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Abstract Funduscopic diseases, including diabetic retinopathy (DR) and age‐related macular degeneration (AMD), significantly impact global visual health, leading to impaired vision and irreversible blindness. Delivering drugs to the posterior segment of the eye remains a challenge due to the presence of multiple physiological and anatomical barriers. Conventional drug delivery methods often prove ineffective and may cause side effects. Nanomaterials, characterized by their small size, large surface area, tunable properties, and biocompatibility, enhance the permeability, stability, and targeting of drugs. Ocular nanomaterials encompass a wide range, including lipid nanomaterials, polymer nanomaterials, metal nanomaterials, carbon nanomaterials, quantum dot nanomaterials, and so on. These innovative materials, often combined with hydrogels and exosomes, are engineered to address multiple mechanisms, including macrophage polarization, reactive oxygen species (ROS) scavenging, and anti‐vascular endothelial growth factor (VEGF). Compared to conventional modalities, nanomedicines achieve regulated and sustained delivery, reduced administration frequency, prolonged drug action, and minimized side effects. This study delves into the obstacles encountered in drug delivery to the posterior segment and highlights the progress facilitated by nanomedicine. Prospectively, these findings pave the way for next‐generation ocular drug delivery systems and deeper clinical research, aiming to refine treatments, alleviate the burden on patients, and ultimately improve visual health globally.

Abstract Venn diagrams serve as invaluable tools for visualizing set relationships due to their ease of interpretation. Widely applied across diverse disciplines such as metabolomics, genomics, transcriptomics, and proteomics, their utility is undeniable. However, the operational complexity has been compounded by the absence of standardized data formats and the need to switch between various platforms for generating different Venn diagrams. To address these challenges, we introduce the EVenn platform, a versatile tool offering a unified interface for efficient data exploration and visualization of diverse Venn diagrams. EVenn (http://www.ehbio.com/test/venn) streamlines the data upload process with a standardized format, enhancing the capabilities for multimodule analysis. This comprehensive protocol outlines various applications of EVenn, featuring representative results of multiple Venn diagrams, data uploads in the centralized data center, and step‐by‐step case demonstrations. Through these functionalities, EVenn emerges as a valuable and user‐friendly tool for the in‐depth exploration of multiomics data.

Abstract Introduction Approximately 30% of individuals with advanced EC have unsatisfactory prognosis. Evidence suggests that TPX2 is frequently upregulated in malignancies and related to cancer progression. Its role and pathological mechanism in EC need further research. Methods GSEA and TPX2 expression, GO, KEGG, and prognostic analyses were performed with TCGA data by bioinformatic approaches. Relationships between TPX2 expression and clinicopathological parameters were investigated immunohistochemically and statistically. shRNA and overexpression plasmids were constructed and transfected into AN3CA and Ishikawa cells to evaluate phenotypic changes and injected into nude mouse axillae. Coimmunoprecipitation and chromatin immunoprecipitation were used to identify interacting proteins and promoter‐binding sequences. Changes in TPX2 expression were identified by Western blotting and RT–qPCR. Results TPX2 expression was significantly higher in EC tissues than in normal tissues in TCGA and in‐house specimens (all p

Abstract Background The L1 cell adhesion molecule (L1CAM, OMIM 308840) gene is primarily expressed in the nervous system and encodes the L1 adhesion molecule protein. Variations in L1CAM cause a wide spectrum of X‐linked neurological disorders summarized as the L1 syndrome. Methods We report a 29‐year‐old pregnant woman who experienced multiple adverse pregnancy outcomes due to recurrent fetal hydrocephalus with an X‐linked recessive inheritance. Genomic DNA was extracted from the third aborted male fetus and analyzed via trio whole‐exome sequencing (WES). Total RNA was isolated from the pregnant woman to assess splicing variation at the mRNA level, and amniotic fluid was extracted from the woman for prenatal diagnosis on her fourth fetus. Results All four male fetuses were affected by severe hydrocephalus. We identified a maternally derived hemizygous splicing variation NM_000425.5:[c.3046 + 1G > A]; NP_000416.1 p.(Gly1016AspfsTer6) (chrX:153130275) in Intron 22 of the L1CAM. This variation disrupts the donor splice site and causes the retention of Intron 22, which results in frame shift and a premature termination codon at position 1021 with the ability to produce a truncated protein without the fifth fibronectin‐repeat III, transmembrane, and cytoplasmic domains or to induce the degradation of mRNAs by nonsense‐mediated mRNA decay. The same hemizygous variant was also detected in the amniocytes. Conclusion This report enhances our knowledge of genetic and phenotypic characteristics of X‐linked fetal hydrocephalus, providing a new genetic basis for prenatal diagnosis and pre‐implantation prenatal diagnosis.

