Tumor-associated macrophages in nanomaterial-based anti-tumor therapy: as target spots or delivery platforms.

Targeting tumor-associated macrophages (TAMs) has emerged as a promising approach in cancer therapy. This article provides a comprehensive review of recent advancements in the field of nanomedicines targeting TAMs. According to the crucial role of TAMs in tumor progression, strategies to inhibit macrophage recruitment, suppress TAM survival, and transform TAM phenotypes are discussed as potential therapeutic avenues. To enhance the targeting capacity of nanomedicines, various approaches such as the use of ligands, immunoglobulins, and short peptides are explored. The utilization of live programmed macrophages, macrophage cell membrane-coated nanoparticles and macrophage-derived extracellular vesicles as drug delivery platforms is also highlighted, offering improved biocompatibility and prolonged circulation time. However, challenges remain in achieving precise targeting and controlled drug release. The heterogeneity of TAMs and the variability of surface markers pose hurdles in achieving specific recognition. Furthermore, the safety and clinical applicability of these nanomedicines requires further investigation. In conclusion, nanomedicines targeting TAMs hold great promise in cancer therapy, offering enhanced specificity and reduced side effects. Addressing the existing limitations and expanding our understanding of TAM biology will pave the way for the successful translation of these nano-therapies into clinical practice.

A real-world cost-effectiveness study of vancomycin versus linezolid for the treatment of late-onset neonatal sepsis in the NICU in China.

BACKGROUND AND OBJECTIVE: Currently, the detection rates of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCoNS) in the blood cultures of neonates with sepsis exceed the national average drug resistance level, and vancomycin and linezolid are the primary antibacterial drugs used for these resistant bacteria according to the results of etiological examinations. However, a comprehensive evaluation of their costs and benefits in late-onset neonatal sepsis in a neonatal intensive care unit (NICU) has not been conducted. This study aimed to compare the cost and effectiveness of vancomycin and linezolid in treating neonatal sepsis in the NICU. METHODS: A cost-effectiveness analysis of real-world data was carried out by retrospective study in our hospital, and the cost and effectiveness of vancomycin and linezolid were compared by establishing a decision tree model. The drug doses in the model were 0.6 g for linezolid and 0.5 g for vancomycin. The cost break down included cost of medical ward, NICU stay, intravenous infusion of vancomycin or linezolid, all monitoring tests, culture tests and drugs. The unit costs were sourced from hospital information systems. The effectiveness rates were obtained by cumulative probability analysis. One-way sensitivity analysis was used to analyze uncertain influencing factors. RESULTS: The effectiveness rates of vancomycin and linezolid in treating neonatal sepsis in the NICU were 89.74% and 90.14%, respectively, with no significant difference. The average cost in the vancomycin group was ¥12261.43, and the average cost in the linezolid group was ¥17227.96. The incremental cost effectiveness was ¥12416.33 cost per additional neonate with treatment success in the linezolid group compared to vancomycin group at discharge. Factors that had the greatest influence on the sensitivity of the incremental cost-effectiveness ratio were the price of linezolid and the effectiveness rates. CONCLUSIONS: The cost for treatment success of one neonate in linezolid group was ¥5449.17 more than that in vancomycin group, indicating that vancomycin was more cost-effective. Therefore, these results can provide a reference for a cost effectiveness treatment scheme for neonatal sepsis in the NICU.

Establishment and validation of a risk prediction model incorporating concentrations of linezolid and its metabolite PNU142300 for linezolid-induced thrombocytopenia.

BACKGROUND: Linezolid-induced thrombocytopenia is the main factor restricting the clinical application of linezolid. OBJECTIVES: To investigate the relationship between PNU-14230 concentration and linezolid-induced thrombocytopenia and further develop and validate a risk model for predicting linezolid-induced thrombocytopenia. METHODS: A regression model was constructed to predict the occurrence of linezolid-induced thrombocytopenia, and further externally validated. The predictive performance was evaluated by receiver operating characteristic curve and Hosmer-Lemeshow test. Linezolid Cmin and PNU-142300 concentrations were compared for different kidney function groups. The Kaplan-Meier method was used to estimate the difference in cumulative incidence of linezolid-induced thrombocytopenia among different kidney function patients. RESULTS: In the derivation (n = 221) and validation (n = 158) cohorts, 28.5% and 24.1% of critically ill patients developed linezolid-induced thrombocytopenia. Logistic regression analysis indicated that the independent risk factors were linezolid Cmin, PNU-142300 concentration, baseline platelet count, renal insufficiency (RI) and continuous venovenous haemofiltration (CVVH). The AUC for the risk model was 0.901, and the model was good (P = 0.633). The model also showed good discrimination (AUC 0.870) and calibration (P = 0.282) in the external validation cohort. Compared with normal kidney function patients, patients with RI and CVVH had higher linezolid Cmin and PNU-142300 concentrations (P < 0.001) and higher cumulative incidence of linezolid-induced thrombocytopenia (P < 0.001). CONCLUSIONS: PNU142300 concentration, as well as linezolid Cmin, might identify patients at risk of linezolid-induced thrombocytopenia. The risk prediction model had good predictive performance for linezolid-induced thrombocytopenia development. Concentrations of linezolid and PNU-142300 accumulated in patients with RI and CVVH.

