The mechanisms linking perceived stress to pilots' safety attitudes: a chain mediation effect of job burnout and cognitive flexibility.

Introduction: Pilots' safety attitude is crucial for aviation safety. Current research shows a correlation between perceived stress and safety attitude, yet the mechanism underlying this association remains unclear. Against the backdrop of heightened attention to pilots' stress, this study aims to thoroughly explore the inherent connection between pilot safety attitudes and their perceived stress, offering targeted insights into preventing and addressing safety attitude issues arising from pilot stress. Methods: Through path analysis of questionnaire data from 106 civil aviation pilots in China, this study systematically investigates the roles of job burnout and cognitive flexibility in the relationship between perceived stress and safety attitude. The study reveals the chain-mediated mechanism of these two factors. Results: The results demonstrate a significantly negative correlation between pilots' perceived stress and safety attitude, with cognitive flexibility and job burnout fully mediating this relationship, and cognitive flexibility affecting job burnout. A detailed analysis of the three dimensions of job burnout reveals varying impacts of emotional exhaustion, depersonalization, and reduced personal accomplishment on the aforementioned path. The research model exhibits a good fit (GFI=0.902), providing new theoretical perspectives on the association between pilots' perceived stress and safety attitude. Discussion: The findings offer practical implications for improving pilots' safety attitude by proposing targeted measures to alleviate the adverse impacts of perceived stress on safety attitude, thereby promoting aviation safety.

Changes of the exotropia deviation in children with basic type of intermittent exotropia before and after monocular occlusion test / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the changes of exotropia deviation in children with basic type of intermittent exotropia before and after monocular occlusion test.METHODS: Prospective clinical study. A total of 258 children with basic type of intermittent exotropia who underwent strabismus correction in our hospital from July 2021 to September 2022 were selected, including 122 males and 136 females, aged from 5 to 12 years, with an average age of 8.0±3.1 years. The exotropia deviation was measured at distance(6 m)and near(33 cm)fixation by prism alternating occlusion method, and the exotropia deviation was checked again after covering the non-dominant eyes of children for 40 min.RESULTS: Before and after the monocular occlusion test, the exotropia deviation at distance(6 m)fixation was 28.23△±10.79△ and 29.79△±10.85△, respectively(t=-0.903, P=0.368), while the exotropia deviation at near(33 cm)fixation was 33.14△±8.89△ and 36.90△±10.76△, respectively(t=-2.377, P=0.019).CONCLUSIONS: Monocular occlusion test has a great impact on the exotropia deviation at near(33 cm)fixation in children with basic type of intermittent exotropia before surgery. It can expose the maximum exotropia deviation, reduce the rate of undercorrection after strabismus surgery, and provide a reliable surgical plan.

Cigarette Smoke Extract-TreatedMouse Airway Epithelial Cells-Derived Exosomal LncRNA MEG3 Promotes M1 Macrophage Polarization and Pyroptosis in Chronic Obstructive Pulmonary Disease by Upregulating TREM-1 via m6A Methylation

Cigarette smoke extract (CSE)-treated mouse airway epithelial cells (MAECs)-derived exosomes accelerate the progression of chronic obstructive pulmonary disease (COPD) by upregulating triggering receptor expressed on myeloid cells 1 (TREM-1); however, the specific mechanism remains unclear. We aimed to explore the potential mechanisms of CSE-treated MAECs-derived exosomes on M1 macrophage polarization and pyroptosis in COPD. In vitro, exosomes were extracted from CSE-treated MAECs, followed by co-culture with macrophages.In vivo, mice exposed to cigarette smoke (CS) to induce COPD, followed by injection or/and intranasal instillation with oe-TREM-1 lentivirus. Lung function and pathological changes were evaluated. CD68 + cell number and the levels of iNOS, TNF-α, IL-1β (M1 macrophage marker), and pyroptosis-related proteins (NOD-like receptor family pyrin domain containing 3, apoptosis-associated speck-like protein containing a caspase-1 recruitment domain, caspase-1, cleaved-caspase-1, gasdermin D [GSDMD], and GSDMD-N) were examined. The expression of maternally expressed gene 3 (MEG3), spleen focus forming virus proviral integration oncogene (SPI1), methyltransferase 3 (METTL3), and TREM-1 was detected and the binding relationships among them were verified. MEG3 increased N6-methyladenosine methylation of TREM-1 by recruiting SPI1 to activate METTL3. Overexpression of TREM-1 or METTL3 negated the alleviative effects of MEG3 inhibition on M1 polarization and pyroptosis. In mice exposed to CS, EXO−CSE further aggravated lung injury, M1 polarization, and pyroptosis, which were reversed by MEG3 inhibition. TREM-1 overexpression negated the palliative effects of MEG3 inhibition on COPD mouse lung injury. Collectively, CSE-treated MAECs-derived exosomal long non-coding RNA MEG3 may expedite M1 macrophage polarization and pyroptosis in COPD via the SPI1/METTL3/TREM-1 axis.

