Construction of ROS-Responsive Hyaluronic Acid Modified Paclitaxel and Diosgenin Liposomes and Study on Synergistic Enhancement of Anti-Ovarian Cancer Efficacy.

Purpose: Ovarian cancer is a fatal gynecologic malignancy with a high rate of abdominal metastasis. Chemotherapy still has a poor clinical prognosis for ovarian cancer patients, with cell proliferation and angiogenesis leading to invasion, migration, and recurrence. To overcome these obstacles, we constructed a novel HA-modified paclitaxel and diosgenin liposome (PEG-TK-HA-PDLPs) using two novel functional materials, DSPE-PEG2000-HA and DSPE-PEG2000-TK-PEG5000, to specifically deliver the drugs to the tumor site in order to reduce OC cell proliferation and anti-angiogenic generation, thereby inhibiting invasion and migration. Methods and Results: PEG-TK-HA-PDLPs were prepared by film dispersion, with ideal physicochemical properties and exhibits active targeting for enhanced cellular uptake. The ZIP synergy score for PTX and Dios was calculated using the online SynergyFinder software to be 3.15, indicating synergy. In vitro results showed that PEG-TK-HA-PDLPs were highly cytotoxic to ID8 cells, induced ID8 cell apoptosis, and inhibited ID8 cell migration and invasion. In vivo studies showed that PEG-TK-HA-PDLPs could prolong the circulation time in the blood, accumulate significantly in the tumor site, and effectively fight against angiogenesis with significant anti-tumor effects. Conclusion: The production of PEG-TK-HA-PDLPs is an effective strategy for the treatment of OC.

Minocycline in the eradication of Helicobacter pylori infection: A systematic review and meta-analysis.

BACKGROUND: Difficulty in obtaining tetracycline, increased adverse reactions, and relatively complicated medication methods have limited the clinical application of the classic bismuth quadruple therapy. Therefore, the search for new alternative drugs has become one of the research hotspots. In recent years, minocycline, as a semisynthetic tetracycline, has demonstrated good potential for eradicating Helicobacter pylori (H. pylori) infection, but the systematic evaluation of its role remains lacking. AIM: To explore the efficacy, safety, and compliance of minocycline in eradicating H. pylori infection. METHODS: We comprehensively retrieved the electronic databases of PubMed, Embase, Web of Science, China National Knowledge Infrastructure, SinoMed, and Wanfang database as of October 30, 2023, and finally included 22 research reports on H. pylori eradication with minocycline-containing regimens as per the inclusion and exclusion criteria. The eradication rates of H. pylori were calculated using a fixed or a random effect model, and the heterogeneity and publication bias of the studies were measured. RESULTS: The single-arm meta-analysis revealed that the minocycline-containing regimens achieved good overall H. pylori eradication rates, reaching 82.3% [95% confidence interval (CI): 79.7%-85.1%] in the intention-to-treat analysis and 90.0% (95%CI: 87.7%-92.4%) in the per-protocol analysis. The overall safety and compliance of the minocycline-containing regimens were good, demonstrating an overall incidence of adverse reactions of 36.5% (95%CI: 31.5%-42.2%). Further by traditional meta-analysis, the results showed that the minocycline-containing regimens were not statistically different from other commonly used eradication regimens in eradication rate and incidence of adverse effects. Most of the adverse reactions were mild to moderate and well-tolerated, and dizziness was relatively prominent in the minocycline-containing regimens (16%). CONCLUSION: The minocycline-containing regimens demonstrated good efficacy, safety, and compliance in H. pylori eradication. Minocycline has good potential to replace tetracycline for eradicating H. pylori infection.

Development and Evaluation of a Quantitative Systems Pharmacology Model for Mechanism Interpretation and Efficacy Prediction of Atezolizumab in Combination with Carboplatin and Nab-Paclitaxel in Patients with Non-Small-Cell Lung Cancer.