Dose optimisation of linezolid in critically ill patients based on a population pharmacokinetic model: A two-centre prospective interventional study.

OBJECTIVES: This study evaluated the intervention effect of clinical pharmacist-mediated optimisation of a linezolid regimen using a population pharmacokinetic (PPK) model. METHODS: Patients treated with linezolid in two medical centres from January 2020 to June 2021 were retrospectively included in the control group; those treated from July 2021 to June 2022 were prospectively enrolled in the intervention group. Clinical pharmacists optimised the dosage regimen according to a published linezolid PPK model in the intervention group. An interrupted times series approach was used to analyse the data. The incidence of linezolid-induced thrombocytopenia (LIT), target attainment of pharmacokinetic/pharmacodynamic parameters and other adverse drug reactions (ADRs) were compared between the two groups. RESULTS: In total, 77 and 103 patients were enrolled in the control and intervention groups, respectively. The intervention group had a lower incidence of LIT and other ADRs than the control group (10.7% vs. 23.4%, P = 0.002; 1.0% vs. 7.8%, P = 0.027). The intervention group exhibited a considerably lower trough concentration (Cmin) and area under the concentration-time curve/MIC ratio (AUC24/MIC) (P = 0.001 and P < 0.001). Cmin and AUC24/MIC rates within the target range were substantially higher in the intervention group (49.6% vs. 20.0%, adjusted P < 0.05; 48.1% vs. 25.6%, adjusted P < 0.05). CONCLUSION: Interventions by clinical pharmacists reduced the incidence of LIT and other ADRs. Implementation of model-informed precision dosing (MIPD) for linezolid markedly increased the Cmin and AUC24/MIC rates within the target range. We recommend MIPD-guided linezolid dose reduction for patients with renal impairment.

The association between visceral adiposity index and decreased renal function: A population-based study.

Aims: We aimed to investigate the association of visceral adiposity index (VAI) with decreased renal function in US adults. Design and methods: Cross-sectional data were analyzed for 35,018 adults in the National Health and Nutrition Examination Survey (NHANES) 2005-2018. VAI was determined using waist circumference, body mass index (BMI), triglycerides (TGs) and high-density lipoprotein-cholesterol. Albuminuria was defined as urinary albumin-to-creatinine ratio (ACR) >30 mg/g. A low estimated-glomerular filtration rate (eGFR) was defined as an eGFR lower than 60 ml/min/1.73 m2. Chronic kidney disease (CKD) was defined as either albuminuria or low-eGFR. A multivariable logistic regression analysis was utilized to explore the relationship of VAI with albuminuria, low-eGFR and CKD. Subgroup analysis and interaction tests were also conducted. Results: A total of 35,018 participants were enrolled with albuminuria, low-eGFR, and CKD prevalence rates of 5.18, 6.42, and 10.62%, respectively, which increased with the higher VAI tertiles. After full adjustment, a positive association of VAI with albuminuria (OR = 1.03, 95% CI: 1.00, 1.06) and CKD (OR = 1.04, 95% CI: 1.02, 1.06) was observed. Participants in the highest VAI tertile had a significantly 30% increased risk for albuminuria (OR = 1.30, 95% CI: 1.07, 1.58) and a 27% increased risk for CKD (OR = 1.27, 95% CI: 1.08, 1.49) compared with those in the lowest VAI tertile. No statistically significant association between VAI and low-eGFR was detected. Subgroup analysis and the interaction term indicated that there was no significant difference among different stratifications. Conclusion: Visceral adiposity accumulation evaluating by VAI was associated with increased likelihood of the decline in renal function.

