Automated segmentation and volume prediction in pediatric Wilms' tumor CT using nnu-net.

BACKGROUND: Radiologic volumetric evaluation of Wilms' tumor (WT) is an important indicator to guide treatment decisions. However, due to the heterogeneity of the tumors, radiologists have main-guard differences in diagnosis that can lead to misdiagnosis and poor treatment. The aim of this study was to explore whether CT-based outlining of WT foci can be automated using deep learning. METHODS: We included CT intravenous phase images of 105 patients with WT and double-blind outlining of lesions by two radiologists. Then, we trained an automatic segmentation model using nnUnet. The Dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (HD95) were used to assess the performance. Next, we optimized the automatic segmentation results based on the ratio of the three-dimensional diameter of the lesion to improve the performance of volumetric assessment. RESULTS: The DSC and HD95 was 0.83 ± 0.22 and 10.50 ± 8.98 mm. The absolute difference and percentage difference in tumor size was 72.27 ± 134.84 cm3 and 21.08% ± 30.46%. After optimization according to our method, it decreased to 40.22 ± 96.06 cm3 and 10.16% ± 9.70%. CONCLUSION: We introduce a novel method that enhances the accuracy of predicting WT volume by integrating AI automated outlining and 3D tumor diameters. This approach surpasses the accuracy of using AI outcomes alone and has the potential to enhance the clinical evaluation of pediatric patients with WT. By intertwining AI outcomes with clinical data, this method becomes more interpretive and offers promising applications beyond Wilms tumor, extending to other pediatric diseases.

Exploration of the causal associations between circulating inflammatory proteins, immune cells, and neuromyelitis optica spectrum disorder: a bidirectional Mendelian randomization study and mediation analysis.

Background: An increasing body of research has demonstrated a robust correlation between circulating inflammatory proteins and neuromyelitis optica spectrum disorders (NMOSD). However, whether this association is causal or whether immune cells act as mediators currently remains unclear. Methods: We employed bidirectional two-sample Mendelian randomization (TSMR) analysis to examine the potential causal association between circulating inflammatory proteins, immune cells, and NMOSD using data from genome-wide association studies (GWAS). Five different methods for Mendelian randomization analyses were applied, with the inverse variance-weighted (IVW) method being the primary approach. Sensitivity analyses were further performed to assess the presence of horizontal pleiotropy and heterogeneity in the results. Finally, a two-step Mendelian randomization (MR) design was employed to examine the potential mediating effects of immune cells. Results: A notable causal relationship was observed between three circulating inflammatory proteins (CSF-1, IL-24, and TNFRSF9) and genetically predicted NMOSD. Furthermore, two immune cell phenotypes, genetically predicted CD8 on naive CD8+ T cells, and Hematopoietic Stem Cell Absolute Count were negatively and positively associated with genetically predicted NMOSD, respectively, although they did not appear to function as mediators. Conclusion: Circulating inflammatory proteins and immune cells are causally associated with NMOSD. Immune cells do not appear to mediate the pathway linking circulating inflammatory proteins to NMOSD.

Lowest Glucagon/Highest C-Peptide in Oral Glucose Tolerance Test: Clinical Utility in Monitoring Glucose Control in Type 2 Diabetes Mellitus.

