The implementation of the guideline for the management of pediatric off-label use of drugs in China: a cross-sectional study.

Background: Previously, we developed the Guidelines for the Management of Pediatric Off-Label Use of Drugs in China in addressing the need for standardization of pediatric off-label drug use. As the implementation of recommendations in Guidelines among healthcare professionals is weak, it is important to identify barriers to guideline implementation for developing appropriate strategies for specific settings and target groups. This study aimed to assess the difficulty and urgency in implementing the recommendations in the Guideline, identifying the factors affecting the implementation of these recommendations to realize the clinical translation of the Guideline.

Predicting Peptide Ionization Efficiencies for Electrospray Ionization Mass Spectrometry Using Machine Learning.

Mass spectrometry (MS) is inherently an information-rich technique. In this era of big data, label-free MS quantification for nontargeted studies has gained increasing popularity, especially for complex systems. One of the cornerstones of successful label-free quantification is the predictive modeling of ionization efficiency (IE) based on solutes' physicochemical properties.

Myelin modulates the process of isoflurane anesthesia through the regulation of neural activity.

Aims: The mechanism underlying the reversible unconsciousness induced by general anesthetics (GA) remains unclear. Recent studies revealed the critical roles of myelin and oligodendrocytes (OLs) in higher functions of the brain. However, it is unknown whether myelin actively participates in the regulation of GA.

Improved clearance of host cell protein impurities at the polishing purification step using multimodal chromatography.

In biotherapeutic protein production, host cell proteins (HCPs) are one of the main process related impurities which must be cleared and controlled through downstream processing. In this paper, we studied a novel therapeutic protein molecule which had a high level of HCP co-purification throughout the downstream process. Here, we focused on the polishing purification step and developed an effective strategy for improving HCP clearance using multimodal chromatography (MMC) resin, Nuvia cPrime.

Paediatric off-label use of drugs in Gansu, China: a multicentre cross-sectional study.

Objective: To examine the current prevalence and cost of paediatric off-label drug prescriptions in Gansu, China, and the potential influencing factors.

Design: The prevalence of off-label prescriptions in paediatrics was evaluated according to the National Medical Products Administration drug instructions in the China Pharmaceutical Reference (China Pharmaceutical Reference, MCDEX) database. The evidence of the prescription was determined by existing clinical practice guidelines and the Thomson Grade in the Micromedex 2021 compendium.

Blood transfusion is correlated with elevated adult all-cause mortality and cardiovascular mortality in the United States: NHANES 1999 to 2018 population-based matched propensity score study.

Background And Aims: The association of blood transfusion with an increase in medium- and short-term mortality in specific populations has been confirmed. However, the correlation between blood transfusion and long-term mortality in the general population remains unclear. This cohort study evaluated the correlation between blood transfusion and overall and cause-specific mortality in the general American adult population.

Pharmacokinetics, Pharmacodynamics, and Safety of Single Dose HSK7653 Tablets in Chinese Subjects with Normal or Impaired Renal Function.

Objective: HSK7653 is a novel, ultralong-acting dipeptidyl peptidase-4 (DPP-4) inhibitor, promising for type 2 diabetes mellitus with a dosing regimen of once every 2 weeks. This trial investigates the pharmacokinetics (PKs), pharmacodynamics (PDs),and safety of HSK7653 in outpatients with normal or impaired renal function.

Methods: This is a multicenter, open-label, nonrandomized, parallel-controlled phase I clinical study that investigates the pharmacokinetic profiles of HSK7653 after a single oral administration in 42 subjects with mild (n = 8), moderate (n = 10), severe renal impairment (n = 10), and end-stage renal disease (without dialysis, n = 5) compared with matched control subjects with normal renal function (n = 9).

m6A-Mediated Biogenesis of circDDIT4 Inhibits Prostate Cancer Progression by Sequestrating ELAVL1/HuR.