Altered Caffeine Metabolism Is Associated With Recurrent Hypoglycemia in Type 2 Diabetes Mellitus: A UPLC-MS-Based Untargeted Metabolomics Study.

Background: Recurrent hypoglycemia (RH) is well known to impair awareness of hypoglycemia and increase the risk of severe hypoglycemia; the underlying mechanism requires further understanding. We aimed to investigate the metabolic characteristic profile for RH in type 2 diabetes mellitus (T2DM) patients and explore the potential metabolic mechanism and prevention strategies. Methods: We screened 553 community-based T2DM patients. T2DM with RH (DH group, n=40) and T2DM without hypoglycemia (DC group, n=40) were assigned in the case-control study, matched by propensity score matching. Non-targeted, global metabolite profiling was conducted using ultra-high performance liquid chromatography-mass spectrometry. Principal component analysis and supervised projections to latent structures-discriminant analysis were constructed to evaluate the potential biomarkers. Metabolites with a fold change of >2.0 or <0.5, a t-test q-value <0.05, and variable importance in projection value of >1 were identified as significantly differential metabolites. MetaboAnalyst was performed to analyze the related metabolic pathways. Results: We identified 12 significantly distinct metabolites as potential biomarkers of RH, which were enriched in five pathways; the caffeine metabolic pathway was the most dominant related one. Caffeine and its main downstream metabolites (theophylline and paraxanthine, all q <0.05) were significantly lower during RH. The combination of these metabolites can serve as a reliable predictor biomarker for RH (area under the curve = 0.88). Regarding lipid metabolism, triglyceride was upregulated (P=0.003) and the O-Acylcarnitine was downregulated (q < 0.001). Besides, RH was accompanied by lower phenylalanine (q=0.003) and higher cortisone (q=0.005) levels. Conclusions: RH in T2DM is accompanied by caffeine, lipolysis, phenylalanine, and cortisone metabolism abnormalities. Caffeine might be a reliable candidate biomarker and potential prevention strategy for RH, but further validation studies are needed. Clinical Trial Registry: Chi CTR 1900026361, 2019-10-3.

Predictive performance of multi-model ensemble forecasts of COVID-19 across European nations

BackgroundShort-term forecasts of infectious disease burden can contribute to situational awareness and aid capacity planning. Based on best practice in other fields and recent insights in infectious disease epidemiology, one can maximise the predictive performance of such forecasts if multiple models are combined into an ensemble. Here we report on the performance of ensembles in predicting COVID-19 cases and deaths across Europe between 08 March 2021 and 07 March 2022. MethodsWe used open-source tools to develop a public European COVID-19 Forecast Hub. We invited groups globally to contribute weekly forecasts for COVID-19 cases and deaths reported from a standardised source over the next one to four weeks. Teams submitted forecasts from March 2021 using standardised quantiles of the predictive distribution. Each week we created an ensemble forecast, where each predictive quantile was calculated as the equally-weighted average (initially the mean and then from 26th July the median) of all individual models predictive quantiles. We measured the performance of each model using the relative Weighted Interval Score (WIS), comparing models forecast accuracy relative to all other models. We retrospectively explored alternative methods for ensemble forecasts, including weighted averages based on models past predictive performance. ResultsOver 52 weeks we collected and combined up to 28 forecast models for 32 countries. We found a weekly ensemble had a consistently strong performance across countries over time. Across all horizons and locations, the ensemble performed better on relative WIS than 84% of participating models forecasts of incident cases (with a total N=862), and 92% of participating models forecasts of deaths (N=746). Across a one to four week time horizon, ensemble performance declined with longer forecast periods when forecasting cases, but remained stable over four weeks for incident death forecasts. In every forecast across 32 countries, the ensemble outperformed most contributing models when forecasting either cases or deaths, frequently outperforming all of its individual component models. Among several choices of ensemble methods we found that the most influential and best choice was to use a median average of models instead of using the mean, regardless of methods of weighting component forecast models. ConclusionsOur results support the use of combining forecasts from individual models into an ensemble in order to improve predictive performance across epidemiological targets and populations during infectious disease epidemics. Our findings further suggest that median ensemble methods yield better predictive performance more than ones based on means. Our findings also highlight that forecast consumers should place more weight on incident death forecasts than incident case forecasts at forecast horizons greater than two weeks. Code and data availabilityAll data and code are publicly available on Github: covid19-forecast-hub-europe/euro-hub-ensemble.

