Publications by authors named "Jing Xiao"

761 Publications

Automated bone mineral density prediction and fracture risk assessment using plain radiographs via deep learning.

Nat Commun 2021 Sep 16;12(1):5472. Epub 2021 Sep 16.

Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.

Dual-energy X-ray absorptiometry (DXA) is underutilized to measure bone mineral density (BMD) and evaluate fracture risk. We present an automated tool to identify fractures, predict BMD, and evaluate fracture risk using plain radiographs. The tool performance is evaluated on 5164 and 18175 patients with pelvis/lumbar spine radiographs and Hologic DXA. The model is well calibrated with minimal bias in the hip (slope = 0.982, calibration-in-the-large = -0.003) and the lumbar spine BMD (slope = 0.978, calibration-in-the-large = 0.003). The area under the precision-recall curve and accuracy are 0.89 and 91.7% for hip osteoporosis, 0.89 and 86.2% for spine osteoporosis, 0.83 and 95.0% for high 10-year major fracture risk, and 0.96 and 90.0% for high hip fracture risk. The tool classifies 5206 (84.8%) patients with 95% positive or negative predictive value for osteoporosis, compared to 3008 DXA conducted at the same study period. This automated tool may help identify high-risk patients for osteoporosis.
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http://dx.doi.org/10.1038/s41467-021-25779-xDOI Listing
September 2021

The added value of an artificial intelligence system in assisting radiologists on indeterminate BI-RADS 0 mammograms.

Eur Radiol 2021 Sep 15. Epub 2021 Sep 15.

Department of Radiology, Shenzhen People's Hospital, Shenzhen, 518020, Guangdong, China.

Objectives: To investigate the value of an artificial intelligence (AI) system in assisting radiologists to improve the assessment accuracy of BI-RADS 0 cases in mammograms.

Methods: We included 34,654 consecutive digital mammography studies, collected between January 2011 and January 2019, among which, 1088 cases from 1010 unique patients with initial BI-RADS 0 assessment who were recalled during 2 years of follow-up were used in this study. Two mid-level radiologists retrospectively re-assessed these BI-RADS 0 cases with the assistance of an AI system developed by us previously. In addition, four entry-level radiologists were split into two groups to cross-read 80 cases with and without the AI. Diagnostic performance was evaluated using the follow-up diagnosis or biopsy results as the reference standard.

Results: Of the 1088 cases, 626 were actually normal (BI-RADS 1 and no recall required). Assisted by the AI system, 351 (56%) and 362 (58%) normal cases were correctly identified by the two mid-level radiologists hence can be avoided for unnecessary follow-ups. However, they would have missed 12 (10 invasive cancers and 2 ductal carcinoma in situ cancers) and 6 (invasive cancers) malignant lesions respectively as a result. These missed lesions were not highly malignant tumors. The inter-rater reliability of entry-level radiologists increased from 0.20 to 0.30 (p < 0.005) by introducing the AI.

Conclusion: The AI system can effectively assist mid-level radiologists in reducing unnecessary follow-ups of mammographically indeterminate breast lesions and reducing the benign biopsy rate without missing highly malignant tumors.

Key Points: • The artificial intelligence system could assist mid-level radiologists in effectively reducing unnecessary BI-RADS 0 mammogram recalls and the benign biopsy rate without missing highly malignant tumors. • The artificial intelligence system was capable of detecting low suspicion lesions from heterogeneously and extremely dense breasts that radiologists tended to miss. • The use of an artificial intelligence system may improve the inter-rater reliability and sensitivity, and reduce the reading time of entry-level radiologists in assessing potential lesions in BI-RADS 0 mammograms.
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http://dx.doi.org/10.1007/s00330-021-08275-0DOI Listing
September 2021

Development and validation of a discrimination model between primary PLA2R-negative membranous nephropathy and minimal change disease confirmed by renal biopsy.

Sci Rep 2021 Sep 10;11(1):18064. Epub 2021 Sep 10.

Department of Nephrology, The First Affiliated Hospital, Zhengzhou University, No. 1, East Jianshe Road, Zhengzhou, 450052, Henan, People's Republic of China.

Membranous nephropathy (MN) and minimal change disease (MCD) are two common causes leading to nephrotic syndrome (NS). They have similar clinical features but different treatment strategies and prognoses. M-type phospholipase A2 receptor (PLA2R) is considered as a specific marker of membranous nephropathy. However, its sensitivity is only about 70%. Therefore, there is a lack of effective and noninvasive tools to distinguish PLA2R-negative MN and MCD patients without renal biopsy. A total 949 patients who were pathologically diagnosed as idiopathic MN or MCD were enrolled in this study, including 805 idiopathic MN and 144 MCD. Based on the basic information and laboratory examination of 200 PLA2R-negative MN and 144 MCD, we used a univariate and multivariate logistic regression to select the relevant variables and develop a discrimination model. A novel model including age, albumin, urea, high density lipoprotein, C3 levels and red blood cell count was established for PLA2R-negative MN and MCD. The discrimination model has great differential capability (with an AUC of 0.904 in training group and an AUC of 0.886 in test group) and calibration capability. When testing in all 949 patients, our model also showed good discrimination ability for all idiopathic MN and MCD.
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http://dx.doi.org/10.1038/s41598-021-97517-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433159PMC
September 2021

Ultrasound-Guided Thermal Ablation of Bethesda IV Thyroid Nodules: A Pilot Study.

Front Endocrinol (Lausanne) 2021 24;12:674970. Epub 2021 Aug 24.

School of Medicine, Nankai University, Tianjin, China.

Objective: The purpose of our study was to evaluate the effectiveness of thermal ablation (TA) for Bethesda IV thyroid nodules, and to compare TA and surgery in terms of treatment outcomes, complications, and costs.

Method: This study was approved by the local ethics committee. From January 2017 to December 2019, 30 patients elected TA and 31 patients elected surgery for treatment of Bethesda IV thyroid nodules. Demographics information and conventional ultrasound before treatment for each patient was obtained. For the TA group, the ablation extent was 3 mm beyond the edge of the tumor to prevent marginal residual and recurrence. Patients were followed up at 1, 3, and 6 months after intervention, and every 6 months thereafter. Postoperative complications, operation time, hospitalization time, blood loss, and incision length were recorded.

Results: In the TA group, the volume reduction ratio (VRR) was 94.63 ± 8.99% (range:76%-100%) at the final follow-up. The mean follow-up time was 16.4 ± 5.2months (range:12-24 months). No recurrences, no metastatic lymph node, and no distant metastases were detected during follow-up. The TA group had fewer complications, shorter operation time, smaller incision length, less blood loss, shorter hospitalization time, and lower treatment costs compared to the surgery group (all <0.001).

