Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 294
Filter
1.
Poult Sci ; 103(1): 103225, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38035860

ABSTRACT

Plumage color is an important economic trait for breed feature identification and consumer's requirements in pigeons. The domestic pigeon has multiple types of plumage color, thereby providing a unique opportunity to identify the genetic basis of plumage coloration. White feather color is common for meat and medicinal use. To investigate the genetic variation associated with white plumage color in pigeons, we use genome resequencing and population genomics to identify the genomic regions with strong selective signature between pigeons with brown and white plumage color. Meanwhile, we obtained some candidate genes with melanin or melanosome biosynthesis in selected regions. Finally, we identified a missense mutation p.E256K in the EDNRB2 completely associated with white plumage color. These findings provide a basis for genetic variation in pigeons with plumage color phenotype.


Subject(s)
Columbidae , Mutation, Missense , Animals , Columbidae/genetics , Metagenomics , Pigmentation/genetics , Chickens/genetics , Feathers , Color
2.
J Biomed Opt ; 28(4): 046009, 2023 04.
Article in English | MEDLINE | ID: mdl-37122476

ABSTRACT

Significance: In photoacoustic tomography (PAT), numerous reconstruction algorithms have been utilized to recover initial pressure rise distribution from the acquired pressure waves. In practice, most of these reconstructions are carried out on a desktop/workstation and the mobile-based reconstructions are far-flung. In recent years, mobile phones are becoming so ubiquitous, and most of them encompass a higher computing ability. Hence, realizing PAT image reconstruction on a mobile platform is intrinsic, and it will enhance the adaptability of PAT systems with point-of-care applications. Aim: To implement PAT image reconstruction in Android-based mobile platforms. Approach: For implementing PAT image reconstruction in Android-based mobile platforms, we proposed an Android-based application using Python to perform beamforming process in Android phones. Results: The performance of the developed application was analyzed on different mobile platforms using both simulated and experimental datasets. The results demonstrate that the developed algorithm can accomplish the image reconstruction of in vivo small animal brain dataset in 2.4 s. Furthermore, the developed application reconstructs PAT images with comparable speed and no loss of image quality compared to that on a laptop. Employing a two-fold downsampling procedure could serve as a viable solution for reducing the time needed for beamforming while preserving image quality with minimal degradation. Conclusions: We proposed an Android-based application that achieves image reconstruction on cheap, small, and universally available phones instead of relatively bulky expensive desktop computers/laptops/workstations. A beamforming speed of 2.4 s is achieved without hampering the quality of the reconstructed image.


Subject(s)
Cell Phone , Tomography, X-Ray Computed , Animals , Algorithms , Point-of-Care Systems , Image Processing, Computer-Assisted , Tomography
3.
Photoacoustics ; 34: 100575, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38174105

ABSTRACT

Accurate needle guidance is crucial for safe and effective clinical diagnosis and treatment procedures. Conventional ultrasound (US)-guided needle insertion often encounters challenges in consistency and precisely visualizing the needle, necessitating the development of reliable methods to track the needle. As a powerful tool in image processing, deep learning has shown promise for enhancing needle visibility in US images, although its dependence on manual annotation or simulated data as ground truth can lead to potential bias or difficulties in generalizing to real US images. Photoacoustic (PA) imaging has demonstrated its capability for high-contrast needle visualization. In this study, we explore the potential of PA imaging as a reliable ground truth for deep learning network training without the need for expert annotation. Our network (UIU-Net), trained on ex vivo tissue image datasets, has shown remarkable precision in localizing needles within US images. The evaluation of needle segmentation performance extends across previously unseen ex vivo data and in vivo human data (collected from an open-source data repository). Specifically, for human data, the Modified Hausdorff Distance (MHD) value stands at approximately 3.73, and the targeting error value is around 2.03, indicating the strong similarity and small needle orientation deviation between the predicted needle and actual needle location. A key advantage of our method is its applicability beyond US images captured from specific imaging systems, extending to images from other US imaging systems.

4.
Article in English | WPRIM (Western Pacific) | ID: wpr-1010268

ABSTRACT

The current review gives a comprehensive overview of the recent development in Chinese medicine (CM) for treating several kinds of acquired nerve deafness and tinnitus, as well as links the traditional principle to well-established pharmacological mechanisms for future research. To date, about 24 herbal species and 40 related ingredients used in CM to treat hearing loss and tinnitus are reported for the treatment of endocochlear potential, endolymph growth, lowering toxic and provocative substance aggregation, inhibiting sensory cell death, and retaining sensory transfer. However, there are a few herbal species that can be used for medicinal purposes. Nevertheless, clinical studies have been hampered by a limited population sample, a deficiency of a suitable control research group, or contradictory results. Enhanced cochlear blood flow, antiinflammatory antioxidant, neuroprotective effects, and anti-apoptotic, as well as multi-target approach on different auditory sections of the inner ear, are all possible benefits of CM medications. There are numerous unknown natural products for aural ailment and tinnitus identified in CM that are expected to be examined in the future utilizing various aural ailment models and processes.


