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Background: The combination of left atrial appendage closure (LAAC) and catheter ablation (CA) in a single procedure is a safe and effective form of treatment for atrial fibrillation (AF). However, several findings have argued that LAAC might increase the risk of AF recurring. Therefore, this study investigated the impact of insufficient ablation on AF recurrence after the hybrid procedures of CA and LAAC. Methods: We reviewed 107 consecutive patients with AF who received the CA and LAAC hybrid procedures (combined group). In the case-control study, another 107 patients who underwent only CA (ablation group) were successfully matched using propensity score matching. After correcting the insufficient ablation, 107 consecutive patients were enrolled prospectively. During the follow-up period, postprocedural 24-hour monitor recordings and a portable electrocardiogram (ECG) monitoring device were used to detect AF recurrence. Transesophageal echocardiography was used to evaluate LAAC. Results: The combined group showed an increase in the risk of AF recurrence after 539.2 ± 304.4 days of follow-up (29.9% vs. 15.9%, p < 0.05). Interestingly, the duration of the procedure was not significantly prolonged when LAAC was added after CA in the combined group, while there was a higher number of ablating attempts, duration of ablation, and additional ablation in the ablation group for both radiofrequency and cryoballoon ablation. After correcting for the insufficient ablation, the corrected group showed a significant decrease in AF recurrence after 420.4 ± 204.8 days of follow-up. Conclusions: Insufficient ablation is common when combining CA and LAAC and may lead to the recurrence of atrial fibrillation. It should be corrected intentionally by sufficient ablation of the pulmonary vein antrum and additional ablation. Clinical Trial Registration: The prospective study is a sub-study of our CAGEDAF study that has already been registered (ChiCTR2000039746).
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Semiconducting carbon nanotubes (CNTs) are considered as the most promising channel material to construct ultrascaled field-effect transistors, but the perfect sp2 CâC structure makes stable doping difficult, which limits the electrical designability of CNT devices. Here, an inner doping method is developed by filling CNTs with 1D halide perovskites to form a coaxial heterojunction, which enables a stable n-type field-effect transistor for constructing complementary metal-oxide-semiconductor electronics. Most importantly, a quasi-broken-gap (BG) heterojunction tunnel field-effect transistor (TFET) is first demonstrated based on an individual partial-filling CsPbBr3/CNT and exhibits a subthreshold swing of 35 mV dec-1 with a high on-state current of up to 4.9 µA per tube and an on/off current ratio of up to 105 at room temperature. The quasi-BG TFET based on the CsPbBr3/CNT coaxial heterojunction paves the way for constructing high-performance and ultralow power consumption integrated circuits.
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BACKGROUND: Postoperative delirium is a common complication in older patients, with poor long-term outcomes. This study aimed to investigate risk factors and develop a predictive model for postoperative delirium in older patients after major abdominal surgery. METHODS: This study retrospectively recruited 7577 patients aged ≥ 65 years who underwent major abdominal surgery between January 2014 and December 2018 in a single hospital in Beijing, China. Patients were divided into a training cohort (n = 5303) and a validation cohort (n = 2224) for univariate and multivariate logistic regression analyses and to build a nomogram. Data were collected for 43 perioperative variables, including demographics, medical history, preoperative laboratory results, imaging, and anesthesia information. RESULTS: Age, chronic obstructive pulmonary disease, white blood cell count, glucose, total protein, creatinine, emergency surgery, and anesthesia time were associated with postoperative delirium in multivariate analysis. We developed a nomogram based on the above 8 variables. The nomogram achieved areas under the curve of 0.731 and 0.735 for the training and validation cohorts, respectively. The discriminatory ability of the nomogram was further assessed by dividing the cases into three risk groups (low-risk, nomogram score < 175; medium-risk, nomogram score 175~199; high-risk, nomogram score > 199; P < 0.001). Decision curve analysis revealed that the nomogram provided a good net clinical benefit. CONCLUSIONS: We developed a nomogram that could predict postoperative delirium with high accuracy and stability in older patients after major abdominal surgery.
