Changes in PM2.5-related diabetes risk under the implementation of the clean air act in Shanghai.

OBJECTIVES: We examined the associations between PM2.5 exposure and Type 2 diabetes mellitus risk under the implementation of the Clean Air Act (CAA) among high-risk population for diabetes in Shanghai. METHODS: A total of 10,499 subjects from the Shanghai High-Risk Diabetic Screen (SHiDS) project between 2002 and 2018, linked with remotely sensed PM2.5 concentrations, were enrolled in this study. Ordinary least squares and logistic regression were applied to explore associations between PM2.5 and diabetes risk in various exposure periods. RESULTS: In year 2002-2013 (before CAA), the diabetes risk increased 7.5 % (95 % CI: 1.018-1.137), 8.0 % (95 % CI: 1.022-1.142) and 7.9 % (95 % CI: 1.021-1.141) under each 10 µg/m3 increase of long-term (1, 2 and 3 years) PM2.5 exposure, respectively. Elevated PM2.5 exposure were also associated with a significant increase in glycemic parameters before CAA implementation. However, in the year 2014-2018 (after CAA), the associations between PM2.5 exposure and diabetes risk were not significant after controlling for potential confounders. CONCLUSION: Our findings suggest that long-term and high-level exposure to PM2.5 was associated with increased prevalence of diabetes. Moreover, the implementation of CAA might ameliorate PM2.5-related diabetes risk.

Phase 1 study of safety and preliminary efficacy of intranasal transplantation of human neural stem cells (ANGE-S003) in Parkinson's disease.

BACKGROUND: Intranasal transplantation of ANGE-S003 human neural stem cells showed therapeutic effects and were safe in preclinical models of Parkinson's disease (PD). We investigated the safety and tolerability of this treatment in patients with PD and whether these effects would be apparent in a clinical trial. METHODS: This was a 12-month, single-centre, open-label, dose-escalation phase 1 study of 18 patients with advanced PD assigned to four-time intranasal transplantation of 1 of 3 doses: 1.5 million, 5 million or 15 million of ANGE-S003 human neural stem cells to evaluate their safety and efficacy. RESULTS: 7 patients experienced a total of 14 adverse events in the 12 months of follow-up after treatment. There were no serious adverse events related to ANGE-S003. Safety testing disclosed no safety concerns. Brain MRI revealed no mass formation. In 16 patients who had 12-month Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) data, significant improvement of MDS-UPDRS total score was observed at all time points (p<0.001), starting with month 3 and sustained till month 12. The most substantial improvement was seen at month 6 with a mean reduction of 19.9 points (95% CI, 9.6 to 30.3; p<0.001). There was no association between improvement in clinical outcome measures and cell dose levels. CONCLUSIONS: Treatment with ANGE-S003 is feasible, generally safe and well tolerated, associated with functional improvement in clinical outcomes with peak efficacy achieved at month 6. Intranasal transplantation of neural stem cells represents a new avenue for the treatment of PD, and a larger, longer-term, randomised, controlled phase 2 trial is warranted for further investigation.

TRIM25 promotes glioblastoma cell growth and invasion via regulation of the PRMT1/c-MYC pathway by targeting the splicing factor NONO.

BACKGROUND: Ubiquitination plays an important role in proliferating and invasive characteristic of glioblastoma (GBM), similar to many other cancers. Tripartite motif 25 (TRIM25) is a member of the TRIM family of proteins, which are involved in tumorigenesis through substrate ubiquitination. METHODS: Difference in TRIM25 expression levels between nonneoplastic brain tissue samples and primary glioma samples was demonstrated using publicly available glioblastoma database, immunohistochemistry, and western blotting. TRIM25 knockdown GBM cell lines (LN229 and U251) and patient derived GBM stem-like cells (GSCs) GBM#021 were used to investigate the function of TRIM25 in vivo and in vitro. Co-immunoprecipitation (Co-IP) and mass spectrometry analysis were performed to identify NONO as a protein that interacts with TRIM25. The molecular mechanisms underlying the promotion of GBM development by TRIM25 through NONO were investigated by RNA-seq and validated by qRT-PCR and western blotting. RESULTS: We observed upregulation of TRIM25 in GBM, correlating with enhanced glioblastoma cell growth and invasion, both in vitro and in vivo. Subsequently, we screened a panel of proteins interacting with TRIM25; mass spectrometry and co-immunoprecipitation revealed that NONO was a potential substrate of TRIM25. TRIM25 knockdown reduced the K63-linked ubiquitination of NONO, thereby suppressing the splicing function of NONO. Dysfunctional NONO resulted in the retention of the second intron in the pre-mRNA of PRMT1, inhibiting the activation of the PRMT1/c-MYC pathway. CONCLUSIONS: Our study demonstrates that TRIM25 promotes glioblastoma cell growth and invasion by regulating the PRMT1/c-MYC pathway through mediation of the splicing factor NONO. Targeting the E3 ligase activity of TRIM25 or the complex interactions between TRIM25 and NONO may prove beneficial in the treatment of GBM.

