Themis: advancing precision oncology through comprehensive molecular subtyping and optimization.

Recent advances in tumor molecular subtyping have revolutionized precision oncology, offering novel avenues for patient-specific treatment strategies. However, a comprehensive and independent comparison of these subtyping methodologies remains unexplored. This study introduces 'Themis' (Tumor HEterogeneity analysis on Molecular subtypIng System), an evaluation platform that encapsulates a few representative tumor molecular subtyping methods, including Stemness, Anoikis, Metabolism, and pathway-based classifications, utilizing 38 test datasets curated from The Cancer Genome Atlas (TCGA) and significant studies. Our self-designed quantitative analysis uncovers the relative strengths, limitations, and applicability of each method in different clinical contexts. Crucially, Themis serves as a vital tool in identifying the most appropriate subtyping methods for specific clinical scenarios. It also guides fine-tuning existing subtyping methods to achieve more accurate phenotype-associated results. To demonstrate the practical utility, we apply Themis to a breast cancer dataset, showcasing its efficacy in selecting the most suitable subtyping methods for personalized medicine in various clinical scenarios. This study bridges a crucial gap in cancer research and lays a foundation for future advancements in individualized cancer therapy and patient management.

The control patterns of affective processing and cognitive reappraisal: insights from brain controllability analysis.

Perceiving and modulating emotions is vital for cognitive function and is often impaired in neuropsychiatric conditions. Current tools for evaluating emotional dysregulation suffer from subjectivity and lack of precision, especially when it comes to understanding emotion from a regulatory or control-based perspective. To address these limitations, this study leverages an advanced methodology known as functional brain controllability analysis. We simultaneously recorded electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data from 17 healthy subjects engaged in emotion processing and regulation tasks. We then employed a novel EEG/fMRI integration technique to reconstruct cortical activity in a high spatiotemporal resolution manner. Subsequently, we conducted functional brain controllability analysis to explore the neural network control patterns underlying different emotion conditions. Our findings demonstrated that the dorsolateral and ventrolateral prefrontal cortex exhibited increased controllability during the processing and regulation of negative emotions compared to processing of neutral emotion. Besides, the anterior cingulate cortex was notably more active in managing negative emotion than in either controlling neutral emotion or regulating negative emotion. Finally, the posterior parietal cortex emerged as a central network controller for the regulation of negative emotion. This study offers valuable insights into the cortical control mechanisms that support emotion perception and regulation.

CD19/CD20 dual-targeted chimeric antigen receptor-engineered natural killer cells exhibit improved cytotoxicity against acute lymphoblastic leukemia.

BACKGROUND: Chimeric antigen receptor natural killer (CAR-NK) cells represent a promising advancement in CAR cell therapy, addressing limitations observed in CAR-T cell therapy. However, our prior study revealed challenges in CAR-NK cells targeting CD19 antigens, as they failed to eliminate CD19+ Raji cells in NSG tumor-bearing mice, noting down-regulation or loss of CD19 antigen expression in some Raji cells. In response, this study aims to enhance CD19 CAR-NK cell efficacy and mitigate the risk of tumor recurrence due to target antigen escape by developing CD19 and CD20 (CD19/CD20) dual-targeted CAR-NK cells. METHODS: Initially, mRNA encoding anti-CD19 CARs (FMC63 scFv-CD8α-4-1BB-CD3ζ) and anti-CD20 CARs (LEU16 scFv-CD8α-4-1BB-CD3ζ) was constructed via in vitro transcription. Subsequently, CD19/CD20 dual-targeted CAR-NK cells were generated through simultaneous electrotransfection of CD19/CD20 CAR mRNA into umbilical cord blood-derived NK cells (UCB-NK). RESULTS: Following co-electroporation, the percentage of dual-CAR expression on NK cells was 86.4% ± 1.83%, as determined by flow cytometry. CAR expression was detectable at 8 h post-electric transfer, peaked at 24 h, and remained detectable at 96 h. CD19/CD20 dual-targeted CAR-NK cells exhibited increased specific cytotoxicity against acute lymphoblastic leukemia (ALL) cell lines (BALL-1: CD19+CD20+, REH: CD19+CD20-, Jurkat: CD19-CD20-) compared to UCB-NK, CD19 CAR-NK, and CD20 CAR-NK cells. Moreover, CD19/CD20 dual-targeted CAR-NK cells released elevated levels of perforin, IFN-γ, and IL-15. Multiple activation markers such as CD69 and cytotoxic substances were highly expressed. CONCLUSIONS: The creation of CD19/CD20 dual-targeted CAR-NK cells addressed the risk of tumor escape due to antigen heterogeneity in ALL, offering efficient and safe 'off-the-shelf' cell products. These cells demonstrate efficacy in targeting CD20 and/or CD19 antigens in ALL, laying an experimental foundation for their application in ALL treatment.

