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@#In recent years, the chimeric antigen receptor T-cell (CAR-T) therapy has achieved breakthrough progress in the treatment of hematologic malignancies. However, when it comes to solid tumors, numerous challenges persist.These include limited CAR-T cell infiltration, susceptibility to T cell exhaustion, off-target effects, and more.Thus, novel therapeutic strategies are imperative to enhance the efficacy of CAR-T therapy for solid tumors. In comparison to standalone CAR-T approaches, the combination of CAR-T with other tumor treatment modalities has demonstrated remarkable effectiveness in both preclinical and clinical research.This review article summarizes the advancements in combining CAR-T with various solid tumor treatments: antibody drugs, oncolytic viruses, tumor vaccines, and nanomedicines.The objective is to furnish a theoretical foundation and novel perspectives for the development of innovative CAR-T combination strategies tailored for solid tumor therapy.
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Objective:To analyze the relevant factors affecting the frequency and behavior of health check-up among the population of medical examinees.Methods:From January to June 2022, 491 health examinees who had health check-ups at the Second Affiliated Hospital of Shandong First Medical University were included.Basic information of the check-up population and their needs for check-up services (form of check-up, content of check-up, cost of check-up, form of feedback on check-up results, and needs for check-up providers) were obtained based on a questionnaire survey.According to the frequency of previous medical check-up, the examinees were divided into never-check-up group (frequency of check-up was 0, n=45), the irregular check-up group (the interval between two physical examinations >1 year, n=49) and the regular check-up group (frequency of check-up=1 year, n=347). The frequency of previous medical check-up was used as the dependent variable, and the age, gender, education level, income, form of medical check-up and cost of medical check-up were used as independent variables to analyse the relevant factors affecting the frequency of their medical check-ups.The above count data were analyzed by one-way analysis using chi-square test, and the count data with statistically significant differences in one-way analysis were analyzed by binary logistic regression.The statistical software was SPSS 21.0. Results:The study included 491 medical examinees, of which 9.16%(45/491) were in the never-check-up group, 20.16%(99/491) in the irregular check-up group and 70.68%(347/491) in the regular check-up group. The impact of demography characteristics of physical examinees on the frequency of health check-up, and there were statistically significant differences in the frequency of health check-up in terms of gender, job, education, and income ( χ2=21.826, 157.113, 104.764, 45.486, all P<0.05). The understanding of health check-up and the attention paid to one's own health were influencing factors that affected the frequency of health check-up. There were statistically significant differences in the frequency of health check-up in necessity of health check-up, attention to one's own health, health check-up forms, health check-up institutions, health check-up price and health check-up contents ( χ2=9.277, 25.863188.239, 59.115, 39.250, 28.314, all P<0.05). Logistic regression analysis showed gender, job type, monthly income, necessity of health check-up, concerns for items of check-up, forms and institutions of check-up were influencing factor of health check-up frequency(all P<0.05). Conclusion:The health check-up behavior of the population and the frequency of regular medical check-ups are influenced by the factors such as gender, education, occupation, income, form of medical check-up, price of medical check-up, choice of medical check-up institution and the degree of concern for one’s own health. The popularisation of health check-ups for special groups such as men, low-income people, low literacy and insufficient awareness of the importance of one’s own health will help improve the overall health awareness of the population.
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Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).
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Objective Construct a scientific and reasonable evaluation index system for clinical specialties of tradi-tional Chinese medicine in Shandong Province to provide a scientific basis for improving the service capacity of clini-cal specia lties of traditional Chinese medicine.Methods Based on relevant policies and literature research,the analytic hierarchy process and Delphi expert consultation method were used to determine the index system and its weight,and 509 clinical specialties of traditional Chinese medicine capacity levels of 178 medical institutions in Shandong Province were evaluated.Results A scientific and effective evaluation index system for clinical specialty capacity of traditional Chinese medicine in Shandong Province was constructed,with 23 secondary indicators in 5 dimen-sions.It comprehensively evaluats the service capacity and management level of orthopedics and traumatology de-partments of traditional Chinese medicine class hospitals in Shandong Province,uses orthopedics and traumatology as an example.Conclusion Driven by the dynamic monitoring of the evaluation index system,improve the service ca-pacity for clinical specialties of traditional Chinese medicine,guide it to strengthen the internal construction of tradi-tional Chinese medicine,and give full play to the advantages of traditional Chinese medicine characteristics.Increase the support for clinical specialties of traditional Chinese medicine in Shandong Province,and then promote the high-quality development of traditional Chinese medicine.
