Special contoured pelvic brim reconstruction titanium plate combined with trans-plate buttress screws (quadrilateral screws) for acetabular fractures with quadrilateral plate involvement through the anterior ilioinguinal approach.

Background: Managing complicated acetabular fractures involving the quadrilateral plate (QLP) can be challenging for surgeons, especially when complicated by comminution and osteoporosis. Traditional implants do not provide sufficient fixed strength or a proper match. The new-type pre-contoured infrapectineal buttress plates may have drawbacks, such as inaccurate fitting on the medial surface of QLP and an inability to apply reversed compression force to resist medial displacement of femoral head. Therefore, the primary purpose of this study is to introduce a novel technique that utilizes a special contoured pelvic brim reconstruction titanium plate combined with quadrilateral screws to reduce and stabilize acetabular fractures involving the QLP through the ilioinguinal approach. Additionally, the secondary purpose is to evaluate both clinical effectiveness and radiological outcomes of this technique for QLP fractures. Methods: We conducted a retrospective analysis of prospectively collected data from 48 patients (31 males and 17 females) who suffered from acute displaced fractures of the QLP and were treated between January 2012 and December 2019 using a special contoured plate combined with quadrilateral screws. The patients' mean age was 47.56 ± 11.31 years (range: 19-73 years). Fracture patterns included 20 both-column fractures, 12 anterior column and posterior hemitransverse fractures, eight T-type fractures, five transverse fractures and three anterior column fractures with the QLP affected, all of which had femoral head protrusion. Immediate postoperative reduction quality was evaluated according to Matta's criteria. Final clinical functions were assessed during follow-up using the modified Merle d'Aubigné and Harris Hip scores (HHS). Results: The patients were followed up for an average of 48.36 ± 12.94 months (ranging from 24 to 84 months). The mean operative time was 246.08 ± 54.30 min (ranging from 178 to 397 min), and the average blood loss was 715.16 ± 263.84 ml (ranging from 400 to 2000ml). The radiological grading at postoperative stage showed anatomical reduction in 30 patients (62.50%), satisfactory reduction in 14 patients (29.17%), and poor reduction in four patients (8.33%). At the final follow-up, no re-protrusion of the femoral head was observed. In terms of functional outcome, the mean modified Merle d'Aubigné-Postel score was excellent in 26 patients (54.17%), good in 17 patients (35.42%), fair in four patients (8.33%), and poor in one patient (2.08%). The HHS was excellent in 23 patients (47.92%), good in 20 patients (41.67%), fair in four patients (8.33%), and poor in one patient (2.08%). The average HHS was 87.38 ± 7.86 (ranging from 52 to 98). Postoperative complications included lateral femoral cutaneous nerve injury in two patients, delayed wound healing and subsequent development of an inguinal hernia in one patient. Late complications were observed in two patients, with one case of heterotopic ossification and another case of post-traumatic osteoarthritis underwent hip arthroplasty within two years after surgery. Conclusion: Our results indicate that employing the contoured plate specifically designed for QLP injuries, in conjunction with quadrilateral screws through the ilioinguinal approach, can lead to positive outcomes in the treatment of displaced acetabular fractures involving the QLP. This straightforward and efficient technique offers a viable option for surgeons who are managing complex acetabular fractures.

Combination of Cytologic Findings and Circulating Tumor DNA From Cerebrospinal Fluid Revealed SCLC Transformation in Patients With Leptomeningeal Metastases of Lung Adenocarcinoma.