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Background: Cerebral blood flow and vascular structures serve as the fundamental components of brain metabolism and circulation. Acupuncture, an alternative and complementary medical approach, has demonstrated efficacy in treating cerebral ischemic stroke (CIS). Nevertheless, the mechanisms underlying the impact of acupuncture on vascular smooth muscle cell (VSMC) function remain uncertain. The objective of this systematic review and meta-analysis is to assess the alterations in VSMC function following acupuncture stimulation in CIS models. Methods: The databases PubMed, Web of Science, SCOPUS, and EMBASE were queried until November 2022 using a predetermined search strategy. The FORMAT BY SYRCLE guidelines were adhered to, and the risk of bias of the included studies was evaluated using the Risk of Bias tool developed by the Systematic Review Centre for Laboratory Animal Experimentation. The random-effects model was employed to estimate the standardized mean difference (SMD). Results: Eighteen articles are included in this review. Acupuncture showed significant positive effects on the region cerebral blood flow (SMD=8.15 [95% CI, 4.52 to 11.78]) and neurological deficiency (SMD=-3.75 [95% CI, -5.54 to -1.97]). Descriptive analysis showed a probable mechanism of acupuncture stimulation in CIS rats related to VSMC function. Limitations and publication bias were presented in the studies. Conclusion: In this systematic review and meta-analysis, our findings indicate that acupuncture stimulation has the potential to improve regional cerebral blood flow and alleviate neurological deficits, possibly by regulating VSMC function. However, it is important to exercise caution when interpreting these results due to the limitations of animal experimental design and methodological quality.
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Semiconductor devices at the nanoscale with low-dimensional materials as channels exhibit quantum transport characteristics, thereby their electrical simulation relies on the self-consistent solution of the Schrödinger-Poisson equations. While the non-equilibrium Green's function (NEGF) method is widely used for solving this quantum many-body problem, its high computational cost and convergence challenges with the Poisson equation significantly limit its applicability. In this study, we investigate the stability of the NEGF method coupled with various forms of the Poisson equation, encompassing linear, analytical nonlinear, and numerical nonlinear forms Our focus lies on simulating carbon nanotube field-effect transistors (CNTFETs) under two distinct doping scenarios: electrostatic doping and ion implantation doping. The numerical experiments reveal that nonlinear formulas outperform linear counterpart. The numerical one demonstrates superior stability, particularly evident under high bias and ion implantation doping conditions. Additionally, we investigate different approaches for presolving potential, leveraging solutions from the Laplace equation and a piecewise guessing method tailored to each doping mode. These methods effectively reduce the number of iterations required for convergence.
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BACKGROUND: In agricultural production, fungal diseases significantly impact the yield and quality of cotton (Gossypium spp.) with Verticillium wilt posing a particularly severe threat. RESULTS: This study is focused on investigating the effectiveness of endophytic microbial communities present in the seeds of disease-resistant cotton genotypes in the control of cotton Verticillium wilt. The technique of 16S ribosomal RNA (16S rRNA) amplicon sequencing identified a significant enrichment of the Bacillus genus in the resistant genotype Xinluzao 78, which differed from the endophytic bacterial community structure in the susceptible genotype Xinluzao 63. Specific enriched strains were isolated and screened from the seeds of Xinluzao 78 to further explore the biological functions of seed endophytes. A synthetic microbial community (SynCom) was constructed using the broken-rod model, and seeds of the susceptible genotype Xinluzao 63 in this community that had been soaked with the SynCom were found to significantly control the occurrence of Verticillium wilt and regulate the growth of cotton plants. Antibiotic screening techniques were used to preliminarily identify the colonization of strains in the community. These techniques revealed that the strains can colonize plant tissues and occupy ecological niches in cotton tissues through a priority effect, which prevents infection by pathogens. CONCLUSION: This study highlights the key role of seed endophytes in driving plant disease defense and provides a theoretical basis for the future application of SynComs in agriculture.
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Microbiota , Verticillium , Verticillium/fisiología , Gossypium/genética , Gossypium/microbiología , ARN Ribosómico 16S/genética , Bacterias/genética , Semillas/genética , Enfermedades de las Plantas/microbiología , Resistencia a la Enfermedad/genéticaRESUMEN
CRISPR-based screens have discovered novel functional genes involving in diverse tumor biology and elucidated the mechanisms of the cancer pathological states. Recently, with its randomness and unbiasedness, CRISPR screens have been used to discover effector genes with previously unknown roles for AML. Those novel targets are related to AML survival resembled cellular pathways mediating epigenetics, synthetic lethality, transcriptional regulation, mitochondrial and energy metabolism. Other genes that are crucial for pharmaceutical targeting and drug resistance have also been identified. With the rapid development of novel strategies, such as barcodes and multiplexed mosaic CRISPR perturbation, more potential therapeutic targets and mechanism in AML will be discovered. In this review, we present an overview of recent progresses in the development of CRISPR-based screens for the mechanism and target identification in AML and discuss the challenges and possible solutions in this rapidly growing field.
