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1.
Am J Transl Res ; 16(7): 2963-2972, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39114718

RESUMO

OBJECTIVE: To investigate the possible mechanism of lncRNA GA binding protein transcription factor beta subunit 1 antisense RNA 1 (GABPB1-AS1) in cerebral ischemia/reperfusion (CI/R) injury. METHODS: RT-qPCR was applied to determine GABPB1-AS1 expression in oxygen-glucose deprivation/reoxygenation (OGD/R) cells. The targeting relationships between GABPB1-AS1 and miR-641, as well as between miR-641 and nuclear casein and cyclin-dependent kinase substrate 1 (NUCKS1) were examined by dual luciferase reporter assay. The protein expression of caspase-3, Bax, Bcl-2 and NUCKS1 was examined by western blot. Cell apoptosis was measured by flow cytometry (FCM) and western blot. Cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: GABPB1-AS1 was significantly elevated in SH-SY5Y cells under OGD/R. Downregulation of GABPB1-AS1 accelerated cell viability and suppressed cell apoptosis. GABPB1-AS1 silencing reduced ROS and MDA levels in OGD/R-treated cells. Furthermore, miR-641 inhibitor aggravated damage from OGD/R, but GABPB1-AS1 silencing notably attenuated this effect. NUCKS1 was proven to be a target gene of miR-641. CONCLUSION: GABPB1-AS1 silencing alleviated CI/R injury through the miR-641/NUCKS1 axis, indicating that GABPB1-AS1 might serve as a therapeutic target for CI/R injury.

2.
Int J Gen Med ; 17: 2757-2766, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895049

RESUMO

Purpose: To explore the computed tomography (CT) features of bronchopneumonia caused by pepper aspiration to improve the diagnosis. Materials and Methods: 28 adult patients diagnosed with obstructive pneumonia caused by pepper aspiration from January 2016 to September 2022 were enrolled. The CT characteristics of bronchial changes and pulmonary lesions caused by pepper were analyzed and summarized. Results: Among 28 patients, the most common symptom was cough (26, 92.9%), followed by expectoration (23, 82.1%). Bronchoscopy revealed that peppers were mainly found in the bronchus of the right lower lobe (n = 18, 64.3%), followed by the bronchus of the left lower lobe (n = 5, 17.9%). In combination with bronchoscopy results, the pepper in the bronchus manifested as circular or V/U-shaped high-density, localized soft tissue, and flocculent opacification in 8 (28.6%), 16 (57.1%), and 3 (10.7%) cases on CT images, respectively. The bronchial wall around the pepper was thickened with localized occlusion (n = 19, 67.9%) and stenosis (n = 9, 32.1%). Regarding adjacent bronchi without peppers, extensive wall thickening with stenosis and/or occlusion was found in 23 (82.1%) cases. Distal pulmonary lesions frequently involved two or three segments (21, 75.0%) and mainly presented as patchy consolidation or atelectasis (24, 85.7%). Conclusion: In combination to a history of eating peppers and clinical symptoms, bronchopneumonia caused by pepper should be highly suspected if U/V-shaped and annular high-density or localized soft tissue density is detected in the bronchi of the lower lobes, accompanied by extensive bronchial wall thickening, stenosis, or occlusion, and consolidation or atelectasis in multiple distal lung segments.

3.
Heliyon ; 10(7): e28681, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38586386

RESUMO

Sonar sound datasets are of significant importance in the domains of underwater surveillance and marine research as they enable experts to discern intricate patterns within the depths of the water. Nevertheless, the task of classifying sonar sound datasets continues to pose significant challenges. In this study, we present a novel approach aimed at enhancing the precision and efficacy of sonar sound dataset classification. The integration of deep long-short-term memory (DLSTM) and convolutional neural networks (CNNs) models is employed in order to capitalize on their respective advantages while also utilizing distinctive feature engineering techniques to achieve the most favorable outcomes. Although DLSTM networks have demonstrated effectiveness in tasks involving sequence classification, attaining their optimal performance necessitates careful adjustment of hyperparameters. While traditional methods such as grid and random search are effective, they frequently encounter challenges related to computational inefficiencies. This study aims to investigate the unexplored capabilities of the fuzzy slime mould optimizer (FUZ-SMO) in the context of LSTM hyperparameter tuning, with the objective of addressing the existing research gap in this area. Drawing inspiration from the adaptive behavior exhibited by slime moulds, the FUZ-SMO proposes a novel approach to optimization. The amalgamated model, which combines CNN, LSTM, fuzzy, and SMO, exhibits a notable improvement in classification accuracy, outperforming conventional LSTM architectures by a margin of 2.142%. This model not only demonstrates accelerated convergence milestones but also displays significant resilience against overfitting tendencies.

