Publications by authors named "Jing Huang"

1,990 Publications

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Development and Validation of a Radiomic Nomogram for Predicting the Prognosis of Kidney Renal Clear Cell Carcinoma.

Front Oncol 2021 6;11:613668. Epub 2021 Jul 6.

Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Purpose: The present study aims to comprehensively investigate the prognostic value of a radiomic nomogram that integrates contrast-enhanced computed tomography (CECT) radiomic signature and clinicopathological parameters in kidney renal clear cell carcinoma (KIRC).

Methods: A total of 136 and 78 KIRC patients from the training and validation cohorts were included in the retrospective study. The intraclass correlation coefficient (ICC) was used to assess reproducibility of radiomic feature extraction. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) as well as multivariate Cox analysis were utilized to construct radiomic signature and clinical signature in the training cohort. A prognostic nomogram was established containing a radiomic signature and clinicopathological parameters by using a multivariate Cox analysis. The predictive ability of the nomogram [relative operating characteristic curve (ROC), concordance index (C-index), Hosmer-Lemeshow test, and calibration curve] was evaluated in the training cohort and validated in the validation cohort. Patients were split into high- and low-risk groups, and the Kaplan-Meier (KM) method was conducted to identify the forecasting ability of the established models. In addition, genes related with the radiomic risk score were determined by weighted correlation network analysis (WGCNA) and were used to conduct functional analysis.

Results: A total of 2,944 radiomic features were acquired from the tumor volumes of interest (VOIs) of CECT images. The radiomic signature, including ten selected features, and the clinical signature, including three selected clinical variables, showed good performance in the training and validation cohorts [area under the curve (AUC), 0.897 and 0.712 for the radiomic signature; 0.827 and 0.822 for the clinical signature, respectively]. The radiomic prognostic nomogram showed favorable performance and calibration in the training cohort (AUC, 0.896, C-index, 0.846), which was verified in the validation cohort (AUC, 0.768). KM curves indicated that the progression-free interval (PFI) time was dramatically shorter in the high-risk group than in the low-risk group. The functional analysis indicated that radiomic signature was significantly associated with T cell activation.

Conclusions: The nomogram combined with CECT radiomic and clinicopathological signatures exhibits excellent power in predicting the PFI of KIRC patients, which may aid in clinical management and prognostic evaluation of cancer patients.
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http://dx.doi.org/10.3389/fonc.2021.613668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290524PMC
July 2021

Emerging neurotropic features of SARS-CoV-2.

J Mol Cell Biol 2021 Jul 21. Epub 2021 Jul 21.

School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.

The prevailing coronavirus disease (COVID-19) caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has presented some neurological manifestations including hyposmia, hypogeusia, headache, stroke, encephalitis, Guillain‒Barre syndrome, and some neuropsychiatric disorders. Although several cell types in the brain express angiotensin converting enzyme-2 (ACE2), the main SARS-CoV-2 receptor, and other related proteins, it remains unclear whether the observed neurological manifestations are attributed to virus invasion into the brain or just comorbidities caused by dysregulation of systemic factors. Here, we briefly review the neurological manifestations of SARS-CoV-2, summarize recent evidence for the potential neurotropism of SARS-CoV-2, and discuss the potential mechanisms of COVID-19-associated neurological diseases.
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http://dx.doi.org/10.1093/jmcb/mjab044DOI Listing
July 2021

Cardiorespiratory responses in healthy young adults with exposure to indoor airborne PAEs: A randomized, crossover trial of air purification.

Environ Int 2021 Jul 17;156:106761. Epub 2021 Jul 17.

Department of Occupational and Environmental Health Sciences, Peking University School of Public Health, Beijing, China.

Background: Phthalic acid esters (PAEs) are widely used as plasticizers in industrial process and consumer products. Nowadays, PAEs are ubiquitous in the environment and are reported to be associated with cardiorespiratory diseases. However, studies about the association between indoor airborne PAEs exposure and cardiorespiratory health were limited, and the potential biological mechanism remains under-recognized.

Methods: A randomized crossover trial was conducted on 57 healthy young adults in Beijing. Repeated health measurements were performed under real and sham indoor air purification with a washout interval of at least 2 weeks. The concentration of indoor airborne PAEs were determined by gas chromatography-orbit ion trap mass spectrometry. Health indicators including blood pressure, lung function, airway inflammation, and circulating biomarkers reflecting blood coagulation and systematic oxidative stress were measured. Linear mixed-effect model was used to examine the between-treatment differences in health indicators, and three models including single-constituent, constituent-fine particulate matter (PM) joint, and single-constituent residual model were used to estimate the association between indoor airborne PAEs and health indicators.

Results: The indoor airborne PAEs were reduced effectively under real air purification. The total indoor airborne di-2-ethylhexyl phthalate (DEHP), bis (4-Methyl-2-pentyl) phthalate (DMPP), diphenyl phthalate (DPP), and diethyl phthalate (DEP) were identified to be most significantly associated with the increase of blood pressure and airway inflammation, and decrease of lung function. A doubling increase in DEHP, DMPP, DPP, DEP was associated with the increase of 17.2% (95% CI: 3.9%, 32.2%), 11.7% (95% CI: 3.5%, 20.6%), 7.0% (95% CI: 2.4%, 11.8%), 6.0% (95% CI: 1.8%, 10.4%) in FeNO, respectively, in single-constituent residual model. Significant associations between specific total indoor airborne PAEs and increased levels of health biomarkers including oxidized low-density lipoprotein (ox-LDL), 8-isoprostane (8-isoPGF2α), and soluble P-selectin (sP-selectin) were observed.

Conclusion: Indoor airborne PAEs may cause adverse cardiorespiratory health effects in young healthy adults, and indoor air purification could ameliorate the adverse cardiorespiratory effects.
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http://dx.doi.org/10.1016/j.envint.2021.106761DOI Listing
July 2021

The Gene rs1799750 Polymorphism Is Associated with Breast Cancer Risk.

Genet Test Mol Biomarkers 2021 Jul;25(7):496-503

Department of Laboratory Medicine, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China.