Subject(s)
Humans , Tinnitus/drug therapy , Medicine, Chinese Traditional , Hearing Loss/drug therapy
5.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-991188

ABSTRACT

Objective:To analyse the clinical efficacy and outcome of early abdominal paracentesis drainage (APD) in the treatment of severe acute pancreatitis (SAP).Methods:The clinical data of 107 SAP patients with massive abdominal fluid in Shanghai General People Hospital from May 2017 to December 2021 were collected and analyzed. Patients were divided into APD group ( n=56) and NO-APD group ( n=51) according to whether they underwent APD or not within 3 days after admission. The APD group was then divided into abdominal compartment syndrome (ACS) subgroup ( n=29) and NO-ACS subgroup ( n=27) according to whether ACS had occurred or not at the time of puncture. Patients' general data, the duration of systemic inflammatory response (SIRS), length of ICU stay, the trends of intra-abdominal pressure and inflammatory indicators (white blood cell count and the content of C-reactive protein) within 1-3 days after admission, incidence of infection complication, step-up therapy, discharge or death were recorded. Results:The intra-abdominal pressure were 18.6±5.6mmHg , 13.7±4.2mmHg (1 mmHg=0.133 kpa) in APD group and NO-APD group, respectively. The intra-abdominal pressure of APD group was significantly higher than that of NO-APD group, and the difference was statistically significant ( P=0.000). Compared with NO-APD group, the duration of SIRS was significantly shortened in APD group [3(2, 4) days vs 4(3, 6) days, P=0.029]. On day 1, 2 and 3 after admission, the intra-abdominal pressure was 18.6±5.6 mmHg, 16.4±4.7 mmHg and 13.5±3.9 mmHg in APD group, and was 13.7±4.2 mmHg, 12.3±3.6 mmHg and 11.0±2.6 mmHg in NO-APD group, respectively. The intra-abdominal pressure of the APD group dropped faster than the NO-APD group ( P=0.004). The white blood cell count was (14.8±4.8), (10.5±4.5) and (9.0±3.8)×10 9/L in APD group, and was (14.2±5.4), (12.3±7.3), (11.7±5.3)×10 9/L in NO-APD group, respectively. Compared with the NO-APD group, the decrease rate of white blood cell count was faster in APD group ( P=0.006). The C-reactive protein content was (153.6±47.1), (150.4±10.5) and (108.8±49.4)mg/L in APD group, and were (174.8±31.1), (191.6±29.4) and (186.8±45.5)mg/L in NO-APD group . The content of C-reactive protein in APD group decreased significantly, while that in NO-APD group did not decrease. There was a significant difference between the two groups ( P=0.009). In the subgroup comparisons, the duration of SIRS in the ACS subgroup was significant longer than that in the NO-ACS subgroup [4(3, 5) days vs 2(1, 3)days, P=0.000]. Compared between the two groups and two subgroups respectively, there were no statistically significant differences on length of ICU stay, infection complication rate, advanced treatment rate and mortality. Conclusions:For SAP patients with abdominal fluid, APD in the early stage could shorten the duration of SIRS, decrease intra-abdominal pressure rapidly, improve inflammatory indicators, but could not improve the clinical outcome.

6.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-991181

ABSTRACT

Objective:To construct a risk prediction model for infection with Klebsiella pneumonia (KP) for patients with severe acute pancreatitis (SAP).Methods:Retrospective analysis was done on the clinical data of 109 SAP patients who were admitted to Shanghai General Hospital, between March 2016 and December 2021. Patients were classified into infection group ( n=25) and non-infection group ( n=84) based on the presence or absence of KP infection, and the clinical characteristics of the two groups were compared. The least absolute shrinkage and selection operator (LASSO) algorithm was used to reduce the dimension of the variables with statistical significance in univariate analysis. A nomogram prediction model was created by incorporating the optimized features from the LASSO regression model into the multivariate logistic regression analysis. Receiver operating characteristic curve (ROC) was drawn and the area under curve (AUC) was calculated; and consistency index (C-index) were used to assess the prediction model's diagnostic ability. Results:A total of 25 strains of KP were isolated from 109 patients with SAP, of which 21(84.0%) had multi-drug resistance. 20 risk factors (SOFA score, APACHEⅡ score, Ranson score, MCTSI score, mechanical ventilation time, fasting time, duration of indwelling of the peritoneal drainage tube, duration of deep vein indwelling, number of invasive procedures, without or with surgical intervention, without or with endoscopic retrograde cholangiopancreatography (ERCP), types of high-level antibiotics used, digestion disorders, abnormalities in blood coagulation, metabolic acidosis, pancreatic necrosis, intra-abdominal hemorrhage, intra-abdominal hypertension, length of ICU stay and total length of hospital stay) were found to be associated with KP infection in SAP patients by univariate analysis. The four variables (APACHEⅡ score, duration of indwelling of the peritoneal drainage tube, types of high-level antibiotics used, and total length of hospital stay) were extracted after reduced by LASSO regression. These four variables were found to be risk factors for KP infection in SAP patients by multiple logistic regression analysis (all P value <0.05). Nomogram prediction model for KP infection in SAP was established based on the four variables above. The verification results of the model showed that the C-index of the model was 0.939, and the AUC was 0.939 (95% CI 0.888-0.991), indicating that the nomogram model had relatively accurate prediction ability. Conclusions:This prediction model establishes integrated the basic clinical data of patients, which could facilitate the risk prediction for KP infection in patients with SAP and thus help to formulate better therapeutic plans for patients.