4.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1010323

RESUMO

OBJECTIVE@#To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification.@*METHODS@#Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway.@*RESULTS@#The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway.@*CONCLUSION@#Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.


Assuntos
Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proliferação de Células , Metaloproteinase 9 da Matriz , Simulação de Acoplamento Molecular , Ciclo Celular , Receptores ErbB , Apoptose , Neoplasias Colorretais/patologia , Linhagem Celular Tumoral
5.
Chinese Journal of Neonatology ; (6): 136-144, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1022551

RESUMO

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

6.
Chinese Journal of School Health ; (12): 899-903, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1036423

RESUMO

Abstract@#Gurrently, healthy behaviors are the cornerstone of both physical and mental wellbeing,and more researches are focusing on improving behaviors to alleviate depression among children and adolescents. Based on the concept of 24 h movement behaviors proposed in recent years, the study examines the relationship among physical activity, sedentary behavior, sleep and depressive symptoms in children and adolescents. The research suggests that physical activity could effectively alleviate depression among children and adolescents, and its effectiveness is influenced by factors including type, intensity, duration and frequency of physical activity. Excessive sedentary behavior may increase depressive symptoms, and the impacts of different types, durations, and frequencies of sedentary behavior on depressive symptoms among children and adolescents vary. In addition to its direct impact on depression, sleep could also serve as a mediator among physical activity, sedentary behavior and depression, and there is also a crowdingout effect of time between physical activity and sedentary behavior. Future research should focus on the mechanisms and pathways underlying how 24 h movement behaviors affecting depression among children and adolescents, in order to provide more accurate solutions for the prevention and treatment of depression.

7.
Chongqing Medicine ; (36): 542-546,554, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1017495

RESUMO

Objective To explore the value of the Physiology and Surgical Severity Score(POSSUM)scoring system in predicting postoperative complications in elderly patients with thoracic surgery,and to ana-lyze its correlation with Clavien-Dindo classification.Methods The data of 182 elderly patients who under-went thoracic surgery in this hospital from October 2019 to March 2023 were retrospectively analyzed.They were divided into the complication group and the non-complication group according to whether there were complications after surgery.The baseline data and POSSUM score of the two groups were analyzed,and the receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of POSSUM for post-operative complications in elderly patients.POSSUM of patients with different Clavien-Dindo classification was compared,and the correlation between POSSUM and Clavien-Dindo classification analyzed.Results The incidence of pulmonary infection was the highest in the complication group,followed by hypoproteinemia.POSSUM in the complication group was higher than that in non-complication group before operation,and the difference was statistically significant(P<0.05).The ROC curve showed that the area under curve(AUC)value of POSSUM was 0.829;In the complication group,according to Clavien-Dindo classification,there were 5 cases of grade Ⅰ,47 cases of grade Ⅱ,8 cases of grade Ⅱ Ⅲ,7 cases of grade Ⅳ and 8 cases of grade V,the difference was statistically significant(P<0.05).The correlation analysis showed that POSSUM score was positively correlated with Clavien-Dindo classification(r>0.513,P<0.05).Conclusion The POSSUM scoring system has a high value in predicting postoperative complications in elderly patients with thoracic surgery.

8.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1018325

RESUMO

Objective:This study was designed to explore the distribution pattern of TCM syndrome types in patients with Chronic Kidney Disease (CKD) stage 3-5 without alternative treatment after objective collection of TCM quad-diagnostic instruments.Methods:The four-diagnostic instruments of Chinese medicine were used to collect the four-diagnostic information of patients with stage CKD 3-5 non-alternative treatment for syndrome determination, and the correlation between TCM syndrome and basic disease characteristics of patients was analyzed.Results:The distribution of TCM syndrome types in 464 patients with CKD 3-5 stage non-substitution therapy was based on deficiency syndrome, and had both standard and solid syndrome. Qi-deficiency syndrome was the most common type, accounting for 24.6% (114/464), followed by kidney-yang deficiency syndrome, heart-qi deficiency syndrome, kidney-yin deficiency syndrome, heart-blood deficiency syndrome, spleen-yang deficiency syndrome and lung-yin deficiency syndrome. The positivism type of this deficiency is blood stasis, dampness-heat, moisture, turbidity and turbidity toxicity. There was no significant difference in gender and age distribution among patients with different CKD stages ( P>0.05), but the proportion of deficiency syndrome gradually increased with the increase of age. There were differences in the distribution of primary deficiency syndrome in different CKD stages ( χ2=57.48, P<0.001), but no difference in the distribution of primary deficiency syndrome ( χ2=2.59, P=0.957). Conclusions:According to the four diagnostic instrument of traditional Chinese medicine, the distribution of TCM syndrome types in patients with stage CKD3-5 non-alternative treatment is based on deficiency syndrome, combined with deficiency of primary and solid syndrome. The syndrome types in CKD3 stage were mainly qi deficiency and kidney qi deficiency, while the TCM syndrome types in CKD stage 4 were qi deficiency and kidney Yang deficiency. With the progression of the disease, the TCM syndromes of stage 5 CKD were mainly heart-qi deficiency and kidney-yang deficiency.

