Investigating amplitude of low-frequency fluctuation and possible links with cognitive impairment in childhood and adolescence onset schizophrenia: a correlation study.

Background: Cognitive impairment (CI) is a distinctive characteristic of schizophrenia, with evidence suggesting that childhood and adolescence onset schizophrenia (CAOS), representing severe but rare forms of schizophrenia, share continuity with adult-onset conditions. While relationships between altered brain function and CI have been identified in adults with schizophrenia, the extent of brain function abnormalities in CAOS remains largely unknown. In this study, we employed resting-state functional magnetic resonance imaging (rs-fMRI) to investigate functional alterations in brain areas among patients with CAOS. To assess CI across multiple cognitive domains, we utilized the Stroop Color and Word Tests (SCWT) and MATRICS Consensus Cognitive Battery (MCCB) tests. Our objective was to explore the associations between functional CI and the amplitude of low-frequency fluctuation (ALFF) levels in these patients. Methods: We enrolled 50 patients diagnosed with CAOS and 33 healthy controls (HCs) matched for sex and age. Cognitive functions were assessed using the MCCB and SCWT methods. Rs-fMRI data were acquired using gradient-echo echo-planar imaging sequences. Voxel-based ALFF group maps were compared through two-sample t-tests in SPM8. Subsequently, correlation analyses were conducted to identify associations between ALFF levels and cognitive scores. Results: In comparison to HCs, patients exhibited significantly increased ALFF levels in the right fusiform gyrus, frontal lobe, and caudate, as well as the left frontal lobe and caudate. Conversely, reduced ALFF levels were observed in the temporal and left medial frontal lobes. Significant differences were identified between HCs and patients in terms of total cognitive scores, ALFF levels, and domain scores. All test scores were decreased, except for TMA. Correlation analyses between ALFF levels and cognitive functions in patients with CAOS differed from those in HCs. Pearson correlation analyses revealed positive associations between Brief Visuospatial Memory Test - Revised (BVMT-R) scores and ALFF levels in the left medial frontal gyrus. Digital Span Test (DST) scores were negatively correlated with ALFF levels in the right caudate, and Maze Test values were negatively correlated with levels in the left caudate. However, Pearson correlation analyses in HCs indicated that color and Hopkins Verbal Learning Test (HVLT-R) scores positively correlated with ALFF levels in the left frontal lobe, while color-word and symbol coding scores negatively correlated with levels in the right caudate. Conclusions: Altered ALFF levels in the brain may be linked to cognitive impairment (CI) in patients with CAOS. We highlighted the pathophysiology of schizophrenia and provide imaging evidence that could potentially aid in the diagnosis of CAOS.

Cerebral Small Vessel Disease Is Associated with Motor, Cognitive, and Emotional Dysfunction in Multiple System Atrophy.

BACKGROUND: Cerebral small vessel disease (CSVD) has not been systematically studied in patients with multiple system atrophy (MSA). OBJECTIVE: We sought to explore whether MSA patients suffer from a heavier CSVD burden relative to healthy individuals and whether CSVD has a relationship with motor, cognitive, and emotional dysfunction in patients with MSA. METHODS: This study consecutively recruited 190 MSA patients and 190 matched healthy controls whose overall CSVD burden and single CSVD imaging markers (including white matter hyperintensity (WMH), microbleeds, lacunes, and enlarged perivascular spaces (EPVS)) were measured. Of the MSA patients, 118 completed multi-dimensional outcome assessments. Spearman's correlations and multivariable linear regressions were performed. RESULTS: We observed a greater burden of overall CSVD, WMH, and EPVS in MSA patients compared with controls, but not for microbleeds and lacunes. Motor dysfunction and cognitive impairment were significantly worse in subjects with severe CSVD than those with none-to-mild CSVD. In patients with MSA, the severity of CSVD burden was positively associated with motor impairments as measured by the Unified Multiple System Atrophy Rating Scale-II (ß= 2.430, p = 0.039) and Scale for the Assessment and Rating of Ataxia (ß= 1.882, p = 0.015). Of CSVD imaging markers, different associations with MSA outcomes were displayed. WMH was associated with motor, cognitive, and emotional deficits, while the EPVS in the centrum semiovale, basal ganglia, and hippocampus regions was correlated only with motor severity, anxiety, and cognition, respectively. Similar findings were noted in MSA-cerebellar and MSA-parkinsonian patients. CONCLUSIONS: Concomitant CSVD may be correlated with worse multi-dimensional dysfunction in patients with MSA.

