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1.
RSC Chem Biol ; 5(4): 372-385, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38576719

RESUMO

Phenotypic screening is a valuable tool to both understand and engineer complex biological systems. We demonstrate the functionality of this approach in the development of cell-free protein synthesis (CFPS) technology. Phenotypic screening identified numerous compounds that enhanced protein production in yeast lysate CFPS reactions. Notably, many of these were competitive ATP kinase inhibitors, with the exploitation of their inherent substrate promiscuity redirecting ATP flux towards heterologous protein expression. Chemoproteomic-guided strain engineering partially phenocopied drug effects, with a 30% increase in protein yield observed upon deletion of the ATP-consuming SSA1 component of the HSP70 chaperone. Moreover, drug-mediated metabolic rewiring coupled with template optimization generated the highest protein yields in yeast CFPS to date using a hitherto less efficient, but more cost-effective glucose energy regeneration system. Our approach highlights the utility of target-agnostic phenotypic screening and target identification to deconvolute cell-lysate complexity, adding to the expanding repertoire of strategies for improving CFPS.

2.
Toxicol Appl Pharmacol ; 485: 116920, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38582373

RESUMO

Asparaginase-associated pancreatitis (AAP) is a severe and potentially life-threatening drug-induced pancreas targeted toxicity in the combined chemotherapy of acute lymphoblastic leukemia among children and adolescents. The toxicological mechanism of AAP is not yet clear, and there are no effective preventive and treatment measures available clinically. Fibroblast growth factor 21 (FGF21) is a secretory hormone that regulates lipid, glucose, and energy metabolism balance. Acinar tissue is the main source of pancreatic FGF21 protein and plays an important role in maintaining pancreatic metabolic balance. In this study, we found that the decrease of FGF21 in pancreas is closely related to AAP. Pegaspargase (1 IU/g) induces widespread edema and inflammatory infiltration in the pancreas of rats/mice. The specific expression of FGF21 in the acinar tissue of AAP rats was significantly downregulated. Asparaginase caused dysregulation of the ATF4/ATF3/FGF21 axis in acinar tissue or cells, and thus mediated the decrease of FGF21. It greatly activated ATF3 in the acinar, which competed with ATF4 for the Fgf21 promoter, thereby inhibiting the expression of FGF21. Pharmacological replacement of FGF21 (1 mg/kg) or PERK inhibitors (GSK2656157, 25 mg/kg) can significantly mitigate the pancreatic tissue damage and reduce markers of inflammation associated with AAP, representing potential strategies for the prevention and treatment of AAP.


Assuntos
Asparaginase , Fatores de Crescimento de Fibroblastos , Pâncreas , Pancreatite , eIF-2 Quinase , Animais , Fatores de Crescimento de Fibroblastos/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Asparaginase/toxicidade , Pancreatite/induzido quimicamente , Pancreatite/metabolismo , Pancreatite/patologia , Masculino , Ratos , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Pâncreas/metabolismo , Camundongos , Ratos Sprague-Dawley , Polietilenoglicóis/toxicidade , Antineoplásicos/toxicidade , Fator 4 Ativador da Transcrição/metabolismo , Fator 4 Ativador da Transcrição/genética , Camundongos Endogâmicos C57BL
3.
Biomed Res Int ; 2024: 6509171, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435540

RESUMO

Objective: To analyze the menstrual characteristics of endometrial carcinoma and investigate whether abnormal uterine bleeding in the perimenopausal period differs from postmenopausal bleeding. Methods: We conducted a retrospective analysis of 928 cases of endometrial carcinoma in patients admitted from January 2016 to December 2022. We gathered fundamental clinical data and analyzed distinct clinical risk factors between the perimenopausal and postmenopausal groups. Furthermore, we computed the statistical variances in menarche, regular menstrual cycles, and the duration of abnormal uterine bleeding. Results: Perimenopausal patients with endometrial carcinoma exhibit similar factors to postmenopausal patients, especially if they have a history of menstrual cycles lasting more than 30 years, hypertension, abnormal uterine bleeding for over 1 year, and a high risk of endometrial carcinoma. Early intervention for abnormal uterine bleeding during the perimenopausal stage can prevent up to 80% of women from developing endometrial carcinoma. Conclusion: Perimenopause women experiencing abnormal uterine bleeding should be mindful of the risk of endometrial carcinoma, as this awareness can substantially decrease the occurrence of the disease.