Conclusions: TA is technically feasible for the complete destruction of Bethesda IV thyroid nodules, and also safe and effective during the follow-up period, with high VRR and low complication rates, especially in patients who were ineligible for or refused surgery.
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http://dx.doi.org/10.3389/fendo.2021.674970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421723PMC
August 2021

[Value of Ultrasound-guided Core-needle Biopsy for Evaluating the Performance of Radiofrequency Ablation for Low-risk Papillary Thyroid Microcarcinoma].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2021 Aug;43(4):584-589

Department of Ultrasound,The First Medical Center,Chinese PLA General Hospital,Beijing 100853,China.

Objective To investigate the clinical value of core-needle biopsy(CNB)for low-risk papillary thyroid microcarcinoma(PTMC)after radiofrequency ablation(RFA). Methods A total of 190 patients(including 142 females and 48 males,20-74 years old)with unifocal low-risk PTMCs[mean volume of(106.29±96.15)mm]treated by RFA from June 2016 to September 2018 were evaluated in this study.During the RFA procedure,enlarged ablation was performed.Patients were followed up 1,3,6,12 months after RFA and every 6 months thereafter.The volume of ablation area and the volume reduction ratio(VRR)were calculated.To evaluate the ablation performance,CNB was performed to the central zone,the peripheral zone,and surrounding thyroid parenchyma 3 or 6 months after RFA. Results The mean follow-up time was(30.04±12.41)months.The mean volume of tumor significantly decreased from(106.29±96.15)mm to(1.47±8.00)mm.Two ablated tumors were diagnosed to have residue by CNB and underwent additional RFA.No recurrence,metastatic lymph nodes,or distal metastasis were found during the follow-up.All the patients were tolerable to RFA and CNB procedure. Conclusion CNB can be used to evaluate the ablation performance after RFA for low-risk PTMC.
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http://dx.doi.org/10.3881/j.issn.1000-503X.13277DOI Listing
August 2021

MommiNet-v2: Mammographic multi-view mass identification networks.

Med Image Anal 2021 Aug 2;73:102204. Epub 2021 Aug 2.

Department of Radiology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University), Shenzhen, Guangdong 518020, China.

Many existing approaches for mammogram analysis are based on single view. Some recent DNN-based multi-view approaches can perform either bilateral or ipsilateral analysis, while in practice, radiologists use both to achieve the best clinical outcome. MommiNet is the first DNN-based tri-view mass identification approach, which can simultaneously perform bilateral and ipsilateral analysis of mammographic images, and in turn, can fully emulate the radiologists' reading practice. In this paper, we present MommiNet-v2, with improved network architecture and performance. Novel high-resolution network (HRNet)-based architectures are proposed to learn the symmetry and geometry constraints, to fully aggregate the information from all views for accurate mass detection. A multi-task learning scheme is adopted to incorporate both Breast Imaging-Reporting and Data System (BI-RADS) and biopsy information to train a mass malignancy classification network. Extensive experiments have been conducted on the public DDSM (Digital Database for Screening Mammography) dataset and our in-house dataset, and state-of-the-art results have been achieved in terms of mass detection accuracy. Satisfactory mass malignancy classification result has also been obtained on our in-house dataset.
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http://dx.doi.org/10.1016/j.media.2021.102204DOI Listing
August 2021

Health-adjusted life expectancy (HALE) in Chongqing, China, 2017: An artificial intelligence and big data method estimating the burden of disease at city level.

Lancet Reg Health West Pac 2021 Apr 2;9:100110. Epub 2021 Mar 2.

Ping An Technology (Shenzhen) Co., Ltd., Ping'an International Financial Center, Futian District, Shenzhen 518001, China.

Background: A universally applicable approach that provides standard HALE measurements for different regions has yet to be developed because of the difficulties of health information collection. In this study, we developed a natural language processing (NLP) based HALE estimation approach by using individual-level electronic medical records (EMRs), which made it possible to calculate HALE timely in different temporal or spatial granularities.

Methods: We performed diagnostic concept extraction and normalisation on 13•99 million EMRs with NLP to estimate the prevalence of 254 diseases in WHO Global Burden of Disease Study (GBD). Then, we calculated HALE in Chongqing, 2017, by using the life table technique and Sullivan's method, and analysed the contribution of diseases to the expected years "lost" due to disability (DLE).

Findings: Our method identified a life expectancy at birth (LE) of 77•9 years and health-adjusted life expectancy at birth (HALE) of 71•7 years for the general Chongqing population of 2017. In particular, the male LE and HALE were 76•3 years and 68•9 years, respectively, while the female LE and HALE were 80•0 years and 74•4 years, respectively. Cerebrovascular diseases, cancers, and injuries were the top three deterioration factors, which reduced HALE by 2•67, 2•15, and 1•19 years, respectively.

Interpretation: The results demonstrated the feasibility and effectiveness of EMRs-based HALE estimation. Moreover, the method allowed for a potentially transferable framework that facilitated a more convenient comparison of cross-sectional and longitudinal studies on HALE between regions. In summary, this study provided insightful solutions to the global ageing and health problems that the world is facing.

Funding: National Key R and D Program of China (2018YFC2000400).
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http://dx.doi.org/10.1016/j.lanwpc.2021.100110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315391PMC
April 2021

Backbone Effects on the Thermoelectric Properties of Ultra-Small Bandgap Conjugated Polymers.

Polymers (Basel) 2021 Jul 28;13(15). Epub 2021 Jul 28.

School of Chemistry, Sun Yat-sen University, Guangzhou 510275, China.

Conjugated polymers with narrower bandgaps usually induce higher carrier mobility, which is vital for the improved thermoelectric performance of polymeric materials. Herein, two indacenodithiophene (IDT) based donor-acceptor (D-A) conjugated polymers (PIDT-BBT and PIDTT-BBT) were designed and synthesized, both of which exhibited low-bandgaps. PIDTT-BBT showed a more planar backbone and carrier mobility that was two orders of magnitude higher (2.74 × 10 cmVs) than that of PIDT-BBT (4.52 × 10 cmVs). Both exhibited excellent thermoelectric performance after doping with 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane, where PIDTT-BBT exhibited a larger conductivity (0.181 S cm) and a higher power factor (1.861 μW m K) due to its higher carrier mobility. The maximum power factor of PIDTT-BBT reached 4.04 μW m K at 382 K. It is believed that conjugated polymers with a low bandgap are promising in the field of organic thermoelectric materials.
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http://dx.doi.org/10.3390/polym13152486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8347066PMC
July 2021

Biallelic -Variants Leading to Developmental Regression With Progressive Spasticity and Brain Atrophy in a Chinese Patient.

Front Genet 2021 12;12:685035. Epub 2021 Jul 12.

