Construction of Near-Infrared Probes with Remarkable Large Stokes Shift Based on a Novel Purine Platform for the Visualization of mtG4 Upregulation during Mitochondrial Disorder in Somatic Cells and Human Sperms.

G-quadruplex structures within the nuclear genome (nG4) is an important regulatory factor, while the function of G4 in the mitochondrial genome (mtG4) still needs to be explored, especially in human sperms. To gain a better understanding of the relationship between mtG4 and mitochondrial function, it is crucial to develop excellent probes that can selectively visualize and track mtG4 in both somatic cells and sperms. Herein, based on our previous research on purine frameworks, we attempted for the first time to extend the conjugated structure from the C-8 site of purine skeleton and discovered that the purine derivative modified by the C-8 aldehyde group is an ideal platform for constructing near-infrared probes with extremely large Stokes shift (>220 nm). Compared with the compound substituted with methylpyridine (PAP), the molecule substituted with methylthiazole orange (PATO) showed better G4 recognition ability, including longer emission (∼720 nm), more significant fluorescent enhancement (∼67-fold), lower background, and excellent photostability. PATO exhibited a sensitive response to mtG4 variation in both somatic cells and human sperms. Most importantly, PATO helped us to discover that mtG4 was significantly increased in cells with mitochondrial respiratory chain damage caused by complex I inhibitors (6-OHDA and rotenone), as well as in human sperms that suffer from oxidative stress. Altogether, our study not only provides a novel ideal molecular platform for constructing high-performance probes but also develops an effective tool for studying the relationship between mtG4 and mitochondrial function in both somatic cells and human sperms.

Reactive oxygen species produced by photodynamic therapy enhance docosahexaenoic acid lipid peroxidation and induce the death of breast cancer cells.

Breast cancer remains a serious threat to women's physical and emotional health. The combination therapies can overcome the deficiency of single therapy, enhance the therapeutic effects and reduce the side effects at the same time. In this study, we synthesize a novel nanomedicine that enhanced the therapeutic effects of breast cancer treatment by combining photodynamic therapy and chemotherapy. The doxorubicin (DOX) and photosensitizer methyl pyropheophorbide-a (MPPa) are loaded into the nano-drug delivery system as DPSPFA/MPPa/DOX. In response to near-infrared (NIR) laser, the drugs were quickly released to the cancer cells. The MPPa produces reactive oxygen species (ROS) under the action of photodynamics. Unsaturated fatty acids with ROS promotes lipid peroxidation and the combination of chemotherapy and photodynamic therapy. The data shows that the DPSPFA/MPPa/DOX has a spherical shape, good dispersibility and stability, and the particle size is roughly 200 nm. The drug loading capability of DOX is about 13 %. Both of MCF7 cell model in vitro and breast cancer model in vivo, DPSPFA/MPPa/DOX showed an excellent anti-tumor effect of 86.9 % and without any obvious side effects. These findings might offer potential for a new approach for breast cancer treatment.

Salvage Latarjet may provide worse outcomes in terms of recurrent instability and returning to sports compared to primary Latarjet: a systematic review of comparative studies.