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Objective To investigate the expression of lncRNA HOTAIR, HOTAIR, CRNDE and AFAP1-AS1 in lung cancer patients with bone metastasis (LCWBM), and to elucidate the diagnostic value of lncRNAs for LCWBM. Methods Serum was collected from 38 LCWBM patients and 38 lung cancer without bone metastasis (LCWOBM) patients. Questionnaires were used to collect basic information of patients. Fasting peripheral venous blood of patients was collected to separate serum. qRT-PCR was used to measure the expression levels of four serum lncRNAs, and their diagnostic value for LCWBM was analyzed. Results The expression of serum HOTAIR was decreased in LCWBM patients, compared with LCWOBM patients (P < 0.05); the AUC of serum HOTAIR diagnosing LCWBM was 0.722 (sensitivity was 70.0%, specificity was 81.3%). And the level of serum HOTTIP was significantly increased in LCWBM patients, compared with LCWOBM patients (P < 0.05); AUC of serum HOTTIP diagnosing LCWBM was 0.784 (sensitivity was 100.0%, specificity was 45.5%). The AUC of serum HOTAIR combined with HOTTIP diagnosing LCWBM was 0.818 (sensitivity, specificity, positive predictive value and negative predictive value were 87.5%, 72.7%, 70.0% and 88.9%, respectively). Conclusion Serum lncRNA HOTAIR and HOTTIP might be potential diagnostic biomarkers for bone metastases in lung cancer patients.
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Eucommiae Folium(EF),a traditional Chinese medicine,has been used to treat secondary hypertension,including renal hypertension and salt-sensitive hypertension,as well as hypertension caused by thoracic aortic endothelial dysfunction,a high-fat diet,and oxidized low-density lipoprotein.The antihyperten-sive components of EF are divided into four categories:flavonoids,iridoids,lignans,and phenyl-propanoids,such as chlorogenic acid,geniposide acid and pinoresinol diglucoside.EF regulates the occurrence and development of hypertension by regulating biological processes,such as inhibiting inflammation,regulating the nitric oxide synthase pathway,reducing oxidative stress levels,regulating endothelial vasoactive factors,and lowering blood pressure.However,its molecular antihypertensive mechanisms are still unclear and require further investigation.In this review,by consulting the relevant literature on the antihypertensive effects of EF and using network pharmacology,we summarized the active ingredients and pharmacological mechanisms of EF in the treatment of hypertension to clarify how EF is associated with secondary hypertension,the related components,and underlying mechanisms.The results of the network pharmacology analysis indicated that EF treats hypertension through a multi-component,multi-target and multi-pathway mechanism.In particular,we discussed the role of EF tar-gets in the treatment of hypertension,including epithelial sodium channel,heat shock protein70,rho-associated protein kinase 1,catalase,and superoxide dismutase.The relevant signal transduction path-ways,the ras homolog family member A(RhoA)/Rho-associated protein kinase(ROCK)and nicotinamide adenine dinucleotide phosphate(NADPH)oxidase/eNOS/NO/Ca2+pathways,are also discussed.