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

Objective: The cytochrome c oxidase assembly factor 7 ( gene encodes a protein localized to mitochondria that is involved in the assembly of mitochondrial respiratory chain complex IV. Here, we report the clinical, genetic and biochemical analysis of a female patient with suspected mitochondrial disorder and novel variants in , that presented with a considerably different phenotype and age of onset than the five patients reported to date.

Methods: We performed trio-exome sequencing in the affected patient and both parents. To verify the pathogenicity of the detected variants in , mitochondrial enzyme activities and oxygen consumption rate were investigated in fibroblasts of the patient and her parents.

Results: A Chinese girl was referred at 9 months of age with a history of developmental delay and regression since 3 months of age. In the following months, she lost previously acquired skills and developed progressive spasticity of the lower extremities. Trio-exome sequencing revealed compound heterzygous variants in (c.511G > A/p.Ala171Thr and c.566A > G/p.Asn189Ser). Functional validation experiments revealed isolated complex IV deficiency and a significantly reduced mitochondrial respiration rate in patient-derived fibroblasts.

Interpretation: Hitherto, characteristic features of patients were described as slowly progressing neuropathy and spinocerebellar ataxia, starting at the toddler age and progressing into adulthood. In contrast, our patient was reported to show developmental delay from 3 months of age, which was found to be due to a rapidly progressive encephalopathy and brain atrophy seen at 9 months of age. Unexpectedly, the genetic investigation revealed a associated mitochondrial disease, which was confirmed functionally. Thus, this report broadens the genetic and clinical spectrum of this heterogeneous mitochondriopathy and highlights the value of the presented unbiased approach.
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http://dx.doi.org/10.3389/fgene.2021.685035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312223PMC
July 2021

Brahma-related gene-1 promotes tubular senescence and renal fibrosis through Wnt/β-catenin/autophagy axis.

Clin Sci (Lond) 2021 Aug;135(15):1873-1895

Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.

Although accelerated cellular senescence is closely related to the progression of chronic kidney disease (CKD) and renal fibrosis, the underlying mechanisms remain largely unknown. Here, we reported that tubular aberrant expression of Brahma-related gene 1 (BRG1), an enzymatic subunit of the SWItch/Sucrose Non-Fermentable complex, is critically involved in tubular senescence and renal fibrosis. BRG1 was significantly up-regulated in the kidneys, predominantly in tubular epithelial cells, of both CKD patients and unilateral ureteral obstruction (UUO) mice. In vivo, shRNA-mediated knockdown of BRG1 significantly ameliorated renal fibrosis, improved tubular senescence, and inhibited UUO-induced activation of Wnt/β-catenin pathway. In mouse renal tubular epithelial cells (mTECs) and primary renal tubular cells, inhibition of BRG1 diminished transforming growth factor-β1 (TGF-β1)-induced cellular senescence and fibrotic responses. Correspondingly, ectopic expression of BRG1 in mTECs or normal kidneys increased p16INK4a, p19ARF, and p21 expression and senescence-associated β-galactosidase (SA-β-gal) activity, indicating accelerated tubular senescence. Additionally, BRG1-mediated pro-fibrotic responses were largely abolished by small interfering RNA (siRNA)-mediated p16INK4a silencing in vitro or continuous senolytic treatment with ABT-263 in vivo. Moreover, BRG1 activated the Wnt/β-catenin pathway, which further inhibited autophagy. Pharmacologic inhibition of the Wnt/β-catenin pathway (ICG-001) or rapamycin (RAPA)-mediated activation of autophagy effectively blocked BRG1-induced tubular senescence and fibrotic responses, while bafilomycin A1 (Baf A1)-mediated inhibition of autophagy abolished the effects of ICG-001. Further, BRG1 altered the secretome of senescent tubular cells, which promoted proliferation and activation of fibroblasts. Taken together, our results indicate that BRG1 induces tubular senescence by inhibiting autophagy via the Wnt/β-catenin pathway, which ultimately contributes to the development of renal fibrosis.
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http://dx.doi.org/10.1042/CS20210447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358963PMC
August 2021

MicroRNA-31-3p/RhoA signaling in the dorsal hippocampus modulates methamphetamine-induced conditioned place preference in mice.

Psychopharmacology (Berl) 2021 Jul 27. Epub 2021 Jul 27.

Institute of Forensic Injury, Institute of Forensic Bio-Evidence, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, Xi'an, People's Republic of China.

Rationale: MicroRNAs (miRNAs) regulate neuroplasticity-related proteins and are implicated in methamphetamine (METH) addiction. RhoA is a small Rho GTPase that regulates synaptic plasticity and addictive behaviors. Nevertheless, the functional relationship between RhoA and upstream miRNAs of METH addiction remains unclear.

Objective: To explore the molecular biology and epigenetic mechanisms of the miR-31-3p/RhoA pathway in METH addiction.

Methods: RhoA protein and its potential upstream regulator, miR-31-3p, were detected. A dual luciferase reporter was employed to determine whether RhoA constituted a specific target of miR-31-3p. Following adeno-associated virus (AAV)-mediated knockdown or overexpression of miR-31-3p or RhoA in the dorsal hippocampus (dHIP), mice were subjected to conditioned place preference (CPP) to investigate the effects of miR-31-3p and RhoA on METH-induced addictive behaviors.

Results: RhoA protein was significantly decreased in the dHIP of CPP mice with a concomitant increase in miR-31-3p. RhoA was identified as a direct target of miR-31-3p. Knockdown of miR-31-3p in the dHIP was associated with increased RhoA protein and attenuation of METH-induced CPP. Conversely, overexpression of miR-31-3p was associated with decreased RhoA protein and enhancement of METH effects. Similarly, knockdown of RhoA in the dHIP enhanced METH-induced CPP, whereas RhoA overexpression attenuated the effects of METH. Parallel experiments using sucrose preference revealed that the effects of miR-31-3p/RhoA pathway modulation were specific to METH.

Conclusions: Our findings indicate that the miR-31-3p/RhoA pathway in the dHIP modulates METH-induced CPP in mice. Our results highlight the potential role of epigenetics represented by non-coding RNAs in the treatment of METH addiction.
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http://dx.doi.org/10.1007/s00213-021-05936-2DOI Listing
July 2021

Ultrasound-guided radiofrequency ablation for the treatment of primary hyperparathyroidism: An efficacy and safety study.

Endocr Pract 2021 Jul 23. Epub 2021 Jul 23.

School of Medicine, Nankai University, No. 94 Weijin Road, Nankai District, Tianjin 300071, China; Department of Ultrasound, the First Medical Center of Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, China. Electronic address:

Objective: To evaluate the efficacy and safety of radiofrequency ablation (RFA) for the treatment of primary hyperparathyroidism (pHPT).