Evaluation of standard breast ultrasonography by adding two-dimensional and three-dimensional shear wave elastography: a prospective, multicenter trial.

OBJECTIVE: To reduce the number of biopsies performed on benign breast lesions categorized as BI-RADS 4-5, we investigated the diagnostic performance of combined two-dimensional and three-dimensional shear wave elastography (2D + 3D SWE) with standard breast ultrasonography (US) for the BI-RADS assessment of breast lesions. METHODS: A total of 897 breast lesions, categorized as BI-RADS 3-5, were subjected to standard breast US and supplemented by 2D SWE only and 2D + 3D SWE analysis. Based on the malignancy rate of less than 2% for BI-RADS 3, lesions assessed by standard breast US were reclassified with SWE assessment. RESULTS: After standard breast US evaluation, 268 (46.1%) participants underwent benign biopsies in BI-RADS 4-5 lesions. By using separated cutoffs for upstaging BI-RADS 3 at 120 kPa and downstaging BI-RADS 4a at 90 kPa in 2D + 3D SWE reclassification, 123 (21.2%) participants underwent benign biopsy, resulting in a 54.1% reduction (123 versus 268). CONCLUSION: Combining 2D + 3D SWE with standard breast US for reclassification of BI-RADS lesions may achieve a reduction in benign biopsies in BI-RADS 4-5 lesions without sacrificing sensitivity unacceptably. CLINICAL RELEVANCE STATEMENT: Combining 2D + 3D SWE with US effectively reduces benign biopsies in breast lesions with categories 4-5, potentially improving diagnostic accuracy of BI-RADS assessment for patients with breast lesions. TRIAL REGISTRATION: ChiCTR1900026556 KEY POINTS: • Reduce benign biopsy is necessary in breast lesions with BI-RADS 4-5 category. • A reduction of 54.1% on benign biopsies in BI-RADS 4-5 lesions was achieved using 2D + 3D SWE reclassification. • Adding 2D + 3D SWE to standard breast US improved the diagnostic performance of BI-RADS assessment on breast lesions: specificity increased from 54 to 79%, and PPV increased from 54 to 71%, with slight loss in sensitivity (97.2% versus 98.7%) and NPV (98.1% versus 98.7%).

Improvement of neurogenic urinary dysfunctions in female rats treated with an injection of botulinum toxin A at the epicenter of the spinal cord injured site.

OBJECTIVE: To assess the effect of an injection of botulinum toxin A (BoNT/A) at the epicenter of the spinal cord injury (SCI) site on the recovery of lower urinary tract function in female rats with thoracic SCI. MATERIALS AND METHODS: Twenty-four female Wistar rats with Sham (laminectomy at T8/T9 level) or SCI (at T8/T9; 30 g compression for 5 s) were assigned into Sham-SS (injected with 5 µL of saline solution), Sham-BoNT/A (injected with 15 pg/rat, equivalent to 7.5 Units/kg of BoNT/A in 5 µL volume), SCI-SS (injured and injected with saline), SCI-BoNT/A (injured and injected with BoNT/A), N = 6 per group. Weekly evaluation of stereotyped micturition behavior, hind-limb nociception, and locomotor activity was performed 1 week before and during 6 weeks after surgery. Subsequently, all groups underwent simultaneous electromyography of the external urethral sphincter (EUS-EMG) and cystometric (CMG) studies. RESULTS: A compression SCI at the T8/T9 thoracic level significantly impairs sensory and locomotive functions, as well as stereotyped micturition behavior. However, these impairments were improved by BoNT/A injection after SCI. Neither injections of saline solution nor BoNT/A had an appreciable effect on the same parameters evaluated in the Sham groups. The combined EUS-EMG and CMG evaluations revealed important improvements of lower urinary tract physiology, particularly a reduction in the frequency of non-voiding contractions and the properties of EUS bursting activity indicated as the amplitude of the EUS-EMG signal and duration of burst electrical activity during effective voiding. CONCLUSION: The severe impairments on sensory and locomotive functions as well stereotyped micturition caused by an SCI could be potentially attenuated by an injection of a small amount of BoNT/A directly into the epicenter of the SCI region. A reduction in the release of neurotoxic neurotransmitters requiring the SNARE complex may be the mechanism triggered by BoNT/A to reduce neurotoxicity and hyperexcitability created in the SCI area to improve the survival of spinal cord cells involved in micturition.

