Association between muscular tissue desaturation and acute kidney injury in older patients undergoing major abdominal surgery: a prospective cohort study.

PURPOSE: Present study was designed to investigate the association between muscular tissue desaturation and acute kidney injury (AKI) in older patients undergoing major abdominal surgery. METHOD: A total of 253 patients (≥ 65 years old) who underwent abdominal surgery with expected duration ≥ 2 h were enrolled. Muscular tissue oxygen saturation (SmtO2) was monitored at quadriceps and bilateral flanks during surgery. Muscular desaturation was defined as SmtO2 < 90% baseline lasting for > 60 s. The primary outcome was the incidence of AKI within postoperative 7 days. The association between muscular desaturation and AKI was analyzed by multivariable logistic regression model. The secondary outcomes indicated the other complications within postoperative 30 days. RESULTS: Among 236 patients, 44 (18.6%) of them developed AKI. The incidence of muscular desaturation at quadriceps was 28.8% (68/236). Patients with muscular desaturation had higher incidence of AKI than those without desaturation (27.9% [19/68], vs. 14.9% [25/168], P = 0.020). After adjustment of confounders, multivariable analysis showed that muscular desaturation at quadriceps was significantly associated with an increased risk of AKI (OR = 2.84, 95% CI 1.21-6.67, P = 0.016). Muscular desaturations at left and right flank were also associated with an increased risk of AKI (OR = 6.38, 95% CI 1.78-22.89, P = 0.004; OR = 8.90, 95% CI 1.42-45.63; P = 0.019, respectively). Furthermore, patients with muscular desaturation may have a higher risk of pulmonary complications, sepsis and stroke at 30-day follow-up. CONCLUSION: Muscular desaturation was associated with postoperative AKI in older patients undergoing major abdominal surgery which may serve as a predictor of AKI.

A multifunctional cascade enzyme system for enhanced starvation/chemodynamic combination therapy against hypoxic tumors.

Starvation therapy has shown promise as a cancer treatment, but its efficacy is often limited when used alone. In this work, a multifunctional nanoscale cascade enzyme system, named CaCO3@MnO2-NH2@GOx@PVP (CMGP), was fabricated for enhanced starvation/chemodynamic combination cancer therapy. CMGP is composed of CaCO3 nanoparticles wrapped in a MnO2 shell, with glucose oxidase (GOx) adsorbed and modified with polyvinylpyrrolidone (PVP). MnO2 decomposes H2O2 in cancer cells into O2, which enhances the efficiency of GOx-mediated starvation therapy. CaCO3 can be decomposed in the acidic cancer cell environment, causing Ca2+ overload in cancer cells and inhibiting mitochondrial metabolism. This synergizes with GOx to achieve more efficient starvation therapy. Additionally, the H2O2 and gluconic acid produced during glucose consumption by GOx are utilized by MnO2 with catalase-like activity to enhance O2 production and Mn2+ release. This process accelerates glucose consumption, reactive oxygen species (ROS) generation, and CaCO3 decomposition, promoting the Ca2+ release. CMGP can alleviate tumor hypoxia by cycling the enzymatic cascade reaction, which increases enzyme activity and combines with Ca2+ overload to achieve enhanced combined starvation/chemodynamic therapy. In vitro and in vivo studies demonstrate that CMGP has effective anticancer abilities and good biosafety. It represents a new strategy with great potential for combined cancer therapy.

Association of preoperative neutrophil-lymphocyte ratios with the emergence delirium in pediatric patients after tonsillectomy and adenoidectomy: an observational prospective study.

PURPOSE: The study aimed to investigate potential risk factors for emergence delirium (ED) in pediatric patients after tonsillectomy and adenoidectomy (T&A). METHODS: This prospective, single-center observational study enrolled children aged 3-7 years who underwent T&A under general anesthesia. ED was assessed according to DSM-IV or V criteria. Receiver operating characteristic curve analysis was performed to evaluate the predicative and cut-off values of risk factors, including age, preoperative anxiety level, postoperative pain and neutrophil-lymphocyte ratio (NLR) for ED. Univariate and multivariate logistic regression analyses were performed to investigate risk factors for ED. RESULTS: 94 pediatric patients who underwent T&A were enrolled and 19 developed ED (an incidence of 25.3%). Receiver operating characteristic analysis indicated that preoperative NLR was a significant predictor of ED with a cut-off value of 0.8719 and an area under the curve (AUC) of 0.671 (95% confidence interval (CI) 0.546-0.796, P = 0.022). Preoperative NLR (< 0.8719) and postoperative pain were independent risk factors associated with ED (odds ratio: 0.168, 95% CI 0.033-0.858, P = 0.032; odds ratio: 7.298, 95% CI 1.563-34.083, P = 0.011) according to multivariate logistic regression analysis. CONCLUSIONS: Preoperative NLR level and postoperative pain were independent risk factors for ED in pediatric patients undergoing T&A.