BACKGROUND: The Latarjet procedure (LP) is performed as a primary stabilization procedure (primary LP) and a salvage procedure when an earlier shoulder stabilization procedure has failed (salvage LP). However, whether primary LP or salvage LP provides better outcomes for anterior shoulder instability remains unknown. METHODS: Two independent reviewers performed the literature search based on the PRISMA guidelines. A comprehensive search of PubMed, Embase, web of science and Cochrane Library was performed from their inception date to December 4, 2023. Inclusion criteria mainly included the comparison of postoperative outcomes between primary and salvage LP, English language, and full text availability. Two reviewers independently examined the literature, collected data, and evaluated the methodological robustness of the included studies. The Methodological Index for Nonrandomized Studies was used to evaluate the quality of nonrandomized studies. Recurrent instability, complications, reoperations, return to sports, patient-reported outcomes, and range of motion were assessed. Statistical evaluations were conducted using Manager V.5.4.1 (The Cochrane Collaboration, Software Update, Oxford, UK). RESULTS: Twelve studies were included in the systematic review, with 940 shoulders undergoing primary LP and 631 shoulders undergoing salvage LP. Statistically significant differences in favor of primary LP were found in 2 of the 11 and 2 of 4 included studies in terms of recurrent instability and returning to the same sports (RTS) at preinjury level, respectively. In terms of the visual analog scale, subjective shoulder value and the Western Ontario Shoulder Instability Index, 2 of the 4, 1 of the 3 and 1 of the 3 included studies reported statistically significant differences in favor of primary LP. Differences were not noticed regarding complications, reoperations, the time to RTS, the Rowe score, the Athletic Shoulder Outcome Scoring System, and forward flexion. CONCLUSION: Current evidence suggests that compared with primary LP, salvage LP may provide inferior postoperative outcomes in terms of recurrent instability and the rate of RTS at preinjury level. Primary and salvage LP may yield comparable efficacy in terms of complications, reoperations, the rate of RTS, the time to RTS, pain, shoulder function, and range of motion. PROSPERO ID: CRD42023492027.

Small diameter vascular grafts: progress on electrospinning matrix/stem cell blending approach.

The exploration of the next-generation small diameter vascular grafts (SDVGs) will never stop until they possess high biocompatibility and patency comparable to autologous native blood vessels. Integrating biocompatible electrospinning (ES) matrices with highly bioactive stem cells (SCs) provides a rational and promising solution. ES is a simple, fast, flexible and universal technology to prepare extracellular matrix-like fibrous scaffolds in large scale, while SCs are valuable, multifunctional and favorable seed cells with special characteristics for the emerging field of cell therapy and regenerative medicine. Both ES matrices and SCs are advanced resources with medical application prospects, and the combination may share their advantages to drive the overcoming of the long-lasting hurdles in SDVG field. In this review, the advances on SDVGs based on ES matrices and SCs (including pluripotent SCs, multipotent SCs, and unipotent SCs) are sorted out, and current challenges and future prospects are discussed.

Extracellular Vesicle-Contained Thrombospondin 1 Retards Age-Related Degenerative Tendinopathy by Rejuvenating Tendon Stem/Progenitor Cell Senescence.

Advanced age is a major risk factor for age-related degenerative tendinopathy. During aging, tendon stem/progenitor cell (TSPC) function declines owing to the transition from a normal quiescent state to a senescent state. Extracellular vesicles (EVs) from young stem cells are reported to possess anti-aging functions. However, it remains unclear whether EVs from young TSPCs (TSPC-EVs) can rejuvenate senescent TSPCs to delay age-related degeneration. Here, this study finds that TSPC-EVs can mitigate the aging phenotypes of senescent TSPCs and maintain their tenogenic capacity. In vitro studies reveal that TSPC-EVs can reinstall autophagy in senescent TSPCs to alleviate cellular senescence, and that the re-establishment of autophagy is mediated by the PI3K/AKT pathway. Mechanistically, this study finds that thrombospondin 1, a negative regulator of the PI3K/AKT pathway, is enriched in TSPC-EVs and can be transported to senescent TSPCs. Moreover, in vivo studies show that the local delivery of TSPC-EVs can rejuvenate senescent TSPCs and promote their tenogenic differentiation, thereby rescuing tendon regeneration in aged rats. Taken together, TSPC-EVs as a novel cell-free approach have promising therapeutic potential for aging-related degenerative tendinopathy.

Hierarchical Chiral Calcium Silicate Hydrate Films Promote Vascularization for Tendon-to-Bone Healing.