Comprehensive molecular analyses of a 7-m6A-related lncRNAs signature for prognosis, tumor immunity and therapeutic effect in patients with hepatocellular carcinoma.

Hepatocellular carcinoma is the most common form of liver tumor. m6A modification and noncoding RNA show indispensable roles in HCC. We sought to establish and verify an appropriate m6A-related long noncoding RNA prognostic tool for predicting hepatocellular carcinoma progression. We extracted the RNA expression levels and the clinicopathologic data from GTEx and TCGA databases. Multivariate Cox regression analysis and receiver operating characteristic curves were performed to test the model's predictive ability. We further built a nomogram for overall survival according to the risk score and clinical features. A competing endogenous RNA network and Gene Ontology assessment were implemented to identify related biological mechanisms and processes. By bioinformatics analysis, a risk model comprising GABPB1-AS1, AC025580.1, LINC01358, AC026356.1, AC009005.1, HCG15, and AC026368.1 was built to offer a prognostic prediction for hepatocellular carcinoma independently. The prognostic tool could better prognosticate hepatocellular carcinoma patients' survival than other clinical characteristics. Then, a nomogram with risk score and clinical characteristics was created, which had strong power to calculate the survival probability in hepatocellular carcinoma. The immune-associated processes involving the differentially expressed genes between the two subgroups were displayed. Analyses of prognosis, clinicopathological characteristics, tumor mutation burden, immune checkpoint molecules, and drug response showed significant differences among the two risk subtypes, hinting that the model could appraise the efficacy of immunotherapy and chemotherapy. The tool can independently predict the prognosis in patients with hepatocellular carcinoma, which benefits drug selection in hepatocellular carcinoma patients.

Development and validation of a general-purpose ReaxFF reactive force field for earth material modeling.

ReaxFF reactive force field bridges the gap between nonreactive molecular simulations and quantum mechanical calculations and has been widely applied during the past two decades. However, its application to earth materials, especially those under high T-P conditions relevant to Earth's interior, is still limited due to the lack of available parameters. Here, we present the development and validation of a ReaxFF force field containing several of the most common elements in Earth's crust, i.e., Si/Al/O/H/Na/K. The force field was trained against a large data set obtained from density functional theory (DFT) calculations, including charges, bond/angle distortion curves, equation of states, ion migration energy profiles, and condensation reaction energies. Different coordination environments were considered in the training set. The fitting results showed that the current force field can well reproduce the DFT data (the Pearson correlation coefficient, Rp, is 0.95). We validated the force field on mineral-water interfaces, hydrous melts/supercritical geofluids, and bulk crystals. It was found that the current force field performed excellently in predicting the structural, thermodynamic, and transport properties of various systems (Rp = 0.95). Moreover, possible applications and future development have been discussed. The results obtained in this study suggest that the current force field holds good promise to model a wide range of processes and thus open opportunities to advance the application of ReaxFF in earth material modeling.

Ultrasonographic changes and impact factors of diaphragmatic function in patients with obstructive sleep apnea-hypopnea syndrome.