Purpose: Understanding factors that influence blood glucose levels in patients with type 2 diabetes mellitus (T2DM) is crucial for managing hyperglycemia. Currently, there is no standardized interpretation method for glucagon levels in oral glucose tolerance test (OGTT). This study aims to assess the relationship between the lowest glucagon/highest C-peptide ratio (Lglc/Hcp) in OGTT and glucose control levels in T2DM. Patients and Methods: Clinical data from 120 patients with T2DM were examined to compare the correlations of Lglc/Hcp and other pancreatic islet function-associated indices with fasting blood glucose (G0), glucose at 120 minutes in OGTT (G120), hemoglobin A1c (HbA1c), and the area under the glucose curve in OGTT (AUCglu). Additionally, the study investigated difference in Lglc/Hcp between patient groups based on the highest blood glucose levels (Hglu) in OGTT (Hglu ≥ 16.7 mmol/L vs Hglu < 16.7 mmol/L). Results: The generalized linear model suggested that Lglc/Hcp significantly correlated with G0 (B = 0.85, P < 0.001), G120(B = 1.46, P < 0.001), HbA1c (B = 0.67, P < 0.001), and AUCglu (B = 3.46, P < 0.001). This correlation surpassed C-peptide and glucagon-related parameters, even after adjusting for confounding factors. Furthermore, Lglc/Hcp was notably higher in patients with Hglu ≥ 16.7 mmol/L compared to those with Hglu < 16.7 mmol/L (Z = -3.71, p < 0.001). Conclusion: Lglc/Hcp in OGTT closely relates to blood glucose control in patients with T2DM, potentially reflecting the overall pancreatic islet function in regulating glucose levels. Moreover, inhibiting glucagon secretion may be a crucial consideration for patients requiring insulin treatment.

Pivotal Evaluation of Novel Dedicated Venous Stent for Iliofemoral Venous Obstruction: A Prospective Cohort Study.

PURPOSE: The purpose was to evaluate the clinical outcomes of a dedicated venous stent with the tripartite composite segments for the treatment of iliofemoral venous obstruction (IVO) in a mixed cohort of nonthrombotic iliac vein lesion (NIVL) and post-thrombotic syndrome (PTS) over a period of 12 months. METHODS: The Grency Trial is a prospective, multicenter, single-arm, open-label, pivotal study, which was conducted at 18 large tertiary hospitals in China from August 2019 to October 2020. A total of 133 hospitalized patients were screened and 110 patients with clinical, etiology, anatomical, and pathophysiology clinical class (CEAP) clinical grade C>3 and iliac vein stenosis >50% or occlusion, including 72 patients with NIVL and 38 patients with PTS, were implanted with Grency venous stents. Primary endpoint was stent patency at 12 months follow-up, and secondary outcomes were technical success; improvement in venous clinical severity score (VCSS) at 3, 6, and 12 month follow-up; and rates of clinical adverse events. RESULTS: Among 110 patients who were implanted with Grency venous stents, 107 patients completed the 12 month follow-up. All 129 stents were successfully implanted in 110 limbs. Twelve-month primary patency rate was 94.39% [95% confidence interval [CI]=88.19%-97.91%] overall, and 100% [94.94%-100%] and 83.33% [67.19%-93.63%] in the NIVL and PTS subgroups, respectively. Venous clinical severity score after iliac vein stenting improved significantly up to 12 months follow-up. There were 3 early major adverse events (1 intracerebral hemorrhage and 2 stent thrombosis events related to anticoagulation therapy), and 7 late major adverse events (1 cardiovascular death, 1 intracranial hemorrhage with uncontrolled hypertension, and 5 in-stent restenosis cases without stent fractures or migration). CONCLUSIONS: The Grency venous stent system appeared excellent preliminary safe and effective for IVO treatment. Further large-scale studies with longer-term follow-up are needed to evaluate long-term patency and durability of stent. CLINICAL IMPACT: The design of venous stents for iliofemoral venous obstruction (IVO) must address engineering challenges distinct from those encountered in arterial stenting. The Grency venous stent, a nitinol self-expanding stent specifically tailored for IVO, features a composite structure designed to meet the stent requirements of various iliac vein segments. The Grency Trial is a prospective, multicenter, single-arm, open-label pivotal study aimed at evaluating the efficacy and safety of the Grency stent system. Following a 12-month follow-up period, the Grency venous stent system has demonstrated both safety and efficacy in treating iliofemoral venous outflow obstruction.

