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1.
Phys Rev Lett ; 128(10): 106802, 2022 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-35333064

RESUMEN

By combining angle-resolved photoemission spectroscopy, scanning tunneling microscopy, atomic force microscope based piezoresponse force microscopy and first-principles calculations, we have studied the low-energy band structure, atomic structure, and charge polarization on the surface of a topological semimetal candidate TaNiTe_{5}. Dirac-like surface states were observed on the (010) surface by angle-resolved photoemission spectroscopy, consistent with the first-principles calculations. On the other hand, piezoresponse force microscopy reveals a switchable ferroelectriclike polarization on the same surface. We propose that the noncentrosymmetric surface relaxation observed by scanning tunneling microscopy could be the origin of the observed ferroelectriclike state in this novel material. Our findings provide a new platform with the coexistence of a ferroelectriclike surface charge distribution and novel surface states.

2.
Exp Neurol ; 379: 114825, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38777251

RESUMEN

Alzheimer's disease (AD) is a devastating neurodegenerative disorder that leads to progressive cognitive decline and neuropathological changes. Pericytes, which are vessel mural cells on the basement membrane of capillaries, play a crucial role in regulating cerebrovascular functions and maintaining neurovascular unit integrity. Emerging research substantiates the involvement of pericytes in AD. This review provides a comprehensive overview of pericytes, including their structure, origin, and markers and various functions within the central nervous system. Emphatically, the review explores the intricate mechanisms through which pericytes contribute to AD, including their interactions with amyloid beta and apolipoprotein E, as well as various signaling pathways. The review also highlights potential for targeted pericyte therapy for AD, with a focus on stem cell therapy and drug treatments. Future research directions include the classification of pericyte subtypes, studies related to aging, and the role of pericytes in exosome-related mechanisms in AD pathology. In conclusion, this review consolidates current knowledge on the pivotal roles of pericytes in AD and their potential as therapeutic targets, providing valuable insights for future research and clinical interventions aimed at addressing the impact of AD on patients' lives.

3.
Naunyn Schmiedebergs Arch Pharmacol ; 396(12): 3503-3528, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37535076

RESUMEN

Mitochondria serve as a vital energy source for nerve cells. The mitochondrial network also acts as a defense mechanism against external stressors that can threaten the stability of the nervous system. However, excessive accumulation of damaged mitochondria can lead to neuronal death. Mitophagy is an essential pathway in the mitochondrial quality control system and can protect neurons by selectively removing damaged mitochondria. In most neurological disorders, dysfunctional mitochondria are a common feature, and drugs that target mitophagy can improve symptoms. Here, we reviewed the role of mitophagy in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, stroke, and traumatic brain injuries. We also summarized drug and non-drug approaches to promote mitophagy and described their therapeutic role in neurological disorders in order to provide valuable insight into the potential therapeutic agents available for neurological disease treatment. However, most studies on mitophagy regulation are based on preclinical research using cell and animal models, which may not accurately reflect the effects in humans. This poses a challenge to the clinical application of drugs targeting mitophagy. Additionally, these drugs may carry the risk of intolerable side effects and toxicity. Future research should focus on the development of safer and more targeted drugs for mitophagy.


Asunto(s)
Enfermedad de Alzheimer , Enfermedad de Parkinson , Animales , Humanos , Mitofagia/fisiología , Mitocondrias/metabolismo , Enfermedad de Parkinson/metabolismo , Enfermedad de Alzheimer/metabolismo
4.
Phys Rev E ; 108(6-2): 065203, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38243529

RESUMEN

We report on the experimental observation of the focusing effect of a 50MeV accelerator electron beam in a gas-discharge plasma target. The plasma is generated by igniting an electric discharge in two collinear quartz tubes, with the currents up to 1.5kA flowing in opposite directions in either of the two tubes. In such plasma current configuration, the electron beam is defocused in the first discharge tube and focused with a stronger force in the second one. With symmetric plasma currents, asymmetric effects are, however, induced on the beam transport process and the beam radius is reduced by a factor of 2.6 compared to the case of plasma discharge off. Experimental results are supported by two-dimensional particle-in-cell simulations.