Altering patterns of sensorimotor network in patients with different pathological diagnoses and glioma-related epilepsy under the latest glioma classification of the central nervous system.

AIMS: We aimed to clarify the relationship between alterations in functional networks and glioma-related epilepsy (GRE) in patients with different molecular diagnoses. METHODS: We enrolled 160 patients with prefrontal gliomas and different histories of GRE. The patients were grouped based on the latest pathological glioma classification and GRE history. Graph theory analysis was applied to reveal alterations in the sensorimotor networks among various subgroups. Binary logistic regression was used to identify risk factors for preoperative GRE onset. RESULTS: Decreasing shortest path length was found in patients with GRE, regardless of the chromosome 1p/19q status. Nodes located in the premotor and supplementary motor areas showed decreased nodal betweenness centrality and vulnerability in patients with GRE and chromosome 1p/19q intact. Additionally, the node on the primary motor area showed decreased nodal vulnerability but the node on the sensory-related thalamus increased in patients with GRE and chromosome 1p/19q co-deletion. Decreased shortest path length, grade 2, and decreased nodal betweenness centrality of the premotor area were risk factors for GRE. CONCLUSION: Decreased shortest path length was a characteristic alteration in GRE and prefrontal glioma. Alterations in global properties were similar, but nodal properties were different in patients with GRE and different chromosome 1p/19q statuses.

Development of an integrated predictive model for postoperative glioma-related epilepsy using gene-signature and clinical data.

BACKGROUND: This study aimed to develop an integrated model for predicting the occurrence of postoperative seizures in patients with diffuse high-grade gliomas (DHGGs) using clinical and RNA-seq data. METHODS: Patients with DHGGs, who received prophylactic anti-epileptic drugs (AEDs) for three months following surgery, were enrolled into the study. The patients were assigned randomly into training (n = 166) and validation (n = 42) cohorts. Differentially expressed genes (DEGs) were identified based on preoperative glioma-related epilepsy (GRE) history. Least absolute shrinkage and selection operator (LASSO) logistic regression analysis was used to construct a predictive gene-signature for the occurrence of postoperative seizures. The final integrated prediction model was generated using the gene-signature and clinical data. Receiver operating characteristic analysis and calibration curve method were used to evaluate the accuracy of the gene-signature and prediction model using the training and validation cohorts. RESULTS: A seven-gene signature for predicting the occurrence of postoperative seizures was developed using LASSO logistic regression analysis of 623 DEGs. The gene-signature showed satisfactory predictive capacity in the training cohort [area under the curve (AUC) = 0.842] and validation cohort (AUC = 0.751). The final integrated prediction model included age, temporal lobe involvement, preoperative GRE history, and gene-signature-derived risk score. The AUCs of the integrated prediction model were 0.878 and 0.845 for the training and validation cohorts, respectively. CONCLUSION: We developed an integrated prediction model for the occurrence of postoperative seizures in patients with DHGG using clinical and RNA-Seq data. The findings of this study may contribute to the development of personalized management strategies for patients with DHGGs and improve our understanding of the mechanisms underlying GRE in these patients.

Association of homotopic areas in the right hemisphere with language deficits in the short term after tumor resection.

OBJECTIVE: It is important to identify language deficit and recovery in the week following a tumor resection procedure. The homotopic Broca's area and the superior longitudinal fasciculus in the right hemisphere participate in language functional compensation. However, the nodes in these structures, as well as their contributions to language rehabilitation, remain unknown. In this study, the authors investigated the association of homotopic areas in the right hemisphere with language deficit. METHODS: The authors retrospectively reviewed the records of 50 right-handed patients with left hemispheric lower-grade glioma that had been surgically treated between June 2020 and May 2022. The patients were divided into normal and aphasia groups based on their postoperative aphasia quotient (AQ) from the Western Aphasia Battery. Preoperative (within 24 hours before surgery) and postoperative (7 days after tumor resection) diffusion tensor images were used to reveal alterations of structural networks by using graphic theory analysis. The shortest distance between the glioma and the nodes belonging to the language network (SDTN) was quantitatively assessed. Pearson's correlation and causal mediation analyses were used to identify correlations and mediator factors among SDTN, topological properties, and AQs. RESULTS: Postoperative nodal local efficiency of the node dorsal Brodmann area (BA) 44 (A44d; p = 0.0330), nodal clustering coefficient of the nodes A44d (p = 0.0402) and dorsal lateral BA6 (A6dl; p = 0.0097), and nodal degree centrality (p = 0.0058) of the node medial BA7 (A7m) were higher in the normal group than in the aphasia group. SDTN was positively correlated with postoperative AQ (r = 0.457, p = 0.0009) and ΔAQ (r = 0.588, p < 0.0001). The nodal local efficiency of node A44d and the nodal efficiency, nodal betweenness centrality, and degree centrality of node A7m were mediators of SDTN and postoperative AQs. CONCLUSIONS: The decreased ability of nodes A44d, A6dl, and A7m to convey information in the right hemisphere was associated with short-term language deficits after tumor resection. A smaller SDTN induced a worsened postoperative language deficit through a significant decrease in the ability to convey information from these three nodes.