Immunotherapy has shown clinical benefit in patients with non-small-cell lung cancer (NSCLC). Due to the limited response of monotherapy, combining immune checkpoint inhibitors (ICIs) and chemotherapy is considered a treatment option for advanced NSCLC. However, the mechanism of combined therapy and the potential patient population that could benefit from combined therapy remain undetermined. Here, we developed an NSCLC model based on the published quantitative systems pharmacology (QSP)-immuno-oncology platform by making necessary adjustments. After calibration and validation, the established QSP model could adequately characterise the biological mechanisms of action of the triple combination of atezolizumab, nab-paclitaxel, and carboplatin in patients with NSCLC, and identify predictive biomarkers for precision dosing. The established model could efficiently characterise the objective response rate and duration of response of the IMpower131 trial, reproducing the efficacy of alternative dosing. Furthermore, CD8+ and CD4+ T cell densities in tumours were found to be significantly related to the response status. This significant extension of the QSP model not only broadens its applicability but also more accurately reflects real-world clinical settings. Importantly, it positions the model as a critical foundation for model-informed drug development and the customisation of treatment plans, especially in the context of combining single-agent ICIs with platinum-doublet chemotherapy.

General anesthesia with endotracheal intubation ensures the quick removal of magnetic foreign bodies: A case report.

BACKGROUND: The incidence of ingestion of magnetic foreign bodies in the gastrointestinal tract has been increasing year by year. Due to their strong magnetic attraction, if multiple gastrointestinal foreign bodies enter the small intestine, it can lead to serious complications such as intestinal perforation, necrosis, torsion, and bleeding. Severe cases require surgical intervention. CASE SUMMARY: We report a 6-year-old child who accidentally swallowed multiple magnetic balls. Under timely and safe anesthesia, the magnetic balls were quickly removed through gastroscopy before entering the small intestine. CONCLUSION: General anesthesia with endotracheal intubation can ensure full anesthesia under the condition of fasting for less than 6 h. In order to prevent magnetic foreign bodies from entering the small intestine, timely and effective measures must be taken to remove the foreign bodies.

Bioinformatics and Systems Biology Approach to Identify the Pathogenetic Link between Heart Failure and Sarcopenia. / Abordagem de Bioinformática e Biologia de Sistemas para Identificar a Ligação Patogenética entre Insuficiência Cardíaca e Sarcopenia.

Despite increasing evidence that patients with heart failure (HF) are susceptible to sarcopenia, the reason for the association is not well understood. The purpose of this study is to explore further the molecular mechanism of the occurrence of this complication. Gene expression datasets for HF (GSE57345) and Sarcopenia (GSE1428) were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using 'edgeR' and "limma" packages of R, and their functions were analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Protein-protein interaction (PPI) networks were constructed and visualized using Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape. Hub genes were selected using the plugin cytoHubba and validation with GSE76701 for HF and GSE136344 for Sarcopenia. The related pathways and molecular mechanisms of the hub genes were performed by Gene set enrichment analysis (GSEA). The statistical analyses were performed using R software. P < 0.05 was considered statistically significant. A total of 114 common DEGs were found. Pathways related to growth factor, Insulin secretion and cGMP-PKG were enriched in both HF and Sarcopenia. CYP27A1, KCNJ8, PIK3R5, TIMP2, CXCL12, KIT, and VCAM1 were found to be significant hub genes after validation, with GSEA emphasizing the importance of the hub genes in the regulation of the inflammatory response. Our study reveals that HF and Sarcopenia share common pathways and pathogenic mechanisms. These findings may suggest new directions for future research into the underlying pathogenesis.