Introduction: Transformation to SCLC is a resistance mechanism to tyrosine kinase inhibitor in EGFR-mutated lung adenocarcinoma (LUAD). Nevertheless, the clinical and molecular features of SCLC transformation in LUAD with leptomeningeal metastases (LM) are scarce. Methods: We retrospectively collected 237 patients with NSCLC who underwent lumbar puncture owing to suggestion of LM. All SCLC transformation in cerebrospinal fluid (CSF) was confirmed by two experienced pathologists using cytologic evaluation. CSF circulating tumor DNA (ctDNA) was tested by next-generation sequencing. Results: Tumor cells in CSF samples were found in 111 patients (111 of 237, 46.8%), and eight cases (eight of 111, 7.2%) were identified as having SCLC cells in CSF. Seven patients carried the EGFR mutation, including four patients with EGFR exon 19 deletion and three patients with EGFR exon 21 L858R mutation. Another patient harbored ERBB2 insertion. Seven of these patients were resistant to targeted therapy. CSF ctDNA analysis reported that TP53 and RB1 mutations were common. The median time from the diagnosis of advanced NSCLC to SCLC transformation found in CSF was 9.7 months (95% confidence interval [CI]: 4.0-17.5 mo). The median overall survival since the initial diagnosis of metastatic NSCLC was 15.3 months (95% CI: 1.2-29.4 mo). The median overall survival after SCLC transformation detected in CSF was 5.0 months (95% CI: 4.0-5.9 mo). Conclusions: SCLC transformation may be revealed in CSF by both cytologic evaluation and ctDNA, not just in tissue that underwent rebiopsy. SCLC transformation of CSF is informative for resistance mechanism in patients with LUAD with LM on tyrosine kinase inhibitor progression, which was associated with poor survival.

Taxonomic composition and functional potentials of gastrointestinal microbiota in 12 wild-stranded cetaceans.

Cetaceans play a crucial role in marine ecosystems; however, research on their gastrointestinal microbiota remains limited due to sampling constraints. In this study, we collected hindgut samples from 12 stranded cetaceans and performed 16S rRNA gene amplicon sequencing to investigate microbial composition and functional potentials. Analysis of ZOTUs profiles revealed that the phyla Firmicutes, Proteobacteria, and Bacteroidetes dominated all hindgut samples. However, unique microbial profiles were observed among different cetacean species, with significant separation of gut microbiota communities according to biological evolutionary lineages. Different genera that contain pathogens were observed distinguishing delphinids from physeteroids/ziphiids. Delphinid samples exhibited higher abundances of Vibrio, Escherichia, and Paeniclostridium, whereas physeteroid and ziphiid samples showed higher abundances of Pseudomonas, Enterococcus, and Intestinimonas. Functional analysis indicated convergence in the gut microbiota among all cetaceans, with shared bacterial infection pathways across hindgut samples. In addition, a comparison of the gastrointestinal microbial composition between a stranded short-finned pilot whale (Globicephala macrorhynchus) and a stranded rough-toothed dolphin (Steno bredanensis) using 16S rRNA gene sequencing revealed distinct microbial community structures and functional capacities. To the best of our knowledge, this study represents the first report on the gastrointestinal microbiota of the pantropical spotted dolphin (Stenella attenuata), Blainville's beaked whale (Mesoplodon densirostris), and rough-toothed dolphin, with various comparisons conducted among different cetacean species. Our findings enhance the understanding of microbial composition and diversity in cetacean gastrointestinal microbiota, providing new insights into co-evolution and complex interactions between cetacean microbes and hosts.

Forming Single-Cell-Derived Colon Cancer Organoid Arrays on a Microfluidic Chip for High Throughput Tumor Heterogeneity Analysis.

Single-cell-derived tumor organoids (STOs) possess a distinct genetic background, making them valuable tools for demonstrating tumor heterogeneity. In order to fulfill the high throughput demands of STO assays, we have developed a microfluidic chip containing 30 000 microwells, which is dedicated to a single cell culture approach for selective expansion and differential induction of cancer stem cells. The microwells are coated with a hydrophilic copolymer to eliminate cell adhesion, and the cell culture is supported by poly(ethylene glycol) (PEG) to establish a nonadhesive culture environment. By utilizing an input cell density of 7 × 103·mL-1, it is possible to construct a 4000 single cell culture system through stochastic cell occupation. We demonstrate that the addition of 15% PEG10000 in the cell culture medium effectively prevents cell loss while facilitating tumor stem cell expansion. As were demonstrated by HCT116, HT29, and SW480 colon cancer cells, the microfluidic approach achieved a STO formation rate of ∼20%, resulting in over 800 STOs generated from a single culture. Comprehensive analysis through histomorphology, immunohistochemistry, drug response evaluation, assessment of cell invasion, and biomarker detection reveals the heterogeneity among individual STOs. Specifically, the smaller STOs exhibited higher invasion and drug resistance capabilities compared with the larger ones. The developed microfluidic approach effectively facilitates STO formation and offers promising prospects for investigating tumor heterogeneity, as well as conducting personalized therapy-focused drug screening.