Revascularization after rotator cuff repair is crucial for tendon-to-bone healing. The chirality of materials has been reported to influence their performance in tissue repair. However, data on the use of chiral structures to optimize biomaterials as a revascularization strategy remain scarce. Here, calcium silicate hydrate (CSO) films with hierarchical chirality on the atomic to micrometer scale are developed. Interestingly, levorotatory CSO (L-CSO) films promote the migration and angiogenesis of endothelial cells, whereas dextral and racemic CSO films do not induce the same effects. Molecular analysis demonstrates that L-chirality can be recognized by integrin receptors and leads to the formation of focal adhesion, which activates mechanosensitive ion channel transient receptor potential vanilloid 4 to conduct Ca2+ influx. Consequently, the phosphorylation of serum response factor is biased by Ca2+ influx to promote the vascular endothelial growth factor receptor 2 signaling pathway, resulting in enhanced angiogenesis. After implanted in a rat rotator cuff tear model, L-CSO films strongly enhance vascularization at the enthesis, promoting collagen maturation, increasing bone and fibrocartilage formation, and eventually improving the biomechanical strength. This study reveals the mechanism through which chirality influences angiogenesis in endothelial cells and provides a critical theoretical foundation for the clinical application of chiral biomaterials.

Use of ozone oxidation in combination with deacetylation for improving the structure and gelation properties of konjac glucomannan.

In this study, oxidized deacetylated konjac glucomannans with different degrees of oxidation were prepared by a combination of deacetylation and ozone oxidation. Carboxyl groups were found to be introduced into the modified konjac glucomannan while acetyl groups were removed. The backbone, branched chains, and crystal structure of modified konjac glucomannan were not significantly affected. The whiteness was enhanced to 97-99 % and the thermal degradation temperature was up to 250 °C after modification. The solubility of the modified konjac glucomannan (oxidized for 60 min) was significantly increased to 84.56 % (p < 0.05), while its viscosity and swelling power were notably decreased owing to the changes in molecular weight (from 106 to 104) and functional groups. Rheological analysis showed that oxidized deacetylated konjac glucomannan has the ability to form soft-textured gels and the potential to develop dysphagia foods. Future studies should focus on the gelation mechanisms of oxidized deacetylated konjac glucomannan.

Evaluation of the efficacy and safety of ramucirumab combined with nab-paclitaxel, lobaplatin, and S-1 in neoadjuvant and conversion therapy for advanced gastric cancer: A study protocol of prospective single-center, randomized controlled and open label clinical trial (RNPLS-01).

Objective: Ramucirumab is a VEGFR2 antagonist. The aim of this trial is to evaluate the efficacy and safety of ramucirumab combined with nab-paclitaxel, lobaplatin and S-1 in neoadjuvant and conversion therapy for advanced gastric cancer. Methods: and analysis: This study is a prospective single-center, randomized controlled and open label clinical study, enrolling a total of 140 patients with advanced gastric cancer distributed across two distinct cohorts (Cohort A n = 70; Cohort B n = 70). The central focus of the study lies in evaluating the pathological complete response (pCR) of the cancer post-neoadjuvant or conversion therapy. Secondary endpoints encompass the assessment of the R0 resection rate subsequent to the aforementioned therapies, the occurrence of adverse events (AE), progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the total response rate and its duration, the disease control rate (DCR), and the duration of overall response (DOR). Ethics: Ethics approval has been obtained from the Ethics Committee at the First Affiliated Hospital (Xijing Hospital) of Air force Military Medical University (KY20232220-F-1). Trial registration: This trial has been registered at the ClinicalTrials.gov: NCT06169410 (registration date: December 5, 2023).

Human amniotic mesenchymal stem cells inhibit immune rejection injury from allogeneic mouse heart transplantation: A preliminary study on the microRNA expression.