Abstract Background Early detection of brain metastasis (BM) is essential for prognostic improvement in breast cancer (BC) patients. The aim was to identify predictors of BCBM in different molecular subtypes on a population‐based level. Methods The Surveillance, Epidemiology, and End Results database was used to select BC patients diagnosed from 2010 to 2018. We evaluated the incidence and risk factors of BCBM and tested the interaction effects between molecular subtypes and other risk factors. Results Among the 527,525 selected patients, molecular subtypes significantly interacted with T stage and extracranial metastasis (ECM) patterns on the risk of BM in the whole BC population (interaction p = 0.002,

Abstract Background The fat mass and nutritional status play important roles in the onset and progression of cancer cachexia. The present study evaluated the joint prognostic value of the fat mass, as indicated by the triceps skinfold thickness (TSF), and the serum albumin level, for mortality in patients with cancer cachexia. Methods We performed a multicentre cohort study including 5134 patients with cancer cachexia from January 2013 to April 2019. The sum of the TSF (mm) and serum albumin (g/L) was defined as the triceps skinfold–albumin index (TA). Harrell's C index, a time‐dependent receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC) were used to evaluate the prognostic performance of the TA and other indices. Optimal stratification was used to identify the thresholds to define a low TA, and the association of the TA with all‐cause mortality was evaluated using Kaplan–Meier analysis and Cox proportional hazard regression models. Results The study enrolled 2408 women and 2726 men with a median age of 58.6 years and a median follow‐up of 44 months. A total of 607 women (TA

Abstract Background Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by pathogenic variants of PKD1 and PKD2. Compared to PKD2‐related patients, patients with PKD1 pathogenic variants have more severe symptoms, present a gradual decline in renal function, and finally progress to end‐stage kidney disease with an earlier mean onset age. Methods In this study, trio exome sequencing (ES) was performed to reveal the genetic etiology in a Chinese family clinically diagnosed with polycystic kidney, followed by validation through Sanger sequencing on both genomic DNA and cDNA levels. Subsequently, targeted preimplantation genetic testing was provided for the family. Results A novel heterozygous PKD1 variant (c.1717_1722+11del) was detected in the proband and other clinically‐affected relatives. Interestingly, cDNA sequencing demonstrated that the variant, despite being annotated as non‐frameshift within exon 8, impacted the splicing of PKD1. Two abnormal transcription products were formed: one induced frameshift, while the other caused 133 amino acids to be inserted between exon 8 and exon 9. Conclusions Our study revealed a novel PKD1 variant using ES as the cause of ADPKD in a Chinese family with multiple affected members. The variant at the exon‐intron boundary would induce alternative splicing, which should not be excluded from genetic analysis. Validated on the cDNA level could provide more comprehensive genetic information for disease stratification. And the novel variant expands the spectrum of PKD1 variants in ADPKD. The recurrent risk could be blocked accordingly for the families' offspring.

Abstract Background Short‐rib thoracic dysplasia (SRTD) and Joubert syndrome (JS) are rare genetic ciliopathies, and individuals with either syndrome can manifest cerebellar malformation and variable developmental delays. However, neither of these conditions is easily diagnosed during pregnancy due to a limited fetal phenotype. Here, we investigated a fetus that was initially observed to have short limbs and polydactyly and discovered a compound heterozygous pathogenesis through exome sequencing (ES). Methods Simultaneous trio‐ES and chromosome microarray analysis was provided for the fetus. The presence and effects of these variants on splicing were further validated at the DNA and RNA levels. Results Only short limbs and post‐axial polydactyly of the fetus were detected during the second trimester. Two variants (c.3940+1G>A and c.3303G>A), affecting splicing of KIAA0586, were identified from amniocytes through ES and validated by Sanger sequencing. More intensive fetal monitoring was applied, and the fetus was also found to have deformed cerebellar malformation and a constricted thoracic cage. Conclusions Herein, we report the genetic pathogenesis of SRTD and/or JS associated with KIAA0586 in a fetus. The novel splicing variants observed expand the spectrum of KIAA0586 in SRTD and/or JS. Based on the genetic data and the distinct corresponding phenotypes discovered by imaging examination, a comprehensive diagnosis was made during pregnancy and more valuable prognostic information was provided for the parents.

