The association between immune cells and breast cancer: insights from mendelian randomization and meta-analysis.

BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide, with 2.3 million new cases and 685,000 deaths annually. It has the highest incidence in North America, Europe, and Australia and lower rates in parts of Asia and Africa. Risk factors include age, family history, hormone replacement therapy, obesity, alcohol consumption, and lack of physical activity. BRCA1 and BRCA2 gene mutations significantly increase the risk. The five-year survival rate is over 90% in developed countries but lower in developing ones. Early screening and diagnosis, using mammography and MRI, are crucial for reducing mortality. In recent years, significant progress has been made in studying BC immunophenotyping, particularly in multicolor flow cytometry, molecular imaging techniques, and tumor microenvironment analysis. These technologies improve diagnosis, classification, and detection of minimal residual disease. Novel immunotherapies targeting the tumor microenvironment, like CAR-T cell therapy, show high efficiency and fewer side effects. High levels of tumor-infiltrating lymphocytes (TILs) correlate with better prognosis, while immune checkpoint molecules (PD-1, PD-L1) help cancer cells evade the immune system. Tumor-associated macrophages (TAMs) promote invasion and metastasis. Blocking molecules like CTLA-4, LAG-3, and TIM-3 enhance anti-tumor responses, and cytokines like IL-10 and TGF-ß aid tumor growth and immune evasion. Mendelian randomization (MR) studies use genetic variants to reduce confounding bias and avoid reverse causation, providing robust causal inferences about immune cell phenotypes and BC. This approach supports the development of precision medicine and personalized treatment strategies for BC. METHODS: This study aims to conduct Mendelian Randomization (MR) analysis on 731 immune cell phenotypes with BC in the BCAC and Finngen R10 datasets, followed by a meta-analysis of the primary results using the inverse-variance weighted (IVW) method and multiple corrections for the significance p values from the meta-analysis. Specifically, the study is divided into three parts: First, data on 731 immune cell phenotypes and BC are obtained and preprocessed from the GWAS Catalog and Open GWAS (BCAC) and the Finngen R10 databases. Second, MR analysis is performed on the 731 immune cell phenotypes with BC data from the BCAC and Finngen R10 databases, followed by a meta-analysis of the primary results using the IVW method, with multiple corrections for the significance p values from the meta-analysis. Finally, the positively identified immune cell phenotypes are used as outcome variables, and BC as the exposure variable for reverse MR validation. RESULTS: The study found that two immune phenotypes exhibited strong significant associations in MR analysis combined with meta-analysis and multiple corrections. For the immune phenotype CD3 on CD28+ CD4-CD8- T cells, the results were as follows: In the BCAC dataset, the IVW result was Odds Ratio (OR) = 0.942 (95% confidence interval (CI) = 0.915 ~ 0.970, P = 6.76 × 10-5), ß = -0.059; MR Egger result was ß = -0.095; and the weighted median result was ß = -0.060. In the Finngen R10 dataset, the IVW result was OR = 0.956 (95% CI = 0.907 ~ 1.01, P = 0.092), ß = -0.045; MR Egger result was ß = -0.070; and weighted median result was ß = -0.035. The ß values were consistent in direction across all three MR methods in both datasets. The meta-analysis of the IVW results from both datasets showed OR = 0.945 (95% CI = 0.922 ~ 0.970, P = 1.70 × 10-5). After Bonferroni correction, the significant P-value was P = 0.01, confirming the immune phenotype as a protective factor against BC. For the immune phenotype HLA DR on CD33- HLA DR+, the results were as follows: In the BCAC dataset, the IVW result was OR = 0.977 (95% CI = 0.964 ~ 0.990, P = 7.64 × 10-4), ß = -0.023; MR Egger result was ß = -0.016; and the weighted median result was ß = -0.019. In the Finngen R10 dataset, the IVW result was OR = 0.960 (95% CI = 0.938 ~ 0.983, P = 6.51 × 10-4), ß = -0.041; MR Egger result was ß = -0.064; and weighted median result was ß = -0.058. The ß values were consistent in direction across all three MR methods in both datasets. The meta-analysis of the IVW results from both datasets showed OR = 0.973 (95% CI = 0.961 ~ 0.984, P = 3.80 × 10-6). After Bonferroni correction, the significant P-value was P = 0.003, confirming this immune phenotype as a protective factor against BC. When the immune cell phenotypes CD3 on CD28+ CD4-CD8- T cells and HLA DR on CD33- HLA DR+ were used as outcomes and BC was used as exposure, the data processing and analysis procedures were the same. The MR analysis results are as follows: Data from the FinnGen database regarding the effect of positive immune phenotypes on malignant neoplasm of the breast indicated a ß coefficient of -0.011, OR = 0.99 (95% CI = -0.117 ~ 0.096, P = 0.846); data from the BCAC database regarding favorable immune phenotypes for BC demonstrated a ß coefficient of -0.052, OR = 0.095 (95% CI = -0.144 ~ 0.040, P = 0.266). The results suggest insufficient evidence in both databases to indicate that BC inversely affects these two immune cell phenotypes. CONCLUSIONS: Evidence suggests that the immune cell phenotypes CD3 on CD28+ CD4-CD8- T cells and HLA DR on CD33- HLA DR+ protect against BC. This protective effect may be achieved through various mechanisms, including enhancing immune surveillance to recognize and eliminate tumor cells; secreting cytokines to inhibit tumor cell proliferation and growth directly; triggering apoptotic pathways in tumor cells to reduce their number; modulating the tumor microenvironment to make it unfavorable for tumor growth and spread; activating other immune cells to boost the overall immune response; and inhibiting angiogenesis to reduce the tumor's nutrient supply. These mechanisms work together to help protect BC patients and slow disease progression. Both immune cell phenotypes are protective factors for BC patients and can be targeted to enhance their function and related pathways for BC treatment.