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Periprosthetic osteolysis is one of the major long-term complications following total joint replacement. Its cause is widely accepted to be wear particle-induced activation of inflammatory macrophages. No effective strategy for the prevention and treatment of periprosthetic osteolysis is yet available. Recently, considerable evidence has shown that icariin effectively protects against estrogen deficiency-related bone loss and bone deterioration. However, the molecular mechanism underlying the inhibitory effect of icariin on wear particle-induced periprosthetic osteolysis is not yet clear. In this study, nanoscale CoCrMo wear particles were obtained by high-vacuum three-electrode direct current from the femoral head implant of a patient diagnosed with aseptic loosening. The effects of icariin on wear particle-induced expression of proinflammatory factors, NF-κB signaling modulation, osteolysis, and estrogen receptor α (ERα) activation were evaluated in vitro and in vivo using bone marrow-derived macrophages and C57/BL6J mice, respectively. A possible link between ERα and the protective effect of icariin was further studied using an ERα antagonist and the ERα-siRNA interference. Chemical composition analysis showed that Cr and Co were the major metallic elements of the nanoscale particles, with a mean size of 150.2 ± 37.4 nm for the CoCrMo particles. Following icariin treatment, significant decreases were observed in CoCrMo wear particle-induced TNF-α and IL-6 mRNA expression in BMDMs, and osteolysis in mice calvaria. Marked decreases in the protein expression level of p-IKKß, p-p65 and p-IκBα were also observed, together with significant decreases in the nuclear import of P65 and macrophage M1 polarization. RNA sequencing revealed that ERα was closely associated with TNF-α and IL-6 in wear particle-stimulated macrophages. Furthermore, marked increases in phospho-ERα Ser118 and phospho-ERα Ser167 protein expression and the nuclear import of ERα were also found in the icariin group. The protective effects of icariin on CoCrMo particle-induced mouse calvarial osteolysis and on the inflammation response in BMDMs were reversed by ERα antagonist and by ERα-siRNA interference. In conclusion, icariin attenuates wear particle-induced inflammation and osteolysis via down-regulation of the ERα-mediated NF-κB signaling pathway in macrophages. The potential application of icariin as a non-hormonal therapy for wear particle-induced periprosthetic osteolysis is worthy of further investigation.
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SARS-CoV-2 inactivated vaccines have shown remarkable efficacy in clinical trials, especially in reducing severe illness and casualty. However, the waning of humoral immunity over time has raised concern over the durability of immune memory following vaccination. Thus, we conducted a non-randomized trial among the healthcare professionals (HCWs) to investigate the long-term sustainability of SARS-CoV-2-specific B cells and T cells stimulated by inactivated vaccines and the potential need for a third booster dose. Although neutralizing antibodies elicited by the standard two-dose vaccination schedule dropped from a peak of 29.3 AU/ml to 8.8 AU/ml 5 months after the second vaccination, spike-specific memory B and T cells were still detectable, forming the basis for a quick recall response. As expected, the faded humoral immune response was vigorously elevated to 63.6 AU/ml by 7.2 folds 1 week after the third dose along with abundant spike-specific circulating follicular helper T cells in parallel. Meanwhile, spike-specific CD4+ and CD8+ T cells were also robustly elevated by 5.9 and 2.7 folds respectively. Robust expansion of memory pools by the third dose potentiated greater durability of protective immune responses. Another key finding in this trial was that HCWs with low serological response to 2 doses were not truly "non-responders" but fully equipped with immune memory that could be quickly recalled by a third dose even 5 months after the second vaccination. Collectively, these data provide insights into the generation of long-term immunological memory by the inactivated vaccine, which could be rapidly recalled and further boosted by a third dose.
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Objective:To investigate the relationship between monocyte to high-density lipoprotein cholesterol ratio(MHR)and the thrombolysis in myocardial infarction(TIMI)risk score in elderly patients with ST elevation myocardial infarction(STEMI).Methods:This was a prospective clinical trial.A total of 152 patients admitted to Tangshan Workers' Hospital were enrolled between January 2015 to February 2018.Of these, 102 STEMI patients undergone primary percutaneous coronary intervention(PCI)were selected as the STEMI group and 50 patients with angiographically normal coronary arteries were selected as the control group.The STEMI patients were divided into two subgroups based on TIMI risk scores.The relationship between MHR and TIMI risk scores in patients with STEMI was analyzed.Logistic regression was used to analyze whether MHR could be used as an independent predictor of acute STEMI and high TIMI scores.Results:The MHR level was significantly higher in the STEMI group than in the control group( P<0.05)and was significantly higher in the high TIMI score subgroup than in the low TIMI score subgroup( P<0.05). In multivariate Logistic regression analysis, MHR was an independent predictor of high TIMI scores in acute STEMI(P<0.05). In correlation analysis, there was a significant positive correlation between MHR and TIMI score in STEMI patients( r=0.396, P<0.01). The ROC curve showed that the area under the curve of MHR was 0.815(95% CI: 0.734-0.896, Z=7.613, P<0.01). When the MHR optimal cut-off value was 2.380, the sensitivity was 55.22% and the specificity was 97.14%. Conclusions:MHR is significantly associated with the TIMI score in patients with STEMI.MHR may be used as a supplementary parameter for assessing the prognosis of STEMI patients.