Numerous studies investigating an association between the matrix metalloproteinase-1 () gene rs1799750 polymorphism and breast cancer (BC) risk have reported inconsistent results. Therefore, this meta-analysis was undertaken to obtain a more precise estimate of the possible association between this genetic locus and BC susceptibility. Eight eligible studies involving 3439 cases and 3517 controls were identified by searching the PubMed, Google, CNKI, and EMBASE databases systematically through October 1, 2020. The rs1799750 polymorphism was associated with a reduced BC risk in the overall study population under the heterozygous model. Stratification analyses indicated that this association is strong in Asians. There is evidence of an association between the rs1799750 polymorphism and BC susceptibility, viewed as a decreased risk factor for BC. More extensive studies with more diverse ethnic populations are necessary to confirm these findings.
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http://dx.doi.org/10.1089/gtmb.2021.0016DOI Listing
July 2021

Evaluation of candidate genes in a Chinese cohort of atypical Rolandic epilepsy.

Epileptic Disord 2021 Jul 16. Epub 2021 Jul 16.

Department of Neurology, Children's Hospital of Soochow University, Suzhou, Jiangsu Province, China.

Objective: We aimed to identify new candidate pathogenic genes for atypical Rolandic epilepsy.

Methods: We retrospectively evaluated the data from 24 Chinese patients with atypical Rolandic epilepsy who underwent whole-exome sequencing. Data were analysed regarding the frequency of affected genes, previously reported disease-related genes, and evaluation based on Kyoto Encyclopaedia of Genes and Genomes (KEGG).

Results: We identified a frameshift mutation in the reported gene PRRT2, which is classified as pathogenic according to American College of Medical Genetics and Genomics guidelines (ACMG). We also identified a novel missense mutation in the PRRT2 gene in a family with three affected patients. Several other candidate genes were found in at least two patients, some of which were associated with other epilepsies (ADGRV1, CACNA1A, CHD2, CLCN2, HECW2, KIF1A, NPRL3, RELN and TSC2), while others were mainly associated with neuropsychiatric disease (SHANK3 and AUTS2). The KEGG analysis of 81 candidate genes associated with atypical Rolandic epilepsy identified a significant association with the GABAergic synapse. Candidate genes involved in the GABAergic synapse pathway included NSF, CACNA1A, as well as others.

Significance: Our study indicates that PRRT2 mutations may be associated with atypical Rolandic epilepsy. Moreover, we identified a number of unreported candidate genes, including ADGRV1, CHD2, CACNA1A, NSF, NPRL3, KIF1A, GJB2 and HECW2, also associated with atypical Rolandic epilepsy.
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http://dx.doi.org/10.1684/epd.2021.1308DOI Listing
July 2021

Protein Kinases: Potential Drug Targets Against .

Front Cell Infect Microbiol 2021 1;11:691757. Epub 2021 Jul 1.

Department of Parasitology, School of Basic Medical Science, Central South University, Changsha, China.

() infection can induce serious organ damage and cause schistosomiasis japonica which is mainly prevalent in Asia and currently one of the most seriously neglected tropical diseases. Treatment of schistosomiasis largely depends on the drug praziquantel (PZQ). However, PZQ exhibits low killing efficacy on juvenile worms and the potential emergence of its drug resistance is a continual concern. Protein kinases (PKs) are enzymes that catalyze the phosphorylation of proteins and can participate in many signaling pathways . Recent studies confirmed the essential roles of PKs in the growth and development of , as well as in schistosome-host interactions, and researches have screened drug targets about PKs from (SjPKs), which provide new opportunities of developing new treatments on schistosomiasis. The aim of this review is to present the current progress on SjPKs from classification, different functions and their potential to become drug targets compared with other schistosomes. The efficiency of related protein kinase inhibitors on schistosomes is highlighted. Finally, the current challenges and problems in the study of SjPKs are proposed, which can provide future guidance for developing anti-schistosomiasis drugs and vaccines.
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http://dx.doi.org/10.3389/fcimb.2021.691757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282181PMC
July 2021

Effects of dexmedetomidine combined with citrate sufentanil on the prognosis of patients with severe pneumonia and respiratory failure requiring mechanical ventilation.

Pak J Pharm Sci 2021 Jan;34(1(Special)):423-428

Intensive Care Unit, Fuyuan Hospital of Yiwu City, Yiwu, Zhejiang Province, China.

To investigate the effects of dexmedetomidine combined with citrate sufentanil on the prognosis of patients with severe pneumonia and respiratory failure requiring mechanical ventilation. 70 patients with severe pneumonia complicated with respiratory failure who were treated with mechanical ventilation were selected and divided into the combined group and the control group. The control group underwent mechanical ventilation treatment and used dexmedetomidine for sedation and analgesia, while the combined group had sufentanil analgesia in addition to the treatment of the control group. Ramsay sedation score, visual analogue scale (VAS) and pulmonary function indicators were compared between the two groups before treatment, 24h after treatment, and after extubation. After 24h treatment and extubation, the blood oxygen saturation (SpO), oxygenation index (OI) and arterial oxygen partial pressure (PaO) in the combined group were higher than those in the control group; at the same time, the serum interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and malondialdehyde (MDA) levels were lower (P<0.05). Mortality during hospitalization of the combined group was lower than the control group (P<0.05). Dexmedetomidine combined with sufentanil citrate can effectively improve sedative and analgesic effects, stress response, pulmonary function and prognosis in patients with severe respiratory failure requiring mechanical ventilation.
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January 2021

Impact of birth season on the years of life lost from respiratory diseases in the elderly related to ambient PM exposure in Ningbo, China.

Environ Health Prev Med 2021 Jul 17;26(1):74. Epub 2021 Jul 17.

Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, 38 Xueyuan Road, Beijing, 100191, China.

Background: Ambient fine particle (PM) pollution is an important public health problem in China. Short-term ambient PM exposure is associated with increased mortality of respiratory diseases. However, few evidence was available on the effect of exposure to ambient PM on the years of life lost (YLL) from respiratory diseases in the elderly. Furthermore, birth season which is frequently applied as a proxy for environmental exposure in early life may influence the health outcome in the later life. Nevertheless, the modification effect of birth season on the relationship of PM exposure and respiratory health need to be explored.

Methods: A time-stratified case-crossover design was used to analyze YLL from respiratory diseases in the elderly related to ambient PM exposure between 2013 and 2016 in Ningbo, China. The modification effect of birth season was explored by subgroup comparisons between different birth seasons.