Safety of selinexor as the only exportin 1 (XPO1) inhibitor so far: a post-marketing study based on the world Health Organization pharmacovigilance database (Vigibase).

BACKGROUND: Exportin 1 (XPO1) inhibitors are being developed as a new agent for anti-cancer therapies. This study aimed to broadly portray the adverse event (AE) profile of selinexor, an XPO1 inhibitor, in actual clinical practice. RESEARCH DESIGN AND METHODS: Disproportionality analyses were conducted by calculating the information component and reporting odds ratio in VigiBase over different reporting periods. All selinexor-related AEs were classified by system organ class (SOC) and preferred term (PT) according to the Medical Dictionary for Regulatory Activities. RESULTS: A total of 116,443 AEs were identified in 2,608 patients that received selinexor. Patients with cardiac disorders had a higher propensity for death. Thirteen SOCs and 125 PTs were identified as having a potential connection with selinexor. Notably, 29 suspected signals detected in our study were defined as significant AEs by the European Medicines Agency, including febrile neutropenia, pancytopenia, and acute kidney injury. Attention should be paid to these AEs, despite most toxicities being manageable and reversible. CONCLUSIONS: This study highlights a number of AEs associated with selinexor. Most toxicities are reversible but require careful management. The benefit of selinexor still outweighs the potential risks, indicating XPO1 inhibitors as promising agents.

In-hospital mortality and length of hospital stay in infants requiring tracheostomy with bronchopulmonary dysplasia.

PURPOSE: To investigate in-hospital mortality and hospital length of stay (LOS) in infants requiring tracheostomy with bronchopulmonary dysplasia (BPD). METHODS: We explored the correlation between tracheostomy with in-hospital mortality and LOS in infant patients hospitalized with BPD, using the data from Nationwide Inpatient Sample between 2008 and 2017 in the United States. In-hospital mortality and LOS was compared in patients who underwent tracheostomy with those patients who did not after propensity-score matching. RESULTS: A total of 10,262 children ≤2 years old hospitalized with BPD, 847 (8%) underwent tracheostomy, and 821 patients underwent tracheostomy were matched with 1602 patients without tracheostomy. Tracheostomy group was correlated with higher in-hospital mortality(OR(95%CI):2.98(2.25-3.95)) and prolonged LOS(absolute difference(95%CI):97.0(85.6-108.4)). CONCLUSIONS: Tracheostomy was correlated with increased in-hospital mortality and prolonged LOS. Such information may contribute to better decision-making process between clinicians and parents regarding tracheostomy to manage parent expectations, as well as better interdisciplinary teamwork.

Characterization of dynamical changes in vital signs during allogeneic human umbilical cord-derived mesenchymal stem cells infusion.

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs), a kind of adult stem cell, were studied for clinical applications in regenerative medicine. To date, the safety evaluations of intravenous infusion of allogeneic hUC-MSCs were focused on fever, infection, malignancy, and death. However, the characteristics of dynamical changes in vital signs during hUC-MSCs infusion are largely unknown. In this study, twenty participants with allogeneic hUC-MSCs transplanted (MSC group) and twenty sex- and age-matched individuals with cardiovascular disease who treated with the equal volume of 0.9% normal saline were recruited (NS group). Heart rate, respiratory rate, oxygen saturation, systolic and diastolic blood pressure, and temperature were monitored at intervals of 15 min during infusion. Adverse events were recorded during infusion and within seven days after infusion. No adverse events were observed during and after infusion in both groups. Compared with the baseline, the mean systolic blood pressure (SBP) levels were significantly decreased at 15 min, 30 min, 45 min and 60 min in the MSC group (all P < 0.05) during infusion. In addition, SBP changed significantly from baseline during hUC-MSCs infusion when compared with that of NS group (P < 0.05). Repeated measures analysis of variance confirmed difference over time on the SBP levels (P < 0.05). Our results showed that the process of allogeneic hUC-MSCs intravenous infusion was safe and the vital signs were stable, whereas a slight decrease in SBP was observed.