5.
Med Phys ; 46(6): 2659-2668, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30972763

RESUMEN

PURPOSE: Accurate segmentation of rectal tumors is a basic and crucial task for diagnosis and treatment of rectal cancer. To avoid tedious manual delineation, an automatic rectal tumor segmentation model is proposed. METHODS: A pretrained Resnet50 model was introduced for feature extraction. To reduce the complexity of the model, all layers after the 13th residual block of ResNet50 were removed, and three side-output modules were added to the hidden layer of ResNet50 to guide multiscale feature learning. The final boundaries of tumors were determined by fusion of the predictions from side-output modules. The proposed model was compared with two other models, and the effects of different region of interest (ROI) sizes, loss functions, and side-output fusion strategy were also evaluated. RESULTS: The models were trained and evaluated on data from four clinical centers; T2-weighted magnetic resonance images (T2W-MRIs) from 461 patients in the first clinical center were used for training, while T2W-MRIs from 51 patients in the same clinical center and 56 patients in three other clinical centers were used for performance evaluation. The proposed model was superior to the two other models and achieved an average Dice similarity coefficient of 82.39%, sensitivity of 86.32%, specificity of 92.25%, and Hausdorff distance of 12.10 px. In addition, when the ROI contained rectal tumors, the smaller the ROI size, the higher the segmentation accuracy. For a certain ROI size, there were no considerable differences in segmentation results among the loss functions. Compared to the models with single side-output module, the proposed model performed better. CONCLUSIONS: The results show that the proposed model has potential clinical applications in rectal cancer treatment, particularly with regard to therapeutic response evaluation and preoperative planning.


Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética , Redes Neurales de la Computación , Neoplasias del Recto/diagnóstico por imagen , Humanos , Reproducibilidad de los Resultados
6.
Comput Math Methods Med ; 2018: 4534579, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29977326

RESUMEN

Transjugular Intrahepatic Portal Systemic Shunt is a comprehensive interventional therapy for portal hypertension. During this intervention, puncturing from hepatic vein into portal vein is a difficult step. Selecting puncture needle with a proper bending angle is vital to accurate puncture. Thus, this prospective study provides a method to calculate the angle of the puncture needle using preinterventional contrast-enhanced CT imaging. According to the geometrical characteristics of puncture needle, Bezier curve equation was adopted to describe its bending part. By testing whether each point in a specific region satisfied the equation set of Bezier curves, the possible position of needle tip was obtained. Then, the bending angle of puncture needle was obtained by calculating curvature. The method was evaluated in 13 patients from 2 centers showing now a success rate of 100% and a duration of the procedure of 141 and 161 minutes. The method based on Bezier curve equation for calculating a proper bending angle of puncture needle was proven to be effective. And the clinical study is preliminary and additional work for clinical evaluation is necessary.


Asunto(s)
Derivación Portosistémica Intrahepática Transyugular/métodos , Cuidados Preoperatorios , Tomografía Computarizada por Rayos X , Adulto , Femenino , Venas Hepáticas , Humanos , Masculino , Persona de Mediana Edad , Vena Porta/diagnóstico por imagen , Estudios Prospectivos , Punciones
7.
Artículo en Zh | WPRIM | ID: wpr-969977