Abstract Aims The N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) is a commonly used biomarker in heart failure for diagnosis and prognostication. We aimed to determine the prevalence of NT‐proBNP testing, distribution of NT‐proBNP concentrations, and factors associated with receiving an NT‐proBNP test in patients with heart failure with reduced ejection fraction (HFrEF), including the subset with a worsening heart failure event (WHFE). Methods and results This was a retrospective cohort study using two US databases: (i) the de‐identified Humana Research Database between January 2015 and December 2018 and (ii) the Veradigm PINNACLE Registry® between July 2013 and September 2017. We included adult patients with a confirmed diagnosis of HFrEF. In each data source, a subgroup of patients with a WHFE was identified, where a WHFE was defined as a heart failure‐related hospitalization or receipt of intravenous diuretics. Bivariate and multivariate analyses were conducted to assess factors associated with receiving NT‐proBNP testing. In Cohort 1 (n = 249 238), 9.2% of patients with HFrEF and 10.8% of patients with a WHFE received NT‐proBNP testing. When restricted to patients with at least one laboratory claim, 11.3% of patients with HFrEF and 13.2% of those with a WHFE received NT‐proBNP testing. In Cohort 2 (n = 91 444), 2.3% of patients with HFrEF were tested. Median (inter‐quartile range) NT‐proBNP concentrations among patients with HFrEF were 1399 (423–4087) pg/mL in Cohort 1 and 394 (142–688) pg/mL in Cohort 2. Median (inter‐quartile range) NT‐proBNP concentrations in the subset of patients with a WHFE in each cohort were 2209 (740–5894) and 464 (174–783) pg/mL, respectively. In Cohort 1, 13.4% of all HFrEF patients receiving NT‐proBNP testing and 18.9% of patients with a WHFE had NT‐proBNP values >8000 pg/mL; in Cohort 2, these percentages were 1.0% and 2.5%, respectively. Conclusions In US clinical practice, NT‐proBNP testing was not frequently performed in patients with HFrEF. NT‐proBNP concentrations varied across data sources and subpopulations within HFrEF.

Background. Tuberculosis (TB), a multisystemic disease with protean presentation, remains a major global health problem. Although concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) cases are commonly observed clinically, knowledge regarding concurrent PTB-EPTB is limited. Here, a large-scale multicenter observational study conducted in China aimed to study the epidemiology of concurrent PTB-EPTB cases by diagnostically defining TB types and then implementing association rules analysis. Methods. The retrospective study was conducted at 21 hospitals in 15 provinces in China and included all inpatients with confirmed TB diagnoses admitted from Jan 2011 to Dec 2017. Association rules analysis was conducted for cases with concurrent PTB and various types of EPTB using the Apriori algorithm. Results. Evaluation of 438,979TB inpatients indicated PTB was the most commonly diagnosed (82.05%) followed by tuberculous pleurisy (23.62%). Concurrent PTB-EPTB was found in 129,422 cases (29.48%) of which tuberculous pleurisy was the most common concurrent EPTB type observed. The multivariable logistic regression models demonstrated that odds ratios of concurrent PTB-EPTB cases varied by gender and age group. For PTB cases with concurrent EPTB, the strongest association was found between PTB and concurrent bronchial tuberculosis (lift = 1.09). For EPTB cases with concurrent PTB, the strongest association was found between pharyngeal/laryngeal tuberculosis and concurrent PTB (lift = 1.11). Confidence and lift values of concurrent PTB-EPTB cases varied with gender and age. Conclusions. Numerous concurrent PTB-EPTB case types were observed, with confidence and lift values varying with gender and age. Clinicians should screen for concurrent PTB-EPTB in order to improve treatment outcomes.