BACKGROUND: Mesenchymal stem cell therapy is a new treatment for immune rejection in heart transplantation. The aim of this paper is to investigate the effect of human amniotic mesenchymal stem cells (hAMSCs) on alleviating immune rejection of allogeneic heart transplantation in mice and its possible underlying mechanism. METHODS: We injected hAMSCs into cervical ectopic heart transplantation model mice via tail vein to observe the survival time, the pathological changes of donor myocardium, and the fluorescent distribution of hAMSCs after the transplantation. MicroRNAs (miRs) with significantly differential expression were obtained by RNA sequencing and bioinformatic analysis, and a dual luciferase reporter gene assay together with real-time quantitative PCR (qRT-PCR) was performed to verify the relationship between miRs and their targeting genes. RESULTS: The intervention of hAMSCs prolonged the graft survival time and alleviated the pathological damage of the donor heart. The injected hAMSCs were distributed mainly in the liver, spleen, and kidney, only a very small portion in the donor and recipient hearts. In the allogeneic transplantation models, the expression of miR-34b-5p significantly increased after hAMSC treatment. MiR-34b-5p showed a knockdown effect on gene Fc gamma receptor 2B (FCGR2B). CONCLUSIONS: hAMSCs can reduce the immune rejection injury after allogeneic heart transplantation. This effect may be associated with the upregulation of miR-34b-5p expression to knock down its targeting gene FCGR2B.

Application of Dual-Layer Spectral-Detector Computed Tomography Angiography in Identifying Symptomatic Carotid Atherosclerosis: A Prospective Observational Study.

BACKGROUND: Dual-layer spectral-detector dual-energy computed tomography angiography (DLCTA) can distinguish components of carotid plaques. Data on identifying symptomatic carotid plaques in patients using DLCTA are not available. METHODS AND RESULTS: In this prospective observational study, patients with carotid plaques were enrolled and received DLCTA. The attenuation for both polyenergetic image and virtual monoenergetic images (40, 70, 100, and 140 keV), as well as Z-effective value, were recorded in the noncalcified regions of plaques. Logistic regression models were used to assess the association between attenuations of DLCTA and the presence of symptomatic carotid plaques. In total, 100 participants (mean±SD age, 64.37±8.31 years; 82.0% were men) were included, and 36% of the cases were identified with the symptomatic group. DLCTA parameters were different between 2 groups (symptomatic versus asymptomatic: computed tomography [CT] 40 keV, 152.63 [interquartile range (IQR), 70.22-259.78] versus 256.78 [IQR, 150.34-408.13]; CT 70 keV, 81.28 [IQR, 50.13-119.33] versus 108.87 [IQR, 77.01-165.88]; slope40-140 keV, 0.91 [IQR, 0.35-1.87] versus 1.92 [IQR, 0.96-3.00]; Z-effective value, 7.92 [IQR, 7.53-8.46] versus 8.41 [IQR, 7.94-8.92]), whereas no difference was found in conventional polyenergetic images. The risk of symptomatic plaque was lower in the highest tertiles of attenuations in CT 40 keV (adjusted odds ratio [OR], 0.243 [95% CI, 0.078-0.754]), CT 70 keV (adjusted OR, 0.313 [95% CI, 0.104-0.940]), Z-effective values (adjusted OR, 0.138 [95% CI, 0.039-0.490]), and slope40-140 keV (adjusted OR, 0.157 [95% CI, 0.046-0.539]), with all P values and P trends <0.05. The areas under the curve for CT 40 keV, CT 70 keV, slope 40 to 140 keV, and Z-effective values were 0.64, 0.61, 0.64, and 0.63, respectively. CONCLUSIONS: Parameters of DLCTA might help assist in distinguishing symptomatic carotid plaques. Further studies with a larger sample size may address the overlap and improve the diagnostic accuracy.

Risk factors of early disease progression and decreased survival for multiple myeloma patients after upfront autologous stem cell transplantation.