FBLN5 as One Presumably Prognostic Gene Potentially Modulating Tumor Immune Microenvironment for Renal Clear Cell Carcinoma in Children and Young Adults.

Objective: To investigate the role of FBLN5in renal clear cell carcinoma (KIRC), in particular on the tumor's immune microenvironment, including children and young adults. Methods: FBLN5 expression in tumor and normal samples was explored using SangerBox, TIMER2.0, GEPIA, UALCAN, HPA databases. The Linkedomics database was used to obtain FBLN5 co-expressed genes in KIRC tissue. SangerBox was also used to estimate immune infiltration of FBLN5 in KIRC. The Kaplan-Meier plotter was used to investigate the survival effects of FBLN5 expression in the presence of immune infiltration. We then collected 48 cases from 7 hospitals over a-20 year period to calculate the impact of FBLN5 on the prognosis of children and young adults with KIRC. Results: FBLN5 expression was significantly reduced in KIRC tissue compared to normal adjacent tissue. FBLN5 was potentially involved in the immune-related biological processes. In addition, FBLN5 expression has been linked to a number of immune checkpoints, cytokines, chemokines and chemokine receptors in KIRC. At the same time, the expression of FBLN5 affected the survival rates differently in KIRC patients with high or low levels of immune infiltration. High expression of FBLN5 in children and young adults with KIRC was associated with a favorable prognosis. Conclusion: This study shed light on the potential of FBLN5 as a prognostic marker in children and young adults with KIRC and as an immune-related target for clinical treatment.

Gastroenteropancreatic neuroendocrine carcinoma in children and adolescents: a population-based study.