PURPOSE: Diaphragmatic impairment has been reported in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients. However, the risk factors of diaphragmatic dysfunction are unclear. This study was conducted to evaluate the diaphragmatic function and to investigate impact factors of ultrasonographic changes of the diaphragm in OSAHS patients. METHODS: This cross-sectional study recruited 150 snoring patients. All patients were divided into the control group (AHI < 5/h, n = 20), the mild-to-moderate OSAHS group (5/h ≤ AHI ≤ 30/h, n = 61), and the severe OSAHS group (AHI > 30/h, n = 69). Diaphragmatic thickness at function residual capacity (TFRC) and total lung capacity (TTLC) were measured by two-dimensional ultrasound, and the diaphragmatic excursion during tidal and deep breath was measured by M-mode ultrasound. The diaphragmatic thickening fraction (TF) was calculated. Spearman analysis and multiple linear stepwise regression analysis were conducted to analyze the impact factors of diaphragmatic function. RESULTS: TFRC in the control group, mild-to-moderate OSAHS group, and severe OSAHS group was 1.23 (1.10, 1.39) mm, 1.60 (1.43, 1.85) mm, and 1.90 (1.70, 2.25) mm; TTLC was 2.75 (2.53, 2.93) mm, 3.25 (2.90, 3.55) mm, and 3.60 (3.33, 3.90) mm, and TF was 119.23% (102.94, 155.97), 96.55% (74.34, 119.11), and 85.29% (60.68,101.22). There were across-group significant differences in TFRC, TTLC, and TF (P < 0.05). The oxygen desaturation index was the influencing factor of TFRC, TTLC, and TF (P < 0.05). CONCLUSION: The diaphragm is thickened and diaphragmatic contractility is decreased in OSAHS patients. Nocturnal intermittent hypoxia is a risk factor for diaphragmatic hypertrophy and impaired diaphragmatic contractility.

Fraxin Ameliorates Ulcerative Colitis by Modulating Oxidative Stress, Inflammation and TLR4/NF-κB and MAPK Signaling Pathways.

Objective: UC is a chronic gastrointestinal disorder of uncertain etiology. However, effective therapeutic drug options for UC are relatively limited. Fraxin represents a principal active constituent within the traditional Chinese medicinal herb known as Cortex Fraxini or Qinpi. Nevertheless, the impact of Fraxin on UC remains uncharted. This study aims to explore the potential of Fraxin, a key component of Cortex Fraxini, in inhibiting DSS-induced intestinal inflammation in mice and to unravel the underlying mechanisms. Methods: In vitro experiment,the RAW264. 7 cells were induced by LPS as the model.In vivo experiment,the mice were induced by DSS as the animal model for a ten day experiment.The ELISA, western blots, measurement of oxidative stress markers and other relevant methods were used to discuss the effect of Fraxin on LPS-induced RAW264.7 cells and the inhibitory effect of Fraxin on intestinal inflammation induced by DSS in mice and underlying mechanisms. Results: Our findings indicated that Fraxin significantly reduced symptoms of UC, such as body weight loss, colonic length shortening, and histological damage. At the molecular level, it inhibited ROS generation, reduced pro-inflammatory cytokines, and regulated key pathways including TLR4/NF-κB and MAPK.The findings indicated that Fraxin diminished the expression of p-NF-κB and p-IκB, downregulated iNOS and COX-2 expression, and lessened p38, JNK and ERK phosphorylation. Conclusion: Taken together, Fraxin ameliorates UC by regulating oxidative stress, inflammation, and TLR4/NF-κB and MAPK pathways, and Fraxin may be a new treatment for UC. Our findings suggest that Fraxin could offer a novel therapeutic approach for UC, targeting oxidative stress and key inflammatory pathways.

Exposure to bisphenol A affects transcriptome-wide N6-methyladenine methylation in ovarian granulosa cells.

Bisphenol A (BPA) is an endocrine disruptor of potential reproductive toxicities. Increasingly research elucidated that BPA exposure to the environment would change the epigenetic modifications of transcriptome, but the mechanism by which BPA affects m6A methylation in interfering with female reproductive health remains uncertain. Therefore, this study preliminarily proposed and tested the hypothesis that BPA exposure alters the m6A modification level in transcripts in female ovarian granulosa cells. After BPA was exposed to granulosa cells for 24 h, RNA methylation related regulatory genes (such as METTL3, METTL14, ALKBH5, FTO) and the global m6A levels showed significant differences. Next, we applied MERIP-seq analysis to obtain information on the genome-wide m6A modification changes and identified 1595 differentially methylated mRNA transcripts, and 50 differentially methylated lncRNA transcripts. Further joint analysis of gene common expression showed that 33 genes were hypermethylated and up-regulated, 71 were hypermethylated and down-regulated, 49 were hypomethylated and up-regulated, and 20 were hypomethylated and down-regulated. Enriched Gene Ontology (GO) and biological pathway analysis revealed that these unique genes were mainly enriched in lipid metabolism, cell proliferation, and apoptosis related pathways. Six of these genes (mRNAs IMPA1, MCOLN1, DCTN3, BRCA2, and lncRNAs MALAT1, XIST) were validated using RT-qPCR and IGV software. Through comprehensive analysis of epitranscriptome and protein-protein interaction (PPI) data, lncRNAs MALAT1 and XIST are expected to serve as new markers for BPA interfering with the female reproductive system. In brief, these data show a novel and necessary connection between the damage of BPA exposure on female ovarian granulosa cells and RNA methylation modification.

