Osteocyte mitochondria inhibit tumor development via STING-dependent antitumor immunity.

Bone is one of the most common sites of tumor metastases. During the last step of bone metastasis, cancer cells colonize and disrupt the bone matrix, which is maintained mainly by osteocytes, the most abundant cells in the bone microenvironment. However, the role of osteocytes in bone metastasis is still unclear. Here, we demonstrated that osteocytes transfer mitochondria to metastatic cancer cells and trigger the cGAS/STING-mediated antitumor response. Blocking the transfer of mitochondria by specifically knocking out mitochondrial Rho GTPase 1 (Rhot1) or mitochondrial mitofusin 2 (Mfn2) in osteocytes impaired tumor immunogenicity and consequently resulted in the progression of metastatic cancer toward the bone matrix. These findings reveal the protective role of osteocytes against cancer metastasis by transferring mitochondria to cancer cells and potentially offer a valuable therapeutic strategy for preventing bone metastasis.

Aspects épidémiologiques, cliniques et thérapeutiques de l'asthme de l'enfant dans le département de pédiatrie du CHU Gabriel Touré / Epidemiological, clinical and therapeutic aspects of childhood asthma in the department of pediatrics of the Gabriel Touré university hospital

Introduction: L'asthme est la maladie chronique de l'enfant la plus fréquente. Il estl'une des principales causes de consultations aux urgences, d'hospitalisation et d'absentéisme scolaire.L'asthme est un véritable problème de santé publique. La prévalence de cette maladie ne cesse d'augmenter dans le monde entier. Patients et méthode : Nous avions mené une étude prospective, auprès des enfants asthmatiques sur une période d'une année, de Janvier 2018à décembre 2018. Résultats : Nous avions recensé105 patients asthmatiques pour un total de 14344 consultations soit une fréquence de 0,73%. Le sex ratio était de 1.9, La tranche d'âge 2-5 ans était la plus fréquente soit 52%, l'âge de la première crise se situait généralement entre 1 et 2 ans soit 75.24%. Nous avions observé que près de 22% des crises survenaient au mois de décembre (21.90%). La fumée et l'humiditéétaient les principaux facteurs déclenchants. Tous les malades avaient bénéficié de la nébulisation par lesB 2 mimétiques. Conclusion : l'éducation de l'enfant asthmatique ainsi que de sa famille et la mise en place de protocoles standards de prise en charge pourraient réduire de façon considérable la morbidité liée à l'asthme dans nos pays

Introduction : Asthma is the most common chronic disease of children. It is a leading cause of emergency room visits, hospitalization and school absenteeism. Asthma is a real public health problem. The prevalence of this disease is increasing worldwide. Patients and method: We had conducted a prospective study, among children with asthma over a period of one year, from January 2018 to December 2018. Results: We counted 105 asthmatic patients for a total of 14344 consultations, or a frequency of 0,73%. The sex ratio was 1,9, the age group 2-5 years was the most frequent, (52%), the age of the first attack was generally between 1 and 2 years, ( 75,24%). We observed that almost 22% of the attacks occurred in December (21,90%). Smoke and humidity were the main triggers. All the patients had benefited from nebulization with B 2 mimetics. Conclusion: Education of asthmatic children, their families and the establishment of standard management protocols could significantly reduce asthmarelated morbidity in our countries.

Surgical Options for Aggressive Vertebral Hemangiomas：A case series, literature review and treatment recommendations.