Comparative Study of Trapeziectomy with Weilby Suspensionplasty versus Implant Arthroplasty for Thumb Carpometacarpal Joint Arthritis in an Asian Population.

Background: This retrospective study compares the outcomes of trapeziectomy and Weilby suspensionplasty procedure versus implant arthroplasty using the TOUCH® prosthesis for basilar thumb arthritis in an Asian population. Methods: A total of 15 consecutive thumbs in 13 patients were included in this study. Six patients (2 male, 4 female, mean age of 62 years old) underwent trapeziectomy and Weilby suspensionplasty procedure. Seven patients (4 male, 3 female, mean age 63 years old) underwent implant CMCJ arthroplasty using the TOUCH® prosthesis. Data collected include demographics, severity of arthritis on plain radiographs of the thumb basilar joint, length of follow-up, pre- and postoperative pain levels, Kapandji thumb opposition score, grip and pinch strength and the time taken to return to work. Results: Patients in the trapeziectomy and Weilby suspensionplasty group had a mean follow-up of 4.5 months, while those in the TOUCH® implant arthroplasty group had a mean follow-up of 14 months. TOUCH® implant arthroplasty patients showed significantly higher grip strengths at 3 months post-surgery and a shorter return to work. There were no differences in pinch strength at 3 months, pinch or grip strength at 6 months or pain scores. Complications included prolonged scar hypersensitivity in two patients who underwent the Weilby suspensionplasty and a dislocated TOUCH® implant cup in one patient. Conclusions: Our study suggests that in the short term, CMCJ implant arthroplasty with the TOUCH® prosthesis produces results comparable to trapeziectomy and Weilby suspensionplasty. Level of Evidence: Level III (Therapeutic).

Observation of 2†µm multiple annular structured vortex pulsed beams by cavity-mode tailoring.

In the past few years, annular structured beams have been extensively studied due to their unique "doughnut" structure and characteristics such as phase and polarization vortices. Especially in the 2 µm wavelength range, they have shown promising applications in fields such as novel laser communication, optical processing, and quantum information processing. In this Letter, we observed basis vector patterns with orthogonality and completeness by finely cavity-mode tailoring with end-mirror space position in a Tm:CaYAlO4 laser. Multiple annular structured beams including azimuthally, linearly, and radially polarized beams (APB, LPB, and RPB) operated at a Q-switched mode-locking (QML) state with a typical output power of ∼18 mW around 1962 nm. Further numerical simulation proved that the multiple annular structured beams are the coherent superposition of different Hermitian Gaussian modes. Using a self-made M-Z interferometer, we have demonstrated that the obtained multiple annular beams have a vortex phase with orbital angular momentum (OAM) of l = ±1. To the best of our knowledge, this is the first observation of vector and scalar annular vortex beams in the 2 µm solid-state laser.

Selected Lark Mitochondrial Genomes Provide Insights into the Evolution of Second Control Region with Tandem Repeats in Alaudidae (Aves, Passeriformes).

The control region (CR) regulates the replication and transcription of the mitochondrial genome (mitogenome). Some avian mitogenomes possess two CRs, and the second control region (CR2) may enhance replication and transcription; however, the CR2 in lark mitogenome appears to be undergoing loss and is accompanied by tandem repeats. Here, we characterized six lark mitogenomes from Alaudala cheleensis, Eremophila alpestris, Alauda razae, and Calandrella cinerea and reconstructed the phylogeny of Passerida. Through further comparative analysis among larks, we traced the evolutionary process of CR2. The mitochondrial gene orders were conserved in all published lark mitogenomes, with Cytb-trnT-CR1-trnP-ND6-trnE-remnant CR2 with tandem repeat-trnF-rrnS. Phylogenetic analysis revealed Alaudidae and Panuridae are sister groups at the base of Sylvioidea, and sporadic losses of CR2 may occur in their common ancestor. CR sequence and phylogeny analysis indicated CR2 tandem repeats were generated within CR2, originating in the ancestor of all larks, rather than inherited from CR1. The secondary structure comparison of tandem repeat units within and between species suggested slipped-strand mispairing and DNA turnover as suitable models for explaining the origin and evolution of these repeats. This study reveals the evolutionary process of the CR2 containing tandem repeat in Alaudidae, providing reference for understanding the evolutionary characteristics and dynamics of tandem repeats.