Apesar das evidências crescentes de que pacientes com insuficiência cardíaca (IC) são suscetíveis à sarcopenia, o motivo da associação não é bem compreendido. O objetivo deste estudo é explorar ainda mais o mecanismo molecular de ocorrência desta complicação. Conjuntos de dados de expressão gênica para HF (GSE57345) e Sarcopenia (GSE1428) foram obtidos do banco de dados Gene Expression Omnibus (GEO). Genes diferencialmente expressos (DEGs) foram identificados usando pacotes 'edgeR' e "limma" de R, e suas funções foram analisadas usando Gene Ontology (GO) e a Enciclopédia de Genes e Genomas de Kyoto (KEGG). Redes de interação proteína-proteína (PPI) foram construídas e visualizadas usando Search Tool for the Retrieval of Interacting Genes (STRING) e Cytoscape. Os genes hub foram selecionados usando o plugin cytoHubba e validados com GSE76701 para IC e GSE136344 para Sarcopenia. As vias relacionadas e os mecanismos moleculares dos genes hub foram realizados pela análise de enriquecimento de genes (GSEA). As análises estatísticas foram realizadas no software R. P < 0,05 foi considerado estatisticamente significativo. Foram encontrados 114 DEGs comuns. As vias relacionadas ao fator de crescimento, secreção de insulina e cGMP-PKG estavam enriquecidas tanto na IC quanto na sarcopenia. Descobriu-se que CYP27A1, KCNJ8, PIK3R5, TIMP2, CXCL12, KIT e VCAM1 são genes hub significativos após validação com GSEA enfatizando a importância dos genes hub na regulação da resposta inflamatória. Nosso estudo revela que a IC e a Sarcopenia compartilham vias e mecanismos patogênicos comuns. Estes achados podem sugerir novas direções para pesquisas futuras sobre a patogênese subjacente.

Effect of large volume red blood cell apheresis on cardiovascular functions in healthy donors.

BACKGROUND: Requirements of blood transfusions rise rapidly in China. Improving the efficiency of blood donation could help maintaining sufficient blood supplement. We conducted a pilot research to investigate the reliability and safety of collecting more units of red blood cell by apheresis. METHODS: Thirty-two healthy male volunteers were randomized into two groups: red blood cell apheresis (RA) (n = 16) and whole blood (WB) donation (n = 16). RA group donated individualized RBC volumes by apheresis according to the volunteers' basal total blood volumes and haematocrit levels, WB group donated 400 mL whole blood. All volunteers were scheduled seven visit times in 8 weeks' study period. The cardiovascular functions were assessed by laboratory examinations, echocardiography and cardiopulmonary functional tests. All results were compared between groups at the same visit time and compared between visit 1(before donation) and other visit times within the same group. RESULTS: The average donated RBC volume in RA group and in WB group was 627.25 ± 109.74 mL and 175.28 ± 8.85 mL, respectively(p < 0.05); the RBC, haemoglobin and haematocrit levels changed significantly between times and between groups (p < 0.05). Cardiac biomarker levels such as NT-proBNP, hs-TnT and CK-MB did not change significantly between times or between groups (p > 0.05). The echocardiographic and cardiopulmonary results did not change significantly between times or between groups during the whole study period(p > 0.05). CONCLUSIONS: We provided an efficient and secure method for RBC apheresis. By harvesting more RBC volumes at one single-time, the cardiovascular functions did not change significantly compared with traditional whole blood donation.

Abordagem de Bioinformática e Biologia de Sistemas para Identificar a Ligação Patogenética entre Insuficiência Cardíaca e Sarcopenia / Bioinformatics and Systems Biology Approach to Identify the Pathogenetic Link between Heart Failure and Sarcopenia

Resumo Fundamento Apesar das evidências crescentes de que pacientes com insuficiência cardíaca (IC) são suscetíveis à sarcopenia, o motivo da associação não é bem compreendido. Objetivo O objetivo deste estudo é explorar ainda mais o mecanismo molecular de ocorrência desta complicação. Métodos Conjuntos de dados de expressão gênica para HF (GSE57345) e Sarcopenia (GSE1428) foram obtidos do banco de dados Gene Expression Omnibus (GEO). Genes diferencialmente expressos (DEGs) foram identificados usando pacotes 'edgeR' e "limma" de R, e suas funções foram analisadas usando Gene Ontology (GO) e a Enciclopédia de Genes e Genomas de Kyoto (KEGG). Redes de interação proteína-proteína (PPI) foram construídas e visualizadas usando Search Tool for the Retrieval of Interacting Genes (STRING) e Cytoscape. Os genes hub foram selecionados usando o plugin cytoHubba e validados com GSE76701 para IC e GSE136344 para Sarcopenia. As vias relacionadas e os mecanismos moleculares dos genes hub foram realizados pela análise de enriquecimento de genes (GSEA). As análises estatísticas foram realizadas no software R. P < 0,05 foi considerado estatisticamente significativo. Resultados Foram encontrados 114 DEGs comuns. As vias relacionadas ao fator de crescimento, secreção de insulina e cGMP-PKG estavam enriquecidas tanto na IC quanto na sarcopenia. Descobriu-se que CYP27A1, KCNJ8, PIK3R5, TIMP2, CXCL12, KIT e VCAM1 são genes hub significativos após validação com GSEA enfatizando a importância dos genes hub na regulação da resposta inflamatória. Conclusão Nosso estudo revela que a IC e a Sarcopenia compartilham vias e mecanismos patogênicos comuns. Estes achados podem sugerir novas direções para pesquisas futuras sobre a patogênese subjacente.