Gamma-band Intermuscular Connectivity Is Associated With Increased Neural Drive to Pelvic Floor Muscles in Women With Interstitial Cystitis/Bladder Pain Syndrome.

PURPOSE: Interstitial cystitis/bladder pain syndrome patients can experience overactive pelvic floor muscle activity at rest. While the frequency power spectrum of pelvic floor muscle has briefly been explored, intermuscular connectivity of the pelvic floor muscle has yet to be studied, which may provide useful insight into the neurological component, ie, neural drive to muscles, in interstitial cystitis/bladder pain syndrome. MATERIALS AND METHODS: High-density surface electromyography was collected from 15 female interstitial cystitis/bladder pain syndrome patients with pelvic floor tenderness and 15 urologically healthy female controls. Intermuscular connectivity was calculated across the maximally active locations of the left and right sides of the pelvic floor muscle as identified from the root mean squared amplitude at rest and compared with Student t tests for common sensorimotor rhythms involved in motor control: alpha (8-12 Hz), beta (13-30 Hz), and gamma (31-70 Hz) frequency bands. The root mean squared amplitudes at rest were also compared across groups. RESULTS: The resting root mean squared amplitude of the pelvic floor muscle was significantly greater in female interstitial cystitis/bladder pain syndrome patients compared to healthy female controls (P = .0046). The gamma-band intermuscular connectivity was significantly different between rest and pelvic floor muscle contraction (P = .0001) for healthy female controls, but not for female patients with interstitial cystitis/bladder pain syndrome (P = .1214). Both results indicate an elevated neural drive to pelvic floor muscle at rest in female interstitial cystitis/bladder pain syndrome patients. CONCLUSIONS: Gamma-band pelvic floor muscle connectivity in female interstitial cystitis/bladder pain syndrome patients is increased at rest. The results of this study may provide insight into the impaired neural drive to pelvic floor muscle implicated with interstitial cystitis/bladder pain syndrome.

Preparation, structural properties, and in vitro and in vivo activities of peptides against dipeptidyl peptidase IV (DPP-IV) and α-glucosidase: a general review.

Diabetes is one of the fastest-growing and most widespread diseases worldwide. Approximately 90% of diabetic patients have type 2 diabetes. In 2019, there were about 463 million diabetic patients worldwide. Inhibiting the dipeptidyl peptidase IV (DPP-IV) and α-glucosidase activity is an effective strategy for the treatment of type 2 diabetes. Currently, various anti-diabetic bioactive peptides have been isolated and identified. This review summarizes the preparation methods, structure-effect relationships, molecular binding sites, and effectiveness validation of DPP-IV and α-glucosidase inhibitory peptides in cellular and animal models. The analysis of peptides shows that the DPP-IV inhibitory peptides, containing 2-8 amino acids and having proline, leucine, and valine at their N-terminal and C-terminal, are the highly active peptides. The more active α-glucosidase inhibitory peptides contain 2-9 amino acids and have valine, isoleucine, and proline at the N-terminal and proline, alanine, and serine at the C-terminal.

Structure, Stability, and Acidity of the Uranyl Arsenate Dimer in Aqueous Solution.

The migration of uranium (U) in the surficial environment has received considerable attention. Due to their high natural abundance and low solubility, autunite-group minerals play a key role in controlling the mobility of U. However, the formation mechanism for these minerals has yet to be understood. In this work, we took the uranyl arsenate dimer ([UO2(HAsO4)(H2AsO4)(H2O)]22-) as a model molecule and carried out a series of first-principles molecular dynamics (FPMD) simulations to explore the early stage of the formation of trögerite (UO2HAsO4·4H2O), a representative autunite-group mineral. By using the potential-of-mean-force (PMF) method and vertical energy gap method, the dissociation free energies and the acidity constants (pKa's) of the dimer were calculated. Our results show that the U in the dimer holds a 4-coordinate structure, which is consistent with the coordination environment observed in trögerite mineralogy, in contrast to the 5-coordinate U in the monomer. Furthermore, the dimerization is thermodynamically favorable in solution. The FPMD results also suggest that tetramerization and even polyreactions would occur at pH > 2, as observed experimentally. Additionally, it is found that trögerite and the dimer have very similar local structural parameters. These findings imply that the dimer could serve as an important link between the U-As complexes in solution and the autunite-type sheet of trögerite. Given the nearly identical physicochemical properties of arsenate and phosphate, our findings suggest that uranyl phosphate minerals with the autunite-type sheet may form in a similar manner. This study therefore fills a critical gap in atomic-scale knowledge of the formation of autunite-group minerals and provides a theoretical basis for regulating uranium mobilization in P/As-bearing tailing water.