Unlabelled: The pathologic significance of the circular RNA DDIT4 (circDDIT4), which is formed by backsplicing at the 3'-untranslated region (UTR) with a 5' splice acceptor site in exon 2 of linear DDIT4 mRNA, has yet to be determined. Our study found that circDDIT4 is downregulated in prostate cancer and functions as a tumor suppressor during prostate cancer progression. By competitively binding to ELAV-like RNA binding protein 1 (ELAVL1/HuR) through its 3'-UTR, circDDIT4 acts as a protein sponge to decrease the expression of prostate cancer-overexpressed anoctamin 7 (ANO7).

Association of serum uric acid with risk of stroke in US adults: A cross-sectional study from NHANES 1999-2020.

Background And Aims: The validity of high uric acid levels as an independent cause of stroke remains controversial, and the association between its low concentration and stroke is unclear. This study determines how different serum uric acid (SUA) levels are associated with stroke risk.

Methods: This cross-sectional study used continuous National Health and Nutrition Examination Survey data in the United States during 1999-2020.

Can adding personalized rule-based feedback improve the therapeutic effect of self-help digital cognitive behavioral therapy for insomnia in young adults?

Introduction: Cognitive-behavioral therapy for insomnia (CBT-I) is recommended as the first-line treatment for insomnia, but low accessibility and relatively high cost limits the dissemination of the treatment. Several forms of digital CBT-I have been developed to increase the accessibility and shown to be effective; however, the treatment effect may be restricted by the lack of interaction within the treatment. The current study examines whether the therapeutic effects of self-help digital CBT-I could be enhanced by adding simple rule-based personalized feedback.

Identification of Long Noncoding RNAs That Exert Transcriptional Regulation by Forming RNA-DNA Triplexes in Prostate Cancer.

Long noncoding RNAs (lncRNAs) are involved in transcriptional regulation, and their deregulation is associated with the development of various human cancers, including prostate cancer (PCa). However, their underlying mechanisms remain unclear. In this study, lncRNAs that interact with DNA and regulate mRNA transcription in PCa were screened and identified to promote PCa development.

Using New Peak Detection to Solve Sequence Variants Analysis Challenges in Bioprocess Development.

Recombinant therapeutic proteins have become the major class of drugs to treat various human diseases in recent years. Low levels of protein sequence variants (SVs) have been reported to be present in recombinant therapeutic proteins. The consequences of potential unwanted immune response from SVs of recombinant therapeutic proteins have increasingly drawn attention from regulatory authorities and the biopharmaceutical industry.

Combined Ultrasound-Guided Thoracic Paravertebral Nerve Block with Subcostal Transversus Abdominis Plane Block for Analgesia After Total Minimally Invasive Mckeown Esophagectomy: A Randomized, Controlled, and Prospective Study.

Introduction: Thoracic paravertebral block (TPVB) and subcostal transverse abdominis plane block (TAP) have been considered to provide an effective analgesic effect for laparoscopic and thoracoscopic surgery, respectively. The purpose of this randomized, controlled, and prospective study was to evaluate the analgesic effect of TPVB combined with TAP in patients undergoing total minimally invasive Mckeown esophagectomy.

Methods: Between February 2020 and December 2021, a total of 168 esophageal cancer patients undergoing McKeown esophagectomy at the Cancer Center of Sun Yat-Sen University, China, were randomly assigned to receive patient-controlled epidural analgesia alone (group PCEA, n = 56), patient-controlled intravenous analgesia alone (group PCIA, n = 56), and TPVB combined with TAP and patient-controlled intravenous analgesia (group PVB, n = 56).

Androgen-Responsive Oncogenic lncRNA RP11-1023L17.1 Enhances c-Myc Protein Stability in Prostate Cancer.

Long noncoding RNAs (lncRNAs) have been found as novel participants in the pathophysiology of prostate cancer (PCa), which is predominantly regulated by androgen and its receptor. The biological function of androgen-responsive lncRNAs remains poorly understood. Here, we identified that lncRNA RP11-1023L17.

Attribute Analytics Performance Metrics from the MAM Consortium Interlaboratory Study.