The role of nanotechnology-based approaches for clinical infectious diseases and public health.

Given the high incidence of infection and the growing resistance of bacterial and viral infections to the traditional antiseptic, the need for novel antiseptics is critical. Therefore, novel approaches are urgently required to reduce the activity of bacterial and viral infections. Nanotechnology is increasingly being exploited for medical purposes and is of significant interest in eliminating or limiting the activity of various pathogens. Due to the increased surface-to-volume ratio of a given mass of particles, the antimicrobial properties of some naturally occurring antibacterial materials, such as zinc and silver, increase as particle size decreases into the nanometer regime. However, the physical structure of a nanoparticle and the way it interacts with and penetrates the bacteria also appear to provide unique bactericidal mechanisms. To measure the efficacy of nanoparticles (diameter 100 nm) as antimicrobial agents, it is necessary to comprehend the range of approaches for evaluating the viability of bacteria; each of them has its advantages and disadvantages. The nanotechnology-based disinfectants and sensors for SARS-CoV-2 provide a roadmap for creating more effective sensors and disinfectants for detecting and preventing coronaviruses and other infections. Moreover, there is an increasing role of nanotechnology-based approaches in various infections, including wound healing and related infection, nosocomial infections, and various bacterial infections. To meet the demand for patient care, nanotechnology-based disinfectants need to be further advanced with optimum approaches. Herein, we review the current burden of infectious diseases with a focus on SARS-CoV-2 and bacterial infection that significantly burdens developed healthcare systems and small healthcare communities. We then highlight how nanotechnology could aid in improving existing treatment modalities and diagnosis of those infectious agents. Finally, we conclude the current development and future perspective of nanotechnology for combating infectious diseases. The overall goal is to update healthcare providers on the existing role and future of nanotechnology in tackling those common infectious diseases.

Temporal trend and factors associated with post-endoscopic retrograde cholangiopancreatography pancreatitis in children in the USA: a nationwide, retrospective cohort study.

Pancreatitis is the most common adverse event following endoscopic retrograde cholangiopancreatography (ERCP). Meanwhile, the national temporal trend of post-ERCP pancreatitis (PEP) in children remains to be reported. The purpose of this study is to investigate the temporal trend and factors associated with PEP in children. We conducted a nationwide study using data from the National Inpatient Sample database during 2008-2017 and included all patients aged ≤ 18 years who underwent ERCP. The primary outcomes were temporal trends and factors associated with PEP. The secondary outcomes were in-hospital mortality, total charges (TC), and total length of stay (LOS). A total of 45,268 hospitalized pediatric patients who underwent ERCP were analyzed; of whom, 2043 (4.5%) were diagnosed with PEP. The prevalence of PEP decreased from 5.0% in 2008 to 4.6% in 2017 (P = 0.0002). In multivariable logistic analysis, adjusted risk factors of PEP were hospitals located in the West (aOR 2.09, 95% CI 1.36-3.20; P < .0001), bile duct stent insertion (aOR 1.49, 95% CI, 1.08-2.05; P = 0.0040), and end-stage renal disease (aOR 8.05, 95% CI 1.66-39.16; P = 0.0098). Adjusted protective factors of PEP were increasing age (aOR 0.95, 95% CI 0.92-0.98; P = 0.0014) and hospitals located in the South (aOR 0.53, 95% CI 0.30-0.94; P < .0001). In-hospital mortality, TC, and LOS were higher in patients with PEP than those without PEP. CONCLUSION: This study shows a decreasing national trend over time and identifies multiple protective and risk factors for pediatric PEP. Endoscopists can use the insights from this study to evaluate relevant factors before performing ERCP in children to prevent PEP and reduce the medical-care burden. WHAT IS KNOWN: • Although ERCP has become indispensable procedure in children as they are in adults, education and training programs for ERCP in children are underdeveloped in many countries. • PEP is the most common and most serious adverse event following ERCP. Research on PEP in adults showed rising hospital admission and mortality rates associated with PEP in the USA. WHAT IS NEW: • The national temporal trend of PEP among pediatric patients in the USA was decreasing from 2008 to 2017. • Older age was a protective factor for PEP in children, while end-stage renal disease and stent insertion into the bile duct were risk factors.