Sirenian genomes illuminate the evolution of fully aquatic species within the mammalian superorder afrotheria.

Sirenians of the superorder Afrotheria were the first mammals to transition from land to water and are the only herbivorous marine mammals. Here, we generated a chromosome-level dugong (Dugong dugon) genome. A comparison of our assembly with other afrotherian genomes reveals possible molecular adaptations to aquatic life by sirenians, including a shift in daily activity patterns (circadian clock) and tolerance to a high-iodine plant diet mediated through changes in the iodide transporter NIS (SLC5A5) and its co-transporters. Functional in vitro assays confirm that sirenian amino acid substitutions alter the properties of the circadian clock protein PER2 and NIS. Sirenians show evidence of convergent regression of integumentary system (skin and its appendages) genes with cetaceans. Our analysis also uncovers gene losses that may be maladaptive in a modern environment, including a candidate gene (KCNK18) for sirenian cold stress syndrome likely lost during their evolutionary shift in daily activity patterns. Genomes from nine Australian locations and the functionally extinct Okinawan population confirm and date a genetic break ~10.7 thousand years ago on the Australian east coast and provide evidence of an associated ecotype, and highlight the need for whole-genome resequencing data from dugong populations worldwide for conservation and genetic management.

Bismuth oxychloride nanosheets anchored aramid separator with sponge-like structure for improved lithium-ion battery performance.

Functional modification of inorganic particles is an effective approach to tackle the issue of Li+ transport and the lithium dendrites formation in lithium-ion batteries (LIBs). In this study, PMIA/BiOCl composite separators are prepared by nonsolvent induce phase separation (NIPS) method using P-type semiconductor bismuth oxychloride (BiOCl) functionalized poly (m-phenylene isophthalamide) (PMIA) separators. Compared with the polypropylene (PP) separator, PMIA has superior thermal stability and the addition of BiOCl further enhances its flame retardancy. And the prepared PMIA/BiOCl separator presents improved porosity (66.47 %), enhanced electrolyte uptake rate (863 %) and higher ionic conductivity (0.49 mS∙cm-1). Besides, the incorporation of BiOCl can anchor PF6- to the three-dimensional network skeleton of the PMIA/BiOCl separators, enabling the desolvation of Li+ and selectively facilitating Li+ transport (the Li+ transfer number is 0.79). Moreover, the uniform porous structure of the PMIA/BiOCl separators and the efficient transport of Li+ uniformly deposite Li+, and minimize the growth of lithium dendrites. Batteries assembled with PMIA/BiOCl separators have a discharge specific capacity of 124.4 mAh∙g-1 and capacity retention of 96.7 % after 200 cycles at 0.2C. Therefore, this work provides an effective route in the design strategy of separators for LIBs.

Vasorin promotes endothelial differentiation of glioma stem cells via stimulating the transcription of VEGFR2.

Gliomas are highly vascularized malignancies, but current anti-angiogenic treatments have not demonstrated practical improvements in patient survival. Studies have suggested that glioma-derived endothelial cell (GdEC) formed by glioma stem cell (GSC) differentiation may contribute to the failure of this treatment. However, the molecular mechanisms involved in GSC endothelial differentiation remain poorly understood. We previously reported that vasorin (VASN) is highly expressed in glioma and promotes angiogenesis. Here, we show that VASN expression positively correlates with GdEC signatures in glioma patients. VASN promotes the endothelial differentiation capacity of GSC in vitro and participates in the formation of GSC-derived vessels in vivo. Mechanistically, vascular endothelial growth factor receptor 2 (VEGFR2) is a critical factor that mediates the regulation of VASN on GSC endothelial differentiation. Separation of cell chromatin fractionation and chromatin immunoprecipitation-sequencing analysis show that VASN interacts with Notch1 and co-translocates into the cell nuclei, where VASN binds to the VEGFR2 gene promoter to stimulate its transcription during the progression of GSC differentiation into GdEC. Together, these findings elucidate the role and mechanisms of VASN in promoting the endothelial differentiation of GSC and suggest VASN as a potential target for anti-angiogenic therapy based on intervention in GdEC formation in gliomas.