RESUMEN

Based on data mining technology, the rules of acupoint selection of acupuncture-moxibustion for scrofula in ancient times were analyzed. The relevant articles of acupuncture and moxibustion for scrofula were searched in the Chinese Medical Code, and the original article, acupoint name, acupoint characteristic, and acupoint meridian tropism, etc. were screened and extracted. The Microsoft Excel 2019 was used to establish a acupoint prescription database, and the frequency of acupoints as well as their meridian tropism and characteristics were analyzed. The SPSS21.0 was applied to perform cluster analysis of acupuncture prescriptions; the SPSS Modeler 18.0 was used to perform the association rules analysis of the neck and the chest-armpit acupoints, respectively. As a result, 314 acupuncture prescriptions were extracted, including 236 single-acupoint prescriptions and 78 multiple-acupoints prescriptions (53 for neck and 25 for chest-armpit). A total of 54 acupoints were involved, with a total frequency of 530. The top 3 commonly-used acupoints were Tianjing (TE 10), Zulinqi (GB 41) and Taichong (LR 3); the most commonly-used meridians were hand shaoyang meridian, foot shaoyang meridian, hand yangming meridian and foot yangming meridian; the most commonly-used special acupoints were he-sea points and shu-stream points. The cluster analysis obtained 6 clusters, and the association rule analysis obtained that the core prescriptions of the neck were Quchi (LI 11), Jianyu (LI 15), Tianjing (TE 10) and Jianjing (GB 21), while the core prescriptions of the chest-armpit were Daling (PC 7), Yanglingquan (GB 34), Danzhong (CV 17), Jianjing (GB 21), Waiguan (TE 5), Zhigou (TE 6), Yuanye (GB 22) and Zhangmen (LR 13). The core prescriptions obtained from association rule analysis by difference areas were basically consistent with those by cluster analysis of total prescriptions.


Asunto(s)
Humanos , Puntos de Acupuntura , Moxibustión , Terapia por Acupuntura , Meridianos , Tuberculosis Ganglionar
8.
Artículo en Zh | WPRIM | ID: wpr-970483

RESUMEN

The present study observed the regulatory effect of total flavonoids of Ziziphora clinopodioides on autophagy and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathways in ApoE~(-/-) mice and explored the mechanism of total flavonoids of Z. clinopodioides against atherosclerosis(AS). ApoE~(-/-) mice were fed on a high-fat diet for eight weeks to induce an AS model. The model mice were randomly divided into a model group, a positive control group, and low-, medium-and high-dose groups of total flavonoids of Z. clinopodioides, while C57BL/6J mice fed on a common diet were assigned to the blank group. The serum and aorta samples were collected after intragastric administration for 12 weeks, and the serum levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein-cholesterol(LDL-C), and high density lipoprotein-cholesterol(HDL-C) were detected by an automatic biochemical analyzer. The serum expression levels of intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), matrix metalloproteinase-2(MMP-2), and matrix metalloprotei-nase-9(MMP-9) were detected by enzyme-linked immunosorbent assay(ELISA). Oil red O staining was used to observe the aortic plaque area in mice. Hematoxylin-eosin(HE) staining was used to observe the aortic plaque and pathological changes in mice. The expression of P62 and LC3 in the aorta was detected by the immunofluorescence method. The protein expression of LC3Ⅱ/Ⅰ, Beclin-1, P62, p-PI3K, p-Akt, and p-mTOR in the aorta of mice was detected by Western blot. The results showed that compared with the blank group, the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2 and MMP-9 in the model group were significantly increased(P<0.01 or P<0.05), the content of HDL-C was decreased(P<0.05), intra-aortic plaque area was enlarged(P<0.01), the expression of LC3 in the aorta was significantly down-regulated, P62 expression was up-regulated(P<0.01 or P<0.05), the expressions of LC3Ⅱ/Ⅰ and Beclin-1 in the aortic lysate were significantly down-regulated, and the expressions of p-PI3K, p-Akt, p-mTOR and P62 were significantly increased(P<0.01). The medium-and high-dose groups of total flavonoids of Z. clinopodioides could reduce the serum levels of TC, TG, LDL-C, ICAM-1, VCAM-1, MMP-2, and MMP-9 in AS model mice(P<0.01 or P<0.05), and increase the content of HDL-C(P<0.01 or P<0.05). The aortic plaque area of mice after middle and high doses of total flavonoids of Z. clinopodioides was significantly reduced(P<0.01), the content of foam cells decrease, and the narrowing of the lumen decreased. The total flavonoids of Z. clinopodioides significantly increased the expression of LC3 in the aorta and the expression of LC3Ⅱ/Ⅰ and Beclin-1 in the lysate, and decreased the expression of P62 in the aorta and the expression of p-PI3K, p-Akt, p-mTOR and P62 in the lysate(P<0.01 or P<0.05). The results showed that the total flavonoids of Z. clinopodioides could improve the content of blood lipids and inflammatory factors, and reduce the generation of foam cells and plaques in aortic tissue, and the mechanism may be related to the regulation of PI3K/Akt/mTOR signaling pathway.