Assuntos
Neoplasias do Endométrio , Pós-Menopausa , Humanos , Feminino , Estudos Retrospectivos , Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/epidemiologia , Hemorragia Uterina , Intervenção Educacional Precoce
4.
Chinese Pharmacological Bulletin ; (12): 234-242, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013621

RESUMO

Aim To investigate the regulatory effect of Cortaetin on pathological myocardial hypertrophy induced by isoprenaline (ISO) and the underlying mechanism. Methods ISO was used to stimulate neonatal rat cardiomyocytes for 24 h, and myocardial hypertrophy model was established at the cellular level. C57BL/6 mice were injected subcutaneously with ISO for one week to establish myocardial hypertrophy model at animal level. RT-qPCR was used to detect the changes of mRNA and Western blot was used to detect the changes of relative protein content. Immunofluorescence was used to measure the subcellular location of Cortaetin and the change of its expression. The overex-pression of Cortaetin by adenovirus infection and the knockdown of Cortaetin by transfection of small interfering RNA were studied. Results On the cellular and animal levels, ISO-induced myocardial hypertrophy models were successfully established, and it was observed that ISO caused the decrease of Cortaetin and N-cadherin protein levels. Overexpression of Cortaetin could reverse the decrease of N-cadherin protein level and myocardial hypertrophy caused by ISO. Knockdown of Cortaetin showed the opposite effect. Conclusion Cortaetin, in combination with N-cadherin, may play a role in combating myocardial hypertrophy by enhancing the connections between cardiomyocytes.

5.
Opt Express ; 31(21): 34300-34312, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37859190

RESUMO

We employ a full-wave theory to systematically investigate two types of spin-orbit interactions and their topological phase transitions for various light beams (e.g., Laguerre-Gaussian, Bessel, and Bessel-Gaussian beams) at optical interfaces, and explore the influence of beam parameters on the spin-Hall shift. It is demonstrated that at small-angle incidence, the beam profile and spin-Hall shift are significantly affected by the beam parameters (e.g., waist radius, radial index, azimuthal index, and cone angle), whereas at large-angle incidence, only the azimuthal index has a salient influence on them. We further find that the Bessel beam and the Gaussian-modulated ones (i.e., Laguerre-Gaussian and Bessel-Gaussian beams) have similar topological phase transition phenomena but different shifts. Quantitative dependences of beam parameters, such as waist radius, radial index, azimuthal index, and cone angle, on the shift are also presented. Our findings offer alternative degrees of freedom in controlling the topological phase transitions of light, and suggest a valuable insight for exploring the applications of SOIs of diverse light fields.

6.
Cells ; 12(17)2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37681869

RESUMO

Higher education has been shown to have neuroprotective effects, reducing the risk of Alzheimer's and Parkinson's diseases, slowing the rate of age-related cognitive decline, and is associated with lower rates of early mortality. In the present study, the association between higher education, fragile X messenger ribonucleoprotein 1 (FMR1) cytosine-guanine-guanine (CGG) repeat number, and mortality before life expectancy was investigated in a population cohort of women born in 1939. The findings revealed a significant interaction between years of higher education and CGG repeat number. Counter to the study's hypothesis, the effects of higher education became more pronounced as the number of CGG repeats increased. There was no effect of years of higher education on early mortality for women who had 25 repeats, while each year of higher education decreased the hazard of early mortality by 8% for women who had 30 repeats. For women with 41 repeats, the hazard was decreased by 14% for each additional year of higher education. The interaction remained significant after controlling for IQ and family socioeconomic status (SES) measured during high school, as well as factors measured during adulthood (family, psychosocial, health, and financial factors). The results are interpreted in the context of differential sensitivity to the environment, a conceptualization that posits that some people are more reactive to both negative and positive environmental conditions. Expansions in CGG repeats have been shown in previous FMR1 research to manifest such a differential sensitivity pattern.


