A decision support system for upper limb rehabilitation robot based on hybrid reasoning with RBR and CBR.

The rehabilitation robot can assist hemiplegic patients to complete the training program effectively, but it only focuses on helping the patient's training process and requires the rehabilitation therapists to manually adjust the training parameters according to the patient's condition. Therefore, there is an urgent need for intelligent training prescription research of rehabilitation robots to promote the clinical applications. This study proposed a decision support system for the training of upper limb rehabilitation robot based on hybrid reasoning with rule-based reasoning (RBR) and case-based reasoning (CBR). The expert knowledge base of this system is established base on 10 professional rehabilitation therapists from three different rehabilitation departments in Shanghai who are enriched with experiences in using desktop-based upper limb rehabilitation robot. The rule-based reasoning is chosen to construct the cycle plan inference model, which develops a 21-day training plan for the patients. The case base consists of historical case data from 54 stroke patients who underwent rehabilitation training with a desktop-based upper limb rehabilitation robot. The case-based reasoning, combined with a Random Forest optimized algorithm, was constructed to adjust the training parameters for the patients in real-time. The system recommended a rehabilitation training program with an average accuracy of 91.5%, an average AUC value of 0.924, an average recall rate of 88.7%, and an average F1 score of 90.1%. The application of this system in rehabilitation robot would be useful for therapists.

Transcription factor ASCL1 targets SLC6A13 to inhibit the progression of hepatocellular carcinoma via the glycine-inflammasome signaling.

The purpose of this research was to clarify the function of achaete-scute family bHLH transcription factor 1 (ASCL1) and solute carrier family 6 member 13 (SLC6A13) in influencing tumor cell behavior, inflammatory responses, and the regulation of inflammasomes. We analyzed the differentially expressed genes (DEGs) in the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database, as well as in the GSE14520 and GSE67764 datasets, to identify the expression changes of SLC6A13 in liver cancer. The prognostic significance of SLC6A13 in LIHC was assessed through Kaplan-Meier survival curve analysis. Transcriptional regulation of SLC6A13 by ASCL1 was explored using the Joint Annotation of the Human Genome and other species by the Systematic Pipeline for the Annotation of Regulatory Regions (JASPAR) database and dual-luciferase assays. In vitro experiments investigated the impact of ASCL1 and SLC6A13 overexpression on hepatocellular carcinoma (HCC) cell growth. Additionally, the effects of ethanol treatment and glycine modulation on the inflammatory response in HCC cell lines were evaluated. HCC samples showed reduced levels of SLC6A13, which correlates with a better prognosis for liver metastases. Elevated SLC6A13 expression correlated with improved overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-specific survival (DSS). ASCL1 upregulated SLC6A13 and inhibited proliferation, migration, and invasion of HCC cells. Ethanol induced the production of inflammatory cytokines, which was enhanced by overexpression of SLC6A13 but counteracted by glycine. This study highlighted elevated expression of SLC6A13 in LIHC which has been correlated with improved OS, PFS, RFS, and DSS. Overexpression of SLC6A13 and ASCL1 in HCC cells enhanced inflammasome activation, which was exacerbated by ethanol and attenuated by glycine.

Pituitary abscess: a descriptive analysis of a series of 19 patients-a multi-center experience.

OBJECTIVES: Pituitary abscess (PA) accounts for only 0.3-0.5% of sellar masses, and the lack of specific clinical symptoms makes diagnosing PA difficult without a surgical biopsy. In clinical practice, PA is often mistaken for cystic pituitary adenoma, craniopharyngioma, and Rathke's cyst. Thus, this study aims to investigate challenges in diagnosing PA and evaluate the importance of combining intraoperative surgery with postoperative antibiotic treatment. METHODS: We conducted a retrospective analysis of 19 patients diagnosed with PA through histopathology. All patients underwent transsphenoidal surgery (TSS) for pituitary adenomas after undergoing comprehensive preoperative evaluations, including routine tests, endocrine assay, and imaging examination. Furthermore, we compared different treatments for pituitary abscess (PA) to determine the most effective approach for achieving a favorable prognosis. RESULTS: The most prevalent symptom of PA was headache, especially in the frontal-temporal and vertex regions, ranging from mild to moderate severity. Hypopituitarism-related symptoms were also frequently observed, including hypaphrodisia, cold sensitivity, fatigue, weight loss, polyuria, and amenorrhea. Twelve patients exhibited abnormalities in endocrinology examinations. Diagnosing PA correctly is challenging. In our study, none of the patients were correctly diagnosed with PA prior to surgery, and many sellar lesions were misdiagnosed. The favorable prognosis was largely attributed to surgical intervention and active postoperative antibiotic therapy. CONCLUSIONS: Given the lack of clarity in preoperative diagnosis, typical intraoperative findings and effective antibiotics treatment are more indicative of the correct diagnosis than other tests. In terms of therapy, optimal surgical intervention and active postoperative antibiotic treatment contribute to resolving the challenges posed by PA.

