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ObjectiveTo preliminarily confirm the effective anti-lung cancer sites of Momordicae Semen and Epimedii Folium and study their mechanism of action. MethodOn the basis of preliminary research, the extraction method of Momordicae Semen and Epimedii Folium was optimized and the effective parts were screened under the guidance of pharmacological effects. Different ethanol elution and water elution sites of Momordicae Semen and Epimedii Folium were obtained through adsorption and elution with D101 macroporous resin. The methylthiazolyldiphenyl-tetrazolium bromide (MTT) colorimetric assay was used to detect the effects of total drug extracts and different elution sites on the proliferation of various tumor cell lines, and to screen for the optimal elution site and tumor sensitive strains. Flow cytometry was used to detect the effect of the elution sites of Momordicae Semen and Epimedii Folium on intracellular reactive oxygen species (ROS) and apoptosis in A549 cells. Western blot was used to compare the expressions of tumor protein 53 (p53), Bcl-2-associated X protein (Bax), cysteinyl aspartate specific proteinase-3 and 9 (Caspase-3 and Caspase-9) proteins in A549 cells. ResultThe inhibitory effect of Momordicae Semen on the proliferation of A549 cells was better than the kernel of Momordicae Semen, with 50% inhibitory concentration (IC50) being (86.83±2.88) mg·L-1 and (95.10±18.13) mg·L-1, respectively. The effect of total extracts of Epimedii Folium on A549 anti proliferation IC50 value was (4.71±0.81) mg·L-1. The IC50 values of the 40%, 60%, and 80% ethanol and anhydrous ethanol eluted macroporous resins of the total extracts of Momordicae Semen and Epimedii Folium inhibiting A549 proliferation were (45.32±4.38)、 (14.95±0.73)、 (17.07±1.76)、 (14.46±2.35)、 (51.7±2.26)、 (12.37±0.67)、 (20.29±0.93)、 and (3.43±0.91) mg·L-1, respectively. Compared with the normal group, the 1∶1 combination of Momordicae Semen and Epimedii Folium inhibited A549 cell proliferation in a time-dependent and concentration-dependent manner. Compared with the normal group, 50 mg·L-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased intracellular ROS expression (P<0.01). Compared with the normal group, 12.5, 25, 50 mg·L-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased the expression of A549 cell apoptosis (P<0.01). Compared with the normal group, 25, 50 mg·L-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased the expression of p53 in A549 cells (P<0.01). Compared with the normal group, 12.5, 25, 50 mg·L-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased the expression of Bax (P<0.01). Compared with the normal group, 50 mg·L-1 of the combination of Momordicae Semen and Epimedii Folium significantly reduced the expressions of Caspase-3 and Caspase-9 (P<0.01). ConclusionThe anti-tumor effect of Momordicae Semen is better than that of the kernel of Momordicae Semen. The anti-tumor substances of Momordicae Semen and Epimedii Folium mainly concentrate in the 60% ethanol to anhydrous ethanol elution site. A549 cells are sensitive to the 1∶1 combination of Momordicae Semen and Epimedii Folium, which can effectively inhibit the cell proliferation. The mechanism may be related to increasing the generation of ROS in A549 cells, promoting their apoptosis, increasing the expressions of apoptotic proteins such as p53 and Bax, and reducing the expressions of Caspase-3 and Caspase-9.
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@#The World Health Organization (WHO) released the “Global report on hypertension” on September 19, 2023. This report systematically summarizes the prevalence, mortality, diagnosis and treatment of hypertension in various countries, and elucidates the current situation of hypertension management, and gives a series of suggestions on how to manage hypertension, providing new thinking and inspiration for countries to optimize hypertension management. Through the summary of relevant studies and reports, this paper further reviews the present situation, early identification and management of hypertension.
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Narrow-band ultraviolet B (NB-UVB) phototherapy has been regarded as the first-line treatment of generalized vitiligo. However, NB-UVB monotherapy exhibits limited efficacy with a long course of treatment. NB-UVB phototherapy combined with other therapies can shorten the course of treatment and improve the therapeutic effect, and has become a commonly used therapeutic regimen in clinical practice. This review summarizes research progress in the combined therapies of NB-UVB with other approaches for the treatment of vitiligo, such as glucocorticoids, afamelanotide, calcineurin inhibitors, Janus kinase inhibitors, platelet-rich plasma, fractional CO 2 laser and surgical treatment, in order to provide more options for clinical treatment of vitiligo.