Characteristics and efficacy of traditional Chinese medicine in the therapeutic strategy of chronic coronary syndrome: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Chronic coronary syndrome (CCS) has always been controversial in its therapeutic strategy. Although invasive treatment and optimal medication therapy (OMT) are the most commonly used treatments, doctors continue to debate the best strategy. However, traditional Chinese medicine (TCM) for CCS is effective clinically. METHODS: To identify potentially eligible observational and experimental studies, we searched Pubmed, the Web of Science, and the China National Knowledge Internet. To be eligible, studies had to report with end-of treatment outcomes, such as major adverse cardiac events (MACE), deaths from myocardial infarctions (MI), all-cause mortality, angina, cardiac mortality, the effectiveness rate of electrocardiographs, and the reduction rate of the Nitroglycerin tablets. Risk differences (RDs) and 95 % confidence intervals (95 % CIs) were calculated based on random-effects models or fixed-effects models. Citation screening, data abstraction, risk assessment, and strength-of-evidence grading were completed by 2 independent reviewers. RESULTS: In Section 1 (13 studies, involving 17,287 patients), showed no significant difference between invasive treatment and medication treatment in MACE (RD = -0.04, 95% CI = -0.08 to 0.00, I2 = 76.4 %), all-cause mortality (RD = -0.01, 95%CI = -0.022 to 0.01, I2 = 73.44 %), MI (RD = 0.00, 95%CI = -0.00 to 0.01, I2 = 0.00 %) and cardiac mortality (RD = 0.00, 95 %CI = -0.01 to 0.01, I2 = 34.9 %). In Section 2 (21 studies, including 1820 patients), compared with WM treatment, TCM + WM treatment increased ECG effectiveness by 18 %, angina effectiveness by 20 %, and stopping or reducing Nitroglycerin tablets by 20 %. In Section 3 (25 studies, including 2859 patients) showed that TCM revealed a better electrocardiogram effective rate (RD = 0.10, 95 %CI = 0.05 to 0.14, I2 = 44.7 %) and angina effective rate (RD = 0.12, 95 %CI = 0.09 to 0.15, I2 = 44.9 %). We identified that TCM treatment properties of "Circulating blood and transforming stasis" and application of warm/heat-properties medicines were frequently used in CCS treatment. CONCLUSIONS: TCM treatment has shown superior beneficial cardioprotective in CCS therapy strategy, among which "Circulating blood and transforming stasis" and the application of warm/heat-properties medicine are its characteristics.

Numerical simulation of ultrawideband supercontinuum generation covering a 2-20 µm waveband in cascaded all-soft-glass fiber.

We designed a cascaded all-soft-glass fiber structure and simulate midinfrared 2-20 µm ultrawideband supercontinuum (SC) generation numerically. The cascaded fiber structure consists of a 1.5 m I n F 3 fiber, a 0.2 m chalcogenide photonic crystal fiber, and a 0.2 m tellurium-based chalcogenide photonic crystal fiber. Using a 2 µm pulse pumping this cascaded structure, the generated SC covering the wavelengths longer than 20 µm has been demonstrated theoretically. The 30 dB bandwidth reaches 20.87 µm from 1.44 to 22.31 µm. The effect of different pulse widths on SC generation is considered. With the increase of peak power and the decrease of pulse width, the energy of SC in the 15-20 µm waveband increases gradually. The mechanism of SC broadening process has also been analyzed. The SC generation of more than 20 µm in this cascade structure is caused by the self-phase modulation, soliton effects, four-wave mixing, and redshifted dispersive wave. This method demonstrates the possibility of generating ultrawide bandwidth SCs up to a 20 µm waveband by a commercial 2 µm pump source and all-fiber structure.

Preparation of Ceramic Fiber Threads with Enhanced Abrasion Resistance Performance.

Ceramic fiber thread is one of the key components in flexible external thermal insulation blankets, and it has been applied in various fields as a flexible ceramic fibrous material with excellent deformability and high-temperature resistance. However, ceramic fiber threads are often subjected to reciprocating friction motion at specific bending angles, making them highly susceptible to abrade and fracture. Enhancing the abrasion resistance performance of ceramic fiber threads under bending conditions is the future trend and remains a significant challenge. Hence, we design and construct a novel polyurethane-modified coating on the ceramic fiber threads to improve their abrasion resistance performance. The effects of the types and concentrations of modifiers on the microstructure, abrasion resistance property, and tensile property of ceramic fiber threads are systematically investigated. The ceramic fiber threads, after modification with hexamethylene diisocyanate waterborne polyurethane (HDI-WPU) with a concentration of 3%, exhibit excellent abrasion resistance properties. The number of friction cycles at fracture of the modified ceramic fiber thread is more than three times, and the tensile strength is more than one and a half times, that of the original ceramic fiber thread, demonstrating the great potential of the HDI-WPU modifier for enhancing the abrasion resistance performance of ceramic fiber threads.

