Comparable cognitive impairment was detected in MACS and CS and alleviated after remission of hypercortisolism in MACS.

Context: Few studies have directly compared the cognitive characteristics of patients with mild autonomous cortisol secretion (MACS) and Cushing's syndrome (CS). The effect of surgical or conservative treatment on cognitive function in patients with MACS is still unclear. Objective: To compare the differences in cognitive function between patients with MACS and CS and evaluate the effect of surgery or conservative treatment on cognitive function. Methods: We prospectively recruited 59 patients with nonfunctional adrenal adenoma (NFA), 36 patients with MACS, and 20 patients with adrenal CS who completed the global cognition and cognitive subdomains assessments. Seventeen MACS patients were re-evaluated for cognitive function after a 12-month follow-up period; of these, eleven underwent laparoscopic adrenalectomy and six received conservative treatment. Results: Patients with MACS and CS performed worse in the global cognition and multiple cognitive domains than those with NFA (all P<0.05). No statistical difference was found in cognitive functions between patients with MACS and CS. Logistic regression analysis showed that patients with MACS (odds ratio [OR]=3.738, 95% confidence intervals [CI]: 1.329-10.515, P=0.012) and CS (OR=6.026, 95% CI: 1.411-25.730, P=0.015) were associated with an increased risk of immediate memory impairment. Visuospatial/constructional, immediate and delayed memory scores of MACS patients were significantly improved at 12 months compared with pre-operation in the surgical treatment group (all P<0.05), whereas there was no improvement in the conservative treatment group. Conclusion: Patients with MACS have comparable cognitive impairment as patients with CS. Cognitive function was partially improved in patients with MACS after adrenalectomy. The current data support the inclusion of cognitive function assessment in the clinical management of patients with MACS.

Utilization of Polycyclic Aromatic Solid Additives for Morphology and Thermal Stability Enhancement in Photoactive Layers of Organic Solar Cells.

Volatile solid additives have emerged as a promising strategy for enhancing film morphology and promoting the power conversion efficiency (PCE) of organic solar cells (OSCs). Herein, a series of novel polycyclic aromatic additives with analogous chemical structures, including fluorene (FL), dibenzothiophene (DBT), and dibenzofuran (DBF) derived from crude oils, are presented and incorporated into OSCs. All these additives exhibit strong interactions with the electron-deficient terminal groups of L8-BO within the bulk-heterojunction OSCs. Moreover, they demonstrate significant sublimation during thermal annealing, leading to increase free volumes for the rearrangement and recrystallization of L8-BO. This phenomenon leads to an improved film morphology and an elevated glass-transition temperature of the photoactive layers. Consequently, the PCE of the PM6:L8-BO blend has been boosted from 16.60% to 18.60% with 40 wt% DBF additives, with a champion PCE of 19.11% achieved for ternary PM6:L8-BO:BTP-eC9 OSCs. Furthermore, the prolonged shelf and thermal stability have been observed in OSCs with these additives. This study emphasizes the synergic effect of volatile solid additives on the performance and thermal stability of OSCs, highlighting their potential for advancing the field of photovoltaics.

Bioremediation of PAHs-contaminated site in a full-scale biopiling system with immobilized enzymes: Removal efficiency and microbial communities.

Bioremediation of PAHs-contaminated soil by immobilized enzymes is a promising technology. Nevertheless, the practical implementation of highly efficient enzymatic remediation remains confined to laboratory settings, with limited experience in full-scale applications. In this study, the extracellular enzymes from white rot fungi are fully applied to treat sites contaminated with PAHs by combining a new hydrogel microenvironment and a biopiling system. The full-scale project was conducted on silty loam soil contaminated with PAHs. In line with China's guidelines for construction land, 7 out of the 12 PAHs identified are considered to be a threat to the soil quality of construction sites, with benzo[a]pyrene levels reaching 1.50 mg kg-1, surpassing the acceptable limit of 0.55 mg kg-1 for the first type of land. After 7 days of remediation, the benzo[a]pyrene level decreased from 1.50 mg kg-1 to 0.51 mg kg-1, reaching the remediation standard of Class I screening values, with a removal rate of 66%. Microbiomes were utilized to assess the microbial biodiversity and structure analyses for PAHs biodegradation. The remediation enhanced the abundance of dominant bacterium (Marinobacter, Pseudomonas, and Truepera) and fugin (Thielavia, Neocosmospora, and Scedosporium). The research offers further insights into the exploration of soil remediation on the full-scale of the immobilized enzyme and biopiling technology.