Multiple myeloma (MM) stands as the second most prevalent hematological malignancy, constituting approximately 10% of all hematological malignancies. Current guidelines recommend upfront autologous stem cell transplantation (ASCT) for transplant-eligible MM patients. This study seeks to delineate factors influencing post-ASCT outcomes in MM patients. Our cohort comprised 150 MM patients from Taipei Veterans General Hospital, with progression-free survival (PFS) as the primary endpoint and overall survival (OS) as the secondary endpoint. A Cox proportional hazards model was employed to discern potential predictive factors for survival. ASCT age ≥ 65 (hazard ratio [HR] 1.94, 95% confidence interval [CI] 1.08-3.47) and the presence of extramedullary disease (HR 2.53, 95% CI 1.53-4.19) negatively impacted PFS. Conversely, treatment response ≥ VGPR before ASCT (HR 0.52, 95% CI 0.31-0.87) and total CD34+ cells collected ≥ 4 × 106 cells/kg on the first stem cell harvesting (HR 0.52, 95% CI 0.32-0.87) were positively associated with PFS. For OS, patients with ISS stage III (HR 2.06, 95% CI 1.05-4.04), the presence of extramedullary disease (HR 3.92, 95% CI 2.03-7.58), light chain ratio ≥ 100 before ASCT (HR 7.08, 95% CI 1.45-34.59), post-ASCT cytomegalovirus infection (HR 9.43, 95% CI 3.09-28.84), and a lower conditioning melphalan dose (< 140 mg/m2; HR 2.75, 95% CI 1.23-6.17) experienced shorter OS. In contrast, post-ASCT day + 15 absolute monocyte counts (D15 AMC) > 500/µl (HR 0.36, 95% CI 0.17-0.79) and post-ASCT day + 15 platelet counts (D15 PLT) > 80,000/µl (HR 0.48, 95% CI 0.24-0.94) were correlated with improved OS. Significantly, early PLT and AMC recovery on day + 15 predicting longer OS represents a novel finding not previously reported. Other factors also align with previous studies. Our study provides real-world insights for post-ASCT outcome prediction beyond clinical trials.

Association between Oxidative Balance Score and Severe Headache or Migraine among American Adults A Cross-Section Study.

BACKGROUND: Migraine is implicated in oxidative stress. The oxidative balance score (OBS) assesses the combined impact of diet and lifestyle on oxidative and antioxidant balance in diseases. However, the association between OBS and migraine remains underexplored. OBJECTIVE: We aimed to examine the relationship between OBS and severe headaches or migraines among American adults. METHODS: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, defining severe headaches or migraine via self-reports and calculating OBS from 16 diaries and 4 lifestyle factors. Multivariable weighted logistic regression models were used to explore the OBS-migraine relationship, with stratified analysis for result validation. RESULTS: The study included 6,653 participants (average age 45.6, 52.1% male), and 19.1% reported severe headaches or migraines. There was a significant inverse association between OBS and severe headache or migraine, with an adjusted odds ratio (OR) of 0.97 (95% [confidence interval] CI: 0.96, 0.98, p < 0.001). The highest OBS tertile had an adjusted OR of 0.58 (95% CI: 0.47, 0.73) compared to the lowest. This pattern was consistent across sexes, with an adjusted OR of 0.98 (0.95, 1.00) in males and 0.97 (0.95, 1.00) in females. The adjusted OR for migraine was 0.61 (0.44, 0.87) and 0.54 (0.37, 0.79) in the highest tertile for males and females, respectively. CONCLUSION: The study highlights a significant association between OBS and severe headaches or migraines, suggesting the potential role of oxidative stress in these conditions. The findings emphasize the importance of a balanced, antioxidant-rich diet and lifestyle in managing severe headaches or migraine.

Aging-Related Rotator Cuff Tears: Molecular Mechanisms and Implications for Clinical Management.

Shoulder pain and disabilities are prevalent issues among the elderly population, with rotator cuff tear (RCT) being one of the leading causes. Although surgical treatment has shown some success, high postoperative retear rates remain a great challenge, particularly in elderly patients. Aging-related degeneration of muscle, tendon, tendon-to-bone enthesis, and bone plays a critical role in the development and prognosis of RCT. Studies have demonstrated that aging worsens muscle atrophy and fatty infiltration, alters tendon structure and biomechanical properties, exacerbates enthesis degeneration, and reduces bone density. Although recent researches have contributed to understanding the pathophysiological mechanisms of aging-related RCT, a comprehensive systematic review of this topic is still lacking. Therefore, this article aims to present a review of the pathophysiological changes and their clinical significance, as well as the molecular mechanisms underlying aging-related RCT, with the goal of shedding light on new therapeutic approaches to reduce the occurrence of aging-related RCT and improve postoperative prognosis in elderly patients.

