P-N Heterojunction Embedded CuS/TiO2 Bifunctional Photocatalyst for Synchronous Hydrogen Production and Benzylamine Conversion.

The coupling of photocatalytic hydrogen production and selective oxidation of benzylamine is a topic of significant research interest. However, enhancing the bifunctional photocatalytic activity in this context is still a major challenge. The construction of Z-scheme heterojunctions is an effective strategy to enhance the activity of bifunctional photocatalysts. Herein, a p-n type direct Z-scheme heterojunction CuS/TiO2 is constructed using metal-organic framework (MOF)-derived TiO2 as a substrate. The carrier density is measured by Mott-Schottky under photoexcitation, which confirms that the Z-scheme electron transfer mode of CuS/TiO2 is driven by the diffusion effect caused by the carrier concentration difference. Benefiting from efficient charge separation and transfer, photogenerated electrons, and holes are directedly transferred to active oxidation and reduction sites. CuS/TiO2 also exhibits excellent bifunctional photocatalytic activity without noble metal cocatalysts. Among them, the H2 evolution activity of the CuS/TiO2 is found to be 17.1 and 29.5 times higher than that of TiO2 and CuS, respectively. Additionally, the yields of N-Benzylidenebenzylamine (NBB) are 14.3 and 47.4 times higher than those of TiO2 and CuS, respectively.

PEGylation renders carnosine resistant to hydrolysis by serum carnosinase and increases renal carnosine levels.

Carnosine's protective effect in rodent models of glycoxidative stress have provided a rational for translation of these findings in therapeutic concepts in patient with diabetic kidney disease. In contrast to rodents however, carnosine is rapidly degraded by the carnosinase-1 enzyme. To overcome this hurdle, we sought to protect hydrolysis of carnosine by conjugation to Methoxypolyethylene glycol amine (mPEG-NH2). PEGylated carnosine (PEG-car) was used to study the hydrolysis of carnosine by human serum as well as to compare the pharmacokinetics of PEG-car and L-carnosine in mice after intravenous (IV) injection. While L-carnosine was rapidly hydrolyzed in human serum, PEG-car was highly resistant to hydrolysis. Addition of unconjugated PEG to carnosine or PEG-car did not influence hydrolysis of carnosine in serum. In mice PEG-car and L-carnosine exhibited similar pharmacokinetics in serum but differed in half-life time (t1/2) in kidney, with PEG-car showing a significantly higher t1/2 compared to L-carnosine. Hence, PEGylation of carnosine is an effective approach to prevent carnosine degradations and to achieve higher renal carnosine levels. However, further studies are warranted to test if the protective properties of carnosine are preserved after PEGylation.

Safety and effectiveness of tunneled peripherally inserted central catheters versus conventional PICC in adult cancer patients.

OBJECTIVES: This study aimed to compare the safety and effectiveness of tunneled peripherally inserted central catheters (T-PICC) vs. conventional PICCs (C-PICC) in adult cancer patients. METHODS: A multicentre randomized controlled trial was conducted between April 2021 and January 2022 in seven hospitals in China. 564 participants were randomly assigned to T-PICC or C-PICC. These data were collected and compared: the baseline characteristics and catheterization-related characteristics, periprocedural complications, and long-term complications. RESULTS: Five-hundred fifty-three participants (aged, 52.6 ± 12.3 years; female, 39.1%) were ultimately analyzed. No significant differences in periprocedural complications were found between the T-PICC and C-PICC groups (all p > 0.05). Compared with C-PICC, T-PICC significantly reduced the incidence of long-term complications (26.4% vs. 39.9%, p < 0.001). Specifically, reduced complications were found in central line-associated bloodstream infection (1.8% vs. 5.1%, p = 0.04), thrombosis (1.1% vs. 4.0%, p = 0.03), catheter dislodgement (4.7% vs. 10.1%, p = 0.01), non-infectious oozing (17.3% vs. 28.6%, p = 0.002), local infection (3.6% vs. 7.6%, p = 0.04), skin irritation (6.1% vs. 10.9%, p = 0.046), and reduced unplanned catheter removal (2.2% vs. 7.2%, p = 0.005). No significant differences were found between T-PICC and C-PICC regarding catheter occlusion (6.5% vs. 5.8%, p = 0.73) or skin damage (2.2% vs. 2.9%, p = 0.58). CONCLUSION: T-PICC is safe and effectively reduces long-term complications. CLINICAL RELEVANCE STATEMENT: The tunneled technique is effective in reducing PICC-related long-term complications. Thus, it is recommended for cancer patients at high risk of PICC-related complications. TRIAL REGISTRATION: The registration number on https://www.chictr.org.cn/ is ChiCTR2100044632. The name of the trial registry is "A multicenter randomized controlled study of clinical use of tunneled vs. non-tunneled PICC". KEY POINTS: Cather-related complications are associated with the technique of catheterization. Compared with conventional PICC, tunneled PICC reduced catheter-related long-term complications. Tunneled PICC placement provides an alternative catheterization method for cancer patients.