Asunto(s)
Animales , Ratones , Apolipoproteínas E , Aterosclerosis/genética , Beclina-1 , LDL-Colesterol , Molécula 1 de Adhesión Intercelular , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Ratones Endogámicos C57BL , Fosfatidilinositol 3-Quinasas/metabolismo , Placa Aterosclerótica , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/genética , Molécula 1 de Adhesión Celular Vascular/genética
9.
Artículo en Zh | WPRIM | ID: wpr-1008835

RESUMEN

In this experiment, the PK/PD fitting model of Chuanxiong(Chuanxiong Rhizoma) in the treatment of rheumatoid arthritis was established in the form of acupoint combined with external application gel paste. Firstly, the rheumatoid arthritis model was induced by ovalbumin, and the articular fluid of rabbits was extracted by microdialysis. The pharmacokinetic process of Chuanxiong in rabbit articular fluid was analyzed by UPLC-MS/MS, and the pharmacokinetic model was established. The pharmacodynamic effects of Chuanxiong on inflammatory factors IL-1β, TNF-α, and IL-6 were analyzed by enzyme-linked immunosorbent assay(ELISA). The pharmacodynamic model was established, and the PK/PD model was obtained by fitting the data of pharmacokinetics and pharmacodynamics. The results of pharmacokinetics showed that the concentration of ligustrolide A in the articular cavity by drug administration on classical acupoint Zusanli(ST 36) was higher than that by Yanglingquan(GB 34), which reflected the advantage of typical acupoint, while ligustrazine concentration was higher after administration through Yanglingquan than through Zusanli, which was different from the traditional acupoint theory. The results of pharmacodynamics showed that the drug had lag effect. The PK/PD model was constructed by fitting the data. When IL-1β was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=115.28C_e/(3 316.72+C_e), E=108.73C_e/(2 993.47+C_e), and E=101.34C_e/(3 028.51+C_e). When TNF-α was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=68.31C_e/(3 285.16+C_e), E=59.27C_e/(2 919.86+C_e), and E=53.61C_e/(2 862.87+C_e). When IL-6 was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=59.92C_e/(3 461.17+C_e), E=58.34C_e/(2 723.51+C_e), and E=49.17C_e/(2 862.76+C_e). The parameters showed that there were significant differences in E_(max), EC_(e50) and k_(eo). The analysis of data found that the PK/PD fitting effect of Zusanli, a typical acupoint, was the best, which proved that it was still the best site for drug administration. To sum up, it shows that there may be bidirectional selectivity between drugs and acupoints.


Asunto(s)
Animales , Conejos , Factor de Necrosis Tumoral alfa , Cromatografía Liquida , Interleucina-6 , Espectrometría de Masas en Tándem , Puntos de Acupuntura , Artritis Reumatoide/tratamiento farmacológico
10.
Artículo en Zh | WPRIM | ID: wpr-1008692