PURPOSE: Gastroenteropancreatic Neuroendocrine Carcinoma (GEP-NEC) in children is an exceptionally rare and aggressive form of cancer. We aimed to conduct a population-based cohort study to predict overall survival (OS) in pediatric patients with GEP-NEC. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was employed to identify all pediatric patients with GEP-NEC diagnosed between 2000 and 2019. To create survival curves based on various criteria, Kaplane-Meier estimations were utilized. The log-rank test was used to compare survival curves. The variables associated with OS were determined using Cox proportional-hazards regression. Furthermore, we developed a nomogram to predict overall survival in pediatric GEP-NEC patients. RESULTS: A total of 103 pediatric GEP-NEC patients were identified. The tumors primarily affected females (62.2%). The majority of GEP-NEC was found in the appendix (63.1%), followed by the pancreas (23.3%) and the intestinal tract (13.6%). The highest rates of localized stage (76.9%) and surgery (98.5%) were found in the NEC of appendix origin. However, pancreatic origins had the largest proportion of distant disease (66.7%) but the lowest percentage of surgery (37.5%). Overall 1-year, 3-year, and 5-year survival rates for all patients were 94.4%, 85.4%, and 85.4%, respectively. Tumors of pancreatic origin had the worst survival compared with those of the appendix and intestinal tract. The Cox proportional hazard regression revealed that only site was an important independent predictor of survival. CONCLUSIONS: Our study revealed that only the primary site was found to be the most important predictor of the OS in pediatric GEP-NEC. It's important to work closely with a multidisciplinary team, including oncologists, surgeons, and other specialists, to determine the most appropriate treatment plan for pediatric GEP-NEC.

Erythrocyte Sedimentation Rate for Assisted Diagnosis of Pediatric Osteomyelitis: A Meta-Analysis.

Objective: For the diagnosis of pediatric osteomyelitis, the sensitivity, specificity, and predictive value of erythrocyte sedimentation rate (ESR) were evaluated in this study. Methods: A systematic computer-based search was performed for relevant articles focusing on the ESR diagnosis of pediatric osteomyelitis in PubMed, Embase, and the Cochrane Library with an inclusion criteria: 1) the diagnostic utility of ESR for diagnosing osteomyelitis patients under the age of 18;2) two-by-two contingency tables can be obtained. Case reports, review papers, and animal experiments were excluded. Results: The diagnostic meta-analysis included 8 studies involving 348 children with osteomyelitis, all of whom were tested for ESR. Diagnostic meta-analysis revealed a sensitivity and specificity of 0.90, 95% confidence interval (CI) (0.86-0.93), and 0.50 (95% CI,0.47-0.54) for ESR in pediatric osteomyelitis diagnosis, respectively. The positive likelihood ratio (LR), negative LR, and diagnostic odds ratio were 1.38,(95% CI,1.08-1.78), 0.46, (95% CI,0.26-0.73), and 3.20, (95% CI,1.33-7.69), respectively. The area under the curve (AUC) was determined to be 0.80 based on the summary receiver operating characteristic curve (SROC). Conclusion: The literature on the use of ESR in pediatric osteomyelitis diagnosis was thoroughly reviewed in this study. It was also found that ESR may be useful as a biomarker for pediatric osteomyelitis diagnosis. Due to its low specificity, it should be used in combination with other markers such as C-reactive protein, neutrophil percentage, and white blood cell count.

Directed evolution rice genes with randomly multiplexed sgRNAs assembly of base editors.

CRISPR-based directed evolution is an effective breeding biotechnology to improve agronomic traits in plants. However, its gene diversification is still limited using individual single guide RNA. We described here a multiplexed orthogonal base editor (MoBE), and a randomly multiplexed sgRNAs assembly strategy to maximize gene diversification. MoBE could induce efficiently orthogonal ABE (<36.6%), CBE (<36.0%), and A&CBE (<37.6%) on different targets, while the sgRNA assembling strategy randomized base editing events on various targets. With respective 130 and 84 targets from each strand of the 34th exon of rice acetyl-coenzyme A carboxylase (OsACC), we observed the target-scaffold combination types up to 27 294 in randomly dual and randomly triple sgRNA libraries. We further performed directed evolution of OsACC using MoBE and randomly dual sgRNA libraries in rice, and obtained single or linked mutations of stronger herbicide resistance. These strategies are useful for in situ directed evolution of functional genes and may accelerate trait improvement in rice.

NEAT1/microRNA 339-5p/SPI1 Axis Feedback Loop Contributes to Osteogenic Differentiation in Acute Suppurative Osteomyelitis in Children.