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AIMS: Left atrial appendage electrical isolation (LAAEI) has demonstrated a significant enhancement in the success rate of atrial fibrillation (AF) ablation. Nevertheless, concerns persist about the safety of LAAEI, particularly regarding alterations in left atrial appendage (LAA) flow velocity and the potential risks of thrombus. This study aimed to assess the efficacy and safety of LAAEI, investigating changes in LAA flow velocity in canines. METHODS AND RESULTS: The study comprised a total of 10 canines. The LAAEI procedure used by a 23â mm cryoballoon of the second generation was conducted at least 180â s. Intracardiac ultrasonography (ICE) was employed to quantify the velocity flow of the LAA both prior to and following LAAEI. Following a 3-month period, subsequent evaluations were performed to assess the LAA velocity flow and the potential reconnection. Histopathological examination was conducted. Left atrial appendage electrical isolation was effectively accomplished in all canines, resulting in a 100% acute success rate (10/10). The flow velocity in the LAA showed a notable reduction during LAAEI as compared with the values before the ablation procedure (53.12 ± 5.89 vs. 42.01 ± 9.22â cm/s, P = 0.007). After the follow-up, reconnection was observed in four canines, leading to a success rate of LAAEI of 60% (6/10). The flow velocity in the LAA was consistently lower (53.12 ± 5.89 vs. 44.33 ± 10.49â cm/s, P = 0.006), and no blood clot development was observed. The histopathological study indicated that there was consistent and complete injury to the LAA, affecting all layers of its wall. The injured tissue was subsequently replaced by fibrous tissue. CONCLUSION: The feasibility of using cryoballoon ablation for LAAEI was confirmed in canines, leading to a significant reduction of LAA flow velocity after ablation. Some restoration of LAA flow velocity after ablation may be linked to the passive movement of the LAA and potential reconnecting. However, this conclusion is limited to animal study; more clinical data are needed to further illustrate the safety and accessibility of LAAEI in humans.
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Apéndice Atrial , Fibrilación Atrial , Criocirugía , Perros , Animales , Apéndice Atrial/cirugía , Criocirugía/métodos , Criocirugía/efectos adversos , Criocirugía/instrumentación , Fibrilación Atrial/cirugía , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/diagnóstico , Diseño de Equipo , Velocidad del Flujo Sanguíneo , Resultado del Tratamiento , MasculinoRESUMEN
Despite the high therapeutic response achieved with B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapy in relapsed and refractory multiple myeloma (R/R MM), primary resistance and relapse exist with single-target immunotherapy. Here, we design bispecific BC19 CAR T cells targeting BCMA/CD19 and evaluate antimyeloma activity in vitro and in vivo. Preclinical results indicate that BC19 CAR specifically recognize target antigens, and BC19 CAR T cells mediate selective killing of BCMA or CD19-positive cancer cells. BC19 CAR T cells also exhibit potent antigen-specific anti-tumor activity in xenograft mouse models. We conduct an open-label, single-arm, phase I/II study of BC19 CAR T cells in 50 patients with R/R MM (ChiCTR2000033567). The primary endpoint was safety. BC19 CAR T cells are well tolerated with grade 3 or higher cytokine release syndrome in 8% of patients and grade 1 neurotoxic events in 4% of patients, which meet the pre-specified primary endpoint. Secondary endpoints include overall response rate (92%), median progression-free survival (19.7 months), median overall survival (19.7 months) and median duration of response (not reached). Our study demonstrates that bispecific BC19 CAR T cells are feasible, safe and effective in treating patients with R/R MM.