Joint Dual Feature Distillation and Gradient Progressive Pruning for BERT compression.

The increasing size of pre-trained language models has led to a growing interest in model compression. Pruning and distillation are the primary methods employed to compress these models. Existing pruning and distillation methods are effective in maintaining model accuracy and reducing its size. However, they come with limitations. For instance, pruning is often suboptimal and biased by transforming it into a continuous optimization problem. Distillation relies primarily on one-to-one layer mappings for knowledge transfer, which leads to underutilization of the rich knowledge in teacher. Therefore, we propose a method of joint pruning and distillation for automatic pruning of pre-trained language models. Specifically, we first propose Gradient Progressive Pruning (GPP), which achieves a smooth transition of indicator vector values from real to binary by progressively converging the values of unimportant units' indicator vectors to zero before the end of the search phase. This effectively overcomes the limitations of traditional pruning methods while supporting compression with higher sparsity. In addition, we propose the Dual Feature Distillation (DFD). DFD adaptively globally fuses teacher features and locally fuses student features, and then uses the dual features of global teacher features and local student features for knowledge distillation. This realizes a "preview-review" mechanism that can better extract useful information from multi-level teacher information and transfer it to student. Comparative experiments on the GLUE benchmark dataset and ablation experiments indicate that our method outperforms other state-of-the-art methods.

Enhanced biodegradation of benzo[a]pyrene with Trametes versicolor stimulated by citric acid.

Polycyclic aromatic hydrocarbons (PAHs) are a class of persistent organic pollutants with carcinogenic, mutagenic and teratogenic effects. The white-rot fungi in the fungal group have significant degradation ability for high molecular weight organic pollutants. However, exogenous fungi are easily antagonized by indigenous microorganisms. Low molecular weight organic acids, a small molecular organic matter secreted by plants, can provide carbon sources for soil microorganisms. Combining organic acids with white rot fungi may improve the nutritional environment of fungi. In this study, immobilized Trametes versicolor was used to degrade benzo[a]pyrene in soil, and its effect on removing benzo[a]pyrene in soil mediated by different low molecular weight organic acids was investigated. The results showed that when the degradation was 35 days, the removal effect of the experimental group with citric acid was the best, reaching 43.7%. The degradation effect of Trametes versicolor on benzo[a]pyrene was further investigated in the liquid medium when citric acid was added, and the effects of citric acid on the biomass, extracellular protein concentration and laccase activity of Trametes versicolor were investigated by controlling different concentrations of citric acid. In general, citric acid can act as a carbon source for Trametes versicolor and promote its extracellular protein secretion and laccase activity, thereby accelerating the mineralization of benzo[a]pyrene by Trametes versicolor. Therefore, citric acid can be used as a biostimulant in the remediation of PAHs contaminated soil with Trametes versicolor.

Recent advances in the development of P2Y14R inhibitors: a patent and literature review (2018-present).

INTRODUCTION: The P2Y14 receptor (P2Y14R), a member of the G protein-coupled receptor family, is activated by extracellular nucleotides. Due to its involvement in inflammatory, immunological and other associated processes, P2Y14R has emerged as a promising therapeutic target. Despite lacking a determined three-dimensional crystal structure, the homology modeling technique based on closely related P2Y receptors' crystallography has been extensively utilized for developing active compounds targeting P2Y14R. Recent discoveries have unveiled numerous highly effective and subtype-specific P2Y14R inhibitors. This study presents an overview of the latest advancements in P2Y14R inhibitors. AREAS COVERED: This review presents an overview of the advancements in P2Y14R inhibitor research over the past five years, encompassing new patents, journal articles, and highlighting the therapeutic prospects inherent in these compounds. EXPERT OPINION: The recent revelation of the vast potential of P2Y14R inhibitors has led to the development of novel compounds that exhibit promising capabilities for the treatment of sterile inflammation of the kidney, potentially diabetes, and asthma. Despite being a relatively nascent class of compounds, certain members have already exhibited their capacity to surmount specific challenges posed by conventional P2Y14R inhibitors. Targeting P2Y14R through small molecules may present a promising therapeutic strategy for effectively managing diverse inflammatory diseases.

Fertility preservation in male adolescents with cancer (2011-2020): A retrospective study in China.