The multi-attribute method (MAM) was conceived as a single assay to potentially replace multiple single-attribute assays that have long been used in process development and quality control (QC) for protein therapeutics. MAM is rooted in traditional peptide mapping methods; it leverages mass spectrometry (MS) detection for confident identification and quantitation of many types of protein attributes that may be targeted for monitoring. While MAM has been widely explored across the industry, it has yet to gain a strong foothold within QC laboratories as a replacement method for established orthogonal platforms.

Regulates the Transcription of AR Target Genes by Antagonizing NONO.

The androgen receptor (AR) and its related signaling pathways play an important role in the development of prostate cancer (PCa). Long non-coding RNAs (lncRNAs) are involved in the regulation of tumorigenesis and development, but their specific mechanism of action remains unclear. This study examines the function and mechanisms of action of lncRNA in the development of PCa.

Comprehensive Characterization of Androgen-Responsive circRNAs in Prostate Cancer.

The androgen receptor (AR) signaling pathway plays an important role in the initiation and progression of prostate cancer. Circular RNAs (circRNAs), the novel noncoding RNAs without 5' to 3' polarity or 3' poly (A), play an important role in multiple diseases. However, the potential roles of androgen-responsive circRNAs in prostate cancer remain unclear.

New Peak Detection Performance Metrics from the MAM Consortium Interlaboratory Study.

The Multi-Attribute Method (MAM) Consortium was initially formed as a venue to harmonize best practices, share experiences, and generate innovative methodologies to facilitate widespread integration of the MAM platform, which is an emerging ultra-high-performance liquid chromatography-mass spectrometry application. Successful implementation of MAM as a purity-indicating assay requires new peak detection (NPD) of potential process- and/or product-related impurities. The NPD interlaboratory study described herein was carried out by the MAM Consortium to report on the industry-wide performance of NPD using predigested samples of the NISTmAb Reference Material 8671.

A nomogram for predicting the risk of no-reflow after primary percutaneous coronary intervention in elderly patients with ST-segment elevation myocardial infarction.

Background: The purpose of this study was to screen the predictive factors of no-reflow after a percutaneous coronary intervention (PCI) in elderly patients with ST-segment elevation myocardial infarction (STEMI), and to construct a nomogram model, to guide clinical treatment.

Methods: A total of 551 elderly STEMI patients (age >65) underwent direct PCI were randomly classified into training group (n=386, 70%) and validation group (n=165, 30%). All patients in the two groups were divided into a no-reflow group and a normal blood flow group according to whether there was a no-reflow phenomenon.

Transcriptional network modulated by the prognostic signature transcription factors and their long noncoding RNA partners in primary prostate cancer.

Background: Transcriptional regulators are seminal players in the onset and progression of prostate cancer. However, clarification of their underlying regulatory circuits and mechanisms demands considerable effort.

Methods: Integrated analyses were performed on genomic, transcriptomic, and clinicopathological profiles of primary prostate cancer and transcription factor-binding profiles, which included estimating transcription factor activity, identifying transcription factors of prognostic values, and discovering cis- and trans-regulations by long noncoding RNAs.

Systematic Investigation of mRNA -Methyladenosine Machinery in Primary Prostate Cancer.

Background: Appreciable findings have pointed out pivotal roles of -methyladenosine (mA) machinery in cancer onset and progression. However, limited efforts have been directed towards relevant research in the prostate cancer area.

Methods: A PubMed search was conducted to acquire components of the mRNA mA machinery.

Comprehensive Characterization of Androgen-Responsive lncRNAs Mediated Regulatory Network in Hormone-Related Cancers.

The AR signaling pathway plays an important role in initiation and progression of many hormone-related cancers including prostate, bladder, kidney, lung, and breast cancer. However, the potential roles of androgen-responsive long noncoding RNAs (lncRNAs) in hormone-related cancers remained unclear. In the present study, we identified 469 novel androgen-responsive lncRNAs using microarray data.