7.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1009417

ABSTRACT

Objective To investigate the role of microRNA-18a (miR-18a) in the pathogenesis of allergic rhinitis in mice. Methods Twenty-two BALB/c mice were randomly divided into a blank group, a model group and a miR-18a group. Mice in the model group and the miR-18a group were injected intraperitoneally with obumin (OVA) suspension to prepare allergic rhinitis models, and mice in the miR-18a group were simultaneously given lentiviral vector plasmid for overexpression of miR-18a. Allergy symptoms were evaluated by the behavioral score and HE staining. The plasma levels of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α) were measured by ELISA. The distribution of CD45+ cells in nasal mucosa was measured by immunofluorescence histochemistry, and CD45+ cells in nasal lavage fluid were measured by flow cytometry. The mRNA expression levels of IL-1β, IL-6 and TNF-α in nasal mucosa tissues were measured by fluorescence quantitative PCR, and the protein expressions of Toll like receptor 4 (TLR4), nuclear factor κB p65 (NF-κB p65), inhibitor of NF-κB α (IκBα) and phosphorylated IκBα (p-IκBα) in nasal mucosa were measured by Western blot analysis. Results Compared with the blank group, the plasma levels of IL-1β, IL-6, and TNF-α in the model group increased significantly. The number of CD45+ cells in both nasal mucosa tissue and nasal irrigation fluid increased, and the mRNA levels of IL-1β, IL-6 and TNF-α and the protein expression levels of TLR4, NF-κB p65 and p-IκBα in nasal mucosa increased. Compared with the model group, the plasma levels of IL-1β, IL-6 and TNF-α in the miR-18a group decreased significantly. The number of CD45+ cells in both nasal mucosa tissue and nasal lavage fluid decreased, and the mRNA levels of IL-1β, IL-6 and TNF-α and the exprotein expression levels of TLR4, NF-κB p65 and p-IκBα in nasal mucosa decreased. Conclusion miR-18a can inhibit the occurrence and development of allergic rhinitis, and its molecular mechanism is related to the inhibition of TLR4/NF-κB pathway activation.


Subject(s)
Animals , Mice , Disease Models, Animal , Inflammation , Interleukin-6/genetics , MicroRNAs/genetics , NF-kappa B/metabolism , NF-KappaB Inhibitor alpha , Rhinitis, Allergic , RNA, Messenger , Toll-Like Receptor 4/metabolism , Tumor Necrosis Factor-alpha/genetics
8.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1008696

ABSTRACT

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 μm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 μL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 μmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.


Subject(s)
Humans , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/chemistry , Asteraceae/chemistry , Lung Neoplasms/drug therapy
9.
Acta Pharmaceutica Sinica ; (12): 616-628, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-965629

ABSTRACT

From the process of human immunodeficiency virus-1 (HIV-1) invading cells, the combination of gp120 and CD4 is the first step for HIV-1 to invade cells. Interfering with this process can prevent HIV from recognizing target cells and inhibit virus replication. Therefore, HIV-1 gp120 is an important part of the HIV-1 life cycle. Fostesavir, a phosphatate prodrug derived from the gp120 inhibitor BMS-626529 modified by the prodrug strategy, was approved for the treatment of adult patients with multidrug resistant HIV-1 infection by the US FDA and the European Medicines Agency in 2020 and 2021, respectively. In this review, we focus on the research progress of small molecule inhibitors targeting the interaction of gp120-CD4 from the perspective of medicinal chemistry, in order to provide reference for the subsequent research of gp120 inhibitors.

10.
J Biomed Opt ; 27(7): 070901, 2022 07.
Article in English | MEDLINE | ID: mdl-36451698

ABSTRACT

Significance: Deep tissue noninvasive high-resolution imaging with light is challenging due to the high degree of light absorption and scattering in biological tissue. Photoacoustic imaging (PAI) can overcome some of the challenges of pure optical or ultrasound imaging to provide high-resolution deep tissue imaging. However, label-free PAI signals from light absorbing chromophores within the tissue are nonspecific. The use of exogeneous contrast agents (probes) not only enhances the imaging contrast (and imaging depth) but also increases the specificity of PAI by binding only to targeted molecules and often providing signals distinct from the background. Aim: We aim to review the current development and future progression of photoacoustic molecular probes/contrast agents. Approach: First, PAI and the need for using contrast agents are briefly introduced. Then, the recent development of contrast agents in terms of materials used to construct them is discussed. Then, various probes are discussed based on targeting mechanisms, in vivo molecular imaging applications, multimodal uses, and use in theranostic applications. Results: Material combinations are being used to develop highly specific contrast agents. In addition to passive accumulation, probes utilizing activation mechanisms show promise for greater controllability. Several probes also enable concurrent multimodal use with fluorescence, ultrasound, Raman, magnetic resonance imaging, and computed tomography. Finally, targeted probes are also shown to aid localized and molecularly specific photo-induced therapy. Conclusions: The development of contrast agents provides a promising prospect for increased contrast, higher imaging depth, and molecularly specific information. Of note are agents that allow for controlled activation, explore other optical windows, and enable multimodal use to overcome some of the shortcomings of label-free PAI.