Updated insights on cardiac risks of CD19-directed chimeric antigen receptor T-cell therapy: a pharmacovigilance study.

Aim: Comprehensively characterize the cardiotoxicity of CD19-directed chimeric antigen receptor T-cell (CAR-T) products. Materials & methods: Data between 2017 and 2021 in the US FDA's Adverse Event Reporting System database were utilized. Disproportionality was measured using reporting odds ratio and information component. Hierarchical clustering analysis was performed to explore the relationships among cardiac events. Results: Tisagenlecleucel exhibited the highest percentage of death (53.24%) and life-threatening (13.39%) outcomes. Axicabtagene ciloleucel and tisagenlecleucel were equal in the number of positive signals (n = 15), while the former had excessive reporting of several cardiac events versus the latter, such as atrial fibrillation, cardiomyopathy, cardiorenal syndrome and sinus bradycardia. Conclusion: Several cardiac risks should be considered for CAR-T treatment and these events might vary in frequency and severity following different CAR-T agents.

Chimeric antigen receptor T-cell (CAR-T) therapy is effective in a wide spectrum of malignancies. However, the complete cardiotoxicity profile associated with this new treatment has not been characterized. This study systematically analyzed the reported cardiac events of four approved CAR-T agents using the US FDA's Adverse Event Reporting System database. It indicated that the type of cardiac events was broad and overlapped a lot with cytokine release syndrome. Pre-therapy assessment, intensive monitoring and appropriate intervention were critical to reduce the level of cardiac damage or the rate of mortality in patients receiving CAR-T.

Combining of immunotherapeutic approaches with chemotherapy for treatment of gastric cancer: Achievements and limitations.

Evidence reveals that gastric cancer (GC) is the fifth most common malignancy in humans, and about 770,000 people die from this cancer yearly. It has been reported that new cases and deaths from GC are more common in men than women. Therapeutic approaches, such as surgery, chemotherapy, and radiotherapy, have been common for treating GC. Nevertheless, due to the complications and limitations of these methods, researchers use novel approaches, such as immunotherapeutic or target therapies, to evaluate the effectiveness of treatment in patients with metastatic GC. Studies have shown that monotherapy is usually associated with unpromising outcomes, and combination therapy can be a more practical option for treating metastatic GC. Therefore, to clarify different aspects of chemotherapy and immunotherapy in patients with metastatic GC, this review discussed the achievements and challenges of combining immunotherapeutic methods with chemotherapeutic agents.

Association between tea consumption and glucose metabolism and insulin secretion in the Shanghai High-risk Diabetic Screen (SHiDS) study.

INTRODUCTION: The relationship between tea consumption and glucose metabolism remains controversial. This study investigated the associations of tea consumption with impaired glucose regulation, insulin secretion and sensitivity in Shanghai High-risk Diabetic Screen project. RESEARCH DESIGN AND METHODS: A total of 2337 Chinese subjects were enrolled in the study from 2014 to 2019. Each participant conducted a 75 g oral glucose tolerance test (OGTT) with five-point glucose and insulin level examined. They also completed a nurse-administered standard questionnaire including tea, coffee, and alcohol consumption, smoking habit, physical activity, education, sleep quality, etc. RESULTS: The result showed that tea consumption was positively associated with plasma glucose levels during OGTT after adjusting for confounder (Ps <0.05) and was associated with worsening glucose tolerance (OR 1.21, 95% CI 1.01-1.44; p=0.034). Strong tea consumption or long-term tea intake (>10 years) had an increased risk of glucose intolerance (all p<0.05). These associations did not vary in participants drinking green tea. In addition, insulin secretion indexes were decreased 7.0%-13.0% in tea consumption group. Logistic regression analysis showed that tea consumption was independently associated with lower insulin secretion (homeostasis model assessment of ß-cell function (HOMA-ß) (OR 0.81, 95% CI 0.68-0.97; p=0.021); Stumvoll first-phase index (OR 0.81, 95% CI 0.68-0.97; p=0.020)) in a fully adjusted model. Green tea consumption showed a negative association with insulin secretion (HOMA-ß (OR 0.77, 95% CI 0.62-0.96; p=0.019)). CONCLUSIONS: Tea intake is associated with an increased risk of glucose intolerance in a large high-risk diabetic Chinese population. Habitual tea consumption subjects might have lower pancreatic ß-cell function.