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Background and rationaleLimited data on the efficacy and safety of currently applied COVID-19 therapeutics and their impact on COVID-19 outcomes have raised additional concern. Aim and MethodsWe estimated the impact of the current treatments on the efficacy and safety of COVID-19 by a meta-analysis. The comprehensive search included studies reporting clinical features and treatment strategies published from January 21, 2020, to May 15, 2020. ResultsWe included 52 studies that involved 13,966 COVID-19 patients. We found that the most prevalent treatments were antivirals (proportion: 0.74, 95% CI1: [0.65, 0.83]) and antibiotics (proportion: 0.73, 95% CI: [0.62, 0.83]). The COVID-19 severity increased among patients taking glucocorticoids (risk ratio (RR)2 = 1.71, 95% CI: [1.06, 2.76]) or immunoglobulins (RR = 3.83, 95% CI: [1.27, 11.53]), and renal replacement therapy (RRT) and glucocorticoids increased the length of ICU stay (RRT3: RR = 11.89, 95% CI: [3.26, 43.39]; glucocorticoids: RR = 3.10, 95% CI: [1.52, 6.29]). The COVID-19 severity and mortality increased among patients taking tocilizumab (severity: F = 25.53, P = 0.02; mortality: F4 = 19.37, P = 0.02). The most effective treatment was the combination of arbidol with lopinavir/ritonavir compared with placebo (mean difference = 0.5, 95% CI [-0.60, 1.66]), and the safest combination was remdesivir and lopinavir/ritonavir (RR = 0.78, 95% CI [0.32, 1.91]). Conclusionglucocorticoids, immunoglobulins, RRT, and tocilizumab might worsen COVID-19 outcomes, and themost effective and safest treatment strategy for COVID-19 is the combination of different antivirals.
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The COVID-19 virus has infected millions of people and resulted in hundreds of thousands of deaths worldwide. By using the logistic regression model, we identified novel critical factors associated with COVID19 cases, death, and case fatality rates in 154 countries and in the 50 U.S. states. Among numerous factors associated with COVID-19 risk, we found that the unitary state system was counter-intuitively positively associated with increased COVID-19 cases and deaths. Blood type B was a protective factor for COVID-19 risk, while blood type A was a risk factor. The prevalence of HIV, influenza and pneumonia, and chronic lower respiratory diseases was associated with reduced COVID-19 risk. Obesity and the condition of unimproved water sources were associated with increased COVID-19 risk. Other factors included temperature, humidity, social distancing, smoking, and vitamin D intake. Our comprehensive identification of the factors affecting COVID-19 transmission and fatality may provide new insights into the COVID-19 pandemic and advise effective strategies for preventing and migrating COVID-19 spread.
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BackgroundAlthough COVID-19 has been well controlled in China, it is rapidly spreading outside the country and may have catastrophic results globally without implementation of necessary mitigation measures. Because the COVID-19 outbreak has made comprehensive and profound impacts on the world, an accurate prediction of its epidemic trend is significant. Although many studies have predicted the COVID-19 epidemic trend, most have used early-stage data and focused on Chinese cases. MethodsWe first built models to predict daily numbers of cumulative confirmed cases (CCCs), new cases (NCs), and death cases (DCs) of COVID-19 in China based on data from January 20, 2020, to March 1, 2020. Based on these models, we built models to predict the epidemic trend across the world (outside China). We also built models to predict the epidemic trend in Italy, Spain, Germany, France, UK, and USA where COVID-19 is rapidly spreading. ResultsThe COVID-19 outbreak will have peaked on February 22, 2020, in China and will peak on May 22, 2020, across the world. It will be basically under control in early April 2020 in China and late August 2020 across the world. The total number of COVID-19 cases will reach around 89,000 in China and 6,126,000 across the world during the epidemic. Around 4,000 and 290,000 people will die of COVID-19 in China and across the world, respectively. The COVID-19 outbreak will have peaked recently in Italy and will peak in Spain, Germany, France, UK, and USA within two weeks. ConclusionThe COVID-19 outbreak is controllable in the foreseeable future if comprehensive and stringent control measures are taken.
