study, we included 2,932 patients with thyroid nodules who underwent thyroid ultrasonogram in our hospital from January 2017 to August 2019. 80% of them were included as training set and 20% as test set. Nodules suspected for malignancy underwent FNA or surgery for pathological results. Two DNN models were trained to diagnose thyroid nodules, and we chose the one with better performance. The features of nodules as well as parenchyma around nodules will be learned by the model to achieve better performance under diffused parenchyma. 10-fold cross-validation and an independent test set were used to evaluate the performance of the algorithm. The performance of the model was compared with that of the three groups of radiologists with clinical experience of <5 years, 5-10 years, >10 years respectively.

Results: In total, 9,127 images were collected from 2,932 patients with 7,301 images for the training set and 1,806 for the test set. 56% of the patients enrolled had Hashimoto's Thyroiditis. The model achieved an AUC of 0.924 for distinguishing malignant and benign nodules in the test set. It showed similar performance under diffused thyroid parenchyma and normal parenchyma with sensitivity of 0.881 0.871 (p = 0.938) and specificity of 0.846 0.822 (p = 0.178). In patients with HT, the model achieved an AUC of 0.924 to differentiate malignant and benign nodules which was significantly higher than that of the three groups of radiologists (AUC = 0.824, 0.857, 0.863 respectively, p < 0.05).

Conclusion: The model showed high performance in diagnosing thyroid nodules under both normal and diffused parenchyma. In patients with Hashimoto's Thyroiditis, the model showed a better performance compared to radiologists with various years of experience.
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http://dx.doi.org/10.3389/fonc.2021.614172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008116PMC
March 2021

Advanced liver fibrosis and the metabolic syndrome in a primary care setting.

Diabetes Metab Res Rev 2021 Mar 23. Epub 2021 Mar 23.

Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.

Aims: The fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) are noninvasive and accessible methods for assessing advanced liver fibrosis risk in primary care. We evaluated the distribution of FIB-4 and NFS scores in primary care patients with clinical signals for nonalcoholic fatty liver disease (NAFLD).

Materials And Methods: This retrospective cohort study of electronic record data between 2007 and 2018 included adults with at least one abnormal aminotransferase and no known (non-NAFLD) liver disease. We calculated patient-level FIB-4 and NFS scores, the proportion of patients with mean values exceeding advanced fibrosis thresholds (indeterminate risk: FIB-4 > 1.3, NFS > -1.455; high-risk: FIB-4 > 2.67, NFS > 0.676), and the proportion of patients with a NAFLD International Classification of Diseases-9/10 code. Logistic regression models evaluated the associations of metabolic syndrome (MetS) components with elevated FIB-4 and NFS scores.

Results: The cohort included 6506 patients with a median of 6 (interquartile range: 3-13) FIB-4 and NFS scores per patient. Of these patients, 81% had at least two components of MetS, 29% had mean FIB-4 and NFS scores for indeterminate fibrosis risk, and 11% had either mean FIB-4 or NFS scores exceeding the high advanced fibrosis risk thresholds. Regression models identified associations of low high-density lipoprotein, hyperglycemia, Black race and male gender with high-risk FIB-4 and NFS values. Only 5% of patients had existing diagnoses for NAFLD identified.

Conclusions: Many primary care patients have FIB-4 and NFS scores concerning for advanced fibrosis, but rarely a diagnosis of NAFLD. Elevated FIB-4 and NFS scores may provide signals for further clinical evaluation of liver disease in primary care settings.
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http://dx.doi.org/10.1002/dmrr.3452DOI Listing
March 2021

Chemical characteristics and source apportionment of PM in a petrochemical city: Implications for primary and secondary carbonaceous component.

J Environ Sci (China) 2021 May 5;103:322-335. Epub 2020 Dec 5.

State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry, Institute of Atmospheric Physics, Chinese Academy of Science, Beijing 100029, China; Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Science, Xiamen 361021, China; University of Chinese Academy of Science, Beijing 100049, China.