Screening for α-glucosidase inhibitors from Selaginella uncinata based on the ligand fishing combined with ultra-high-performance liquid chromatography-quadrupole time-of-flight-tandem mass spectrometry.

Biflavonoids are naturally occurring compounds consisting of two flavonoid moieties that have received substantial attention from researchers. Although many kinds of biflavonoids are typically distributed in Selaginella uncinata with hypoglycemic effect, their anti-α-glucosidase activities are not yet clear. In this study, a ligand fishing strategy for fast screening of α-glucosidase inhibitors from S. uncinata was proposed. α-Glucosidase was first immobilized on Fe3 O4 magnetic nanoparticles (MNPs) and then the α-glucosidase-functionalized MNPs were incubated with crude extracts of S. uncinata to fish out the ligands. Furthermore, considering the similarity and easy confusion of the structures of biflavonoids, the fragmentation patterns of different types of biflavonoids were studied. Based on this, 11 biflavonoids ligands with α-glucosidase inhibitory activities were accurately and quickly identified from S. uncinata with ultra-high-performance liquid chromatography-quadrupole time-of-flight-tandem mass spectrometry. Furthermore, these ligands were confirmed to be potential inhibitors through the in vitro inhibitory assay and molecular docking.

Data mining and analysis for emicizumab adverse event signals based on the Food and Drug Administration Adverse Event Reporting System database.

BACKGROUND: Emicizumab is the latest treatment for patients with hemophilia A. Its safety in real-world data is limited, and regulatory agencies and clinical researchers have raised concerns about the risk of adverse events. AIM: This study aimed to detect potential adverse event signals of emicizumab using the FDA Adverse Event Reporting System (FAERS) database. METHOD: Data in FAERS from the fourth quarter of 2017 to the second quarter of 2021 were searched. Cases of adverse events were extracted using the Preferred Term in the Medical Dictionary for Regulatory Activities (version 24.0). Disproportionality analysis was performed using the reporting odds ratio (ROR) and information component (IC) methods based on statistical shrinkage transformation. RESULTS: A total of 5,598,717 patients were included, of which 1,244 took emicizumab. A total of 703 emicizumab-related adverse event signals were mined, and 101 positive signals were detected. Haemarthrosis (ROR/ROR975/ROR025 = 155.62/184.34/131.38, IC/IC975/IC025 = 7.28/7.48/7.01), haemorrhage (ROR/ROR975/ROR025 = 71.01/81.18/62.12, IC/IC975/IC025 = 6.15/6.31/5.94), muscle haemorrhage (ROR/ROR975/ROR025 = 53.38/75.83/37.58, IC/IC975/IC025 = 5.74/6.16/5.15), traumatic haemorrhage (ROR/ROR975/ROR025 = 27.78/46.29/16.67, IC/IC975/IC025 = 4.80/5.40/3.92), haematoma (ROR/ROR975/ROR025 = 18.15/26.35/12.51, IC/IC975/IC025 = 4.18/4.63/3.55), device-related thrombosis (ROR/ROR975/ROR025 = 21.27/37.57/12.04, IC/IC975/IC025 = 4.41/5.08/3.43), and activated partial thromboplastin time prolonged (ROR/ROR975/ROR025 = 20.68/36.51/11.71, IC/IC975/IC025 = 4.37/5.04/3.39) had the strongest signal intensities. Haemorrhage, haemarthrosis, arthralgia, fall, and injection site pain were reported more frequently. CONCLUSION: This study found that mild arthralgia and injection site reaction were associated with emicizumab. Attention should also be paid to other serious adverse events related to emicizumab, such as acute myocardial infarction and sepsis, to ensure patient safety.

Identification of yeast α-glucosidase inhibitors from Pueraria lobata by ligand fishing based on magnetic mesoporous silicon combined with knock-out/knock-in technology.

