Polyethylene microplastics induced inflammation via the miR-21/IRAK4/NF-κB axis resulting to endoplasmic reticulum stress and apoptosis in muscle of carp.

As a widespread environmental pollutant, microplastics pose a great threat to the tissues and organs of aquatic animals. The carp's muscles are necessary for movement and survival. However, the mechanism of injury of polyethylene microplastics (PE-MPs) to carp muscle remains unclear. Therefore, in this study, PE-MPs with the diameter of 8 µm and the concentration of 1000 ng/L were used to feed carp for 21 days, and polyethylene microplastic treatment groups was established. The results showed that PE-MPs could cause structural abnormalities and disarrangement of muscle fibers, and aggravate oxidative stress in muscles. Exposure to PE-MPs reduced microRNA (miR-21) in muscle tissue, negatively regulated Interleukin-1 Receptor Associated Kinase 4 (IRAK4), activated Nuclear Factor Kappa-B (NF-κB) pathway, induced inflammation, and led to endoplasmic reticulum stress and apoptosis. The present study provides different targets for the prevention of muscle injury induced by polyethylene microplastics.

Secondary hypogonadism following hand, foot, and mouth disease in an adult: a case report and review of literature.

BACKGROUND: Previous reports have described hypogonadism associated with virus infection such as hantavirus, human immunodeficiency virus (HIV) or severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). However, to our best knowledge there has been no case report of secondary hypogonadism following hand, foot, and mouth disease (HFMD). CASE PRESENTATION: A previously healthy 28-year-old man with no history of major physical and psychological trauma, presented with bilateral gynecomastia and erectile dysfunction 2 weeks after HFMD. Laboratory testament showed the level of gonadotropin hormones declined. Imaging examination demonstrated no major abnormal change in pituitary or reproductive system. The diagnosis of hypogonadism was established. Then the patient was ordered to maintain mental health outward of hospital without drug intervention. One month after presentation, his gonadotropin hormone level and sexual desire had recovered, while bilateral gynecomastia and erectile dysfunction symptoms disappeared. CONCLUSIONS: Physicians should notice the possibility for hypogonadism in adult patients with a recent history of HFMD.

Biological Application of Novel Biodegradable Cellulose Composite as a Hemostatic Material.

Degradable hemostatic materials have unique advantages in reducing the amount of bleeding, shortening the surgical operation time, and improving patient prognosis. However, none of the current hemostatic materials are ideal and have disadvantages. Therefore, a novel biodegradable cellulose-based composite hemostatic material was prepared by crosslinking sodium carboxymethyl cellulose (CCNa) and hydroxyethyl cellulose (HEC), following an improved vacuum freeze-drying method. The resulting cellulose composite material was neutral in pH and spongy with a density of 0.042 g/cm3, a porosity of 77.68%, and an average pore size of 13.45 µm. The composite's compressive and tensile strengths were 0.1 MPa and 15.2 MPa, respectively. Under in vitro conditions, the composites were degraded gradually through petite molecule stripping and dissolution, reaching 96.8% after 14 days and 100% degradation rate at 21 days. When implanted into rats, the degradation rate of the composite was slightly faster, reaching 99.7% in 14 days and 100% in 21 days. Histology showed a stable inflammatory response and no evidence of cell degeneration, necrosis, or abnormal hyperplasia in the tissues around the embedded material, indicating good biocompatibility. In the hemorrhagic liver model, the time to hemostasis and the total blood loss in the cellulose composite group was significantly lower than in the medical gauze group and the blank control group (P < 0.05). These data indicate that the novel cellulose composite is a promising implantable hemostatic material in clinical settings.

[Pharmacokinetics and pharmacodynamics of pegylated recombinant human granulocyte colony-stimulating factor in children with acute lymphoblastic leukemia: a prospective control trial].