BACKGROUND: According to the studies, more than 80% of pediatric patients with cancer can achieve a survival rate greater than 5 years; however, long-term chemotherapy and/or radiation therapy may seriously affect their reproductive ability. Fertility preservation in adolescents with cancer in China was initiated late, and related research is lacking. Analyze data to understand the current situation and implement measures to improve current practices. METHODS: From 2011 to 2020, data on 275 male adolescents with cancer whose age ranged from 0 to 19 years old were collected from 16 human sperm banks for this retrospective study. Methods include comparing the basic situation of male adolescents with cancer, the distribution of cancer types, and semen quality to analyze the status of fertility preservation. RESULTS: The mean age was 17.39 ± 1.46 years, with 13 cases (4.7%) aged 13-14 years and 262 cases (95.3%) aged 15-19 years. Basic diagnoses included leukemia (55 patients), lymphomas (76), germ cell and gonadal tumors (65), epithelial tumors (37), soft tissue sarcomas (14), osteosarcoma (7), brain tumors (5), and other cancers (16). There are differences in tumor types in different age stages and regions. The tumor type often affects semen quality, while age affects semen volume. Significant differences were found in sperm concentration and progressive motility before and after treatment (p < 0.001). Moreover, 90.5% of patients had sperm in their semen and sperm were frozen successfully in 244 patients (88.7%). CONCLUSIONS: The aim of this study is to raise awareness of fertility preservation in male adolescents with cancer, to advocate for fertility preservation prior to gonadotoxic therapy or other procedures that may impair future fertility, and to improve the fertility status of future patients.

Changes in brain structure and function during early aging in patients with chronic low back pain.

Objective: To explore the structural and functional changes in cognition-related brain regions in patients with chronic low back pain (CLBP) at earlier ages, and explore the impact of the interaction between CLBP and age on the brain. Methods: Seventy-six patients with CLBP were recruited and divided into "younger" age group (20-29 years, YA), "middle" age group (30-39 years, MA), and "older" age group (40-49 years, OA). All patients underwent functional magnetic resonance imaging (fMRI) as well as clinical psychological and pain-related symptoms assessments. Results: Structural analysis showed that patients in OA group had lower gray matter (GM) volumes in the orbitofrontal cortex (OFC) bilaterally and the right superior frontal gyrus (SFG) compared to YA group. The resting-state brain activity analysis showed that amplitude of low-frequency fluctuation (ALFF) values in the bilateral postcentral gyrus and left ventral medial prefrontal cortex (mPFC) were significantly different in the OA group. The functional connectivity (FC) in the right ventral dorsolateral prefrontal cortex (DLPFC) and the right insula was significantly decreased in the OA group compared to the YA and MA groups. Likewise, the FC in the left caudal parahippocampal gyrus (PHG) and left inferior parietal lobule (IPL) were significantly lower in the MA and OA groups compared to the YA group. In addition, both the structural properties and the FC values of these brain regions were significantly correlated with age. Conclusion: This preliminary study concludes that CLBP affects the aging process. The synergistic effects of CLBP and aging accelerate the functional and structural decline of certain areas of the brain, which not only affects pain processing, but are also may be associated with cognitive declines.

LABS: linear amplification-based bisulfite sequencing for ultrasensitive cancer detection from cell-free DNA.

Methylation-based liquid biopsies show promises in detecting cancer using circulating cell-free DNA; however, current limitations impede clinical application. Most assays necessitate substantial DNA inputs, posing challenges. Additionally, underrepresented tumor DNA fragments may go undetected during exponential amplification steps of traditional sequencing methods. Here, we report linear amplification-based bisulfite sequencing (LABS), enabling linear amplification of bisulfite-treated DNA fragments in a genome-wide, unbiased fashion, detecting cancer abnormalities with sub-nanogram inputs. Applying LABS to 100 patient samples revealed cancer-specific patterns, copy number alterations, and enhanced cancer detection accuracy by identifying tissue-of-origin and immune cell composition.

Renin-angiotensin system inhibitors prescriptions in Chinese hospitalized chronic kidney disease patients.