In this study, a ligand fishing technique based on magnetic mesoporous silicon was established and used to screen α-glucosidase inhibitors from Pueraria lobata. To clarify quantity-activity relationships in a holistic view, the knock-out/knock-in technology was used to analyse the interactions of several active constituents in P. lobata. Magnetic mesoporous silicon with a large specific surface area and better biocompatibility was synthesised. Subsequently, α-glucosidase was immobilised on -NH2-modified magnetic mesoporous silicon, and the compounds in the crude extract of P. lobata were screened across enzyme binding. The structures of the ligands were elucidated using UPLC-Q-TOF-MS/MS, and their activities were verified by knock-out/knock-in experiments and molecular docking. Daidzein and puerarin showed α-glucosidase inhibitory activities with an IC50 of 0.088 ± 0.003 mg mL-1 and 0.414 ± 0.005 mg mL-1, respectively. Among them, puerarin, which accounted for more than 40% of the total content, showed synergistic effects with other components and was the main contributor to the α-glucosidase inhibitory activity of P. lobata.

The Effect of Brief Mindfulness Meditation on Suicidal Ideation, Stress and Sleep Quality.

OBJECTIVES: Suicide is the fourth leading cause of death for individuals aged 15-29 years, and early intervention on suicidal ideation and risk factors should be priortized. Brief mindfulness meditation (BMM) is convenient and cost-effective in improving physical and mental well-being, but less is known about its efficacy for suicidal ideation, stress and sleep quality. We investigated the effects of BMM on suicidal ideation, stress, and sleep quality for individuals with suicide risk. METHODS: Sixty-four college students with high suicidal ideation (aged 18-30 years) were randomly allocated to either a BMM (n = 32) or control group (n = 32). The BMM was based on Anapanasati and core mindfulness concepts. Sixty participants completed all scheduled sessions including pretest, one month of intervention or waiting, and posttest. Suicidal ideation was measured with the Beck Scale for Suicidal Ideation. Stress was evaluated using the Perceived Stress Scale and salivary cortisol levels. Sleep was measured using the Pittsburgh Sleep Quality Index and actigraphy accompanied with 7-day sleep diaries. RESULTS: Post-intervention, the BMM group showed significant decrease in suicidal ideation with a large effect size; the decrease showed a medium effect size in the control group. The BMM group, but not the control group, showed significant decrease in morning salivary cortisol and sleep latency, and improved sleep efficiency. CONCLUSIONS: BMM could help reduce suicidal ideation, stress, and sleep disturbance for individuals with high suicidal ideation and it may implicate effective suicide prevention strategy.

Safety of sugammadex for reversal of neuromuscular block: A postmarketing study based on the World Health Organization pharmacovigilance database.

AIM: Residual neuromuscular blockade is a common complication after general anaesthesia. Sugammadex can reverse the action of aminosteroid neuromuscular blockers. This study aimed to explore sugammadex safety issues in the real world and determine the spectrum of adverse reactions. METHODS: All sugammadex-related adverse events reported in VigiBase between 2010 and 2019 were classified by group queries according to the Medical Dictionary for Regulatory Activities. A disproportionality analysis of data was performed using the information component (IC); positive IC values were deemed significant. RESULTS: Overall, 16 219 410 adverse events were reported and 2032 were associated with sugammadex. The frequent reactions were recurrence of neuromuscular blockade (n = 54, IC 6.74, IC025 6.33), laryngospasm (n = 53, IC 6.05, IC025 5.64), bronchospasm (n = 119, IC 5.63, IC025 5.36) and bradycardia (n = 169, IC 5.13, IC025 4.90). Fatal cases were more likely among patients with cardiac disorders, especially those over 65 years. In addition, the common adverse drug reactions (ADRs) differed between different age groups (P < .01). ADRs were higher in the 0-17 years age group than in other age groups. The onset time of common ADRs was typically within 1 day and 68.9% occurred within half an hour after sugammadex administration. CONCLUSIONS: Anaesthesiologists should carefully monitor the anaesthesia recovery period to correct the ADRs caused by sugammadex and recommend monitoring neuromuscular function throughout the anaesthesia process. Sugammadex should be used carefully in patients with cardiovascular diseases, and electrocardiography and hemodynamic changes should be monitored after medication.

LncRNA LINC01018/miR-942-5p/KNG1 axis regulates the malignant development of glioma in vitro and in vivo.