Abstract Background Despite increasing evidence that patients with heart failure (HF) are susceptible to sarcopenia, the reason for the association is not well understood. Objective The purpose of this study is to explore further the molecular mechanism of the occurrence of this complication. Methods Gene expression datasets for HF (GSE57345) and Sarcopenia (GSE1428) were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using 'edgeR' and "limma" packages of R, and their functions were analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Protein-protein interaction (PPI) networks were constructed and visualized using Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape. Hub genes were selected using the plugin cytoHubba and validation with GSE76701 for HF and GSE136344 for Sarcopenia. The related pathways and molecular mechanisms of the hub genes were performed by Gene set enrichment analysis (GSEA). The statistical analyses were performed using R software. P < 0.05 was considered statistically significant. Results A total of 114 common DEGs were found. Pathways related to growth factor, Insulin secretion and cGMP-PKG were enriched in both HF and Sarcopenia. CYP27A1, KCNJ8, PIK3R5, TIMP2, CXCL12, KIT, and VCAM1 were found to be significant hub genes after validation, with GSEA emphasizing the importance of the hub genes in the regulation of the inflammatory response. Conclusion Our study reveals that HF and Sarcopenia share common pathways and pathogenic mechanisms. These findings may suggest new directions for future research into the underlying pathogenesis.

Circulating miRNA-1-3p as Biomarker of Accelerated Sarcopenia in Patients Diagnosed with Chronic Heart Failure.

Background: While sarcopenia is an important clinical finding in individuals diagnosed with chronic heart failure (CHF), efforts to identify a reliable biomarker capable of predicting the overall muscular and functional decline in CHF patients have been unsuccessful to date. Objectives: The objectives of this study were to study the diagnostic utility of MicroRNA (miRNA)-1-3p as a predictor of sarcopenia status in individuals diagnosed with CHF. Methods: In total, 80 individuals with heart failure exhibiting a left ventricular ejection fraction < 50% were enrolled in this study. All patients were analyzed to assess miR-1-3p expression levels, with body composition being evaluated through dual-energy X-ray absorptiometry and sarcopenia being defined based on the sum of appendicular lean muscle mass (ALM) divided by height in meters squared and handgrip strength (HGS). In addition, the activation of the Akt/mTOR signaling pathway was evaluated in these individuals. Results: In total, 40 of the enrolled patients (50%) exhibited sarcopenia. Sarcopenic patients presented with increased miR-1-3p expression levels as compared to non-sarcopenic individuals (1.69 ± 0.132 vs. 1.22 ± 0.106; p < 0.05). With respect to sarcopenic indices, appendicular skeletal mass index was most strongly correlated with miR-1-3p expression, which was also strongly correlated with HGS. High levels of Akt/mTOR signaling pathway components were expressed in sarcopenic individuals, highlighting a significant relationship between miR-1-3p activity and signaling through this pathway. Moreover, miR-1-3p was identified as a specific marker for sarcopenia in individuals with CHF. Conclusions: These results suggest that circulating miR-1-3p levels are related to Akt/mTOR pathway activation and can offer valuable insight into the overall physical capacity and muscular integrity of CHF patients as a predictor of sarcopenia. (Rev Invest Clin. 2022;74(5):276-83).