Subject(s)
Contrast Media , Molecular Probes , Spectrum Analysis , Tomography, X-Ray Computed
11.
- IMPACC group; Al Ozonoff; Joanna Schaenman; Naresh Doni Jayavelu; Carly E. Milliren; Carolyn S. Calfee; Charles B. Cairns; Monica Kraft; Lindsey R. Baden; Albert C. Shaw; Florian Krammer; Harm Van Bakel; Denise Esserman; Shanshan Liu; Ana Fernandez Sesma; Viviana Simon; David A. Hafler; Ruth R. Montgomery; Steven H. Kleinstein; Ofer Levy; Christian Bime; Elias K. Haddad; David J. Erle; Bali Pulendran; Kari C. Nadeau; Mark M. Davis; Catherine L. Hough; William B. Messer; Nelson I. Agudelo Higuita; Jordan P. Metcalf; Mark A. Atkinson; Scott C. Brakenridge; David B. Corry; Farrah Kheradmand; Lauren I. R. Ehrlich; Esther Melamed; Grace A. McComsey; Rafick Sekaly; Joann Diray-Arce; Bjoern Peters; Alison D. Augustine; Elaine F. Reed; Kerry McEnaney; Brenda Barton; Claudia Lentucci; Mehmet Saluvan; Ana C. Chang; Annmarie Hoch; Marisa Albert; Tanzia Shaheen; Alvin Kho; Sanya Thomas; Jing Chen; Maimouna D. Murphy; Mitchell Cooney; Scott Presnell; Leying Guan; Jeremy Gygi; Shrikant Pawar; Anderson Brito; Zain Khalil; James A. Overton; Randi Vita; Kerstin Westendorf; Cole Maguire; Slim Fourati; Ramin Salehi-Rad; Aleksandra Leligdowicz; Michael Matthay; Jonathan Singer; Kirsten N. Kangelaris; Carolyn M. Hendrickson; Matthew F. Krummel; Charles R. Langelier; Prescott G. Woodruff; Debra L. Powell; James N. Kim; Brent Simmons; I.Michael Goonewardene; Cecilia M. Smith; Mark Martens; Jarrod Mosier; Hiroki Kimura; Amy Sherman; Stephen Walsh; Nicolas Issa; Charles Dela Cruz; Shelli Farhadian; Akiko Iwasaki; Albert I. Ko; Evan J. Anderson; Aneesh Mehta; Jonathan E. Sevransky; Sharon Chinthrajah; Neera Ahuja; Angela Rogers; Maja Artandi; Sarah A.R. Siegel; Zhengchun Lu; Douglas A. Drevets; Brent R. Brown; Matthew L. Anderson; Faheem W. Guirgis; Rama V. Thyagarajan; Justin Rousseau; Dennis Wylie; Johanna Busch; Saurin Gandhi; Todd A. Triplett; George Yendewa; Olivia Giddings; Tatyana Vaysman; Bernard Khor; Adeeb Rahman; Daniel Stadlbauer; Jayeeta Dutta; Hui Xie; Seunghee Kim-Schulze; Ana Silvia Gonzalez-Reiche; Adriana van de Guchte; Holden T. Maecker; Keith Farrugia; Zenab Khan; Joanna Schaenman; Elaine F. Reed; Ramin Salehi-Rad; David Elashoff; Jenny Brook; Estefania Ramires-Sanchez; Megan Llamas; Adreanne Rivera; Claudia Perdomo; Dawn C. Ward; Clara E. Magyar; Jennifer Fulcher; Yumiko Abe-Jones; Saurabh Asthana; Alexander Beagle; Sharvari Bhide; Sidney A. Carrillo; Suzanna Chak; Rajani Ghale; Ana Gonzales; Alejandra Jauregui; Norman Jones; Tasha Lea; Deanna Lee; Raphael Lota; Jeff Milush; Viet Nguyen; Logan Pierce; Priya Prasad; Arjun Rao; Bushra Samad; Cole Shaw; Austin Sigman; Pratik Sinha; Alyssa Ward; Andrew - Willmore; Jenny Zhan; Sadeed Rashid; Nicklaus Rodriguez; Kevin Tang; Luz Torres Altamirano; Legna Betancourt; Cindy Curiel; Nicole Sutter; Maria Tercero Paz; Gayelan Tietje-Ulrich; Carolyn Leroux; Jennifer Connors; Mariana Bernui; Michele Kutzler; Carolyn Edwards; Edward Lee; Edward Lin; Brett Croen; Nicholas Semenza; Brandon Rogowski; Nataliya Melnyk; Kyra Woloszczuk; Gina Cusimano; Matthew Bell; Sara Furukawa; Renee McLin; Pamela Marrero; Julie Sheidy; George P. Tegos; Crystal Nagle; Nathan Mege; Kristen Ulring; Vicki Seyfert-Margolis; Michelle Conway; Dave Francisco; Allyson Molzahn; Heidi Erickson; Connie Cathleen Wilson; Ron Schunk; Trina Hughes; Bianca Sierra; Kinga K. Smolen; Michael Desjardins; Simon van Haren; Xhoi Mitre; Jessica Cauley; Xiofang Li; Alexandra Tong; Bethany Evans; Christina Montesano; Jose Humberto Licona; Jonathan Krauss; Jun Bai Park Chang; Natalie Izaguirre; Omkar Chaudhary; Andreas Coppi; John Fournier; Subhasis Mohanty; M. Catherine Muenker; Allison Nelson; Khadir Raddassi; Michael Rainone; William Ruff; Syim Salahuddin; Wade L. Schulz; Pavithra Vijayakumar; Haowei Wang; Elsio Wunder Jr.; H. Patrick Young; Yujiao Zhao; Miti Saksena; Deena Altman; Erna Kojic; Komal Srivastava; Lily Q. Eaker; Maria Carolina Bermudez; Katherine F. Beach; Levy A. Sominsky; Arman Azad; Juan Manuel Carreno; Gagandeep Singh; Ariel Raskin; Johnstone Tcheou; Dominika Bielak; Hisaaki Kawabata; Lubbertus CF Mulder; Giulio Kleiner; Laurel Bristow; Laila Hussaini; Kieffer Hellmeister; Hady Samaha; Andrew Cheng; Christine Spainhour; Erin M. Scherer; Brandi Johnson; Amer Bechnak; Caroline R. Ciric; Lauren Hewitt; Bernadine Panganiban; Chistopher Huerta; Jacob Usher; Erin Carter; Nina Mcnair; Susan Pereira Ribeiro; Alexandra S. Lee; Evan Do; Andrea Fernandes; Monali Manohar; Thomas Hagan; Catherine Blish; Hena Naz Din; Jonasel Roque; Samuel S. Yang; Amanda E. Brunton; Peter E. Sullivan; Matthew Strnad; Zoe L. Lyski; Felicity J. Coulter; John L. Booth; Lauren A. Sinko; Lyle Moldawer; Brittany Borrensen; Brittney Roth-Manning; Li-Zhen Song; Ebony Nelson; Megan Lewis-Smith; Jacob Smith; Pablo Guaman Tipan; Nadia Siles; Sam Bazzi; Janelle Geltman; Kerin Hurley; Giovanni Gabriele; Scott Sieg; Matthew C. Altman; Patrice M. Becker; Nadine Rouphael.
Preprint in English | medRxiv | ID: ppmedrxiv-22273396