To study the pollution features and underlying mechanism of PM in Luoyang, a typical developing urban site in the central plain of China, 303 PM samples were collected from April 16 to December 29, 2015 to analyze the elements, water soluble inorganic ions, organic carbon and elemental carbon. The annual mean concentration of PM was 142.3 μg/m, and 75% of the daily PM concentrations exceeded the 75 μg/m. The secondary inorganic ions, organic matter and mineral dust were the most abundant species, accounting for 39.6%, 19.2% and 9.3% of the total mass concentration, respectively. But the major chemical components showed clear seasonal dependence. SO was most abundant specie in spring and summer, which related to intensive photochemical reaction under high O concentration. In contrast, the secondary organic carbon and ammonium while primary organic carbon and ammonium significantly contributed to haze formation in autumn and winter, respectively. This indicated that the collaboration effect of secondary inorganic aerosols and carbonaceous matters result in heavy haze in autumn and winter. Six main sources were identified by positive matrix factorization model: industrial emission, combustion sources, traffic emission, mineral dust, oil combustion and secondary sulfate, with the annual contribution of 24%, 20%, 24%, 4%, 5% and 23%, respectively. The potential source contribution function analysis pointed that the contribution of the local and short-range regional transportation had significant impact. This result highlighted that local primary carbonaceous and precursor of secondary carbonaceous mitigation would be key to reduce PM and O during heavy haze episodes in winter and autumn.
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http://dx.doi.org/10.1016/j.jes.2020.11.012DOI Listing
May 2021

Predicting Outcomes in Patients Undergoing Pancreatectomy Using Wearable Technology and Machine Learning: Prospective Cohort Study.

J Med Internet Res 2021 Mar 18;23(3):e23595. Epub 2021 Mar 18.

Washington University in St Louis, St Louis, MO, United States.

Background: Pancreatic cancer is the third leading cause of cancer-related deaths, and although pancreatectomy is currently the only curative treatment, it is associated with significant morbidity.

Objective: The objective of this study was to evaluate the utility of wearable telemonitoring technologies to predict treatment outcomes using patient activity metrics and machine learning.

Methods: In this prospective, single-center, single-cohort study, patients scheduled for pancreatectomy were provided with a wearable telemonitoring device to be worn prior to surgery. Patient clinical data were collected and all patients were evaluated using the American College of Surgeons National Surgical Quality Improvement Program surgical risk calculator (ACS-NSQIP SRC). Machine learning models were developed to predict whether patients would have a textbook outcome and compared with the ACS-NSQIP SRC using area under the receiver operating characteristic (AUROC) curves.

Results: Between February 2019 and February 2020, 48 patients completed the study. Patient activity metrics were collected over an average of 27.8 days before surgery. Patients took an average of 4162.1 (SD 4052.6) steps per day and had an average heart rate of 75.6 (SD 14.8) beats per minute. Twenty-eight (58%) patients had a textbook outcome after pancreatectomy. The group of 20 (42%) patients who did not have a textbook outcome included 14 patients with severe complications and 11 patients requiring readmission. The ACS-NSQIP SRC had an AUROC curve of 0.6333 to predict failure to achieve a textbook outcome, while our model combining patient clinical characteristics and patient activity data achieved the highest performance with an AUROC curve of 0.7875.

Conclusions: Machine learning models outperformed ACS-NSQIP SRC estimates in predicting textbook outcomes after pancreatectomy. The highest performance was observed when machine learning models incorporated patient clinical characteristics and activity metrics.
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http://dx.doi.org/10.2196/23595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074869PMC
March 2021

Systematic review and meta-analysis of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators tested for antinociceptive effects in animal models of injury-related or pathological persistent pain.