Programmable Birefringent Patterns from Modulating the Localized Orientation of Cellulose Nanocrystals.

Birefringence has been attracting broad attention due to its strong potential for applications in biomedicine and optics, such as biomedical diagnosis, colorimetric sensing, retardant, and polarization encoding. However, engineering architectures with precisely controllable birefringence remains a challenge due to the lack of effective modulation of the localized orientation. Here, by taking advantage of the inherently one-dimensional (1D) anisotropic structure of cellulose nanocrystals (CNCs), we demonstrate an approach to tune the alignment of CNCs with a well-controllable orientation at localized preciseness, which is in contrast to the previously reported unidirectional/radical orientation of CNC-based birefringent structures. The localized modulation of CNC orientation is facilitated by directing the 1D nanocrystals to align along the template periphery and the migrated three-phase contact line during the evaporation. The resultant CNC films exhibit birefringent extinction patterns under polarized light, in which versatile pattern designs can be obtained by employing templates with different shapes and template arrays with varied layouts. Due to the locally modulated orientation of CNCs, the films indicate "kaleidoscope-like" dynamically transformable designs of the birefringent patterns depending on the polarized angle, which has barely been observed previously. Furthermore, an N-nary encoding system for abundant information storage is demonstrated based on the sunlight-transparent CNC films, but with visible extinction patterns under polarized light, which is promising for encryptions, anticounterfeiting, and imaging, enriching the attractive research area of bio-based photonics.

Isoalantolactone Enhances the Antitumor Activity of Doxorubicin by Inducing Reactive Oxygen Species and DNA Damage.

Colon cancer is one of the most common cancer in the world. Doxorubicin (DOX) is a classical anti-tumor drug which widely used in treatment of cancers, however, high toxicity limited its further clinical application. Thus, it is urgent to find new drugs with low toxicity and high efficiency to treat colon cancer. Isoalantolactone (IATL), an isomeric sesquiterpene lactone isolated from the plant of inula helenium, has been reported to have anti-cancer activity against a variety of cancer cells. However, the function of IATL in colon cancer remains unclear. Here, we demonstrated that IATL inhibited colon cancer cell growth by increasing cellular reactive oxygen species (ROS) production. Further study showed that ROS accumulation contributed to DNA damage and JNK signaling pathway activation. In addition, we found that IATL markedly enhanced DOX-induced cell cytotoxicity in colon cancer cells. IATL in combination with DOX significantly increased the ROS production, induced DNA damage and activated JNK signaling pathway. Taken together, our data suggested that combined treatment with IATL and DOX may serve as a potential therapeutics for colon cancer.

Calcium channel blocker and risk of postoperation lymphatic-related complications among gynecologic malignances.

Purpose: This study was performed to assess the association of calcium channel blockers (CCB) and other potential factors with postoperative lymphatic-related morbidity in patients with cervical cancer and endometrial carcinoma. Methods: Patients diagnosed with cervical cancer or endometrial carcinoma with pelvic lymphadenectomy between January 2017 and January 2022 were enrolled. Postoperative lymphatic-related morbidity was evaluated by calculating the lymph cyst occurrence within 3 months after surgery and the duration of pelvic drainage. Univariate analyses evaluating the risk factors for lymphatic-related morbidity were performed. Results: Of a total of 251 patients, 52 patients were diagnosed with lymphatic cysts by B-ultrasound or computed tomography, and the duration of drainage from 110 patients exceeded the average number of days. Univariable analysis revealed that hypertension, CCB, and lymph node metastasis were independent predictors of postoperative complications. Conclusions: This study demonstrated that CCB may be a factor associated with the incidence of postoperation lymph cysts, and CCB usage prolongs the duration of pelvic drainage.