Circulating miRNA-1-3p as Biomarker of Accelerated Sarcopenia in Patients Diagnosed with Chronic Heart Failure

ABSTRACT Background: While sarcopenia is an important clinical finding in individuals diagnosed with chronic heart failure (CHF), efforts to identify a reliable biomarker capable of predicting the overall muscular and functional decline in CHF patients have been unsuccessful to date. Objectives: The objectives of this study were to study the diagnostic utility of MicroRNA (miRNA)-1-3p as a predictor of sarcopenia status in individuals diagnosed with CHF. Methods: In total, 80 individuals with heart failure exhibiting a left ventricular ejection fraction < 50% were enrolled in this study. All patients were analyzed to assess miR-1-3p expression levels, with body composition being evaluated through dual-energy X-ray absorptiometry and sarcopenia being defined based on the sum of appendicular lean muscle mass (ALM) divided by height in meters squared and handgrip strength (HGS). In addition, the activation of the Akt/mTOR signaling pathway was evaluated in these individuals. Results: In total, 40 of the enrolled patients (50%) exhibited sarcopenia. Sarcopenic patients presented with increased miR-1-3p expression levels as compared to non-sarcopenic individuals (1.69 ± 0.132 vs. 1.22 ± 0.106; p < 0.05). With respect to sarcopenic indices, appendicular skeletal mass index was most strongly correlated with miR-1-3p expression, which was also strongly correlated with HGS. High levels of Akt/mTOR signaling pathway components were expressed in sarcopenic individuals, highlighting a significant relationship between miR-1-3p activity and signaling through this pathway. Moreover, miR-1-3p was identified as a specific marker for sarcopenia in individuals with CHF. Conclusion: These results suggest that circulating miR-1-3p levels are related to Akt/mTOR pathway activation and can offer valuable insight into the overall physical capacity and muscular integrity of CHF patients as a predictor of sarcopenia.

Self-assembled liquid crystal architectures for soft matter photonics.

Self-assembled architectures of soft matter have fascinated scientists for centuries due to their unique physical properties originated from controllable orientational and/or positional orders, and diverse optic and photonic applications. If one could know how to design, fabricate, and manipulate these optical microstructures in soft matter systems, such as liquid crystals (LCs), that would open new opportunities in both scientific research and practical applications, such as the interaction between light and soft matter, the intrinsic assembly of the topological patterns, and the multidimensional control of the light (polarization, phase, spatial distribution, propagation direction). Here, we summarize recent progresses in self-assembled optical architectures in typical thermotropic LCs and bio-based lyotropic LCs. After briefly introducing the basic definitions and properties of the materials, we present the manipulation schemes of various LC microstructures, especially the topological and topographic configurations. This work further illustrates external-stimuli-enabled dynamic controllability of self-assembled optical structures of these soft materials, and demonstrates several emerging applications. Lastly, we discuss the challenges and opportunities of these materials towards soft matter photonics, and envision future perspectives in this field.

Association of admission hyperglycemia and all-cause mortality in acute myocardial infarction with percutaneous coronary intervention: A dose-response meta-analysis.