Diagnostic value of double contrast-enhanced ultrasound in renal cystic lesions: a comparative study with enhanced magnetic resonance and intravenous pyelogram / 中华超声影像学杂志

Objective:To explore the application value of dual contrast-enhanced ultrasound in the differential diagnosis of renal cystic lesions.Methods:Eighty-four cases with renal cysts who were diagnosed by routine ultrasound in Zhejiang Cancer Hospital and Zhejiang Xiaoshan Hospital from January 2019 to October 2020 were included in the study. Intravenous contrast-enhanced ultrasound and enhanced MRI were performed to differentiate benign and malignant cysts. Patients with benign cysts underuent intravenous pyelography and intracapsular contrast-enhanced ultrasound. Before sclerotheraphy to exclude renal pelvic cysts. The diagnostic results of dual radiography were compared with MRI and intravenous pyelography.Results:Among 84 patients with suspected renal cysts, the diagnostic accuracy of enhanced MRI for cystic renal cancer was 97.62%, and the sensitivity was 97.62%. The diagnostic accuracy of intravenous contrast-enhanced ultrasound was 98.81, the sensitivity was 100%, and the specificity was 98.73%. There was no statistically significant difference between the two groups (all P>0.05). 77 cases were diagnosed as benign renal cysts, the detection rate of intravenous pyelography was 9.1% (7/77), the detection rate of renal pelvic cysts by intracystic ultrasonography was 6.5% (5/77). With intravenous pyelography as the gold standard, the diagnostic accuracy of intracapsular contrast-enhanced ultrasound was 97.4% (75/77), the sensitivity was 71.4% (5/7), and the specificity was 100% (70/70). Conclusions:Compared with enhanced magnetic resonance and intravenous pyelography before renal cyst sclerosing therapy, there is no difference in diagnostic efficiency of double contrast ultrasound for benign and malignant cysts. The diagnostic efficiency of renal pelvic cysts is high, and the operation is convenient. It can identify cystic renal cancer and cysts from the renal pelvis and improve the safety of sclerotherapy.

Projected resurgence of COVID-19 in the United States in July-December 2021 resulting from the increased transmissibility of the Delta variant and faltering vaccination

What is already known about this topic?The highly transmissible SARS-CoV-2 Delta variant has begun to cause increases in cases, hospitalizations, and deaths in parts of the United States. With slowed vaccination uptake, this novel variant is expected to increase the risk of pandemic resurgence in the US in July--December 2021. What is added by this report?Data from nine mechanistic models project substantial resurgences of COVID-19 across the US resulting from the more transmissible Delta variant. These resurgences, which have now been observed in most states, were projected to occur across most of the US, coinciding with school and business reopening. Reaching higher vaccine coverage in July--December 2021 reduces the size and duration of the projected resurgence substantially. The expected impact of the outbreak is largely concentrated in a subset of states with lower vaccination coverage. What are the implications for public health practice?Renewed efforts to increase vaccination uptake are critical to limiting transmission and disease, particularly in states with lower current vaccination coverage. Reaching higher vaccination goals in the coming months can potentially avert 1.5 million cases and 21,000 deaths and improve the ability to safely resume social contacts, and educational and business activities. Continued or renewed non-pharmaceutical interventions, including masking, can also help limit transmission, particularly as schools and businesses reopen.

