Strain Differences of Macrophage Distribution in the Experimental Colorectal Cancer Model

論文Original PaperColorectal cancer (CRC) is one of the most common forms of malignancy in humans. Patients with long-standing ulcerative colitis (UC) have an increased risk for developing CRC compared to the general population. For investigation of the mechanisms and prevention of UC, and UC-related CRC, we first induced UC by DSS and then induced CRC by DMH. It took only 3 months to found the CRC model in Wister rats. The important similarities of the model may be seen in the clinical and pathological findings in animals and patients with CRC developing from UC. It is especially suited to the study of UC and CRC. In this study the mean percent of ED1, and ED3 positive macrophages in Wistar rats was higher than that in DA and Lewis rats (p < 0.05). The mean percent of Marl, and Mar3 positive macrophages in DA and Lewis rats was higher than that in Wistar rats (p < 0.05). These results suggested that the existence of four types of macrophages may play an important role in inducing colitis and rectal cancer. Furthermore, the mechanisms of strain difference in the experimental models are discussed

The methylation status of ASPP CpG island is changed in cancer cell lines retaining wild-type

原著Original ArticleThe p53 protein is one of the best-known tumor suppressors. Recently discovered ASPP1 and ASPP2 are specific activators of p53. To understand if ASPP inactivation offers a selective advantage to tumors that have wild-type p53, we measured the mRNA expression of ASPP1 and ASPP2 in tumor cell lines retaining wide-type p53. In addition, the CpG island methlyation status of ASPP1 gene and ASPP2 gene in the 5\u27-untranslated region was also investigated in order to understand the possible cause of abnormal expression of ASPP1 and ASPP2 in the tumor cell lines retaining wide-type p53. The data showed that mRNA expression of ASPP1 and ASPP2 is downregulated and CpG island tested is hypermethylated. These results indicated that ASPP CpG island aberrant methylation could be one molecular and genetic alteration in wild-type p53 tumors and one of the reasons that are responsible for the loss of ASPP activity

Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. METHODS: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥ 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. DISCUSSION: This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020

Association of inpatient use of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19

Rationale: Use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. Objective: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in COVID-19 patients with hypertension. Methods and Results: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [IQR 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [IQR 57-69]; 53.5% men), who were admitted to nine hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. Unadjusted mortality rate was lower in the ACEI/ARB group versus the non-ACEI/ARB group (3.7% vs. 9.8%; P = 0.01). In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted HR, 0.42; 95% CI, 0.19-0.92; P =0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted HR, 0.37; 95% CI, 0.15-0.89; P = 0.03). Further subgroup propensity score-matched analysis indicated that, compared to use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted HR, 0.30; 95%CI, 0.12-0.70; P = 0.01) in COVID-19 patients with hypertension. Conclusions: Among hospitalized COVID-19 patients with hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB non-users. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk

Evaluation of LFP Battery SOC Estimation Using Auxiliary Particle Filter

State of charge (SOC) estimation of lithium batteries is one of the most important unresolved problems in the field of electric vehicles. Due to the changeable working environment and numerous interference sources on vehicles, it is more difficult to estimate the SOC of batteries. Particle filter is not restricted by the Gaussian distribution of process noise and observation noise, so it is more suitable for the application of SOC estimation. Three main works are completed in this paper by taken LFP (lithium iron phosphate) battery as the research object. Firstly, the first-order equivalent circuit model is adapted in order to reduce the computational complexity of the algorithm. The accuracy of the model is improved by identifying the parameters of the models under different SOC and minimum quadratic fitting of the identification results. The simulation on MATLAB/Simulink shows that the average voltage error between the model simulation and test data was less than 24.3 mV. Secondly, the standard particle filter algorithm based on SIR (sequential importance resampling) is combined with the battery model on the MATLAB platform, and the estimating formula in recursive form is deduced. The test data show that the error of the standard particle filter algorithm is less than 4% and RMSE (root mean square error) is 0.0254. Thirdly, in order to improve estimation accuracy, the auxiliary particle filter algorithm is developed by redesigning the importance density function. The comparative experimental results of the same condition show that the maximum error can be reduced to less than 3.5% and RMSE is decreased to 0.0163, which shows that the auxiliary particle filter algorithm has higher estimation accuracy

The effect of the formyl group position upon asymmetric isomeric diarylethenes bearing a naphthalene moiety

Three new isomeric asymmetric diarylethenes with a naphthyl moiety and a formyl group at the para, meta or ortho position of the terminal benzene ring were synthesized. Their photochromism, fluorescent-switch, and electrochemical properties were investigated. Among these diarylethenes, the one with a formyl group at the ortho position of benzene displayed the largest molar absorption coefficients and fluorescence quantum yield. The cyclization quantum yields of these compounds increased in the order of para < ortho < meta, whereas their cycloreversion quantum yields decreased in the order of meta > para > ortho. Additionally, all of these diarylethenes functioned as effective fluorescent switches in both solution and PMMA films. Cyclic voltammograms proved that the formyl group and its position could effectively modulate the electrochemical behaviors of these diarylethene derivatives

Photochromism of Asymmetrical Diarylethenes with a Pyrrole Unit: Effects of Aromatic Stabilization Energies of Aryl Rings

Four novel asymmetrical diarylethenes with a pyrrole and a variable aryl unit have been synthesized. Their crystal structures and photochromic performance were systematically studied to elucidate the effects of the aromatic stabilization energy (ASE) of aryl units. Experimental results showed that their thermal stability as well as cyclization quantum yield, photoconversion ratio, fluorescence modulation efficiency, and fatigue resistance exhibited a strong correlation with ASE

Photochromism of Asymmetrical Diarylethenes with a Pyrrole Unit: Effects of Aromatic Stabilization Energies of Aryl Rings

Four novel asymmetrical diarylethenes with a pyrrole and a variable aryl unit have been synthesized. Their crystal structures and photochromic performance were systematically studied to elucidate the effects of the aromatic stabilization energy (ASE) of aryl units. Experimental results showed that their thermal stability as well as cyclization quantum yield, photoconversion ratio, fluorescence modulation efficiency, and fatigue resistance exhibited a strong correlation with ASE