Results: Each 10 μg/m increase in daily ambient PM was associated with an increment of 1.61 (95% CI 0.12, 3.10) years in YLL from respiratory diseases in the elderly population. Individuals who were born in winter had significantly higher YLL from respiratory diseases associated with ambient PM exposure than those who were born in other seasons.

Conclusions: Birth season which reflects the early-life PM exposure level that may influence the lung development has a potential effect on the disease burden of respiratory diseases related to ambient PM exposure in later life. The results would provide theoretical basis to protect vulnerable population defined by birth season when exploring the adverse effects of ambient PM in the respiratory health.
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http://dx.doi.org/10.1186/s12199-021-00994-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286574PMC
July 2021

Neoadjuvant chemotherapy combined with radical surgery for stage IB2/IIA2 cervical squamous cell carcinoma: a prospective, randomized controlled study of 35 patients.

World J Surg Oncol 2021 Jul 12;19(1):209. Epub 2021 Jul 12.

Department of Chemotherapy Center, Ganzhou Cancer Hospital, No.19, Hua Yuan Qian Road, Ganzhou, 341000, Jiangxi Province, China.

Objective: This study aimed to evaluate the clinical outcomes for patients with stage IB2/IIA2 cervical squamous cell carcinoma treated with neoadjuvant chemotherapy combined with radical surgery.

Methods: A total of 68 patients with cervical squamous cell carcinoma were randomly divided into the experimental group (n = 35) and the control group (n = 33). The patients in the experimental group received paclitaxel plus cisplatin neoadjuvant chemotherapy for two cycles, then underwent radical hysterectomy and bilateral adnexectomy at 2 weeks post-chemotherapy. The control group only underwent radical hysterectomy and bilateral adnexectomy after the diagnosis of cervical squamous cell carcinoma. The toxic and side effects of chemotherapy in the experimental group were observed. Also, the operation method, operation time, blood loss, grade of wound healing, complications, and postoperative pathology were noted in the two groups. Primary foci and pelvic lymph node recurrence and distant metastasis were observed, and 3-year and 5-year survival rates were calculated.

Results: Only one patient in the experiment had grade III bone marrow suppression; no other grade III and IV chemotherapy toxic reactions were observed. The operation was successfully completed in all patients. The operation time, intraoperative blood loss, placement of the ureteral catheter, bladder injury, ureteric injury, postoperative urinary tub, pelvic drainage tube indwelling time, anal exhaust time, postoperative complications, and metastatic ratio of lymph nodes were not significantly different between the two groups (P > 0.05). The number of dissected lymph nodes, deep myometrial invasion, and vascular tumor emboli showed a significant difference in the experimental group compared with the control group (P < 0.05). The 3-year disease-free survival (82.9% vs 81.9%), 5-year disease-free survival (71.4% vs 60.6%), 3-year overall survival (91.4% vs 87.8%), and 5-year overall survival (82.9% vs 75.6%) were not statistically significantly different between the experimental group and the control group (P > 0.05).

Conclusions: Neoadjuvant chemotherapy in IB2/IIA2 stage cervical squamous cell carcinoma showed low toxic side effects. Radical surgery after chemotherapy is safe and feasible. It plays a coordinating role in reducing the tumor infiltration depth of the deep muscle layer and the incidence of vascular tumor emboli, reducing the use of postoperative adjuvant therapy, and improving the quality of life of patients, but does not improve the 3-year/5-year survival rate.
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http://dx.doi.org/10.1186/s12957-021-02318-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276376PMC
July 2021

Full-Dimensional Global Potential Energy Surface for the KRb + KRb → KRb* → K + Rb Reaction with Accurate Long-Range Interactions and Quantum Statistical Calculation of the Product State Distribution under Ultracold Conditions.

J Phys Chem A 2021 Jul 12;125(28):6198-6206. Epub 2021 Jul 12.

Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, New Mexico 87131, United States.

A full-dimensional global potential energy surface (PES) for the KRb + KRb → KRb* → K + Rb reaction is reported based on high-level calculations. The short-range part of the PES is fit with the permutationally invariant polynomial-neural network method, while the long-range parts of the PES in both the reactant and product asymptotes are represented by an asymptotically correct form. The long- and short-range parts are connected with intermediate-range parts to make them smooth. Within a statistical quantum model, this PES reproduces both the measured loss rates of ultracold KRb molecules and the K and Rb product state distributions, underscoring the important role of tunneling in ultracold chemistry. The PES also correctly predicts the lifetime of the KRb* intermediate complex within the Rice-Ramsperger-Kassel-Marcus limit. It thus provides a reliable platform for future dynamical studies of the prototypical reaction.
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http://dx.doi.org/10.1021/acs.jpca.1c04506DOI Listing
July 2021

Airway resistance variation correlates with prognosis of critically ill COVID-19 patients: A computational fluid dynamics study.

Comput Methods Programs Biomed 2021 Jun 25;208:106257. Epub 2021 Jun 25.

Department of Critical Care Medicine, Southeast University Zhongda Hospital, Nanjing, Jiangsu, China. Electronic address:

Objective: To evaluate the quantitative changes of respiratory functions for critically ill COVID-19 patients with mechanical ventilation, computational fluid dynamics (CFD) analysis was performed based on patient-specific three-dimensional airway geometry.

Methods: 37 cases of critically ill patients with COVID-19 admitted to the ICU of Huangshi Traditional Chinese Medicine Hospital from February 1st to March 20th, 2020 were retrospectively analyzed. 5 patients whose clinical data met the specific criteria were finally cataloged into death group (2 patients) and survival group (3 patients). The patient-specific three-dimensional airways were reconstructed from the central airways down to the 4th-5th bifurcation of the tracheobronchial tree. The volume changes of bronchi were calculated during the disease progression according to the comparison of two CT scans. Additionally, the changes of air flow resistance were analyzed using numerical simulation of CFD.

Results: Pearson correlation analysis demonstrated that there was negative correlation between the change of volume (ΔV) and the change of resistance (ΔR) for all COVID-19 patients (r=-0.7025). For total airway volume, an average decrease of -11.41±15.71% was observed in death group compared to an average increase of 1.86±10.80% in survival group (p=0.0232). For air flow through airways in lower lobe, the resistance increases for death group by 10.97±77.66% and decreases for survival group by -45.49±42.04% (p=0.0246).