ABSTRACT

BackgroundBetter understanding of the association between characteristics of patients hospitalized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management. MethodsImmunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1,164 patients from 20 hospitals across the United States. Disease severity was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multivariable logistic regression was performed. FindingsThe median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsupervised clustering of ordinal score over time revealed distinct disease course trajectories. Risk factors associated with prolonged hospitalization or death by day 28 included age [≥] 65 years (odds ratio [OR], 2.01; 95% CI 1.28-3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13-2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63-4.80) or troponin (OR 1.89; 95% 1.03-3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61-2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96-5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17-2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) having at least one symptom consistent with PASC, most commonly dyspnea (56% among symptomatic patients). Female sex was the only associated risk factor for PASC. InterpretationIntegration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19. FundingNIH RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSWe did a systematic search of the PubMed database from January 1st, 2020 until April 24th, 2022 using the search terms: "hospitalized" AND "SARS-CoV-2" OR "COVID-19" AND "Pro-spective" AND "Antibody" OR "PCR" OR "long term follow up" and applying the following filters: "Multicenter Study" AND "Observational Study". No language restrictions were applied. While clinical, laboratory, and radiographic features associated with severe COVID-19 in hospitalized adults have been described, description of the kinetics of SARS-CoV-2 specific assays available to clinicians (e.g. PCR and binding antibody) and their integration with other variables is scarce for both short and long term follow up. The current literature is comprised of several studies with small sample size, cross-sectional design with laboratory data typically only recorded at a single point in time (e.g., on admission), limited clinical characteristics, variable duration of follow up, single-center setting, retrospective analyses, kinetics of either PCR or antibody testing but not both, and outcomes such as death or, mechanical ventilation that do not allow delineation of variations in clinical course. Added value of this studyIn our large longitudinal multicenter cohort, the description of outcome severity, was not limited to survival versus death, but encompassed a clinical trajectory approach leveraging longitudinal data based on time in hospital, disease severity by ordinal scale based on degree of respiratory illness, and presence or absence of limitations at discharge. Fatal COVID-19 cases had the lowest ratio of antibody to viral load levels over time as compared to non-fatal cases. Integration of PCR cycle threshold and antibody values with demographics, baseline comorbidities, and laboratory/radiographic findings identified additional risk factors for outcome severity over the first 28 days. However, female sex was the only variable associated with persistence of symptoms over time. Persistence of symptoms was not associated with clinical trajectory over the first 28 days, nor with antibody/viral loads from the acute phase. Implications of all the available evidenceThe described calculated ratio (binding IgG/PCR Ct value) is unique compared to other studies, reflecting host pathogen interactions and representing an accessible approach for patient risk stratification. Integration of SARS-CoV-2 viral load and binding antibody kinetics with other laboratory as well as clinical characteristics in hospitalized COVID-19 patients can identify patients likely to have the most severe short-term outcomes, but is not predictive of symptom persistence at one year post-discharge.