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Mieloma Múltiple , Receptores Quiméricos de Antígenos , Animales , Humanos , Ratones , Antígenos CD19 , Antígeno de Maduración de Linfocitos B , Inmunoterapia Adoptiva/métodos , Mieloma Múltiple/terapia , Recurrencia Local de NeoplasiaRESUMEN
Few studies have reported the associations of granulocyte colony-stimulating factor (G-CSF) with cytokine release syndrome (CRS), neurotoxic events (NEs) and efficacy after chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We present a retrospective study of 67 patients with R/R B-ALL who received anti-CD19 CAR T-cell therapy, 41 (61.2%) patients received G-CSF (G-CSF group), while 26 (38.8%) did not (non-G-CSF group). Patients had similar duration of grade 3-4 neutropenia between the two groups. The incidences of CRS and NEs were higher in G-CSF group, while no differences in severity were found. Further stratified analysis showed that the incidence and severity of CRS were not associated with G-CSF administration in patients with low bone marrow (BM) tumor burden. None of the patients with low BM tumor burden developed NEs. However, there was a significant increase in the incidence of CRS after G-CSF administration in patients with high BM tumor burden. The duration of CRS in patients who used G-CSF was longer. There were no significant differences in response rates at 1 and 3 months after CAR T-cell infusion, as well as overall survival (OS) between the two groups. In conclusion, our results showed that G-CSF administration was not associated with the incidence or severity of CRS in patients with low BM tumor burden, but the incidence of CRS was higher after G-CSF administration in patients with high BM tumor burden. The duration of CRS was prolonged in G-CSF group. G-CSF administration was not associated with the efficacy of CAR T-cell therapy.
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Síndromes de Neurotoxicidad , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores Quiméricos de Antígenos , Humanos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Inmunoterapia Adoptiva/efectos adversos , Estudios Retrospectivos , Síndrome de Liberación de Citoquinas , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Tratamiento Basado en Trasplante de Células y TejidosRESUMEN
BACKGROUND: Tocilizumab is commonly used for the management of chimeric antigen receptor (CAR) T-cell therapy-associated cytokine release syndrome (CRS). However, it remains unknown whether tocilizumab or its dosage affects the efficacy and safety of CAR T-cell therapy. The objective of this multicenter retrospective study was to explore the impact of tocilizumab on CAR T-cell therapy. METHODS: In total, 93 patients with B-cell acute lymphoblastic leukemia (B-ALL) receiving humanized anti-CD19 CAR T cells were recruited from May 2016 to November 2022. Forty-five patients received tocilizumab (tocilizumab group), whereas 48 patients did not (nontocilizumab group). Thirteen patients received >1 dose of tocilizumab. The primary end point was the effect of tocilizumab on the efficacy and safety of CAR T cells. Additionally, proliferation, killing, and cytokine assays of CAR T cells were performed in vitro in the presence of tocilizumab. RESULTS: The median age of the patients was 33 years, with 47 males and 46 females. Patients in the tocilizumab group showed similar complete response (CR) rate, overall survival (OS), and event-free survival (EFS) compared with the nontocilizumab group. Compared with patients who received ≤1 dose of tocilizumab, receiving >1 dose of tocilizumab did not affect their CR rate, OS, or EFS. In the tocilizumab group, all patients experienced CRS and 26.7% experienced immune effector cell-associated neurotoxicity syndrome (ICANS). In the nontocilizumab group, 64.6% of patients experienced CRS and 8.3% experienced ICANS. Up to 75% of ICANS and 87.5% of grade ≥3 ICANS occurred in the tocilizumab group. In vitro, tocilizumab did not impair the proliferation and killing effects of CAR T cells. CONCLUSIONS: Tocilizumab does not affect the efficacy of CAR T cells but may increase the likelihood of ICANS.