Conclusion: The variation of flow resistance in the airway could be used as a non-invasive functional evaluation for the prognosis and outcome of critically ill patients with COVID-19. The 'virtual' pulmonary function test by integrating follow-up CT scans with patient-derived CFD analysis could be a potentially powerful way in improving the efficiency of treatment for critically ill patients with COVID-19.
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http://dx.doi.org/10.1016/j.cmpb.2021.106257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231702PMC
June 2021

Mechanism study of how lipid vesicle electroformation is suppressed by the presence of sodium chloride.

Colloids Surf B Biointerfaces 2021 Jun 29;206:111951. Epub 2021 Jun 29.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400030, China. Electronic address:

Giant lipid vesicles (GLVs) are usually adopted as models of cell membranes and electroformation is the most commonly used method for GLV formation. However, GLV electroformation are known to be suppressed by the presence of salt and the mechanism is not clear so far. In this paper, the lipid hydration and GLV electroformation were investigated as a function of the concentration of sodium chloride by depositing the lipids on the bottom substrates and top substrates. In addition, the electrohydrodynamic force generated by the electroosmotic flow (EOF) on the lipid phase was calculated with COMSOL Multiphysics. It was found that the mechanisms for the failure of GLV electroformation in salt solutions are: 1) the presence of sodium chloride decreases the membrane permeability to aqueous solution by accelerating the formation of well-packed membranes, suppressing the swelling and detachment of the lipid membranes; 2) the presence of sodium chloride decreased the electrohydrodynamic force by increasing the medium conductivity.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111951DOI Listing
June 2021

A Semi-Automatic Step-by-Step Expert-Guided LI-RADS Grading System Based on Gadoxetic Acid-Enhanced MRI.

J Hepatocell Carcinoma 2021 29;8:671-683. Epub 2021 Jun 29.

Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.

Purpose: Liver imaging reporting and data system (LI-RADS) classification, especially the identification of LR-3 to 5 lesions with hepatocellular carcinoma (HCC) probability, is of great significance to treatment strategy determination. We aimed to develop a semi-automatic LI-RADS grading system on multiphase gadoxetic acid-enhanced MRI using deep convolutional neural networks (CNN).

Patients And Methods: An internal data set of 439 patients and external data set of 71 patients with suspected HCC were included and underwent gadoxetic acid-enhanced MRI. The expert-guided LI-RADS grading system consisted of four deep 3D CNN models including a tumor segmentation model for automatic diameter estimation and three classification models of LI-RADS major features including arterial phase hyper-enhancement (APHE), washout and enhancing capsule. An end-to-end learning system comprising single deep CNN model that directly classified the LI-RADS grade was developed for comparison.

Results: On internal testing set, the segmentation model reached a mean dice of 0.84, with the accuracy of mapped diameter intervals as 82.7% (95% CI: 74.4%, 91.7%). The area under the curves (AUCs) were 0.941 (95% CI: 0.914, 0.961), 0.859 (95% CI: 0.823, 0.890) and 0.712 (95% CI: 0.668, 0.754) for APHE, washout and capsule, respectively. The expert-guided system significantly outperformed the end-to-end system with a LI-RADS grading accuracy of 68.3% (95% CI: 60.8%, 76.5%) vs 55.6% (95% CI: 48.8%, 63.0%) (<0.0001). On external testing set, the accuracy of mapped diameter intervals was 91.5% (95% CI: 81.9%, 100.0%). The AUCs were 0.792 (95% CI: 0.745, 0.833), 0.654 (95% CI: 0.602, 0.703) and 0.658 (95% CI: 0.606, 0.707) for APHE, washout and capsule, respectively. The expert-guided system achieved an overall grading accuracy of 66.2% (95% CI: 58.0%, 75.2%), significantly higher than the end-to-end system of 50.1% (95% CI: 43.1%, 58.1%) (<0.0001).

Conclusion: We developed a semi-automatic step-by-step expert-guided LI-RADS grading system (LR-3 to 5), superior to the conventional end-to-end learning system. This deep learning-based system may improve workflow efficiency for HCC diagnosis in clinical practice.
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http://dx.doi.org/10.2147/JHC.S316385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255313PMC
June 2021

The efficacy of vaccination to prevent human papilloma viruses infection at anal and oral: a systematic review and meta-analysis.

Public Health 2021 Jul 3;196:165-171. Epub 2021 Jul 3.

Medical Laboratory, Liang Ping People's Hospital of Chongqing, Liangping, 405200, Chongqing City, China. Electronic address:

Objective: The objective of this study was to review evidence on the effectiveness of vaccination in the prevention of human papilloma virus (HPV) infection at the cervix, anal, and oral.

Study Design: Systematic review and meta-analysis.

Methods: The key search limitations are as follows: "Human Papilloma Virus", "Papilloma Virus, Human" "Human Papillomavirus Virus", "HPV" and "oral", "anus", "anal", "penis", "cervical," and "vaccine". Randomized controlled studies were searched and analyzed the risk ratio by Review Manager 5.3; funnel plot was adopted for publication bias analysis.

Results: Five randomized controlled studies enrolling 13,686 participants were retrieved, analyzed, and showed that HPV vaccination can effectively block HPV infection at cervical, anal, and oral. Subgroup analysis, moreover, proved that HPV 16/18 is more effective than HPV 6/11/16/18 in preventing anal and oral infections.

Conclusion: HPV vaccine is efficacious in preventing HPV infection not only at cervical but also at anal and oral, as evidence supported by relevant studies.
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http://dx.doi.org/10.1016/j.puhe.2021.05.012DOI Listing
July 2021

A De Novo SEMA6B Variant in a Chinese Patient with Progressive Myoclonic Epilepsy-11 and Review of the Literature.

J Mol Neurosci 2021 Jul 4. Epub 2021 Jul 4.

Department of Neurology, Soochow University Affiliated Children's Hospital, Suzhou, Jiangsu, China.