Clinical study of transcranial sonography image characteristics in patients with obstructive sleep apnea.

OBJECTIVE: This study aimed to explore the relationship between patients with obstructive sleep apnea (OSA) from subgroups of varying severity and substantia nigra (SN) hyperechogenicity as well as cerebral blood flow detected by transcranial sonography (TCS). The study also explored if there were differences in damage of the SN and in the cerebral blood flow between the bilateral sides. METHODS: Right-handed men diagnosed with OSA by polysomnography were recruited from August 2018 to August 2020. The included patients were divided into 3 subgroups (mild, moderate, and severe OSA), and all patients underwent TCS. RESULTS: Among the 157 study patients (30 with mild OSA, 25 moderate, and 102 severe), the overall prevalence of SN hyperechogenicity was 15% (23/157). The hyperechogenicity detection rates were 3% (4/157) in the right SN subgroup and 13% (20/157) in the left SN subgroup, which were significantly different. The left side always had reduced blood flow on TCS (P < 0.05). No correlation was observed between the severity of OSA and the detection rates of SN hyperechogenicity (P > 0.05). CONCLUSION: Patients with OSA showed a higher detection rate of SN hyperechogenicity on the left compared with the right side. The left middle cerebral arteries had reduced blood flow, which was consistent with the more severe damage of the left SN. No relationship was observed between the severity of OSA and the detection rate of SN hyperechogenicity or hemodynamic parameters.

Sarcopenia is associated with non-motor symptoms in Han Chinese patients with Parkinson's Disease: a cross-sectional study.

BACKGROUND: Sarcopenia is commonly seen in the older adults and increases in incidence with age, also in Parkinson's disease (PD). Although research has indicated that the development of sarcopenia in patients with PD may be related to both motor symptoms and non-motor symptoms (NMS), the precise relationship between the two conditions remains unclear. Therefore, we aimed to investigate the incidence of sarcopenia in patients with PD and its association with NMS. METHODS: The study included 123 patients with PD and 38 age- and sex-matched healthy controls (HC). All participants were evaluated for sarcopenia using the 2019 Asian Sarcopenia Diagnostic Criteria, and patients with PD underwent standard assessments of motor symptoms and NMS. Multiple logistic regression and receiver operating characteristic (ROC) curve analyses were used to examine the association between sarcopenia and NMS in patients with PD. RESULTS: The incidence of sarcopenia was significantly higher in patients with PD than in HC (26.8% vs. 10.4%, p = 0.046). Multiple logistic regression analysis revealed that poorer sleep quality (odds ratio [OR]: 1.245; 95% confidence interval [CI]: 1.011-1.533; p = 0.040) and fatigue (OR: 1.085, 95% CI: 1.006-1.170, p = 0.034) were independently associated with sarcopenia. ROC analysis indicated that the optimal cut-off value for Pittsburgh Sleep Quality Index (PSQI) scores was 10, with 72.7% sensitivity and 74.4% specificity (area under the curve [AUC] = 0.776, 95% CI: 0.683-0.868, p < 0.001). The optimal cut-off value for Fatigue Severity Scale (FSS) scores was 39, with 87% sensitivity and 50% specificity (AUC = 0.725, 95% CI: 0.629 -0.820, p < 0.001). Joint use of FSS and PSQI scores increased the predictive value for sarcopenia(AUC = 0.804, 95% CI: 0.724-0.885, p < 0.001). CONCLUSION: Patients with PD are more susceptible to sarcopenia than healthy older adults, and fatigue and poorer sleep are positively associated with sarcopenia. Further longitudinal studies are needed to clarify the causal relationships.

Platelet-rich Plasma Promotes Restoration of the Anterior Vaginal Wall for the Treatment of Pelvic Floor Dysfunction in Rats.