The sugar moiety in protopanaxadiol ginsenoside affects its ability to target glucocorticoid receptor to regulate lipid metabolism.

Ginsenosides are natural products with hydrophobic rings adorned with sugar molecules. The elucidation of the impact of ginsenosides structure on their activity is crucial for facilitating precision-oriented modifications, thereby enhancing their suitability for drug development. Here, utilizing an ob/ob mouse model, we demonstrated that as the number of sugar moiety on the protopanaxadiol-type ginsenosides decreased, the hypolipidemic potency increased, while the aglycon exhibited negligible activity. Mechanistically, we demonstrated the dependency of ginsenosides on the glucocorticoid receptor (GR) for the regulation of lipid metabolism. Interestingly, ginsenoside CK was found to promote the transcription of lipid metabolism-related genes via GR contrast to the effects of glucocorticoids, suggesting a unique mode of action. Furthermore, we observed that a reduction in the number of sugar molecules strengthened the binding affinity of ginsenosides to GR, as determined by microscale thermophoresis. These findings highlight the critical role of the sugar moiety in modulating the lipid-regulating capacity of ginsenosides, providing valuable insights for the development of these compounds as potential therapeutic agents.

The mediating role of loneliness between psychological resilience and health-related quality of life among patients with nasopharyngeal carcinoma: a cross-sectional study using structural equation modeling.

BACKGROUND: Cancer patients' health-related quality of life (HRQoL) has always been a hot discussion spot. Loneliness and psychological resilience are considered to be significant psychosocial factors impacting the HRQoL of the cancer population. However, there is a lack of studies on the interrelationship among loneliness, resilience, and HRQoL in patients with nasopharyngeal carcinoma (NPC). This study aims to explore the relationship between resilience and HRQoL among NPC patients and to recognize the potential mediating role of loneliness in this relationship. METHODS: A cross-sectional study was performed in this study. A convenience sampling method was conducted to recruit participants. A total of 155 patients with nasopharyngeal carcinoma were required to complete the socio-demographic questionnaire, the Cancer Loneliness Scale (CLS), the 10-item Connor-Davidson Resilience Scale (CD-RISC-10), and the European Organization for Research and Treatment of Quality of Life Questionnaire C-30 (EORTC QLQ-C30) from April 2022 to August 2022 in a tertiary grade A hospital in Guangzhou, China. The multiple linear regression analysis was used to identify influencing factors, and structural equation modeling with the bootstrap method was performed to test the mediating role of loneliness. This study complied with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. RESULTS: HRQoL was at a median level among NPC patients, with a mean score of 64.19 (24.38) on the Global health status/quality of life (GHS/QoL) scale. Monthly household income (B = 4.973, P < 0.001), cancer stage (B=-4.342, P = 0.004), psychological resilience (B = 0.914, P < 0.001), and loneliness (B =-1.083, P < 0.001) were independent factors related to HRQoL, explaining 36.7% of the variance of HRQoL. Psychological resilience exerted its direct negative impact on loneliness (ß = -0.199, BC95%CI = -0.318/-0.089), and it also had a both direct and indirect positive impact on HRQoL (ß = 0.653, BC95%CI = 0.423/0.912; ß = 0.142, BC95%CI = 0.046/0.296). Loneliness exerted a partially mediating impact on the relationship between psychological resilience and HRQoL. CONCLUSIONS: NPC patients with higher monthly household, early stages of cancer, higher resilience, and lower loneliness show a better HRQoL. Resilience has an indirect positive impact on HRQoL by influencing loneliness in NPC patients. It is suggested that healthcare staff should strive to enhancing resilience and reducing loneliness as new strategies to promote NPC patients' HRQoL further.