9.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1018738

RESUMO

α7 nicotinic acetylcholine receptor(α7nAChR)is widely expressed in the central nervous system and immune system,and plays a neuro-immunoregulatory role.On the one hand,α7nAChR is involved in the transmission of neurotransmitters,the conduction of excitatory signals and the maintenance of synaptic plasticity,which is of great significance for maintaining the normal and stable neurocognitive function.On the other hand,as an important part of the cholinergic anti-inflammatory pathway,α7nAChR is involved in the regulation of physiological and pathological processes such as inflammatory response,oxidative stress,apoptosis and autophagy in the central system,and plays an immunomodulatory and neuroprotective role,thus being potential target for improving perioperative neurocognitive function.This article reviews the biological characteristics of α7nAChR and its effect on perioperative neurocognitive function,in order to provide ideas and methods for clinical improvement of perioperative neurocognitive function in surgical patients.

10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1020042

RESUMO

The long-term efficacy and complications of implantable diaphragm pacer (IDP) in a child with cervical spinal cord injury (CSCI) in the Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center in September 2022 were retrospective analyzed.A male child had quadriplegia without an obvious cause at the age of 12 years, and he was then lived completely with the assistance of mechanical ventilation.At the age of 14 years, he could wean off the ventilator in unilateral diaphragmatic pacing mode.However, mechanical ventilation was re-given for months after 5 years due to pneumonia, and then the IDP was re-given with the self-felt decreased pacing effect.After hospitalization, the patient was examined with mild diaphragmatic atrophy, secondary flat chest, and mild scoliosis.After optimization of the transdiaphragmatic pacing threshold and rehabilitation, his respiratory function improved.IDP can be used in CSCI for long time, while flat chest and scoliosis that limited the expansion of the lungs should be considered.At the meantime, the increased abdominal spasm affected the abdominal compliance, leading to the decrease in the efficiency of the diaphragm.

11.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1021374

RESUMO

BACKGROUND:Cadmium is a common environmental pollutant,which can damage multiple organs and tissues,such as the kidney and bone,but its effect on annulus fibrosus cells in the intervertebral disc has been less reported. OBJECTIVE:To investigate the effect of cadmium chloride on the senescence of annulus fibrosus cells and the role of PI3K/Akt signaling pathway. METHODS:Annulus fibrosus cells from Sprague-Dawley rat intervertebral discs were harvested and passage 3 cells were intervened with different concentrations of cadmium chloride(0,1,5,10,20 μmol/L).Cell viability and proliferation were detected by cell counting kit-8 assay.Transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis were performed on annulus fibrosus cells with or without cadmium chloride addition.Passage 3 annulus fibrosus cells were divided into control group,cadmium chloride group and LY294002 group.Cell proliferation rate was detected by EdU method,positive cell rate was detected by senescence-associated β-galactosidase staining,and expressions of senescence-associated proteins(p16,p21 and p53)and p-Akt at protein and mRNA levels were measured by western blot,RT-PCR and immunofluorescence. RESULTS AND CONCLUSION:5 μmol/L cadmium chloride could inhibit the proliferation of annulus fibrosus cells.Results from the Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis showed that the main signal transduction pathways included PI3K/Akt,cell cycle and p53 signaling pathways,which were related to cell senescence and proliferation.PI3K/Akt signaling pathways with significant differential expression were selected for validation.Compared with the control group,the EdU-positive rate was significantly decreased in the cadmium chloride group(P<0.05),while the β-galactosidase-positive rate,the expression of senescence-associated proteins(p16,p21 and p53)and p-Akt significantly increased(P<0.05).Compared with the cadmium chloride group,the EdU-positive rate and p-Akt expression were significantly decreased in the LY294002 group(P<0.05),while the β-galactosidase-positive rate and the expression of senescence-associated proteins(p16,p21 and p53)significantly increased(P<0.05).To conclude,cadmium chloride can regulate the senescence of annulus fibrosus cells by activating the PI3K/Akt signaling pathway,thereby inducing the occurrence and progression of intervertebral disc degeneration.