Marangoni Flow Manipulated Concentric Assembly of Cellulose Nanocrystals.

Tunable assembly of cellulose nanocrystals (CNCs) is important for a variety of emerging applications in optics, sensing, and security. Most exploited assembly and optical property of CNCs are cholesteric assembly and corresponding circular dichroism. However, it still remains challenge to obtain homogenous and high-resolution cholesteric assembly. Distinct assembly and optical property of CNCs are highly demanded for advanced photonic materials with novel functions. Herein, a facile and programmable approach for assembling CNCs into a novel concentric alignment using capillary flow and Marangoni effect, which is in strike contrast to conventional cholesteric assembly, is demonstrated. The concentric assembly, as quantitatively evidenced by polarized synchrotron radiation Fourier transform infrared imaging, demonstrates Maltese cross optical pattern with good uniformity and high resolution. Furthermore, this Maltese cross can be readily regulated to "on/off" states by temperature. By combining with 3D inkjet technology, a functional binary system composed of "on"/"off" CNCs optical patterns with high spatial resolution, fast printing speed, good repeatability, and precisely controllable optical property is established for information encryption and decryption. This concentric assembly of CNCs and corresponding tunable optical property emerge as a promising candidate for information security, anticounterfeiting technology, and advanced optics.

Prediction of premature all-cause mortality in patients receiving peritoneal dialysis using modified artificial neural networks.

Premature all-cause mortality is high in patients receiving peritoneal dialysis (PD). The accurate and early prediction of mortality is critical and difficult. Three prediction models, the logistic regression (LR) model, artificial neural network (ANN) classic model and a new structured ANN model (ANN mixed model), were constructed and evaluated using a receiver operating characteristic (ROC) curve analysis. The permutation feature importance was used to interpret the important features in the ANN models. Eight hundred fifty-nine patients were enrolled in the study. The LR model performed slightly better than the other two ANN models on the test dataset; however, in the total dataset, the ANN models fit much better. The ANN mixed model showed the best prediction performance, with area under the ROC curves (AUROCs) of 0.8 and 0.79 for the 6-month and 12-month datasets. Our study showed that age, diastolic blood pressure (DBP), and low-density lipoprotein cholesterol (LDL-c) levels were common risk factors for premature mortality in patients receiving PD. Our ANN mixed model had incomparable advantages in fitting the overall data characteristics, and age is a steady risk factor for premature mortality in patients undergoing PD. Otherwise, DBP and LDL-c levels should receive more attention for all-cause mortality during follow-up.

Compensatory combination of mTOR and TrxR inhibitors to cause oxidative stress and regression of tumors.

Background: Cancer is a leading cause of death worldwide. Extensive research over decades has led to the development of therapies that inhibit oncogenic signaling pathways. The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in the development of many cancers. Several mTOR inhibitors are approved for the treatment of cancers. However, the anticancer efficacies of mTOR inhibitor monotherapy are still limited. Methods: Western blot was used to detect the expression of indicated molecules. Thioredoxin reductase (TrxR) activity in cells was determined by the endpoint insulin reduction assay. Immunofluorescence staining was used to analyze precise location and expression of target proteins. Nude mice were used for xenograft tumor models. Results: We identified a synergistic lethal interaction of mTOR and TrxR inhibitors and elucidated the underlying molecular mechanisms of this synergism. We demonstrated that mTOR and TrxR inhibitors cooperated to induce cell death by triggering oxidative stress, which led to activation of autophagy, endoplasmic reticulum (ER) stress and c-Jun N-terminal Kinase (JNK) signaling pathway in cancer cells. Remarkably, we found that auranofin (AF) combined with everolimus significantly suppressed tumor growth in HCT116 and SGC-7901 xenograft models with no significant signs of toxicity. Conclusion: Our findings identify a promising therapeutic combination for cancer and has important implications for developing mTOR inhibitor-based combination treatments.