Effectiveness of functional magnetic resonance imaging for early identification of chronic kidney disease: A systematic review and network meta-analysis.

PURPOSE: The commonly used clinical indicators are not sensitive enough on detecting early chronic kidney disease (CKD), whether functional magnetic resonance imaging (fMRI) can be regarded as a new noninvasive method to identify early stages of CKD and even different stages remains unknown. We performed a network meta-analysis to explore the question. METHODS: Five databases were searched to identify eligible articles from 2000 to 2022. The outcome indicators were imaging biomarkers of fMRI techniques, including apparent diffusion coefficient (ADC) by diffusion-weighted imaging (DWI), fractional anisotropy (FA) by diffusion tensor imaging (DTI), diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) by intravoxel incoherent motion imaging (IVIM), and apparent relaxation rate (R2*) by blood oxygen level-dependent (BOLD). RESULTS: A total of 21 articles with 1472 patients were included for analysis. Cortical FA, f, and R2* values in CKD stages 1-2 were found statistically different with healthy controls (mean difference (MD), -0.03, 95% confidence interval (CI) -0.05, -0.01; MD, -0.04, 95% CI -0.06, -0.02; MD, 2.22, 95% CI 0.87, 3.57, respectively), and cortical ADC values were significantly different among different CKD stages (stages 3 and 1-2: MD, -0.15, 95% CI -0.23, -0.06; stages 4-5 and 3: MD -0.27, 95% CI -0.39, -0.14). CONCLUSION: The results indicated fMRI techniques had great efficacy in assessing early stages and different stages of CKD, among which DTI, IVIM, and BOLD exerted great superiority in differentiating early CKD patients from the general population, while DWI showed the advantage in distinguishing different CKD stages.

Effectiveness of Microecological Preparations for Improving Renal Function and Metabolic Profiles in Patients With Chronic Kidney Disease.

Background: Determining whether microecological preparations, including probiotics, prebiotics, and synbiotics, are beneficial for patients with chronic kidney disease (CKD) has been debated. Moreover, determining which preparation has the best effect remains unclear. In this study, we performed a network meta-analysis of randomized clinical trials (RCTs) to address these questions. Methods: MEDLINE, EMBASE, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials were searched. Eligible RCTs with patients with CKD who received intervention measures involving probiotics, prebiotics, and/or synbiotics were included. The outcome indicators included changes in renal function, lipid profiles, inflammatory factors, and oxidative stress factors. Results: Twenty-eight RCTs with 1,373 patients were ultimately included. Probiotics showed greater effect in lowering serum creatinine [mean difference (MD) -0.21, 95% confidence interval (CI) -0.34, -0.09] and triglycerides (MD -9.98, 95% CI -19.47, -0.49) than the placebo, with the largest surface area under the cumulative ranking curve, while prebiotics and synbiotics showed no advantages. Probiotics were also able to reduce malondialdehyde (MDA) (MD -0.54, 95% CI -0.96, -0.13) and increase glutathione (MD 72.86, 95% CI 25.44, 120.29). Prebiotics showed greater efficacy in decreasing high-sensitivity C-reactive protein (MD -2.06, 95% CI -3.79, -0.32) and tumor necrosis factor-α (MD -2.65, 95% CI -3.91, -1.39). Synbiotics showed a partially synergistic function in reducing MDA (MD -0.66, 95% CI -1.23, -0.09) and high-sensitivity C-reactive protein (MD -2.01, 95% CI -3.87, -0.16) and increasing total antioxidant capacity (MD 145.20, 95% CI 9.32, 281.08). Conclusion: The results indicated that microbial supplements improved renal function and lipid profiles and favorably affected measures of oxidative stress and inflammation in patients with CKD. After thorough consideration, probiotics provide the most comprehensive and beneficial effects for patients with CKD and might be used as the best choice for microecological preparations. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022295497, PROSPERO 2022, identifier: CRD42022295497.

Higher visceral adiposity index is associated with increased likelihood of abdominal aortic calcification.