Circular RNAs: Regulators of endothelial cell dysfunction in atherosclerosis.

Endothelial cell (EC) dysfunction is associated with atherosclerosis. Circular RNAs (circRNAs) are covalently closed loops formed by back-splicing, are highly expressed in a tissue-specific or cell-specific manner, and regulate ECs mainly through miRNAs (mircoRNAs) or protein sponges. This review describes the regulatory mechanisms and physiological functions of circRNAs, as well as the differential expression of circRNAs in aberrant ECs. This review focuses on their roles in inflammation, proliferation, migration, angiogenesis, apoptosis, senescence, and autophagy in ECs from the perspective of signaling pathways, such as nuclear factor κB (NF-κB), nucleotide-binding domain, leucine-rich-repeat family, pyrin-domain-containing 3 (NLRP3)/caspase-1, Janus kinase/signal transducer and activator of transcription (JAK/STAT), and phosphoinositide-3 kinase/protein kinase B (PI3K/Akt). Finally, we address the issues and recent advances in circRNAs as well as circRNA-mediated regulation of ECs to improve our understanding of the molecular mechanisms underlying the progression of atherosclerosis and provide a reference for studies on circRNAs that regulate EC dysfunction and thus affect atherosclerosis.

Nanomaterials for small diameter vascular grafts: overview and outlook.

Small-diameter vascular grafts (SDVGs) cannot meet current clinical demands owing to their suboptimal long-term patency rate. Various materials have been employed to address this issue, including nanomaterials (NMs), which have demonstrated exceptional capabilities and promising application potentials. In this review, the utilization of NMs in different forms, including nanoparticles, nanofibers, and nanofilms, in the SDVG field is discussed, and future perspectives for the development of NM-loading SDVGs are highlighted. It is expected that this review will provide helpful information to scholars in the innovative interdiscipline of cardiovascular disease treatment and NM.

SEL1L3 as a link molecular between renal cell carcinoma and atherosclerosis based on bioinformatics analysis and experimental verification.

BACKGROUND: Renal cancer, the most common type of kidney cancer, develops in the renal tubular epithelium. Atherosclerosis of the aorta is the primary cause of atherosclerosis. However, the underlying mechanisms remain unclear. METHODS: The renal clear cell carcinoma RNA sequence profile was obtained from The Cancer Genome Atlas (TCGA) database, and the atherosclerosis datasets GSE28829 and GSE43292 based on GPL570 and GPL6244 was obtained from the Gene Expression Omnibus (GEO) database. The difference and hub genes were identified by the Limma protein-protein interaction (PPI) network in R software. Functional enrichment, survival, and immunoinfiltration analyses were performed. The role of SEL1L3 in the ErbB/PI3K/mTOR signaling pathway, apoptosis, invasion, cell cycle, and inflammation was analyzed using western blotting. RESULTS: 764 DEGs were identified from TCGA Kidney Renal Clear Cell Carcinoma (KIRC) dataset. A total of 344 and 117 DEGs were screened from the GSE14762 and GSE53757 datasets, respectively. Functional enrichment analysis results primarily indicated enrichment in the transporter complex, DNA-binding transcription activator activity, morphogenesis of the embryonic epithelium, stem cell proliferation, adrenal overactivity and so on. Fifteen common DEGs overlapped among the three datasets. The PPI network revealed that SEL1L3 was the core gene. Survival analysis showed that lower SEL1L3 expression levels led to a worse prognosis. Immune cell infiltration analysis showed that SEL1L3 expression was significantly correlated with antibody-drug conjugates (aDC), B cells, eosinophils, interstitial dendritic cells (iDC), macrophages, and more. CONCLUSIONS: SEL1L3 plays an important role in renal clear cell carcinoma and atherosclerosis and may be a potential link between them.