Methods: 25 patients who were treated with RFA for pHPT from September 2015 to January 2020 were enrolled in our study. The serum intact parathyroid hormone (iPTH), calcium and phosphate levels were tested within 1 week before RFA and at 1 day, 1 month, 3months, 6months and 12months after ablation. The ablation areas were evaluated by US at 1, 3, 6 and 12 months after RFA. Postoperative complications including voice hoarseness, hematoma, postoperative pain, incision infections, hypoparathyroidism and hypocalcemia were recorded.

Results: A total of 25 pHPT patients (53.9 ± 10.9 years, 22 women and 3 men) with 29 enlarged parathyroid glands were treated by RFA. 22 of them were treated in one session and the other three were treated in two sessions. Serum iPTH and calcium levels decreased significantly at 1 day after RFA (all P < 0.05). 21 patients had normal levels of serum iPTH and calcium after RFA, with a cure rate of 84%. 26 treated parathyroid glands exhibited a volume reduction rate greater than 70% at the 12 months follow-up. There were only some minor complications, including four postoperative pain (4/25, 16%) and one mild postoperative transient hypocalcemia (1/25, 4%).

Conclusions: US-guided RFA is an effective and safe technique for the treatment of carefully selected patients with pHPT. Larger sample size and longer follow-up are still need to further confirm its clinical value.
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http://dx.doi.org/10.1016/j.eprac.2021.07.012DOI Listing
July 2021

DeepPrognosis: Preoperative prediction of pancreatic cancer survival and surgical margin via comprehensive understanding of dynamic contrast-enhanced CT imaging and tumor-vascular contact parsing.

Med Image Anal 2021 Jun 29;73:102150. Epub 2021 Jun 29.

PAII Inc., Bethesda, MD 20817, USA.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and carries a dismal prognosis of ∼10% in five year survival rate. Surgery remains the best option of a potential cure for patients who are evaluated to be eligible for initial resection of PDAC. However, outcomes vary significantly even among the resected patients who were the same cancer stage and received similar treatments. Accurate quantitative preoperative prediction of primary resectable PDACs for personalized cancer treatment is thus highly desired. Nevertheless, there are a very few automated methods yet to fully exploit the contrast-enhanced computed tomography (CE-CT) imaging for PDAC prognosis assessment. CE-CT plays a critical role in PDAC staging and resectability evaluation. In this work, we propose a novel deep neural network model for the survival prediction of primary resectable PDAC patients, named as 3D Contrast-Enhanced Convolutional Long Short-Term Memory network (CE-ConvLSTM), which can derive the tumor attenuation signatures or patterns from patient CE-CT imaging studies. Tumor-vascular relationships, which might indicate the resection margin status, have also been proven to hold strong relationships with the overall survival of PDAC patients. To capture such relationships, we propose a self-learning approach for automated pancreas and peripancreatic anatomy segmentation without requiring any annotations on our PDAC datasets. We then employ a multi-task convolutional neural network (CNN) to accomplish both tasks of survival outcome and margin prediction where the network benefits from learning the resection margin related image features to improve the survival prediction. Our presented framework can improve overall survival prediction performances compared with existing state-of-the-art survival analysis approaches. The new staging biomarker integrating both the proposed risk signature and margin prediction has evidently added values to be combined with the current clinical staging system.
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http://dx.doi.org/10.1016/j.media.2021.102150DOI Listing
June 2021

Celecoxib-induced drug fever: A rare case report and literature review.

J Clin Pharm Ther 2021 Jul 20. Epub 2021 Jul 20.

Department of Pharmacy, The Third Xiangya Hospital of Central South University, Changsha, China.

What Is Known And Objective: Drug fever is frequently misdiagnosed, especially during concurrent infection. Celecoxib causes various adverse effects; however, celecoxib-induced drug fever is rarely reported.

Case Summary: A 32-year-old man presented with pyrexia after 17 days of celecoxib therapy, which was reintroduced following 3-day total drug cessation. His fever recurred after this unsuspected rechallenge, which aided in the ultimate identification of the offending drug. A Naranjo Score of 8 led us to infer that drug fever was "probably" caused by celecoxib.

What Is New And Conclusion: This is the first report of celecoxib-induced drug fever, aimed at assisting its diagnosis, particularly with rarely suspected causative drugs.
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http://dx.doi.org/10.1111/jcpt.13490DOI Listing
July 2021

Comparison of Untargeted Metabolomic Profiling vs Traditional Metabolic Screening to Identify Inborn Errors of Metabolism.

JAMA Netw Open 2021 Jul 1;4(7):e2114155. Epub 2021 Jul 1.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.

Importance: Recent advances in newborn screening (NBS) have improved the diagnosis of inborn errors of metabolism (IEMs); however, many potentially treatable IEMs are not included on NBS panels, nor are they covered in standard, first-line biochemical testing.

Objective: To examine the utility of untargeted metabolomics as a primary screening tool for IEMs by comparing the diagnostic rate of clinical metabolomics with the recommended traditional metabolic screening approach.

Design, Setting, And Participants: This cross-sectional study compares data from 4464 clinical samples received from 1483 unrelated families referred for trio testing of plasma amino acids, plasma acylcarnitine profiling, and urine organic acids (June 2014 to October 2018) and 2000 consecutive plasma samples from 1807 unrelated families (July 2014 to February 2019) received for clinical metabolomic screening at a College of American Pathologists and Clinical Laboratory Improvement Amendments-certified biochemical genetics laboratory. Data analysis was performed from September 2019 to August 2020.

Exposures: Metabolic and molecular tests performed at a genetic testing reference laboratory in the US and available clinical information for each patient were assessed to determine diagnostic rate.

Main Outcomes And Measures: The diagnostic rate of traditional metabolic screening compared with clinical metabolomic profiling was assessed in the context of expanded NBS.

Results: Of 1483 cases screened by the traditional approach, 912 patients (61.5%) were male and 1465 (98.8%) were pediatric (mean [SD] age, 4.1 [6.0] years; range, 0-65 years). A total of 19 families were identified with IEMs, resulting in a 1.3% diagnostic rate. A total of 14 IEMs were detected, including 3 conditions not included in the Recommended Uniform Screening Panel for NBS. Of the 1807 unrelated families undergoing plasma metabolomic profiling, 1059 patients (58.6%) were male, and 1665 (92.1%) were pediatric (mean [SD] age, 8.1 [10.4] years; range, 0-80 years). Screening identified 128 unique cases with IEMs, giving an overall diagnostic rate of 7.1%. In total, 70 different metabolic conditions were identified, including 49 conditions not presently included on the Recommended Uniform Screening Panel for NBS.

Conclusions And Relevance: These findings suggest that untargeted metabolomics provided a 6-fold higher diagnostic yield compared with the conventional screening approach and identified a broader spectrum of IEMs. Notably, with the expansion of NBS programs, traditional metabolic testing approaches identify few disorders beyond those covered on the NBS. These data support the capability of clinical untargeted metabolomics in screening for IEMs and suggest that broader screening approaches should be considered in the initial evaluation for metabolic disorders.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.14155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276086PMC
July 2021

[Comparison of Quality of Life of Patients with Papillary Thyroid Microcarcinoma Treated by Different Modalities].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2021 Jun;43(3):328-337

Department of Ultrasound,the First Medical Center of Chinese PLA General Hospital,Beijing 100853,China.