Construction of Risk-Prediction Models for Autogenous Arteriovenous Fistula Thrombosis in Patients on Maintenance Hemodialysis.

INTRODUCTION: Autogenous arteriovenous fistula (AVF) is the preferred vascular access in patients undergoing maintenance hemodialysis (MHD). However, complications such as thrombosis may occur. This study aimed to construct and validate a machine learning-based risk-prediction model for AVF thrombosis, hypothesizing that such a model can effectively predict occurrences, providing a foundation for early clinical intervention. METHODS: The retrospective longitudinal study included a total of 270 patients who underwent MHD at the Hemodialysis Center of the Second Affiliated Hospital of Harbin Medical University between March 2021 and December 2022. During this study, baseline data and scale information of patients between March 2020 and December 2021 were collected. We recorded outcome indicators between March 2021 and December 2022 for subsequent analyses. Five machine learning models were developed (artificial neural network, logistic regression, ridge classification, random forest, and adaptive boosting). The sensitivity (recall), specificity, accuracy, and precision of each model were evaluated. The effect size of each variable was analyzed and ranked. Models were assessed using the area under the receiver-operating characteristic (AUROC) curve. RESULTS: Among the 270 included patients, 105 had AVF thrombosis (55 male and 50 female patients; age range, 29-79 years; mean age, 56.72 years; standard deviation [SDs], ±13.10 years). Conversely, 165 patients did not have AVF thrombosis (99 male and 66 female patients; age range, 23-79 years; mean age, 53.58 years; SD, ± 13.33 years). During the observation period, approximately 52.6% of patients with AVF experienced long-term complications. The most common complications associated with AVF were thrombosis (105; 38.9%), aneurysm formation (27; 10%), and excessively high output flow (10; 3.7%). Fifty-four (20%) patients with AVF required intervention because of complications associated with vascular access. The AUROC curve of the testing set was between 0.858 and 0.903. CONCLUSION: In this study, we developed five machine learning models to predict the risk of AVF thrombosis, providing a reference for early clinical intervention.

Mitochondrial genomes of Nemourinae species (Plecoptera: Nemouridae) and the phylogenetic implications.

Currently, the classification system of 2 subfamilies within Nemouridae has been widely accepted. However, monophyly of 2 subfamilies has not been well supported by molecular evidence. To date, only mitogenomes from genus Nemoura of the subfamily Nemourinae were used in previous phylogenetic studies and produced conflicting results with morphological studies. Herein, we analyzed mitogenomes of 3 Nemourinae species to reveal their mitogenomic characteristics and to examine genus-level classification among Nemouridae. In this study, the genome organization of 3 mitogenomes is highly conserved in gene order, nucleotide composition, codon usage, and amino acid composition. In 3 Nemourinae species, there is a high variation in nucleotide diversity among the 13 protein-coding genes (PCGs). The Ka/Ks values for all PCGs were far lower than 1, indicating that these genes were evolving under purifying selection. The phylogenetic analyses highly support Nemurella as the sister group to Ostrocerca. Meanwhile, Nemoura is recovered as the sister group of Malenka; they are grouped with other Amphinemurinae and emerged from a paraphyletic Nemourinae. More molecular data from different taxonomic groups are needed to understand stoneflies phylogeny and evolution.

Effect of nonpharmacological interventions on nutrition status, complications and quality of life in head and neck cancer patients undergoing radiotherapy: A systematic review and meta-analysis.