Purpose: We retrospectively study twenty-nine surgical cases of aggressive vertebral hemangiomas (AVHs) with neurological deficits and extradural compression to determine the optimal surgical treatment strategy for AVHs at a single institution. Methods: Patients with AVHs with neurological deficits who underwent partial tumor resection plus decompression with or without vertebroplasty (VP), and radiotherapy between 2010 and 2021 were included in this study. Clinical characteristics, surgical outcomes, and follow-up data of the patients were reviewed retrospectively. Results: Twenty-nine AVH cases with neurological deficits and spinal instability were included in this study and treated surgically. The mean operation time of patients with decompression surgery plus VP (Groupe A) was 215.9 (120-265 min), shorter than that of decompression surgery without VP (Group B) 240.2 (120-320 min). Intraoperative blood loss was 273.3 (100-550 mL) in group A and 635.3 (200-1600 mL) in group B. In addition, a significant reduction in blood loss was observed in group A compared to the group B (p=0.0001). All patients experienced immediate pain relief and improvement in their neurological symptoms. Neurological function was assessed by the Frankel score, ASIA score, and the visual analogue scale (VAS) pain score decreased from 7.4 (4-9) to 1.3 (0-3). Of twenty-nine patients in this study,  only 7% (2/29 patients) showed signs of recurrence. Conclusion: Decompression plus VP achieve good tumor control and decrease surgical complication. Preoperative vascular embolization and VP can reduce intraoperative bleeding in the treatment of AVH surgery. Moreover, postoperative radiotherapy seems to be a good technique to prevent tumor recurrence.

Rejuvenation of tendon stem/progenitor cells for functional tendon regeneration through platelet-derived exosomes loaded with recombinant Yap1.

The regenerative capabilities including self-renewal, migration and differentiation potentials shift from the embryonic phase to the mature period of endogenous tendon stem/progenitor cells (TSPCs) characterize restricted functions and disabilities following tendon injuries. Recent studies have shown that tendon regeneration and repair rely on multiple specific transcription factors to maintain TSPCs characteristics and functions. Here, we demonstrate Yap, a Hippo pathway downstream effector, is associated with TSPCs phenotype and regenerative potentials through gene expression analysis of tendon development and repair process. Exosomes have been proven an efficient transport platform for drug delivery. In this study, purified exosomes derived from donor platelets are loaded with recombinant Yap1 protein (PLT-Exo-Yap1) via electroporation to promote the stemness and differentiation potentials of TSPCs in vitro. Programmed TSPCs with Yap1 import maintain stemness and functions after long-term passage in vitro. The increased oxidative stress levels of TSPCs are related to the phenotype changes in duplicative senescent processes. The results show that treatment with PLT-Exo-Yap1 significantly protects TSPCs against oxidative stressor-induced stemness loss and senescence-associated secretory phenotype (SASP) through the NF-κB signaling pathway. In addition, we fabricate an Exos-Yap1-functioned GelMA hydrogel with a parallel-aligned substrate structure to enhance TSPCs adhesion, promote cell stemness and force regenerative cells toward the tendon lineage for in vitro and in vivo tendon regeneration. The application of Exos-Yap1 functioned implant assists new tendon-like tissue formation with good mechanical properties and locomotor functions in a full-cut Achilles tendon defect model. Thus, PLT-Exo-Yap1-functionalized GelMA promotes the rejuvenation of TSPCs to facilitate functional tendon regeneration. STATEMENT OF SIGNIFICANCE: This is the first study to explore that the hippo pathway downstream effector Yap is involved in tendon aging and repair processes, and is associated with the regenerative capabilities of TSPCs. In this syudy, Platelet-derived exosomes (PLT-Exos) act as an appropriate carrier platform for the delivery of recombinant Yap1 into TSPCs to regulate Yap activity. Effective Yap1 delivery inhibit oxidative stress-induced senescence associated phenotype of TSPCs by blocking ROS-mediated NF-κb signaling pathway activation. This study emphasizes that combined application of biomimetic scaffolds and Yap1 loaded PLT-Exos can provide structural support and promote rejuvenation of resident cells to assist functional regeneration for Achilles tendon defect, and has the prospect of clinical setting.

Finite element analysis of sacral-alar-iliac screw fixation for sacroiliac joint dislocation.