OBJECTIVE: To study the pharmacokinetic characteristics, clinical effect, and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in children with acute lymphoblastic leukemia (ALL). METHODS: A prospective study was performed on children with ALL who cyclophosphamide, cytarabine, and 6-mercaptopurine were used for consolidation therapy. PEG-rhG-CSF (PEG-rhG-CSF group) or rhG-CSF (rhG-CSF group) was injected after chemotherapy. The plasma concentration of PEG-rhG-CSF was measured, and clinical outcome and safety were observed for both groups. RESULTS: A total of 17 children with ALL were enrolled, with 9 children in the PEG-rhG-CSF group and 8 children in the rhG-CSF group. In the PEG-rhG-CSF group, the peak concentration of PEG-rhG-CSF was 348.2 ng/mL (range 114.7-552.0 ng/mL), the time to peak was 48 hours (range 12-72 hours), and the half life was 14.1 hours (range 11.1-18.1 hours). The plasma concentration curve of PEG-rhG-CSF was consistent with the mechanism of neutrophil-mediated clearance. Compared with the rhG-CSF group, the PEG-rhG-CSF group had a significantly shorter median time to absolute neutrophil count (ANC) recovery (P<0.05). There were no significant differences between the two groups in ANC nadir, incidence rate of febrile neutropenia, duration of grade IV neutropenia, incidence rate of infection, and length of hospital stay. No bone pain or muscle soreness was observed in either group (P>0.05). CONCLUSIONS: The pharmacokinetic characteristics of PEG-rhG-CSF in children with ALL receiving consolidation chemotherapy are consistent with the mechanism of neutrophil-mediated clearance, with a short half life and fast recovery of ANC, and there are no significant differences in safety between PEG-rhG-CSF and rhG-CSF.

Onychomadesis and potential association with HFMD outbreak in a kindergarten in Hubei province, China, 2017.

BACKGROUND: In 2017, an outbreak of onychomadesis occurred in kindergarten H, Hubei province, China. We investigated the field to learn about the magnitude and reason of the outbreak. METHODS: The case definition was that a child with onychomadesis or transverse ridging (Beau's line) in fingernails and toenails without previous traumatic or systemic disease in kindergarten H from Sep. 1st to Nov. 30th, 2017. A retrospective cohort study was carried out to analyze the epidemiological relationship between onychomadesis and the hand-foot-mouth disease (HFMD) in Primary Class #2, kindergarten H. We also performed a serological survey for neutralizing antibodies against coxsackie virus A6 (CVA6), coxsackie virus A10 (CVA10) among 15 cases and six healthy children in the kindergarten. Meanwhile, some children were carried out with routine blood, fungal microscopic and microelement tests. Indoor environment examinations had been done for all classes. RESULTS: A total of 20 cases were identified in Kindergarten H. Seventy-five percent (15/20) cases occurred in Primary Class #2. Fifty-five percent of the cases (11/20) had suffered from HFMD within two months. The median time between onychomadesis and HFMD was 45 days (ranging from 31 to 58 days). A retrospective cohort study in Primary Class #2 showed the attack rate was 90.0% among 10 children who suffered from HFMD in the past two months compared to 30.0% among 20 children who didn't (Rate Ratio [RR] =3.0, 95% Confidence Interval [CI] =1.5-6.0). The positive rates of neutralizing antibodies were 66.7% for CVA6 and 26.7% for CVA10 in tested cases. The result of routine blood, fungal microscopic, microelements tests were normal in cases. The indicators of environment were within the normal range. CONCLUSION: The results of this study suggested that the outbreak of onychomadesis in Hubei province was probably associated with HFMD epidemic within two months.

Optimal virtual monoenergetic image in "TwinBeam" dual-energy CT for organs-at-risk delineation based on contrast-noise-ratio in head-and-neck radiotherapy.

PURPOSE: Dual-energy computed tomography (DECT) using TwinBeam CT (TBCT) is a new option for radiation oncology simulators. TBCT scanning provides virtual monoenergetic images which are attractive in treatment planning since lower energies offer better contrast for soft tissues, and higher energies reduce noise. A protocol is needed to achieve optimal performance of this feature. In this study, we investigated the TBCT scan schema with the head-and-neck radiotherapy workflow at our clinic and selected the optimal energy with best contrast-noise-ratio (CNR) in organs-at-risks (OARs) delineation for head-and-neck treatment planning. METHODS AND MATERIALS: We synthesized monochromatic images from 40 keV to 190 keV at 5 keV increments from data acquired by TBCT. We collected the Hounsfield unit (HU) numbers of OARs (brainstem, mandible, spinal cord, and parotid glands), the HU numbers of marginal regions outside OARs, and the noise levels for each monochromatic image. We then calculated the CNR for the different OARs at each energy level to generate a serial of spectral curves for each OAR. Based on these spectral curves of CNR, the mono-energy corresponding to the max CNR was identified for each OAR of each patient. RESULTS: Computed tomography scans of ten patients by TBCT were used to test the optimal monoenergetic image for the CNR of OAR. Based on the maximized CNR, the optimal energy values were 78.5 ± 5.3 keV for the brainstem, 78.0 ± 4.2 keV for the mandible, 78.5 ± 5.7 keV for the parotid glands, and 78.5 ± 5.3 keV for the spinal cord. Overall, the optimal energy for the maximum CNR of these OARs in head-and-neck cancer patients was 80 keV. CONCLUSION: We have proposed a clinically feasible protocol that selects the optimal energy level of the virtual monoenergetic image in TBCT for OAR delineation based on the CNR in head-and-neck OAR. This protocol can be applied in TBCT simulation.