Preclinical Evaluation of a Modular Inner-Branched Stent Graft to Reconstruct the Left Subclavian Artery in Thoracic Endovascular Aortic Repair: Experimental Study in Pigs.

PURPOSE: In approximate 40% of thoracic endovascular aortic repair (TEVAR) procedures, the left subclavian artery (LSA) needs to be covered to obtain sufficient proximal sealing zone. To preserve the LSA during the TEVAR for type B aortic dissection (TBAD) adjacent to LSA, our team designed a modular single inner-branched stent graft. This study was performed to evaluate the safety and feasibility of deploying a modular single inner-branched stent graft in a porcine model. MATERIALS AND METHODS: Modular inner-branched stent grafts were implanted in 14 pigs via right femoral and right carotid arterial access. Computed tomography angiography (CTA) and angiography were performed in all pigs to appraise the morphological characteristics of the stent grafts at the end of follow-up. The pigs were then euthanized, and tissues were collected for gross and histological examination. RESULTS: The technical success rate was 100% (14/14). One pig suddenly died 5 hours after operation, and 1 pig died after completing the follow-up CTA. During the follow-up period, all surviving pigs showed good mental state, normal diets and activities. Computed tomography angiography examinations showed that all stent grafts were intact without fracture. All bridging covered stents were patent. Angiography showed that the position, shape, and adhesion of the stent grafts were good, and no obvious endoleaks were found. Histological examination showed that the biocompatibility of the stent grafts was good. CONCLUSIONS: This study's outcomes demonstrate that it is safe and feasible to deploy a modular single inner-branched stent graft in a porcine model. CLINICAL IMPACT: This device is the first modular device designed to treat TBAD adjacent to LSA in China. This device is a modular two-component system consisting of a thoracic aortic stent graft with a retrograde inner branch and a bridging covered stent. The modular design and the retrograde inner branch are the two important innovations of this device. Theoretically, the device could make it easier and safer for clinicians to treat TBAD adjacent to the LSA.

Positive psychological capital, post-traumatic growth, social support, and quality of life in patients with systemic lupus erythematosus: A cross-sectional study.

OBJECTIVE: This study aimed to investigate the correlation between positive psychological capital, post-traumatic growth, social support, and quality of life (QOL) in patients with systemic lupus erythematosus (SLE). METHODS: A cross-sectional study was conducted at the First Affiliated Hospital of Xinjiang Medical University from October 2022 to May 2023. A sample of 330 hospitalized SLE patients was selected for this study. The collected data included demographic information, the SLE disease activity index, the Positive Mental Capital Questionnaire, the Chinese version of the Post-Traumatic Growth Scale, the Social Support Rating Scale, and the Chinese version of the Lupus Quality of Life Scale. RESULTS: The QOL score among the 330 SLE patients was measured as M(P25, P75) of 105 (83.00,124.00). Positive psychological capital, post-traumatic growth, and social support demonstrated significant positive correlations with the QOL in SLE patients (p < 0.05). Multiple linear regression analysis revealed that literacy, disease level, disease duration, occupation, marital status, psychological capital, social support, and post-traumatic growth were influential factors associated with the QOL in SLE patients. CONCLUSION: Medical professionals should be attentive to the psychological well-being of SLE patients and should consider implementing early psychological interventions. These interventions are crucial for enhancing the QOL for individuals diagnosed with SLE.

Chemisorption-Induced Robust and Homogeneous Tungsten Disulfide Interlayer Enables Stable PEDOT-Free Organic Solar Cells with Over 19% Efficiency.