BACKGROUND: The negative effects of visceral adiposity accumulation on cardiovascular health have drawn much attention. However, the association between the Visceral Adiposity Index (VAI) and Abdominal Aortic Calcification (AAC) has never been reported before. The authors aimed to investigate the association between the VAI and AAC in US adults. METHODS: Cross-sectional data were derived from the 2013 to 2014 National Health and Nutrition Examination Survey (NHANES) of participants with complete data of VAI and AAC scores. Weighted multivariable regression and logistic regression analysis were conducted to explore the independent relationship between VAI and AAC. Subgroup analysis and interaction tests were also performed. RESULTS: A total of 2958 participants were enrolled and participants in the higher VAI tertile tended to have a higher mean AAC score and prevalence of severe AAC. In the fully adjusted model, a positive association between VAI and AAC score and severe AAC was observed (ß = 0.04, 95% CI 0.01‒0.08; OR = 1.04, 95% CI 1.01‒1.07). Participants in the highest VAI tertile had a 0.41-unit higher AAC score (ß = 0.41, 95% CI 0.08‒0.73) and a significantly 68% higher risk of severe AAC than those in the lowest VAI tertile (OR = 1.68, 95% CI 1.04‒2.71). Subgroup analysis and interaction tests indicated that there was no dependence for the association of VAI and AAC. CONCLUSION: Visceral adiposity accumulation evaluated by the VAI was associated with a higher AAC score and an increased likelihood of severe AAC.

Olanzapine add-on treatment promotes neuronal differentiation of neural stem cells compared with fluoxetine alone.

The addition of olanzapine to fluoxetine produces an antidepressant effect on fluoxetine nonresponders. Promoting hippocampal neurogenesis is associated with the successful treatment of depression. The present study aimed to investigate the interaction of olanzapine and fluoxetine in regulating neurogenesis. We found that fluoxetine alone does not affect cell proliferation and inhibits the neuronal differentiation of cultured neural stem cells (NSCs), but promotes NSCs proliferation and exerts no effect on neuronal fate when NSCs are cocultured with neurons. In addition, fluoxetine alone also does not alter the neuronal fate of newborn hippocampal cells in vivo. Although fluoxetine treatment elicits different results, our data consistently show that olanzapine alone does not affect the proliferation and neuronal differentiation of NSCs. The combination of olanzapine and fluoxetine has no profound effect on NSCs proliferation compared with fluoxetine alone, but olanzapine add-on treatment produces a greater number and percentage of differentiated neurons from NSCs. Further investigations are needed to explore the underlying mechanisms of the increased neurogenesis caused by the combination of olanzapine with fluoxetine.

Continuous infusion versus intermittent infusion of vancomycin in critically ill patients undergoing continuous venovenous hemofiltration: a prospective interventional study.

BACKGROUND: A prospective interventional study comparing outcomes in critically ill patients receiving intermittent infusion (II) or continuous infusion (CI) of vancomycin during continuous venovenous hemofiltration (CVVH) is lacking. The objective of this study was to compare the pharmacokinetic/pharmacodynamics (PK/PD) target attainment, therapeutic efficacy and safety among critically ill patients who received CI or II of vancomycin in a prospective interventional trial and to explore the correlations of effluent flow rate (EFR) with PK/PD indices. METHODS: This prospective interventional study was conducted in two independent intensive care units (ICUs) from February 2021 to January 2022. Patients in one ICU were assigned to receive CI (intervention group) of vancomycin, whereas patients in the other ICU were assigned to receive II regimen (control group). The primary outcome was to compare the PK/PD target attainment, including target concentration and target area under the curve over 24 h to minimum inhibitory concentration (AUC24/MIC). RESULTS: Overall target attainment of PK/PD indices was higher with CI compared with II, irrespective of target concentration (78.7% vs. 40.5%; P < 0.05) or AUC24/MIC (53.2% vs. 28.6%; P < 0.05). There were no significant differences in clinical success (72.2% vs. 50.0%; P = 0.183) and microbiological success (83.3% vs. 75.0%, P = 0.681) between the patients treated with CI or II of vancomycin. Adverse reactions occurred at similar rates (0.0% vs. 4.4%; P = 0.462), and mortality between the two modalities was also not significant different (21.7% vs. 17.9%; P = 0.728). Correlation analysis showed a weak to moderately inverse correlation of EFR with observed concentration (r = - 0.3921, P = 0.01) and AUC24/MIC (r = - 0.3811, P = 0.013) in the II group, whereas the correlation between EFR and observed concentration (r = - 0.5711, P < 0.001) or AUC24/MIC (r = - 0.5458, P < 0.001) in the CI group was stronger. CONCLUSION: As compared to II, CI of vancomycin in critically ill patients undergoing CVVH was associated with improved attainment of PK/PD indices. Furthermore, the inverse correlation of PK/PD indices with EFR was stronger among patients treated with CI of vancomycin. Trial registration The trial was registered in the Chinese clinical trial registration center (21/01/2021-No. ChiCTR2100042393).