Progressive myoclonic epilepsy is a group of neurodegenerative diseases with complex clinical and genetic heterogeneity, which is associated with spontaneous or action-induced myoclonus and progressive neurodegeneration. Since 2020, 4 families with progressive myoclonic epilepsy-11 [OMIM#618876] have been reported with a very limited spectrum of SEMA6B pathogenic variants. In our study, whole-exome sequencing was used in a proband from a nonconsanguineous Chinese family presenting with growth retardation and recurrent atonic seizures. A deletion mutation (c.1960_1978del, p.Leu654Argfs*25) in the last exon of SEMA6B was detected, which is a de novo variant and pathogenic. The new genetic evidence we reported here strengthened the gene-disease relationship, and the gene curation level between SEMA6B and progressive myoclonic epilepsy-11 became "strong" following the ClinGen SOP. Therefore, the results of this study broaden the mutation spectrum of SEMA6B in different ethnic groups and strengthen the gene-disease relationship between SEMA6B and progressive myoclonic epilepsy-11.
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http://dx.doi.org/10.1007/s12031-021-01880-0DOI Listing
July 2021

TSPAN1 silencing protects against cerulein-induced pancreatic acinar cell injury via targeting AGR2.

Drug Dev Res 2021 Jul 1. Epub 2021 Jul 1.

Department of Clinical Laboratory, Lishui People's Hospital, Lishui City, Zhejiang Province, China.

Acute pancreatitis (AP) is an inflammatory gastrointestinal disorder affecting the pancreas. Previous study reported that tetraspanin 1 (TSPAN1) expression was significantly upregulated in the pancreas of AP patients. However, the underlying molecular mechanism of TSPAN1 in the pathogenesis of AP remains unclear. Thus, the aim of the present study was to investigate the potential role of TSPAN1 in development of AP. RT-qPCR was carried out to quantify the relative mRNA levels of TSPAN1 and anterior gradient-2 (AGR2). The CCK-8 assay was used to detect the cell viability. The TUNEL assay was performed to visualize the apoptotic cells. Western blot was performed to determine the expressions of proteins related to endoplasmic reticulum (ER) stress and apoptosis. ELISA kits were adopted to detect the concentration of inflammatory cytokines including TNF-α and IL-6. Finally, immunoprecipitation (IP) was used to verify the interaction between TSPAN1 and AGR2. TSPAN1 was upregulated in serum of AP patients and AP cell models. TSPAN1 silencing promoted the cell proliferation and inhibited inflammatory response in cerulein-induced AR42J cells. Moreover, TSPAN1 induced endoplasmic reticulum stress by binding AGR2. Interestingly, the overexpression of AGR2 abolished the effects of TSPAN1 silencing on cell proliferation and inflammatory response in cerulein-induced AR42J cells. In summary, TSPAN1 silencing protects against cerulein-induced pancreatic acinar cell injury through inhibiting ER stress-mediated by AGR2. Hence, TSPAN1 may serve as a promising therapeutic target for AP treatment.
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http://dx.doi.org/10.1002/ddr.21855DOI Listing
July 2021

NLM-HS: Navigation Learning Model Based on a Hippocampal-Striatal Circuit for Explaining Navigation Mechanisms in Animal Brains.

Brain Sci 2021 Jun 17;11(6). Epub 2021 Jun 17.

Faculty of Information Technology, Beijing University of Technology, Beijing 100124, China.

Neurophysiological studies have shown that the hippocampus, striatum, and prefrontal cortex play different roles in animal navigation, but it is still less clear how these structures work together. In this paper, we establish a navigation learning model based on the hippocampal-striatal circuit (NLM-HS), which provides a possible explanation for the navigation mechanism in the animal brain. The hippocampal model generates a cognitive map of the environment and performs goal-directed navigation by using a place cell sequence planning algorithm. The striatal model performs reward-related habitual navigation by using the classic temporal difference learning algorithm. Since the two models may produce inconsistent behavioral decisions, the prefrontal cortex model chooses the most appropriate strategies by using a strategy arbitration mechanism. The cognitive and learning mechanism of the NLM-HS works in two stages of exploration and navigation. First, the agent uses a hippocampal model to construct the cognitive map of the unknown environment. Then, the agent uses the strategy arbitration mechanism in the prefrontal cortex model to directly decide which strategy to choose. To test the validity of the NLM-HS, the classical Tolman detour experiment was reproduced. The results show that the NLM-HS not only makes agents show environmental cognition and navigation behavior similar to animals, but also makes behavioral decisions faster and achieves better adaptivity than hippocampal or striatal models alone.
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http://dx.doi.org/10.3390/brainsci11060803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235547PMC
June 2021

Increased Global-Brain Functional Connectivity Is Associated with Dyslipidemia and Cognitive Impairment in First-Episode, Drug-Naive Patients with Bipolar Disorder.

Neural Plast 2021 5;2021:5560453. Epub 2021 Jun 5.

National Clinical Research Center on Mental Disorders and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China.

Objectives: Previous researches have demonstrated that abnormal functional connectivity (FC) is associated with the pathophysiology of bipolar disorder (BD). However, inconsistent results were obtained due to different selections of regions of interest in previous researches. This study is aimed at examining voxel-wise brain-wide functional connectivity (FC) alterations in the first-episode, drug-naive patient with BD in an unbiased way.

Methods: A total of 35 patients with BD and 37 age-, sex-, and education-matched healthy controls underwent resting-state functional magnetic resonance imaging (rs-fMRI). Global-brain FC (GFC) was applied to analyze the image data. Support vector machine (SVM) was adopted to probe whether GFC abnormalities could be used to identify the patients from the controls.

Results: Patients with BD exhibited increased GFC in the left inferior frontal gyrus (LIFG), pars triangularis and left precuneus (PCu)/superior occipital gyrus (SOG). The left PCu belongs to the default mode network (DMN). Furthermore, increased GFC in the LIFG, pars triangularis was positively correlated with the triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) and negatively correlated with the scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) coding test and Stroop color. Increased GFC values in the left PCu/SOG can be applied to discriminate patients from controls with preferable sensitivity (80.00%), specificity (75.68%), and accuracy (77.78%).

Conclusions: This study found increased GFC in the brain regions of DMN; LIFG, pars triangularis; and LSOG, which was associated with dyslipidemia and cognitive impairment in patients with BD. Moreover, increased GFC values in the left PCu/SOG may be utilized as a potential biomarker to differentiate patients with BD from controls.
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http://dx.doi.org/10.1155/2021/5560453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203345PMC
June 2021

The CTNNBIP1-CLSTN1 fusion transcript regulates human neocortical development.