Objective: The aim of this study is to evaluate the associations between admission hyperglycemia and the risk of all-cause mortality in patients with acute myocardial infarction (AMI) with or without diabetes, to find optimal admission glucose intervention cut-offs, and to clarify the shape of the dose-response relations. Methods: Medline/PubMed and EMBASE were searched from inception to 1 April 2022. Cohort studies reporting estimates of all-cause mortality risk in patients with admission hyperglycemia with AMI were included. The outcomes of interest include mortality and major adverse cardiac events (MACEs). A random effect dose-response meta-analysis was conducted to access linear trend estimations. A one-stage linear mixed effect meta-analysis was used for estimating dose-response curves. Relative risks and 95% confidence intervals were pooled using a random-effects model. Results: Of 1,222 studies screened, 47 full texts were fully reviewed for eligibility. The final analyses consisted of 23 cohort studies with 47,177 participants. In short-term follow-up, admission hyperglycemia was associated with an increased risk of all-cause mortality (relative risk: 3.12, 95% confidence interval 2.42-4.02) and MACEs (2.34, 1.77-3.09). In long-term follow-up, admission hyperglycemia was associated with an increased risk of all-cause mortality (1.97, 1.61-2.41) and MACEs (1.95, 1.21-3.14). A linear dose-response association was found between admission hyperglycemia and the risk of all-cause mortality in patients with or without diabetes. Conclusion: Admission hyperglycemia was significantly associated with higher all-cause mortality risk and rates of MACEs. However, the association between admission hyperglycemia and long-term mortality risk needs to be determined with caution. Compared with current guidelines recommendations, a lower intervention cut-off and more stringent targets for admission hyperglycemia may be appropriate. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022317280], identifier [CRD42022317280].

Nano-silica particles synergistically IgE-mediated mast cell activation exacerbating allergic inflammation in mice.

Background: Allergic respiratory diseases have increased dramatically due to air pollution over the past few decades. However, studies are limited on the effects of inorganic components and particulate matter with different particle sizes in smog on allergic diseases, and the possible molecular mechanism of inducing allergies has not been thoroughly studied. Methods: Four common mineral elements with different particle sizes in smog particles were selected, including Al2O3, TiO2, Fe2O3, and SiO2. We studied the relationship and molecular mechanism of smog particle composition, particle size, and allergic reactions using mast cells, immunoglobulin E (IgE)-mediated passive cutaneous anaphylaxis (PCA) model, and an ovalbumin (OVA)-induced asthmatic mouse model in vitro and in vivo, combined with transmission electron microscopy, scanning transmission X-ray microscopy analysis, and transcriptome sequencing. Results: Only 20 nm SiO2 particles significantly increased ß-hexosaminidase release, based on dinitrophenol (DNP)-human serum albumin (HSA) stimulation, from IgE-sensitized mast cells, while other particles did not. Meanwhile, the PCA model showed that Evan's blue extravasation in mice was increased after treatment with nano-SiO2 particles. Nano-SiO2 particles exposure in the asthmatic mouse model caused an enhancement of allergic airway inflammation as manifested by OVA-specific serum IgE, airway hyperresponsiveness, lung inflammation injury, mucous cell metaplasia, cytokine expression, mast cell activation, and histamine secretion, which were significantly increased. Nano-SiO2 particles exposure did not affect the expression of FcϵRI or the ability of mast cells to bind IgE but synergistically activated mast cells by enhancing the mitogen-activated protein kinase (MAPK) signaling pathway, especially the phosphorylation levels of the extracellular signal-regulated kinase (ERK)1/2. The ERK inhibitors showed a significant inhibitory effect in reducing ß-hexosaminidase release. Conclusion: Our results indicated that nano-SiO2 particles stimulation might synergistically activate IgE-sensitized mast cells by enhancing the MAPK signaling pathway and that nano-SiO2 particles exposure could exacerbate allergic inflammation. Our experimental results provide useful information for preventing and treating allergic diseases.

Quantum interference and domain-wall-like magnetic correlations in hexagonal graphene nanodisks.

Quantum interference and traditional domain wall effects are two common ways to manipulate the magnetism in magnetic materials. Here, we report both effects emerge in the designed graphene nanodisks simultaneously, and thus providing an accessible way to engineer the magnetism in graphene nanostructures. By adjusting the length of the armchair edges at the corners of hexagonal disk, connecting the adjacent zigzag edges, we show that the quantum interference among the zigzag edges remains robust and consequently determines the magnetic structure in the small-size systems, in analogy with the nanoribbons. More importantly, a domain-wall-like magnetic mechanism is numerically identified to dominate the larger-size disks. In particular, a magnetic state with fully spin-polarized edges achieved in a wide parameter region promises the future applications for spintronics.

Programmable self-propelling actuators enabled by a dynamic helical medium.