Dose Optimization of Teicoplanin for Critically Ill Patients With Renal Dysfunction and Continuous Renal Replacement Therapy: Experience From a Prospective Interventional Study.

Background: Due to the lack of updated information on teicoplanin (TEI) for continuous renal replacement therapy (CRRT), no exact dosage regimen has been recommended. The aim of this study was to optimize the dosage regimen of TEI in renal dysfunction patients with or without CRRT, evaluate the influence factors of the eradication of Gram-positive bacteria, and evaluate the effect of CRRT on the clearance of TEI. Methods: Patients with renal dysfunction receiving TEI treatment in the ICU were prospectively recruited and divided into CRRT and non-CRRT groups. Logistic regression analysis was used to screen the factors affecting the eradication of Gram-positive bacteria. The filtrate concentration of the CRRT group was measured at the time of TEI Cmin, and the filtration coefficient of TEI was calculated to evaluate the effect of CRRT on the clearance of TEI. Results: A total of 106 patients were included, 40 cases in the CRRT group and 66 cases in the non-CRRT group. After giving high-loading doses of TEI, 75.8 and 70% of TEI Cmin in the non-CRRT and CRRT groups reached the range of 10-30 mg/L before the 3rd dose, respectively. The risk of G+ bacteria being uneradicated was higher while the APACHEⅡscore was higher than 22.5. The albumin level before the start of TEI administration and before the 6th-8th dose was lower than 32.8 g/L and 29.3 g/L, respectively, and Cmin before the 3rd dose and 6th-8th dose was lower than 13.2 mg/L and 17.1 mg/L, respectively, with the duration of TEI therapy shorter than 10.5 days. The correlation coefficient (r) was 0.6490 between Cmin before the 3rd dose and the albumin level (p < 0.001). The filtration coefficient of TEI was 10.7 ± 2.4% at Cmin and 11.1 ± 2.5% at Cmax. The GFR had no correlation with the filtration coefficient (r = -0.06204; r = -0.08059). The clearance of TEI in CRRT patients was negatively correlated with the albumin level (r = -0.6305, p = 0.0013). Conclusion: The early stage of the albumin level can significantly affect the initial Cmin and clinical efficacy of TEI, and also had effect on the clearance of TEI by CRRT. The filtration coefficient of TEI was stable, even with a higher ultrafiltration rate.

The Impact of a Multifaceted Pharmacist-Led Antimicrobial Stewardship Program on Antibiotic Use: Evidence From a Quasi-Experimental Study in the Department of Vascular and Interventional Radiology in a Chinese Tertiary Hospital.

Objective: The objective of the study was to assess the impact of multifaceted clinical pharmacist-led antimicrobial stewardship (AMS) program on the rational use of antibiotics for patients who receive vascular and interventional radiology therapies. Methods: A quasi-experimental retrospective intervention design with a comparison group was applied to the practice of antibiotic use in the department of vascular and interventional radiology in a Chinese tertiary hospital. We used difference-in-differences (DID) analysis to compare outcomes before and after the AMS intervention between the intervention group and control group, to determine whether intervention would lead to changes in irrationality of antibiotic prescribing, antibiotic utilization, cost of antibiotics, and length of hospital stay. Results: The DID results showed that the intervention group was associated with a reduction in the average consumption of antibiotics (p = 0.017) and cost of antibiotics (p = 0.006) and cost per defined daily dose (DDD) (p = 0.000). There were no significant differences in the mean change of total costs and length of stay between the two groups (p > 0.05). The average inappropriate score of perioperative antimicrobial prophylaxis in the intervention group declined by 0.23, while it decreased by 0.02 in the control group [0.21 (95% CI, -0.271 to -0.143); p = 0.000]. The average inappropriate score of non-surgical antimicrobial prophylaxis in the intervention group declined by 0.14, while it increased by 0.02 in the control group [0.16 (95% CI, -0.288 to -0.035); p = 0.010]. The average inappropriate score of the therapeutic use of antibiotics in the intervention group declined by 0.07, while it decreased by 0.01 in the control group [0.06 (95% CI, -0.115 to -0.022); p = 0.003]. Conclusions: This study provides evidence that implementation of AMS interventions was associated with a marked reduction of antibiotic use, cost of antibiotics, and irrationality of antibiotic prescribing in China.