Assuntos
Disfunção Cognitiva , Fármacos Neuroprotetores , Doença de Parkinson , Humanos , Feminino , Idoso de 80 Anos ou mais , Adulto , Citosina , Guanina , Proteína do X Frágil da Deficiência Intelectual/genética
7.
Sensors (Basel) ; 23(17)2023 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-37688070

RESUMO

Knowledge distillation (KD) is a well-established technique for compressing neural networks and has gained increasing attention in object detection tasks. However, typical object detection distillation methods use fixed-level semantic features for distillation, which might not be best for all training stages and samples. In this paper, a multilayer semantic feature adaptive distillation (MSFAD) method is proposed that uses a routing network composed of a teacher and a student detector, along with an agent network for decision making. Specifically, the inputs to the proxy network consist of the features output by the neck structures of the teacher and student detectors, and the output is a decision on which features to choose for distillation. The MSFAD method improves the distillation training process by enabling the student detector to automatically select valuable semantic-level features from the teacher detector. Experimental results demonstrated that the proposed method increased the mAP50 of YOLOv5s by 3.4% and the mAP50-90 by 3.3%. Additionally, YOLOv5n with only 1.9 M parameters achieved detection performance comparable to that of YOLOv5s.

8.
Opt Express ; 31(14): 23621-23630, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37475442

RESUMO

The topological phase transitions (TPT) of light refers to a topological evolution from one type of spin-orbit interaction to another, which has been recently found in beam scattering at optical interfaces and propagation in uniaxial crystals. In this work, the focusing of off-axis and partially masked circular-polarization Gaussian beams are investigated by using of a full-wave theory. Moreover, two different types of spin-orbit interactions (i.e., spin-dependent vortex generation and photonic spin-Hall effect) in the focusing system are unified from the perspective of TPT. It is demonstrated that as the off-axis distance or the masked area increases, a TPT phenomenon in the focused optical field takes place, evolving from the spin-dependent vortex generation to the spin-Hall shift of the beam centroids. The intrinsic mechanism is attributed to the cylindrical symmetry-breaking of the system. This symmetry-breaking induced TPT based on the method of vortex mode decomposition is further examined. The main difference between the TPT phenomenon observed here and that trigged by oblique incidence at optical interfaces or oblique propagation in uniaxial crystals is also uncovered. Our findings provide fruitful insights for understanding the spin-orbit interactions in optics, providing an opportunity for unifying the TPT phenomena in various spin-orbit photonics systems.

9.
Foot Ankle Surg ; 29(3): 233-238, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36754689

RESUMO

BACKGROUND: Metal screws are the most widely used in treating syndesmotic injuries, but failure and the rigidity of the screws can threaten the success of the treatment and increase the cost of care. We have provided an alternative with an olive wire and external fixator(OWEF) used for syndesmotic fixation. METHODS: A retrospective longitudinal follow-up study was conducted. From February 2011 to January 2018, 58 of 72 patients with ankle fractures and associated syndesmotic disruption were treated with either screw or OWEF fixation. The costs, complications, and clinical outcomes using Olerud-Molander score and Visual Analog score in screw and OWEF fixation group were compared. RESULTS: We found the severity of the injury, BMI of the patients and the different fixation methods were determinants of the complications and clinical outcomes. But if no malreduction of the syndesmosis was present, no difference in clinical result was detected. CONCLUSION: The OWEF method appeared to be at least equally functional and effective to screw fixation while maintaining possible lower complication rate. LEVELS OF CLINICAL EVIDENCE: Level 3.