AIMS: Since the inhibitory effect of KNG1 on glioma has been proved, this study further explores the regulation of the lncRNA/miRNA axis on KNG1 in glioma. METHODS: The miRNAs that target KNG1 and the lncRNA that targets miR-942-5p were predicted by bioinformatics analysis and verified by experiments. The correlations between miR-942-5p and the survival of patients and between KNG1 and miR-942-5p were analyzed. After transfection, cell migration, invasion, proliferation, and cell cycle were detected through wound healing, Transwell, colony formation, and flow cytometry assays. A mouse subcutaneous xenotransplanted tumor model was established. The expressions of miR-942-5p, KNG1, LINC01018, and related genes were evaluated by quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR), Western blot, or immunohistochemistry. RESULTS: MiR-942-5p targeted KNG1, and LINC01018 sponged miR-942-5p. The high survival rate of patients was related to low miR-942-5p level. MiR-942-5p was highly expressed, whereas KNG1 was lowly expressed in glioma. MiR-942-5p was negatively correlated with KNG1. Silent LINC01018 or KNG1 and miR-942-5p mimic enhanced the migration, invasion, and proliferation of glioma cells, and regulated the expressions of metastasis-related and proliferation-related genes. LINC01018 knockdown and miR-942-5p mimic promoted glioma tumor growth in mice. The levels of miR-942-5p and KNG1 were decreased by LINC01018 knockdown, and LINC01018 expression was suppressed by miR-942-5p mimic. MiR-942-5p inhibitor, KNG1, and LINC01018 had the opposite effect to miR-942-5p mimic. CONCLUSION: LINC01018/miR-942-5p/KNG1 pathway regulates the development of glioma cells in vitro and in vivo.

Worse Outcomes After Readmission to a Different Hospital After Sepsis: A Nationwide Cohort Study.

BACKGROUND: In the United States, sepsis accounts for 13% of the total hospital expenses and > 50% of hospital deaths. Moreover, people with sepsis are more likely to be readmitted. OBJECTIVE: The aim of this study was to assess the prevalence and outcomes of different hospital readmissions (DHRs) in patients with sepsis, and the factors associated with DHR. METHODS: We used data from the Nationwide Readmissions Database of the United States in 2017 to identify patients admitted for sepsis. Multivariable logistic regression analysis was used to evaluate the factors associated with DHR; five models were constructed to elucidate the relationship between DHR and in-hospital outcomes. RESULTS: In 2017, 85,120 (21.97%) of all patients with sepsis readmitted within 30 days in the United States were readmitted to a different hospital. The most common reason for readmission was infection irrespective of hospital status. Compared with the patients with sepsis who were readmitted to the same hospital, DHR was associated with higher hospitalization costs ($2264; 95% CI $1755-$2772; p < 0.001), longer length of stay (0.58 days; 95% CI 0.44-0.71 days; p < 0.001), and higher risk of in-hospital mortality (odds ratio 1.63; 95% CI 1.55-1.72; p < 0.001). CONCLUSIONS: DHR occurred in one-fifth of patients with sepsis in the United States. Our findings suggest that patients readmitted to a different hospital within 30 days may experience higher in-hospital mortality, longer length of stay, and higher hospitalization costs. Future studies need to examine whether continuity of care can improve the prognosis of patients with sepsis.

Rapid Screening of Lipase Inhibitors in Scutellaria baicalensis by Using Porcine Pancreatic Lipase Immobilized on Magnetic Core-Shell Metal-Organic Frameworks.

As for ligand fishing, the current immobilization approaches have some potential drawbacks such as the small protein loading capacity and difficult recycle process. The core-shell metal-organic frameworks composite (Fe3O4-COOH@UiO-66-NH2), which exhibited both magnetic characteristics and large specific surface area, was herein fabricated and used as magnetic support for the covalent immobilization of porcine pancreatic lipase (PPL). The resultant composite Fe3O4-COOH@UiO-66-NH2@PPL manifested a high loading capacity (247.8 mg/g) and relative activity recovery (101.5%). In addition, PPL exhibited enhanced tolerance to temperature and pH after immobilization. Then, the composite Fe3O4-COOH@UiO-66-NH2@PPL was incubated with the extract of Scutellaria baicalensis to fish out the ligands. Eight lipase inhibitors were obtained and identified by UPLC-Q-TOF-MS/MS. The feasibility of the method was further confirmed through an in vitro inhibitory assay and molecular docking. The proposed ligand fishing technique based on Fe3O4-COOH@UiO-66-NH2@PPL provided a feasible, selective, and effective platform for discovering enzyme inhibitors from natural products.