12.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1025315

RESUMO

This paper analyzes the main obstacles in the process of promoting the integration of medicine and prevention in China,including the mindset of prioritizing medical care over prevention,fragmented system architecture,conflicting direction of funding and incentives,and inherent contradictions in the division of labor and cooperation in service provision.Furthermore,this article attempts to present the current status and constraints of medical and health integration in China from the perspectives of management mechanisms and service mechanisms,highlighting the mismatch between these two aspects as the root cause.It proposes that the reform logic of current medical and health integration practices should prioritize the service mechanism.This involves clarifying the service interface of medicine and prevention integration and establishing patient-centered service pathways for integration.In the establishment of the service mechanism,a balance should be struck between efficiency and quality,while also integrating based on division of labor.Subsequently,adjustments to the management mechanism should be made in accordance with the medicine and prevention integration service mechanism.In the reform of the management mechanism,various stakeholders'interests should be coordinated and the costs of reform should be controlled.

13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1025324

RESUMO

Objective:Operational efficiency and influencing factors of China's basic medical insurance system from 2020 to 2021 is conducted to provide reference for improving the operational efficiency and optimizing the input-output relationship.Methods:The super-efficiency SBM model based on unexpected output and the Malmquist index are used to measure the static and dynamic efficiency of resident medical insurance in 31 provinces in China,and Tobit regression analysis is employed to analyze the influencing factors.Results:The overall operational efficiency of resident medical insurance still needs improvement.The operational efficiency of resident medical insurance in the central and western regions is lower than that in the eastern region,and the gap is significant.Different levels and regions have differentiated main constraints on the operational efficiency of resident medical insurance.In terms of dynamic efficiency,the total factor productivity of resident medical insurance operation shows an increasing trend,mainly due to technological progress.In terms of influencing factors,the degree of aging,the level of medical expenses and the level of medical insurance supervision have a significant impact on the operational efficiency.Suggestions:Efforts should be made to bridge regional disparities,promote the equitable development of medical insurance,reasonably control the level of medical expenses,strengthen the supervision of medical insurance funds,and implement active aging policies.

14.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1026839

RESUMO

Immune factors play an important role in recurrent spontaneous abortion(RSA),and immune imbalance affects embryo implantation,growth,and development.There is currently no consensus on the etiology and pathogenesis of RSA caused by immune factors.Based on the theory of latent toxic in TCM and combined with the pathological mechanism of the dynamic changes of immune abnormal substances in the body,this article proposed that latent toxic is the key cause of RSA caused by immune factors.Furthermore,it expounded the pathogenic characteristics of latent toxic:combination of heat and blood stasis hidden in the womb,and latent toxic plays a role in embryo formation under qi deficiency conditions.It is established that latent toxin stagnation in the membrane is the pathogenic mechanism.Moreover,this article revealed the variable pathological changes such as the blockage of the inner membrane system and the outer membrane system.Treatment should be based on the basic methods of tonifying qi and nourishing blood,tonifying kidney to secure the Thoroughfare Vessel,clearing heat and cooling blood,promoting blood circulation and removing blood stasis.This article could provide a theoretical basis for TCM syndrome differentiation and treatment of RSA caused by immune factors.