Objective: Long non-coding RNA plays an important role in osteogenic differentiation. Nuclear enriched abundant transcript 1 (NEAT1) has been revealed to promote osteogenic differentiation in human bone marrow mesenchymal stem cells (hBMSCs), but the underlying regulatory mechanism remains unknown in acute suppurative osteomyelitis of children. Methods: Osteogenic medium (OM) was used to induce osteogenic differentiation. Quantitative real-time PCR and Western blotting were used to evaluate gene expression. The effects of NEAT1, microRNA 339-5p (miR-339-5p), and salmonella pathogenicity island 1 (SPI1) on osteogenic differentiation were assessed in vitro using alizarin red S staining assays and alkaline phosphatase activity. Interactions between NEAT1, miR-339-5p, and SPI1 were identified using immunoprecipitation, luciferase reporter assays, and chromatin immunoprecipitation. Results: During osteogenic differentiation, expression of NEAT1 was up-regulated in hBMSCs, and miR-339-5p level was down during osteogenic differentiation. Knockdown of NEAT1 reduced the osteogenic differentiation of hBMSCs, and down-regulation of miR-339-5p may counteract the effect of NEAT1 silencing. SPI1 was a target of miR-339-5p by luciferase reporter assay and was also a transcription factor of NEAT1 by chromatin immunoprecipitation. A positive NEAT1-miR-339-5p-SPI1 feedback loop was found to be present during osteogenic differentiation in hBMSCs. Conclusion: It was the first study to reveal that the NEAT1-miR-339-5p-SPI1 feedback loop can promote osteogenic differentiation in hBMSCs and shed a new light on the role of NEAT1 during osteogenic differentiation.

Douyin as a source of information and education on humeral supracondylar fracture of children during the COVID-19 pandemic in Chinese Mainland: An observational study.

We aimed to investigate whether Douyin videos on pediatric humeral supracondylar fractures could be a useful source during the COVID-19 pandemic. A search was conducted using the term "humeral supracondylar fracture of children" on Douyin. The top 100 videos were selected based on view count. 74 was the final analysis, after excluding 26 videos for various reasons. First, the videos were classified into medical and the non-medical groups based on authorship. The medical team videos were about explanations or detailed surgical procedures directly related to child's fracture. There were also non-medical videos, mostly about personal experiences and other things. The videos were then also divided into 2 groups abased on the year of COVID-19 pandemic. The number of views, content type, video duration and number of likes about the video were analyzed. Among the 74 videos included in this study, had a total of 19,647,988 views (median 205,129, range 7874-1,495,004). Compared to the medical group, the non-medical group had more views (P = .004), likes (P = .000), view ratio (P = .019), and video power index (P = .024). During the COVID-19 pandemic, views (P = .033), view ratio (P = .006), and video power index (P = .043) also increased. Douyin has been a valuable source of health information for patients during COVID-19 pandemic regarding the occurrence of humeral supracondylar fracture in children. Medical professionals and institutions should upload credible, informative videos and clear, high-quality, scientifically reviewed surgical footage of children with humeral supracondylar fracture. And the videos uploaded by medical professionals and filtered by Douyin's staff appear to be necessary.

Exploring the Ecological Performance of China's Tourism Industry: A Three-Stage Undesirable SBM-DEA Approach with Carbon Footprint.

The environmental impact of carbon emissions and the carbon footprint from tourism activities are significant for promoting low-carbon development in the tourism industry. This paper employed a bottom-up approach to estimate the carbon footprint and energy consumption of China's tourism industry. Then, the three-stage undesirable SBM-DEA model was employed to evaluate and decompose the eco-efficiency of China's provincial tourism industry from 2008 to 2017. The results showed that the eco-efficiency of most provinces has experienced a slight increase during the past ten years, while management inefficiency within the tourism industry has been the main restriction of the utilization of tourism resources in most regions. The decomposition and quadrant analysis indicated that scale efficiency was the direct driver of the poor ecological performance in Northeast China, while technical efficiency dominated the tourism eco-efficiency in South-Central China. These two issues have together led to the poor utilization of the rich tourism resources and the natural environment in Southwest China. On the basis of these discussions, differentiated policy implications towards different kinds of regions were provided to promote low-carbon development and to realize the potential of tourism resources in China's tourism industry.

Identification of ST3GAL5 as a prognostic biomarker correlating with CD8+ T cell exhaustion in clear cell renal cell carcinoma.