Rotation-translation conversion is a popular way to achieve power transmission in machinery, but it is rarely selected by nature. One unique case is that of bacteria swimming, which is based on the collective reorganization and rotation of flagella. Here, we mimic such motion using the light-driven evolution of a self-organized periodic arch pattern. The range and direction of translation are altered by separately varying the alignment period and the stimulating photon energy. Programmable self-propelling actuators are realized via a specific molecular assembly within a photoresponsive cholesteric medium. Through rationally presetting alignments, parallel transports of microspheres in customized trajectories are demonstrated, including convergence, divergence, gathering, and orbital revolution. This work extends the understanding of the rotation-translation conversion performed in an exquisitely self-organized system and may inspire future designs for functional materials and intelligent robotics.

Strontium ions protect hearts against myocardial ischemia/reperfusion injury.

Timely restoration of blood supply following myocardial infarction is critical to save the infarcted myocardium, while reperfusion would cause additional damage. Strontium ions have been shown to promote angiogenesis, but it is unknown whether they can save the damaged myocardium. We report that myocardial ischemia/reperfusion (I/R)-induced functional deterioration and scar formation were notably attenuated by injection of strontium ion-containing composite hydrogels into murine infarcted myocardium at 20 minutes of reperfusion following 60 minutes of ischemia. These beneficial effects were accompanied by reduced cardiomyocyte apoptosis and increased angiogenesis. The effects of strontium ions were further confirmed by the enhanced viability of cardiomyocytes and stimulated angiogenesis in vitro. These findings are the first to reveal the cardioprotective effects of strontium ions against I/R injury, which may provide a new therapeutic approach to ischemic heart disease at a lower cost, with higher stability, and with potentially greater safety.

Structural insights into targeting of the colchicine binding site by ELR510444 and parbendazole to achieve rational drug design.

Microtubules consisting of α- and ß-tubulin heterodimers have proven to be an efficient drug target for cancer therapy. A broad range of agents, including ELR510444 and parbendazole, can bind to tubulin and interfere with microtubule assembly. ELR510444 and parbendazole are colchicine binding site inhibitors with antiproliferative activities. However, the lack of structural information on the tubulin-ELR510444/parbendazole complex has hindered the design and development of more potent drugs with similar scaffolds. Therefore, we report the crystal structures of tubulin complexed with ELR510444 at a resolution of 3.1 Å and with parbendazole at 2.4 Å. The structure of these complexes revealed the intermolecular interactions between the two colchicine binding site inhibitors and tubulin, thus providing a rationale for the development of novel benzsulfamide and benzimidazole derivatives targeting the colchicine binding site.

Comorbidity Patterns of Older Lung Cancer Patients in Northeast China: An Association Rules Analysis Based on Electronic Medical Records.

PURPOSES: This study aims to identify the comorbidity patterns of older men with lung cancer in China. METHODS: We analyzed the electronic medical records (EMRs) of lung cancer patients over age 65 in the Jilin Province of China. The data studied were obtained from 20 hospitals of Jilin Province in 2018. In total, 1510 patients were identified. We conducted a rank-frequency analysis and social network analysis to identify the predominant comorbidities and comorbidity networks. We applied the association rules to mine the comorbidity combination with the values of confidence and lift. A heatmap was utilized to visualize the rules. RESULTS: Our analyses discovered that (1) there were 31 additional medical conditions in older patients with lung cancer. The most frequent comorbidities were pneumonia, cerebral infarction, and hypertension. (2) The network-based analysis revealed seven subnetworks. (3) The association rules analysis provided 41 interesting rules. The results revealed that hypertension, ischemic cardiomyopathy, and pneumonia are the most frequent comorbid combinations. Heart failure may not have a strong implicating role in these comorbidity patterns. Cerebral infarction was rarely combined with other diseases. In addition, glycoprotein metabolism disorder comorbid with hyponatremia or hypokalemia increased the risk of anemia by more than eight times in older lung cancer patients. CONCLUSIONS: This study provides evidence on the comorbidity patterns of older men with lung cancer in China. Understanding the comorbidity patterns of older patients with lung cancer can assist clinicians in their diagnoses and contribute to developing healthcare policies, as well as allocating resources.