PURPOSE: To evaluate the effect of nonpharmacological therapies on nutrition status, complications and quality of life in head and neck cancer patients and to provide a basis for clinical practice. METHODS: This systematic review was reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Ten databases were systematically searched for all available articles from construction to November 2023. Two researchers independently conducted literature screening, data extraction and quality evaluation. Cochrane Review Manager 5.3 was used for meta-analysis. RESULTS: Finally, 27 RCT studies including 2814 patients with head and neck cancer were included. Five categories of interventions were used: nutritional support, exercise, swallowing function training, psychological intervention and low-level laser therapy. Nonpharmacological interventions can improve body weight loss in patients with HNC at the end of treatment (MD: 1.66 kg; 95% CI: 0.80 to 2.51), and subgroup analysis showed that nutritional support, psychological intervention and low-level laser therapy were effective. Nonpharmacological interventions can also ameliorate decreases in BMI (MD: 0.71; 95% CI: 0.16 to 1.26) and reduce the incidence of malnutrition (RR: 0.76; 95% CI: 0.67 to 0.86), oral mucositis (RR: 0.54; 95% CI: 0.37 to 0.80) and gastrointestinal complications (RR: 0.61; 95% CI: 0.38 to 0.96) during radiotherapy; however, no significant differences were found in other complications and quality of life. CONCLUSION: Nonpharmacological interventions can improve the nutrition status of patients with head and neck cancer and reduce the incidence of severe oral mucositis and gastrointestinal complications during radiotherapy but have no significant impact on quality of life.

Preparation, characterization, bacteriostatic efficacy, and mechanism of zinc/selenium-loaded sodium humate.

In recent years, metal-based complexes including selenium (Se) and zinc (Zn)-containing compounds have been widely explored for their therapeutic properties due to their roles in biological processes and modulation of diverse molecular targets. Humic acid, as a metal complexing agent, is also widely used in biomedical field. In this work, three kinds of modified sodium humate (HNa), including Zn-HNA, Se-HNa, and Zn/Se-HNa, were prepared by ion exchange reaction method. The modified HNa was characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and elemental mapping. The bacteriostatic activity and mechanism of modified HNa against gram-positive and gram-negative bacteria were investigated by testing bacterial inhibition zone, minimum inhibitory concentration, and capacity to destroy integrity of the bacterial membrane, promoting ROS generation level and prevention of biofilms. FTIR results showed that HNa could combine with zinc ions and selenite ions. The main XRD peaks did not change significantly. In the modified HNa, the particle shape was irregular. Compared to HNa, Zn-HNA, and Se-HNa, Zn/Se-HNa showed the strongest bacteriostatic activity. Zn/Se-HNa exhibited high bacteriostatic activity against gram-negative bacteria (Escherichia coli, Salmonella typhimurium, Klebsiella pneumoniae) and gram-positive bacteria (Staphylococcus aureus), but showed weak antibacterial activity against another gram-positive bacteria, Bacillus subtilis. The bacteriostasis was achieved by altering the permeability of bacterial cell membranes, generating ROS, and preventing the formation of biofilms. In conclusion, Zn/Se-HNa has high bacteriostatic activity, making it a suitable alternative to antibiotics in fields like the treatment of trauma infections and animal husbandry. KEY POINTS: • Preparate and characterize zinc- and selenium-loaded sodium humate (Zn/Se-HNa). • The combination of Zn and Se enhanced the bacteriostatic activity of HNa. • Zn/Se-HNa alters the permeability of bacterial cell membranes and promotes generation of ROS.

Construction of a risk prediction model for detecting postintensive care syndrome-mental disorders.

BACKGROUND: Postintensive care syndrome (PICS) has adverse multidimensional effects on nearly half of the patients discharged from ICU. Mental disorders such as anxiety, depression and post-traumatic stress disorder (PTSD) are the most common psychological problems for patients with PICS with harmful complications. However, developing prediction models for mental disorders in post-ICU patients is an understudied problem. AIMS: To explore the risk factors of PICS mental disorders, establish the prediction model and verify its prediction efficiency. STUDY DESIGN: In this cohort study, data were collected from 393 patients hospitalized in the ICU of a tertiary hospital from April to September 2022. Participants were randomly assigned to modelling and validation groups using a 7:3 ratio. Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was performed to select the predictors, multiple logistic regression analysis was used to establish the risk prediction model, and a dynamic nomogram was developed. The Hosmer-Lemeshow (HL) test was performed to determine the model's goodness of fit. The area under the receiver operating characteristic (ROC) curve was used to evaluate the model's prediction efficiency. RESULTS: The risk factors of mental disorders were Sepsis-related organ failure assessment (SOFA) score, Charlson comorbidity index (CCI), delirium duration, ICU depression score and ICU sleep score. The HL test revealed that p = .249, the area under the ROC curve = 0.860, and the corresponding sensitivity and specificity were 84.8% and 71.0%, respectively. The area under the ROC curve of the verification group was 0.848. A mental disorders dynamic nomogram for post-ICU patients was developed based on the regression model. CONCLUSIONS: The prediction model provides a reference for clinically screening patients at high risk of developing post-ICU mental disorders, to enable the implementation of timely preventive management measures. RELEVANCE TO CLINICAL PRACTICE: The dynamic nomogram can be used to systematically monitor various factors associated with mental disorders. Furthermore, nurses need to develop and apply accurate nursing interventions that consider all relevant variables.

