PEGylated Gambogic Acid Nanoparticles Enable Efficient Renal-Targeted Treatment of Acute Kidney Injury.

Acute kidney injury (AKI) is a common clinical syndrome lacking effective pharmacotherapy. Gambogic acid (GA), as an active ingredient of herbal medicines, exhibits antioxidant and anti-inflammatory effects that benefit the treatment of AKI, but its poor aqueous solubility limits effective renal delivery. We, for the first time, developed GA-based nanoparticles (GA-NPs) with preferential renal uptake for AKI treatment. By PEGylating with NH2-PEG5000-NOTA, hydrophobic GA was self-assembled into ∼4.5 nm nanoparticles, which showed the enhanced renal accumulation in AKI models from PET images. Importantly, the in vitro cell assays and in vivo tests of the two AKI models have confirmed the obvious nephroprotective effects and biosafety of GA-NPs. Therefore, this work indicates that GA-NPs can be a promising therapeutic candidate for the management of AKI.

The role of dry mouth in screening sleep apnea.

PURPOSE OF THE STUDY: Effective screening questionnaires are essential for early detection of obstructive sleep apnea (OSA). The STOP-Bang questionnaire has high sensitivity but low specificity. Dry mouth is a typical clinical sign of OSA. We hypothesised that adding dry mouth in the STOP-Bang questionnaire would improve its specificity. STUDY DESIGN: A survey of the incidence of dry mouth was performed in a general population group and suspected sleep apnea clinical population group. Patients with suspected OSA were assessed by laboratory polysomnography and STOP-Bang questionnaire was performed. Adding the option of dry mouth to the OSA screening questionnaire resulted in a new quesionnaire, where cut-off value, diagnostic efficacy and the predictive parameters (sensitivity, specificity, positive predictive value and negative predictive value) were explored. RESULTS: (In the 912 general population group, the incidence of dry mouth in the snoring group (54.0%) was much higher than that in the non-snoring group (30.5%) (p<0.05). In 207 patients with suspected OSA, the incidence of dry mouth in the OSA group was much higher than that in the non-OSA group (p<0.05). The sensitivity and specificity of the STOP-Bang questionnaire were 88.8% and 23.7% for identifying OSA, and 92.2% and 23.1% for identifying moderate and severe OSA, respectively. Adding the option of dry mouth (dry mouth every morning) to the STOP-Bang questionare resulted in a new questionnaire (STOP-Bang-dry-mouth questionnarie) with 9 items. Its sensitivity and specificity were 81.70% and 42.10% for identifying OSA, and 89.10% and 42.30% for identifying moderate and severe OSA, respectively. CONCLUSIONS: The dry mouth symptom correlated with snoring and sleep apnea. The specificity of the STOP-Bang questionnaire can be improved by integrating dry mouth. The diagnostic accuracy of the STOP-Bang-dry mouth questionnaire is yet to be further verified in prospective studies.

One-Step Instantaneous Detection of Multiple Military and Improvised Explosives Facilitated by Colorimetric Reagent Design.

Although colorimetric detection based on reagents has been widely used in the fields of practical trace analysis, its versatility for detecting multitargets remains the most challenging problem. As a proof of concept, a general colorimetric reagent based on potassium isopropanol (C3H7KO) and dimethyl sulfoxide for one-step instantaneous detection and discrimination of typical military and improvised explosives was designed. Vivid colors from none to purple red, blue green, yellow green, and green were shown, respectively, when detecting 2,4,6-trinitrotoluene (TNT), 2,4-dinitrotoluene (DNT), elemental sulfur (S), and potassium permanganate (KMnO4). The unique design including the specific nucleophilic addition reaction and the base-catalyzed oxidation-induced electron transfer ensures perfect selectivity even upon facing more than 20 interferents. It is further experimentally demonstrated that the confinement effect introduced by Tween-20 plays an essential role in enhancing the color signal on the surface and thus boosts the detection performance even with a mass as low as 1.45 ng. The applicability of this versatile colorimetric reagent was further verified by integrating the reagent onto paper strips for the in-field identification of TNT, DNT, S, and KMnO4 with the help of a portable smartphone-based microscope apparatus, and a practical detection mass of 10.3 ng could be realized. We expect the present colorimetric reagent design strategy would pave a way for one-step instantaneous visual detection toward trace multianalytes.

Correlation of morning dry mouth with clinical features of OSA in a community population: a cross-sectional study.