Construction of a high-quality charge transport layer (CTL) with intimate contact with the substrate via tailored interface engineering is crucial to increase the overall charge transfer kinetics and stability for a bulk-heterojunction (BHJ) organic solar cell (OSC). Here, we demonstrate a surface chemistry strategy to achieve a homogeneous composite hole transport layer (C-HTL) with robust substrate contact by self-assembling two-dimensional tungsten disulfide (WS2) nanosheets on a thin molybdenum oxide (MoO3) film-evaporated indium tin oxide (ITO) substrate. It is found that over such a well-defined C-HTL, WS2 is homogeneously tethered on the ITO/MoO3 substrate stemming from the strong electronic coupling interaction between the building blocks, which enables a favorable interfacial configuration in terms of uniformity. As a result, the D18:L8-BO-based OSC with C-HTL exhibits a power conversion efficiency (PCE) of 19.23%, an 11% improvement over the WS2-based control device, and the highest efficiency among single-junction PEDOT-free binary BHJ OSCs.

Activation of testosterone-androgen receptor mediates cerebrovascular protection by photobiomodulation treatment in photothrombosis-induced stroke rats.

RATIONALE: Numerous epidemiological studies have reported a link between low testosterone levels and an increased risk of cerebrovascular disease in men. However, there is ongoing controversy surrounding testosterone replacement therapy due to potential side effects. PBMT has been demonstrated to improve cerebrovascular function and promote testosterone synthesis in peripheral tissues. Despite this, the molecular mechanisms that could connect PBMT with testosterone and vascular function in the brain of photothrombosis (PT)-induced stroke rats remain largely unknown. METHODS: We measured behavioral performance, cerebral blood flow (CBF), vascular permeability, and the expression of vascular-associated and apoptotic proteins in PT-induced stroke rats treated with flutamide and seven consecutive days of PBM treatment (350 mW, 808 nM, 2 min/day). To gain further insights into the mechanism of PBM on testosterone synthesis, we used testosterone synthesis inhibitors to study their effects on bEND.3 cells. RESULTS: We showed that PT stroke caused a decrease in cerebrovascular testosterone concentration, which was significantly increased by 7-day PBMT (808 nm, 350 mW/cm2 , 42 J/cm2 ). Furthermore, PBMT significantly increased cerebral blood flow (CBF) and the expression of vascular-associated proteins, while inhibiting vascular permeability and reducing endothelial cell apoptosis. This ultimately mitigated behavioral deficits in PT stroke rats. Notably, treatment with the androgen receptor antagonist flutamide reversed the beneficial effects of PBMT. Cellular experiments confirmed that PBMT inhibited cell apoptosis and increased vascular-associated protein expression in brain endothelial cell line (bEnd.3) subjected to oxygen-glucose deprivation (OGD). However, these effects were inhibited by flutamide. Moreover, mechanistic studies revealed that PBMT-induced testosterone synthesis in bEnd.3 cells was partly mediated by 17ß-hydroxysteroid dehydrogenase 5 (17ß-HSD5). CONCLUSIONS: Our study provides evidence that PBMT attenuates cerebrovascular injury and behavioral deficits associated with testosterone/AR following ischemic stroke. Our findings suggest that PBMT may be a promising alternative approach for managing cerebrovascular diseases.

Mechanisms of isomerization and hydration reactions of typical ß-diketone at the air-droplet interface.