The mediating role of self-efficacy in the association between perceived stigma and psychosocial adjustment: a cross-sectional study among nasopharyngeal cancer survivors.

OBJECTIVE: This study aims to examine the levels of and associations between perceived stigma, self-efficacy, and psychosocial adjustment (PA) among nasopharyngeal carcinoma (NPC) survivors, and to identify the mediating role of self-efficacy between stigma and PA and explore the influencing factors of PA. METHODS: A cross-sectional survey was conducted and 307 NPC survivors were recruited by convenience sampling method in Southern China from July 2019 to January 2020. Data analyses were performed with the SPSS WIN 25.0 program and PROCESS macro version 3.3. RESULTS: Stigma and self-efficacy were positively associated with PA among Chinese NPC survivors. Tumor-free survival time, late toxicities (fatigue, dizziness and headache, and hearing loss), stigma, and self-efficacy entered the final regression model and explained 55.9% of the variance of PA. The total and direct effects of stigma on PA and its subscales were significant (p < 0.05). Positive indirect effects were found for stigma on PA via self-efficacy (point estimate = 0.159, SE = 0.032, 95% CI [0.102 to 0.229]). CONCLUSIONS: Stigma and self-efficacy are significantly associated with PA, and self-efficacy is also a mediating variable between stigma and PA among NPC survivors. Medical staff could improve the PA of NPC survivors by alleviating their stigma, enhancing their self-efficacy, and relieving their late toxicities (fatigue, dizziness and headache, and hearing loss).

Stigma, self-efficacy and late toxicities among Chinese nasopharyngeal carcinoma survivors.

OBJECTIVE: This study explores the level of stigma among Chinese nasopharyngeal carcinoma survivors, its influencing factors and relationship with self-efficacy. METHODS: In total, 281 nasopharyngeal carcinoma survivors were recruited from China, who completed the demographic, disease-related and late toxicities questionnaire, as well as the General Self-Efficacy Scale and Social Impact Scale. RESULTS: The mean scores for stigma and self-efficacy were 57.22 ± 9.58 and 28.06 ± 3.97, respectively, both showing a moderate level. The late toxicities with the highest incidence were xerostomia (91.8%), fatigue (78.3%) and hearing loss (63.0%). Stigma was significantly and negatively related to self-efficacy (r = -0.295, P < 0.001). Multivariable linear regression showed that self-efficacy, number of children, educational level, perceived support from spouse and other family members and some late toxicities (nasal obstruction and toothache) were influencing factors of stigma, accounting for 49.4% of the variance. CONCLUSION: Medical staff should be more aware of stigma among Chinese nasopharyngeal carcinoma survivors, especially those with more children and weaker educational backgrounds who are at a higher risk of stigma. They should take effective measures to alleviate stigma by improving patients' self-efficacy, relieving late toxicities and encouraging spouses and family members to provide more support for them.

Prospective assessment of a nasopharyngeal carcinoma risk score in a population undergoing screening.