Decreasing distance from tumor to the language network causes language deficit.

Preoperative language deficits are associated with alterations in the language networks of patients with gliomas. This study investigated how gliomas affect language performance by altering the language network. Ninety patients with lower-grade gliomas were included, and their preoperative language performance was evaluated using the Western Aphasia Battery. We also calculated the topological properties based on resting state functional magnetic resonance imaging. All patients were classified according to aphasia quotient (AQ) into the aphasia (AQ < 93.8), mild anomia (AQ > 93.8 and naming section <9.8), and normal groups (AQ > 93.8). The shortest distance from the tumor to the language network (SDTN) was evaluated to identify the effect on language performance induced by the tumor. One-way analysis of variance and post hoc analysis with Sidak correction were used to analyze the differences in topological properties among the three groups. Causal mediation analysis was used to identify indirectly affected mediators. Compared with the mild anomia group, longer shortest path length (p = .0016), lower vulnerability (p = .0331), and weaker nodal efficiencies of three nodes (right caudal Brodmann area [BA] 45, right caudal BA 22, and left BA 41/42, all p < .05) were observed in the aphasia group. The SDTN mediated nodal degree centrality and nodal vulnerability (left rostroventral BA 39), which negatively affected the AQs. Conventional language eloquent and mirrored areas participated in the language network alterations induced by gliomas. The SDTN was a mediator that affected the preoperative language status in patients with gliomas.

Expression changes in ion channel and immunity genes are associated with glioma-related epilepsy in patients with diffuse gliomas.

BACKGROUND: Glioma-related epilepsy (GRE) is a common symptom in patients with diffuse gliomas. However, the underlying mechanisms of GRE remain unclear. The current study aimed to investigate the underlying epileptogenic mechanisms of GRE through RNA sequencing analysis. METHODS: Demographic, RNA sequencing, and follow-up data of 643 patients were reviewed. Patients were divided into test and validation groups (223 and 420 patients, respectively) by different time periods for RNA sequencing. The differentially expressed genes (DEGs) associated with preoperative GRE were identified using R software. Functional enrichment analysis was subsequently performed, and tissue-infiltrating immune cells were also estimated. Weighted correlation network analysis (WGCNA) was conducted to further identify key modules exhibiting the highest correlation with preoperative GRE. Overlapping genes between the DEG set and key gene set identified by WGCNA were selected and verified in the validation cohort. The protein-protein interaction (PPI) network analysis was then constructed to identify hub genes for preoperative GRE. RESULTS: A total of 219 DEGs were identified, among which 112 were upregulated and 107 downregulated in patients with GRE. Functional enrichment analysis revealed that upregulated DEGs were related to ion channel activity, while downregulated genes were related to immunity. Forty-two genes were further selected from overlapping DEGs and the key gene set. Among these genes, 31 genes showed significant differences in the validation cohort. Finally, the PPI network analysis identified six genes, including SCN3B, KCNIP2, KCNJ11, VEGFA, MMP9, and ANXA2, as hub genes for GRE. CONCLUSION: The current study revealed that ion channel activity and immunity dysfunction in diffuse glioma patients contributed to the occurrence of GRE, and SCN3B might be a shared therapeutic target for both diffuse gliomas and GRE. These findings could improve the understanding of the mechanisms of GRE and promote individualized medications for glioma management.

Contralesional Sensorimotor Network Participates in Motor Functional Compensation in Glioma Patients.