A Fluorescence Immunochromatographic Assay Using Europium (III) Chelate Microparticles for Rapid, Quantitative and Sensitive Detection of Creatine Kinase MB.

The isoenzyme creatine kinase MB is very important for diagnosis of acute myocardial infarction (AMI). Some CK-MB immunoassays are sensitive, accurate and available for clinical application, but they are expensive and time-consuming procedures. Furthermore, conventional fluorescence immunochromatographic assays (FL-ICAs) have suffered from background fluorescence interference and low analytical sensitivity. A rapid and simple FL-ICA with Eu (III) chelate polystyrene microparticles was developed to determine CK-MB in 50uL serum samples using a portable test strip reader by measuring the fluorescence peak heights of the test line (HT) and the control line (HC) in 12 min. The assay was reliable with a good correlation coefficient between HT/HC ratio and CK-MB concentration in samples. A linear range was 0.85-100.29 ng/mL for CK-MB, and the LOD was 0.029 ng/mL. The intra- and inter-assay coefficients of variation (CV) were both <10 % and the average recoveries were from 90.17 % -112.63 % for CK-MB. The system performed well in interference experiments. Furthermore, a highly significant correlation (r = 0.9794, P < 0.001) between this method and the commercially available bioMérieux mini VIDAS system were attained for measuring 120 CK-MB samples. These results indicated that the Eu (III) chelate microparticles-based FL-ICA is simple, fast, highly sensitive, reliable, and reproducible for point-of-care testing of CK-MB concentrations in serum. Graphical Abstract ᅟ.

Rapid fabricated in-situ polymerized lignin hydrogel sensor with highly adjustable mechanical properties.

Conductive hydrogels have been widely used as sensors owing to their tissue-like properties. However, the synthesis of conductive hydrogels with highly adjustable mechanical properties and multiple functions remains difficult to achieve yet highly needed. In this study, lignin hydrogel characterized by frost resistance, UV resistance, high conductivity, and highly adjustable mechanical properties without forming by-products was prepared through a rapid in-situ polymerization of acrylic acid/zinc chloride (AA/ZnCl2) aqueous solution containing lignin extract induced by the reversible quinone-catechol redox of the ZnCl2-lignin system at room temperature. Results revealed that the PAA/ZnCl2/lignin hydrogel exhibited mechanical properties with tensile stress (ranging from 0.08 to 3.28 MPa), adhesion to multiple surfaces (up to 62.05 J m-2), excellent frost resistance (-70-20 °C), UV resistance, and conductivity (0.967 S m-1), which further endow the hydrogel as potential strain and temperature sensor with wide monitor range (0-300 %), fatigue resistance, and quick response (70 ms for 150 % strain). This study proposed and developed a green, simple, economical, and efficient processing method for a hydrogel sensor in flexible wearable devices and man-machine interaction fields.

Satellite-Type Sulfur Atom Distribution in Trithiocarbonate Bond-Bridged Dimeric Prodrug Nanoassemblies: Achieving Both Stability and Activatability.

Homodimeric prodrug nanoassemblies (HDPNs) hold promise for improving the delivery efficiency of chemo-drugs. However, the key challenge lies in designing rational chemical linkers that can simultaneously ensure the chemical stability, self-assembly stability, and site-specific activation of prodrugs. The "in series" increase in sulfur atoms, such as trisulfide bond, can improve the assembly stability of HDPNs to a certain extent, but limits the chemical stability of prodrugs. Herein, trithiocarbonate bond (─SC(S)S─), with a stable "satellite-type" distribution of sulfur atoms, is developed via the insertion of a central carbon atom in trisulfide bonds. ─SC(S)S─ bond effectively addresses the existing predicament of HDPNs by improving the chemical and self-assembly stability of homodimeric prodrugs while maintaining the on-demand bioactivation. Furthermore, ─SC(S)S─ bond inhibits antioxidant defense system, leading to up-regulation of the cellular ROS and apoptosis of tumor cells. These improvements of ─SC(S)S─ bond endow the HDPNs with in vivo longevity and tumor specificity, ultimately enhancing the therapeutic outcomes. ─SC(S)S─ bond is, therefore, promising for overcoming the bottleneck of HDPNs for efficient oncological therapy.

Effect of endoscopic full-thickness resection assisted by distal serosal turnover with floss traction for gastric submucosal masses.

BACKGROUND: Complex and high-risk surgical complications pose pressing challenges in the clinical implementation and advancement of endoscopic full-thickness resection (EFTR). Successful perforation repair under endoscopy, thereby avoiding surgical intervention and postoperative complications such as peritonitis, are pivotal for effective EFTR. AIM: To investigate the effectiveness and safety of EFTR assisted by distal serosal inversion under floss traction in gastric submucosal tumors. METHODS: A retrospective analysis of patients with gastric and duodenal submucosal tumors treated with EFTR assisted by the distal serosa inversion under dental floss traction from January 2023 to January 2024 was conducted. The total operation time, tumor dissection time, wound closure time, intraoperative bleeding volume, length of hospital stay and incidence of complications were analyzed. RESULTS: There were 93 patients, aged 55.1 ± 12.1 years. Complete tumor resection was achieved in all cases, resulting in a 100% success rate. The average total operation time was 67.4 ± 27.0 min, with tumor dissection taking 43.6 ± 20.4 min. Wound closure times varied, with gastric body closure time of 24.5 ± 14.1 min and gastric fundus closure time of 16.6 ± 8.7 min, showing a significant difference (P < 0.05). Intraoperative blood loss was 2.3 ± 4.0 mL, and average length of hospital stay was 5.7 ± 1.9 d. There was no secondary perforation after suturing in all cases. The incidence of delayed bleeding was 2.2%, and the incidence of abdominal infection was 3.2%. No patient required other surgical intervention during and after the operation. CONCLUSION: Distal serosal inversion under dental-floss-assisted EFTR significantly reduced wound closure time and intraoperative blood loss, making it a viable approach for gastric submucosal tumors.

Effects of hydrolysis conditions on the morphology of cellulose II nanocrystals (CNC-II) derived from mercerized microcrystalline cellulose.

The properties of cellulose nanocrystals with allomorph II (CNC-II) vary with the sources and the treatments received. In this work, the influences of hydrolysis time, temperature, and the applied acid concentration on the crystal size of CNC-II were investigated by the surface response experimental design. The results showed that temperature was the most significant factor affecting the crystal size of CNC-II during hydrolysis from mercerized cellulose. Then the morphology and colloidal properties of CNC-II were revealed by dynamic laser scattering (DLS), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), etc. XRD results indicated that CNC-II had slightly lower crystallinity (80.89 % vs 82.7 %) and larger crystallite size (5.21 vs. 5.13 nm) than CNC-I. TEM and AFM results showed that the morphology of CNC-II were disc-like and rod-like particles, with an average diameter of 14.6 ± 4.7 nm (TEM) and a thickness of 4- 8 nm (AFM). TG and XPS revealed the reduced thermal stability was due to the introduced sulfate groups in CNC-II during hydrolysis. This investigation has addressed the features of CNC-II derived from mercerized cellulose, and it would be promising in fabricating advanced materials.

Hydrostability, mechanical resilience, and biodegradability of paper straws fabricated through lignin-based polyurethane and chitosan binary emulsion bonding.

This study focuses on enhancing the strength and water stability of paper straws through a novel approach involving a binary emulsion of lignin-based polyurethane and chitosan. Kraft lignin serves as the raw material for synthesizing a blocked waterborne polyurethane, subsequently combined with carboxylated chitosan to form a stable binary emulsion. The resulting emulsion, exhibiting remarkable stability over at least 6 months, is applied to the base paper. Following emulsion application, the paper undergoes torrefaction at 155 °C. This process deblocks isocyanate groups, enabling their reaction with hydroxyl groups on chitosan and fibers, ultimately forming ester bonds. This reaction significantly improves the mechanical strength and hydrophobicity of paper straws. The composite paper straws demonstrate exceptional mechanical properties, including a tensile strength of 47.21 MPa, Young's modulus of 4.33 GPa, and flexural strength of 32.38 MPa. Notably, its water stability is greatly enhanced, with a wet tensile strength of 40.66 MPa, surpassing commercial paper straws by 8 folds. Furthermore, the composite straw achieves complete biodegradability within 120 days, outperforming conventional paper straws in terms of environmental impact. This innovative solution presents a promising and sustainable alternative to plastic straws, addressing the urgent need for eco-friendly products.

Cholesterol sulfate-mediated ion-pairing facilitates the self-nanoassembly of hydrophilic cationic mitoxantrone.

HYPOTHESIS: Hydrophilic cationic drugs such as mitoxantrone hydrochloride (MTO) pose a significant delivery challenge to the development of nanodrug systems. Herein, we report the use of a hydrophobic ion-pairing strategy to enhance the nano-assembly of MTO. EXPERIMENTS: We employed biocompatible sodium cholesteryl sulfate (SCS) as a modification module to form stable ion pairs with MTO, which balanced the intermolecular forces and facilitated nano-assembly. PEGylated MTO-SCS nanoassemblies (pMS NAs) were prepared via nanoprecipitation. We systematically evaluated the effect of the ratio of the drug module (MTO) to the modification module (SCS) on the nanoassemblies. FINDINGS: The increased lipophilicity of MTO-SCS ion pair could significantly improve the encapsulation efficiency (∼97 %) and cellular uptake efficiency of MTO. The pMS NAs showed prolonged blood circulation, maintained the same level of tumor antiproliferative activity, and exhibited reduced toxicity compared with the free MTO solution. It is noteworthy that the stability, cellular uptake, cytotoxicity, and in vivo pharmacokinetic behavior of the pMS NAs increased in proportion to the molar ratio of SCS to MTO. This study presents a self-assembly strategy mediated by ion pairing to overcome the challenges commonly associated with the poor assembly ability of hydrophilic cationic drugs.

A Core Structural Protein That Builds the Locust Mandible with a Mechanical Gradient.

Natural materials, such as locust mandibles and squid beaks, define significant mechanical gradients that have been attributed to the chemical gradients of their specialized structural proteins (SPs). However, the mechanism by which SPs form chemical gradients in these materials remains unknown. In this study, a highly abundant histidine-rich structural protein (LmMHSP) was identified in the mandible of a migratory locust (Locusta migratoria). LmMHSP was proven by both in vivo and in vitro evidence to act as a core building block of the mandible with a variety of synergistic functions including chitin binding, matrix formation via liquid-liquid phase separation, chemical cross-linking, and metal coordination. Furthermore, we found that the SP gradient in the locust mandible stems from the chitin-binding activity of LmMHSP and different microstructures of chitin scaffolds in different regions. These findings advance our understanding of the formation mechanisms of natural biomaterials and have implications for the fabrication of biomimetic materials.

Interlocking-interface-enabled thermally deformable liquid metal/polymer membrane with high bonding strength.

HYPOTHESIS: The high surface tension of liquid metal (LM) causes interface incompatibility and poor bonding strength with many substrates. Fine adjustment towards the properties of the surface area is sufficient to introduce strong bonding. Hence, we hypothesize that the interlocking structure using hydrophilic polyvinyl alcohol (PVA) as a "bridge" should be helpful for tight interfacial bonding of LM with polymeric substrates, thus achieving high-performance LM/polymer membranes, which have wide applications in the field of soft sensors and robotics. EXPERIMENTS: The bulk EGaIn was fabricated into LM nanoparticles (LMNPs@PVA) solution. Then, PVA molecules were "doped" into the surface crosslink of the plasma treated polymer substrate by an interfacial penetrating method. Afterward, the solution was evenly dropped on the surface of the treated substrate to obtain the LMNP/polymer membrane after the water evaporated. Photothermal actuators were fabricated based on the membranes. FINDINGS: During the interlocking structure, PVA macromolecules could be doped and trapped onto the top surfaces of various polymer substrates as binding "bridges" between the LMNPs and the matrix materials. The achieved LMNP membrane exhibites satisfactory bonding strength, durability and water-assisted erase-reprint, which can be used as soft photothermal actuators with remote laser control.

Non-linear association between daily mean temperature and children's hand foot and mouth disease in Chongqing, China.

Chongqing was seriously affected by hand, foot, and mouth disease (HFMD), but the relationships between daily mean temperature and the incidence of HFMD remain unclear. This study used distributed lag nonlinear model to evaluate the effect of daily mean temperature on the incidence of HFMD in children aged < 5 years in Chongqing. Daily HFMD data from 2012 to 2019 in Chongqing were retrieved from the notifiable infectious disease surveillance system. A total of 413,476 HFMD cases aged < 5 years were reported in Chongqing from 2012 to 2019. The exposure-response curve of daily mean temperature and daily HFMD cases was wavy-shaped. The relative risks (RRs) increased as daily mean temperature below 5.66 °C or above 9.43 °C, with two peaks at 16.10 °C and 26.68 °C. The RRs reached the highest when the daily mean temperature at 26.68 °C on the current day (RR = 1.20, 95% CI 1.09-1.32), followed by the daily mean temperature at 16.10 °C at lag 5 days (RR = 1.07, 95% CI 1.05-1.08). The RRs for girls and daycare children were much higher than those for boys and scattered children, respectively. Taken together, daily mean temperature has strong effect on HFMD in children aged < 5 years old in Chongqing, particularly for girls and daycare children.

Controllably Self-Assembled Antibacterial Nanofibrils Based on Insect Cuticle Protein for Infectious Wound Healing.

Developing self-assembled biomedical materials based on insect proteins is highly desirable due to their advantages of green, rich, and sustainable characters as well as excellent biocompatibility, which has been rarely explored. Herein, salt-induced controllable self-assembly, antibacterial performance, and infectious wound healing performance of an insect cuticle protein (OfCPH-2) originating from the Ostrinia furnacalis larva head capsule are investigated. Interestingly, the addition of salts could trigger the formation of beaded nanofibrils with uniform diameter, whose length highly depends on the salt concentration. Surprisingly, the OfCPH-2 nanofibrils not only could form functional films with broad-spectrum antibacterial abilities but also could promote infectious wound healing. More importantly, a possible wound healing mechanism was proposed, and it is the strong abilities of OfCPH-2 nanofibrils in promoting vascular formation and antibacterial activity that facilitate the process of infectious wound healing. Our exciting findings put forward instructive thoughts for developing innovative bioinspired materials based on insect proteins for wound healing and related biomedical fields.

Ultrasound GLCM texture analysis of radiation-induced parotid-gland injury in head-and-neck cancer radiotherapy: an in vivo study of late toxicity.

PURPOSE: Xerostomia (dry mouth), secondary to irradiation of the parotid glands, is one of the most common side effects of head-and-neck cancer radiotherapy. Diagnostic tools able to accurately and efficiently measure parotid gland injury have yet to be introduced into the clinic. This study's purpose is to investigate sonographic textural features as potential imaging signatures for quantitative assessment of parotid-gland injury after head-and-neck radiotherapy. METHODS: The authors have investigated a series of sonographic features obtained from the gray level co-occurrence matrix (GLCM) - a second order statistical method of texture analysis. These GLCM textural features were selected based on empirical observations that the normal parotid gland exhibits homogeneous echotexture, whereas the postradiotherapy parotid gland often exhibits heterogeneous echotexture. We employed eight sonographic features: (1) angular second moment (ASM), (2) inverse differential moment (IDM), (3) contrast, (4) variance, (5) correlation, (6) entropy, (7) cluster shade, and (8) cluster prominence. Altogether, sonographic properties of the parotid glands were quantified by their degrees of homogeneity (ASM and IDM), heterogeneity (contrast and variance), smoothness (correlation), randomness (entropy), and symmetry (cluster shade and prominence). The sonographic features were tested in a pilot study of 12 postradiotherapy patients and 7 healthy volunteers. The mean follow-up time for the postradiotherapy patients was 17.2 months (range: 12.1-23.9 months) and the mean radiation dose to the parotid glands was 32.3 Gy (range: 11.0-63.4 Gy). Each participant underwent one ultrasound study in which longitudinal (vertical) ultrasound scans were performed on the bilateral parotids - a total of 24 postirradiation and 14 normal parotid glands were examined. The 14 normal parotid glands served as the control group. A radiologist contoured the parotid glands on the B-mode images and the sonographic features were computed from the contoured region-of-interest. RESULTS: The authors observed significant differences (p < 0.05) in all sonographic features between the normal and postradiotherapy parotid glands. The sonographic findings were consistent with the clinical observations of the ultrasound images: normal parotid glands exhibited homogeneous texture, while the postradiotherapy parotid glands exhibited heterogeneous echotexture (e.g., hyperechoic lines and spots), which likely represents fibrosis. CONCLUSIONS: The authors have demonstrated the feasibility of ultrasonic texture evaluation of parotid glands; and the sonographic features may serve as imaging signatures to assess radiation-induced parotid injury.

Combined Ibuprofen-Nanoconjugate Micelles with E-Selectin for Effective Sunitinib Anticancer Therapy.

Introduction: Sunitinib, a first-line therapy with a certain effect, was utilized in the early stages of renal cell carcinoma treatment. However, its clinical toxicity, side effects, and its limited bioavailability, resulted in inadequate clinical therapeutic efficacy. Building neoteric, simple, and safe drug delivery systems with existing drugs offers new options. Therefore, we aimed to construct a micelle to improve the clinical efficacy of sunitinib by reusing ibuprofen. Methods: We synthesized the sialic acid-poly (ethylene glycol)-ibuprofen (SA-PEG-IBU) amphipathic conjugate in two-step reaction. The SA-PEG-IBU amphiphilic conjugates can form into stable SPI nanomicelles in aqueous solution, which can be further loaded sunitinib (SU) to obtain the SPI/SU system. Following nanomicelle creation, sialic acid exposed to the nanomicelle surface can recognize the overexpressed E-selectin receptor on the membrane of cancer cells to enhance cellular uptake. The properties of morphology, stability, and drug release about the SPI/SU nanomicelles were investigated. Confocal microscopy and flow cytometry were used to assess the cellular uptake efficiency of nanomicelles in vitro. Finally, a xenograft tumor model in nude mice was constructed to investigate the body distribution and tumor suppression of SPI/SU in vivo. Results: The result showed that SPI nanomicelles exhibited excellent tumor targeting performance and inhibited the migration and invasion of tumor cell in vitro. The SPI nanomicelles can improve the accumulation of drugs in the tumor site that showed effective tumor inhibition in vivo. In addition, H&E staining and immunohistochemical analysis demonstrated that the SPI/SU nanomicelles had a superior therapeutic effect and lower biotoxicity. Conclusion: The SPI/SU nanomicelles displayed excellent anti-tumor ability, and can suppress the metastasis of tumor cell by decreasing the expression of Cyclooxygenase-2 due to the ibuprofen, providing an optimistic clinical application potential by developing a simple but safe drug delivery system.

Multi-organ auto-delineation in head-and-neck MRI for radiation therapy using regional convolutional neural network.

Magnetic resonance imaging (MRI) allows accurate and reliable organ delineation for many disease sites in radiation therapy because MRI is able to offer superb soft-tissue contrast. Manual organ-at-risk delineation is labor-intensive and time-consuming. This study aims to develop a deep-learning-based automated multi-organ segmentation method to release the labor and accelerate the treatment planning process for head-and-neck (HN) cancer radiotherapy. A novel regional convolutional neural network (R-CNN) architecture, namely, mask scoring R-CNN, has been developed in this study. In the proposed model, a deep attention feature pyramid network is used as a backbone to extract the coarse features given by MRI, followed by feature refinement using R-CNN. The final segmentation is obtained through mask and mask scoring networks taking those refined feature maps as input. With the mask scoring mechanism incorporated into conventional mask supervision, the classification error can be highly minimized in conventional mask R-CNN architecture. A cohort of 60 HN cancer patients receiving external beam radiation therapy was used for experimental validation. Five-fold cross-validation was performed for the assessment of our proposed method. The Dice similarity coefficients of brain stem, left/right cochlea, left/right eye, larynx, left/right lens, mandible, optic chiasm, left/right optic nerve, oral cavity, left/right parotid, pharynx, and spinal cord were 0.89 ± 0.06, 0.68 ± 0.14/0.68 ± 0.18, 0.89 ± 0.07/0.89 ± 0.05, 0.90 ± 0.07, 0.67 ± 0.18/0.67 ± 0.10, 0.82 ± 0.10, 0.61 ± 0.14, 0.67 ± 0.11/0.68 ± 0.11, 0.92 ± 0.07, 0.85 ± 0.06/0.86 ± 0.05, 0.80 ± 0.13, and 0.77 ± 0.15, respectively. After the model training, all OARs can be segmented within 1 min.