Despite evidence suggesting the utility of Epstein-Barr virus (EBV) markers to stratify individuals with respect to nasopharyngeal carcinoma (NPC) risk in NPC high-risk regions, no validated NPC risk prediction model exists. We aimed to validate an EBV-based NPC risk score in an endemic population undergoing screening for NPC. This prospective study was embedded within an ongoing NPC screening trial in southern China initiated in 2008, with 51 235 adult participants. We assessed the score's discriminatory ability (area under the receiver-operator-characteristics curve, AUC). A new model incorporating the EBV score, sex and family history was developed using logistic regression and internally validated using cross-validation. AUCs were compared. We also calculated absolute NPC risk combining the risk score with population incidence and competing mortality data. A total of 151 NPC cases were detected in 2008 to 2016. The EBV-based score was highly discriminating, with AUC = 0.95 (95% CI = 0.93-0.97). For 90% specificity, the score had 87.4% sensitivity (95% CI = 81.0-92.3%). As specificity increased from 90% to 99%, the positive predictive value increased from 2.4% (95% CI = 1.9-3.0%) to 12.5% (9.9-15.5%). Correspondingly, the number of positive tests per detected NPC case decreased from 272 (95% CI = 255-290) to 50 (41-59). Combining the score with other risk factors (sex, first-degree family history of NPC) did not improve AUC. Men aged 55 to 59 years with the highest risk profile had the highest 5-year absolute NPC risk of 6.5%. We externally validated the discriminatory accuracy of a previously developed EBV score in a high-risk population. Adding nonviral risk factors did not improve NPC prediction.

Multidimensional fatigue in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy: incidence, severity, and risk factors.

PURPOSE: To explore the incidence, severity, and risk factors of multidimensional fatigue in patients with nasopharyngeal carcinoma (NPC) receiving concurrent chemoradiotherapy (CCRT). METHODS: This prospective study included 79 patients with NPC in Guangzhou (China) from June 2015 to July 2018. Data were collected before and after CCRT, including demographic and clinical characteristics, nutritional parameters, and fatigue scores, based on completion of the Multiple Dimensional Inventory-20 Questionnaire, with five subscales: General Fatigue, Mental Fatigue, Physical Fatigue, Reduced Activity, and Reduced Motivation. RESULTS: Increased general fatigue was found to be associated with lower lymphocyte count and body mass index <23 kg/m2. Increased physical fatigue was related to age > 42 years. Higher scores for reduced activity were associated with age > 42 years, female sex, and lower serum sodium. Increased mental fatigue was related with lower lymphocyte count and unemployment; and increased total fatigue was associated with lower lymphocyte count, age > 42 years, and 3-6 courses of treatment. Furthermore, 3-6 courses of treatment was an independent predictor of severe general fatigue, while age >42 years was an independent predictor of severe physical fatigue. Importantly, cancer stage IVB and 3-6 courses of treatment could predict severe total fatigue. CONCLUSIONS: Our data demonstrate that fatigue is increased in all dimensions in NPC patients following CCRT, and that the predictors differ for each fatigue dimension. These results could guide the development of targeted interventions that may reduce the impact of cancer-related fatigue in patients with NPC.

Construction of a comprehensive nutritional index and comparison of its prognostic performance with the PNI and NRI for survival in older patients with nasopharyngeal carcinoma: a retrospective study.

OBJECTIVES: To explore the relationship between the Comprehensive Nutritional Index (CNI) and survival in older patients with nasopharyngeal carcinoma (NPC) and to compare the prognostic performance of three nutritional indicators (CNI, Prognostic Nutritional Index (PNI), and Nutritional Risk Index (NRI)) for overall survival (OS). METHODS: This retrospective study involved 309 older NPC patients in Guangzhou (China) from November 2006 to November 2017. The CNI comprised five parameters: the body mass index (BMI), usual body weight percentage (UBW%), hemoglobin (Hb) level, albumin level, and total lymphocyte count (TLC). All single nutritional indicators were evaluated before and immediately after treatment. The principal component analysis (PCA) was used for calculation of the CNI by single nutritional indicators after treatment. The cutoff point for the CNI was evaluated and logistic regression used to explore the risk factors for the CNI. Univariable, multivariable Cox regression, and Kaplan-Meier methods were applied for OS and disease-free survival (DFS) analyses. Cox proportional hazards models were used to compare the prognostic value of the CNI, PNI, and NRI for OS. RESULTS: All single nutritional indicators decreased significantly after treatment (P < 0.05). The CNI cutoff point for mortality was 0.027, and the logistic regression indicated more complex treatments or higher cancer stage for NPC was associated with a low CNI (HR = 0.179; 95% CI: 0.037-0.856; 0.545, 0.367-0.811, respectively). In multivariable Cox regression, the CNI remained an independent prognostic factor of OS and DFS (HR = 0.468, 95% CI: 0.263-0.832; 0.527, 0.284-0.977, respectively). Kaplan-Meier curves showed that a low CNI was associated with worse OS and DFS (P = 0.001 and 0.013, respectively). The prognostic predictive performance of the CNI was superior to that of the PNI or NRI. CONCLUSIONS: The CNI can be recommended as an appropriate indicator reflecting the integrated nutritional status of older NPC patients. A low CNI predicted a poor survival outcome and the prognostic performance of CNI was superior to PNI or NRI.