Aberrant sialylation is frequently observed in tumor development, but which sialyltransferases are involved in this event are not well known. Herein, we performed comprehensive analyses on six ST3GAL family members, the α-2,3 sialyltransferases, in clear cell renal cell carcinoma (ccRCC) from public datasets. Only ST3GAL5 was consistently and significantly overexpressed in ccRCC (n = 791 in total), compared with normal kidney tissues. Its overexpression was positively correlated with tumor stage, grade, and the poor prognosis in ccRCC patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses indicated the involvement of ST3GAL5 in tumor immunoregulation. Then we revealed that ST3GAL5 expression showed a positive correlation with CD8+ T cell infiltration, using multiple tools on TIMER2.0 web server. Notably, ST3GAL5 overexpression was further identified to be associated with expression signature of CD8+ T cell exhaustion in ccRCC samples from three datasets (n = 867 in total; r > 0.3, p < 0.001). In our own ccRCC cohort (n = 45), immunohistochemistry and immunofluorescence staining confirmed that ST3GAL5 overexpression was accompanied by high CD8+ T cell infiltration with the increased exhaustion markers. Altogether, ST3GAL5 as a promising prognostic biomarker with CD8+ T cell exhaustion in ccRCC is indicated.

Industrial agglomeration and haze pollution: Evidence from China.

The rapid industrialization has contributed to the miracle of economic growth in China, while also caused a series of environmental problems. As one of the most concerning urban disease in China, the aggravation of haze pollution is closely related to the accelerating urbanization and industrialization process in recent years, and the strong spatial diffusion makes the negative externality of haze pollution more harmful. This characteristic of haze pollution is closely related to the spatial structure of industrial sectors, especially the agglomeration of industrial sectors. This paper established a spatial economic framework to investigate the spillover effect of industrial agglomeration on haze pollution based on satellite raster map data of PM2.5 and location entropy index, and further discuss the question that whether industrial agglomeration can achieve a balanced development for both economic growth and environmental quality. The results indicated that there is an inverted U-shaped relationship between industrial agglomeration and haze pollution, and the indirect effect from spatial spillover dominated this impact. Industrial agglomeration has a single threshold effect on the knowledge spillover and the utilization of pollution disposal infrastructure of industrial sectors. Only when the agglomeration level reaches the threshold value, the scale effect can be realized to promote the air quality. The resource allocation efficiency and knowledge spillovers of industrial agglomeration need to be promoted in order to reach the inflection point and realize the win-win situation.

The environmental-adjusted energy efficiency of China's construction industry: a three-stage undesirable SBM-DEA model.

The construction industry is a pillar industry of China's national economy but its problems of high energy consumption, high pollution, and low energy efficiency are increasingly prominent. The study on the energy efficiency of the construction industry is of great significance for improving development quality and achieving the goal of energy saving and emission reduction. In this paper, a three-stage undesirable SBM-DEA model was employed to measure the energy efficiency in the construction industry during 2005-2016. The CO2 directly emitted by the construction industry and indirectly emitted in the production of building materials were used as the undesirable output and the three-stage framework was employed to analyze and eliminate the influence of external environment. The empirical results showed that low efficiency of management in the construction industry is an important factor leading to the low level of energy efficiency in China's construction industry. For the energy efficiency value before and after adjustment, the "high-high" provinces have made full use of the superior external environment by their high management level, while the "high-low" provinces need to fully realize the potential in promoting energy efficiency of its external environment by improving its own management of the construction industry. On the contrary, the "low-high" provinces need to improve the external environment to ease its restrictions on the level of management in the construction industry. Environmental factors and management level should be considered simultaneously for different provinces to improve energy efficiency of the construction industry.

Increased expression of the RNA-binding motif protein 47 predicts poor prognosis in non-small-cell lung cancer.