Cell Rep 2021 Jun;35(13):109290

School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China. Electronic address:

Fusion transcripts or RNAs have been found in both disordered and healthy human tissues and cells; however, their physiological functions in the brain development remain unknown. In the analysis of deposited RNA-sequence libraries covering early to middle embryonic stages, we identify 1,055 fusion transcripts present in the developing neocortex. Interestingly, 98 fusion transcripts exhibit distinct expression patterns in various neural progenitors (NPs) or neurons. We focus on CTNNBIP1-CLSTN1 (CTCL), which is enriched in outer radial glial cells that contribute to cortex expansion during human evolution. Intriguingly, downregulation of CTCL in cultured human cerebral organoids causes marked reduction in NPs and precocious neuronal differentiation, leading to impairment of organoid growth. Furthermore, the expression of CTCL fine-tunes Wnt/β-catenin signaling that controls cortex patterning. Together, this work provides evidence indicating important roles of fusion transcript in human brain development and evolution.
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http://dx.doi.org/10.1016/j.celrep.2021.109290DOI Listing
June 2021

Dietary niacin affects intestinal morphology and functions modulating cell proliferation in weaned piglets.

Food Funct 2021 Jun 29. Epub 2021 Jun 29.

Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process; National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production; Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan 410125, China.

Niacin deficiency leads to inflammation of mucous membranes and diarrhoea. There are few reports on the effects of niacin on the intestinal health of weaned piglets. The present study was conducted to analyse the effects of niacin in weaned piglets along with its underlying mechanism. A total of 48 25-day-old weaned piglets (24 females and 24 males) were randomly allotted into four groups, each treatment were supplemented with 22.5, 30, 45, and 75 mg kg-1 niacin for a period of 14 days, with 12 piglets per diet and 1 piglet per pen. Six piglets (3 males and 3 females) were randomly selected from each treatment group and euthanised for intestinal tissue sampling on days 7 and 14 after the weaning day (day 0), respectively. Dietary niacin did not affect the growth performance of weaned piglets but quadratically affected (P < 0.05) the diarrhoea rate from days 7 to 14. The duodenal villus height and width and crypt depth in the 30 mg kg-1 niacin group were greater than those in the 45 mg kg-1 niacin group on day 7, and the jejunal crypt depth, ileal crypt depth, villus height and villus width decreased (linear, P < 0.05) with the increase in dietary niacin. However, the dietary supplementation with niacin increased (linear, P < 0.001) the jejunal villus height, crypt depth and villus width on day 14. Dietary niacin increased (linear, P < 0.05) the alkaline phosphatase activity in the jejunal mucosa of weaned piglets on day 7 but decreased (linear, P < 0.05) its activity on day 14. The number of Ki67 positive cells per crypt was decreased (linear, P < 0.05) with the dietary niacin on day 7 but increased (linear, P < 0.05) with dietary niacin contents on day 14. Moreover, dietary niacin altered (P < 0.05) SLC5A1, SLC15A1, SLC6A19, TJP-1, occludin and claudin-1 mRNA expression in the small intestine. These results indicate that dietary niacin has different effects on intestinal morphology and functions in the first and second weeks postweaning and that the dietary supplementation with niacin may, by modulating intestinal cell proliferation, affect the intestinal health.
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http://dx.doi.org/10.1039/d0fo03097jDOI Listing
June 2021

Osteopontin isoform c promotes the survival of cisplatin-treated NSCLC cells involving NFATc2-mediated suppression on calcium-induced ROS levels.

BMC Cancer 2021 Jun 29;21(1):750. Epub 2021 Jun 29.

School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.

Background: Tumor microenvironment (TME) critically contributed to the malignant progression of transformed cells and the chemical responses to chemotherapy reagents. Osteopontin (OPN) is a secretory onco-protein with several splicing isoforms, all of which were known to regulate tumor growth and able to alter cell-cell or cell-TME communication, however, the exact role and regulation of the OPN splicing isoforms was not well understood.

Methods: In this study, the effects of conditioned medium from the culture of OPN splicing isoforms overexpressing cells on cell functions were evaluated. The methods of nuclear calcium reporter assays and subcellular distribution of nuclear factor of activated T cells c2 (NFATc2) assays were used to investigate the molecular mechanism underlining the roles of OPN splicing isoforms.

Results: We found that the survival of NSCLC cells treated with cisplatin was increased by secretory OPNc in the condition medium, where reduction of apoptosis by OPNc was associated with the activation of cellular calcium signals and subsequent nuclear translocation of NFATc2.

Conclusions: The results revealed a mechanism of OPN and downstream signal for tumor cells to survive in chemo-stressed TME, which emphasized the importance of secretory proteins in alternative splicing isoforms. Our study not only demonstrated the importance of OPN neutralization for anti-tumor effects, but also implied that modulation in calcium/NFATc2/ROS axis could be a novel approach for improving the long-term outcome of NSCLC treatment.
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http://dx.doi.org/10.1186/s12885-021-08495-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243455PMC
June 2021

Effect of dietary protein on growth performance, and serum biochemical index in late pregnant Hu ewes and their offspring.

Anim Biotechnol 2021 Jun 30:1-9. Epub 2021 Jun 30.

Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, College of Life Sciences, Hunan Normal University, Changsha, China.

The purpose of this study was to investigate the effects of different protein levels in late pregnancy on ewe and lamb growth performance, serum biochemical indexes. Thirty-three ewes (46.4 ± 1.38 kg initial weight) were randomly divided into 3 groups, with 11 ewes in each group. The protein levels of three diets formulated to provide components to meet 10.00 MJ/kg ME requirements diets were: 10.12%, 11.26%, 12.4%. Ewes were raised from the 90th day of pregnancy to the end of delivery, and the lambs were weaned at 60 days. Dietary protein levels had significant effects on blood urea nitrogen, glucose, ammonia nitrogen and triglyceride of ewes ( < 0.05). The height, chest depth, chest circumference, straight crown hip length and curved crown hip length of lambs decreased at first and then increased with the increase of protein. The body length, chest circumference, head width and head length of weaned lambs decreased at first and then increased with the increase of protein. The results showed that when the dietary protein level was increased to 12.4%, the amino acid, glucose and fat metabolism of ewes were affected. The body size development of lambs was better than 10.12% and 11.26% proteins.
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http://dx.doi.org/10.1080/10495398.2021.1939042DOI Listing
June 2021

Effects of nearly four decades of long-term fertilization on the availability, fraction and environmental risk of cadmium and arsenic in red soils.

J Environ Manage 2021 Jun 26;295:113097. Epub 2021 Jun 26.