12.
Preprint in English | bioRxiv | ID: ppbiorxiv-483032

ABSTRACT

The emerging SARS-CoV-2 variants of concern (VOCs) exhibit enhanced transmission and immune escape, reducing the efficacy and effectiveness of the two FDA-approved mRNA vaccines. Here, we explored various strategies to develop novel mRNAs vaccines to achieve safer and wider coverage of VOCs. Firstly, we constructed a cohort of mRNAs that feature a furin cleavage mutation in the spike (S) protein of predominant VOCs, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2). Not present in the mRNA vaccines currently in use, the mutation abolished the cleavage between the S1 and S2 subunits, potentially enhancing the safety profile of the immunogen. Secondly, we systematically evaluated the induction of neutralizing antibodies (nAb) in vaccinated mice, and discovered that individual VOC mRNAs elicited strong neutralizing activity in a VOC-specific manner. Thirdly, the IgG produced in mice immunized with Beta-Furin and Washington (WA)-Furin mRNAs showed potent cross-reactivity with other VOCs, which was further corroborated by challenging vaccinated mice with the live virus of VOCs. However, neither WA-Furin nor Beta-Furin mRNA elicited strong neutralizing activity against the Omicron variant. Hence, we further developed an Omicron-specific mRNA vaccine that restored protection against the original and the sublineages of Omicron variant. Finally, to broaden the protection spectrum of the new Omicron mRNA vaccine, we tested the concept of bivalent immunogen. Instead of just fusing two RBDs head-to-tail, we for the first time constructed an mRNA-based chimeric immunogen by introducing the RBD of Delta variant into the entire S antigen of Omicron. The resultant chimeric mRNA was capable of inducing potent and broadly acting nAb against Omicron (both BA.1 and BA.2) and Delta, which paves the way to develop new vaccine candidate to target emerging variants in the future.

13.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-928149

ABSTRACT

The methods for determining the characteristic chromatogram and index components content of Xuanfu Daizhe Decoction were established to provide a scientific basis for the quality evaluation of substance benchmarks and preparations. Eighteen batches of Xuanfu Daizhe Decoction were prepared with the decoction pieces of different batches and of the same batch were prepared respectively, and the HPLC characteristic chromatograms of these samples were established. The similarities of the chromatographic fingerprints were analyzed. With liquiritin, glycyrrhizic acid, 6-gingerol, ginsenoside Rg_1, and ginsenoside Re as index components, the high performance liquid chromatography was established for content determination with no more than 70%-130% of the mass average as the limit. The results showed that there were 19 characteristic peaks corresponding to the characteristic chromatograms of 18 batches of Xuanfu Daizhe Decoction, including 8 peaks representing liquiritin, 1,5-O-dicaffeoylqunic acid, ginsenoside Rg_1, ginsenoside Re, 1-O-acetyl britannilactone, ginsenoside Rb_1, glycyrrhizic acid, and 6-gingerol, and the fingerprint similarity was greater than 0.97. The contents of liquiritin, glycyrrhizic acid, 6-gingerol, and ginsenosides Rg_1 + Re in the prepared Xuanfu Daizhe Decoction samples were 0.53%-0.86%, 0.61%-1.2%, 0.023%-0.068%, and 0.33%-0.66%, respectively. Except for several batches, most batches of Xuanfu Daizhe Decoction showed stable contents of index components, with no discrete values. The characteristic chromatograms and index components content characterized the information of Inulae Flos, Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, and Zingiberis Rhizoma Recens in Xuanfu Daizhe Decoction. This study provides a scientific basis for the further research on the key chemical properties of substance benchmark and preparations of Xuanfu Daizhe Decoction.