RESUMEN

This study developed an optimal pre-processing technique for the reference substance of the classic formula Gualou Xiebai Banxia Decoction(GXBD) and established a comprehensive quality control method for GXBD reference substance to provide a reference for its overall quality evaluation. The authors prepared 15 batches of GXBD samples and innovatively used the extracted ion chromatogram under the base peak chromatogram mode to establish a liquid chromatography-mass spectrometry(LC-MS) fingerprint, identify characteristic peaks, and perform quantitative analysis of indicator components. The yield of the 15 batches of GXBD samples ranged from 50.28% to 76.20%. In the positive ion mode, 12 common characteristic peaks were detected in the LC-MS fingerprint, and the structures of five common peaks were identified by comparison with reference standards. The similarity between the fingerprint profiles of different batches of samples and the reference fingerprint profile ranged from 0.920 to 0.984. Finally, liquid chromatography-triple quadrupole mass spectrometry(LC-QQQ/MS) in multiple reaction monitoring(MRM) mode was used to determine the content of eight indicator components in GXBD, including loliolide, chrysoeriol, rutin, cucurbitacin D, macrostemonoside Ⅰ, 25S-timosaponin B Ⅱ, 25R-timosaponin B Ⅱ, and peptide proline-tryptophan-valine-proline-glycine(PWVPG). The method established in this study can reduce matrix interference in the compound, and it has good accuracy, stability, and practical value. It effectively reflects the quality attributes of GXBD samples and can be used for the comprehensive quality control of GXBD.


Asunto(s)
Cromatografía Liquida , Espectrometría de Masas en Tándem/métodos , Medicamentos Herbarios Chinos/química , Prolina , Cromatografía Líquida de Alta Presión/métodos
11.
Protein & Cell ; (12): 683-697, 2023.
Artículo en Inglés | WPRIM | ID: wpr-1010771

RESUMEN

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.


Asunto(s)
Animales , Ratones , Metilación , Cromatina , Histonas/metabolismo , ARN Mensajero/genética , Metiltransferasas/metabolismo , ARN/metabolismo
12.
Artículo en Zh | WPRIM | ID: wpr-981511

RESUMEN

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.


Asunto(s)
Animales , Conejos , Factor de Necrosis Tumoral alfa , Fluorescencia , Artritis Reumatoide/tratamiento farmacológico , Interleucina-1 , Artritis Experimental/tratamiento farmacológico
13.
Croat Med J ; 48(6): 800-6, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18074414

RESUMEN

AIM: To explore whether killer cell immunoglobulin-like receptors (KIR) gene polymorphisms are associated with susceptibility to persistent hepatitis B virus (HBV) infection or HBV clearance. METHODS: Fifteen known KIR genes were determined in 150 chronic hepatitis B patients, 251 spontaneously recovered controls, and 412 healthy controls by the sequence specific primer polymerase chain reaction (SSP-PCR) method. KIR genotype frequency (gf) differences were tested for significance by two-tailed Fisher exact test or chi(2) test. Multifactorial analysis was also performed by logistic analysis (the SAS system). RESULTS: Framework genes KIR2DL4, KIR3DL2, KIR3DL3, and KIRZ were present in all individuals. The frequencies of KIR2DS2 and KIR2DS3 were higher in chronic hepatitis B patients, than in both healthy and spontaneously recovered controls. The frequencies of activating KIR2DS1, KIR3DS1, and the inhibitory KIR2DL5 were higher in spontaneously recovered controls than in chronic hepatitis B patients and healthy controls. CONCLUSION: KIR polymorphisms may be associated with susceptibility to HBV infection or HBV clearance. It could be suggested that KIR2DS2 and KIR2DS3 were HBV-susceptive genes, which induced a persistent yet weak inflammatory reaction that resulted in continuous injury of live tissues and chronic hepatitis. KIR2DS1, KIR3DS1, and KIR2DL5, on the other hand, may be protective genes that facilitated the clearance of HBV.