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Except for IgA nephropathy, membranous nephropathy (MN) is the most common primary glomerulonephritis in China. Neural epidermal growth factor-like 1 protein (NELL-1) has been currently considered as one of the target antigens for diagnosis of primary MN. Moyamoya syndrome is a syndrome with clinical and imaging manifestations of moyamoya disease and possible vascular stenosis. By far, primary MN complicated with moyamoya syndrome has not been reported internationally. The paper reports a case of NELL-1-related MN complicated with moyamoya syndrome and reviews relevant literature to provide evidence for clinical diagnosis and treatment.
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Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a group of systemic small vasculitis characterized by the detection of ANCA in serum. Bactericidal permeability enhancing protein (BPI) is one of the target antigens of ANCA. BPI-ANCA-associated vasculitis is not common clinically, and the combination of bronchiectasis is not accidental. The paper reported a case of BPI-ANCA-associated vasculitis with renal damage combined with bronchiectasis. We reviewed relevant literature to explore the characteristics of BPI-ANCA-associated vasculitis and the correlation between bronchiectasis and ANCA-associated vasculitis, so as to improve the clinician's understanding on this disease.
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@#The Chinese Guidelines on Diagnosis and Management of Atrial Fibrillation, jointly formulated by the Chinese Society of Cardiology, Chinese Medical Association and the Heart Rhythm Committee of Chinese Society of Biomedical Engineering, was first released on June 15, 2023. The guidelines elaborate the various aspects of atrial fibrillation management, in which emergency management of atrial fibrillation is also an integral part. This article interpreted the emergency management part in the guidelines in detail by reviewing relevant literature.
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@#Obesity, sleep disorders, psychological stress, sedentary are modifiable cardiovascular risk factors. There is growing evidence that these risk factors may accelerate the chronic inflammatory process of atherosclerosis and lead to myocardial infarction. Studies on the role of immune cells and their related immune mechanisms in atherosclerosis have shown that the above modifiable risk factors can affect the hematopoiesis of the bone marrow system, affect the production of immune cells and phenotypes, and then affect the progress of atherosclerosis. This review will focus on the effects of modifiable cardiovascular risk factors on the progression of atherosclerosis through the role of the innate immune system.
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ObjectiveTo investigate the effects of different cultivation modes on the yield of Gentiana crassicaulis and its microbial diversity and secondary metabolite content in the rhizosphere soil. MethodWith G. crassicaulis of different cultivation modes and its rhizosphere soil as the research objects, the composition of bacterial and fungal communities, dominant bacteria, and differential microorganisms in the rhizosphere soil were analyzed by high-throughput sequencing technology. HPLC was used to determine the content of iridoids in G. crassicaulis with different cultivation modes. ResultCompared with plastic film mulching, planting without mulch and intercropping of peony, white kidney bean, potato, and corn increased the yield of fresh products by 16.11%-17.68%, 22.48%-26.34%, 29.37%-32.19%, 34.82%-36.57%, and 35.34%-39.71%, respectively, and increased the yield of dry products by 19.75%-23.17%, 25.86%-29.32%, 30.18%-34.94%, 35.22%-39.87%, and 39.72%-43.73%. The total content of four iridoids, including gentiopicrin, loganic acid, sweroside, and swertiamarin, increased by 10.17%-37.83%, 5.93%-47.44%, 9.09%-28.84%, and 10.71%-28.57%, respectively. The diversity of bacterial and fungal communities in the rhizosphere soil increased significantly (P<0.05). The relative abundance of pathogenic bacteria such as Sordariomycetes, Leotiomycetes, Tremellomycetes, Eurotiomycetes, Fusarium, and Cladophialophora decreased, and the proportions of beneficial bacteria such as Proteobacteria, Acidobacteria, and Actinobacteriota increased and they gradually became the dominant bacteria. ConclusionDifferent cultivation modes can affect the yield of G. crassicaulis and its microbial diversity and iridoid content in the rhizosphere soil. Cultivation without mulch and intercropping patterns have certain advantages, which can provide theoretical references for the planting of G. crassicaulis.