Subject(s)
Benchmarking , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/chemistry , Ginsenosides/analysis , Glycyrrhizic Acid/analysis , Quality Control
14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-927973

ABSTRACT

Following the preparation of substance benchmarks in Huanglian Decoction from 18 batches, the method for detecting their characteristic spectra was established to identify the similarity range and peak attribution. The content and transfer rate ranges of the index components coptisine, palmatine, berberine, liquiritin, glycyrrhizic acid, 6-gingerol, and cinnamaldehyde and the extraction amount were combined for analyzing the quality value transfer from the Chinese medicinal pieces to substance benchmarks and clarifying the key quality attributes of substance benchmarks in Huanglian Decoction. The results showed that the substance benchmarks in Huang-lian Decoction of 18 batches exhibited good similarity in characteristic spectra(all greater than 0.98). There were 17 characteristic peaks identified in the substance benchmarks of Huanglian Decoction, including 10 from Coptidis Rhizoma, 3 from Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle(processed with water), 1 from Zingiberis Rhizoma, and 3 from Cinnamomi Ramulus. The contents and average transfer rates of the index components were listed as follows: coptisine 2.20-6.46 mg·g~(-1) and 18.50%±2.93%; palmatine 3.03-8.13 mg·g~(-1) and 26.56%±4.69%; berberine 7.71-22.29 mg·g~(-1) and 17.34%±3.00%; liquiritin 0.88-2.18 mg·g~(-1) and 9.88%±4.88%; glycyrrhizic acid 1.83-4.44 mg·g~(-1) and 8.50%±3.72%; 6-gingerol 0.56-1.43 mg·g~(-1) and 11.36%±2.37%; cinnamaldehyde 1.55-3.48 mg·g~(-1) and 19.02%±4.36%. The extraction amount of the substance benchmarks from the 18 batches was controlled at 10.65%-13.88%. In this paper, the quality value transfer of substance benchmarks in Huanglian Decoction was analyzed based on the characteristic spectra, the index component contents and the extraction amount, which has provided a basis for the subsequent development of Huanglian Decoction and the quality control of its related preparations.


Subject(s)
Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/standards , Quality Control
15.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-927972

ABSTRACT

A total of 18 batches of Zhuru Decoction samples were prepared. Chromatographic fingerprints were established for Zhuru Decoction and single decoction pieces, the content of which was then determined. The extraction rate ranges, content, and transfer rate ranges of puerarin, liquiritin, and glycyrrhizic acid, together with the common peaks and the similarity range of the fingerprints, were determined to clarify key quality attributes of Zhuru Decoction. The 18 batches of Zhuru Decoction samples had 25 common peaks and the fingerprint similarity higher than 0.95. Puerariae Lobatae Radix, Glycyrrhizae Radix et Rhizoma, and Zingiberis Rhizoma Recens had 21, 3, and 1 characteristic peaks, respectively. The 18 batches of samples showed the extraction rates within the range of 18.45%-25.29%. Puerarin had the content of 2.20%-3.07% and the transfer rate of 38.5%-45.9%; liquiritin had the content of 0.24%-0.85% and the transfer rate of 15.9%-37.5%; glycyrrhizic acid had the content of 0.39%-1.87% and the transfer rate of 16.2%-32.8%. In this paper, the quality value transmitting of substance benchmarks of Zhuru Decoction was analyzed based on chromatographic fingerprints, extraction rate, and the content of index components. A scientific and stable method was preliminarily established, which provided a scientific basis for the quality control and formulation development of Zhuru Decoction.


Subject(s)
Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/standards , Glycyrrhizic Acid/analysis , Quality Control , Rhizome/chemistry
16.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-927861

ABSTRACT

Mechanical stimulus is critical to cardiovascular development during embryogenesis period.The mechanoreceptors of endocardial cells and cardiac myocytes may sense mechanical signals and initiate signal transduction that induce gene expression at a cellular level,and then translate molecular-level events into tissue-level deformations,thus guiding embryo development.This review summarizes the regulatory roles of mechanical signals in the early cardiac development including the formation of heart tube,looping,valve and septal morphogenesis,ventricular development and maturation.Further,we discuss the potential mechanical transduction mechanisms of platelet endothelial cell adhesion molecule 1-vascular endothelial-cadherin-vascular endothelial growth factor receptor 2 complex,primary cilia,ion channels,and other mechanical sensors that affect some cardiac malformations.


Subject(s)
Animals , Humans , Heart/embryology , Mechanotransduction, Cellular , Myocytes, Cardiac/physiology , Vascular Endothelial Growth Factor A/metabolism
17.
Chinese Journal of Endemiology ; (12): 986-989, 2022.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-991559

ABSTRACT

Objective:To analyze the results of plague surveillance in Qinghai Province from 2011 to 2020, master the epidemic situation in recent years, and provide scientific basis for prevention and control of the plague in the future.Methods:The human plague epidemic data (from the human case database of Qinghai Institute for Endemic Disease Prevention and Control) and animal plague epidemic data (from plague monitoring data and plague focus survey data of Qinghai Province) from 2011 to 2020 were collected and analyzed with descriptive epidemiological methods, including human plague epidemic, animal plague epidemic regional distribution, host animal monitoring results, pathogenic monitoring results and serological monitoring results.Results:From 2011 to 2020, there was a human plague epidemic in Qinghai Province, which was infected due to the infection of a middle finger of the right hand that was accidentally scratched when peeling marmots, and Yersinia pestis was isolated from heart, liver, lung, lymph node puncture fluid, tracheal secretion and throat swab samples of the deceased. There were 16 animal plague epidemics and endemic areas were distributed in Haixi Prefecture, Yushu Prefecture and Haibei Prefecture, among which the animal plague epidemic was the most prevalent in Haixi Prefecture, with 13 outbreaks in recent 10 years. According to the monitoring of host animals, the main host animal was the Himalayan marmot, with an average density of 0.07/hm 2. Pathgenic monitoring showed that 31 strains of Yersinia pestis were isolated, of which 27 strains were isolated from Haixi Prefecture. The host animals of Yersinia pestis were mainly Himalayan marmot, accounting for 77.42% (24/31) of the total. Serological monitoring showed that 66 plague F1 antibody positive sera were detected, of which 43 were dog positive sera; the Himalayan marmot took the second place, 20. Conclusion:From 2011 to 2020, the animal plague in Qinghai Province has continued for many years, with some areas showing an active trend, and the overall situation of plague prevention and control is severe.