Asunto(s)
Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad , Hepatitis B Crónica/genética , Polimorfismo Genético , Receptores Inmunológicos/genética , Estudios de Casos y Controles , Estudios de Cohortes , Frecuencia de los Genes , Hepatitis B Crónica/etnología , Humanos , Reacción en Cadena de la Polimerasa , Receptores KIR2DL4 , Receptores KIR2DL5 , Receptores KIR3DL2 , Receptores KIR3DS1
14.
Artículo en Zh | WPRIM | ID: wpr-930503

RESUMEN

Childhood asthma is one of the most-common chronic respiratory diseases in the world.The incidence of asthma is increasing, and therefore, controlling the occurrence and development of asthma has been the current research hotspot.A growing number of evidences have shown that the changes of maternal internal and uterine environment during pregnancy are related to the occurrence of asthma in offspring.The influence of maternal mental, disease, nutrition, environment, drug exposure on the occurrence of asthma in offspring were summarized, providing a new idea for understanding the mechanism, prevention and treatment of children asthma.

15.
Chinese Journal of Pediatrics ; (12): 302-306, 2022.
Artículo en Zh | WPRIM | ID: wpr-935691

RESUMEN

Objective: To investigate the effect of maternal exposure to lipopolysaccharide during pregnancy on allergic asthma in offspring in mice. Methods: Animal experimental research was carried out from June 2019 to June 2021.Pregnant C57BL/6J mice were randomly divided into 2 groups by intraperitoneal injection with 7 μg/kg lipopolysaccharide (LPS) or phosphate buffered saline (PBS) at day 15.5 of gestation. After birth, 6 offspring were randomly chosen from each group at the age of 4 weeks, and stimulated with house dust mites (HDM) or PBS, further divided into 4 groups, such as LPS+PBS group, LPS+HDM group, PBS+PBS group, PBS+HDM group, with 3 mice in each group. The cough and wheezing were observed, the histological changes in lung tissue were examined after HE staining, and the expression of inflammatory factors including interleukin (IL)-4, IL-6, IL-17A, IL-23, interferon (IFN)-α and IFN-β in the lung tissue were detected by high-throughput liquid protein chip detection. T test or rank sum test was used for the comparison among these groups. Results: The asthma-like airway inflammation was more obvious in PBS+HDM group after stimulated by HDM than that in PBS+PBS group, nevertheless, this manifestation in LPS+HDM group was milder than that in PBS+HDM group. HE staining showed that inflammatory cell aggregation in the lung tissue in PBS+HDM group was significantly higher than that in PBS+PBS group (4.0 (3.5, 4.0) vs. 0 (0, 0.5), Z=2.02, P=0.043), while it was much lower in LPS+HDM group compared to PBS+HDM group (1.0 (0.5, 1.5) vs. 4.0 (3.5, 4.0), Z=1.99, P=0.046). High-throughput liquid protein chip detection of lung tissue showed that IL-6, IL-23 and IFN-β levels were significantly higher in PBS+HDM group when compared to those in PBS+PBS group ((114±3) vs. (94±4) ng/L, (210±4) vs. (173±7) ng/L, (113±2) vs. (94±4) ng/L, t=4.37, 4.84, 3.96, all P<0.05), while the levels of IL-6, IL-23, IFN-α, IFN-β in LPS+HDM group were significantly lower than those in PBS+HDM group ((87±5) vs. (114±3) ng/L, (171±7) vs. (210±4) ng/L, (16.1±0.6) vs. (20.9±0.3) ng/L, (95±1) vs. (113±2) ng/L, t=5.07, 5.07, 7.28, 7.47, all P<0.05). Conclusions: Prenatal low dose LPS exposure can reduce offspring's airway inflammatory reactions and prevent the development of allergic disease. Maternal infection during pregnancy may affect the occurrence and development of allergic asthma in offspring.


Asunto(s)
Animales , Femenino , Humanos , Ratones , Embarazo , Asma/etiología , Modelos Animales de Enfermedad , Inflamación , Interleucina-23 , Interleucina-6 , Lipopolisacáridos , Pulmón , Exposición Materna/efectos adversos , Ratones Endogámicos C57BL , Pyroglyphidae
16.
Chinese Journal of Oncology ; (12): 1369-1375, 2022.
Artículo en Zh | WPRIM | ID: wpr-969797