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Anticuerpos Monoclonales Humanizados , Antígenos CD19 , Síndrome de Liberación de Citoquinas , Inmunoterapia Adoptiva , Receptores Quiméricos de Antígenos , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Masculino , Femenino , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Adulto , Antígenos CD19/inmunología , Estudios Retrospectivos , Persona de Mediana Edad , Adolescente , Adulto Joven , Síndrome de Liberación de Citoquinas/etiología , Receptores Quiméricos de Antígenos/inmunología , Niño , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológicoRESUMEN
BACKGROUND AIMS: Chimeric antigen receptor-T (CAR-T) cells have exhibited remarkable efficacy in treating refractory or relapsed multiple myeloma (R/R MM). Although obesity has a favorable value in enhancing the response to immunotherapy, less is known about its predictive value regarding the efficacy and prognosis of CAR-T cell immunotherapy. METHODS: We conducted a retrospective study of 111 patients with R/R MM who underwent CAR-T cell treatment. Using the body mass index (BMI) classification, the patients were divided into a normal-weight group (73/111) and an overweight group (38/111). We investigated the effect of BMI on CAR-T cell therapy outcomes in patients with R/R MM. RESULTS: The objective remission rates after CAR-T cell infusion were 94.7% and 89.0% in the overweight and normal-weight groups, respectively. The duration of response and overall survival were not significant difference between BMI groups. Compared to normal-weight patients, overweight patients had an improved median progression-free survival. There was no significant difference in cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome between the subgroups. In terms of hematological toxicity, the erythrocyte, hemoglobin, platelet, leukocyte and neutrophil recovery was accelerated in the overweight group. Fewer patients in the overweight group displayed moderate percent CD4 and CD4/CD8 ratios compared to the normal-weight group. Furthermore, the percent CD4 ratios were positively correlated with the levels of cytokines [interleukin-2 (IL-2) (day 14), interferon gamma (IFN-γ) (day 7) and tumor necrosis factor alpha (TNF-α) (days 14 and 21)] after cells infusion. On the other hand, BMI was positively associated with the levels of IFN-γ (day 7) and TNF-α (days 14 and 21) after CAR-T cells infusion. CONCLUSIONS: Overall, this study highlights the potential beneficial effect of a higher BMI on CAR-T cell therapy outcomes.
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Índice de Masa Corporal , Inmunoterapia Adoptiva , Mieloma Múltiple , Humanos , Mieloma Múltiple/terapia , Mieloma Múltiple/inmunología , Mieloma Múltiple/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Inmunoterapia Adoptiva/métodos , Anciano , Estudios Retrospectivos , Adulto , Receptores Quiméricos de Antígenos/inmunología , Resultado del Tratamiento , PronósticoAsunto(s)
Antígenos CD19 , Miastenia Gravis , Receptores Colinérgicos , Humanos , Miastenia Gravis/inmunología , Miastenia Gravis/terapia , Miastenia Gravis/tratamiento farmacológico , Receptores Colinérgicos/inmunología , Antígenos CD19/inmunología , Antígeno de Maduración de Linfocitos B/inmunología , Inmunoterapia Adoptiva/métodos , Femenino , Autoanticuerpos/sangre , Masculino , Persona de Mediana Edad , AdultoRESUMEN
The current CAR-T cell therapy products have been hampered in their druggability due to the personalized preparation required, unclear pharmacokinetic characteristics, and unpredictable adverse reactions. Enabling standardized manufacturing and having clear efficacy and pharmacokinetic characteristics are prerequisites for ensuring the effective practicality of CAR-T cell therapy drugs. This review provides a broad overview of the different approaches for controlling behaviors of CAR-T cells in vivo. The utilization of genetically modified vectors enables in vivo production of CAR-T cells, thereby abbreviating or skipping the lengthy in vitro expansion process. By equipping CAR-T cells with intricately designed control elements, using molecule switches or small-molecule inhibitors, the control of CAR-T cell activity can be achieved. Moreover, the on-off control of CAR-T cell activity would yield potential gains in phenotypic remodeling. These methods provide beneficial references for the future development of safe, controllable, convenient, and suitable for standardized production of CAR-T cell therapy products.
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Inmunoterapia Adoptiva , Neoplasias , Receptores Quiméricos de Antígenos , Humanos , Inmunoterapia Adoptiva/métodos , Animales , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Linfocitos T/inmunologíaRESUMEN
Developing low-power FETs holds significant importance in advancing logic circuits, especially as the feature size of MOSFETs approaches sub-10 nanometers. However, this has been restricted by the thermionic limitation of SS, which is limited to 60 mV per decade at room temperature. Herein, we proposed a strategy that utilizes 2D semiconductors with an isolated-band feature as channels to realize sub-thermionic SS in MOSFETs. Through high-throughput calculations, we established a guiding principle that combines the atomic structure and orbital interaction to identify their sub-thermionic transport potential. This guides us to screen 192 candidates from the 2D material database comprising 1608 systems. Additionally, the physical relationship between the sub-thermionic transport performances and electronic structures is further revealed, which enables us to predict 15 systems with promising device performances for low-power applications with supply voltage below 0.5 V. This work opens a new way for the low-power electronics based on 2D materials and would inspire extensive interests in the experimental exploration of intrinsic steep-slope MOSFETs.