Background: Some gliomas in sensorimotor areas induce motor deficits, while some do not. Cortical destruction and reorganization contribute to this phenomenon, but detailed reasons remain unclear. This study investigated the differences of the functional connectivity and topological properties in the contralesional sensorimotor network (cSMN) between patients with motor deficit and those with normal motor function. Methods: We retrospectively reviewed 65 patients (32 men) between 2017 and 2020. The patients were divided into four groups based on tumor laterality and preoperative motor status (deficit or non-deficit). Thirty-three healthy controls (18 men) were enrolled after matching for sex, age, and educational status. Graph theoretical measurement was applied to reveal alterations of the topological properties of the cSMN by analyzing resting-state functional MRI. Results: The results for patients with different hemispheric gliomas were similar. The clustering coefficient, local efficiency, transitivity, and vulnerability of the cSMN significantly increased in the non-deficit group and decreased in the deficit group compared to the healthy group (p < 0.05). Moreover, the nodes of the motor-related thalamus showed a significantly increased nodal efficiency and nodal local efficiency in the non-deficit group and decreased in the deficit group compared with the healthy group (p < 0.05). Conclusions: We posited the existence of two stages of alterations of the preoperative motor status. In the compensatory stage, the cSMN sacrificed stability to acquire high efficiency and to compensate for impaired motor function. With the glioma growing and the motor function being totally damaged, the cSMN returned to a stable state and maintained healthy hemispheric motor function, but with low efficiency.

Decreasing Shortest Path Length of the Sensorimotor Network Induces Frontal Glioma-Related Epilepsy.

BACKGROUND: Glioma-related epilepsy (GRE) is a common symptom in patients with prefrontal glioma. Epilepsy onset is associated with functional network alterations. This study investigated alterations of functional networks in patients with prefrontal glioma and GRE. METHODS: Sixty-five patients with prefrontal lobe gliomas were retrospectively assessed and classified into GRE and non-GRE groups. Additionally, 25 healthy participants were enrolled after matching for general information. Imaging data were acquired within 72 h in pre-operation. The sensorimotor network was used to delineate alterations in functional connectivity (FC) and topological properties. One-way analysis of variance and post-hoc analysis with Bonferroni correction were used to calculate differences of FC and topological properties. RESULTS: All significant alterations were solely found in the sensorimotor network. Irrespective of gliomas located in the left or right prefrontal lobes, the edge between medial Brodmann area 6 and caudal ventrolateral Brodmann area 6 decreased FC in the GRE group compared with the non-GRE group [p < 0.0001 (left glioma), p = 0.0002 (right glioma)]. Moreover, the shortest path length decrease was found in the GRE group compared with the non-GRE group [p = 0.0292 (left glioma) and p = 0.0129 (right glioma)]. CONCLUSIONS: The reduction of FC between the medial BA 6 (supplementary motor area) and caudal ventrolateral BA 6 in the ipsilateral hemisphere and the shortening of the path length of the sensorimotor network were characteristics alterations in patients with GRE onset. These findings fill in the gap which is the relationship between GRE onset and the alterations of functional networks in patients with prefrontal glioma. SIGNIFICANCE STATEMENT: Glioma related epilepsy is the most common symptom of prefrontal glioma. It is important to identify characteristic alterations in functional networks in patients with GRE. We found that all significant alterations occurred in the sensorimotor network. Moreover, a decreased FC in the supplementary motor area and a shortening of the path's length are additional characteristics of glioma-related epilepsy. We believe that our findings indicate new directions of research that will contribute to future investigations of glioma-related epilepsy onset.

Targeted Regulation of the Electronic States of Nickel Toward the Efficient Electrosynthesis of Benzonitrile and Hydrogen Production.

Highly efficient electro-oxidation of benzylamine to generate value-added chemicals coupled with the hydrogen evolution reaction (HER) is crucial but challenging. Herein, targeted regulation of the electronic states of Ni sites was realized via simple yet precise nitridation engineering. Benefiting from the insertion of N atoms into the Ni lattice, the Ni3N electrode exhibits superior activity, selectivity, and stability for the benzylamine oxidation reaction (BOR). Especially, under the industrially relevant current (∼250 mA), the Ni3N catalyst remains ∼95% selective for benzonitrile production, reaching 1.43 mmol h-1 cm-2. Experimental and theoretical findings reveal that the formation of Ni-N bonds upshifts the Ni d-band center and optimizes the electrophilic properties of Ni sites, which contributes to the adsorption and dehydrogenations process of benzylamine. Furthermore, due to the work function difference between Ni and Ni3N, a strong mutual interaction occurs at the heterogeneous interface for Ni-Ni3N, which endows it with the appropriate H* adsorption energy and thus excellent HER performance. Impressively, the integrated solar-energy-driven BOR coupled with the HER electrolyzer affords 10 mA cm-2 at an ultralow voltage of 1.4 V and exhibits a promising practical application (ηsolar-to-hydrogen = 13.8%). This work offers a new perspective for the bifunctional design of nitrides in the field of electrosynthesis.