Assuntos
Fraturas do Tornozelo , Olea , Humanos , Fraturas do Tornozelo/diagnóstico por imagem , Fraturas do Tornozelo/cirurgia , Seguimentos , Estudos Retrospectivos , Articulação do Tornozelo/cirurgia , Fixação Interna de Fraturas/métodos , Resultado do Tratamento , Parafusos Ósseos , Fixadores Externos
10.
Am J Intellect Dev Disabil ; 128(1): 1-20, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36548377

RESUMO

Variation in the FMR1 gene may affect aspects of cognition, such as executive function and memory. Environmental factors, such as stress, may also negatively impact cognitive functioning. Participants included 1,053 mothers of children with and without developmental disabilities. Participants completed self-report measures of executive function, memory, and stress (i.e., life events, parenting status), and provided DNA to determine CGG repeat length (ranging from 7 to 192 CGGs). Stress exposure significantly predicted greater self-reported difficulties in executive function and the likelihood of memory problems. Cubic CGG effects independently predicted executive function and memory difficulties, suggesting effects of both genetic variation and environmental stress exposure on cognitive functioning.


Assuntos
Cognição , Proteína do X Frágil da Deficiência Intelectual , Mães , Estresse Psicológico , Expansão das Repetições de Trinucleotídeos , Criança , Feminino , Humanos , Função Executiva , Proteína do X Frágil da Deficiência Intelectual/genética , Mães/psicologia , Autorrelato , Estresse Psicológico/genética
11.
Sichuan Mental Health ; (6): 235-241, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-986746

RESUMO

BackgroundFunctional near-infrared spectroscopy (fNIRS) is a new generation of imaging tool that can be used to assist the diagnosis of psychiatric disorders. However, whether the patterns of prefrontal cortex activation observed by fNIRS are specific for different psychiatric disorders remains to be explored. ObjectiveTo investigate the characteristics of prefrontal cortex activation in patients with depression, anxiety disorder, bipolar disorder and schizophrenia in verbal fluency task (VFT) using fNIRS. MethodsFrom September to December 2021, 39 patients with schizophrenia, 205 patients with depressive disorder, 212 patients with anxiety disorder and 77 patients with bipolar disorder meeting the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) were recruited in the outpatient and inpatient department of West China Hospital, Sichuan University. fNIRS was used to monitor the prefrontal cortex hemodynamic changes of patients under VFT, and the clinical symptoms of patients were assessed by Symptom Checklist 90 (SCL-90) and Hypomania Checklist-32 items(HCL-32). Differences in mean oxyhemoglobin (HbO2) concentration and the initial slope from 2 to 7 second during VFT were compared among patients with different diseases, and the correlation between mean HbO2 concentration/initial slope and clinical symptoms was analyzed by partial correlation analysis. ResultsThe concentration of HbO2 in channel 4 (Z=2.828, P=0.028) and channel 6 (Z=2.912, P=0.022) in patients with depression were significantly higher than those in patients with schizophrenia. Patients with anxiety had significantly higher changes in mean HbO2 concentration in channel 4 (Z=3.154, P=0.010), channel 5 (Z=3.021, P=0.015), channel 6 (Z=2.980, P=0.017) and of all channels (Z=2.881, P=0.024) than those of schizophrenia patients. There was a statistically significant difference in the initial slope of channel 3 between patients with depressive disorder and those with bipolar disorder (Z=2.691, P=0.039). Among patients with bipolar disorder, the anger-hostility scores of SCL-90 were negatively correlated with the mean HbO2 concentration changes in channel 4 (r=-0.505, P=0.004), channel 6 (r=-0.390, P=0.004), channel 15 (r=-0.546, P=0.002), channel 16 (r=-0.550, P=0.002) and the mean HbO2 concentration changes of all channels (r=-0.491, P=0.006). ConclusionPatients with schizophrenia had lower activation in frontopolar and orbitofrontal region than patients with depression and anxiety disorder, and the initial slope of the right frontopolar, inferior frontal and orbitofrontal region in patients with depression is higher than patients with bipolar disorder. In addition, patients with bipolar disorder had less activation in the frontopolar and orbitofrontal lobe, the insular cover of Broca's area and the upper outer frontal cortex, and were more irritable and hostile. [Funded by 1·3·5 Project for Disciplines of Excellence-Clinical Research Incubation Project, West China Hospital, Sichuan University (number, ZYJC21083)]