BACKGROUND: Many guidelines have recommended renin-angiotensin system inhibitors (RASI) as the first-line treatment for patients with chronic kidney disease (CKD). We studied RASI prescription trends from 2010 to 2019, and analyzed the characteristics associated with RASI prescription in Chinese hospitalized CKD patients. AIM: To study the prescription of renin angiotensin system inhibitors in hospitalized patients with CKD in China. METHODS: It was retrospectively, cross-sectional reviewed RASI prescriptions in hospitalized CKD patients in China from 2010 to 2019. RASI prescribing trends were analyzed from 2010 to 2019, and bivariate and multivariate logistic regression analyses were conducted to identify characteristics associated with RASI prescription. RESULTS: A total of 35090 CKD patients were included, with 10043 (28.6%) RASI prescriptions. Among these patients, 18919 (53.9%) met the criteria for RASI treatments based on the 2012 kidney disease: Improving global outcomes guidelines. Of these, 7246 (38.3%) patients received RASI prescriptions. RASI prescriptions showed an initial rapid increase from 2011 to 2012, reached its peak around 2015 and 2016, and then exhibited a subsequent slight decreasing trend. Both bivariate and multivariate analyses showed that several characteristics, including the male gender, age less than 60-year-old, nephrology department admission, lower CKD stage, history of hypertension or diabetes, proteinuria, glomerulonephritis as the CKD etiology, and non-acute kidney injury were associated with RASI prescriptions. CONCLUSION: The frequency of RASI prescriptions showed an initial increase but a slight decreasing trend in more recent years. CKD patients with certain characteristics such as elderly age, advanced disease stage, surgery department admission, or acute kidney injury were less likely to receive RASI prescriptions. In the application of RASI in hospitalized CKD patients is insufficient. The actual clinical practice needs to be improved. The development of related research is helpful to guide the correct choice of clinical treatment strategy.

A 5-Hydroxymethylcytosine-Based Noninvasive Model for Early Detection of Colorectal Carcinomas and Advanced Adenomas: The METHOD-2 Study.

PURPOSE: Detection of colorectal carcinomas at a time when there are more treatment options is associated with better outcomes. This prospective case-control study assessed the 5-hydroxymethylcytosine (5hmC) biomarkers in circulating cell-free DNA (cfDNA) for early detection of colorectal carcinoma and advanced adenomas (AA). EXPERIMENTAL DESIGN: Plasma cfDNA samples from 2,576 study participants from the multicenter METHOD-2 study (NCT03676075) were collected, comprising patients with newly diagnosed colorectal carcinoma (n = 1,074), AA (n = 356), other solid tumors (n = 80), and non-colorectal carcinoma/AA controls (n = 1,066), followed by genome-wide 5hmC profiling using the 5hmC-Seal technique and the next-generation sequencing. A weighted diagnostic model for colorectal carcinoma (stage I-III) and AA was developed using the elastic net regularization in a discovery set and validated in independent samples. RESULTS: Distribution of 5hmC in cfDNA reflected gene regulatory relevance and tissue of origin. Besides being confirmed in internal validation, a 96-gene model achieved an area under the curve (AUC) of 90.7% for distinguishing stage I-III colorectal carcinoma from controls in 321 samples from multiple centers for external validation, regardless of primary location or mutation status. This model also showed cancer-type specificity as well as high capacity for distinguishing AA from controls with an AUC of 78.6%. Functionally, differential 5hmC features associated with colorectal carcinoma and AA demonstrated relevance to colorectal carcinoma biology, including pathways such as calcium and MAPK signaling. CONCLUSIONS: Genome-wide mapping of 5hmC in cfDNA shows promise as a highly sensitive and specific noninvasive blood test to be integrated into screening programs for improving early detection of colorectal carcinoma and high-risk AA.

A comparative analysis reveals the genomic diversity among 8 Muscovy duck populations.

The Muscovy duck (Cairina moschata) is a waterfowl indigenous to the neotropical regions of Central and South America. It has low demand for concentrated feed and strong adaptability to different rearing conditions. After introduced to China through Eurasian commercial trade, Muscovy ducks have a domestication history of around 300 years in the Fujian Province of China. In the 1990s, the commodity Muscovy duck breed "Crimo," cultivated in Europe, entered the Chinese market for consumption and breeding purposes. Due to the different selective breeding processes, Muscovy ducks have various populational traits and lack transparency of their genetic background. To remove this burden in the Muscovy duck breeding process, we analyzed genomic data from 8 populations totaling 83 individuals. We identify 11.24 million single nucleotide polymorphisms (SNPs) and categorized these individuals into the Fujian-bred and the Crimo populations according to phylogenetic analyses. We then delved deeper into their evolutionary relationships through assessing population structure, calculating fixation index (FST) values, and measuring genetic distances. Our exploration of runs of homozygosity (ROHs) and homozygous-by-descent (HBD) uncovered genomic regions enriched for genes implicated in fatty acid metabolism, development, and immunity pathways. Selective sweep analyses further indicated strong selective pressures exerted on genes including TECR, STAT2, and TRAF5. These findings provide insights into genetic variations of Muscovy ducks, thus offering valuable information regarding genetic diversity, population conservation, and genome associated with the breeding of Muscovy ducks.