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With the proliferation of synthetic drugs, research on the mechanism of action of addictive drugs and treatment methods is of great significance. Among them, methamphetamine (METH) is the most representative amphetamine synthetic drug, and the treatment of METH addiction has become an urgent medical and social problem. In recent years, the therapeutic effects of Chinese herbal medicines on METH addiction have gained widespread attention because of their non-addictiveness, multiple targets, low side effects, low cost, and other characteristics. Previous studies have identified a variety of Chinese herbal medicines with effects on METH addiction. Based on the research on METH in recent years, this article summarizes the mechanism of action of METH as the starting point and briefly reviews the Chinese herbal medicine-based treatment of METH.
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Humanos , Metanfetamina/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Anfetamina/uso terapêutico , Comportamento Aditivo/tratamento farmacológico , Transtornos Relacionados ao Uso de Anfetaminas/tratamento farmacológicoRESUMO
Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.
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Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.
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This study explored the effect and underlying mechanism of Stellera chamaejasme extract(SCE) on multidrug resistance of breast cancer. The chemotherapy-sensitive breast cancer cell line MCF-7 and adriamycin(ADR)-resistant cell line MCF-7/ADR were used as experimental subjects. MTT assay was used to detect cell proliferation activity. Pi staining was used to detect the cell cycle. 4',6-Diamidino-2-phenylindole, dihydrochloride(DAPI) staining and flow cytometry were used to detect apoptosis. Dansylcadaverine(MDC) staining and GFP-LC3B-Mcherry adenovirus transfection were used to detect autophagy. The protein expression of Bcl-2, Bax, caspase-9, caspase-3, LC3B, p62, and Beclin-1 was detected by Western blot. The results showed that SCE could significantly inhibit the proliferation of both sensitive and resistant breast cancer cell lines. The drug resistance factor was 0.53, which was significantly lower than 59 of ADR. Meanwhile, the proportion of sensitive/resistant cells in the G_0/G_1 phase increased significantly after SCE treatment. In addition, DAPI staining showed that a series of apoptosis phenomena such as nuclear pyknosis, staining deepening, and nuclear fragmentation appeared in sensitive/resistant cell lines after SCE administration. Moreover, the results of flow cytometry double staining showed that the proportion of apoptotic cells in sensitive/resistant cell lines increased significantly after SCE administration. Besides, Western blot showed that the protein expression levels of caspase-3, caspase-9, and Bcl-2 significantly decreased and the expression level of Bax protein significantly increased in both breast cancer cell lines after SCE administration. Furthermore, SCE could also increase the positive fluorescent spots after MDC staining and yellow fluorescent spots after GFP-LC3B-mcherry transfection, and up-regulate the expression levels of autophagy-related proteins LC3B-Ⅱ, p62, and Beclin-1 in breast cancer cells. In summary, SCE may play the role of anti-multidrug resistance by blocking the cell cycle of breast cancer multidrug-resistant cells, blocking autophagy flow, and ultimately interfering with the apoptosis resistance of drug-resistant cells.
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Humanos , Feminino , Neoplasias da Mama/metabolismo , Células MCF-7 , Caspase 3/metabolismo , Caspase 9/metabolismo , Proteína Beclina-1/farmacologia , Apoptose , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Proliferação de CélulasRESUMO
Inflammasomes play an important role in the innate immunity of the liver; however, the excessive activation of inflammasomes can lead to liver inflammation and injury. The mechanism of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome-mediated liver injury has been extensively studied. Related studies have shown that the development of various liver diseases may be associated with the excessive activation of inflammasomes, especially NLRP3 inflammasome. This article reviews inflammasomes, the activation mechanism of NLRP3 inflammasome, and the role of NLRP3 inflammasome in different liver diseases, so as to provide a reference for the treatment targets of liver diseases from the perspective of NLRP3 inflammasome.
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Liver fibrosis is the common consequence of various chronic liver injuries and is mainly characterized by the imbalance between the production and degradation of extracellular matrix, which leads to the accumulation of interstitial collagen and other matrix components. Matrix metalloproteinases (MMPs) and their specific inhibitors, i.e., tissue inhibitors of metalloproteinases (TIMPs), play a crucial role in collagen synthesis and lysis. Through a literature review, this article reviews the experimental studies of liver fibrosis based on MMPs/TIMPs, summarizes the components that may exert an anti-liver fibrosis effect by affecting the expression or activity of MMPs/TIMPs, and attempts to clarify the mechanism of MMPs/TIMPs in regulating collagen homeostasis, so as to provide support for the development of anti-liver fibrosis drugs.