18.
Chinese Pharmacological Bulletin ; (12): 110-118, 2022.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1014181

ABSTRACT

Aim To study the nephrotoxicity effects of the main monomers in Zuojin Pills. Methods CCK-8 and high-content toxicity screening were used to preliminarily screen the main alkaloids in Zuojin Pills that may cause renal cell damage. Further, by confirmation of cell morphology, release rate of lactate dehydrogenase and cytochrome C, and expression of apoptosis-related proteins, the alkaloids causing cell damage were preliminarily identified, providing in vitro toxicological evidence for the compatibility of components of traditional Chinese medicine and compatibility attenuation. Results Preliminary screening using CCK-8 method and high-content technology showed that evodiamine (EVO) could significantly reduce cell number, increase cell membrane permeability, and reduce mitochondrial membrane potential. In addition, cell morphology, apoptosis and cytochrome C expression were consistent with the results of high-content screening. Western blot experiments indicate that EVO could induce apoptosis and cause renal cell damage. Conclusions EVO can obviously cause renal cell damage, and may induce apoptosis by affecting mitochondria, cytochrome C and cell membrane permeability.

19.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-934120

ABSTRACT

Clinical data of 210 patients with early colorectal cancer and precancerous lesion treated by endoscopic submucosal dissection (ESD) in the Digestive Endoscopy Center of the Seventh Medical Center of Chinese PLA General Hospital from January 2015 to March 2018 were collected and analyzed retrospectively. Patients were divided into two groups according to the age: the elderly group (≥65 years old, 100 cases) and the non-elderly group (<65 years old, 110 cases). The en bloc resection rate, complete resection rate,and curative resection rate of the elderly group were 92.0% (92/100), 91.0% (91/100) and 89.0% (89/100), respectively. The above indicators of the non-elderly group were 90.9% (100/110) ( P=0.972), 90.0% (99/110) ( P=0.991) and 88.2% (97/110) ( P=1.000), respectively. The incidence of intraoperative perforation in the elderly group was 4.0% (4/100) and in the non-elderly group was 6.4% (7/110) ( P=0.543). Delayed postoperative bleeding rate was 2.0% (2/100) in the elderly group, and 0 (0/110) in the non-elderly group ( P=0.226). ESD is effective and safe in treating early colorectal cancer and precancerous lesion in elderly patients.

20.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-934100

ABSTRACT

To investigate the efficacy and safety of endoscopic bougie dilation and stent implantation for pediatric caustic esophageal stenosis. Clinical characteristics, diagnosis and treatment of children with pediatric caustic esophageal stenosis from October 2009 to December 2019 at Department of Gastroenterology, the Seventh Medical Center of PLA General Hospital were retrospectively analyzed. A total of 50 caustic esophageal stenosis cases were enrolled, among whom, 94.0% (47/50) received conservative treatment before sending to our hospital. Thirty-six (72.0%) of them accidently ingested caustic substance of alkali and 22.0% (11/50) of them accidently ingested caustic substance of acid. Forty-six children (92.0%) who ingested caustic agents were younger than 7 years old. The stenosis was more common in the upper esophagus, accounting for 64.0% (32/50). Twenty-seven cases (54.0%) underwent simple bougie dilation and 16 cases (32.0%) underwent bougie dilation combined with stent treatment. All 50 children underwent a total of 1 260 expansions. The numbers of simple dilations and dilations combined with stent implantation were 37.8±26.2, 20.9±12.6 respectively with significant difference ( t=2.453, P=0.021). Among them, 2 cases (4.0%) underwent surgery, 5 cases (10.0%) underwent surgery combined with dilatation and stent implantation. The stenosis diameter widened significantly after treatment (1.1±0.2 cm VS 0.2±0.1 cm, t=23.004, P<0.001), and the Stooler grade of dysphagia improved significantly (grade 3.5±0.5 VS 1.2±0.7, t=19.925, P<0.001). Perforation occurred in only 1 patient, who was cured by conservative treatment with stent implantation. The total effective rate was 100.0% (50/50) and the satisfaction rate was 98.0% (49/50). Endoscopic bougie dilation and bougie dilation combined with stent implantation is safe and effective for pediatric caustic esophageal stenosis. Combination with stent implantation can reduce the number of dilation times.

SELECTION OF CITATIONS
SEARCH DETAIL
...