Lung cancer is the leading cause of cancer-associated mortality worldwide. In China, in particular, lung cancer mortality has markedly increased and is likely to continue to rise. RNA-binding proteins are pivotal to the development and progression of a variety of cancer types, including non-small cell lung cancer (NSCLC). RNA-binding motif protein 47 (RBM47) has been found to act as a tumor suppressor in breast cancer and NSCLC. However, to the best of our knowledge, RBM47 expression in NSCLC tissues has yet to be investigated. Analysis via the online database, Gene Expression Omnibus, revealed that RBM47 was upregulated in NSCLC and associated with pathological type, suggesting that RBM47 may play different roles in lung adenocarcinoma and lung squamous cell carcinoma. In the present study, the expression of RBM47 was examined by immunohistochemistry in 175 pairs of tumor and adjacent non-cancerous tissues resected from patients with NSCLC. The results indicated that the expression of RBM47 was significantly increased in NSCLC samples compared with that in the matched non-cancerous samples. Furthermore, RBM47 expression was higher in Xuanwei compared with that in non-Xuanwei NSCLC, suggesting that RBM47 is a more sensitive biomarker in Xuanwei NSCLC, and that it may serve as a candidate therapeutic target. In addition, RBM47 expression was associated with the pathological type, however not with the age, sex, lymph node metastasis, pT stage or pathological Tumor-Node-Metastasis stage of the patients. The increased expression level of RBM47 may indicate a worse overall survival rate for patients with NSCLC. In addition, multivariate survival analysis showed that the Xuanwei area is associated with poor prognosis for patients with NSCLC. In conclusion, the present study revealed that the upregulation of RBM47 accelerated the malignant progression of NSCLC, indicating that RBM47 may be a potential biomarker for NSCLC progression and a therapeutic target for NSCLC.

Study on the Quality Evaluation of Compound Danshen Preparations Based on the xCELLigence Real-Time Cell-Based Assay and Pharmacodynamic Authentication.

Objective: To perform a preliminary study on the quality evaluation of compound Danshen preparations based on the xCELLigence Real-Time Cell-based Assay (RTCA) system and make a pharmacodynamics verification. Methods: The compound Danshen was discussed as a methodological example, and the bioactivity of the compound Danshen preparations were evaluated by real-time cell electronic analysis technology. Meanwhile, an in vivo experiment on an acute blood stasis rat model was performed in order to verify this novel evaluation through the curative effect of dissipating blood stasis. Results: We determined the cell index (CI) and IC50 of the compound Danshen preparations and produced time/dose-dependent cell response profiles (TCRPs). The quality of the three kinds of compound Danshen preparations was evaluated through the RTCA data. The trend of CI and TCRPs reflected the effect of drugs on the cell (promoting or inhibiting), and it was verified that the results correlated with the biological activity of the drugs using a pharmacodynamics experiment. Conclusion: The RTCA system can be used to evaluate the quality of compound Danshen Preparations, and it can provide a new idea and new method for quantitatively characterizing the biological activity of traditional Chinese medicines (TCMs).

Experiment on the treatment of acid mine drainage with optimized biomedical stone particles by response surface methodology.

The immobilized particles were used to treat acid mine drainage (AMD) in the study, which owns the characteristics of serious pollution and high managing cost. The immobilized particles were prepared with sulfate reducing bacteria (SRB) and medical stones. In order to investigate the interactive influence of medical stones on the particle properties, the salt modification condition, content, and size of the medical stone were taken as the influential factors. At the same time, the removal rate of SO42- and Mn2+, the release of total irons (TFe) and chemical oxygen demand (COD) and pH value were taken as the response values in the experiment. On the basis of the orthogonal experimental research, a response surface model was established. The experimental analysis showed that the particles can get the best treatment effect, when using the salt-modified medical stone with the content of 15% and particle size of 200~300 mesh. At this time, the removal rates of Mn2+ and SO42- in wastewater were 83.10 and 96.22%, respectively. The release contents of TFe and COD were 2.99 mg L-1 and 1828.54 mg L-1, respectively, and the pH value was 7.05. Then, biological medical stone particles were prepared according to the optimal ratio in the response surface experiment. The adaptability of biomedical stone particles was studied at different concentrations of SO42-, Mn2+ and pH value. The results showed that the high concentration of SO42- inhibited the metabolism of SRB, while Mn2+ had a less effect. The biomedical stone particles could regulate pH value very well.

[Screen absorption enhancer for intranasal administration preparations of paeoniflorin based on nasal perfusion method in rats].