All Models Are Useful: Bayesian Ensembling for Robust High Resolution COVID-19 Forecasting

Timely, high-resolution forecasts of infectious disease incidence are useful for policy makers in deciding intervention measures and estimating healthcare resource burden. In this paper, we consider the task of forecasting COVID-19 confirmed cases at the county level for the United States. Although multiple methods have been explored for this task, their performance has varied across space and time due to noisy data and the inherent dynamic nature of the pandemic. We present a forecasting pipeline which incorporates probabilistic forecasts from multiple statistical, machine learning and mechanistic methods through a Bayesian ensembling scheme, and has been operational for nearly 6 months serving local, state and federal policymakers in the United States. While showing that the Bayesian ensemble is at least as good as the individual methods, we also show that each individual method contributes significantly for different spatial regions and time points. We compare our models performance with other similar models being integrated into CDC-initiated COVID-19 Forecast Hub, and show better performance at longer forecast horizons. Finally, we also describe how such forecasts are used to increase lead time for training mechanistic scenario projections. Our work demonstrates that such a real-time high resolution forecasting pipeline can be developed by integrating multiple methods within a performance-based ensemble to support pandemic response. ACM Reference FormatAniruddha Adiga, Lijing Wang, Benjamin Hurt, Akhil Peddireddy, Przemys-law Porebski,, Srinivasan Venkatramanan, Bryan Lewis, Madhav Marathe. 2021. All Models Are Useful: Bayesian Ensembling for Robust High Resolution COVID-19 Forecasting. In Proceedings of ACM Conference (Conference17). ACM, New York, NY, USA, 9 pages. https://doi.org/10.1145/nnnnnnn.nnnnnnn

Using Mobility Data to Understand and Forecast COVID19 Dynamics

Disease dynamics, human mobility, and public policies co-evolve during a pandemic such as COVID-19. Understanding dynamic human mobility changes and spatial interaction patterns are crucial for understanding and forecasting COVID-19 dynamics. We introduce a novel graph-based neural network(GNN) to incorporate global aggregated mobility flows for a better understanding of the impact of human mobility on COVID-19 dynamics as well as better forecasting of disease dynamics. We propose a recurrent message passing graph neural network that embeds spatio-temporal disease dynamics and human mobility dynamics for daily state-level new confirmed cases forecasting. This work represents one of the early papers on the use of GNNs to forecast COVID-19 incidence dynamics and our methods are competitive to existing methods. We show that the spatial and temporal dynamic mobility graph leveraged by the graph neural network enables better long-term forecasting performance compared to baselines.

Interplay of global multi-scale human mobility, social distancing, government interventions, and COVID-19 dynamics

This work quantifies mobility changes observed during the different phases of the pandemic world-wide at multiple resolutions - county, state, country - using an anonymized aggregate mobility map that captures population flows between geographic cells of size 5 km2. As we overlay the global mobility map with epidemic incidence curves and dates of government interventions, we observe that as case counts rose, mobility fell and has since then seen a slow but steady increase in flows. Further, in order to understand mixing within a region, we propose a new metric to quantify the effect of social distancing on the basis of mobility.Taking two very different countries sampled from the global spectrum, We analyze in detail the mobility patterns of the United States (US) and India. We then carry out a counterfactual analysis of delaying the lockdown and show that a one week delay would have doubled the reported number of cases in the US and India. Finally, we quantify the effect of college students returning back to school for the fall semester on COVID-19 dynamics in the surrounding community. We employ the data from a recent university outbreak (reported on August 16, 2020) to infer possible Reff values and mobility flows combined with daily prevalence data and census data to obtain an estimate of new cases that might arrive on a college campus. We find that maintaining social distancing at existing levels would be effective in mitigating the extra seeding of cases. However, potential behavioral change and increased social interaction amongst students (30% increase in Reff) along with extra seeding can increase the number of cases by 20% over a period of one month in the encompassing county. To our knowledge, this work is the first to model in near real-time, the interplay of human mobility, epidemic dynamics and public policies across multiple spatial resolutions and at a global scale.