Institute of Agro-environment and Ecology, Hunan Academy of Agricultural Sciences, Changsha, Hunan, 410125, China. Electronic address:

Fertilizers are important for agricultural production because they can effectively promote crop productivity. However, long-term fertilization can cause heavy metal accumulation in soils and crops. This study utilized sequential extraction, the diffusive gradient in the thin films (DGT) technique and risk assessment models to estimate the effects of the longest long-term fertilization (38 years) in China on cadmium (Cd) and arsenic (As) accumulation in soils. The treatments included no fertilization (CK); inorganic nitrogen, phosphorus, and potassium fertilization (NPK); manure fertilization (M); and NPK plus M cofertilization (NPKM). The results indicated that the soils treated with NPKM, M and NPK had significantly increased total and available concentrations of Cd and As after 38 years of long-term fertilization. Cd mainly originates from cattle manure, while As originates from phosphate fertilizer. Sequential extraction results indicated that the application of manure increased the acid/exchangeable fraction (F1) and organic matter-bound fraction (F3) of Cd and As. The risk assessment results showed that the environmental risks of both Cd and As increased during long-term fertilization, and Cd contamination in the soil was at a moderate-high level, while As remained at a relatively low level. According to the calculations of the maximum numbers of years of soil productivity and rice production, Cd was labile and accumulated in the soils, and As was more labile than Cd in terms of accumulating in rice, indicating that the true risk from As in rice is higher than that from Cd. Controlling the heavy metals in fertilizers, mitigating effective amendments, and identifying plant types that accumulate low amounts of contaminants may be good choices for cleaner crop production.
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http://dx.doi.org/10.1016/j.jenvman.2021.113097DOI Listing
June 2021

On specification tests for composite likelihood inference.

Biometrika 2020 Dec 14;107(4):907-917. Epub 2020 Jun 14.

Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, U.S.A.

Composite likelihood functions are often used for inference in applications where the data have a complex structure. While inference based on the composite likelihood can be more robust than inference based on the full likelihood, the inference is not valid if the associated conditional or marginal models are misspecified. In this paper, we propose a general class of specification tests for composite likelihood inference. The test statistics are motivated by the fact that the second Bartlett identity holds for each component of the composite likelihood function when these components are correctly specified. We construct the test statistics based on the discrepancy between the so-called composite information matrix and the sensitivity matrix. As an illustration, we study three important cases of the proposed tests and establish their limiting distributions under both null and local alternative hypotheses. Finally, we evaluate the finite-sample performance of the proposed tests in several examples.
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http://dx.doi.org/10.1093/biomet/asaa039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232013PMC
December 2020

Low BDNF levels in serum are associated with cognitive impairments in medication-naïve patients with current depressive episode in BD II and MDD.

J Affect Disord 2021 Jun 18;293:90-96. Epub 2021 Jun 18.

National Clinical Research Center for Mental Disorders, Department of Psychiatry, China National Technology Institute on Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China. Electronic address:

Objective: This study aimed to investigate the role of Brain-derived neurotrophic factor (BDNF) in clinical and cognitive outcomes in medication-naïve patients with Bipolar type II disorder (BD II) and Major depressive disorder (MDD).

Methods: 45 outpatients with BD II, 40 outpatients with MDD and 40 healthy controls (HCs) were recruited, and sociodemographic and clinical data were collected. Their BDNF serum levels were measured and analyzed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

Results: BDNF levels were significantly lower in BD II patients than in MDD patients and HCs (p = 0.001). BD II and MDD patients had similar cognitive performance deficits shown on Attention (p = 0.001), Delayed memory (p = 0.001), and RBANS total score (p = 0.001). BDNF levels were positively associated with Visuospatial / constructional and Stroop color-word in BD II group, and with language in MDD group. The area under the curve (AUC) of the ROC analysis in BD II vs. MDD was 0.664, therefore, BDNF levels could not distinguish BD II from MDD.

Conclusion: Our study showed the decreased serum BDNF in MDD and BD II patients, suggesting BDNF may be involved in the pathophysiology of MDD and BD II. BDNF and cognitive deficits are both of low efficiency in distinguishing BD II from MDD. Decrease of BDNF may potentially indicate cognitive dysfunction in BD II and MDD patients with a current depressive episode.
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http://dx.doi.org/10.1016/j.jad.2021.06.018DOI Listing
June 2021

A Risk Prediction Model of Readmission for Chinese Patients after Coronary Artery Bypass Grafting.

Heart Surg Forum 2021 May 25;24(3):E479-E483. Epub 2021 May 25.

Wuhan Puren Hospital, Wuhan, Hubei, China.

Background: Predictive models can be used to assess the risk of readmission for patients after coronary artery bypass grafting (CABG). However, the majority of the existing prediction models have been developed based on data of western population. Our objective was to develop and validate a risk prediction model for Chinese patients after CABG.

Methods: This study was conducted among 1983 patients who underwent CABG in Wuhan Asian Heart Hospital from January 2017 to October 2019. Pearson's chi-squared and multivariate logistic regression were performed to investigate the risk factors of readmission after CABG. The area under the ROC curve and Hosmer-Lemeshow test were used to validate the discrimination and calibration of the model, respectively.

Results: Six risk factors were predictive of readmission: age≥65 years (odds ratio [OR] = 2.19; 95% confidence interval [CI]: 1.11-4.34; P = 0.024),  female (OR = 2.46; 95%CI: 1.26-4.80; P = 0.008), private insurance (OR = 4.23; 95%CI: 1.11-16.11; P = 0.034), diabetes (OR = 2.351; 95%CI: 1.20-4.59; P = 0.012), hypertension (OR = 2.33; 95%CI: 1.16-4.66; P = 0.017), and congenital heart disease (OR = 6.93;95%CI: 2.04-23.52; P = 0.002). The area under the curve c-statistic was 0.876 in the derivation sample and 0.865 in the validation sample. Hosmer-Lemeshow test: P=0.561.

Conclusion: The risk prediction model in our study can be used to predict the risk of readmission in Chinese patients after CABG.
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http://dx.doi.org/10.1532/hsf.3773DOI Listing
May 2021

Bioinspired Heteromultivalent Chitosan--Fe₂O₃/Gadofullerene Hybrid Composite for Enhanced Antibiotic-Resistant Bacterial Pneumonia.

J Biomed Nanotechnol 2021 Jun;17(6):1217-1228

Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, and Institute of Respiratory Diseases, Guangzhou 510000, PR China.