Comorbidity in Older Patients Hospitalized with Cancer in Northeast China based on Hospital Discharge Data.

Patients with cancer often carry the dual burden of the cancer itself and other co-existing medical conditions. The problems associated with comorbidities among elderly cancer patients are more prominent compared with younger patients. This study aimed to identify common cancer-related comorbidities in elderly patients through routinely collected hospital discharge data and to use association rules to analyze the prevalence and patterns of these comorbidities in elderly cancer patients at different cancer sites. We collected the discharge data of 80,574 patients who were diagnosed with cancers of the esophagus, stomach, colorectum, liver, lung, female breast, cervix, and thyroid between 2016 and 2018. The same number of non-cancer patients were randomly selected as the control group and matched with the case group by age and gender. The results showed that cardiovascular diseases, metabolic diseases, digestive diseases, and anemia were the most common comorbidities in elderly patients with cancer. The comorbidity patterns differed based on the cancer site. Elderly patients with liver cancer had the highest risk of comorbidities, followed by lung cancer, gastrointestinal cancer, thyroid cancer, and reproductive cancer. For example, elderly patients with liver cancer had the higher risk of the comorbid infectious and digestive diseases, whereas patients with lung cancer had the higher risk of the comorbid respiratory system diseases. The findings can assist clinicians in diagnosing comorbidities and contribute to the allocation of medical resources.

On-orbit radiometric calibration of the optical sensors on-board SuperView-1 satellite using three independent methods.

On-orbit radiometric calibration of the optical sensors on-board SuperView-1 satellites is the foundation for further quantitative applications. A field calibration campaign was orchestrated to radiometrically calibrate the SuperView-1 optical sensors at the Baotou calibration site in China during September 2018. Based on the collected datasets, three independent methods (reflectance-based, radiance-based, and cross-calibration) were used to determine the radiometric calibration coefficients of the SuperView-1 optical sensors with multiple permanent artificial calibration targets. Comparisons of the desert top-of-atmosphere radiance calculated based on the coefficients determined with independent methods were analyzed. Comparison results show that the minimum and maximum relative differences of the radiometrically-calibrated desert TOA radiance between the reflectance-based and radiance-based methods are 1.26% and 4.23% for SV0102 and SV0104, respectively. While, the minimum and maximum relative differences of the radiometrically-calibrated desert TOA radiance between the reflectance-based and radiance-based methods are 0.82% and 6.83% for SV0101 and SV0103, respectively. The reasonably good agreement of the radiometrically calibrated coefficients of the SuperView-1 on-board sensors between these independent methods is encouraging. An uncertainty analysis was also discussed, and the results suggest that the overall uncertainties of the predicted TOA radiance are less than 4.5%, 4.0%, and 5.15% for the reflectance-based, radiance-based, and cross-calibration methods, respectively.

Association of vitamin D status with coronary artery disease in postmenopausal women.

The relationship between coronary artery disease (CAD) and low serum 25-hydroxyvitamin D (25(OH)D) levels has emerged. Postmenopausal (PM) women are at increased risk of CAD and vitamin D (VitD) deficiency.To investigate the relationship between CAD and VitD levels in PM women.This case-control study included 93 consecutive female patients aged 50 to 79 years old undergoing coronary angiography for evaluation of CAD and 119 age-matched controls. Serum 25(OH)D concentrations were classed as adequate (serum 25(OH)D: ≥20 ng/mL); insufficient (serum 25(OH)D: 10 to <20 ng/mL); and deficient (serum 25(OH)D: <10 ng/mL). Major cardiovascular risk factors were also explored.CAD occurred in 67/127 (52.8%) patients with VitD deficiency; 21/66 (31.8%) patients that were VitD insufficient; and in 5/19 (26.3%) patients with adequate VitD levels. Multivariate regression analysis suggested that a deficiency of VitD increased CAD (odds ratio = 2.891; 95% confidence interval = 1.459-7.139, P < .001).VitD deficiency should be evaluated in PM women as a possible cause of CAD.