Key points for the prevention and treatment of the novel coronavirus pneumonia in the elderly / 中华老年医学杂志

The population is commonly susceptible to the 2019 novel coronavirus(2019-nCoV), especially the elderly with comorbidities.Elderly patients infected with 2019-nCoV tend to have higher rates of severe illnesses and mortality.Immunoaging is an important cause of severe novel coronavirus pneumonia(NCP)in the elderly.Due to the combination of underlying diseases, elderly patients may exhibit a typical manifestations in clinical symptoms, supplementary examinations and pulmonary imaging, deserving particular attention.The general condition of the elderly should be considered during diagnosis and treatment.In addition to routine care and measures such as oxygen therapy, antiviral therapy and respiratory support, treatment of underlying disease, nutritional support, sputum expectoration, complication prevention and psychological support should also be considered for elderly patients.Based on literature review and expert panel discussion, we drafted the Key Points for the Prevention and Treatment of the Novel Coronavirus Pneumonia in the elderly, aiming to provide help with the prevention and treatment of NCP and the reduction of harm to the elderly population.

Key points for the prevention and treatment of the novel coronavirus pneumonia in the elderly / 中华老年医学杂志

The population is commonly susceptible to the 2019 novel coronavirus(2019-nCoV), especially the elderly with comorbidities.Elderly patients infected with 2019-nCoV tend to have higher rates of severe illnesses and mortality.Immunoaging is an important cause of severe novel coronavirus pneumonia(NCP)in the elderly.Due to the combination of underlying diseases, elderly patients may exhibit atypical manifestations in clinical symptoms, supplementary examinations and pulmonary imaging, deserving particular attention.The general condition of the elderly should be considered during diagnosis and treatment.In addition to routine care and measures such as oxygen therapy, antiviral therapy and respiratory support, treatment of underlying disease, nutritional support, sputum expectoration, complication prevention and psychological support should also be considered for elderly patients.Based on literature review and expert panel discussion, we drafted the Key Points for the Prevention and Treatment of the Novel Coronavirus Pneumonia in the elderly, aiming to provide help with the prevention and treatment of NCP and the reduction of harm to the elderly population.

Biological parameters and cardiac physiological function of the mice overexpressing human Slit2 gene / 中国实验动物学报

Objective The basic biological, echocardiography and gene sequencing parameters of mice overexpressing Slit2 gene (Slit2-Tg mice) were collected and evaluated, and to provide a reference for the application of Slit2-Tg mice in biomedical research. Methods Slit2-Tg and C57BL/6 J mice were inbred. The genotypes of the mice were determined by a PCR assay. The blood samples were collected for blood routine and biochemical tests. The tissues of main organs were collected for protein expression and pathological analysis. Echocardiography and transcriptome sequencing was carried out for analyzing the heart function and gene expression, respectively. Results The litter size was significantly higher in the Slit2-Tg mice than in C57BL/6 J mice. Human Slit2 gene and protein expressions were detected in the main organs of Slit2-Tg mice. Organ coefficient of spleen was significantly increased in Slit2-Tg mice, but the tissue structure appeared normal. There were significant changes in the counts of erythrocytes, platelets, eosinophils, and biochemistry of glucose, globulin, urea nitrogen, triglycerides, HDL, and atherosclerosis index. Echocardiography showed no significant differences in the morphology and function of the Slit2-Tg hearts except in the left ventricular anterior wall thickness at the end-diastolic state. Compared with the C57BL/6 J mice, 535 genes out of 17513 genes in the Slit2-Tg hearts were increased or decreased, mainly involving 15 biological process or signal transduction pathways. Conclusions This study has collected the biological parameters of Slit2-Tg mice and suggests that this model animal is suitable for the studies of cardiovascular diseases.