Abstract Centenarians, who show mild infections and low incidence of tumors, are the optimal model to investigate healthy aging. However, longevity related immune characteristics has not been fully revealed largely due to lack of appropriate controls. In this study, single‐cell transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) derived from seven centenarians (CEN), six centenarians’ offspring (CO), and nine offspring spouses or neighbors (Control, age‐matched to CO) are performed to investigate the shared immune features between CEN and CO. The results indicate that among all 12 T cell clusters, the cytotoxic‐phenotype‐clusters (CPC) and the naïve‐phenotype‐clusters (NPC) significantly change between CEN and ontrol. Compared to Control, both CEN and CO are characterized by depleted NPC and increased CPC, which is dominated by CD8+ T cells. Furthermore, CPC from CEN and CO share enhanced signaling pathways and transcriptional factors associated with immune response, and possesse similar T‐cell‐receptor features, such as high clonal expansion. Interestingly, rather than a significant increase in GZMK+ CD8 cells during aging, centenarians show accumulation of GZMB+ and CMC1+ CD8 T cells. Collectively, this study unveils an immune remodeling pattern reflected by both quantitative increase and functional reinforcement of cytotoxic T cells which are essential for healthy aging.

Abstract Background Type III Bartter syndrome (BS), often known as classic Bartter syndrome is caused by variants in CLCNKB gene, which encoding the basolateral chloride channel protein ClC‐Kb, and is characterized by renal salt wasting, hypokalemia, metabolic alkalosis, increased renin, and aldosterone levels. Methods A 2‐year‐old boy presented severe malnutrition, severe metabolic alkalosis and severe hypokalemia and was clinically diagnosed with BS. The trio exome sequencing (ES) was performed to discover the genetic cause of this patient, followed by validation using Sanger sequencing and quantitative polymerase chain reaction subsequently. Results The genetic analysis indicated that this patient with a compound heterozygous variants of CLCNKB gene including a novel nonsense variant c.876 T > A and a whole‐gene deletion. The two variants were inherited from his parents, respectively. Subsequently, target sequencing of CLCNKB gene was performed for next pregnancy, and prenatal genetic diagnosis was provided for the family. Conclusions The results of current study identified the compound heterozygous variants in a patient with classic BS. The novel variant expands the spectrum of CLCNKB variants in BS. Our study also indicates that ES is an alternative tool to simultaneously detect single‐nucleotide variants and copy‐number variants.

Abstract The deep‐sea environment is characterized by darkness, hypoxia, and high hydrostatic pressure. Mitochondria play a vital role in energy metabolism; thus, they may endure the selection process during the adaptive evolution of deep‐sea organisms. In the present study, the mitogenome of Phymorhynchus sp. from the Haima methane seep was completely assembled and characterized. This mitogenome is 16,681 bp in length and contains 13 protein‐coding genes, 2 rRNAs, and 22 tRNAs. The gene order and orientation were identical to those of most sequenced conoidean gastropods. Some special elements, such as tandem repeat sequences and AT‐rich sequences, which are involved in the regulation of the replication and transcription of the mitogenome, were observed in the control region. Phylogenetic analysis revealed that Conoidea is divided into two separate clades with high nodal support. Positive selection analysis revealed evidence of adaptive changes in the mitogenomes of deep‐sea conoidean gastropods. Eight residues located in atp6, cox1, cytb, nad1, nad4, and nad5 were determined to have undergone positive selection. This study explores the adaptive evolution of deep‐sea conoidean gastropods and provides valuable clues at the mitochondrial level regarding the exceptional adaptive ability of organisms in deep‐sea environments.

Abstract Aims The aim of this study is to characterize healthcare resource utilization and costs in patients with heart failure with reduced ejection fraction (HFrEF) following a worsening heart failure event. Methods and results This was a retrospective observational cohort analysis. Patients with HFrEF were identified from the PINNACLE Registry and linked to a nationwide pharmacy and medical claims database. Worsening heart failure was defined as stable heart failure with a subsequent hospitalization and/or intravenous diuretic therapy. Healthcare resource use and costs in 2015 US dollars were analysed for dispensed prescriptions, outpatient encounters, and hospital encounters. Among 11 064 patients with HFrEF, 3087 (27.9%) experienced a worsening heart failure event during an average follow‐up of 973 days. During the first 30 days after the worsening event, 19.8% of patients had hospital readmissions with heart failure as the primary or secondary diagnosis. During that same time period, mean per patient heart failure‐related healthcare resource use included 1.3 prescriptions, 0.5 practitioner visits, and 0.5 hospital encounters (admissions, observations, or emergency care), for an average total medical cost of $8779 per patient including $5359 in heart failure‐related costs. During the first year following worsening heart failure onset, mean per patient total and heart failure‐related costs were $62 615 and $35 329, respectively. Conclusions The economic burden following a worsening heart failure event calls for further review of methods to prevent progressive disease, improve adherence to guideline‐directed therapy, and develop novel treatments and care strategies to moderate further progression.