STUDY OBJECTIVE: To determine the efficacy of using platelet-rich plasma (PRP) for vaginal wall repair in rats with vaginal wall impairment induced by vaginal distension (VD). DESIGN: A single-blind, randomized study. SETTING: A certified animal research facility. ANIMALS: Twenty-four female Sprague Dawley rats. INTERVENTIONS: Female Sprague Dawley rats were divided into sham (n = 8), VD (n = 8), and VD + PRP (n = 8) groups. Vaginal tissues from the VD group were dissected at 28-day post injury. VD + PRP rats received vaginal PRP injections on the 1st, 7th, 14th, and 21st day after VD and sacrificed on the 28th day. MEASUREMENTS AND MAIN RESULTS: Urodynamic tests were performed in all rats. Immunohistochemistry was used to evaluate matrix metalloprotease-2 (MMP-2) and matrix metalloprotease-9 (MMP-9). Masson's staining was used to evaluate collagen fibers and calculate collagen volume fraction. Collagen fiber damage was confirmed in the VD group, evidenced by thinner and sparse distribution of collagen fibers, with significantly higher MMP-2 and MMP-9 expression than the sham group (p <.05). The collagen fiber damage in the vaginal wall likely led to pelvic floor dysfunction (PFD), evidenced by significantly decreased bladder leak-point pressure (p <.01) and abdominal leak-point pressure (p <.01) in the VD group compared with the sham group. After completion of the PRP treatment, a significantly higher collagen volume fraction (p <.01) and significantly increased bladder leak-point pressure (p <.05) and abdominal leak-point pressure (p <.01) were achieved in the VD + PRP compared with the VD group, thus indicating repair of the vaginal wall and improvement of PFD. CONCLUSION: PRP injections facilitate the regeneration of vaginal wall tissue, particularly collagen fiber, after VD, leading to functional improvement of PFD. Findings support the feasibility of using PRP as a novel treatment for PFD.

Differential eye movement features between Alzheimer's disease patients with and without depressive symptoms.

BACKGROUND: Accurately diagnosing depressive symptoms in Alzheimer's disease (AD) patients is often challenging. Eye movement parameters have been demonstrated as biomarkers for assessing cognition and psychological conditions. AIM: To investigate the differences in eye movement between AD patients with and without depressive symptoms. METHODS: Eye movement data of 65 AD patients were compared between the depressed AD (D-AD) and non-depressed AD (nD-AD) groups. Logistic regression analysis was employed to identify diagnostic biomarkers and the ROC curve was plotted. The correlation between eye movement and HAMD-17 scores was assessed by partial correlation analysis. RESULTS: The D-AD patients showed longer saccade latency and faster average/peak saccade velocities in the overlap prosaccade test, longer average reaction time and faster average saccade velocity in the gap prosaccade test, longer start-up durations, slower pursuit velocity, more offsets, and larger total offset degrees in the smooth pursuit test, and poorer fixation stability in both the central and lateral fixation tests compared to nD-AD patients. The start-up duration in the smooth pursuit test and the number of offsets in the central fixation test were identified as the diagnostic eye movement parameters for D-AD patients with the area under the ROC curves of 0.8011. Partial correlation analysis revealed that the start-up duration and pursuit velocity in the smooth pursuit test and the total offset degrees in the lateral fixation test were correlated with HAMD-17 scores in D-AD patients. DISCUSSION AND CONCLUSIONS: Eye movement differences may help to differentiate D-AD patients from nD-AD patients in a non-invasive and cost-effective manner.

CeRNA regulates network and expression and SNP effect on NFKBIA of cashmere fineness.

In this study, a total of 1140 Liaoning Cashmere Goats (LCG) were genotyped for single nucleotide polymorphism (SNP) of NFKBIA gene. There are 15 SNPs and 7 genotypes have been found, and G1547A (GG) genotype has been associated with cashmere fineness and cashmere yield. An integrated ceRNA regulatory network of NFKBIA gene was made. To prove NFKBIA and these non-coding RNAs (ncRNAs) may be related to cashmere fineness, we performed qPCR on these ncRNA in LCG coarse type skin (CT-LCG) and LCG fine type skin (FT-LCG). The result of qPCR showed lncRNA XLOC_011060 and ciRNA452 are at high expression level in CT-LCG, all miRNAs appear high expressed in FT-LCG, and mir-93 was the most significant difference between CT-LCG and FT-LCG. In addition, five miRNAs were selected for qPCR in different genotypes. The qPCR results showed that mir-93 might negatively regulate cashmere fineness and mir-17-5p may play a positive role in regulating cashmere fineness of individuals with G1355A (AG) genotype. These results demonstrated that NFKBIA gene is associated with cashmere fineness of LCG and G1547A (GG) genotype is the preferred marker genotype for cashmere fineness.