15.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1038440

RESUMO

ObjectiveTo carry out an epidemiological analysis on an outbreak of Mycoplasma pneumoniae infection at a welfare institution to provide a theoretical basis for the corresponding prevention and control measures. MethodsUsing the method of field epidemiological investigation, special field treatment was carried out in September 2022. Serum samples from cases and close contacts in the same ward area were collected for detection of nine respiratory tract infection pathogens (Mycoplasma pneumoniae, chlamydia, influenza, human metapneumosis, respiratory syncytial, human boca, parainfluenza type 1‒4 virus, and Middle East respiratory syndrome, severe acute respiratory syndrome coronavirus) by immunofluorescence immunoglobulin M (IgM) antibody test. ResultsA total of 14 Mycoplasma pneumoniae cases were identified, all of whom were residents of the welfare institution. The first case occurred on September 4, while the last case was reported on September 13. The incidence rate of the fifth ward area where the first case reported was 12.82% (10/78), and it was 3.57% (3/84) in the third ward area and 1.20% (1/83) in the first ward area. There was a significant difference in incidence rates between ward areas (χ2=8.90, P<0.05), but no significant difference was observed in age distribution and length of hospitalization. Thirty-three samples were collected for detection of nine kinds of IgM antibodies against respiratory pathogens. The results showed that the Mycoplasma pneumoniae IgM antibody was weakly positive in the 14 cases. ConclusionBased on the epidemiological history, clinical symptoms and laboratory tests, it was concluded that it was an outbreak of Mycoplasma pneumoniae infection within the welfare institution. Welfare institutions should continue to control the occurrence and outbreak of infection through effective routine hygiene, ventilation, and disinfection so as to ensure the health and safety of their clients.

16.
Chinese Pharmacological Bulletin ; (12): 483-489, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013640

RESUMO

Aim Based on the apoptotic pathway mediated by receptor interacting protein kinase(RIP)1-RIP3-mixed spectrum kinase domain like protein(MLKL), to explore the effects of naringenin on ovarian granulosa cell apoptosis in rats with polycystic ovary syndrome(PCOS). Methods SD rats were randomly assigned into normal control group, model group, naringenin group, RIP1 inhibitor(Nec-1)group, RIP1-RIP3-MLKL necrosis signal activator(Z-VAD-fmk)group, naringenin+Z-VAD-fmk group, 15 rats per group. ELISA method was performed to measure the levels of IL-1β and TNF-α in ovarian tissue. HE method was performed to observe the shape of the ovary. Granular cells were isolated from ovarian tissue, and flow cytometry was performed to measure apoptosis rate and necrosis rate. Immunohistochemistry was performed to measure the positive expression of p-RIP1 in ovarian tissue. Western blot was employed to detect the expression of RIP1-RIP3-MLKL pathway. Results RIP1 specific inhibitor Nec-1 and naringenin could block the phosphorylation and activation of RIP1, inhibit the RIP1-RIP3-MLKL signaling pathway, reduce the inflammation level in PCOS rats, and alleviate the necrosis and apoptosis of ovarian granulosa cells(P<0.05). Z-VAD-fmk could promote the activation of RIP1-RIP3-MLKL pathway, aggravate the apoptosis of ovarian granulosa cells, and partially weaken the anti-apoptosis effect of naringenin(P<0.05). Conclusions Naringenin may inhibit the apoptosis of ovarian granulosa cells in PCOS rats by blocking the activation of the necrotic apoptotic pathway mediated by RIP1-RIP3-MLKL.

17.
Chinese Pharmacological Bulletin ; (12): 521-528, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013645

RESUMO

Aim To investigate the protective effect of dimethyl fumarate on spleen injury induced by gamma radiation in mice and the related mechanism. Methods C57BL/6 mice were randomly divided into the blank control group, radiation model group and DMF administration group, which were administered once at 12 h before irradiation and once at 0. 5 h, 12 h, 24 h and 48 h after irradiation. The 30-day survival rate, body weight and pathological injury of spleen were measured after a one-time total body irradiation of Co 7 rays (8 Gy). TUNEL staining was used to detect apoptosis of spleen cells. Enzyme-linked immunoassay ( ELISA) was applied to detect the contents of TNF-a, IL-1 p, IL-6, IL-18, NLRP3 and AIM2 in spleen. Western blot test and immunofluorescence staining test was employed to verify the changes of NLRP3 and AIM2 contents in spleen tissue after irradiation. Results DMF could obviously improve the survival rate of irradiated mice, improve the weight loss of irradiated mice, re-duce the pathological injury of spleen, and inhibit the apoptosis of spleen cells after irradiation. ELISA results showed that DMF could significantly inhibit the increase of spleen inflammatory cytokines TNF-a, IL-lp, IL-6, IL-18 and inflammasome components NL-RP3 and AIM2 induced by irradiation. Western blot and tissue immunofluorescence staining also confirmed that DMF could inhibit the increase of NLRP3 and AIM2 inflammasome protein levels caused by irradiation. Meanwhile, NLRP3 agonist and AIM2 agonist could antagonize the radiation protection effect of DMF on spleen cells. Conclusion DMF can ameliorate spleen injury of Co 7-ray injured mice, and its mechanism is closely related to NLRP3/AIM2 inflamma-somes, which can be used as a potential protective drug for radiation injury.