Abstract High‐performance flexible pressure sensors have attracted a great deal of attention, owing to its potential applications such as human activity monitoring, man–machine interaction, and robotics. However, most high‐performance flexible pressure sensors are complex and costly to manufacture. These sensors cannot be repaired after external mechanical damage and lack of tactile feedback applications. Herein, a high‐performance flexible pressure sensor based on MXene/polyurethane (PU)/interdigital electrodes is fabricated by using a low‐cost and universal spray method. The sprayed MXene on the spinosum structure PU and other arbitrary flexible substrates (represented by polyimide and membrane filter) act as the sensitive layer and the interdigital electrodes, respectively. The sensor shows an ultrahigh sensitivity (up to 509.8 kPa–1), extremely fast response speed (67.3 ms), recovery speed (44.8 ms), and good stability (10 000 cycles) due to the interaction between the sensitive layer and the interdigital electrodes. In addition, the hydrogen bond of PU endows the device with the self‐healing function. The sensor can also be integrated with a circuit, which can realize tactile feedback function. This MXene‐based high‐performance pressure sensor, along with its designing/fabrication, is expected to be widely used in human activity detection, electronic skin, intelligent robots, and many other aspects.

Pancreatic cancer (PC) is one of the most common human malignancies worldwide and remains a major clinical challenge. Here, we found that benproperine phosphate (BPP), a cough suppressant, showed a significant anticancer effect on PC both in vitro and in vivo via the induction of autophagy‐mediated cell death. Mechanistic studies revealed that BPP triggered AMPK/mTOR‐mediated autophagy initiation and disturbed Ras‐related protein Rab‐11A (RAB11A)‐mediated autophagosome–lysosome fusion, resulting in excessive accumulation of autophagosomes. Inhibition of autophagy or overexpression of RAB11A partially reversed BPP‐induced growth inhibition in PC cells, suggesting that BPP might induce lethal autophagy arrest in PC cells. In conclusion, our results identify BPP as a potent antitumor agent for PC via the induction of autophagy arrest, therefore providing a new potential therapeutic strategy for the treatment of PC.

Abstract Cow milk (CM) allergy is one of the most common food allergies worldwide; the most abundant CM proteins, such as casein (CN), β‐lactoglobulin (β‐LG), and ɑ‐lactalbumin (ɑ‐LA), are all potentially allergenic. Reducing the antigenicity of CM continues to be a major challenge. However, previous studies have focused on the antigenicity of individual allergic CM proteins. Thus, in the present study, we aimed to evaluate the effects of different food‐grade enzymes on the antigenicity of CN, β‐LG, ɑ‐LA in natural CM. The degree of hydrolysis (DH) and molecular mass (MW) distribution of CM hydrolysates were assessed. Additionally, the residual antigenicity of CM hydrolysates was evaluated through enzyme‐linked immunosorbent assay and Western blotting with anti‐CN, anti‐β‐LG, and anti‐ɑ‐LA rabbit polyclonal antibodies. The results showed that Alcalase‐ and Protamex‐mediated hydrolysis could efficiently reduce the antigenicity of CN, β‐LG, and ɑ‐LA, inducing a higher DH, the loss of density of CM proteins, and the increasing levels of low MW (

Abstract Estuarine organisms grow in highly heterogeneous habitats, and their genetic differentiation is driven by selective and neutral processes as well as population colonization history. However, the relative importance of the processes that underlie genetic structure is still puzzling. Scirpus mariqueter is a perennial grass almost limited in the Changjiang River estuary and its adjacent Qiantang River estuary. Here, using amplified fragment length polymorphism (AFLP), a moderate‐high level of genetic differentiation among populations (range FST: 0.0310–0.3325) was showed despite large ongoing dispersal. FLOCK assigned all individuals to 13 clusters and revealed a complex genetic structure. Some genetic clusters were limited in peripheries compared with very mixing constitution in center populations, suggesting local adaptation was more likely to occur in peripheral populations. 21 candidate outliers under positive selection were detected, and further, the differentiation patterns correlated with geographic distance, salinity difference, and colonization history were analyzed with or without the outliers. Combined results of AMOVA and IBD based on different dataset, it was found that the effects of geographic distance and population colonization history on isolation seemed to be promoted by divergent selection. However, none‐liner IBE pattern indicates the effects of salinity were overwhelmed by spatial distance or other ecological processes in certain areas and also suggests that salinity was not the only selective factor driving population differentiation. These results together indicate that geographic distance, salinity difference, and colonization history co‐contributed in shaping the genetic structure of S. mariqueter and that their relative importance was correlated with spatial scale and environment gradient.