A Regression Model to Predict Linezolid Induced Thrombocytopenia in Neonatal Sepsis Patients: A Ten-Year Retrospective Cohort Study.

Background: Linezolid-induced thrombocytopenia (LIT) is the main factor limiting the clinical application of linezolid (LZD). The incidence and risk factors of LIT in neonatal patients were possibly different from other populations based on pathophysiological characteristics. The purpose of this study was to establish a regression model for predicting LIT in neonatal sepsis patients. Methods: We retrospectively included 518 patients and divided them into the LIT group and the non-LIT group. A logistic regression analysis was used to analyze the factors related to LIT, and a regression model was established. A receiver operating characteristic (ROC) curve was drawn to evaluate the model's predictive value. We prospectively collected 39 patients' data to validate the model and evaluate the effect of LZD pharmacokinetics on LIT. Results: Among the 518 patients, 103 patients (19.9%) developed LIT. The Kaplan-Meier plot revealed that the overall median time from the initiation of LZD treatment to the onset of LIT in preterm infants was much shorter when compared with term infants [10 (6, 12) vs. 13 (9.75, 16.5), p = 0.004]. Multiple logistic regression analysis indicated that the independent risk factors of LIT were lower weight at medication, younger gestational ages, late-onset sepsis, necrotizing enterocolitis, mechanical ventilation, longer durations of LZD treatment, and lower baseline of platelet level. We established the above seven-variable prediction regression model and calculated the predictive probability. The ROC curve showed that the predicted probability of combined body weight, gestational age, duration of LZD treatment, and baseline of platelet had better sensitivity (84.4%), specificity (74.2%), and maximum AUC (AUC = 0.873). LIT occurred in 9 out of 39 patients (23.1%), and the accuracies of positive and negative predictions of LIT were 88.9 and 76.7%, respectively. Compared with the non-LIT patients, the LIT patients had higher trough concentration [11.49 (6.86, 15.13) vs. 5.51 (2.80, 11.61) mg/L; p = 0.028] but lower apparent volume of distribution (Vd) [0.778 (0.687, 1.421) vs. 1.322 (1.099, 1.610) L; p = 0.010]. Conclusion: The incidence of LIT was high in neonatal sepsis patients, especially in preterm infants. LIT occurred earlier in preterm infants than in term infants. The regression model of seven variables had a high predictive value for predicting LIT. LIT was correlated with higher trough concentration and lower Vd.

Facile Separator Modification Strategy for Trapping Soluble Polyphosphides and Enhancing the Electrochemical Performance of Phosphorus Anode.

Phosphorus anode is one of the most promising candidates for high-energy-density lithium-ion batteries. Recent studies found the lithiation process of phosphorus is accompanied by the soluble intermediates of lithium polyphosphides. The trans-separator diffusion of polyphosphides is responsible for the capacity decay. Herein, a facile separator modification strategy is proposed for improving the performance of phosphorus anode. The lightweight CNT-modified layer that has a continuous conductive skeleton, a dense structure, and a strong interaction with the soluble lithium polyphosphides can trap, stabilize, and reactivate the active material. Without sophisticated electrode structure design, the cyclability and high-rate performance of the phosphorus anode has been significantly improved, leading to a higher specific capacity of 1505 mAh/g at 250 mA/g (200th cycle) and 1312 mAh/g at 2 A/g. With the advantages of simplicity and low cost, the separator modification strategy provides a new feasible way for further improvement of the phosphorus-based anode.

Comparison of Image-Guided Iodine-125 Seed Interstitial Brachytherapy and Local Chemotherapy Perfusion in Treatment of Advanced Pancreatic Cancer.