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Objective:To investigate the possible mechanism of learning and memory damage induced by arsenic exposure through studying the effects of arsenic exposure on levels of brain-derived neurotrophic factor (BDNF) and tyrosine kinases B (TrkB) in hippocampus of offspring mice at different developmental stages.Methods:Twenty-four pregnant Kunming mice were divided into control (distilled water) group and 15, 30 and 60 mg/L sodium arsenite (NaAsO 2) groups according to random number table method, six mice in each group. The pregnant mice were exposed to NaAsO 2 until weaning. After weaning, the offspring mice were still exposed to NaAsO 2 through drinking water till postnatal day (PND) 40. Morris water maze was used to determine the effects of arsenic exposure on learning and memory ability in PND 40 mice. The body weight of the mice was measured at PND 10, 20 or 40, and brain tissues were taken after the mice were sacrificed and the hippocampus was isolated. The levels of BDNF and TrkB mRNA in the hippocampus of offspring mice were measured by Real-time PCR. Results:There was significant difference in body weight of PND 20 offspring mice among the control, 15, 30 and 60 mg/L NaAsO 2 groups [(14.42 ± 1.88), (13.50 ± 1.38), (13.00 ± 1.14), (11.75 ± 0.82) g, F = 4.000, P < 0.05], the body weight of offspring mice in 60 mg/L NaAsO 2 group decreased significantly than that in control group( P < 0.05); there was significant difference in body weight of PND 40 offspring mice among groups [(38.58 ± 2.35), (37.17 ± 1.78), (35.67 ± 1.69), (33.83 ± 1.47) g, F = 7.248, P < 0.05], the body weights of offspring mice in 30 and 60 mg/L NaAsO 2 groups were significantly lower than that in control group, and the body weight of PND 40 offspring mice in 60 mg/L NaAsO 2 group was significantly lower than that in 15 mg/L NaAsO 2 group ( P < 0.05); the results of Morris water maze showed that there were significant differences in the escape latency of offspring mice among groups since 3 - 5 days of training ( F = 3.380, 6.788, 7.240, P < 0.05), the escape latency of offspring mice in NaAsO 2 groups [(67.76 ± 6.45), (71.47 ± 12.19), (73.96 ± 10.42), (58.63 ± 9.24), (60.20 ± 3.74), (67.96 ± 15.41) s] was significantly longer than that in control group [(52.83 ± 8.33), (43.39 ± 8.98) s] since 4 - 5 days of training ( P < 0.05); on the other hand, in the probe trail, there was significant difference in time spent in the target quadrant of offspring mice among groups ( F = 5.709, P < 0.05), time spent in the target quadrant of offspring mice in 30 and 60 mg/L NaAsO 2 groups [(18.85 ± 3.97), (16.90 ± 1.62) s] was significantly less than that in control group [(24.48 ± 3.18) s, P < 0.05]; there was significant difference in BDNF mRNA levels (1.00 ± 0.05, 0.98 ± 0.06, 0.85 ± 0.06, 0.68 ± 0.03) of PND 20 mice among groups ( F = 9.368, P < 0.05), BDNF mRNA level of mice exposed to 60 mg/L NaAsO 2 was significantly lower than that in control, 15 and 30 mg/L NaAsO 2 groups ( P < 0.05); there was significant difference in BDNF mRNA levels (1.00 ± 0.03, 0.75 ± 0.02, 0.76 ± 0.03, 0.73 ± 0.06) of PND 40 mice among groups ( F = 3.998, P < 0.05), and that of PND 40 mice exposed to NaAsO 2 decreased significantly than that in control group ( P < 0.05); there was significant difference in TrkB mRNA levels (1.00 ± 0.08, 0.71 ± 0.02, 0.73 ± 0.02, 0.68 ± 0.09) of PND 20 mice among groups ( F = 16.158, P < 0.05), and that of PND 20 mice exposed to NaAsO 2 were significantly lower than that in control group ( P < 0.05). Conclusion:Arsenic exposure could decrease the mRNA levels of BDNF and TrkB in the hippocampus of offspring mice, which may affect the ability of learning and memory.