Objective. Abnormal signaling pathways play a crucial role in the mechanisms of podocyte injury in diabetic nephropathy. They also affect the recovery of podocytes after islet transplantation (IT). However, the specific signaling abnormalities that affect the therapeutic effect of IT on podocytes remains unclear. The purpose of this study was to assess whether the RhoA/ROCK/NF-κB signaling pathway is related to podocyte restoration after IT. Methods. A mouse model of diabetic nephropathy was established in vivo using streptozotocin. The mice were then subsequently reared for 4 weeks after islet transplantation to determine the effect of IT. Islet cells, CCG-1423 (RhoA Inhibitor), and fasudil (ROCK inhibitor) were then cocultured with podocytes in vitro to assess their protective effects on podocyte injury induced by high glucose (HG). Protein expression levels of RhoA, ROCK1, synaptopodin, IL-6, and MCP-1 in kidney tissues were then measured using immunohistochemistry and Western blotting techniques. Results. Islet transplantation reduced the expression levels of RhoA/ROCK1 and that of related inflammatory factors such as IL-6 and MCP-1 in the kidney podocytes of diabetic nephropathy. In the same line, islet cells reduced the expression of RhoA, ROCK1, and pp65 in immortalized podocytes under high glucose (35.0 mmol/L glucose) conditions. Conclusions. Islet transplantation can reverse podocyte injury in diabetes nephropathy by inhibiting the RhoA/ROCK1 signaling pathway. Islet cells have a strong protective effect on podocytes treated with high glucose (35.0 mmol/L glucose). Discovery of signaling pathways affecting podocyte recovery is helpful for individualized efficacy evaluation and targeted therapy of islet transplantation patients.

The data are ever increasing with the increase in population, communication of different devices in networks, Internet of Things, sensors, actuators, and so on. This increase goes into different shapes such as volume, velocity, variety, veracity, and value extracting meaningful information and insights, all are challenging tasks and burning issues. Decision-making based on multicriteria is one of the most critical issues solving ways to select the most suitable decision among a number of alternatives. Deep learning algorithms and multicriteria-based decision-making have effective applications in big data. Derivations are made based on the use of deep algorithms and multicriteria. Due to its effectiveness and potentiality, it is exploited in several domains such as computer science and information technology, agriculture, and business sector. The aim of the proposed study is to present a systematic literature study in order to show the applications of deep learning algorithms and multicriteria decision approaches for the problems of big data. The research finds novel means to make the decision support system for the problems of big data using multiple criteria in integration with machine learning and artificial intelligence approaches.

Based on the formation of carbodiimide compounds between carboxyl and primary amines, hollow microspheres arising from the folic acid (folate-FA) grafted onto the surface of the modified hydroxyapatite were successfully prepared. The hollow morphology and composition of the FA-grafted hydroxyapatite microspheres were confirmed by scanning electron microscopy (SEM) and other characterizations. Brunauer-Emmett-Teller (BET) assay revealed the specific surface area and average pore size of the microspheres were 34.58m2/g and 17.80 nm, respectively. As a drug carrier, the kinetic investigation of doxorubicin (DOX) loaded shows that the adsorbed behavior of drug on the adsorbent is more suitable to be described with pseudo-first-order model. Furthermore, the release rate can reach 83% at pH 5.7, which is greater than the release of 39% at pH 7.4, indicating an excellent performance of controlled drug release for response pH. The release mechanism of DOX coincides with Fickian diffusion as a result of Korsmeyer-Peppas model analysis and the release phenomena can be well explained by Fickian diffusion second law.