This experiment was aimed to screen the absorption enhancer for intranasal administration preparations of paeoniflorin. In this study, HPLC method for determination of paeoniflorin in perfusion liquid was established and the improved model of nasal perfusion in rats was used to screen out the species and amounts of absorption enhancer. In order to avoid the influence of the secretion and absorption of nasal cavity on the volume of perfusion fluid, the residual dose was calculated by using the volume correction method. Linear regression was carried out between the logarithm to the percentage of the residual dose and the corresponding time, and the slope of the regression line was exactly the absorption rate constant. Experimental results showed that hydroxypropyl-ß-cyclodextrin and water-soluble azone can significantly improve the nasal absorption of paeoniflorin. Furthermore, water-soluble azone had the highest absorption rate constant and the best promoting penetration effect on intranasal administration preparations of paeoniflorin. It was also found that when the mass concentration of water-soluble azone in the perfusion liquid increased from 5 g•L⁻¹ to 20 g•L⁻¹, the absorption rate constant was gradually increased and peaked at 20 g•L⁻¹. When the mass concentration was increased to 30 g•L⁻¹, the absorption rate constant was decreased, indicating that the best mass concentration of water-soluble azone was 20 g•L⁻¹.

Clinical application of intra-aortic balloon pump in patients with cardiogenic shock during the perioperative period of cardiac surgery.

Intra-aortic balloon pumps (IABP) have saved many patients with cardiogenic shock during the perioperative period of cardiac surgery. However, the ideal insertion timing is controversial. In the present study, we aimed to optimize the insertion timing, in order to increase the survival rate of the patients. A total of 197 patients with cardiogenic shock during the perioperative period of cardiac surgery and implemented IABP from January 2011 to October 2015 were selected for the study. Patients were divided into five groups on the basis of application timing of IABP: 0-60, 61-120, 121-180, 181-240 and >240 min. The 30-day mortality, application rate of continuous renal replacement therapy (CRRT), duration of mechanical ventilation, duration of hospital stay and hospitalization charges were analyzed in the above groups. The risk factors related to mortality and the occurrence of IABP complications were also analyzed. The mortality in the 0-60, 61-120, 121-180, 181-240 and >240 min groups were 42.17, 36.6, 77.3, 72.7 and 79.3%, respectively. Earlier IABP insertion resulted in less patients receiving CRRT from acute renal failure and less daily hospitalization charges. However, the IABP application timing had no effect on indexes such as hospitalization duration, duration of mechanical ventilation and total hospitalization charges. Multifactor logistic regression analysis indicated that the independent risk factors of death in patients with cardiogenic shock during cardiac surgery were related to IABP support timing and vasoactive-inotropic score (VIS) before balloon insertion. In the first 120 min of cardiogenic shock during the perioperative period of cardiac surgery, IABP application decreased 30-day mortality. Mortality was related with VIS score of patients, which can be used to predict the prognosis of patients with cardiogenic shock.

Safety and Efficacy of Transplantation with Allogeneic Skin Tumors to Treat Chemically-Induced Skin Tumors in Mice.

BACKGROUND Transplantation with allogeneic cells has become a promising modality for cancer therapy, which can induce graft-versus-tumor (GVT) effect. This study was aimed at assessing the safety, efficacy, and tissue type GVT (tGVT) response of transplantation with allogeneic skin tumors to treat chemically-induced skin tumors in mice. MATERIAL AND METHODS FVB/N and ICR mice were exposed topically to chemicals to induce skin tumors. Healthy ICR mice were transplanted with allogeneic skin tumors from FVB/N mice to test the safety. The tumor-bearing ICR mice were transplanted with, or without, allogeneic skin tumors to test the efficacy. The body weights (BW), body condition scores (BCS), tumor volumes in situ, metastasis tumors, overall survival, and serum cytokines were measured longitudinally. RESULTS Transplantation with no more than 0.03 g allogeneic skin tumors from FVB/N mice to healthy ICR mice was safe. After transplantation with allogeneic skin tumors to treat tumor-bearing mice, it inhibited the growth of tumors slightly at early stage, accompanied by fewer metastatic tumors at 24 days after transplantation (21.05% vs. 47.37%), while there were no statistically significant differences in the values of BW, BCS, tumor volumes in situ, metastasis tumors, and overall survival between the transplanted and non-transplanted groups. The levels of serum interleukin (IL)-2 were significantly reduced in the controls (P<0.05), but not in the recipients, which may be associated with the tGVT response. CONCLUSIONS Our results suggest that transplantation with allogeneic skin tumors is a safe treatment in mice, which can induce short-term tGVT response mediated by IL-2.