RESUMEN

Objective: To explore the metabolite profile and metabolic pathways of newly diagnosed multiple myeloma (MM). Methods: Gas chromatography-mass spectrometry (GC-MS) was employed for the high-throughput detection and identification of serum samples from 55 patients with MM and 37 healthy controls matched for age and sex from 2016 to 2017 collected at the First Affiliated Hospital of Soochow University. The relative standard deviation (RSD) of quality control (QC) samples was employed to validate the reproducibility of GC-MS approach. The differential metabolites between patients with MM and healthy controls were detected by partial least squares discrimination analysis (PLS-DA), and t-test with false discovery rate (FDR) correction. Metabolomics pathway analysis (MetPA) was employed to construct metabolic pathways. Results: There were 55 MM patients, including 34 males and 21 females. The median age was 60 years old (42-73 years old). There were 30 cases of IgG type, 9 cases of IgA type, 1 case of IgM type, 2 cases of non-secreted type, 1 case of double clone type and 12 cases of light chain type, including 3 cases of kappa light chain type and 9 cases of lambda light chain type. The result of QC sample test showed that the proportion of compounds with the RSD of the relative content of metabolites < 15% was 70.21% obtained by the reproducibility of GC-MS experimental data, which implied that the experimental data were reliable. A total of 17 metabolites were screened differently with the healthy control group, including myristic acid, hydroxyproline, cysteine, palmitic acid, L-leucine, stearic acid, methionine, phenylalanine, glycerin, serine, isoleucine, tyrosine, valine, citric acid, inositol, threonine, and oxalic acid (VIP>1, P<0.05). Metabolic pathway analysis suggested that metabolic disorders in MM patients comprised mainly phenylalanine metabolism, glyoxylic acid and dicarboxylic acid metabolism, phosphoinositide metabolism, cysteine and methionine metabolism, glycerolipid metabolism, glycine, serine, and threonine metabolism. Conclusion: Compared with normal people, patients with newly diagnosed MM have obvious differences in metabolic profiles and metabolic pathways.


Asunto(s)
Masculino , Femenino , Humanos , Persona de Mediana Edad , Adulto , Anciano , Cisteína , Mieloma Múltiple/diagnóstico , Reproducibilidad de los Resultados , Metaboloma , Metabolómica/métodos , Redes y Vías Metabólicas , Metionina , Serina , Fenilalanina , Treonina , Biomarcadores
17.
Artículo en Zh | WPRIM | ID: wpr-1015822

RESUMEN

Inflammatory bowel disease (IBD) is an, intractable inflammatory autoimmune disease characterized by T-cell infiltration to the colon. Mesenchymal stem cells (MSCs), owing to their immunosuppressive capabilities, have the potential to rescue IBD. But the therapeutic effectiveness of MSCs is sometime thwarted by their variable immunomodulatory ability in vivo. In the present study, we produced engineered MSCs that secrete interleukin10 (IL-10) and evaluated their therapeutic potential in IBD mouse model. The MSCs maintained the phenotype and cell proliferation rate after overexpression of IL-10 by lentivirus (LV) infection. Immune cells and MSCs in vitro co-culture systems exhibited that relative to unmodified MSCs, immune cells co-cultured with IL-10-overexpressing MSCs had significantly lower numbers of T helper 1 cells (Th1) and T helper 17 cells (Th17) (P0.05). Overall, LV induced MSCs overexpressing IL-10 might be a promising alternative therapeutic option for the treatment of IBD.