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Drug-induced liver injury (DILI) is one of the common adverse drug reactions and is the main cause of withdrawal of drugs after marketing, which has attracted more and more attention of the public, and herb-induced liver injury (HILI) is a special type of DILI. In recent years, the frequent occurrence of HILI not only seriously endangers the health of patients, but also causes the controversy over the safety of traditional Chinese medicine. Therefore, this article reviews the potential risk factors for HILI from the three aspects of "patient", "drug", and "use", so as to provide a basis for the objective identification, prevention, and control of HILI and a reference for the construction of traditional Chinese medicine pharmacovigilance system represented by liver injury.
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Consecutively hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) in Wuhan, China were retrospectively enrolled from January 2020 to March 2020 to investigate the association between the use of renin-angiotensin system inhibitor (RAS-I) and the outcome of this disease. Associations between the use of RAS-I (angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)), ACEI, and ARB and in-hospital mortality were analyzed using multivariate Cox proportional hazards regression models in overall and subgroup of hypertension status. A total of 2771 patients with COVID-19 were included, with moderate and severe cases accounting for 45.0% and 36.5%, respectively. A total of 195 (7.0%) patients died. RAS-I (hazard ratio (HR)= 0.499, 95% confidence interval (CI) 0.325-0.767) and ARB (HR = 0.410, 95% CI 0.240-0.700) use was associated with a reduced risk of all-cause mortality among patients with COVID-19. For patients with hypertension, RAS-I and ARB applications were also associated with a reduced risk of mortality with HR of 0.352 (95% CI 0.162-0.764) and 0.279 (95% CI 0.115-0.677), respectively. RAS-I exhibited protective effects on the survival outcome of COVID-19. ARB use was associated with a reduced risk of all-cause mortality among patients with COVID-19.
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Humanos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , COVID-19 , Hipertensão/tratamento farmacológico , Sistema Renina-Angiotensina , Estudos RetrospectivosRESUMO
Breast cancer, as a kind of malignant tumor with high incidence rate in female population, poses a great threat to people's health. At present, chemotherapy is the main treatment for breast cancer besides surgery and radiotherapy. However, chemotherapy is often accompanied by multidrug resistance (MDR), which results in a series of severe consequences such as low efficacy, relapse of cancer after drug withdrawal, increased consumption of medical resources, and increased burden of medical system. Previous studies showed that the mechanism of MDR in breast cancer was quite complex, involving drug efflux, deoxyribonucleic acid (DNA) damage repair, tumor microenvironment, autophagy, epigenetic regulation, tumor stem cells, lipid metabolism, and so on. In addition, there were extensive connections among the mechanisms of MDR. Therefore, it is necessary to reveal the mechanism of MDR and develop corresponding drugs to reverse MDR, thus improving the effect of chemotherapy on treating breast cancer. Chinese medicine has the advantages of high efficiency, low toxicity, multi targets, and overall regulation. Various studies found that Chinese medicine monomer, single drug, and compound were able to reverse MDR in breast cancer by regulating the expression of drug efflux protein, promoting apoptosis, and regulating autophagy, showing the potential of anti-MDR in breast cancer. This paper summarized the research progress of the mechanism of MDR in breast cancer and the strategies of Chinese medicine in coping with MDR in breas cancer in recent years, and provided references for further research.