Objectives. Using patient global impression of change (PGIC) as an anchor, an approximately 30% reduction on an 11-point numeric pain intensity rating scale (PI-NRS) is considered a clinically important difference (CID) in pain. Our objective was to define the CID for another pain measure, the worst pain severity (WPS) item of the modified Brief Pain Inventory (m-BPI). Methods. In this post hoc analysis of a double-blind, placebo-controlled, phase 2 study, 452 randomized patients with diabetic peripheral neuropathic pain (DPNP) were followed over 5 weeks, with m-BPI data collected weekly and PGIC at treatment conclusion. Receiver operating characteristic (ROC) curves (via logistic regression) were used to determine the changes in the m-BPI-WPS score that best predicted ordinal clinical improvement thresholds (i.e., “minimally improved” or better) on the PGIC. Results. Similar to the PI-NRS, a change of −3 (raw) or −33.3% from the baseline on the m-BPI-WPS optimized prediction for the “much improved” or better PGIC threshold and represents a CID. There was a high correspondence between observed and predicted PGIC categories at each PGIC threshold (ROC AUCs were 0.78–0.82). Conclusions. Worst pain on the m-BPI may be used to assess clinically important improvements in DPNP studies. Findings require validation in larger studies.

Purpose. Lanosterol synthase (LSS) abnormity contributes to lens opacity in rats, mice, dogs, and human congenital cataract development. This study examined whether LSS pathway has a role in different subtypes of age-related cataract (ARC). Methods. A total of 390 patients with ARC and 88 age-matched non-ARC patients were enrolled in this study. LSS expression was analyzed by western blot and enzyme-linked immunosorbent assay (ELISA). To further examine the function of LSS, we used U18666A, an LSS inhibitor in rat lens culture system. Results. In lens epithelial cells (LECs), LSS expression in LECs increased with opaque degree C II, while it decreased with opaque degree C IV and C V. While in the cortex of age-related cortical cataract (ARCC), LSS expression was negatively related to opaque degree, while lanosterol level was positively correlated to opaque degree. No obvious change in both LSS and lanosterol level was found in either LECs or the cortex of age-related nuclear cataract (ARNC) and age-related posterior subcapsular cataract (ARPSC). In vitro, inhibiting LSS activity induced rat lens opacity and lanosterol effectively delayed the occurrence of lens opacity. Conclusions. This study indicated that LSS and lanosterol were localized in the lens of human ARC, including ARCC, ARNC, and ARPSC. LSS and lanosterol level are only correlated with opaque degree of ARCC. Furthermore, activated LSS pathway in lens is protective for lens transparency in cortical cataract.

Purpose. To investigate the changes of corneal surface shape and optical quality during orthokeratology. Methods. 49 eyes of 26 patients (10.63 ± 2.02 years old) who underwent overnight orthokeratology for myopia were prospectively examined. The corneal surface shape parameters, including surface regularity index (SRI) and surface asymmetry index (SAI), were attained with an OPD-III SCAN. The higher-order aberrations and higher-order Strehl ratios were calculated under a 3 mm pupil diameter before orthokeratology, 1 month, 3 months, and 6 months after orthokeratology. A P value of less than 0.05 was statistically significant. Results. Months after orthokeratology, SRI and SAI were both showing a significant increase in comparison with those before orthokeratology (P

OBJECTIVE: To assess the effect of adalimumab on work productivity and indirect costs in patients with Crohn’s disease (CD) using a meta-analysis of clinical trials.

Recently, a study reported that single nucleotide polymorphisms (SNP) in endothelial nitric oxide synthase (eNOS) were associated with primary angle closure glaucoma (PACG) in Australian cohort. In this study, we aimed to investigate whether those eNOS SNPs are associated with primary angle closure (PAC) or ocular biometric characteristics such as axial length (AL), anterior chamber depth (ACD), and diopter of spherical power (DS) in Han Chinese. The samples consisted of 232 PAC subjects and 306 controls collected from a population-based prevalence survey conducted in Funing County of Jiangsu, China. The rs3793342 and rs11771443 in eNOS were genotyped by TaqMan-MGB probe using the RT-PCR system. Our data did not identify any association of the eNOS SNPs with PAC. However, the analysis on the quantitative traits of ocular biometrics showed that the ACD of rs11771443 AA and GA carriers is significantly deeper than that of rs11771443 GG carriers (P=0.0025), even though the AL and DS are not associated with rs11771443 genotypes. Rs3793342 was not associated with any biometric parameters including ACD, AL and DS. In summary, our data indicates that eNOS rs11771443 is associated with ACD and its role in the pathogenesis of PACG warranted further study.