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Objective To investigate the epidemiological data of ventilator-associated pneumonia (VAP) occurred in adults after cardiac surgery and exploring the relationship between ventilator-associated pneumonia related factors, and all purpose is to provide strong theoretical advice and technical guidance for prevent the occurrence of ventilator-associated pneumonia in post-cardiac surgery patients. Methods Using literature research method to determine 55 VAP related factors, and 21 nursing experts were selected to conduct 2 rounds of enquiries. Based on the results of the consultation, a retrospective questionnaire was formed. A total of 150 patients who underwent ICU mechanical ventilation after cardiac surgery from September 2016 to August 2017 were retrospectively selected. The related factors of VAP and its etiological characteristics were retrospectively observed. Results Delphi experts consultation results: the response rate two rounds were 86.4% and 100.0% respectively; the coefficient of reliability ascertained the authority of evaluation was 0.857 and 0.903 respectively;Kendall’s W were 0.406 and 0.304 respectively (P all < 0.01). The average incidence of VAP was 25.10/1 000 ventilation days. In the VAP infection group, a total of 84 strains were detected, in which gram-negative bacteria accounted for 69.05% (58/84), fungi 26.19% (22/84), and gram-positive bacteria 4.76% (4/84).The most of them were Acinetobacterbaumannii 27.38% (23/84). Multiple infections were more than the proportion of 48% . Univariate analysis showed that there were 26 statistically significant items (P all < 0.01). Non-conditional binary logistic regression analysis showed that there were 4 independent risk factors with statistical significance: length of ventilator using> 5 days, length of cardiopulmonary ≥2h, perioperative blood transfusion >1 200 ml and perioperative using of acid inhibitors. Conclusions The study showed that most of the predictable VAP factors cannot be artificially intervened. Basing on the occurrence and development of VAP and the status of nursing interventions, Medical staff should take enhanced measures to prevent the occurrence of VAP and improve the quality of medical care
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Objective@#To investigate the epidemiological data of ventilator-associated pneumonia(VAP) occurred in adults after cardiac surgery and exploring the relationship between ventilator-associated pneumonia related factors, and all purpose is to provide strong theoretical advice and technical guidance for prevent the occurrence of ventilator-associated pneumonia in post-cardiac surgery patients.@*Methods@#Using literature research method to determine 55 VAP related factors, and 21 nursing experts were selected to conduct 2 rounds of enquiries. Based on the results of the consultation, a retrospective questionnaire was formed. A total of 150 patients who underwent ICU mechanical ventilation after cardiac surgery from September 2016 to August 2017 were retrospectively selected. The related factors of VAP and its etiological characteristics were retrospectively observed.@*Results@#Delphi experts consultation results: the response rate two rounds were 86.4% and 100.0% respectively; the coefficient of reliability ascertained the authority of evaluation was 0.857 and 0.903 respectively; Kendall’s W were 0.406 and 0.304 respectively (P all < 0.01). The average incidence of VAP was 25.10/1 000 ventilation days. In the VAP infection group, a total of 84 strains were detected, in which gram-negative bacteria accounted for 69.05% (58/84), fungi 26.19% (22/84), and gram-positive bacteria 4.76% (4/84).The most of them were Acinetobacterbaumannii 27.38% (23/84). Multiple infections were more than the proportion of 48%. Univariate analysis showed that there were 26 statistically significant items (P all < 0.01). Non-conditional binary logistic regression analysis showed that there were 4 independent risk factors with statistical significance: length of ventilator using> 5 days, length of cardiopulmonary ≥2h, perioperative blood transfusion >1 200 ml and perioperative using of acid inhibitors.@*Conclusions@#The study showed that most of the predictable VAP factors cannot be artificially intervened. Basing on the occurrence and development of VAP and the status of nursing interventions, Medical staff should take enhanced measures to prevent the occurrence of VAP and improve the quality of medical care
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Objective To construct a eukaryotic expression vector pEGFP N1/IL-37b of full-length and mature IL-37b,and to detect the expression of both full-length and mature IL-37b in RAW 264.7 cells, a mouse macrophage cell line. Methods To construct the eukaryotic vectors of full-length and mature IL-37b by using plasmid pUBC/IL-37b as a template containing the coding region of IL-37b full-length gene. To detect the expression of IL-37b by western blot and confocal microscopy after transfected the recombinant plasmid into RAW 264.7 cells, and to detect the inhibition of full-length and mature IL-37b on IL-6 production by real-time PCR. Results Eukaryotic vectors pEGFP N1/IL-37b expressed full-length and mature IL-37b after transfection in cells, which inhibited LPS-induced IL-6 production. Conclusions Eukaryotic vectors of full-length and mature IL-37b can be successfully constructed,and lays a foundation for further study of anti-inflammation functions and mechanisms of IL-37b.