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Adipocyte enhancer binding protein 2, as a component protein of Polycomb repressive complex (PRC2), is involved in the proliferation and migration of many tumor cells. However, its role in HCC is still unclear. In this study, we identify that AEBP2 was upregulated in HCC samples from the UALCAN and Kaplan-Meier Plotter database, which was correlated to the overall survival time of HCC patients. Real-time quantitative PCR and Western blotting confirmed that the expression of AEBP2 in HCC cells was higher than normal liver cells. After silencing AEBP2 in HepG2 and Huh-7 cells, the effects of the proliferation, apoptosis, migration and invasion were detected by colony formation, CCK-8, flow cytometry, scratch healing and Transwell chamber, respectively. Compared with the control group, down-regulation of AEBP2 expression inhibited the proliferation, migration and invasion in HepG2 and Huh-7 cells, as well as promoted apoptosis (P<0. 05). Immunofluorescence and Western blotting results showed that AEBP2 silencing inhibited epithelial-mesenchymal transformation (EMT) (P < 0. 05). Bioinformatics analysis showed that AEBP2 is involved the PI3K/Akt signaling pathway. Western blotting results confirmed that silencing AEBP2 down-regulated the expression levels of PI3K, p-AKT (S473), mTOR, MMP-2 and MMP-9 proteins (P<0. 05). In addition, the effects of AEBP2 silencing on HepG2 cells migration and invasion could be reversed by PI3K/Akt pathway agonist insulin-like Growth Factors (IGF-1) (P < 0. 01). In summary, our study showed that AEBP2 promoted the proliferation and migration of HCC cell by regulating PI3K/AKT pathway. This study provided a theoretical basis for the role of AEBP2 in HCC.
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Aim To investigate the effect of terpinene 4-alcohol(T4O)on the malignant behavior of colorectal cancer cell RKO and HCT116 and the underlying mechanism. Methods RKO and HCT116 cells were treated with 0, 1, 2, 4 μmol·L-1 T4O and 4 μmol·L-1 5-Fu, respectively. The proliferation, clonal formation, apoptosis, cell cycle, migration and invasion of RKO and HCT116 cells were detected by CCK-8, colony formation, flow cytometry, wound healing and Transwell assay; the expressions of E-Cadherin, N-Cadherin, p21, CyclinB1 and cleaved-Caspase7 in each group of cells were detected by Western blot. Based on pharmacophore, the target of T4O was analyzed and then the effects of T4O on the expression and degradation rate of NR3C1 were explored. NR3C1 knockdown cells were constructed, and the effects of NR3C1 knockdown on the proliferating and migrating inhibition induced by T4O were detected by wound healing and CCK-8 assay. Results T4O significantly inhibited the proliferation, colony formation, migration and invasion of RKO and HCT116 cells, as well as induced apoptosis and G1 phase arrest(P all <0. 05). The effect of T4O was better than that induced by 5-Fu with the same dose. T4O obviously reduced N-Cadherin and Cyclin B1 expression, and elevated the E-Cadherin, p21 and cleaved-Caspase7 expression(P all <0. 05). A total of 10 targets of T4O were discovered, among which NR3C1 had the highest binding score. After T4O treatment, NR3C1 level in cells increased obviously, and the degradation rate decreased markedly(P<0.05). NRC3C1 knockdown significantly relieved the inhibitory effects of T4O on cell prolfieration and migration(P<0.05). Conclusion T4O can inhibit the malignant behavior of colorectal cancer cells RKO and HCT116 by maintaining the stability of NR3C1 protein.
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Objective:To study the value of autoregressive integrated moving average (ARIMA) and autoregressive (AR) models in predicting the daily number of ambulances in prehospital emergency medical services demand in Guangzhou.Methods:Matlab simulation software was used to analyze the emergency dispatching departure records in Guangzhou from January 1, 2021 to December 31, 2021. A time series for the number of ambulances per day was calculated. After identifying the time series prediction model, ARIMA(1,1,1), AR(4) and AR(7) models were obtained. These models were used to predict the number of ambulances per day. ARIMA(1,1,1) model divided the time series into the training set and test set. Prony method was used for parameter calculation, and the demands of number of ambulances of the next few months were forecasted. AR(4) and AR(7) models used uniformity coefficient to forecast the demands of number of ambulances on that very day.Results:ARIMA(1,1,1), AR(4) and AR(7) can effectively predict the number of ambulances per day. The prediction fitting error of ARIMA (1,1,1) decreased with the extension of prediction time. The mean absolute percentage error (MAPE) of forecast results of daily vehicle output of emergency dispatching within two months was less than 6% and the predicted results were almost within the 95% confidence interval. The residual analysis of the model verified that the model was significantly effective.Conclusions:ARIMA model can make a long-term within two months and effective prediction fitting of the daily vehicle output of emergency dispatching, and AR model can make a short-term and effective prediction of the daily vehicle output of emergency dispatching.