Enrichment of Total Flavonoids and Licochalcone A from Glycyrrhiza inflata Bat. Residue Based on a Combined Membrane-Macroporous Resin Process and a Quality-Control Study.

Glycyrrhiza inflata Bat. produces a lot of licorice waste after water extraction, which also retains abundant total flavonoids (TFs) and licochalcone A. However, licorice residue is often wasted due to the lack of good utilization of resources in practical applications. This study first screened the optimal membrane pore size and resin type and then explored the mechanism and conditions of the adsorption of TFs on the resin. Then, different combinations and sequences of membrane and macroporous resin (MR) methods were investigated. It was found that using the membrane method for initial purification, followed by the MR method for further purification, yielded the best purification results. Next, response surface methodology was utilized to investigate the resin's dynamic desorption conditions for TFs. Finally, the TF purity increased from 32.9% to 78.2% (2.38-fold) after purification by a combined membrane-MR process; the purity of licochalcone A increased from 11.63 mg·g-1 to 22.70 mg·g-1 (1.95-fold). This study verified the feasibility of enriching TFs and licochalcone A from licorice residue using a membrane-MR coupling method. In addition, a quality-control method was established using a fingerprinting method on the basis of ultrahigh-performance liquid chromatography (UPLC) to ensure the stability of the enrichment process.

Sexual Harassment Among Chinese Psychiatrists and Its Impact on Quality of Life: A Cross-Sectional Survey.

Objectives: Sexual harassment (SH) is a prevalent issue in various professional fields worldwide. The current study aims to investigate the incidence of SH targeting psychiatrists in China and explore its impact on quality of life (QOL). Methods: A consecutive recruitment of 1093 psychiatrists was conducted from 6 hospitals in China. The recorded data included participants' socio-demographic characteristics, experiences of workplace SH within the previous year, and their QOL. SH comprised verbal harassment, physical harassment, and displaying of sexual organs. The Chinese version of the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) was employed to assess QOL. We compared the demographic characteristics and QOL between the SH group and the non-SH group. Multiple logistic regression analysis was used to identify independent demographic correlates of SH. Results: In total, 13.8% (n = 151) of the psychiatrists reported SH, with 5.8% reporting it once, 4.4% reporting it twice, and 3.6% reporting it three times or more. Psychiatrists who had encountered SH exhibited lower QOL across social, psychological, physical, and environmental domains. Multiple logistic regression analysis revealed that young physicians and those with shorter work experience had a higher likelihood of experiencing SH. Conclusion: The high prevalence of SH among Chinese psychiatrists is of concern. Given its detrimental effects on the well-being of physicians and the quality of medical care they provide, it is crucial to develop specialized employee training programs for this population to effectively manage workplace SH.

Risk and prognosis of secondary lung cancer after radiation therapy for thoracic malignancies.

OBJECTIVE: Radiation therapy (RT) may increase the risk of second cancer. This study aimed to determine the association between exposure to radiotherapy for the treatment of thoracic cancer (TC) and subsequent secondary lung cancer (SLC). MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (from 1975 to 2015) was queried for TC. Univariate Cox regression analyses and multiple primary standardized incidence ratios (SIRs) were used to assess the risk of SLC. Subgroup analyses of patients stratified by latency time since TC diagnosis, age at TC diagnosis, and calendar year of TC diagnosis stage were also performed. Overall survival and SLC-related death were compared among the RT and no radiation therapy (NRT) groups by using Kaplan-Meier analysis and competitive risk analysis. RESULTS: In a total of 329 129 observations, 147 847 of whom had been treated with RT. And 6799 patients developed SLC. Receiving radiotherapy was related to a higher risk of developing SLC for TC patients (adjusted HR, 1.25; 95% CI, 1.19-1.32; P < 0.001). The cumulative incidence of developing SLC in TC patients with RT (3.8%) was higher than the cumulative incidence (2.9%) in TC patients with NRT(P). The incidence risk of SLC in TC patients who received radiotherapy was significantly higher than the US general population (SIR, 1.19; 95% CI, 1.14-1.23; P < 0.050). CONCLUSIONS: Radiotherapy for TC was associated with higher risks of developing SLC compared with patients unexposed to radiotherapy.

Whole-genome sequences restore the original classification of dabbling ducks (genus Anas).