Objective To compare the health-related quality of life(HRQoL)of patients with papillary thyroid microcarcinoma(PTMC)treated by different modalities. Methods The PTMC patients after treatment who came to our department for follow-up from October to December in 2019 were enrolled and assigned into three groups according to treatment modalities:radiofrequency ablation(RFA)group(=80), hemithyroidectomy(HT)group(=34), and total thyroidectomy(TT)group(=35).All patients completed three scales:short form 36-item health survey(SF-36), thyroid cancer-specific health-related quality of life questionnaire(THYCA-QoL), and fear of progression questionnaire-short form(FoP-Q-SF).Multivariate linear regression analysis was employed to adjust for confounders and the quality of life scores were compared among the three treatment modalities. Results In the SF-36, physical component summary(PCS)(=0.006, =0.033)and role-physical(RP)(=0.003, =0.001)scores of patients in the RFA and HT groups were significantly higher than those in the TT group, whereas PCS(=1.000)and RP(=1.000)showed no significant difference between the RFA group and the HT group.In addition, the mental component summary(MCS)score in RFA group was higher than that in TT group(=0.034).The THYCA-QoL demonstrated that the patients in TT group complained more about scar than the patients in HT(=0.003)and RFA(<0.001)groups, and the patients in the RFA group complained less about weight gain than those in the HT(=0.028)and TT(<0.001)groups.In the FoP-Q-SF, the scores of the quality of life of patients concerned about disease progression had no significant difference among the three groups(> 0.05).Conclusion Compared with traditional open surgery, ultrasound-guided RFA has unique advantages in improving patients' quality of life and can be used as an alternative to open surgery for PTMC.
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http://dx.doi.org/10.3881/j.issn.1000-503X.13334DOI Listing
June 2021

D1R/PP2A/p-CaMKIIα signaling in the caudate putamen is involved in acute methamphetamine-induced hyperlocomotion.

Neurosci Lett 2021 08 6;760:136102. Epub 2021 Jul 6.

College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, People's Republic of China; Institute of Forensic Injury, Institute of Forensic Bioevidence, Western China Science and Technology Innovation Harbor, Xi'an Jiaotong University, People's Republic of China. Electronic address:

Drug addiction is underscored by the transition from experimental use to dependent use of addictive drugs. Acute use of methamphetamine (METH) causes a range of clinical symptoms, including hyperlocomotion. Dopamine D1 receptor (D1R)-mediated negative regulation of phosphorylated calcium/calmodulin-dependent protein kinase IIα (p-CaMKIIα, threonine [Thr] 286) is involved in the acute effects induced by single METH administration. Protein phosphatase 2A (PP2A) is a potential bridge that links D1R and p-CaMKIIα (Thr 286) after acute METH administration. However, the mechanisms underlying hyperlocomotion induced by single METH administration remain unclear. In this study, SCH23390 (a D1R inhibitor) and LB100 (a PP2A inhibitor) were administered to examine the involvement of D1R and PP2A signaling in acute METH-induced hyperlocomotion in mice. The protein levels of methylated PP2A-C (m-PP2A-C, leucine [Leu] 309), phosphorylated PP2A-C (p-PP2A-C, tyrosine [Tyr] 307), PP2A-C, p-CaMKIIα (Thr 286), and CaMKIIα in the prefrontal cortex (PFc), nucleus accumbens (NAc), and caudate putamen (CPu) were measured. Administration of 0.5 mg/kg SCH23390 reversed the acute METH-induced increase in protein levels of m-PP2A-C (Leu 309) and the decrease in protein levels of p-PP2A-C (Tyr 307) in the CPu, but not in the PFC and NAc. Moreover, prior administration of 0.1 mg/kg LB100 attenuated hyperlocomotion induced by single METH administration and reversed the decrease in protein levels of p-CaMKII (Thr 286) in the PFC, NAc, and CPu. Collectively, these results indicate that the D1R/PP2A/p-CaMKIIα signaling cascade in the CPu may be involved in hyperlocomotion after a single administration of METH.
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http://dx.doi.org/10.1016/j.neulet.2021.136102DOI Listing
August 2021

[Knockdown of hexokinase 2 (HK2) inhibits breast cancer cell proliferation and reduces their resistance to fluorouracil].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Aug;37(8):722-727

University of Tibetan Medicine, Lasa 850000, China. *Corresponding author, E-mail:

Objective To investigate the effect of knocking down hexokinase 2 (HK2) on the proliferation and drug resistance of breast cancer cells and its mechanism. Methods The MDA-MB-231 breast cancer cells were transfected with the short hairpin RNA (shRNA) plasmid. The mRNA and protein levels of HK2 were detected by real-time quantitative PCR and Western blotting, respectively; MTT assay was used to detect the effect of HK2 on the proliferation and 5-fluorouraci (5-FU) resistance of breast cancer cells; Lactate assay and extracellular acidification rate (ECAR) were used to detect the effect of HK2 on the glycolysis of breast cancer cells. Results The breast cancer cell line with stable & low expression of HK2 was obtained, and the mRNA and protein levels of HK2 were significantly reduced. Knockdown of HK2 significantly inhibited the proliferation of breast cancer cells and enhanced the killing effect of 5-FU on them. Down regulation of HK2 significantly inhibited the lactate secretion and lowered the glycolysis baseline in breast cancer cells. Conclusion Knockdown of HK2 inhibits the proliferation of MDA-MB-231 breast cancer cells and reduce their resistance to 5-FU.
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August 2021

Spatiotemporal expression of Rap1 and Ras mediates the acquisition and reinstatement of methamphetamine-induced conditioned place preference in mice via extracellular signal-regulated kinase activation.

Neuroreport 2021 08;32(12):1035-1040

College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi.