OBJECTIVES: Morning dry mouth, commonly seen in Obstructive Sleep Apnea (OSA) patients, is absent in current OSA screening tools. This study evaluated the link between morning dry mouth and OSA's clinical symptoms and complications, aiming to determine its viability as a screening indicator. METHODS: This research analyses baseline data from a prospective cohort study (the PIFCOPD study). Demographic information, medical history, and the presence of morning dry mouth symptoms were collected. The STOP-Bang questionnaire was performed for OSA screening. Logistic regression analyses were employed to establish the correlations between morning dry mouth and the clinical symptoms and comorbidities of OSA. RESULT: 1291 participants (62.1±7.5 years; 501 males, 790 females) were included, of which 416 reported morning dry mouth (32.2%). 42.6% in the high-risk OSA group and 22.1% in the low-risk group reported morning dry mouth. Individuals with morning dry mouth also showed higher STOP-Bang scores (3.3±1.6 vs. 2.3±1.4, P<0.01). Significant associations were found between morning dry mouth and loud snoring, observed sleep apnea, daytime fatigue, and hyperlipidemia (P<0.01), but not with alcohol consumption, tea consumption, diabetes, or hypertension. CONCLUSION: Morning dry mouth is associated with increased OSA risk and its clinical signs, suggesting its potential as an OSA screening symptom. CLINICAL TRIAL REGISTRATION: This study has been registered at www.ClinicalTrials.gov (registration identifier: NCT03532893) on 21 May 2018.

Modified STOP-bang questionnaire incorporating morning dry mouth and BMI adjustment in China: a retrospective study of 590 patients.

BACKGROUND: Morning dry mouth (MDM) is a common symptom of Obstructive Sleep Apnea (OSA) yet current OSA screening tools overlook it. OBJECTIVE: To enhance the specificity of the Stop-Bang questionnaire (SBQ) by adding an MDM symptom. METHOD: A retrospective analysis on 590 patients from Peking University First Hospital (2013-2018) suspected of OSA was conducted. They underwent polysomnography. The research incorporated the MDM symptom into SBQ and adjusted the body mass index (BMI) threshold to 28 kg/m2. Predictive parameters were then calculated. RESULTS: 83.1% patients were diagnosed with OSA, with 61.4% reporting MDM. Multivariate regression confirmed MDM significantly influenced Apnea-Hypopnea Index (AHI). Adjusted SBQ with MDM showed a slight decrease in sensitivity but improved specificity, especially when using a BMI threshold of > 28 kg/m2. For AHI ≥ 5 events/h and AHI ≥ 15 events/h, adjusted SBQ with MDM (BMI >28 kg/m2) obtained the highest Youden index. CONCLUSION: Incorporating the MDM symptom into SBQ and adjusting the BMI threshold enhances the diagnostic specificity for OSA.

Multivariate analysis approach for correlations between material properties and tablet tensile strength of microcrystalline cellulose.

In this study we applied statistical multivariate analysis techniques to establish correlations between material properties and tablet tensile strength (TS) of microcrystalline cellulose (MCC) with different types and manufacturers. There were sixteen MCC samples included in this analysis described by 22 material parameters. For data analysis, principal component analysis (PCA) was used to model and evaluate the various relationships between the material properties and TS. Furthermore, partial least squares regression (PLS) analysis was performed to quantify the relationships between the material properties and TS and to predict the most influential MCC parameters contributing to the compactibility. The results showed that the moisture content, hygroscopicity and crystallinity did not exhibit significant impact on TS. The turgidity, maximum water uptake, degree of polymerization and molecular weight presented a strong positive influence on TS, while the density property, bulk and tap density, exhibited an obvious negative impact. The present work demonstrated that multivariate data analysis techniques (PCA and PLS) are useful for interpreting complex relations between 22 material properties and the tabletting properties of MCC. Furthermore, the method can be used for material classification.

Impact of Upper Airway Characteristics on Disease Severity and CPAP Therapy in Chinese Patients With OSA: An Observational Retrospective Study.

Objective: The characteristics of the upper airway (UA) are important for the evaluation and treatment of obstructive sleep apnea (OSA). This study aimed to investigate the association of UA characteristics with OSA severity, titration pressure, and initiation of and 3-month compliance with continuous positive airway pressure (CPAP). Methods: This retrospective study included consecutive patients examined using a semi-quantitative UA evaluation system (combination with physical examination and awake endoscopy) during 2008-2018 at the Department of Respiratory and Critical Care Medicine, Peking University First Hospital. First, the differences in UA characteristics were compared between patients with simple snorers and mild OSA and those with moderate-to-severe OSA. Then, the effect of UA characteristics on the initiation to CPAP therapy and 3-month adherence to CPAP was conducted. Results: Overall, 1,002 patients were included, including 276 simple snorers and patients in the mild OSA group [apnea-hypopnea index (AHI) <15] and 726 patients in the moderate-to-severe OSA group (AHI ≥15). Tongue base hypertrophy, tonsillar hypertrophy, mandibular recession, neck circumstance, and body mass index (BMI) were independent risk factors for moderate-to-severe OSA. Among those patients, 119 patients underwent CPAP titration in the sleep lab. The CPAP pressures in patients with thick and long uvulas, tonsillar hypertrophy, lateral pharyngeal wall stenosis, and tongue hypertrophy were higher than those of the control group (P < 0.05, respectively). The logistic regression analysis showed that nasal turbinate hypertrophy, mandibular retrusion, and positive Müller maneuver in the retropalate and retroglottal regions were independent predictors for the initiation of home CPAP treatment. Conclusion: Multisite narrowing and function collapse of the UA are important factors affecting OSA severity, CPAP titration pressure, and the initiation of home CPAP therapy. Clinical evaluation with awake endoscopy is a safe and effective way for the assessment of patients with OSA in internal medicine.