Anas, is a genus of dabbling ducks and encompasses a considerable number of species, among which some are the progenitors of domestic ducks. However, the taxonomic position of the Anas genus remains uncertain because several of its species, initially categorized as Anas based on morphological characteristics, were subsequently reclassified and grouped with the South American genus Tachyeres, primarily based on analysis of their mitochondrial gene sequences. Here, we constructed a phylogenetic tree using nine of our recently assembled Anas genomes, two Tachyeres genomes, and one Cairina genome that are publicly available. The results showed that the Northern shoveler (Anas clypeata) and Baikal teal (Anas formosa) clustered with the other Anas species at the whole-genome level rather than with the Steamer ducks (genus Tachyeres). Therefore, we propose to restore the original classification of the Anas genus, which includes the Northern shoveler and Baikal teal species, 47 species in total. Moreover, our study unveiled extensive incomplete lineage sorting and an ancient introgression event from Tachyeres to Anas, which has led to notable phylogenetic incongruence within the Anas genome. This ancient introgression event not only supports the theory that Anas originated in South America but also that it played a significant role in shaping the evolutionary trajectory of Anas, including the domestic duck.

Pd-Catalyzed Three-Component Coupling of Cyclopropenones via Sequential C-C Bond Activation and Allylation.

A novel Pd-catalyzed three-component domino reaction for the stereoselective synthesis of highly functionalized allyl cinnamates has been developed. In this protocol, a sequential process of C-C bond activation and intermolecular allylic substitution was well-organized. The key for this transformation is the in situ generated hydrolysis product of cyclopropenone, which triggered a new reaction with vinylethylene carbonates. The reaction mechanism was investigated, demonstrating the high stereoselectivity and excellent atomic economy in this process.

Breathable and wearable graphene/waterborne polyurethane coated regenerated polyethylene terephthalate fabrics for motion sensing and thermal therapy.

The functional utilization of recycled polymers has emerged as a current prominent and timely subject. Flexible wearable devices with high sensitivity to conductivity have garnered significant attention in the fields of human healthcare monitoring and personal heat management. One significant obstacle that needs to be addressed is the simultaneous maintenance of both sensing functionality and durability in composite fabrics. In this paper, a collection of durable, breathable, and flexible smart fabric was produced using the scratch coating method. The fabrics were created by utilizing a regenerated polyethylene terephthalate fabric as a base material, incorporating graphene microsheets (G) as a conductive agent, and applying a waterborne polyurethane layer as a surface protective coating. Furthermore, an investigation was conducted to assess their sensing performance and electrothermal performance. The composite fabric exhibits significant advantages in terms of high conductivity (592 S/m), wide strain range, high sensitivity (Gauge factor = 6.04) and fantabulous dynamic stability (2000 cycles) at a mass ratio of Graphene/WPU loading of 8:2. These sensors were successfully utilized to monitor various degrees of real-time human body movements, ranging from significant deformation bending of elbows to slight deformation swallowing. Furthermore, the sensors also exhibit a significant electric heating effect. Specifically, when a voltage of 10 V is applied, the sensors can reach a steady state temperature of 53.3 °C within a mere 30 s. This discovery holds potential for the development of wearable heaters that can be used for on-demand thermal therapy, functional protective clothing, and medical electric heating wearables.

Population pharmacokinetic analysis for dose regimen optimization of vancomycin in Southern Chinese children.

Changes in physiological factors may result in large pharmacokinetic variability of vancomycin in pediatric patients, thereby leading to either supratherapeutic or subtherapeutic exposure and potentially affecting clinical outcomes. This study set out to characterize the disposition of vancomycin, quantify the exposure target and establish an optimal dosage regimen among the Southern Chinese pediatric population. Routine therapeutic drug monitoring data of 453 patients were available. We performed a retrospective population pharmacokinetic analysis of hospitalized children prescribed intravenous vancomycin using NONMEM® software. A one-compartment PPK model of vancomycin with body weight and renal functions as covariates based on a cutoff of 2 years old children was proposed in this study. Both internal and external validation showing acceptable and robust predictive performance of the model to estimate PK parameters. The value of area under the curve over 24 h to minimum inhibitory concentration ratio (AUC0-24/MIC) ≥ 260 was a significant predictor for therapeutic efficacy. Monte Carlo simulations served as a model-informed precision dosing approach and suggested that different optimal dose regimens in various scenarios should be considered rather than flat dosing. The evaluation of vancomycin exposure-efficacy relationship indicated that lower target level of AUC0-24/MIC may be needed to achieve clinical effectiveness in children, which was used to derive the recommended dosing regimen. Further prospective studies will be needed to corroborate and elucidate these results.