Construction of greenly biodegradable bacterial cellulose/UiO-66-NH2 composite separators for efficient enhancing performance of lithium-ion battery.

The disposal of waste lithium batteries, especially waste separators, has always been a problem, incineration and burial will cause environmental pollution, therefore, the development of degradable and high-performance separators has become an important challenge. Herein, UiO-66-NH2 particles were successfully anchored onto bacterial cellulose (BC) separators by epichlorohydrin (ECH) as a crosslinker, then a BC/UiO-66-NH2 composite separator was prepared by vacuum filtration. The ammonia groups (-NH2) from UiO-66-NH2 can form hydrogen bonds with PF6- in the electrolyte, promoting lithium-ion transference. Additionally, UiO-66-NH2 can store the electrolyte and tune the porosity of the separator. The lithium ion migration number (0.62) of the battery assembled with BC/UiO-66-NH2 composite separator increased by 50 % compared to the battery assembled with commercial PP separator (0.45). The discharge specific capacity of the battery assembled with BC/UIO-66-NH2 composite separator after 50 charge and discharge cycles is 145.4 mAh/g, which is higher than the average discharge specific capacity of 114.3 mAh/g of the battery assembled with PP separator. When the current density is 2C, the minimum discharge capacity of the battery assembled with BC/UiO-66-NH2 composite separator is 85.3 mAh/g. The electrochemical performance of the BC/UiO-66-NH2 composite separator is significantly better than that of the commercial PP separator. In addition, -NH2 can offer a nitrogen source to facilitate degradation of the BC separators, whereby the BC/UiO-66-NH2 composite separator could be completely degraded in 15 days.

Calmodulin-like protein MdCML15 interacts with MdBT2 to modulate iron homeostasis in apple.

BTB and TAZ domain proteins (BTs) function as specialized adaptors facilitating substrate recognition of the CUL3-RING ubiquitin ligase (CRL3) complex that targets proteins for ubiquitination in reaction to diverse pressures. Nonetheless, knowledge of the molecular mechanisms by which the apple scaffold protein MdBT2 responds to external and internal signals is limited. Here we demonstrate that a putative Ca 2+ sensor, calmodulin-like 15 (MdCML15), acts as an upstream regulator of MdBT2 to negatively modulate its functions in plasma membrane H+-ATPase regulation and iron deficiency tolerance. MdCML15 was identified to be substantially linked to MdBT2, and to result in the ubiquitination and degradation of the MdBT2 target protein MdbHLH104. Consequently, MdCML15 repressed the MdbHLH104 target, MdAHA8's expression, reducing levels of a specific membrane H+-ATPase. Finally, the phenotype of transgenic apple plantlets and calli demonstrated that MdCML15 modulates membrane H+-ATPase-produced rhizosphere pH lowering alongside iron homeostasis through an MdCML15-MdBT2-MdbHLH104-MdAHA8 pathway. Our results provide new insights into the relationship between Ca2+ signaling and iron homeostasis.

Clinical and genetic analyses of APMR4 syndrome caused by novel biallelic LSS variants.

Alopecia intellectual disability syndromes 4 (APMR4) caused by Lanosterol synthase (LSS) gene variants is a very rare autosomal recessive neuroectodermal syndrome. It is characterized by congenital alopecia and variable degrees of intellectual disability (ID), frequently associated with developmental delay (DD) and epilepsy. Currently, only three studies regarding LSS-related APMR4 have been reported, the pathogenesis of APMR4 is poorly understood. We studied one patient with LSS-related APMR4 who presented with severe intellectual disability, alopecia, early-onset epilepsy and developmental delay. She is absence of hair on the eyebrows, eyelashes, and scalp. Two novel LSS variants (c.401 T > G and c.369C > G) were detected with whole-exome sequencing (WES). Analysis via WB experiment indicated that c.369 > G reduced the protein expression level of LSS. Analysis of protein stability prediction showed a destabilizing for LSS caused by the variant c.401 T > G. This study is the first study in Asia to date. These findings expanded the variantal spectrum of LSS-related APMR4 and revealed the potential pathogenic mechanism of LSS gene variants.