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Objective To investigate the expression of recombinant IL-37b protein and removal of the endotoxin, and identify its biological activity.Methods The prokaryotic expression vector pET28/IL-37b was constructed and to transform Escherichia coli (E.coli) Rosetta.After induction with IPTG, the recombinant protein was purified through Ni2+-NTA gel column and identified by SDS-PAGE and Coomassie brilliant blue staining.Then, the endotoxin protein was removed and was treated with LPS-stimulated RAW 264.7 cells.The culture supernatant was collected.The expression of IL-6 was detected by ELISA and the biological activity of the protein was identified.Results The recombinant IL-37b with high purity was expressed and the endotoxin produced by prokaryotic expression was reduced, and it was identified to have good biological activity.Conclusions In this study a recombinant IL-37b protein with high biological activity is successfully obtained.
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Objective To establish lentiviral expression vectors for Smurf1 silencing and assess the effects of Smurf1 silencing on cell migration.Methods HeLa and A549 cells were infected with lentiviral expression vectors for Smurf1 silencing respectively.After 7 days,the stable cell lines with Smurf1 silencing were obtained after puromycin-resistance screening,enrichment and expansion.The intracellular gene and protein levels of Smurf1 were detected by qPCR and western blot.Transwell assay was used to assess the effect of Smurf1 silencing on cell migration.Results The stable cell lines with Smurf1 silencing are constructed successfully.Silencing of Smurf1 down-regulated cell migration rate detected by Transwell assay.Conclusion Smurf1 promotes cell migration.
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Objective To establish a C57BL/6 mouse model of intestinal infection induced by S.Typhimurium.Methods In order to improve the infectious sensitivity of S.Typhimurium, C57BL/6 mice were intragastrically given 5% (w/v) NaHCO3.Then mice were challenged with S.Typhimurium.The health condition, survival and body weight of mice were observed from day 0 to day 7 after the bacterial infection.The pathological changes were also examined.Results the mice challenged with S.Typhimurium showed decreased body weight and typical clinical signs, including in appetence, piloerection and low survival rate.Macroscopic dissection revealed that intestinal hyperemia and swelling were founded in the mice challenged with S.Typhimurium.Histopathology showed intestinal epithelial and mucosal damages.Conclusions We have successfully established a C57BL/6 mouse model of S.Typhimurium infection.This model may be of crucial significance for studying the biological functions of associated immunological molecules or cytokines in the process of inflammatory bowel disease induced by S.Typhimurium.
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Objective To investigate the effect of Smad3 on cell migration of A549 and HeLa cells.Methods Primers for pCMV-Myc-Smad3 plasmid construction and siRNA targeting Smad 3 were designed and synthesized .pCMV-Myc-Smad3 plasmid was constructed with molecular cloning techniques .Overexpression of Smad 3 with Myc-tag or silencing of endogenous Smad3, and then scratch assay was used to detect the migration ability of A 549 and HeLa cells in vitro. Results pCMV-Myc-Smad3 plasmid was successfully constructed .Overexpression of Smad 3 significantly up-regulated the migration rate of A549 and HeLa cells.Conversely, in the same cells, silencing of endogenous Smad3 or treatment with Smad3 inhibitor, SIS3, down-regulated the migration rate .Conclusions Smad3 promotes cell migration of A549 and HeLa cells.