Inhibitory effect of atrial natriuretic peptide(ANP)on the tumor growth of ANP knockout mouse and C57BL/6J mouse models of subcutaneous xenotransplanted melanoma / 中国比较医学杂志

Objective To study the effect of atrial natriuretic peptide(ANP)deletion on melanoma growth. Methods A subcutaneous xenotransplanted melanoma model was established in ANP knockout mice and C57BL/6J mice. The tumor volume was measured at the sixth day after establishment of the subcutaneous transplantation. Tumor cell proliferation and tumor-induced angiogenesis were detected by immunohistochemical staining. Results The volume and weight of xenotransplanted melanoma were significantly decreased in the ANP knockout mice compared with those in the C57BL/6J mice. The proliferative tumor cells and microvessel density were significantly decreased in the tumor tissues of ANP knockout mice compared with those in the C57BL/6J mice. Conclusions ANP deletion significantly suppresses xenotransplanted melanoma growth through inhibiting the tumor cell proliferation and angiogenesis.

Effect of atrial natriuretic peptide ( ANP) on pulmonary melanoma metastasis in ANP knockout mice and C57BL／6J mice / 中国比较医学杂志

Objective To investigate the role of atrial natriuretic peptide (ANP) in lung metastasis of melanoma. Methods Melanoma B16F10 cells were intravenously injected into ANP knockout mice and C57BL／6J mice. After three weeks, the mice were sacrificed, and the lungs were removed, embedded, and examined by pathology using HE staining. The numbers of metastatic foci on the lung surface and micrometastatic foci in the lung tissues were counted. Results The ANP knockout mice displayed fewer metastatic foci on the lung surface and less micrometastatic foci in the lung tissues of ANP knockout mice than in the C57BL／6J mice. Conclusions ANP deletion significantly suppresses the metastasis of melanoma in the lung of mice.

Effects and mechanism ofandrographolide on diabetic nephropathy mice / 中国药科大学学报

To investigate the effects and mechanism of andrographolide(Andro)on type II diabetic nephropathy in Leprdb/dbmice,levels of urinary protein,serum creatinine and blood urea nitrogen after 24 h of Andro(1 mg/kg,ip)treatment on Leprdb/dbmice were measured by kit.The changes on renal pathology and sugar levels in diabetic mice treated by Andro were observed by HE staining and PAS staining.The expression of fibronectin (FN)and NOX-4 protein were analyzed by immunofluorescence.Results showed that levels of urinary protein, serum creatinine and blood urea nitrogen in Leprdb / dbmice after Andro treatment for 24 h were significantly lower than those of the control group. Kidney pathologic change was inhibited, and FN and NOX-4 expression were markedly decrease in the Andro group.In conclusion,Andro can significantly reduce the diabetic nephropathy in Leprdb/dbmice with spontaneous type II diabetes mellitus.

Effects of oridonin on endoplasmic reticulum stress in ulcerative colitis mouse model / 重庆医学

Objective To explore the effect of oridonin on the endoplasmic reticulum stress (ERS) in colonic epithelium of ulcerative colitis (UC) mice.Methods The UC mice model was established by sodium dextran sulfate (DSS),and the intervention group of oridonin and sulfasalazine was set up,the disease activity index (DAD was measured,the colonic tissue was evaluated by histopathologidscore (HPS),and RT-qPCR was used to detect the expression of inflammatory cytokines tumor factor-α (TNF-α),interleukin 6 (IL-6),cyclooxygenase 2 (COX-2),glucose-regulated protein 78 (GRP78),transcription factor EBP homologous protein (CHOP),activator transcription factor 6 (ATF6),protein kinase R like endoplasmic reticulum kinase (PERK) and inositol requiring enzyme 1α (IRE1α).Results The expression of TNF-α,IL-6,COX-2,GRP78,ATF6,CHOP,PERK and IRE1α mRNA in the colonic epithelium of the model group were all up-regulated obviously as compared with the healthy control group(P＜0.05,P＜0.01).When compared with the model group,DAI and HPS in oridonin-treated group were significantly decreased (P＜0.05,P＜0.01),which the curative effect was similar to that of the sulfasalazine group(P＞0.05,P＜0.01).The expression of TNF-α,IL-6,COX-2,GRP78,CHOP,ATF6 and PERK mRNA levels were significantly reduced in oridonin-treated group(P＜ 0.05,P＜0.01).Conclusion Oridonin can alleviate colonic inflammation induced by DSS and its mechanism may be related to ERS of colonic epithelial tissue.