Reversible Constrained Dissociation and Reassembly of MXene Films.

Enabling materials to undergo reversible dynamic transformations akin to the behaviors of living organisms represents a critical challenge in the field of material assembly. The pursuit of such capabilities using conventional materials has largely been met with limited success. Herein, the discovery of reversible constrained dissociation and reconfiguration in MXene films, offering an effective solution to overcome this obstacle is reported. Specifically, MXene films permit rapid intercalation of water molecules between their distinctive layers, resulting in a significant expansion and exhibiting confined dissociation within constrained spaces. Meanwhile, the process of capillary compression driven by water evaporation reinstates the dissociated MXene film to its original compact state. Further, the adhesive properties emerging from the confined disassociation of MXene films can spontaneously induce fusion between separate films. Utilizing this attribute, complex structures of MXene films can be effortlessly foamed and interlayer porosity precisely controlled, using only water as the inducer. Additionally, a parallel phenomenon has been identified in graphene oxide films. This work not only provides fresh insights into the microscopic mechanisms of 2D materials such as MXene but also paves a transformative path for their macroscopic assembly applications in the future.

The NEDD8 activating enzyme inhibitor MLN4924 mitigates doxorubicin-induced cardiotoxicity in mice.

Doxorubicin (DOX) is a widely utilized chemotherapeutic agent in clinical oncology for treating various cancers. However, its clinical use is constrained by its significant side effects. Among these, the development of cardiomyopathy, characterized by cardiac remodeling and eventual heart failure, stands as a major concern following DOX chemotherapy. In our current investigation, we have showcased the efficacy of MLN4924 in mitigating doxorubicin-induced cardiotoxicity through direct inhibition of the NEDD8-activating enzyme, NAE. MLN4924 demonstrated the ability to stabilize mitochondrial function post-doxorubicin treatment, diminish cardiomyocyte apoptosis, alleviate oxidative stress-induced damage in the myocardium, enhance cardiac contractile function, mitigate cardiac fibrosis, and impede cardiac remodeling associated with heart failure. At the mechanistic level, MLN4924 intervened in the neddylation process by inhibiting the NEDD8 activating enzyme, NAE, within the murine cardiac tissue subsequent to doxorubicin treatment. This intervention resulted in the suppression of NEDD8 protein expression, reduction in neddylation activity, and consequential manifestation of cardioprotective effects. Collectively, our findings posit MLN4924 as a potential therapeutic avenue for mitigating doxorubicin-induced cardiotoxicity by attenuating heightened neddylation activity through NAE inhibition, thereby offering a viable and promising treatment modality for afflicted patients.

[Effectiveness of injured vertebra fixation with inclined-long pedicle screws combined with interbody fusion for thoracolumbar fracture dislocation with disc injury].