12.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-986067

RESUMO

Trimethyltin chloride is a highly toxic substance, which is absorbed through respiratory tract, skin and digestive tract, with central nervous system injury as the main clinical manifestations, and can be accompanied by damage to various organs. In this paper, the treatment process of 3 patients with acute trimethyltin chloride poisoning was reviewed, and their clinical manifestations, auxiliary examination, diagnosis and treatment were analyzed. Three patients were misdiagnosed as mental abnormality, encephalitis, and hepatic encephalopathy in different hospitals in the early stage of medical treatment, suggesting that clinicians should pay attention to the occupational contact history of poisoned patients and conduct toxicant detection in time to avoid misdiagnosis and mistreatment.

13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-986028

RESUMO

Objective: To investigate the wearing of masks and the knowledge of masks among high-risk positions for overseas import and pollution transmission. Methods: From May 14 to 17, 2022, a convenient sampling method was used to conduct an online survey among 963 workers in high-risk positions for overseas import and pollution transmission in Beijing. The behaviors of individual use and wearing masks, the distribution and supervision of the unit, the knowledge of personal mask protection and the subjective feelings of wearing masks were analyzed. The χ(2) test and logistic regression model were used to analyze the influencing factors of the correct selection of masks. Results: The majority of the workers in high-risk positions for overseas import and pollution transmission were male (86.0%, 828/963), age concentration in 18-44 years old (68.2%, 657/963), and the majority of them had college or bachelor degrees (49.4%, 476/963). 79.4%(765/963) of the workers chose the right type of masks, female, 45-59 years old and high school education or above were the risk factors for correct selection of masks (P <0.05). Workers had good behaviors such as wearing/removing masks, but only 10.5% (101/963) could correctly rank the protective effect of different masks. 98.4% (948/963) of the workers believed that their work units had provided masks to their employees, and 99.1% (954/963) and 98.2%(946/963) of them had organized training and supervision on the use of masks, respectively. 47.4%(456/963) of the workers were uncomfortable while wearing masks. Conclusion: The overall selection and use of masks among occupational groups in high-risk positions for overseas import and pollution transmission in China need to be further standardized. It is necessary to strengthen supervision and inspection on the use of masks among occupational groups, and take improvement measures to improve the comfort of wearing masks.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Estudos Transversais , Máscaras , China , Inquéritos e Questionários , Pequim
14.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-971875

RESUMO

ObjectiveTo analyze the effect of moderate intensity aerobic combined with low intensity resistance exercise on old patients with coronary heart disease and hypertension. MethodsFrom November, 2021 to May, 2022, 16 patients with coronary heart disease and hypertension in Wuhan Donghu Hospital were divided into control group (n = 8) and experimental group (n = 8). Based on the World Health Organization Family of International Classification (WHO-FICs), the exercise intervention program was constructed. The control group accepted routine treatment, and the experimental group accepted moderate intensity aerobic combined with low intensity resistance exercise in addition, for eight weeks. They were measured lung function and cardiac function with cardiopulmonary exercise test system, and assessed with Timed 'Up and Go' Test, 6-Minute Walk Distance, 2-Minute Step Test, 30-Second Sit to Stand Test and grip strength before and after intervention. ResultsThe vital capacity, forced vital capacity, forced expiratory volume in the first second, forced expiratory volume in the one second as percentage of predicted volume, peak expiratory flow and maximal voluntary ventilation improved in the experimental after intervention (|t| > 2.391, P < 0.05), and the vital capacity, force vital capacity and maximal voluntary ventilation were more in the experimental group than in the control group (|t| > 2.207, P < 0.05). Peak oxygen uptake, anaerobic subthreshold oxygen uptake, metabolic equivalents, oxygen pulse, maximum work load and exercise load time improved in the experimental group after intervention (|t| > 2.823, P < 0.05), and they all were better in the experimental group than in the control group (|t| > 2.295, P < 0.05). Systolic blood pressure improved in both the groups (|t| > 4.608, P < 0.01), and diastolic blood pressure improved in the experimental group (t = 5.964, P < 0.01); while systolic blood pressure was less in the experimental group than in the control group (t = -3.654, P < 0.01). The performances of Timed 'Up and Go' Test, 6-Minute Walk Distance, 2-Minute Step Test, 30-Second Sit to Stand Test and grip strength improved in the experimental group after intervention (|t| > 2.996, P < 0.05), and all the performances were better in the experimental group than in the control group (|t| > 2.220, P < 0.05). ConclusionThe moderate intensity aerobic combined with low resistance exercise developed based on WHO-FICs can improve the cardiac function, lung function, cardiac load and motor function of old patients with coronary heart disease and hypertension.