Pharmacokinetics and pharmacodynamics of enrofloxacin treatment of Escherichia coli in a murine thigh infection modeling.

BACKGROUND: Enrofloxacin is an antibacterial drug with broad-spectrum activity that is widely indicated for veterinary use. We aim to develop the clinical applications of Enrofloxacin against colibacillosis by using the neutropenic mice thigh infection model. RESULTS: The minimum inhibitory concentration (MIC) distribution of 67 isolated E. coli strains to ENR was calculated using CLSI guidelines. Whereas, the MIC50 value calculation was considered as the population PD parameter for ENR against E. coli strains. The MIC values of 15 E. coli strains were found to be nearest to the MIC50 i.e., 0.25 µg/mL. Of all the tested strains, the PK-PD and E. coli disease model was established via selected E. coli strain i.e., Heilong 15. We analyzed the PK characteristics of ENR and its metabolite ciprofloxacin (CIP) following a single subcutaneous (s.c.) injection of ENR (1.25, 2.5, 5, 10 mg/kg). The concentration-time profiling of ENR within the plasma specimens was determined by considering the non-compartmental analysis (NCA). The basic PK parameters of ENR for the peak drug concentration (Cmax) and the area under the concentration-time curve (AUC) values were found to be in the range of 0.27-1.97 µg/mL and 0.62-3.14 µg.h/mL, respectively. Multiple s.c. injection over 24 h (1.25, 2.5, 5, 10 mg/kg at various time points i.e., 6, 8, 12, and 24 h respectively) were administered to assess the targeted PD values. The Akaike Information Criterion (AIC) was used to choose PD models, and the model with the lowest AIC was chosen. The inhibitory Emax model was employed to calculate the related PK-PD parameters. The results of our study indicated that there was a strong correlation between the AUC/MIC and various antibacterial activities (R2 = 0.9928). The target values of dividing AUC/MIC by 24 h for bacteriostatic action were 1-log10 reduction, 2-log10 reduction, and 3-log10 reduction 0.325, 0.4375, 0.63, and 0.95 accordingly. CONCLUSION: The identified pharmacodynamics targets for various antibacterial effects will be crucial in enhancing ENR clinical applications and serving as a key step in reducing bacterial resistance.

Machine learning-based patient classification system for adult patients in intensive care units: A cross-sectional study.

AIM: This study aimed to develop a patient classification system that stratifies patients admitted to the intensive care unit based on their disease severity and care needs. BACKGROUND: Classifying patients into homogenous groups based on clinical characteristics can optimize nursing care. However, an objective method for determining such groups remains unclear. METHODS: Predictors representing disease severity and nursing workload were considered. Patients were clustered into subgroups with different characteristics based on the results of a clustering algorithm. A patient classification system was developed using a partial least squares regression model. RESULTS: Data of 300 patients were analysed. Cluster analysis identified three subgroups of critically patients with different levels of clinical trajectories. Except for blood potassium levels (p = .29), the subgroups were significantly different according to disease severity and nursing workload. The predicted value ranges of the regression model for Classes A, B and C were <1.44, 1.44-2.03 and >2.03. The model was shown to have good fit and satisfactory prediction efficiency using 200 permutation tests. CONCLUSIONS: Classifying patients based on disease severity and care needs enables the development of tailored nursing management for each subgroup. IMPLICATIONS FOR NURSING MANAGEMENT: The patient classification system can help nurse managers identify homogeneous patient groups and further improve the management of critically ill patients.

Tumor-associated antigen-based personalized dendritic cell vaccine in solid tumor patients.