Relationship between sarcopenia and sleep status in female patients with mild to moderate Alzheimer's disease.

BACKGROUND: Sleep disorders and sarcopenia could contribute to the development of Alzheimer's disease (AD), which are risk factors that rapidly deteriorate cognitive functions. However, few studies have evaluated the relationship between sarcopenia and sleep disorders in female AD patients, who have a higher prevalence than male patients. This study aimed to investigate the relationship between sarcopenia and sleep status in female patients with mild to moderate AD. METHODS: This cross-sectional study recruited 112 female outpatients aged between 60 and 85 years. Demographic characteristics, appendicular skeletal muscle mass index (ASMI), grip strength, and gait speed were assessed. Sarcopenia was diagnosed according to criteria of the Asian Working Group for Sarcopenia. Pittsburgh Sleep Quality Index (PSQI) assessed sleep variables. Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) assessed cognitive function. Binary logistic regression models explored the relationship between sleep variables and cognitive function and sarcopenia, adjusting for potential cofounders. RESULTS: The outpatients were divided into 36 AD patients with sarcopenia (ADSa) and 76 AD patients without sarcopenia (ADNSa), with a prevalence of 32.1%. ADSa had lower ASMI, weaker grip strength, slower gait speed, a higher incidence of poor sleep quality and poorer cognitive function. Multivariate binary logistic regression analysis showed that high total scores of PSQI (odds ratio (OR) = 1.13), poor sleep quality (OR = 2.73), poor subjective sleep quality (OR = 1.83), low MMSE (OR = 0.77) and MoCA (OR = 0.76) scores were associated with high odds of sarcopenia. Compared to sleep time ≤ 15 min, >60 min (OR = 5.01) were associated with sarcopenia. Sleep duration <6 h (OR = 3.99), 8-9 h (OR = 4.48) and ≥9 h (OR = 6.33) were associated with sarcopenia compared to 7-8 h. CONCLUSIONS: More sleep symptoms and cognitive impairment exist in female patients with sarcopenia. The higher total scores of PSQI, poorer subjective sleep quality, longer sleep latency, excessive and insufficient sleep duration and poorer cognitive function are associated with higher odds of sarcopenia in female patients with mild to moderate AD.

Relationship between sarcopenic obesity and cognitive function in patients with mild to moderate Alzheimer's disease.

BACKGROUND: Previous research has linked sarcopenic obesity (SO) to cognitive function; however, the relationship between cognitive performance and SO Alzheimer's disease (AD) patients remains unclear. This study aimed to investigate their relationship in AD patients. METHODS: One hundred and twenty mild to moderate AD patients and 56 normal controls were recruited. According to sarcopenia or obesity status, AD patients were classified into subgroups: normal, obesity, sarcopenia, and SO. Body composition, demographics, and sarcopenia parameters were assessed. Cognitive performance was evaluated using neuropsychological scales. RESULTS: Among the 176 participants, the prevalence of SO in the moderate AD group was higher than in the normal control group. The moderate AD group had the lowest appendicular skeletal muscle mass index (ASMI) and the highest percentage of body fat (PBF). Hypertension and diabetes were more prevalent in the SO group than in the normal group among the subgroups. The sarcopenia and SO groups exhibited worse global cognitive function compared to the normal and obesity groups. Partial correlation analysis revealed that ASMI, PBF, and visceral fat area were associated with multiple cognitive domains scores. In logistic regression analysis, after adjusting for confounders, obesity was not found to be associated with AD. However, sarcopenia (odds ratio (OR) = 5.35, 95% CI: 1.27-22.46) and SO (OR = 5.84, 95% CI: 1.26-27.11) were identified as independent risk factors for AD. CONCLUSIONS: SO was associated with cognitive dysfunction in AD patients. Moreover, the impact of SO on cognitive decline was greater than that of sarcopenia. Early identification and intervention for SO may have a positive effect on the occurrence and progression of AD.