15.
Acta Pharmaceutica Sinica ; (12): 928-937, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-978750

RESUMO

Dayuanyin (DYY) has been shown to reduce lung inflammation in both coronavirus disease 2019 (COVID-19) and lung injury. This experiment was designed to investigate the efficacy and mechanism of action of DYY against hypoxic pulmonary hypertension (HPH) and to evaluate the effect of DYY on the protection of lung function. Animal welfare and experimental procedures are approved and in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Science. Male C57/BL6J mice were randomly divided into 4 groups: control group, model group, DYY group (800 mg·kg-1), and positive control sildenafil group (100 mg·kg-1). The animals were given control solvents or drugs by gavage three days in advance. On day 4, the animals in the model group, DYY group and sildenafil group were kept in a hypoxic chamber containing 10% ± 0.5% oxygen, and the animals in the control group were kept in a normal environment, and the control solvent or drugs continued to be given continuously for 14 days. The right ventricular systolic pressure, right ventricular hypertrophy index, organ indices and other metrics were measured in the experimental endpoints. Meantime, the expression levels of the inflammatory factors in mice lung tissues were measured. The potential therapeutic targets of DYY on pulmonary hypertension were predicted using network pharmacology, the expression of nuclear factor kappa B (NF-κB) signaling pathway-related proteins were measured by Western blot assay. It was found that DYY significantly reduced the right ventricular systolic pressure, attenuated lung injury and decreased the expression of inflammatory factors in mice. It can also inhibit hypoxia-induced activation of NF-κB signaling pathway. DYY has a protective effect on lung function, as demonstrated by DYY has good efficacy in HPH, and preventive administration can slow down the disease progression, and its mechanism may be related to inhibit the activation of NF-κB and signal transducer and activator of transcription 3 (STAT3) by DYY.

16.
Protein & Cell ; (12): 477-496, 2023.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-982528

RESUMO

Although somatic cells can be reprogrammed to pluripotent stem cells (PSCs) with pure chemicals, authentic pluripotency of chemically induced pluripotent stem cells (CiPSCs) has never been achieved through tetraploid complementation assay. Spontaneous reprogramming of spermatogonial stem cells (SSCs) was another non-transgenic way to obtain PSCs, but this process lacks mechanistic explanation. Here, we reconstructed the trajectory of mouse SSC reprogramming and developed a five-chemical combination, boosting the reprogramming efficiency by nearly 80- to 100-folds. More importantly, chemical induced germline-derived PSCs (5C-gPSCs), but not gPSCs and chemical induced pluripotent stem cells, had authentic pluripotency, as determined by tetraploid complementation. Mechanistically, SSCs traversed through an inverted pathway of in vivo germ cell development, exhibiting the expression signatures and DNA methylation dynamics from spermatogonia to primordial germ cells and further to epiblasts. Besides, SSC-specific imprinting control regions switched from biallelic methylated states to monoallelic methylated states by imprinting demethylation and then re-methylation on one of the two alleles in 5C-gPSCs, which was apparently distinct with the imprinting reprogramming in vivo as DNA methylation simultaneously occurred on both alleles. Our work sheds light on the unique regulatory network underpinning SSC reprogramming, providing insights to understand generic mechanisms for cell-fate decision and epigenetic-related disorders in regenerative medicine.