Downregulation of ceramide synthase 1 promotes oral cancer through endoplasmic reticulum stress.

C18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma. However, the function of ceramide synthase 1, a key enzyme in C18 ceramide synthesis, in oral squamous cell carcinoma is still unclear. The aim of our study was to investigate the relationship between ceramide synthase 1 and oral cancer. In this study, we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell lines. In a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide, ceramide synthase 1 knockout was associated with the severity of oral malignant transformation. Immunohistochemical studies showed significant upregulation of PCNA, MMP2, MMP9, and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area. In addition, ceramide synthase 1 knockdown promoted cell proliferation, migration, and invasion in vitro. Overexpression of CERS1 obtained the opposite effect. Ceramide synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA upregulation. Activating transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional upregulation. In addition, mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin resistance. Taken together, our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance.

Disturbance of myocardial metabolism participates in autoantibodies against ß1 -adrenoceptor-induced cardiac dysfunction.

Cardiac dysfunction is involved in disorders of energy metabolism. High-titre autoantibodies against the ß1 -adrenoceptor (ß1 -AAs) have been reported to exist in patients with cardiac dysfunction; however, the mechanism by which ß1 -AAs affect cardiac function is unknown. This study aimed to determine whether ß1 -AAs disturb myocardium energy metabolism and cause cardiac dysfunction. ß1 -AA monoclonal antibodies (ß1 -AAmAbs) were successfully pre-synthesized by hybridoma clones and used in all experiments. ß1 -AAmAbs impaired cardiac function and induced a myocardial metabolic disturbance, as evidenced by decreased left ventricular ejection fraction and fractional shortening. In addition, ß1 -AAmAbs decreased the adenosine triphosphate level and increased cardiac energy consumption (rate-pressure product). We further showed that the effects of ß1 -AAmAbs on heart tissue might involve the mitochondria and metabolic pathways via the ß1 -adrenoceptor based on an immunoprecipitation and mass spectrometry. Additionally, we found that ß1 -AAmAbs impaired myocardial mitochondrial structure, decreased the membrane potential, and induced insufficient mitophagy. In conclusion, ß1 -AAmAb-induced cardiac dysfunction is partly due to a disturbance in myocardial energy metabolism.

The Construction of Primary Screening Model and Discriminant Model for Chronic Obstructive Pulmonary Disease in Northeast China.

Objective: The diagnosis of chronic obstructive pulmonary disease (COPD) is challenging, especially in the primary institution which lacks spirometer. To reduce the rate of COPD missed diagnoses in Northeast China, which has a higher prevalence of COPD, this study aimed to establish efficient primary screening and discriminant models of COPD in this region. Patients and Methods: Subjects from Northeast China were enrolled from December 2017 to April 2019 from The First Hospital of China Medical University. Pulmonary function tests and questionnaire were given to all participants. Using illness or no illness as the goal for screening models and disease severity as the goal for discriminant models, multivariate linear regression, logical regression, linear discriminant analysis, K-nearest neighbor, decision tree and support vector machine were constructed through R language and Python software. After comparing effectiveness among them, the most optimal primary screening and discriminant models were established. Results: Enrolled were 232 COPD patients (124 GOLD I-II and 108 GOLD III-IV) and 218 normal controls. Eight primary screening models were established. The optimal model was Y = -1.2562-0.3891X4 (education level) + 1.7996X5 (dyspnea) + 0.5102X6 (cooking fuel grade) + 1.498X7 (smoking index) + 0.8077X9 (family history)-0.5552X11 (BMI) + 0.538X13 (cough with sputum) + 2.0328X14 (wheezing) + 1.3378X16 (farmers) + 0.8187X17 (mother's smoking exposure history during pregnancy)-0.389X18 (kitchen ventilation) + 0.6888X19 (childhood heating). Six discriminant models were established. The optimal model was decision tree (the optimal variables: dyspnea (x5), cooking fuel grade (x6), second-hand smoking index (x8), BMI (x11), cough (x12), cough with sputum (x13), wheezing (x14), farmer (x16), kitchen ventilation (x18), and childhood heating (x19)). The code was established to combine the discriminant model with computer technology. Conclusion: Many factors were related to COPD in Northeast China. Stepwise logistic regression and decision tree were the optimal screening and discriminant models for COPD in this region.