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JOURNAL/nrgr/04.03/01300535-202419110-00030/figure1/v/2024-03-08T184507Z/r/image-tiff The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord injury. Ruxolitinib, a JAK-STAT inhibitor, exhibits effectiveness in autoimmune diseases, arthritis, and managing inflammatory cytokine storms. Although studies have shown the neuroprotective potential of ruxolitinib in neurological trauma, the exact mechanism by which it enhances functional recovery after spinal cord injury, particularly its effect on astrocytes, remains unclear. To address this gap, we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord injury. Transcriptome sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury, restored EAAT2 expression, reduced glutamate levels, and alleviated excitatory toxicity. Furthermore, ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1ß, interleukin-6, and tumor necrosis factor-α. Additionally, in glutamate-induced excitotoxicity astrocytes, ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3, thereby reducing glutamate-induced neurotoxicity, calcium influx, oxidative stress, and cell apoptosis, and increasing the complexity of dendritic branching. Collectively, these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes, reduces neurotoxicity, and effectively alleviates inflammatory and immune responses after spinal cord injury, thereby promoting functional recovery after spinal cord injury.
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The present research focused on identifying necroptosis-related differentially expressed genes (NRDEGs) in spinal cord injury (SCI) to highlight potential therapeutic and prognostic target genes in clinical SCI. Three SCI-related datasets were downloaded, including GSE151371, GSE5296 and GSE47681. MSigDB and KEGG datasets were searched for necroptosis-related genes (NRGs). Differentially expressed genes (DEGs) and NRGs were intersected to obtain NRDEGs. The MCC algorithm was employed to select the first 10 genes as hub genes. A protein-protein interaction (PPI) network related to NRDEGs was developed utilizing STRING. Several databases were searched to predict interactions between hub genes and miRNAs, transcription factors, potential drugs, and small molecules. Immunoassays were performed to identify DEGs using CIBERSORTx. Additionally, qRT-PCR was carried out to verify NRDEGs in an animal model of SCI. Combined analysis of all datasets identified 15 co-expressed DEGs and NRGs. GO and KEGG pathway analyses highlighted DEGs mostly belonged to pathways associated with necroptosis and apoptosis. Hub gene expression analysis showed high accuracy in SCI diagnosis was associated with the expression of CHMP7 and FADD. A total of two hub genes, i.e. CHMP7, FADD, were considered potential targets for SCI therapy.
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MicroARNs , Traumatismos de la Médula Espinal , Animales , Necroptosis/genética , Biología Computacional , Perfilación de la Expresión Génica , MicroARNs/genética , Traumatismos de la Médula Espinal/diagnóstico , Traumatismos de la Médula Espinal/genéticaRESUMEN
PURPOSE: Previous studies have suggested a potential association between gut microbiota and neurological and psychiatric disorders. However, the causal relationship between gut microbiota and cognitive performance remains uncertain. METHODS: A two-sample Mendelian randomization (MR) study used SNPs linked to gut microbiota (n = 18,340) and cognitive performance (n = 257,841) from recent GWAS data. Inverse-variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode were employed. Heterogeneity was assessed via Cochran's Q test for IVW. Results were shown with funnel plots. Outliers were detected through leave-one-out method. MR-PRESSO and MR-Egger intercept tests were conducted to address horizontal pleiotropy influence. LIMITATIONS: Limited to European populations, generic level, and potential confounding factors. RESULTS: IVW analysis revealed detrimental effects on cognitive perfmance associated with the presence of genus Blautia (P = 0.013, 0.966[0.940-0.993]), Catenibacterium (P = 0.035, 0.977[0.956-0.998]), Oxalobacter (P = 0.043, 0.979[0.960-0.999]). Roseburia (P < 0.001, 0.935[0.906-0.965]), in particular, remained strongly negatively associated with cognitive performance after Bonferroni correction. Conversely, families including Bacteroidaceae (P = 0.043, 1.040[1.001-1.081]), Rikenellaceae (P = 0.047, 1.026[1.000-1.053]), along with genera including Paraprevotella (P = 0.044, 1.020[1.001-1.039]), Ruminococcus torques group (P = 0.016, 1.062[1.011-1.115]), Bacteroides (P = 0.043, 1.040[1.001-1.081]), Dialister (P = 0.027, 1.039[1.004-1.074]), Paraprevotella (P = 0.044, 1.020[1.001-1.039]) and Ruminococcaceae UCG003 (P = 0.007, 1.040[1.011-1.070]) had a protective effect on cognitive performance. CONCLUSIONS: Our results suggest that interventions targeting specific gut microbiota may offer a promising avenue for improving cognitive function in diseased populations. The practical application of these findings has the potential to enhance cognitive performance, thereby improving overall quality of life.