Assuntos
Masculino , Camundongos , Animais , Reprogramação Celular/genética , Tetraploidia , Células-Tronco Pluripotentes/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Metilação de DNA , Espermatogônias/metabolismo , Células Germinativas/metabolismo
17.
International Eye Science ; (12): 592-596, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-965783

RESUMO

Chorioretinal disease has become a significant problem affecting human vision. Abnormal expression of vascular endothelial growth factor(VEGF)leads to increased fundus permeability and neovascularization. Vitreous injection of anti-VEGF agents can rapidly inhibit the level of VEGF in the eye and effectively control the development of the disease. At present, anti-VEGF agents are widely administered in ophthalmology. However, studies have shown that intravitreal anti-VEGF agents can reduce plasma VEGF concentration after entering the circulatory system, and the pointless off-target effects of drugs may lead to systemic adverse reactions. For elderly patients, patients with serious comorbidities, lactating women, premature infants and other special populations, attention should be paid to systemic VEGF inhibition after multiple injections. In this paper, in order to provide reference for clinical anti-VEGF therapy, the pharmacokinetics therapy, systemic adverse reactions, contralateral eye effects, and effects of anti-VEGF on breast milk and preterm infants were discussed, and the systemic effects of vitreous injection of anti-VEGF agents were reviewed.

18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-982093

RESUMO

OBJECTIVE@#To investigate the effect and relative mechanism of Recombinant Human Thrombopoietin (rhTPO) on long-term hematopoietic recovery in mice with acute radiation sickness.@*METHODS@#Mice were intramuscularly injected with rhTPO (100 μg/kg) 2 hours after total body irradiation with 60Co γ-rays (6.5 Gy). Moreover, six months after irradiation, peripheral blood, hematopoietic stem cells (HSC) ratio, competitive transplantation survival rate and chimerization rate, senescence rate of c-kit+ HSC, and p16 and p38 mRNA expression of c-kit+ HSC were detected.@*RESULTS@#Six months after 6.5 Gy γ-ray irradiation, there were no differences in peripheral blood white blood cells, red blood cells, platelets, neutrophils and bone marrow nucleated cells in normal group, irradiated group and rhTPO group (P>0.05). The proportion of hematopoietic stem cells and multipotent progenitor cells in mice of irradiated group was significantly decreased after irradiation (P<0.05), but there was no significant changes in rhTPO group (P>0.05). The counts of CFU-MK and BFU-E in irradiated group were significantly lower than that in normal group, and rhTPO group was higher than that of the irradiated group(P<0.05). The 70 day survival rate of recipient mice in normal group and rhTPO group was 100%, and all mice died in irradiation group. The senescence positive rates of c-kit+ HSC in normal group, irradiation group and rhTPO group were 6.11%, 9.54% and 6.01%, respectively (P<0.01). Compared with the normal group, the p16 and p38 mRNA expression of c-kit+ HSC in the irradiated mice were significantly increased (P<0.01), and it was markedly decreased after rhTPO administration (P<0.01).@*CONCLUSION@#The hematopoietic function of mice is still decreased 6 months after 6.5 Gy γ-ray irradiation, suggesting that there may be long-term damage. High-dose administration of rhTPO in the treatment of acute radiation sickness can reduce the senescence of HSC through p38-p16 pathway and improve the long-term damage of hematopoietic function in mice with acute radiation sickness.