18.
Artículo en Zh | WPRIM | ID: wpr-912772

RESUMEN

Objective:To analyze original medical humanities articles written by staff of the hospital and extract key elements of hospital culture for staff perception, for recommendations on homogenous development of multiple campuses of the hospital.Methods:Original medical humanities articles written by staff of the hospital were collected from the WeChat accounts, websites and printouts of a tertiary hospital in Beijing from January 2013 to December 2019, with text mining made by Python3.7; Bert and Tencent open-source 8 million Chinese word dataset were used as entity identification training dataset; K-Means cluster analysis was used to analyze and select cluster results of higher degree of fitting; TextRank was used to screen keywords of each clustered category. Significance of each category was summarized in the end based on keywords following the screening.Results:Among the 341 articles collected, high frequency words were work, hospital, patient, sick person, development, medicine, medical treatment, doctor, outpatient service and clinic. The words fell into ten categories: process recall, work attribute, work responsibility, diagnosis and treatment behavior, growth experience, team cooperation, professionalism, management innovation, doctor-patient communication and others.Conclusions:Research on hospital staff culture perception is conducive to identifying the cultural content of the hospital. In the homogenous development of multiple campuses of the hospital, it is imperative to nurture the staff′s sense of identify and belonging to the hospital, enhance their sense of gain and happiness, and strengthen the scientific management system centering on patients.

19.
Artículo en Zh | WPRIM | ID: wpr-910369

RESUMEN

As a method for local treatment, radiotherapy plays a key role in the management of tumors. In the past few decades, great progress has been made in radiotherapy technology, with improvements in conformity, homogeneity, and radiotherapy efficiency, and the results are encouraging. Nevertheless, the maximum tolerated dose of normal tissue has limited the further increase in radiotherapy dose in the tumor area. If radiation-induced toxicities can be reduced, a higher radiotherapy dose can be delivered to tumor tissue, so as to achieve a better treatment response. In recent years, the unique FLASH effect of ultra-high-dose-rate radiotherapy (FLASH-RT) is capable of maintaining a consistent tumor response whilst reducing radiation-induced toxicities in normal tissue, and therefore, FLASH-RT has become a research hotspot in the field of radiotherapy across the world. At present, some scholars tend to explain the FLASH effect using the theory of acute oxygen depletion, but the protective effect of FLASH-RT on normal tissue remains to be clarified. In addition, preliminary clinical studies have been conducted for FLASH-RT, and the results are promising. Based on existing evidence, this article elaborates on the research advances in FLASH-RT in the treatment of malignant tumor, so as to provide a reference for the translation and application of this new technique.

20.
Artículo en Zh | WPRIM | ID: wpr-880129

RESUMEN

OBJECTIVE@#To investigate the expression of WTAP gene in acute myeloid leukemia (AML) and its clinical significance.@*METHODS@#74 acute myeloid leukemia patients with non-M3 type and 19 normal donors were selected, and real-time quantitative polymerase chain reaction was used to detect the mRNA expression level of WTAP gene in their bone marrow cells. The relationship between the mRNA expression level of WTAP gene and the clinical characteristics was analyzed.@*RESULTS@#The relative mRNA expression of WTAP gene in the non-M3 AML group was significantly higher than that in the healthy control group, and the difference showed statistically significant (P0.05) according to the classification of FAB. The mRNA expression level of WTAP gene in FLT3-ITD mutated AML patients was higher than that in FLT3-ITD unmutated group (P=0.016), and the mRNA expression level of WTAP gene in AML patients with CEBPα mutation was lower than that in CEBPα unmutated group (P=0.016). The expression level of WTAP mRNA was positively correlated with WT1 expression (r=0.6866, P0.05). The expression level of WTAP mRNA showed no obvious effect on the complete remission of patients after first treatment. The different expression level of WTAP gene at initial diagnosis showed also no effect on the overall survival time of patients.@*CONCLUSION@#The expression level of WTAP gene is increasing in new diagnosed non-M3 acute myeloid leukemia. There is a positive correlation between the expression level of WTAP gene and the expression level of WT1 fusion gene. WTAP mRNA always shows higher expression in patients with FLT3-ITD mutation than that in patients without FLT3-ITD mutation, and shows lower expression in patients with CEBPα mutation than that in unmutated group.


Asunto(s)
Humanos , Proteínas de Ciclo Celular , Cariotipo , Leucemia Mieloide Aguda/genética , Mutación , Pronóstico , Factores de Empalme de ARN , Inducción de Remisión , Tirosina Quinasa 3 Similar a fms/genética
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