Triptolide reverses apatinib resistance in gastric cancer cell line MKN45 via inhibition of heat shock protein 70 / 中华肿瘤杂志

Objective@#To investigate the effect of triptolide, a specific inhibitor of heat shock protein 70 (HSP70), on apatinib resistance in gastric cancer cells line MKN45.@*Methods@#The apatinib-resistant cells (MKN45/AR) and MKN45 parental cells were treated with apatinib, triptolide and apatinib combined with triptolide, respectively. CCK-8 assay was performed to determine the half maximal inhibitory concentration (IC50) of MKN45/AR and MKN45 cells in the presence of different treatment. The mRNA expression of heat shock protein gene (HSPA1A and HSPA1B) was detected by RT-PCR, while the protein expression of heat shock protein 70 was analyzed using Western blot in MKN45/AR and MKN45 cells.@*Results@#The IC50 values of apatinib-sensitive and apatinib-resistant MKN45 cells were 10.411 μmol/L and 70.527 μmol/L, respectively, showing a significant difference (P<0.05). The mRNA expression of HSPA1A and HSPA1B in MKN45/AR cells was significantly higher than that in MKN45 cells (P<0.001). The protein expression of heat shock protein 70 was significantly decreased after 0.25 μmol/L triptolide treatment in MKN45/AR cells (P<0.01). When heat shock protein 70 was inhibited by triptolide, the IC50 value of apatinib in MKN45/AR cells was reduced to 11.679 μmol/L, which was significantly lower than cells treated with apatinib alone (P<0.05).@*Conclusions@#The apatinib-resistant MKN45 cells have high levels of heat shock protein 70. Low doses of triptolide can significantly inhibit heat shock protein 70, leading to reverse the resistance phenotype of MKN45/AR cells. Therefore, inhibition of heat shock protein 70 provides a new therapy strategy for patients with apatinib resistance.

Effects of P-selectin gene knockout on the biological characteristics of mice / 中国实验动物学报

Objective To investigate the effects of P-selectin gene knockout on the biological characteristics of mice. Methods P?selectin knockout (PKO) mice and C57BL/6 mice were housed in SPF environment. To make sure that the mice were pure PKO mice by gene identification. To determine the general condition, the activity status, reproduction of P?selectin knockout mice were observed and tested. HE staining was used to observed the histological morphology and struc?tures of 6?week?old and 18?week?old P?selectin knockoutout mice. Results PKO mice and C57 mice have similar multiplica?tion, there was no significant difference in reproduction and blood routine test. The stuctures of liver, spleen, lung and kid?ney were normal. Conclusions P?selectin knockout has no significant effects on reproduction, blood routine test and major organs. This research provides animal model theoretical basis for further study on the effects of P?selection in diseases.

Effects of Shkbp1 deletion on mouse T lymphocyte subsets / 中国比较医学杂志

Objective Shkbp is also called Shkbp1,can competitively inhibit binding CIN85 and c-Cbl,thereby blocking the epidermal growth factor receptor (EGFR) endocytosis and degradation,to play a role in tumor promotion.This study aims to explore the changes in blood cell classification and T cell subsets in blood,bone marrow,and spleen in Shkbp1-deletion (Shkbp-1-/-) mice.Methods Shkbp-1-/-transgenic mice were identified by PCR genotyping.Blood cell classification was performed using an automatic classification system.Flow cytometry was used to detect the T lymphocyte subsets in the blood,bone marrow,and spleen of Shkbp-1-/-and control mice.Results Routine blood examination showed that neutrophils and eosinophils tended to increase and showing significant differences,and there was no significant difference in lymphocytes.The flow cytometry results showed that there was a decrease of CD4+CD8+ double positive cells and increase of bone marrow CD3+ and CD4+ cells in the control group.However,there was a decreasing trend of CD3+,CD4+,CD8+,and CD4+CD8+ cells in the spleen tissues.Conclusions Shkbp1 is involved in the maturation and differentiation of blood cells,and affects the number of immune cells.This study lays a foundation for the study of how Shkbp1 is involved in the differentiation of blood cells.