Objective: To investigate the effectiveness of injured vertebra fixation with inclined-long pedicle screws combined with interbody fusion for thoracolumbar fracture dislocation with disc injury. Methods: Between January 2017 and June 2022, 28 patients with thoracolumbar fracture dislocation with disc injury were underwent posterior depression, the injured vertebra fixation with inclined-long pedicle screws, and interbody fusion. There were 22 males and 6 females, with a mean age of 41.4 years (range, 22-58 years). The causes of injury included falling from height in 18 cases, traffic accident in 5 cases, and bruise in 5 cases. Fracture segment included 1 case of T 11, 7 cases of T 12, 9 cases of L 1, and 11 cases of L 2. According to the American Spinal Injury Association (ASIA) scale, the spinal injuries were graded as grade A in 4 cases, grade B in 2 cases, grade C in 11 cases, and grade D in 11 cases. Preoperative spinal canal encroachment ratio was 17.7%-75.3% (mean, 44.0%); the thoracolumbar injury classification and severity score (TLICS) ranged from 9 to 10 (mean, 9.9). Seventeen patients were associated with other injuries. The time from injury to operation ranged from 1 to 4 days (mean, 2.3 days). The perioperative indicators (operation time, intraoperative blood loss, and the occurrence of complications), clinical evaluation indicators [visual analogue scale (VAS) score and Oswestry Disability Index (ODI)], radiologic evaluation indicators [anterior vertebral height ratio (AVHR), kyphosis Cobb angle (KCA), intervertebral space height (ISH), vertebral wedge angle (VWA), displacement angle (DA), and percent fracture dislocation displacement (PFDD)], neurological function, and interbody fusion were recorded. Results: The operation time was 110-159 minutes (mean, 130.2 minutes). The intraoperative blood loss was 200-510 mL (mean, 354.3 mL). All incisions healed by first intention, and no surgical complications such as wound infection or hematoma occurred. All patients were followed up 12-15 months (mean, 12.7 months). The chest and lumbar pain significantly relieved, VAS scores and ODI after operation were significantly lower than those before operation, and further decreased with the extension of postoperative time, with significant differences ( P<0.05). At last follow-up, the ASIA classification of neurological function of the patients was grade A in 3 cases, grade B in 1 case, grade C in 1 case, grade D in 10 cases, and grade E in 13 cases, which was significantly different from preoperative one ( Z=-4.772, P<0.001). Imaging review showed that AVHR, KCA, ISH, VWA, DA, and PFDD significantly improved at 1 week, 3 months and last follow-up ( P<0.05). There was no significant difference between different time points after operation ( P>0.05). At last follow-up, according to the modified Brantigan score, all patients achieved good intervertebral bone fusion, including 22 complete fusion and 6 good intervertebral fusion with a few clear lines. No complications such as internal fixation failure or kyphosis occurred during follow-up. Conclusion: The injured vertebra fixation with inclined-long pedicle screws combined with interbody fusion is an effective treatment for thoracolumbar fracture dislocation with disc injury, which can correct the fracture dislocation, release the nerve compression, restore the injured vertebral height, and reconstruct spinal stabilization.

The experience of shared decision-making for people with asthma: A systematic review and metasynthesis of qualitative studies.

OBJECTIVES: To identify, describe and synthesise the views and experiences of adults living with asthma regarding shared decision-making (SDM) in the existing qualitative literature METHODS: We conducted a comprehensive search of 10 databases (list databases) from inception until September 2023. Screening was performed according to inclusion criteria. Tools from the Joanna Briggs lnstitute were utilised for the purposes of data extraction and synthesis in this study. The data extraction process in this study employed the Capability, Opportunity and Motivation Model of Behaviour (COM-B model) as a framework, and a pragmatic meta-aggregative approach was employed to synthesise the collected results. RESULTS: Nineteen studies were included in the metasynthesis. Three synthesised themes were identified: the capability of people living with asthma, the opportunities of people living with asthma in SDM, and the motivation of the people living with asthma in SDM. CONCLUSIONS: We have identified specific factors influencing people living with asthma engaging in SDM. The findings of this study can serve as a basis for the implementation of SDM in people living with asthma and provide insights for the development of their SDM training programs. The ConQual score for the synthesised findings was rated as low. To enhance confidence, future studies should address dependability and credibility factors. PRACTICE IMPLICATIONS: This review contemplates the implementation of SDM from the perspective of people living with asthma, with the aim of providing patient-centred services for them. The results of this review can benefit the implementation of SDM and facilitate information sharing. It offers guidance for SDM skills training among adults living with asthma, fosters a better doctor-patient relationship and facilitates consensus in treatment decisions, thereby enabling personalised and tailored medical care. PATIENT OR PUBLIC CONTRIBUTION: Three nursing graduate students participated in the data extraction and integration process, with two students having extensive clinical experience that provided valuable insights for the integration.

Vasorin Exocytosed from Glioma Cells Facilitates Angiogenesis via VEGFR2/AKT Signaling Pathway.