OBJECTIVE: To compare the efficacy and safety of iodine-125 seed interstitial brachytherapy and local chemotherapy perfusion in treatment of advanced pancreatic cancer. METHODS: The present open prospective randomized control study included a total of 165 cases of advanced pancreatic cancer patients who were admitted in our hospital during December 2016 to April 2019. All patients were randomized into two groups with 84 cases in iodine-125 group and 81 cases in chemotherapy perfusion group. Basic clinical characteristics and demographic data were collected. The main outcome was the tumor efficiency. The pain condition was measured by visual analogue scale (VAS) and the Karnofsky score was also measured at different time points, before the treatment, 1 d, 7 d, 14 d, 1 mon, 2 mon and 3 mon after treatment. Serum levels of CEA, CA19-9 and CA50 were measured by immunochemiluminescence. The overall survival was analyzed by K-M curve. RESULTS: The ratio of partial remission patients was significantly higher, and the ratio of stable disease (SD)+progressive disease patients was also remarkably lower in iodine-125 group than the chemotherapy perfusion group. The mean VAS scores decreased markedly after treatment and were significantly lower and the mean Karnofsky scores were remarkably higher in iodine-125 group than the chemotherapy perfusion group. The levels of CA19-9 and CA50 were remarkably lower in iodine-125 group, however no significant difference was found for CEA. The survival analysis by K-M curve showed the iodine-125 patients had longer overall survival time than the chemotherapy perfusion group. No infection, pancreatic fistula, biliary fistula, intestinal fistula, gastrointestinal obstruction or radiation enteritis was found in both groups. CONCLUSION: Iodine-125 seed interstitial brachytherapy could achieve better efficacy with no increased side complications than chemotherapy perfusion in advanced pancreatic cancer.

Higher visceral adiposity index is associated with increased likelihood of abdominal aortic calcification

Abstract Background: The negative effects of visceral adiposity accumulation on cardiovascular health have drawn much attention. However, the association between the Visceral Adiposity Index (VAI) and Abdominal Aortic Calcification (AAC) has never been reported before. The authors aimed to investigate the association between the VAI and AAC in US adults. Methods: Cross-sectional data were derived from the 2013 to 2014 National Health and Nutrition Examination Survey (NHANES) of participants with complete data of VAI and AAC scores. Weighted multivariable regression and logistic regression analysis were conducted to explore the independent relationship between VAI and AAC. Subgroup analysis and interaction tests were also performed. Results: A total of 2958 participants were enrolled and participants in the higher VAI tertile tended to have a higher mean AAC score and prevalence of severe AAC. In the fully adjusted model, a positive association between VAI and AAC score and severe AAC was observed (β = 0.04, 95% CI 0.01‒0.08; OR = 1.04, 95% CI 1.01‒1.07). Participants in the highest VAI tertile had a 0.41-unit higher AAC score (β = 0.41, 95% CI 0.08‒0.73) and a significantly 68% higher risk of severe AAC than those in the lowest VAI tertile (OR = 1.68, 95% CI 1.04‒2.71). Subgroup analysis and interaction tests indicated that there was no dependence for the association of VAI and AAC. Conclusion: Visceral adiposity accumulation evaluated by the VAI was associated with a higher AAC score and an increased likelihood of severe AAC.

A Regression Model to Predict Augmented Renal Clearance in Critically Ill Obstetric Patients and Effects on Vancomycin Treatment.

Background: Augmented renal clearance (ARC) risk factors and effects on vancomycin (VCM) of obstetric patients were possibly different from other populations based on pathophysiological characteristics. Our study was to establish a regression model for prediction of ARC and analyze the effects of ARC on VCM treatment in critically ill obstetric patients. Methods: We retrospectively included 427 patients, grouped into ARC and non-ARC patients. Logistic regression analysis was used to analyze the factors related to ARC. Receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of the model for ARC. Patients who received VCM therapy were collected. The published VCM population pharmacokinetic (PPK) model was used to calculate pharmacokinetic parameters. A linear regression analysis was made between the predicted and measured concentrations. Results: Of the 427 patients, ARC was present in 201 patients (47.1%). The independent risk factors of ARC were heavier, greater gestational age, higher albumin level, fewer caesarean section, severe preeclampsia and vasoactive drug; more infection, hypertriglyceridemia and acute pancreatitis. We established the above nine-variable prediction regression model and calculated the predicted probability. ROC curve showed that the predicted probability of combined weight, albumin and gestational age had better sensitivity (70.0%) and specificity (89.8%) as well as the maximal area under the curve (AUC, AUC = 0.863). 41 cases received VCM; 21 cases (51.2%) had ARC. The initial trough concentration in ARC patients was lower than in non-ARC patients (7.9 ± 3.2 mg/L vs 9.5 ± 3.3 mg/L; p = 0.033). Comparing the predicted trough concentration of two published VCM PPK models with the measured trough concentration, correlation coefficients (r) were all more than 0.8 in the ARC group and non-ARC group. AUC was significantly decreased in the ARC group (p = 0.003; p = 0.013), and clearance (CL) increased in the ARC group (p < 0.001; p = 0.008) when compared with the non-ARC group. Conclusion: ARC is a common state in critically ill obstetric patients. The regression model of nine variables had high predictive value for predicting ARC. The published VCM PPK models had good predictive performance for predicting trough concentrations of obstetric patients. Pharmacokinetic parameters of VCM are different in ARC obstetric patients, which results in enhanced VCM clearance and decreased trough concentration.