Drug addiction is a chronic recurrent brain disease characterized by compulsive drug use and a high tendency to relapse. We previously reported that the Ras-extracellular signal-regulated kinase (ERK)-ΔFosB pathway in the caudate putamen (CPu) was involved in methamphetamine-induced behavioral sensitization. Rap1, as an antagonist of Ras originally, was found to participate in neuronal synaptic plasticity recently, but the role of Rap1 in methamphetamine addiction is unclear. First, in this study, we constructed the acquisition, extinction and reinstatement of methamphetamine-induced conditioned place preference (CPP) in mice, respectively. Then, protein levels of Rap1, Ras and pERK/ERK in the prefrontal cortex (PFc), CPu and hippocampus of CPP mice on three phases were detected. We found that protein levels of Rap1, Ras and pERK/ERK in the CPu were significantly increased after repeated methamphetamine administration, as well as Rap1 and pERK/ERK in the hippocampus. However, protein levels of Rap1 and pERK/ERK in the CPu were decreased on the reinstatement of CPP mice. Therefore, Rap1 and Ras in the CPu and Rap1 in the hippocampus may participate in the regulation of the acquisition of methamphetamine-induced CPP in mice by activating ERK. Moreover, Rap1-ERK cascade in the CPu contributes to both the acquisition and reinstatement of methamphetamine-induced CPP in mice.
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http://dx.doi.org/10.1097/WNR.0000000000001686DOI Listing
August 2021

Ni(OH) Templated Synthesis of Ultrathin Ni S Nanosheets as Bifunctional Electrocatalyst for Overall Water Splitting.

Small 2021 Aug 6;17(33):e2102097. Epub 2021 Jul 6.

School of Materials Science and Engineering, Beihang University, Beijing, 100191, P. R. China.

Ultrathin nickel (Ni)-based sulfide nanosheets have been reported as excellent electrocatalysts for overall water splitting; however, the uncontrollability over thickness due to the nonlayered structure still hampers its practical application. Herein, a simple topochemical conversion strategy is employed to synthesize cobalt-doped Ni S (Co-Ni S ) ultrathin nanosheets on Ni foam. The Co-Ni S nanosheets are controlled synthesized by using Co-Ni(OH) ultrathin nanosheets as templates with anneal and sulfurization treatment, showing exceptional electrocatalytic activity. This template-assisted method can also be applied to obtain Ni, NiO, and NiP nanosheets, providing a universal strategy to synthesize ultrathin nanosheets of nonlayered materials. The overall water splitting of this Co-Ni S ultrathin nanosheets achieves a low voltage of 1.54 V at a current density of 10 mA cm and high durability in 1 m KOH, comparable to the best performance of electrochemical water splitting ever reported. The detailed structural transformation of Ni-based sulfides in the catalytic process and its mechanism are further explored both experimentally and theoretically.
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http://dx.doi.org/10.1002/smll.202102097DOI Listing
August 2021

Neuroticism vulnerability factors of anxiety symptoms in adolescents and early adults: an analysis using the bi-factor model and multi-wave longitudinal model.

PeerJ 2021 22;9:e11379. Epub 2021 Jun 22.

Beijing Key Laboratory of Learning and Cognition, School of Psychology, Capital Normal University, Beijing, China.

Background: Neuroticism and stress are important vulnerability factors in the development and outcome of anxiety symptoms. However, as neuroticism is a heterogeneity trait, it is still unclear how different neuroticism factors contribute to anxiety symptoms independently or in conjunction with stress. Thus, different factors of neuroticism were extracted in the present longitudinal study using the bi-factor model. The prediction effect of these different factors on anxiety symptoms and their combined effects with stress in both adolescent and adult samples were examined.

Method: Participants (592 adolescents and 638 young adults) in Hunan China were included. In the initial assessment in our longitudinal study, participants were asked to complete measurements that assessed neuroticism, stress, and anxiety symptoms. Next, a monthly assessment of stress and anxiety symptoms was completed for the subsequent 6 months. The bi-factor model was used to extract different factors of neuroticism. The hierarchical linear model was used to analyze longitudinal multi-wave data.

Result: Several model fit indices were used to evaluate the bi-factor model fit for neuroticism (adolescent: Tucker-Lewis index (TLI) = 0.957, comparative fit index (CFI) = 0.973, RMSEA = 0.040, Chi-Square = 80.471; early adults: TLI = 0.957, CFI = 0.973, RMSEA = 0.042, Chi-Square = 88.465). The results of hierarchical linear modeling analyses indicated that the general factor of neuroticism possessed a predictive effect on anxiety symptoms (adolescents: F = 36.77, < 0.0001, early adults: F = 30.44, < 0.0001); The negative effect factor only had the prediction effect on anxiety symptoms in early adults (adolescents: F = 0.65, > 0.05; early adults: F = 4.84, < 0.05); No prediction of self-reproach factor was found on anxiety symptoms (adolescents: F = 3.79, > 0.05; early adults: F = 0.02, > 0.05); the interactive effects of the general factor and stress on anxiety symptoms were only found in early adulthood (adolescents: F = 0.13, > 0.05; early adults: F = 11.55, < 0.01).

Conclusion: Our results suggested that the bi-factor model achieved a satisfactory fit for neuroticism measurement and supported that the anxiety symptoms were induced by the main effects of the general factor in both age samples and the negative factor only in adults. The general factor of neuroticism, but not the negative factor could make an additive effect for anxiety symptoms in face of stress, which meant that the homogeneity of neuroticism played a more significant role in further anxiety symptoms than heterogeneity when coping with stress.
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http://dx.doi.org/10.7717/peerj.11379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231313PMC
June 2021

Association of serum 25-hydroxyvitamin D with metabolic syndrome and type 2 diabetes: a one sample Mendelian randomization study.

BMC Geriatr 2021 06 29;21(1):391. Epub 2021 Jun 29.

Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, No.9 Seyuan Road, Chongchuan District, Nantong, Jiangsu, P.R. China, 226019.

Background: Vitamin D deficiency has been associated with type 2 diabetes (T2D) and metabolic syndrome (MS) and its components. However, it is unclear whether a low concentration of vitamin D is the cause or consequence of these health conditions. Thus, this study aimed to evaluate the association of vitamin D concentrations and its genetic risk scores (GRSs) with MS and its component diseases, such as T2D, in middle-aged and elderly participants from rural eastern China.

Methods: A subset of 2393 middle-aged and elderly individuals were selected from 70,458 participants of the Nantong Chronic Diseases Study of 2017-2018 in China. We used two 25-hydroxyvitamin D (25[OH]D) synthesis single-nucleotide polymorphisms (SNPs) (DHCR7-rs12785878 and CYP2R1-rs10741657) and two 25(OH) D metabolism SNPs (GC-rs2282679 and CYP24A1-rs6013897) for creating GRSs, which were used as instrumental variables to assess the effect of genetically lowered 25(OH) D concentrations on MS and T2D based on the Wald ratio. F statistics were used to validate that the four SNPs genetically determined 25(OH) D concentrations.

Results: Compared to vitamin D sufficient individuals, individuals with vitamin D insufficiency had an odds ratio (OR [95% confidence interval {CI}]) of MS of 1.30 (1.06-1.61) and of T2D of 1.32 (1.08-1.64), individuals with vitamin D deficiency had an ORs (95% CI) of MS of 1.50 (1.24-1.79) and of T2D of 1.47 (1.12-1.80), and those with vitamin D severe deficiency had an ORs (95% CI) of MS of 1.52 (1.29-1.85) and of T2D of 1.54 (1.27-1.85). Mendelian randomization analysis showed a 25-nmol/L decrease in genetically instrumented serum 25(OH) D concentrations using the two synthesis SNPs (DHCR7 and CYP2R1 genes) associated with the risk of T2D and abnormal diastolic blood pressure (DBP) with ORs of 1.10 (95%CI: 1.02-1.45) for T2D and 1.14 (95%CI: 1.03-1.43) for DBP.