Glioma is a highly vascularized tumor of the central nervous system. Angiogenesis plays a predominant role in glioma progression and is considered an important therapeutic target. Our previous study showed that vasorin (VASN), a transmembrane protein, is overexpressed in glioma and promotes angiogenesis; however, the potential mechanism remains unclear. In this study, we found that human vascular endothelial cells (hEC) co-cultured with VASN-overexpressing glioma cells exhibited accelerated migration ability and increased expression of VASN originated from glioma cells. VASN was found in exosomes secreted by glioma cells and could be taken up by hECs. hECs showed more edge filopodia and significantly upregulated expression of endothelial tip cell marker gene and protein levels after co-culture with VASN-overexpressing glioma cells. In clinical glioma tissue and orthotopic transplantation glioma tissue, the vascular density and the number of vascular endothelial cells with a tip cell phenotype in VASN-overexpressed tissues were significantly higher than in tissues with low expression. At the molecular level, VASN interacted with VEGFR2 and caused internalization and autophosphorylation of VEGFR2 protein, and then activated the AKT signaling pathway. Our study collectively reveals the function and mechanism of VASN in facilitating angiogenesis in glioma, providing a new therapeutic target for glioma. IMPLICATIONS: These findings demonstrate that VASN exocytosed from glioma cells enhanced the migration of vascular endothelial cells by VEGFR2/AKT signaling pathway.

Zanubrutinib plus Cytarabine in Patients with Refractory/Relapsed Primary Central Nervous System Lymphoma.

INTRODUCTION: Primary central nervous system lymphoma (PCNSL) is a rare subtype of aggressive extranodal non-Hodgkin lymphoma. Currently, there is no standard of care for the treatment of refractory or relapsed PCNSL (r/r PCNSL). We conducted a prospective single-arm phase II study to evaluate zanubrutinib plus cytarabine for r/r PCNSL. METHODS: Using Simon's two-stage design, we analyzed 34 patients who received high-dose cytarabine (3.0 g/m2 once daily) for 2 days and zanubrutinib (160 mg twice daily) for 21 days each cycle for up to 6 cycles. The study was registered at www.chictr.org.cn as #ChiCTR2000039229. RESULTS: The median follow-up was 19 months. The overall response rate was 64.7% (95% confidence interval [CI], 47.9-78.5%) with a complete remission or unconfirmed complete remission rate of 47.1% (16/34) and a partial remission rate of 17.6% (6/34). The median progression-free survival was 4.5 months (95% CI, 1.5-9.4), and the median OS was 18 months (95% CI, 9.5 to not estimable). The median duration of the response was 9 months (95% CI, 3.2 to not estimable). The most common treatment-emergent adverse events were thrombocytopenia (55.9%). No treatment-related death occurred. CONCLUSION: Zanubrutinib and cytarabine showed efficacy in r/r PCNSL with an acceptable safety profile.

USP7 as an emerging therapeutic target: A key regulator of protein homeostasis.

Maintaining protein balance within a cell is essential for proper cellular function, and disruptions in the ubiquitin-proteasome pathway, which is responsible for degrading and recycling unnecessary or damaged proteins, can lead to various diseases. Deubiquitinating enzymes play a vital role in regulating protein homeostasis by removing ubiquitin chains from substrate proteins, thereby controlling important cellular processes, such as apoptosis and DNA repair. Among these enzymes, ubiquitin-specific protease 7 (USP7) is of particular interest. USP7 is a cysteine protease consisting of a TRAF region, catalytic region, and C-terminal ubiquitin-like (UBL) region, and it interacts with tumor suppressors, transcription factors, and other key proteins involved in cell cycle regulation and epigenetic control. Moreover, USP7 has been implicated in the pathogenesis and progression of various diseases, including cancer, inflammation, neurodegenerative conditions, and viral infections. Overall, characterizing the functions of USP7 is crucial for understanding the pathophysiology of diverse diseases and devising innovative therapeutic strategies. This article reviews the structure and function of USP7 and its complexes, its association with diseases, and its known inhibitors and thus represents a valuable resource for advancing USP7 inhibitor development and promoting potential future treatment options for a wide range of diseases.