Isodeoxyelephantopin Inactivates Thioredoxin Reductase 1 and Activates ROS-Mediated JNK Signaling Pathway to Exacerbate Cisplatin Effectiveness in Human Colon Cancer Cells.

Colon cancer is one of the leading causes of cancer-related death in the world. The development of new drugs and therapeutic strategies for patients with colon cancer are urgently needed. Isodeoxyelephantopin (ESI), a sesquiterpene lactone isolated from the medicinal plant Elephantopus scaber L., has been reported to exert antitumor effects on several cancer cells. However, the molecular mechanisms underlying the action of ESI is still elusive. In the present study, we found that ESI potently suppressed cell proliferation in human colon cancer cells. Furthermore, our results showed that ESI treatment markedly increased cellular reactive oxygen species (ROS) levels by inhibiting thioredoxin reductase 1 (TrxR1) activity, which leads to activation of the JNK signaling pathway and eventually cell death in HCT116 and RKO cells. Importantly, we found that ESI markedly enhanced cisplatin-induced cytotoxicity in HCT116 and RKO cells. Combination of ESI and cisplatin significantly increased the production of ROS, resulting in activation of the JNK signaling pathway in HCT116 and RKO cells. In vivo, we found that ESI combined with cisplatin significantly suppressed tumor growth in HCT116 xenograft models. Together, our study provide a preclinical proof-of-concept for ESI as a potential strategy for colon cancer treatment.

Effects of parathyroid hormone and vitamin D supplementation on stroke among patients receiving peritoneal dialysis.

BACKGROUND: Continuous ambulatory peritoneal dialysis (CAPD) patients have a high incidence of stroke and commonly have increased parathyroid hormone levels and vitamin D insufficiency. We seek to investigate the incidence of stroke and the role of parathyroid hormone and vitamin D supplementation in stroke risk among CAPD patients. METHODS: This study employed a retrospective design. We enrolled a Chinese cohort of 980 CAPD patients who were routinely followed in our department. The demographic and clinical data were recorded at the time of initial CAPD and during follow-up. The included patients were separated into non-stroke and stroke groups. The effects of parathyroid hormone and vitamin D supplementation on stroke in CAPD patients was evaluated. The primary endpoint is defined as the first occurrence of stroke, and composite endpoint events are defined as death or switch to hemodialysis during follow-up. RESULTS: A total of 757 eligible CAPD patients with a mean follow-up time of 54.7 (standard deviation, 33) months were included in the study. The median incidence of stroke among our CAPD patients was 18.9 (interquartile range, 15.7-22.1) per 1000 person-years. A significant nonlinear correlation between baseline iPTH and hazard of stroke (p-value of linear association = 0.2 and nonlinear association = 0.002) was observed in our univariate Cox regression analysis, and low baseline iPTH levels (≤150 pg/ml) were associated with an increased cumulative hazard of stroke. Multivariate Cox regression analysis indicated a significant interaction effect between age and iPTH after adjusting for other confounders. Vitamin D supplementation during follow-up was a predictive factor for stroke in our cohort. CONCLUSIONS: CAPD patients suffered a high risk of stroke, and lower iPTH levels were significantly correlated with an increased risk of stroke. Nevertheless, vitamin D supplementation may reduce the risk of stroke in these patients.

Curcuminoid WZ26, a TrxR1 inhibitor, effectively inhibits colon cancer cell growth and enhances cisplatin-induced cell death through the induction of ROS.