Fe3O4 microplate filled PEI matrix composite with remarkable nonlinear conductive characteristics, dielectric property, and low percolation threshold.

As the presence of a percolating network formed by filler is indispensable for field grading composite, particulate fillers often result in high filler content that can be unfavorable in some aspects. The utilization of fillers with high aspect ratio is an effective way of reducing percolation threshold. In this work, Fe3O4 microplate (FMP) was prepared by a PVP-assisted hydrothermal method and it was adopted to fabricate composite films with different filler content by using polyetherimide (PEI) as the matrix. The composite film exhibited a percolation threshold of approximately 8 phr. The nonlinear coefficient measured 6.28 at a filler content of 10 phr. The nonlinearity in the conductive behavior of the composites was attributed to tunneling effect and Schottky emission. The filling of the FMP into PEI resulted in increase in dielectric constant and the dielectric loss maintained low. This study suggests that the FMP is a promising filler of low-filler-content field grading composite.

Activation of astrocytes in the basal forebrain in mice facilitates isoflurane-induced loss of consciousness and prolongs recovery.

OBJECTIVES: General anesthesia results in a state of unconsciousness that is similar to sleep. In recent years, increasing evidence has reported that astrocytes play a crucial role in regulating sleep. However, whether astrocytes are involved in general anesthesia is unknown. METHODS: In the present study, the designer receptors exclusively activated by designer drugs (DREADDs) approach was utilized to specifically activate astrocytes in the basal forebrain (BF) and observed its effect on isoflurane anesthesia. One the other side, L-α-aminoadipic acid was used to selectively inhibit astrocytes in the BF and investigated its influence on isoflurane-induced hypnotic effect. During the anesthesia experiment, cortical electroencephalography (EEG) signals were recorded as well. RESULTS: The chemogenetic activation group had a significantly shorter isoflurane induction time, longer recovery time, and higher delta power of EEG during anesthesia maintenance and recovery periods than the control group. Inhibition of astrocytes in the BF delayed isoflurane-induced loss of consciousness, promoted recovery, decreased delta power and increased beta and gamma power during maintenance and recovery periods. CONCLUSIONS: The present study suggests that astrocytes in the BF region are involved in isoflurane anesthesia and may be a potential target for regulating the consciousness state of anesthesia.

Development and validation of a prognostic nomogram for gastrointestinal stromal tumors in the postimatinib era: A study based on the SEER database and a Chinese cohort.

BACKGROUND: After the standardization, recording and follow-up of imatinib use that significantly prolongs survival of gastrointestinal stromal tumors (GISTs), a comprehensive reassessment of the prognosis of GISTs is necessary and more conductive to treatment options. METHODS: A total of 2185 GISTs between 2013 and 2016 were obtained from the Surveillance, Epidemiology, and End Results database and comprised our training (n = 1456) and internal validation cohorts (n = 729). The risk factors extracted from univariate and multivariate analyses were used to establish a predictive nomogram. The model was evaluated and tested in the validation cohort internally and in 159 patients with GIST diagnosed between January 2015 and June 2017 in Xijing Hospital externally. RESULTS: The median OS was 49 months (range, 0-83 months) in the training cohort and 51 months (0-83 months) in the validation cohort. The concordance index (C-index) of the nomogram was 0.777 (95% CI, 0.752-0.802) and 0.7787 (0.7785, bootstrap corrected) in training and internal validation cohorts, respectively, and 0.7613 (0.7579, bootstrap corrected) in the external validation cohort. Receiver operating characteristic curves and calibration curves for 1-, 3-, and 5-year overall survival (OS) showed a high degree of discrimination and calibration. The area under the curve showed that the new model performed better than the TNM staging system. In addition, the model could be dynamically visualized on a webpage. CONCLUSION: We developed a comprehensive survival prediction model for assessing the 1-, 3- and 5-year OS of patients with GIST in the postimatinib era. This predictive model outperforms the traditional TNM staging system and sheds light on the improvement of the prognostic prediction and the selection of treatment strategies for GISTs.