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Microbioma Gastrointestinal , Trastornos Mentales , Humanos , Microbioma Gastrointestinal/genética , Análisis de la Aleatorización Mendeliana , Calidad de Vida , CogniciónRESUMEN
BACKGROUND: Sleep disturbances in the peri-operative period have been associated with adverse outcomes, including postoperative delirium (POD). However, research on sleep quality during the immediate postoperative period is limited. OBJECTIVES: This study aimed to investigate the association between sleep quality on the night of the operative day assessed using the Sleep Quality Numeric Rating Scale (SQ-NRS), and the incidence of POD in a large cohort of surgical patients. DESIGN: A prospective cohort study. SETTING: A tertiary hospital in China. PATIENTS: This study enrolled patients aged 65âyears or older undergoing elective surgery under general anaesthesia. The participants were categorised into the sleep disturbance and no sleep disturbance groups according to their operative night SQ-NRS. MAIN OUTCOME MEASURES: The primary outcome was delirium incidence, whereas the secondary outcomes included acute kidney injury, stroke, pulmonary infection, cardiovascular complications and all-cause mortality within 1 year postoperatively. RESULTS: In total, 3072 patients were included in the analysis of this study. Among them, 791 (25.72%) experienced sleep disturbances on the night of operative day. Patients in the sleep disturbance group had a significantly higher risk of developing POD (adjusted OR 1.43, 95% CI 1.11 to 1.82, P â=â0.005). Subgroup analysis revealed that age 65-75âyears; male sex; ASA III and IV; haemoglobin more than 12âgâl -1 ; intra-operative hypotension; surgical duration more than 120âmin; and education 9âyears or less were significantly associated with POD. No interaction was observed between the subgroups. No significant differences were observed in the secondary outcomes, such as acute kidney injury, stroke, pulmonary infection, cardiovascular complications and all-cause mortality within 1 year postoperatively. CONCLUSIONS: The poor subjective sleep quality on the night of operative day was independently associated with increased POD risk, especially in certain subpopulations. Optimising peri-operative sleep may reduce POD. Further research should investigate potential mechanisms and causal relationships. TRIAL REGISTRY: chictr.org.cn: ChiCTR1900028545.
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Lesión Renal Aguda , Infecciones Cardiovasculares , Delirio , Delirio del Despertar , Accidente Cerebrovascular , Anciano , Humanos , Masculino , Infecciones Cardiovasculares/complicaciones , Delirio/diagnóstico , Delirio/epidemiología , Delirio/etiología , Delirio del Despertar/diagnóstico , Delirio del Despertar/epidemiología , Delirio del Despertar/etiología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Factores de Riesgo , Calidad del Sueño , FemeninoRESUMEN
BACKGROUND: Peripheral T-cell lymphomas (PTCL) are an aggressive group of mature T-cell neoplasms, often associated with poor outcomes, in part, due to frequent relapsed/refractory disease. The objective of this study was to assess the prognostic impact of disease progression within 24 months (POD24) on overall survival (OS) for patients diagnosed with PTCL. METHODS: A retrospective analysis was conducted on a cohort of patients with newly diagnosed PTCL who underwent chemotherapy at the Affiliated Hospital of Xuzhou Medical University between January 2010 and September 2021. Prognostic assessment was limited to patients who were evaluable for POD24. RESULTS: Records were reviewed for 106 patients with PTCL, of whom 66 patients experienced POD24 (referred to as the POD24 group) and 40 patients did not experience POD24 (referred to as the no POD24 group). Significant differences were observed between the POD24 group and the no POD24 group in regard to clinical stage, Eastern Cooperative Oncology Group (ECOG) performance status (PS), International Prognostic Index (IPI) score, lactate dehydrogenase (LDH) levels, ß2-microglobulin (ß2-MG) levels, prealbumin and albumin levels. Patients in the POD24 group had a significant shorter median OS compared to the no POD24 group (11.9 months vs not reached, respectively; P < 0.001). Non response (NR) to treatment and POD24 were identified as independent negative prognostic factors for survival in patients with PTCL. CONCLUSION: POD24 is a prognostic factor associated with unfavorable outcomes in patients with PTCL and can be used to identify high-risk patients and guide treatment decisions.