Colon cancer is one of the leading causes of cancer-related deaths. Chemotherapy has improved survival in patients with colon cancer, but has a narrow therapeutic window due to its toxicity. Therefore, novel therapies for colon cancer are urgently needed. We previously developed a curcumin analog WZ26 as an anti-cancer agent in pre-clinical evaluation. In the present study, we further explored the mechanism and target of WZ26 in colon cancer cells. Our results show that WZ26 targets thioredoxin reductase 1 (TrxR1) and increases cellular reactive oxygen species (ROS) levels, which results in the activation of JNK signaling pathway in human colon cancer cells. Furthermore, we found that WZ26 significantly enhances cisplatin-induced cell growth inhibition in colon cancer cells. WZ26 combined with cisplatin markedly increases the accumulation of ROS, and thereby induces DNA damage and activation of JNK signaling pathway. Pretreatment with antioxidant N-acetyl-l-cysteine (NAC) significantly abrogates the combined treatment-induced ROS generation, DNA damage and cell death. In addition, the activation of JNK signaling pathway prompted by WZ26 and cisplatin was also reversed by NAC pretreatment. In vivo, WZ26 combined with cisplatin significantly inhibits tumor growth in a colon cancer xenograft model. Remarkably, WZ26 attenuates the body weight loss evoked by cisplatin treatment. This study discloses a previously unrecognized mechanism underlying the biological activity of WZ26, and reveals that WZ26 and cisplatin combinational treatment might potentially become a more effective regimen in colon cancer therapy.

Amplitude of low-frequency fluctuations in childhood-onset schizophrenia with or without obsessive-compulsive symptoms: a resting-state functional magnetic resonance imaging study.

INTRODUCTION: Childhood-onset schizophrenia with obsessive-compulsive symptoms (COSO) and without obsessive-compulsive symptoms (COS) share considerable overlap in clinical features and genetic risk factors. However, the extent of brain functional abnormalities in COSO and COS is poorly understood. MATERIAL AND METHODS: A total of 51 first-episode childhood schizophrenic patients and 30 healthy age- and sex-matched controls were recruited. We used the Yale-Brown Obsessive Compulsive Scale to divide patients into COSO (n = 21) and COS (n = 30) groups. Resting-state functional magnetic resonance imaging images were obtained using a gradient-echo echo-planar imaging sequence. Voxel-based analysis of amplitude of low-frequency fluctuation (ALFF) maps between the two groups was performed. RESULTS: The COS group showed significantly increased ALFF in the right caudate body, middle temporal gyrus and inferior parietal lobule (p < 0.05), while showing decreased ALFF in the left cerebellum posterior lobe (p < 0.05). The COSO group showed significantly increased ALFF in the left and right frontal lobe, cerebellum posterior lobe and precuneus (p < 0.05). When comparing the two groups, COSO showed significantly higher ALFF in the left cerebellum posterior lobe, frontal lobe, supramarginal gyrus, precuneus, right inferior frontal gyrus and medial frontal gyrus (p < 0.05). Interestingly, significantly lower ALFF was found in the right fusiform gyrus, corpus callosum and inferior parietal lobule in the group of patients with obsessive-compulsive symptoms (p < 0.05). CONCLUSIONS: Our findings increase the understanding of the pathophysiology of schizophrenia and may provide imaging evidence for early diagnosis of COSO or COS.

Effects of sleep disorders and sedative-hypnotic medications on health-related quality of life in dialysis patients.