The percutaneous sacroiliac (SI) screw is a common fixation option for posterior ring disruption in pelvic fractures. However, SI screw placement is difficult and can injure adjacent neurovascular structures. The sacral-alar-iliac screw (SAI) is a safe, reliable free-hand sacral pelvic fixation technique. To investigate the biomechanical stability of SAI for SI joint dislocation, finite element analysis was performed in unstable Tile-Type B and C pelvic ring injuries. The displacement in S1 (fixation of a unilateral S1 segment with one SI screw), TS1 (fixation of the S1 segment with a transsacra 1 screw), TS2 (fixation of the S2 segment with a transsacra 2 screw), S1AI, and S2AI exceeded the normal SI joint mobility. Sufficient stability after SI joint dislocation was obtained with (TS1 + TS2), (TS2 + S1), (S1AI + S2AI + rod), (S1AI + S2AI), and (S1 + S2AI + S1 pedicle) fixation. The TS1 + TS2 group had the smallest displacement and lowest peak screw stress, followed by (S1 + S2AI + S1 pedicle) placement. Our findings suggest that SAI screws are a valuable option for SI joint dislocation.

Enhancement of T cell infiltration via tumor-targeted Th9 cell delivery improves the efficacy of antitumor immunotherapy of solid tumors.

Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy (ACT) against solid tumors. Here, we present a facile immune cell surface engineering strategy aiming to substantially enhance the anti-tumor efficacy of Th9-mediated ACT by rapidly identifying tumor-specific binding ligands and improving the infiltration of infused cells into solid tumors. Non-genetic decoration of Th9 cells with tumor-targeting peptide screened from phage display not only allowed precise targeted ACT against highly heterogeneous solid tumors but also substantially enhanced infiltration of CD8+ T cells, which led to improved antitumor outcomes. Mechanistically, infusion of Th9 cells modified with tumor-specific binding ligands facilitated the enhanced distribution of tumor-killing cells and remodeled the immunosuppressive microenvironment of solid tumors via IL-9 mediated immunomodulation. Overall, we presented a simple, cost-effective, and cell-friendly strategy to enhance the efficacy of ACT against solid tumors with the potential to complement the current ACT.

Establishment and Verification of Prognostic Nomograms for Young Women With Breast Cancer Bone Metastasis.

Purpose: The prognosis of patients with metastatic breast cancer usually varies greatly among individuals. At present, the application of nomogram is very popular in metastatic tumors. The present study was conducted to identify independent survival predictors and construct nomograms among young women with breast cancer bone metastasis (BCBM). Patients and Methods: We searched the Surveillance, Epidemiology, and End Results (SEER) database to identify young women diagnosed with BCBM between 2010 and 2016. We first analyzed the potential risk factors of overall survival (OS) and cancer-specific survival (CSS) by applying univariate Cox regression analysis. Then we conducted multivariate Cox analysis to identify independent survival predictors. Based on significant independent predictors, we developed and validated novel prognostic nomograms by using the R version 4.1.0 software. Results: We finally identified 715 eligible young women with BCBM for survival analysis, of which 358 patients were in the training set, and 357 patients in the validation set. Approximately four-fifths of patients are between 31 and 40 years old. The 5-year OS and CSS rates of this research population were 41.9 and 43.3%, respectively. Multivariate analysis revealed seven independent predictors of both OS and CSS, including race, tumor subtype, tumor size, surgical treatment, brain metastasis, liver metastasis, and lung metastasis. Based on these predictors, we developed and validated OS and CSS nomograms. The C-index of the OS nomogram reached 0.728 and 0.73 in the training and validation sets, respectively. The C-index of the CSS nomogram reached 0.743 and 0.695 in the training and validation sets, respectively. Meanwhile, high quality calibration plots were revealed in both OS and CSS nomograms. Conclusion: The current novel nomograms can provide an individualized survival evaluation of young women with BCBM and instruct clinicians to treat them appropriately.

Circular RNA circPDSS1 promotes osteosarcoma progression by sponging miR-502-3p and miR-4436a.