Assuntos
Humanos , Camundongos , Animais , Trombopoetina/metabolismo , Células-Tronco Hematopoéticas , Plaquetas , Proteínas Recombinantes/uso terapêutico , Lesões por Radiação , RNA Mensageiro/metabolismo
19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-982005

RESUMO

OBJECTIVES@#To investigate the distribution characteristics of non-bacterial pathogens in community-acquired pneumonia (CAP) in children.@*METHODS@#A total of 1 788 CAP children admitted to Shenyang Children's Hospital from December 2021 to November 2022 were selected. Multiple RT-PCR and capillary electrophoresis were used to detect 10 viral pathogens and 2 atypical pathogens, and serum antibodies of Chlamydial pneumoniae (Ch) and Mycoplasma pneumoniae (MP) were detected. The distribution characteristics of different pathogens were analyzed.@*RESULTS@#Among the 1 788 CAP children, 1 295 children were pathogen-positive, with a positive rate of 72.43% (1 295/1 788), including a viral pathogen positive rate of 59.68% (1 067/1 788) and an atypical pathogen positive rate of 22.04% (394/1 788). The positive rates from high to low were MP, respiratory syncytial virus (RSV), influenza B virus (IVB), human metapneumovirus (HMPV), human rhinovirus (HRV), human parainfluenza virus (HPIV), influenza A virus (IVA), bocavirus (BoV), human adenovirus (HADV), Ch, and human coronavirus (HCOV). RSV and MP were the main pathogens in spring; MP had the highest positive rate in summer, followed by IVA; HMPV had the highest positive rate in autumn; IVB and RSV were the main pathogens in winter. The positive rate of MP in girls was higher than that in boys (P<0.05), and there were no significant differences in other pathogens between genders (P>0.05). The positivity rates of certain pathogens differed among age groups (P<0.05): the positivity rate of MP was highest in the >6 year-old group; the positivity rates of RSV and Ch were highest in the <1 year-old group; the positivity rates of HPIV and IVB were highest in the 1 to <3 year-old group. RSV, MP, HRV, and HMPV were the main pathogens in children with severe pneumonia, while MP was the primary pathogen in children with lobar pneumonia, and MP, IVB, HMPV, RSV, and HRV were the top 5 pathogens in acute bronchopneumonia.@*CONCLUSIONS@#MP, RSV, IVB, HMPV, and HRV are the main pathogens of CAP in children, and there are certain differences in the positive rates of respiratory pathogens among children of different ages, genders, and seasons.


Assuntos
Humanos , Criança , Feminino , Masculino , Lactente , Pré-Escolar , Pneumonia , Vírus Sincicial Respiratório Humano , Anticorpos , Infecções Comunitárias Adquiridas , Hospitalização , Vírus da Influenza B , Mycoplasma pneumoniae
20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-981987

RESUMO

OBJECTIVES@#To summarize the clinical features of neonates infected with Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).@*METHODS@#The medical data of 23 neonates with Omicron variant of SARS-CoV-2 infection admitted to the City North Campus of Urumqi First People's Hospital from October to December 2022 were retrospectively reviewed.@*RESULTS@#All 23 infants had a history of exposure to confirmed caregivers with SARS-CoV-2 infection after birth, and none of them was vertically transmitted. Clinical classification: 5 cases of asymptomatic infection, 18 cases of mild infection, and no cases of moderate, severe, or critically ill. The first symptoms were fever in 13 cases, cough in 3 cases, nasal congestion in 1 case, and diarrhea in 1 case. Blood white blood cell counts decreased in 2 cases, and C-reactive protein increased in 1 case. Seven infants underwent chest X-ray examination due to cough or shortness of breath, and one of which showed focal exudative changes, while the rest showed no abnormal changes. All infants were discharged after symptomatic treatment and the median hospital stay was 6 days. The duration of nucleic acid positivity of SARS-CoV-2 was negatively correlated with N gene Ct values and ORF1ab gene Ct values (rs=-0.719 and -0.699, respectively; P<0.05). One month after discharge, all infants had no symptoms or signs of nucleic acid re-positivity.@*CONCLUSIONS@#The clinical manifestations are usually mild or asymptomatic in neonates infected with SARS-CoV-2 Omicron variant. The lower the Ct values of the N and ORF1ab genes of SARS-CoV-2, the longer the duration of nucleic acid positivity. Neonates infected with SARS-CoV-2 Omicron variant can have a good prognosis after symptomatic treatment.


Assuntos
Humanos , Recém-Nascido , Tosse , COVID-19 , Estudos Retrospectivos , SARS-CoV-2
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