The synthesis of greenish phosphorus on carbon substrates.

A phosphorus allotrope called greenish phosphorus was successfully synthesized via a simple chemical vapor deposition method. We revealed that the critical factors in the formation mechanism of greenish phosphorus are the partial pressure of the phosphorus vapor and the structure of the substrate. On the substrates of a glassy carbon wafer and carbon paper, the edge carbon structure can activate P4 molecules, allowing them to polymerize due to strong adsorption (Ead = -1.62 eV). Greenish phosphorus possesses a distinct crystal structure, different from red phosphorus and black phosphorus, thus leading to unique physical and chemical properties, and potential applications in optical, electrical, and magnetic fields.

The Deubiquitinating Enzyme UCHL1 Induces Resistance to Doxorubicin in HER2+ Breast Cancer by Promoting Free Fatty Acid Synthesis.

Ubiquitin C-terminal hydrolase L1 (UCHL1), which is a deubiquitinating enzyme, is known to play a role in chemoresistance in cancers. However, its potential roles and mechanisms in the chemoresistance of breast cancer (BC) remain unclear. In this study, we examined its expression in patients with BC and employed Kaplan-Meier analysis and the log-rank test for survival analyses. It was found that up-regulated UCHL1 expression was positively associated with both chemoresistance and poor prognosis, especially in patients with HER2+ BC. Moreover, UCHL1 expression was elevated in HER2+ BC cells (SK-BR-3 and BT474). Similarly, doxorubicin (DOX)-resistant BC cells (MCF-7/DOX) had higher UCHL1 levels than MCF-7 cells. CCK-8 assay showed that BC cells with higher UCHL1 levels were more resistant to DOX. Furthermore, by inhibiting UCHL1 in BC cells with elevated UCHL1 expression, we demonstrated that UCHL1 promoted DOX-resistance in BC. Mechanistically, UCHL1 probably promoted DOX-resistance of BC by up-regulating free fatty acid (FFA) synthesis, as exhibited by reduced FFA synthase expression and resurrected DOX-sensitivity upon UCHL1 inhibition. Overall, UCHL1 up-regulation is associated with DOX-resistance and poor prognosis in patients with HER2+ BC. UCHL1 induces DOX-resistance by up-regulating FFA synthesis in HER2+ BC cells. Thus, UCHL1 might be a potential clinical target for overcoming DOX resistance in patients with HER2+ BC.

A Covalent P-C Bond Stabilizes Red Phosphorus in an Engineered Carbon Host for High-Performance Lithium-Ion Battery Anodes.

The red phosphorus (RP) anode has attracted great attention due to its high theoretical specific capacity (2596 mAh/g) and suitable lithiation potential. To solve the inherent poor electrical conductivity and the large volume expansion due to the lithiation process, a vaporization-condensation strategy is considered as a promising method. However, there are two important issues that deserve attention in the vaporization-condensation process. First, the low P mass loading in the carbon-based frameworks (∼30 wt %) limits the energy density. Second, a residual white phosphorus (WP) leads to the safety problems of flammability and high toxicity. Herein, we found that the edge structure of carbon framework can offer the strong adsorption for P4 and form a P-C bond, which accelerate the adsorption and polymerization of P4 leading to high P mass loading and safety. When the porous carbon (PC) with plenty of edge carbons was used as the matrix to load P by vaporization-condensation, the RP loading is close to the highest theoretical mass loading of ∼50 wt % calculated based on the feeding ratio of RP/PC = 1/1. Therefore, the RP-PC anode provides a high specific capacity of 965.2 mAh/g even after 1100 cycles at 1000 mA/g (equivalent to 1 C) and a high-rate capacity of 496.8 mAh/g at 8320 mA/g (equivalent to 16.7 C) after 1000 cycles (the specific capacity and current density are calculated based on the total weight of RP and PC).