Acetylacetone (AcAc) is a typical class of ß-diketones with broad industrial applications due to the property of the keto-enol isomers, but its isomerization and chemical reactions at the air-droplet interface are still unclear. Hence, using combined molecular dynamics and quantum chemistry methods, the heterogeneous chemistry of AcAc at the air-droplet interface was investigated, including the attraction of AcAc isomers by the droplets, the distribution of isomers at the air-droplet interface, and the hydration reactions of isomers at the air-droplet interface. The results reveal that the preferential orientation of two AcAc isomers (keto- and enol-AcAc) to accumulate and accommodate at the acidic air-droplet interface. The isomerization of two AcAc isomers at the acidic air-droplet interface is more favorable than that at the neutral air-droplet interface because the "water bridge" structure is destroyed by H3O+, especially for the isomerization from keto-AcAc to enol-AcAc. At the acidic air-droplet interface, the carbonyl or hydroxyl O-atoms of two AcAc isomers display an energetical preference to hydration. Keto-diol is the dominant products to accumulate at the air-droplet interface, and excessive keto-diol can enter the droplet interior to engage in the oligomerization. The photooxidation reaction of AcAc will increase the acidity of the air-droplet interface, which indirectly facilitate the uptake and formation of more keto-diol. Our results provide an insight into the heterogeneous chemistry of ß-diketones and their influence on the environment.

Compound Danshen dripping pills prevent early diabetic retinopathy: roles of vascular protection and neuroprotection.

Introduction: Diabetic retinopathy (DR) represents a major cause of adult blindness, and early discovery has led to significant increase in the number of patients with DR. The drugs currently used for treatment, such as ranibizumab, mainly focus on the middle and late periods of DR, and thus do not meet the clinical need. Here, the potential mechanisms by which compound Danshen Dripping Pills (CDDP) might protect against early DR were investigated. Methods: Db/db mice were used to establish a DR model. The initial weights and HbA1c levels of the mice were monitored, and retinal pathology was assessed by hematoxylin-eosin (HE) staining. The vascular permeability of the retina and thickness of each retinal layer were measured, and electroretinogram were performed together with fundus fluorescein angiography and optical coherence tomography. The levels of inflammatory factors were examined in retinal tissue, as well as those of intercellular adhesion molecule 1 (ICAM-1), IL-6, and monocyte chemoattractant protein 1 (MCP-1) in the serum using ELISA. Immunohistochemistry was used to evaluate levels of vascular endothelial growth factor (VEGF), B-cell lymphoma 2 (Bcl-2), and Bclassociated X protein (Bax). Retinal cell injury and apoptosis were examined by TdT-mediated dUTP Nick End Labeling (TUNEL) assays. Results: The data showed that CDDP significantly improved cellular disarrangement. Imaging data indicated that CDDP could reduce vascular permeability and the amplitude of oscillatory potentials (OPs), and restore the thickness of the ganglion cell layer. Moreover, CDDP reduced the expression levels of inflammatory factors in both the retina and serum. Conclusion: These findings strongly suggest that CDDP prevents early DR through vascular and neuroprotection.

Gut microbiota composition and changes in patients with sepsis: potential markers for predicting survival.

BACKGROUND: Sepsis can cause immune dysregulation and multiple organ failure in patients and eventually lead to death. The gut microbiota has demonstrated its precise therapeutic potential in the treatment of various diseases. This study aimed to discuss the structural changes of the gut microbiota in patients with sepsis and to analyze the differences in the gut microbiota of patients with different prognoses. METHODS: We conducted a multicenter study in which rectal swab specimens were collected on the first and third days of sepsis diagnosis. A total of 70 specimens were collected, and gut microbiota information was obtained by 16S rRNA analysis. RESULTS: The relative abundance of Enterococcus decreased in rectal swab specimens during the first three days of diagnosis in patients with sepsis, while the relative abundance of inflammation-associated Bacillus species such as Escherichia coli, Enterobacteriaceae, and Bacteroidetes increased. By comparing the differences in the flora of the survival group and the death group, we found that the abundance of Veillonella and Ruminococcus in the death group showed an increasing trend (p < 0.05), while the abundance of Prevotella_6 and Prevotella_sp_S4_BM14 was increased in surviving patients (p < 0.05). CONCLUSIONS: The Firmicutes/Bacteroidetes ratio, reflecting overall gut microbial composition, was significantly lower on day three of sepsis diagnosis. Changes in the abundance of specific gut microbiota may serve as prognostic markers in patients with sepsis.

Wavelength selection method for near-infrared spectroscopy based on Max-Relevance Min-Redundancy.