PURPOSE: Sleep disorders are very common among dialysis patients, leading patients to frequently take sedative-hypnotic medications; however, the effects of sleep disorders and the use of such drugs on health-related quality of life (HRQOL) have rarely been investigated. METHODS: The Pittsburgh Sleep Quality Index and Short Form-12 were used to assess sleep quality and patient health situations, respectively. Logistic regression was employed to identify factors associated with deterioration of the mental component summary (MCS) score and the physical component summary (PCS) score. RESULTS: A total of 461 patients undergoing dialysis were recruited. The prevalence of sleep disorders was 67.0%. Among the study population, 30.4% of patients took sedative-hypnotic medications to improve their sleep quality. Both the PCS (81.25 vs. 71.88, p < 0.001) and MCS scores (78.63 vs. 74.63, p < 0.001), which indicate HRQOL, were decreased among patients with sleep disorders compared with good sleepers. However, neither the PCS nor MCS scores showed any significant difference between patients with sleep disorders who used sedative-hypnotic medications and those who did not. CONCLUSION: Sleep disorders were closely associated with deterioration of both mental HRQOL and physical HRQOL. Sedative-hypnotic medication use did not affect HRQOL among patients with sleep disorders undergoing dialysis.

Characteristics and clinical significance of recurrent laryngeal nerve lymph node metastasis in esophageal squamous cell carcinoma.

PURPOSE: The recurrent laryngeal nerve lymph nodes (RLN LNs) are among the most common metastatic sites in esophageal cancer, and the dissection of these lymph nodes (LNs) is considered beneficial. The purpose of this study was to evaluate the characteristics of RLN LN metastases from esophageal squamous cell carcinoma, and the effects of these metastases on the prognosis of patients. In addition, we aimed to determine the reasonable range of dissection of regional LNs. METHODS: The clinical data from 348 patients who underwent resection for esophageal carcinoma were retrospectively analyzed. RESULTS: Recurrent laryngeal nerve palsy occurred in 37.6% of the patients. In a subgroup of patients with lower esophageal tumors, cervical LN metastases were significantly more common in patients with positive rather than negative RLN LNs. The primary tumor site, tumor differentiation, and tumor invasion depth were factors that significantly influenced RLN LN metastasis. Multivariate analysis revealed that RLN LN metastasis was a significant factor associated with overall survival (OS) and disease-free survival (DFS) (p<0.001). CONCLUSION: Metastasis to RLN LNs is a reliable indicator of cervical LN metastasis in middle/lower thoracic esophageal cancer. RLN LN metastasis may act as a prognostic indicator for patients with esophageal squamous cell carcinoma.

A microrna screen to identify regulators of peritoneal fibrosis in a rat model of peritoneal dialysis.

BACKGROUND: Peritoneal fibrosis is a common complication in patients treated with long-term peritoneal dialysis. The aim of this study was to identify the microRNAs (miRNAs) involved in regulation of peritoneal fibrosis in a rat model of peritoneal dialysis. METHODS: Twenty-four Sprague-Dawley (SD) rats were randomly allocated into three groups: (i) Control group (Cg, n = 8); (ii) Saline group (Sg, n = 8): daily intraperitoneal injection with 0.9% normal saline; (iii) Hypertonic dialysate group (HDg, n = 8): daily intraperitoneal injection with 4.25% peritoneal dialysis solution. Rats were sacrificed after four weeks for histological evaluation of peritoneal membrane and the expression of α-SMA and COL-1. A miRNA screen was performed using microarray analysis to identify differentially expressed miRNAs, which were then validated by real-time PCR. RESULTS: Compared with the control and the saline groups, hypertonic dialysate group showed impaired peritoneal function accompanied by a spectrum of morphological changes including thicker peritoneal membrane, higher collagen deposition, infiltration of mononuclear cells and neovascularization in the peritoneum. Increased mRNA and protein levels of α-SMA and COL-1 were observed in hypertonic dialysate group, indicating the progression of peritoneal fibrosis. The miRNA screen identified 8 significantly down-regulated miRNAs (miR-31, miR-93, miR-100, miR-152, miR-497, miR-192, miR-194 and miR-200b) and one highly up-regulated miRNA (miR-122) in the hypertonic dialysate group. The results were confirmed by real-time PCR. CONCLUSIONS: Altered miRNA expression in peritoneum was found in the rat model of peritoneal fibrosis, indicating that these miRNAs may be associated with pathogenesis of peritoneal fibrosis.