18.
Acta Pharmaceutica Sinica ; (12): 382-394, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1016643

RESUMO

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

19.
Front Immunol ; 14: 1190678, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37691922

RESUMO

Background: Focal adhesion serves as a bridge between tumour cells and the extracellular matrix (ECM) and has multiple roles in tumour invasion, migration, and therapeutic resistance. However, studies on focal adhesion-related genes (FARGs) in head and neck squamous cell carcinoma (HNSCC) are limited. Methods: Data on HNSCC samples were obtained from The Cancer Genome Atlas and GSE41613 datasets, and 199 FARGs were obtained from the Molecular Signatures database. The integrated datasets' dimensions were reduced by the use of cluster analysis, which was also used to classify patients with HNSCC into subclusters. A FARG signature model was developed and utilized to calculate each patient's risk score using least extreme shrinkage and selection operator regression analysis. The risk score was done to quantify the subgroups of all patients. We evaluated the model's value for prognostic prediction, immune infiltration status, and therapeutic response in HNSCC. Preliminary molecular and biological experiments were performed to verify these results. Results: Two different HNSCC molecular subtypes were identified according to FARGs, and patients with C2 had a shorter overall survival (OS) than those with C1. We constructed an FARG signature comprising nine genes. We constructed a FARG signature consisting of nine genes. Patients with higher risk scores calculated from the FARG signature had a lower OS, and the FARG signature was considered an independent prognostic factor for HNSCC in univariate and multivariate analyses. FARGs are associated with immune cell invasion, gene mutation status, and chemosensitivity. Finally, we observed an abnormal overexpression of MAPK9 in HNSCC tissues, and MAPK9 knockdown greatly impeded the proliferation, migration, and invasion of HNSCC cells. Conclusion: The FARG signature can provide reliable prognostic prediction for patients with HNSCC. Apart from that, the genes in this model were related to immune invasion, gene mutation status, and chemosensitivity, which may provide new ideas for targeted therapies for HNSCC.


Assuntos
Adesões Focais , Neoplasias de Cabeça e Pescoço , Humanos , Adesão Celular , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Prognóstico , Neoplasias de Cabeça e Pescoço/genética
20.
Indian J Dermatol ; 68(3): 318-326, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37529461

RESUMO

To investigate the regularity and characteristics of adverse drug reaction (ADR) of reactive cutaneous capillary endothelial proliferation caused by Camrelizumab, so as to provide reference for clinical rational use of drugs. Searching for case reports of Camrelizumab-induced reactive cutaneous capillary endothelial proliferation (RCCEP) in databases such as China Biology Medicine disc, VIP Database, CNKI, Wanfang Medical, PubMed, Wiley online library, Embase with "Carritzumab/Ericab," "SHR-1210," "Reactive cutaneous capillary endothelial proliferation," "Reactive capillary hemangiomas," and "Capillary proliferation" as search terms. The retrieval time is from the establishment of the database to February 2022. After eliminating clinical trials and incomplete literature, information of patients included in the literature was analyzed, which included gender, age, reason for medication, usage and dosage, time of ADR, concomitant medication, clinical manifestations, intervention measures, outcomes of patients, etc. A total of 11 articles involving 16 patients were included, including 11 males and five females, with an average age of 60.5 years. Reasons for medication included nine cases of non-small cell lung cancer (NSCLC), four cases of liver cancer, one case of small cell lung cancer (SCLC), one case of synovial sarcoma, and one case of Hodgkin lymphoma. Thirteen patients recorded in detail that the dosage of Camrelizumab was 200 mg, and the frequency of medication was q2w~q4w. Eight patients were treated with Camrelizumab alone, and eight patients were treated with combined medication. RCCEP occurred in nine patients after the first medication, and in seven patients after two-four cycles of medication, the average medication cycle was two cycles, and the average occurrence time was 12.5 days after the last medication. The main clinical manifestations were that several different sizes of growths such as red nevus-like, pearl-like, and mulberry-like growths appear on the head, face, neck, torso, limbs, and other parts of the body, all of which were grade 1-2. The RCCEP of all patients was controlled after treatment. During the treatment, 11 patients were stable and five patients were local remission. RCCEP is caused by Camrelizumabis a special skin immune response, which will not cause life-threatening to patients. However, clinicians and pharmacists should be familiar with the characteristics and regularities of the adverse reaction, to do a good job in medication monitoring and management, as for ensuring the safety of patients with medication.

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