Association of CXCR1 and 2 expressions with gastric cancer metastasis in ex vivo and tumor cell invasion in vitro.

BACKGROUND: CXCR1 and CXCR2, cell surface receptors of interleukin-8, regulate cell migration and alteration of their expression has been associated with poor prognosis of various cancers. The aim of this study was to detect their expression in gastric cancer to identify associations with another cell adhesion molecule, matrix metalloproteinase-9 (MMP9), and with clinicopathological data ex vivo, and then explore their potential role in gastric cancer cells in vitro. MATERIALS AND METHODS: A total of 172 cases of gastric cancer tissue specimens were collected for immunohistochemical analysis of CXCR1, CXCR2, and MMP9 expression. Expression of CXCR1 and CXCR2 proteins was knocked in or down using their cDNA and shRNA, respectively, in gastric cancer cell lines to assess the changed cell phenotypes and gene expression. RESULTS: CXCR1, CXCR2, and MMP9 were expressed in 61.0%, 77.9%, and 75.6% of gastric cancer tissues, respectively. Moreover, CXCR1 and CXCR2 expression was associated with tumor differentiations, advanced clinical stages, lymph node, and distant metastasis of gastric cancer. Similarly, MMP9 expression was associated with CXCR1 and CXCR2. Expression of these three proteins was interrelated. In vitro study showed that levels of CXCR1 and CXCR2 proteins were associated with the capacity of gastric cancer cell migration, while knockdown of their expression inhibited gastric cancer cell migration and invasion abilities in vitro. In contrast, overexpression of CXCR1 and CXCR2 proteins promoted tumor cell migration and invasion. At the gene levels, knockdown of CXCR1 or CXCR2 expression suppressed expression of Ets-1, SRC-1, and JNK proteins and phosphorylated c-Jun and Erk1/2. Conversely, upregulation of CXCR1 or CXCR2 promoted expression of Ets-1, SRC-1, JNK, and c-Jun proteins and phosphorylated JNK, c-Jun and Erk1/2. CONCLUSIONS: These findings suggest that CXCR1 and CXCR2 play an important role in gastric cancer progression. Further study will be performed to investigate whether target of their expression can be used as a novel strategy in clinical control of gastric cancer metastasis.

Andrographolide inhibits intimal hyperplasia in a rat model of autogenous vein grafts.

The saphenous vein is considered a common conduit for coronary artery bypass grafting. A major limitation involved is the high graft occlusion rate. We evaluated the effect and mechanism of andrographolide on intimal hyperplasia (IH) of autografted rat veins. For this purpose, 140 female Sprague-Dawley rats were randomly divided into experimental (andro) and control groups. Andro rats received andrographolide (200 mg/kg) lavaged once daily for 2 days before surgery while controls received normal saline. The external jugular vein was grafted into the ipsilateral carotid artery. The animals were killed at 1/3 days and 1/2/4/6/8 weeks postoperatively. The neointima to media area (I/M) ratio was determined. Expression of the p65, E-selectin and MMP-9 proteins/mRNA was also determined. Autografted rat veins displayed IH postoperatively. In andro rats, compared with controls, IH was significantly reduced (P < 0.01) at 2/4/6/8 weeks but not at 1/3/7 days postoperatively. Andrographolide also significantly (P < 0.05) reduced the expression of E-selectin and MMP-9 proteins/mRNAs at 2/4/6/8 weeks postoperatively whereas p65 protein/mRNA was significantly (P < 0.05) diminished at 1/3 days and 1/2/4/6/8 weeks postoperatively as compared with controls. Therefore, it was concluded that andrographolide inhibited IH in autografted rat veins through the suppression of p65, E-selectin, and MMP-9 at the transcriptional level.