Polyethyleneimine-capped copper nanoclusters for detection and discrimination of 2,4,6-trinitrotoluene and 2,4,6-trinitrophenol.

The detection and discrimination of 2,4,6-trinitrotoluene (TNT) and 2,4,6-trinitrophenol (TNP) from analogues are of great importance to global security and are full of challenges in the field of trace sensing. Here, benefitting from the strong electrophilicity of TNT, a sensing strategy is established by synthesizing polyethyleneimine capped copper nanoclusters (PEI-Cu NCs) with abundant -NH2 groups. By carefully controlling the size and structure of PEI-Cu NCs, Förster resonance energy transfer (FRET) from PEI-Cu NCs to the Meisenheimer complex occurs resulting from their spectral overlap when detecting TNT, while, due to the energy level match of TNP with PEI-Cu NCs, as well as the strong affinity between its -OH and -NH2 in PEI-Cu NCs, photo-induced electron transfer (PET) is feasibly expected. As a result, TNT and TNP could be detected from 26 types of analogues and cations with a limit of detection (LOD) of 26.57 and 12.82 nM, respectively. Besides, owing to the brown color of the Meisenheimer complex, the discrimination of TNT and TNP could be additionally realized by colorimetric detection. We expect that the proposed methodology would not only shine light on the detection and discrimination of TNT and TNP that mitigate against public security concerns, but also pave a way for the deep understanding of FRET and PET related fluorescence quenching mechanisms from the aspect of controllable sensing material design and synthesis.

Highly Retentive, Anti-Interference, and Covert Individual Marking Taggant with Exceptional Skin Penetration.

The development of high-performance individual marking taggants is of great significance. However, the interaction between taggant and skin is not fully understood, and a standard for marking taggants has yet to be realized. To achieve a highly retentive, anti-interference, and covert individual marking fluorescent taggant, Mn2+ -doped NaYF4 :Yb/Er upconversion nanoparticles (UCNPs), are surface-functionalized with polyethyleneimine (PEI) to remarkably enhance the interaction between the amino groups and skin, and thus to facilitate the surface adhesion and chemical penetration of the taggant. Electrostatic interaction between PEI600 -UCNPs and skin as well as remarkable penetration inside the epidermis is responsible for excellent taggant retention capability, even while faced with robust washing, vigorous wiping, and rubbing for more than 100 cycles. Good anti-interference capability and reliable marking performance in real cases are ensured by an intrinsic upconversion characteristic with a distinct red luminescent emission under 980 nm excitation. The present methodology is expected to shed light on the design of high-performance individual marking taggants from the perspective of the underlying interaction between taggant and skin, and to help advance the use of fluorescent taggants for practical application, such as special character tracking.

Paclitaxel liposome for injection (Lipusu) plus cisplatin versus gemcitabine plus cisplatin in the first-line treatment of locally advanced or metastatic lung squamous cell carcinoma: A multicenter, randomized, open-label, parallel controlled clinical study.

BACKGROUND: Lipusu is the first commercialized liposomal formulation of paclitaxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma (LSCC) in a small-scale study. Here, we conducted a multicenter, randomized, phase 3 study to compare the efficacy and safety of cisplatin plus Lipusu (LP) versus cisplatin plus gemcitabine (GP) as first-line treatment in locally advanced or metastatic LSCC. METHODS: Patients enrolled were aged between 18 to 75 years, had locally advanced (clinical stage IIIB, ineligible for concurrent chemoradiation or surgery) or metastatic (Stage IV) LSCC, had no previous systemic chemotherapy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors (version 1.1) before administration of the trial drug. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. To explore the possible predictive value of plasma cytokines for LP treatment, plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology. The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses. RESULTS: The median duration of follow-up was 15.4 months. 237 patients in the LP group and 253 patients in the GP group were included in the per protocol set (PPS). In the PPS, the median PFS was 5.2 months versus 5.5 months in the LP and GP group (hazard ratio [HR]: 1.03, P = 0.742) respectively. The median OS was 14.6 months versus 12.5 months in the LP and GP group (HR: 0.83, P = 0.215). The ORR (41.8% versus 45.9%, P = 0.412) and DCR (90.3% versus 88.1%, P = 0.443) were also similar between the LP and GP group. A significantly lower proportion of patients in the LP group experienced adverse events (AEs) leading to treatment interruptions (10.9% versus 26.4%, P < 0.001) or treatment termination (14.3% versus 23.1%, P = 0.011). The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR, and 15 cytokines were associated with improved PFS, with 14 cytokines, including TNF-α, IFN-γ, IL-6, and IL-8, demonstrating an overlapping trend. CONCLUSION: The LP regimen demonstrated similar PFS, OS, ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles. The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen.