Highly resilient and fatigue-resistant poly(4-methyl-ε-caprolactone) porous scaffold fabricated via thiol-yne photo-crosslinking/salt-templating for soft tissue regeneration.

Elastomeric scaffolds, individually customized to mimic the structural and mechanical properties of natural tissues have been used for tissue regeneration. In this regard, polyester elastic scaffolds with tunable mechanical properties and exceptional biological properties have been reported to provide mechanical support and structural integrity for tissue repair. Herein, poly(4-methyl-ε-caprolactone) (PMCL) was first double-terminated by alkynylation (PMCL-DY) as a liquid precursor at room temperature. Subsequently, three-dimensional porous scaffolds with custom shapes were fabricated from PMCL-DY via thiol-yne photocrosslinking using a practical salt template method. By manipulating the Mn of the precursor, the modulus of compression of the scaffold was easily adjusted. As evidenced by the complete recovery from 90% compression, the rapid recovery rate of >500 mm min-1, the extremely low energy loss coefficient of <0.1, and the superior fatigue resistance, the PMCL20-DY porous scaffold was confirmed to harbor excellent elastic properties. In addition, the high resilience of the scaffold was confirmed to endow it with a minimally invasive application potential. In vitro testing revealed that the 3D porous scaffold was biocompatible with rat bone marrow stromal cells (BMSCs), inducing BMSCs to differentiate into chondrogenic cells. In addition, the elastic porous scaffold demonstrated good regenerative efficiency in a 12-week rabbit cartilage defect model. Thus, the novel polyester scaffold with adaptable mechanical properties may have extensive applications in soft tissue regeneration.

Enhancing mesenchymal stem cells cultivated on microcarriers in spinner flasks via impeller design optimization for aggregated suspensions.

During the ex vivo expansion of umbilical cord-derived mesenchymal stem cells (hUCMSCs) in a stirred tank bioreactor, the formation of cell-microcarrier aggregates significantly affects cell proliferation and physiological activity, making it difficult to meet the quantity and quality requirements for in vitro research and clinical applications. In this study, computational fluid dynamic (CFD) simulations were used to investigate the effect of an impeller structure in a commercial spinner flask on flow field structure, aggregate formation, and cellular physiological activity. By designing a modified impeller, the aggregate size was reduced, which promoted cell proliferation and stemness maintenance. This study showed that increasing the stirring speed reduced the size of hUCMSC-microcarrier aggregates with the original impeller. However, it also inhibited cell proliferation, decreased activity, and led to spontaneous differentiation. Compared to low stirring speeds, high stirring speeds did not alter the radial flow characteristics and vortex distribution of the flow field, but did generate higher shear rates. The new impeller's design changed the flow field from radial to axial. The use of the novel impeller with an increased axial pumping rate (Qz) at a similar shear rate compared to the original impeller resulted in a 43.7% reduction in aggregate size, a 37.4% increase in cell density, and a better preservation of the expression of stemness markers (SOX2, OCT4 and NANOG). Increasing the Qz was a key factor in promoting aggregate suspension and size reduction. The results of this study have significant implications for the design of reactors, the optimisation of operating parameters, and the regulation of cellular physiological activity during MSC expansion.

Role of MPR image reconstruction in guiding the diagnosis and treatment strategy of facial nerve schwannoma.

BACKGROUND: Facial nerve schwannomas tend to be overlooked due to their mild early clinical presentation and slow progression. AIMS/OBJECTIVES: To describe the role of facial nerve reconstruction in guiding the diagnosis and treatment strategy of facial nerve schwannoma. MATERIAL AND METHODS: Multi-plane reformation (MPR) of the facial nerve was conducted to evaluate the facial nerve lesion segments, radiological characteristics, and mastoid decompression in 13 patients. RESULTS: Bone canal loss could be seen in lesions involving the geniculate ganglion and tympanic segment and those protruding toward the tympanum in two patients. Expansive space occupying lesions could be seen in the facial nerve involving the tympanic segment to the parotid segment in five patients. A 'trumpet mouth' spherical expansive space-occupying lesion centered in the mastoid segment and enlarged stylomastoid foramen could be seen in lesions involving the mastoid segment to the parotid segment in six patients. Treatment methods suitable for the patient were performed based on the facial palsy, tumor size, hearing loss, and social requirements. CONCLUSIONS AND SIGNIFICANCE: Facial nerve MPR reconstruction can comprehensively and intuitively display the lesion segment and area of the facial nerve in the temporal bone, estimate the facial nerve length, bone encapsulation, and mastoid decompression, and has characteristic presentations that can aid preliminary diagnosis and identification.

Loureirin C and Xanthoceraside Prevent Abnormal Behaviors Associated with Downregulation of Brain Derived Neurotrophic Factor and AKT/mTOR/CREB Signaling in the Prefrontal Cortex Induced by Chronic Corticosterone Exposure in Mice.

Brain derived neurotrophic factor (BDNF) is one of the most abundant neurotrophic factors, and its deficits are involved in the pathogenesis of major depressive disorders (MDD). Loureirin C (Lou C) is a compound derived from red resin extracted from the stems of Chinese dragon's blood. Xanthoceraside (Xan) is a triterpenoid saponin extracted from the husks of Xanthoceras sorbifolia Bunge. These compounds have neuroprotective effects through upregulation of BDNF. The present study aimed to evaluate whether Lou C and Xan attenuate abnormal behaviors induced by chronic corticosterone (CORT) administration. CORT was administered subcutaneously to mice for 3 weeks, and Lou C and Xan, dispensed orally once a day during the last 2 weeks of CORT administration. Chronic CORT administration induced abnormal behaviors such as prolonged starting latency in the open field test, decreased social interaction time in the social interaction test and prolonged latency to eat in the novelty suppressed feeding test. Chronic CORT administration decreased the expression levels of BDNF and the phosphorylation of protein kinase B (Akt), mammalian target of rapamycin (mTOR), and the cAMP response element binding protein (CREB) in the prefrontal cortex. Lou C and Xan dose-dependently prevented the abnormal behaviors and decreased the expression levels of BDNF and in phosphorylation of AKT, mTOR, and CREB in the prefrontal cortex of CORT mice. These results suggest that Lou C and Xan could be attractive candidates for pharmacotherapy of MDD at least in part, given their propensity to increase BDNF expression and phosphorylation of AKT, mTOR, and CREB.

Loureirin C and Xanthoceraside Attenuate Depression-Like Behaviors and Expression of Interleukin-17 in the Prefrontal Cortex Induced by Chronic Unpredictable Mild Stress in Mice.

Major depressive disorder (MDD) is the most prevalent and serious psychiatric disease involving inflammation. Loureirin C and Xanthoceraside are extracts of dragon's blood and Xanthoceras sorbifolia Bunge, respectively, which have neuroprotective and anti-inflammatory properties. In this study, we examined whether Loureirin C and Xanthoceraside attenuated depression-like behaviors and inflammation induced by chronic unpredicted mild stress (CUMS) in mice. Adult C57BL/6 J mice exposed to CUMS for 4 weeks showed depression-like behaviors characterized by hyperactivity in a novel environment, decreased interaction time in the social interaction test, prolongation of eating latency in the novelty suppressed feeding test, and increased immobility in the forced swimming test. CUMS increased the expression of interleukin-17 (IL-17) in the prefrontal cortex (PFC). One week after exposure to CUMS, the mice were treated with Loureirin C (0.64 mg/kg) or Xanthoceraside (1.28 mg/kg) once a day for 3 weeks during CUMS. Loureirin C and Xanthoceraside significantly attenuated CUMS-induced behavioral impairment. Furthermore, both Loureirin C and Xanthoceraside prevented IL-17 expression induced by CUMS in the PFC. This data suggests that Loureirin C and Xanthoceraside have antidepressant-like properties that may be associated with the inhibition of IL-17 expression.

Osteogenically differentiated mesenchymal stem cells promote the apoptosis of human umbilical vein endothelial cells in vitro.

The absence of blood vessels in tissue engineered bone often leads to necrosis of internal cells after implantation, ultimately affecting the process of bone repair. Herein, mesenchymal stem cells (MSCs) and human umbilical vein endothelial cells (HUVECs) were cocultured to induce osteogenesis and angiogenesis. Based on the findings, the number of HUVECs in the coculture system increased in the growth medium group, but decreased in the osteogenic induction medium (OIM) group. Considering that the paracrine effects of MSCs had changed, we tested the genes expression of osteogenically differentiated MSCs. The expression of osteogenic genes in MSCs increased during osteogenesis. Further, the expression levels of pigment epithelial-derived factor (PEDF) gene and protein, an antivascular factor, were also increased. To verify whether MSCs promote HUVECs apoptosis via PEDF, PEDF was silenced via siRNA. The conditioned medium of differentiated MSCs with PEDF silencing significantly improved the proliferation and apoptosis of HUVECs. Based on further experiments, PEDF mediated the apoptosis and proliferation of HUVECs through p53, BAX/BCL-2, FAS, and c-Caspase-3. However, when PEDF was silenced with siRNA, the osteogenic potential of MSCs was affected. The results of this study provide a theoretical basis for the construction of prevascularized bone tissues in vitro.

A multifunctional green antibacterial rapid hemostasis composite wound dressing for wound healing.

Rapid hemostasis and antibacterial properties are essential for novel wound dressings to promote wound healing. In particular, timely and rapid hemostasis could be of benefit to reduce the mortality caused by excessive bleeding loss. Herein, we present a novel strategy of combining electrospinning technology with post-modification technology to prepare a multifunctional wound dressing, cellulose diacetate-based composite wound dressing (CDCE), with rapid hemostasis and antibacterial activity. It is interesting that the CDCE wound dressing had superhydrophilicity, high water absorption, and strong absorbing capacity, which could eliminate the exudate around the wound in a timely manner and further promote rapid hemostasis. Additionally, its excellent antibacterial properties could inhibit severe infection in the wound and accelerate wound healing. Based on these advantages, the novel CDCE wound dressing could promote wound contraction and further accelerate wound healing compared with the common traditional wound dressing gauze. Taken together, the multifunctional CDCE wound dressing has high potential for clinical application in the future.

Accuracy of individualized 3D modeling of ossicles using high-resolution computed tomography imaging data.

BACKGROUND: The present study aimed to investigate the visibility of small ossicle parts/landmarks on high-resolution computed tomography (HRCT)/3D reconstruction (3D) to investigate what improvements in scanning resolution are needed before accurate 3D printing of patient-specific ossicles is possible. METHODS: A total of 24 patients with sudden deafness sought consultation at the Department of Otorhinolaryngology Head and Neck Surgery at the Sixth Medical Center of People's Liberation Army General Hospital between October 2013 and June 2014 were enrolled in the study. All participants underwent a 256-slice spiral HRCT temporal bone axial scan, yielding a Digital Imaging and Communications in Medicine documents series. These documents were then inputted into Mimics 16.0 interactive medical image processing software for data conversion and the creation of 3D segmentation and visualizations of the ossicles. Finally, the 3D images were compared using multiplanar reformation (MPR) and 3D volume-rendering (VR) reconstructed images of ossicles to verify their consistency. These were then compared with the normal ossicle structure to evaluate the accuracy of the restoration. RESULTS: The findings indicated that the morphology of the ossicles from the converted Mimics 16.0 data achieved a display rate of ≥90% when used to display 7 landmarks (the caput mallei, collum mallei, processus lateralis mallei, manubrium mallei, corpus incudis, crus longum incudis, and crus breve incudis). This demonstrates excellent matching with the images of ossicles obtained from MPR and 3D VR reconstruction. Kappa consistency testing found that the κ-value was higher than 0.75. When displaying the lenticular process, caput stapedis, crus anterius stapedis, and crus posterius stapedis landmarks. The display rate was around 60%, which shows good matching with the ossicles' images obtained from MPR and 3D VR reconstruction, with a κ-value >0.4. However, the display rate of the stapes footplate was only 25%, showing greater differences with the images obtained from MPR (76.4%) and 3D VR reconstruction (52.8%), with a κ-value <0.4. CONCLUSIONS: The accuracy of the visualization of the malleus and incus after restoration via Mimics 16.0 software, based on temporal bone HRCT data, was high, and the degree of restoration was good. However, the accuracy and degree of restoration of the stapes footplate require further improvement.

Clinical Characteristics and CT Findings in 148 Non-COVID-19 Influenza-Like Illness Cases: A Retrospective Control Study.

Background: This study was to collect clinical features and computed tomography (CT) findings of Influenza-Like Illness (ILI) cases, and to evaluate the correlation between clinical data and the abnormal chest CT in patients with the Influenza-Like Illness symptoms. Methods: Patients with the Influenza-Like Illness symptoms who attended the emergency department of The Six Medical Center of The PLA General Hospital from February 10 to April 1, 2020 were enrolled. Clinical and imaging data of the enrolled patients were collected and analyzed. The association between clinical characteristics and abnormal chest CT was also analyzed. Results: A total of 148 cases were enrolled in this study. Abnormalities on chest CT were detected in 61/148 (41.2%) patients. The most common abnormal CT features were as follows: patchy consolidation 22/61(36.1%), ground-glass opacities 21/61(34.4%), multifocal consolidations 17/61(27.9%). The advanced age and underlying diseases were significantly associated with abnormal chest CT. Conclusions: Abnormal chest CT is a common condition in Influenza-Like Illness cases. The presence of advanced age and concurrent underlying diseases is significantly associated with abnormal chest CT findings in patients with ILI symptoms. The chest CT characteristic of ILI is different from the manifestation of COVID-19 infection, which is helpful for differential diagnosis.

Chronic unpredictable mild stress-induced behavioral changes are coupled with dopaminergic hyperfunction and serotonergic hypofunction in mouse models of depression.

Accumulating evidence shows that stressful events evoke molecular alterations in the brain, considered a pathology in major depressive disorder (MDD). However, the abnormalities of neurotransmissions as well as intracellular signaling pathways affected by chronic stress in brain have not been fully explored. We investigated the effect of chronic unpredictable mild stress (CUMS) on the emotional behaviors, dopaminergic and serotoninergic function, and intracellular signaling in the nucleus accumbens, hippocampus and prefrontal cortex. Male C57BL/6J mice were exposed to CUMS for 4 weeks. CUMS was shown to induce hyperactivity in a novel environment, decrease interaction time in the social interaction test, prolong feeding latency in the novelty suppressed feeding test and enhance immobility in the forced swimming test. The levels of dopamine, its metabolites and turnover, and protein level of tyrosine hydroxylase (TH) were increased by CUMS in the nucleus accumbens (NAc). The level of serotonin and protein levels of tryptophan hydroxylase (TPH) and TH were decreased by CUMS in the hippocampus (HPC) and prefrontal cortex (PFC). Accompanying the increase in dopaminergic function, phosphorylation levels of extracellular signal-regulated kinases (ERK), protein kinase B (Akt) and cAMP response element-binding protein (CREB) were increased by CUMS in the NAc. Administration of fluoxetine (selective serotonin re-uptake inhibitor: 20 mg/kg i.p.) and aripiprazole (dopamine D2 receptor partial agonist: 0.1 mg/kg i.p.) during CUMS, prevented behavioral changes and increase of dopamine level in the NAc. These data suggest that CUMS-induced depression-like behaviors are coupled with dopaminergic hyperfunction in the NAc and serotonergic hypofunction in the HPC and PFC.

Xanthoceraside modulates neurogenesis to ameliorate cognitive impairment in APP/PS1 transgenic mice.

Neuronal loss is reported to be an important pathological process in Alzheimer's disease (AD). Neurogenesis is a process of generation of new neurons to fill the neuronal loss. Xanthoceraside has been shown to attenuate the cognitive deficits in several AD animal models. However, little is known about the effect of xanthoceraside on neurogenesis in APP/PS1 transgenic mice. Thus, in this study, we investigated whether xanthoceraside can ameliorate learning and memory impairment by promoting NSCs proliferation and neuronal differentiation. The results suggested that xanthoceraside significantly ameliorated the cognitive impairment and induced NSCs proliferation and neuronal differentiation in APP/PS1 transgenic mice. Meanwhile, in vitro study revealed that xanthoceraside increased the size of NSCs and induced NSCs differentiation into neurons compared with amyloid beta-peptide (25-35) (Aß25-35) treatment. Furthermore, we found that xanthoceraside significantly increased the expression of Wnt3a and p-GSK3ß, decreased the expression of p-ß-catenin, and induced nuclear translocation of ß-catenin in APP/PS1 transgenic mice. Furthermore, in vitro study found that the effect of xanthoceraside on inducing NSCs proliferation and neuronal differentiation were inhibited by Wnt pathway inhibitor Dickkopf-1 (Dkk-1). Our data demonstrated that xanthoceraside may promote the proliferation and differentiation of NSCs into neurons by up-regulating the Wnt/ß-catenin pathway to fill the neuronal loss, thereby improving learning and memory impairment in APP/PS1 transgenic mice.

Value of section plane, MPR, and 3D-CTVR techniques in the fine differential diagnosis of ossicular chain in the case of conductive hearing loss with intact tympanic membrane.

AIM: To assess the quality of high-resolution CT section planes (HRCT), multi-planar reformation (MPR) and 3-dimensional volume rendered computer tomography (3D-CTVR) were here used in the fine differential diagnosis of ossicular chain in the case of conductive hearing loss with intact tympanic membrane. METHODS: Here, 17 cases of otosclerosis and 22 cases of ossicular chain deformity were selected. All patients had normal external ear canals, intact tympanic membranes, conductive hearing loss, type A tympanograms, and negative Gelle's tests. The respective radiological reports of the status of the ossicles via 3 protocols were compared to surgical findings. The quantitative assessments of the representation of different segments of the ossicular chain were based on a 3-point scoring system. RESULTS: MPR and CTVR imaging both showed the integrity of whole ossicular chain well. MPR and CTVR imaging were found to be superior to section planes with respect to showing the superstructure of the stapes and malformations (P > 0.05). CONCLUSION: CTVR and MPR imaging were found to be better able to show the whole ossicular chain in the conductive hearing loss with normal tympanic membranes. Furthermore, the use of these techniques can have profound contributive value in the differential diagnosis of otosclerosis and ossicular chain absence or malformation.

Quality assessment of 3D-CTVR, MPR and section plane techniques in ossicular chain reconstruction in middle ear cholesteatoma.

AIM: To assess the quality of three-dimensional volume rendered computer tomography (3D-CTVR), multi-planar reformation (MPR) and CT section plane in the fine diagnosis of ossicular chain in middle ear cholesteatoma. METHODS: Sixty patients with middle ear cholesteatoma were selected in this retrospective study. All cases underwent pre-operative CT scan. The respective radiologic reports of the ossicles status via three protocols were then compared to surgical findings. RESULTS: Quality assessment of these three protocols in the fine diagnosis of fine ossicles buried inside the soft tissue showed that both CTVR and MPR are more superior to conventional section plane, especially CTVR. CONCLUSION: The uses of CTVR and MPR, in conjunction with conventional section plane, are better able to show where the true and fine ossicular chain in the cholesteatoma mass is. In the final analysis, we believe that the use of CTVR and MPR techniques can have profound contributive value in future clinical work.

CT two-dimensional reformation versus three-dimensional volume rendering with regard to surgical findings in the preoperative assessment of the ossicular chain in chronic suppurative otitis media.

PURPOSE: To assess the role of three-dimensional volume rendering (3DVR) in the preoperative assessment of the ossicular chain in chronic suppurative otitis media (CSOM). MATERIALS AND METHODS: Sixty-six patients with CSOM were included in this prospective study. Temporal bone was scanned with a 128-channel multidetector row CT and the axial data was transferred to the workstation for multiplanar reformation (MPR) and 3DVR reconstructions. Evaluation of the ossicular chain according to a three-point scoring system on two-dimensional reformation (2D) and 3DVR was performed independently by two radiologists. The evaluation results were compared with surgical findings. RESULTS: 2D showed over 89% accuracy in the assessment of segmental absence of the ossicular chain in CSOM, no matter how small the segmental size was. 3DVR was as accurate as 2D for the assessment of segmental absence. However, 3DVR was found to be more accurate than 2D in the evaluation of partial erosion of segments. CONCLUSION: Both 3DVR and 2D are accurate and reliable for the assessment of the ossicular chain in CSOM. The inclusion of 3DVR images in the imaging protocol improves the accuracy of 2D in detecting ossicular erosion from CSOM.