Near-infrared spectroscopy (NIRS) is a rapid, nondestructive analytical technique utilized in various fields. However, the NIR data, which consists of hundreds of dimensions, may exhibit considerable duplication in the spectrum information. This redundancy might impair modeling effectiveness. As a result, feature selection on the spectral data becomes critical. The Max-Relevance Min-Redundancy (mRMR) method stands out among the different feature selection techniques for dimensional reduction. The approach depends on mutual information (MI) between random variables as the basis for feature selection and is unaffected by modeling methods. However, it is necessary to clarify the benefits of the maximum correlation minimal redundancy algorithm in the context of near-infrared spectral feature selection, as well as its adaptability to various modeling methods. This research focuses on the NIR spectral dataset of maize germination rate, and the mRMR method is utilized to select spectral features. Based on the preceding foundation, we create models for Support Vector Regression, Gaussian Process Regression, Random Forest, and Neural Networks. The experimental findings demonstrate that, among the feature selection methods employed in this paper, the Max-Relevance Min-Redundancy algorithm outperforms others regarding the corn germination rate dataset.

Analysis of age-specified and genotype distribution of HPV multiple infections in the Chinese population.

Multiple infections are a key component of HPV pathogenesis and have a direct impact on how an infection turns out. It's crucial to look at the associations between HPV multiple infections and both age and HPV genotypes in the Chinese population, searching for the causative factors of multiple infections with a view to providing new ideas for the treatment and prevention of multiple infections. In this study, we retrospectively analyzed the data of HPV infections among outpatients from the 2019 year to the 2021 year of Shandong Maternal and Child Health Hospital. Analyzed the correlation between HPV multiple infections and age using logistic regression. Differences in the percentage of multiple infections between age groups were compared using the chi-square test. The chi-square test compared the differences in the distribution of 15 common HPV genotypes in mono- versus multiple infections. A two-dimensional matrix presented the frequency of HPV genotype combinations. Logistics regression analysis showed that age was significantly associated with the occurrence of multiple infections, with a dominance ratio OR 1.026 (95% CI 1.02-1.04). Interestingly, the proportion of HPV multiple infections among HPV-positive individuals increases with age in people older than 30 years of age. The chi-square test showed there was a difference in the distribution of HPV genotypes between multiple infections and mono- HPV infection (χ2 = 76.4; p = 0.000), a difference in the composition of HPV genotypes for dual versus single infections (χ2 = 90.6; p = 0.000) and a difference in HPV genotypes for triple versus single infections (χ2 = 56.7; p = 0.000). A 2 × 2 matrix showed that the combination of HPV52/HPV58 (30; 6.4%) was the combination of the highest frequency of infection for dual infections; The HPV52/HPV58 (21; 4.8%) combination was the highest frequency of HPV triple infection combination. HPV multiple infections were positively correlated with age; increasing age was positively correlated with the proportion of HPV multiple infections in the total infected population; the distribution of the 15 common genotypes of HPV differed between multiple infections and single infections; and HPV52:58 was a common type of infection combination in the Shandong population.

Enhancing axonal myelination: Clemastine attenuates cognitive impairment in a rat model of diffuse traumatic brain injury.

Traumatic brain injury (TBI) has a significant impact on cognitive function, affecting millions of people worldwide. Myelin loss is a prominent pathological feature of TBI, while well-functioning myelin is crucial for memory and cognition. Utilizing drug repurposing to identify effective drug candidates for TBI treatment has gained attention. Notably, recent research has highlighted the potential of clemastine, an FDA-approved allergy medication, as a promising pro-myelinating drug. Therefore, in this study, we aim to investigate whether clemastine can enhance myelination and alleviate cognitive impairment following mild TBI using a clinically relevant rat model of TBI. Mild diffuse TBI was induced using the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA). Animals were treated with either clemastine or an equivalent volume of the vehicle from day 1 to day 14 post-injury. Following treatment, memory-related behavioral tests were conducted, and myelin pathology in the cortex and hippocampus was assessed through immunofluorescence staining and ProteinSimple® capillary-based immunoassay. Our results showed that TBI leads to significant myelin loss, axonal damage, glial activation, and a decrease in mature oligodendrocytes in both the cortex and hippocampus. The TBI animals also exhibited notable deficits in memory-related tests. In contrast, animals treated with clemastine showed an increase in mature oligodendrocytes, enhanced myelination, and improved performance in the behavioral tests. These preliminary findings support the therapeutic value of clemastine in alleviating TBI-induced cognitive impairment, with substantial clinical translational potential. Our findings also underscore the potential of remyelinating therapies for TBI.