Osteosarcoma (OS) is a highly aggressive bone cancer. Patients with OS frequently develop drug resistance in clinical treatment, and the prognosis has not been improved significantly. There is an urgent need to identify novel markers and therapeutic targets. In this study, we focused on the highly expressed noncoding circular RNA circPDSS1 in OS, and studied its functional roles and downstream targets in OS cells by CCK-8, clone formation assay, transwell assays. Additionally, we performed luciferase reporter assay, RNA pull-down experiment and qRT-PCR to validate the micoRNA targets of circPDSS1. The involvement of circPDSS1 in tumorigenesis was also investigated in mouse xenografts model. The expression of circPDSS1 was significantly upregulated in OS tissues and cell lines. Patients with high circPDSS1 expression were associated with poorer progression-free survival (PFS) and overall survival (OS) as compared to those with low circPDSS1 expression. CircPDSS1 knockdown significantly inhibited the viability, clone formation ability and invasion ability of OS cells, and induced cell apoptosis, which were associated with the upregulation of proapoptotic proteins and the impairment of prosurvival signaling. Molecular mechanism study further demonstrated that circPDSS1 modulates OS cell functions by regulating the expression of miR-502-3p and miR-4436a. Our data suggest that circPDSS1 acts as a molecular sponge of miR-502-3p and miR-4436a regulates the proliferation and invasion of OS cells and promote the malignant progression of OS.

Malian Thick Porridges (tô) of Pearl Millet Are Made Thinner in Urban Than Rural Areas and Decrease Satiety.

BACKGROUND: Changes in preparation, preference, and consumption of traditional staple foods between rural and urban areas in sub-Saharan Africa may be associated with the nutrition transition. OBJECTIVE: Millet porridge thickness and postprandial hunger were investigated in Mali with the aim of understanding consumer preference and satiety properties. METHODS: Rural and urban residents from 3 regions (N = 60) were surveyed regarding their porridge consumption frequency and thickness preference. Influence of millet porridge thickness on satiety was investigated. Ten participants consumed 4 porridges of different thicknesses (3 of millet and 1 thin porridge of rice) and rated their subjective hunger on 4 different days. RESULTS: Thicker porridges were consumed more frequently in rural areas than in urban (P < .05). For the satiety study, thicker porridges induced higher satiety than thinner ones at 2 and 4 hours postconsumption (P < .05; Visual Analog Scale rating). A greater amount of flour, but not volume, was consumed for the thicker porridges (P < .05). CONCLUSIONS: Urban participants preferred and consumed porridges that are less satiating, potentially contributing to higher food consumption related to the nutrition transition in Africa.

Treatment for lumbar spinal stenosis secondary to ligamentum flavum hypertrophy using percutaneous endoscopy through interlaminar approach: a retrospective study.

BACKGROUND: This paper is to describe percutaneous endoscopy in the treatment of lumbar spinal stenosis secondary to ligamentum flavum hypertrophy targeted and to investigate the efficacy and safety of percutaneous endoscopy in the treatment of this kind of lumbar spinal stenosis in elderly patients. METHOD: A retrospective analysis of 40 elderly patients with lumbar spinal stenosis secondary to ligamentum flavum hypertrophy admitted between January 2016 and January 2018 was performed. According to different surgical methods, they were divided into two groups: the control group and the endoscopy group (interlaminar approach), 20 people per group. There were 9 males and 11 females in the control group; the age of patients was 65.65 ± 4.44 years, and the average disease duration was 4.55 ± 1.85 years. Besides, there were 10 males and 10 females in the endoscopy group; the age of patients was 67.30 ± 4.23 years, and the average disease duration was 4.95 ± 2.04 years. Collect and count surgical-related indicators, preoperative and postoperative radiologic findings, incision visual analog scale (VAS), lumbar and leg pain VAS, lumbar Japanese Orthopaedic Association (JOA), and Oswestry disability index (ODI) scores of all patients. RESULT: A series of surgical indicators (including the operation time, the quantity of bleeding, and postoperative hospital stay) in the endoscopy group was significantly lower than that in the control group (p < 0.05). The incision VAS score in the endoscopy group was also significantly lower than that in the control group at each time after surgery (p < 0.05). Besides, compared with the control group, in the endoscopy group, the leg pain VAS score and lumbar ODI score after surgery were significantly decreased (p < 0.05). Compared with the control group, in the endoscopy group, the lumbar JOA score was significantly higher (p < 0.05). CONCLUSION: Percutaneous endoscopic technique is a small trauma, quick recovery, safe, and effective minimally invasive surgery for patients with lumbar spinal stenosis secondary to ligamentum flavum hypertrophy.