Pain 2021 Jul;162(Suppl 1):S26-S44

Molecular Neuropharmacology and Genetics Laboratory, Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Abstract: We report a systematic review and meta-analysis of studies that assessed the antinociceptive efficacy of cannabinoids, cannabis-based medicines, and endocannabinoid system modulators on pain-associated behavioural outcomes in animal models of pathological or injury-related persistent pain. In April 2019, we systematically searched 3 online databases and used crowd science and machine learning to identify studies for inclusion. We calculated a standardised mean difference effect size for each comparison and performed a random-effects meta-analysis. We assessed the impact of study design characteristics and reporting of mitigations to reduce the risk of bias. We meta-analysed 374 studies in which 171 interventions were assessed for antinociceptive efficacy in rodent models of pathological or injury-related pain. Most experiments were conducted in male animals (86%). Antinociceptive efficacy was most frequently measured by attenuation of hypersensitivity to evoked limb withdrawal. Selective cannabinoid type 1, cannabinoid type 2, nonselective cannabinoid receptor agonists (including delta-9-tetrahydrocannabinol) and peroxisome proliferator-activated receptor-alpha agonists (predominantly palmitoylethanolamide) significantly attenuated pain-associated behaviours in a broad range of inflammatory and neuropathic pain models. Fatty acid amide hydrolase inhibitors, monoacylglycerol lipase inhibitors, and cannabidiol significantly attenuated pain-associated behaviours in neuropathic pain models but yielded mixed results in inflammatory pain models. The reporting of criteria to reduce the risk of bias was low; therefore, the studies have an unclear risk of bias. The value of future studies could be enhanced by improving the reporting of methodological criteria, the clinical relevance of the models, and behavioural assessments. Notwithstanding, the evidence supports the hypothesis of cannabinoid-induced analgesia.
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http://dx.doi.org/10.1097/j.pain.0000000000002269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216112PMC
July 2021

Effect of a church-based intervention on abstinence communication among African-American caregiver-child dyads: the role of gender of caregiver and child.

Health Educ Res 2021 04;36(2):224-238

Drexel University, College of Nursing and Health Professions, 1601 Cherry Street, Philadelphia, PA 19102, USA.

Parent-child sexual-health communication is critical. Religious involvement is important in many African-American families, but can be a barrier to sexual-health communication. We tested a theory-based, culturally tailored intervention to increase sexual-abstinence communication among church-attending African-American parent-child dyads. In a randomized controlled trial, 613 parent-child dyads were randomly assigned to one of three 3-session interventions: (i) faith-based abstinence-only; (ii) non-faith-based abstinence-only; or (iii) attention-matched health-promotion control. Data were collected pre- and post-intervention, and 3-, 6-, 12- and 18-months post-intervention. Generalized-estimating-equations Poisson-regression models revealed no differences in communication by intervention arm. However, three-way condition � sex-of-child � sex-of-parent interactions on children's reports of parent-child communication about puberty [IRR=0.065, 95% CI: (0.010, 0.414)], menstruation or wet dreams [IRR=0.103, 95% CI: (0.013, 0.825)] and dating [IRR=0.102, 95% CI: (0.016, 0.668)] indicated that the non-faith-based abstinence intervention's effect on increasing communication was greater with daughters than with sons, when the parent was the father. This study highlights the importance of considering parent and child gender in the efficacy of parent-child interventions and the need to tailor interventions to increase fathers' comfort with communication.
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http://dx.doi.org/10.1093/her/cyab009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041458PMC
April 2021

Clinical and CT features of ovarian torsion in infants, children and adolescents.

Int J Gynaecol Obstet 2021 Feb 23. Epub 2021 Feb 23.

Department of Radiology, Qilu Hospital of Shandong University, Jinan, China.

Objective: To investigate the clinical features and computed tomography (CT) findings of pediatric ovarian torsion.

Methods: A retrospective analysis of the clinical and CT data of 61 newborns, infants, children, and adolescents with ovarian torsion confirmed by histopathology was performed.

Results: Clinical features included abdominal mass, abdominal pain, nausea and vomiting, and fever. The tumor marker α-fetoprotein was increased in five cases. Ovarian enlargement was found in 26 cases, and follicles were detected in the peripheral region of the ovary in 21 cases. Twenty-one cases presented as solid mixed-density masses on CT images. A total of 30 cases of ovarian torsion were associated with a benign ovarian mass. Among 27 cases of cystic or predominantly cystic masses, the mass had a thickened wall in 26 cases and showed an uneven density in 23 cases. Among all 61 patients, a torsed pedicle was detected in 47 cases. A torsed ovary or mass exhibited mild contrast enhancement in seven cases. Uterine deviation toward the involved side, blurred fat space around lesions, and pelvic free fluid were also found.