Herein, we have designed and developed a heteromultivalent chitosan base -Fe₂O₃/Gadofullerene (GdF) hybrid composite through a simple chemical precipitation method. Unlike other methods, the addition of external stabilizing agents to generate GdF nanoparticles (NPs) was not necessary herein. The prepared chitosan--Fe₂O₃/GdF hybrid nanocomposites were characterized using UV, FT-IR, XRD and morphological microscopic analyses. The results showed that -Fe₂O₃ and GdF hybrid nanocomposites were successfully grown on the surface of chitosan. The FT-IR vibration peaks showed the formation of Fe₂O₃ NPs, and the vibration peak for Fe-O was 568 cm. The broad absorption peak observed in the range of 250-350 nm and a sharp absorption peak at 219 nm represents the UV absorption of the synthesized hybrid composites. XRD pattern showed sharp peaks of crystallinity and purity of -Fe₂O₃ nanoparticles. Finally, the synthesized chitosan--Fe₂O₃/GdF hybrid composites were screened for their antibacterial resistance against the , and . In addition, biocompatibility results exhibited that developed hybrid samples have provided high cell compatibility with fibroblast (L929) cell line. The bio inspired nanotherapeutics have the potential action to effective inhibition ability on antibiotic-resistant , which has been main factor of inducing pneumonia. In conclusion, we expect biomimicking systems combined with the effective antibacterial agent could be the suitable next generation therapeutic potential factors for prevention and treatment of antibiotic-resistant pneumonia.
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http://dx.doi.org/10.1166/jbn.2021.3093DOI Listing
June 2021

Development and validation of a reporter gene assay for bioactivity determination of Anti-CGRP monoclonal antibodies.

Anal Biochem 2021 Jun 20:114291. Epub 2021 Jun 20.

Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control, No.31, Huatuo Road, Biomedical Base, Daxing District, Beijing, 102629, China. Electronic address:

Calcitonin gene-related peptide (CGRP) is critical for the pathophysiology of migraine, and four therapeutic antibodies targeting CGRP and its corresponding receptors have been approved by the Food and Drug Administration (FDA), while many others are in the different stages of clinical trials. Bioactivity determination is essential for the quality control and clinical application of therapeutic monoclonal antibodies (mAbs). However, no bioassay has been reported to date. In this study, we developed a reporter gene assay (RGA) based on SK-N-MC cells stably expressing firefly luciferase driven by cAMP response element (CRE). The key assay parameters were optimized according to signal-to-noise (SNR), the response value, and the fitted dose-response curve. Validation of the RGA in accordance with ICH-Q2 guidelines showed that the method had good specificity, accuracy, linearity, and precision. The established RGA can be utilized as a reference method for release testing and stability studies of relevant antibodies.
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http://dx.doi.org/10.1016/j.ab.2021.114291DOI Listing
June 2021

DDB1 binds histone reader BRWD3 to activate the transcriptional cascade in adipogenesis and promote onset of obesity.

Cell Rep 2021 Jun;35(12):109281

Shanghai Key Laboratory of Metabolic Remodeling and Disease, Institute of Metabolism and Integrative Biology, Zhongshan Hospital, Fudan University, and Shanghai Qi Zhi Institute, Shanghai, China; State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, China. Electronic address:

Obesity has become a global pandemic. Identification of key factors in adipogenesis helps to tackle obesity and related metabolic diseases. Here, we show that DDB1 binds the histone reader BRWD3 to promote adipogenesis and diet-induced obesity. Although typically recognized as a component of the CUL4-RING E3 ubiquitin ligase complex, DDB1 stimulates adipogenesis independently of CUL4. A DDB1 mutant that does not bind CUL4A or CUL4B fully restores adipogenesis in DDB1-deficient cells. Ddb1 mice show delayed postnatal development of white adipose tissues and are protected from diet-induced obesity. Mechanistically, by interacting with BRWD3, DDB1 is recruited to acetylated histones in the proximal promoters of ELK1 downstream immediate early response genes and facilitates the release of paused RNA polymerase II, thereby activating the transcriptional cascade in adipogenesis. Our findings have uncovered a CUL4-independent function of DDB1 in promoting the transcriptional cascade of adipogenesis, development of adipose tissues, and onset of obesity.
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http://dx.doi.org/10.1016/j.celrep.2021.109281DOI Listing
June 2021

Perioperative and Oncologic Outcomes of Single-Port Multiport Robot-Assisted Radical Prostatectomy: A Meta-Analysis.

J Endourol 2021 Jul 21. Epub 2021 Jul 21.

Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.

Although single-port robot-assisted radical prostatectomy (SP-RARP) is considered a safe and feasible approach for radical prostatectomy, the comparative performance of the SP robot with earlier models, including da Vinci Xi or Si, is elusive. This systematic review summarizes the current evidence on SP-RARP and compares its perioperative, functional, and oncologic outcomes to multiport robot-assisted radical prostatectomy (MP-RARP). We performed a systematic search in PubMed, Embase, Web of Science, and Cochrane Library database for randomized control trials (RCTs) and non-RCTs that compare SP-RARP to MP-RARP. The primary outcomes included perioperative, functional, oncologic, and painful outcomes. The odds ratio (OR) and weighted mean difference (WMD) were applied for the comparison of dichotomous and continuous variables with 95% confidence intervals (CIs). Seven studies, including 1239 patients, were enrolled in the meta-analysis. We reported similar results for SP-RARP and MP-RARP in terms of the operative time, blood loss, continence and potency rates, complication rate, positive surgical margin, and biochemical recurrence. However, hospital stay (WMD -17.86 hours, 95% CI -27.80 to -7.92;  = 0.0004), catheterization time (WMD -1.51 days, 95% CI -2.60 to -0.41;  = 0.007), and the rate of opioid use (OR 0.26, 95% CI 0.13 to 0.53;  = 0.0002) were less with SP-RARP. In addition, more patients did not require any pain medication during the hospital stay with SP-RARP (OR 14.41, 95% CI 5.22 to 39.76;  < 0.00001). SP-RARP is associated with a shorter hospital stay and catheterization time, and the need for postoperative pain medication is lower compared to MP-RARP, with comparable perioperative, functional, and oncologic outcomes.
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http://dx.doi.org/10.1089/end.2021.0210DOI Listing
July 2021
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