Conclusions: This one sample Mendelian randomization analysis shows genetic evidence for a causal role of lower 25(OH) D concentrations in promoting of T2D and abnormal DBP in middle-aged and elderly participants from rural China.
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http://dx.doi.org/10.1186/s12877-021-02307-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244233PMC
June 2021

The Efficacy and Safety of Radiofrequency Ablation for Bilateral Papillary Thyroid Microcarcinoma.

Front Endocrinol (Lausanne) 2021 11;12:663636. Epub 2021 Jun 11.

Department of Ultrasound, First Medical Center, Chinese PLA General Hospital, Beijing, China.

Objective: To investigate the long-term clinical results of radiofrequency ablation (RFA) for bilateral papillary thyroid microcarcinoma (PTMC).

Materials And Methods: From October 2014 to February 2018, 47 patients (37 females, 10 males, mean age 43.39 ± 9.26 years) with 100 bilateral PTMC (mean volume 75.22 ± 73.87 mm) treated by RFA were included in this retrospective study. Bilateral PTMC was defined as at least one tumor located in the contralateral lobe. Patients were followed up at 1, 3, 6, 12 months and every 6-12 months thereafter. Volume, volume reduction ratio (VRR) and local tumor recurrence were evaluated during the follow-up period.

Results: After a mean follow-up period of 47.77 ± 11.54 months, the mean volume of bilateral PTMC decreased from 75.22 ± 73.87 mm to 0.09 ± 0.44 mm. The mean VRR was 99.94 ± 0.28% and the complete disappearance rate was 92.00%. During the follow-up, one patient (2.13%) developed lymph node metastasis and two patients (4.26%) had recurrent PTMC. All the recurrent lesions underwent additional RFA and two of them disappeared completely. No life-threatening or delayed complications occurred.

Conclusions: With sufficient preoperative evaluation, RFA might be a promising alternative for bilateral PTMC patients who were unsuitable for surgery or refused surgery.
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http://dx.doi.org/10.3389/fendo.2021.663636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227434PMC
June 2021

Prognostic Analysis and Risk Factors Associated with Fetal Ventriculomegaly.

Pediatr Neurosurg 2021 25;56(5):407-415. Epub 2021 Jun 25.

Department of Neurosurgery, Affiliated Hospital of Guilin Medical University, Guilin, China.

Background: This study aimed to investigate the clinical outcome and related risk factors of fetal lateral ventriculomegaly (VM).

Methods: A retrospective analysis was performed on 255 cases diagnosed as fetal VM. Prenatal imaging examination was carried out. The pregnancy outcomes were investigated through follow-up. According to the prognosis of children, they were divided into case group and control group. Multivariate logistic regression was used to analyze the factors influencing the prognosis of hydrocephalus.

Results: After excluding the cases with either loss of follow-up or incomplete information, 102 cases were followed up. Twelve cases with poor prognosis were set as the case group. According to the maternal age, gestational age, gender of children, and follow-up time, 3 cases were selected from the other 90 cases for each child in the case group, respectively, and selected as the control group. Paired comparative analysis was performed on 48 cases. Using prognosis as a dependent variable, multivariate logistic regression analysis of the statistically significant factors indicated that the change speed of width ratio (CSWR) and maximum lateral ventricular width (MW) were associated with fetal prognosis.

Conclusions: Our results suggested that CSWR and MW may have the value of predicting fetal prognosis.
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http://dx.doi.org/10.1159/000516378DOI Listing
June 2021

Roflumilast Suppresses Adipogenic Differentiation  AMPK Mediated Pathway.

Front Endocrinol (Lausanne) 2021 7;12:662451. Epub 2021 Jun 7.

Department of Endocrine, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang City, China.

Obesity and related disorders have increasingly become global health problems over the years. In recent years, obesity has been recognized as the most important risk factor for a variety of diseases including cardiovascular diseases, type 2 diabetes, steatohepatitis, and cancer. The medical anti-obesity treatment is to intervene in the metabolic process of adipocytes by suppressing adipogenesis and promoting lipolysis. The Phosphodiesterase-4 (PDE4) pathway is involved in fat mass control and metabolic regulation. The present study aimed to investigate the effects of Roflumilast, a selective PDE4 inhibitor, on the differentiation of 3T3-L1 cells and the high fat diet-induced obesity in mice. We showed that treatment with Roflumilast inhibited lipid accumulation and triglycerides storage in mature 3T3-L1 cells, suggesting that Roflumilast suppressed adipogenesis. Mechanistically, we found that Roflumilast decreased the differentiation-induced expression of the adipogenesis genes including SREBP1C, FABP4, and Glut4, as well as their regulators including PPAR-γ and C/EBPα. Moreover, we proved that the effect of Roflumilast was dependent on the activation of the metabolic regulator AMPKα. The treatment with Roflumilast remarkably decreased the animals' body weight, visceral adipose tissue weight, and adipocyte size in high fat diet-induced obese mice. In conclusion, our study revealed that Roflumilast suppressed adipogenesis and promoted lipolysis in cell culture and mice models AMPK-mediated inhibition of PPAR-γ and C/EBPα. These findings imply roflumilast could have therapeutic potential in obesity-related diseases.
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http://dx.doi.org/10.3389/fendo.2021.662451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215703PMC
June 2021

Untargeted serum metabolomics and tryptophan metabolism profiling in type 2 diabetic patients with diabetic glomerulopathy.

Ren Fail 2021 Dec;43(1):980-992

Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.