Development of tenofovir monobenzyl ester phosphonoamidate prodrugs with improved anti-hepatitis B virus activity and intrahepatic tenofovir enrichment.

Various tenofovir (TFV) prodrugs have been developed by introducing masking groups to the hydroxyls of the monophosphonate group to enhance intestinal absorption efficiency and therapeutic effects. However, the reported TFV prodrugs have drawbacks such as low bioavailability, systemic toxicity caused by their breakdown in non-targeted tissues, and potential low intracellular conversion efficiency. In the present study, we developed a class of TFV monobenzyl ester phosphonoamidate prodrugs without substitutions on the benzene ring. Compared with previous TFV prodrugs, compounds 3a and 3b developed in the present study showed higher anti-hepatitis B virus activity, stronger stability and higher levels of intrahepatic enrichment of the metabolic product (TFV), indicating the potential of these compounds as novel prodrugs with high efficiency and low systemic toxicity for the treatment of hepatitis B.

Ultrahigh Degree of Cationic Disorder, Configurational Entropy in New Type of High-Entropy Pseudobrookite Phase.

High-entropy ceramics exhibit various excellent properties owing to their high configurational entropy, which is caused by multi-principal elements sharing one lattice site. The configurational entropy will further increase significantly if multi-principal elements randomly share two different lattice sites. For this purpose, pseudobrookite phase containing two cationic lattice sites (A and B sites) is selected, and corresponding high-entropy pseudobrookite (M2+ 0.4 M3+ 1.2 )Ti1.4 O5 is synthesized. Herein, the distribution of the 2-valent and 3-valent cations in the A and B sites are analysed in depth. The distance between the A and B sites in the crystal structure models which are constructed by the Rietveld analysis is calculated and defined as distance d. Meanwhile, the atomic column positions in the STEM images are quantified by a model-based mathematical algorithm, and the corresponding distance d are calculated. By comparing the distance d, it is determine that the 2-valent and 3-valent cations are jointly and disorderly distributed in the A and B sites in high-entropy (M2+ 0.4 M3+ 1.2 )Ti1.4 O5 . The density functional theory (DFT) simulations also demonstrate that this type of crystal structure is more thermodynamically stable. The higher degree of cationic disorder leads to a higher configurational entropy in high-entropy (M2+ 0.4 M3+ 1.2 )Ti1.4 O5 , and endows high-entropy (M2+ 0.4 M3+ 1.2 )Ti1.4 O5 with very low thermal conductivity (1.187-1.249 W m-1  K-1 ).

Soluble Nanographene C222: Synthesis and Applications for Synergistic Photodynamic/Photothermal Therapy.

Nanographene C222, which consists of a planar graphenic plane containing 222 carbon atoms, holds the record as the largest planar nanographene synthesized to date. However, its complete insolubility makes the processing of C222 difficult. Here we addressed this issue by introducing peripheral substituents perpendicular to the graphene plane, effectively disrupting the interlayer stacking and endowing C222 with good solubility. We also found that the electron-withdrawing substituents played a crucial role in the cyclodehydrogenation process, converting the dendritic polyphenylene precursor to C222. After disrupting the interlayer stacking, the introduction of only a few peripheral carboxylic groups allowed C222 to dissolve in phosphate buffer saline, reaching a concentration of up to 0.5 mg/mL. Taking advantage of the good photosensitizing and photothermal properties of the inner C222 core, the resulting water-soluble C222 emerged as a single-component agent for both photothermal and photodynamic tumor therapy, exhibiting an impressive tumor inhibition rate of 96%.