Tumor-associated antigens (TAAs) have been tested in various clinical trials in cancer treatment but the patterns of specific T cell response to personalized TAA immunization remains to be fully understood. We report antigen-specific T cell responses in patients immunized with dendritic cell vaccines pulsed with personalized TAA panels. Tumor samples from patients were first analyzed to identify overexpressed TAAs. Autologous DCs were then transfected with pre-manufactured mRNAs encoding the full-length TAAs, overexpressed in the patients' tumors. Patients with glioblastoma multiforme (GBM) or advanced lung cancer received DC vaccines transfected with personalized TAA panels, in combination with low-dose cyclophosphamide, poly I:C, imiquimod and anti-PD-1 antibody. Antigen-specific T cell responses were measured. Safety and efficacy were evaluated. A total of ten patients were treated with DC vaccines transfected with personalized TAA panels containing 3-13 different TAAs. Among the seven patients tested for anti-TAA T cell responses, most of the TAAs induced antigen-specific CD4+ and/or CD8+ T cell responses, regardless of their expression levels in the tumor tissues. No Grade III/IV adverse events were observed among these patients. Furthermore, the treated patients were associated with favorable overall survival when compared to patients who received standard treatment in the same institution. Personalized TAA immunization-induced-specific CD4+ and CD8+ T cell responses without obvious autoimmune adverse events and was associated with favorable overall survival. These results support further studies on DC immunization with personalized TAA panels for combined immunotherapeutic regimens in solid tumor patients.Trial registration ClinicalTrials.gov, NCT02709616 (March, 2016), NCT02808364 (June 2016), NCT02808416 (June, 2016).

Dihydromethysticin, a natural molecule from Kava, suppresses the growth of colorectal cancer via the NLRC3/PI3K pathway.

Dihydromethysticin (DHM), a natural compound derived from Kava, has been reported to be effective against mental disorders and some malignant tumors. However, little is known about the inhibitory effect of DHM on colorectal cancer (CRC). First, we examined the impact of DHM on human colon cancer cell lines, which demonstrated that DHM inhibits proliferation, migration, and invasion and promotes apoptosis and cell cycle arrest in colon cancer cells in vitro. Using small hairpin RNA, we inhibited nucleotide-oligomerization domain-like receptor subfamily C3 (NLRC3)/phosphoinositide 3-kinase (PI3K) pathway to elucidate the partial signaling of DHM-mediated tumor suppression. Additionally, using an ectopic human CRC model, we verified whether DHM inhibits tumor growth and angiogenesis via the NLRC3/PI3K pathway in vivo. Overall, DHM showed an inhibitory effect on CRC by altering cell proliferation, migration, invasion, apoptosis, cell cycle, and angiogenesis, possibly via the NLRC3/PI3K pathway. Thus, DHM may be a promising candidate for CRC therapy.

A Becn1 mutation mediates hyperactive autophagic sequestration of amyloid oligomers and improved cognition in Alzheimer's disease.

Impairment of the autophagy pathway has been observed during the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder characterized by abnormal deposition of extracellular and intracellular amyloid ß (Aß) peptides. Yet the role of autophagy in Aß production and AD progression is complex. To study whether increased basal autophagy plays a beneficial role in Aß clearance and cognitive improvement, we developed a novel genetic model to hyperactivate autophagy in vivo. We found that knock-in of a point mutation F121A in the essential autophagy gene Beclin 1/Becn1 in mice significantly reduces the interaction of BECN1 with its inhibitor BCL2, and thus leads to constitutively active autophagy even under non-autophagy-inducing conditions in multiple tissues, including brain. Becn1F121A-mediated autophagy hyperactivation significantly decreases amyloid accumulation, prevents cognitive decline, and restores survival in AD mouse models. Using an immunoisolation method, we found biochemically that Aß oligomers are autophagic substrates and sequestered inside autophagosomes in the brain of autophagy-hyperactive AD mice. In addition to genetic activation of autophagy by Becn1 gain-of-function, we also found that ML246, a small-molecule autophagy inducer, as well as voluntary exercise, a physiological autophagy inducer, exert similar Becn1-dependent protective effects on Aß removal and memory in AD mice. Taken together, these results demonstrate that genetically disrupting BECN1-BCL2 binding hyperactivates autophagy in vivo, which sequestrates amyloid oligomers and prevents AD progression. The study establishes new approaches to activate autophagy in the brain, and reveals the important function of Becn1-mediated autophagy hyperactivation in the prevention of AD.