Diabetic glomerulopathy (DG) remains the prevalent microvascular complication and leading cause of shortened lifespan in type-2 diabetes mellitus (T2DM) despite improvement in hyperglycemia control. Considering the pivotal role of kidney in metabolism, using untargeted metabolomic techniques to globally delineate the serum metabolite profiles will help advance understanding pathogenetic underpinnings of renal biopsy-confirmed DG from the perspective of metabolism specifically. Fourteen pathologically diagnosed DG patients secondary to T2DM and 14 age- and gender-matched healthy controls (HCs) were recruited for study. We employed mass spectrometry-based untargeted metabolomic methods to reveal the metabolite profiles of serum samples collected from all included subjects. We identified a total of 334 and 397 metabolites in positive and negative ion mode respectively. One hundred and eighty-two important differential metabolites whose variable importance in projection (VIP) > 1 and value <0.05 were selected and annotated to metabolic pathways. KEGG pathway enrichment analysis revealed enriched most significantly. Among the tryptophan derivatives, L-tryptophan (L-Trp) and serotonin were relatively accumulated in DGs compared with HCs, while 5-hydroxyindoleacetic acid (5-HIAA) and indole-3-acetamide were depleted. Correlation analysis showed serotonin and L-Trp are negatively correlated with 24 h urine protein and glycosylated hemoglobin (Ghb). To exclude the interference of preexisting T2DM on DG exacerbation, we selected 5-HIAA and 3-(3-hydroxyphenyl) propionic acid (3-OHPPA) which are not correlated with Ghb and analyzed their correlation relationship with crucial renal indices. We found 3-OHPPA is positively correlated with urine total protein and creatinine ratio (T/Cr) and 24 h urine protein, 5-HIAA is positively correlated with serum creatinine and urea.
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http://dx.doi.org/10.1080/0886022X.2021.1937219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231361PMC
December 2021

Optimization of the Administration Strategy for the Armed Oncolytic Adenovirus ZD55-IL-24 in Both Immunocompromised and Immunocompetent Mouse Models.

Hum Gene Ther 2021 Jul 28. Epub 2021 Jul 28.

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.

ZD55-IL-24 is an armed oncolytic adenovirus similar but superior to ONYX-015. Virotherapeutic strategies using ZD55-IL-24 have been demonstrated to be effective against several cancer types. However, it is unclear whether the traditional administration strategy is able to exert the maximal antitumor efficacy of ZD55-IL-24. In this study, we sought to optimize the administration strategy of ZD55-IL-24 in both A375-bearing immunocompromised mouse model and B16-bearing immunocompetent mouse model. Although the underlying antitumor mechanisms are quite different, the obtained results are similar in these two mouse tumor models. We find that the antitumor efficacy of ZD55-IL-24 increases as injection times increase in both of these two models. However, no obvious increase of efficacy is observed as the dose of each injection increases. Our further investigation reveals that the administration strategy of sustained ZD55-IL-24 therapy can achieve a better therapeutic effect than the traditional administration strategy of short-term ZD55-IL-24 therapy. Furthermore, there is no need to inject every day; every 2 or 3 days of injection achieves an equivalent therapeutic efficacy. Finally, we find that the sustained rather than the traditional short-term ZD55-IL-24 therapy can synergize with anti-PD-1 therapy to reject tumors in B16-bearing immunocompetent mouse model. These findings suggest that the past administration strategy of ZD55-IL-24 is in fact suboptimal and the antitumor efficacy can be further enhanced through administration strategy optimization. This study might shed some light on the development of clinically applicable administration regimens for ZD55-IL-24 therapy.
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http://dx.doi.org/10.1089/hum.2021.036DOI Listing
July 2021

Ultra-compact electro-optic modulator based on alternative plasmonic material.

Appl Opt 2021 Jun;60(17):5252-5257

We propose an ultra-compact electro-optic microring modulator based on a hybrid plasmonic waveguide. In comparison to previously proposed structures, the present structure utilizes aluminum-doped zinc oxide (AZO), rather than noble metals, for plasmon excitation. AZO can be used to simultaneously tune both the real and imaginary parts of the dielectric constant by changing the carrier concentration. The modulation depth and insertion loss of the microring modulator are 18.70 and 2.76 dB. The proposed modulator has a high modulation speed because its capacitance is 0.22 fF. This device could be used in high-density integrated optical circuits.
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http://dx.doi.org/10.1364/AO.425679DOI Listing
June 2021

Influence of occupation type on the association between sleep duration and impaired fasting glucose: results from a Chinese population-based study.

BMJ Open 2021 06 16;11(6):e042066. Epub 2021 Jun 16.

Department of Epidemiology and Medical Statistics, Nantong University, Nantong, China

Objectives: Systematic evaluation of the influence of occupation type on the association between sleep-glucose metabolism DESIGN: A cross-sectional study.

Setting: The Nantong Metabolic Syndrome Study is a Chinese population-based study.

Participants: 20 502 participants aged 18-74 years old.

Intervention: No intervention.

Primary And Secondary Outcome Measures: Impaired fasting glucose (IFG).

Results: A total of 1503 participants (7.33%) with a slightly longer sleep duration had IFG. After being stratified according to occupation, a sleep duration of ≥10 hours daily corresponded to a 1.321-fold risk of IFG (95% CI 1.071 to 1.628, p=0.0092) among moderate and heavy physical workers compared with those with a daily sleep duration of 7-9 hours. There was no significant relationship between sleep and IFG among other types of workers. Moreover, we discovered a gender difference in the influence of occupation on the sleep-IFG. A positive association among moderate and heavy physical men and a negative association among light or sedentary men were established, but not in unemployed men. However, a positive association was evident only in unemployed women; there was no significant association among other occupations.

Conclusion: This study highlights the role of occupation in the relationship of sleep-glucose metabolism. A gender difference was found to have been influenced by occupational types on the sleep-metabolic association.
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http://dx.doi.org/10.1136/bmjopen-2020-042066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211085PMC
June 2021

How Chinese Herbal Medicine Prevents Epidemics: From Ancient Pestilences to COVID-19 Pandemic.

Am J Chin Med 2021 5;49(5):1017-1044. Epub 2021 Jun 5.

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, P. R. China.

The ongoing coronavirus disease 2019 (COVID-19) pandemic calls for effective control and prevention. Chinese medicine (CM) has developed systematic theories and approaches for infectious disease prevention over 2000 years. Here, we review and analyze Chinese herbal medicines (CHM) used in infectious disease prevention from ancient pestilences to modern epidemics and pandemics to share cumulative preventive medical experience. A total of 829 formulas, including 329 herbs from 189 ancient books, 131 formulas with 152 herbs, and 13 Chinese patent medicines (CPM) from 30 official Chinese prevention programs used in ancient epidemics, SARS, influenza and COVID-19 prevention, were reviewed and analyzed. Preventive CHM mainly has four functions and can be taken orally or applied externally. CHM that kill pathogens ( [Xionghuang], [Guanzhong]) were commonly used externally for disinfection in ancient prevention while CHM tonifying Qi ( [Huangq], [Gancao]) are used for modern prevention. Taking CHM that expel pathogens ( [Xionghuang], [Jinyinhua]) and CHM eliminating dampness ( [Cangzhu], [Guanghuoxiang]) have been commonly used from ancient times to COVID-19. Damp toxins are a common characteristic of infectious diseases such as SARS and COVID-19. Thus, taking CHM expelling damp toxins and tonifying Qi are the main methods for SARS and COVID-19 prevention. CHM with different approaches have been widely used in infectious disease prevention from ancient times to the present. Multiple CM prevention methods may provide new perspectives for future pandemics.
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http://dx.doi.org/10.1142/S0192415X2150049XDOI Listing
July 2021
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