Conclusion: Pediatric ovarian torsion presents a relatively characteristic CT appearance. Correct diagnosis can be established based on clinical and imaging features.
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http://dx.doi.org/10.1002/ijgo.13657DOI Listing
February 2021

Study on Defective T Junction-Mediated Strand Displacement Amplification and Its Application in Microchip Electrophoretic Detection of Longer Bacterial 16S rDNA.

Anal Chem 2021 02 11;93(7):3551-3558. Epub 2021 Feb 11.

School of Chemistry and Molecular Engineering, East China Normal University, 500 Dongchuan Road, Shanghai 200241, P. R. China.

Current strand displacement amplification (SDA)-based nucleic acid sensing methods generally rely on a ssDNA template that involves complementary bases to the endonuclease recognition sequence, which has the limitation of detecting only short nucleic acids. Herein, a new SDA method in which the defective T junction structure is first used to support SDA (dT-SDA) was proposed and applied in longer DNA detection. In dT-SDA, an auxiliary probe and a primer were designed to specifically identify the target gene, following the formation of a stable defective T junction structure through proximity hybridization, and the formation of defective T junctions could further trigger cascade SDA cycling to produce numerous ssDNA products. The quantity of these ssDNA products was detected through microchip electrophoresis (MCE) and could be transformed to the concentration of the target gene. Moreover, the applicability of this developed strategy in detecting long genomic DNA was verified by detecting bacterial 16S rDNA. This proposed dT-SDA strategy consumes less time and has satisfactory sensitivity, which has great potential for effective bacterial screening and infection diagnosis.
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http://dx.doi.org/10.1021/acs.analchem.0c04991DOI Listing
February 2021

Outdoor pollen-related changes in lung function and markers of airway inflammation: A systematic review and meta-analysis.

Clin Exp Allergy 2021 May 18;51(5):636-653. Epub 2021 Feb 18.

Allergy and Lung Health Unit, Melbourne School of Population and Global Health, The University of Melbourne, Carlton, VIC, Australia.

Background: Experimental challenge studies have shown that pollen can have early and delayed effects on the lungs and airways. Here, we qualitatively and quantitatively synthesize the evidence of outdoor pollen exposure on various lung function and airway inflammation markers in community-based studies.

Methods: Four online databases were searched: Medline, Web of Science, CINAHL and Google Scholar. The search strategy included terms relating to both exposure and outcomes. Inclusion criteria were human-based studies published in English that were representative of the community. Additionally, we only considered cross-sectional or short-term longitudinal studies which investigated pollen exposure by levels or season. Study quality assessment was performed using the Newcastle-Ottawa scale. Meta-analysis was conducted using random-effects models.

Results: We included 27 of 6551 studies identified from the search. Qualitative synthesis indicated associations between pollen exposure and predominantly type-2 inflammation in both the upper and lower airways, but little evidence for lung function changes. People with ever asthma and/or seasonal allergic rhinitis (SAR) were at higher risk of such airway inflammation. Meta-analysis confirmed a positive relationship between pollen season, eosinophilia and eosinophil cationic protein (ECP) in people with ever SAR but the results between studies were highly variable. Heterogeneity was reduced after further subgrouping by age, and the forest plots indicated that eosinophilic airway inflammation to outdoor pollen exposure increased with age.

Conclusion: Among people with ever asthma and ever SAR, exposure to increased ambient pollen triggers type-2 upper and lower airway inflammation rather than a non-specific or innate inflammation. These findings can lead to the formulation of specific pollen immunotherapy for susceptible individuals. Future research should be directed towards investigating lagged associations and effect modifications using larger and more generalized populations.

Systematic Review Registration: CRD42020146981 (PROSPERO).
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http://dx.doi.org/10.1111/cea.13842DOI Listing
May 2021