Decomposition and comparative analysis of depressive symptoms between older adults living alone and with others in China.

Objective: This research dealt with investigating and measuring the contribution of the factors that impact depression in older adults living alone vs. those living with others (hereafter referred to as "not alone") in China. Design: This investigation adopts a cross-sectional research design. The dataset employed for this study comprises data from 2018 the Chinese Longitudinal Health Longevity Survey (CLHLS). Setting: The research involved data sourced from China, specifically from 23 of its provinces. From the 8th CLHLS, 12,197 older adults were selected who met the study requirements. Measures: Binary logistic regression models were established to delve into the primary factors impacting the depressive symptoms of the individuals. Furthermore, Fairlie models were employed to assess these factors between older adults living alone and those not living alone. This approach facilitated an in-depth analysis of their respective contributions. Results: It was observed that the demographic of Chinese older adults exhibited depressive symptoms at a rate of 11.92%. Older adults who resided alone (15.76%) exhibited a higher prevalence of depressive symptoms in comparison to their counterparts living in not-alone settings (11.15%). Employing Fairlie decomposition analysis, it was determined that this observed disparity in depressive symptoms, amounting to 55.33% of the overall difference, could be primarily attributed to distinct factors. This encompassed variance in marital status (20.55%), years of school (4.63%), self-reported local income status (7.25%), self-reported sleep status (17.56%), and self-reported health status (4.24%). Conclusion: The resulting data indicated that depressive symptoms exhibited an elevated prevalence in older adults living alone than in those living not alone. This discrepancy was predominantly attributed to variance in socioeconomic marital status, years of school, self-reported local income status, self-reported sleep status, and self-reported health status by living alone vs. not alone. Mitigating these influential factors could help develop targeted and meticulous intervention strategies, precisely tailored to improve the mental well-being of older adults at high risk.

Depleted uranium induces thyroid damage through activation of ER stress via the thrombospondin 1-PERK pathway.

Depleted uranium (DU) can cause damage to the body, but its effects on the thyroid are unclear. The purpose of this study was to investigate the DU-induced thyroid damage and its potential mechanism in order to find new targets for detoxification after DU poisoning. A model of acute exposure to DU was constructed in rats. It was observed that DU accumulated in the thyroid, induced thyroid structure disorder and cell apoptosis, and decreased the serum T4 and FT4 levels. Gene screening showed that thrombospondin 1 (TSP-1) was a sensitive gene of DU, and the expression of TSP-1 decreased with the increase of DU exposure dose and time. TSP-1 knockout mice exposed to DU had more severe thyroid damage and lower serum FT4 and T4 levels than wild-type mice. Inhibiting the expression of TSP-1 in FRTL-5 cells aggravated DU-induced apoptosis, while exogenous TSP-1 protein alleviated the decreased viability in FRTL-5 cells caused by DU. It was suggested that DU may caused thyroid damage by down-regulating TSP-1. It was also found that DU increased the expressions of PERK, CHOP, and Caspase-3, and 4-Phenylbutyric (4-PBA) alleviated the DU-induced FRTL-5 cell viability decline and the decrease levels of rat serum FT4 and T4 caused by DU. After DU exposure, the PERK expression was further up-regulated in TSP-1 knockout mice, and the increased expression of PERK was alleviated in TSP-1 over-expressed cells, as well as the increased expression of CHOP and Caspase-3. Further verification showed that inhibition of PERK expression could reduce the DU-induced increased expression of CHOP and Caspase-3. These findings shed light on the mechanism that DU may activate ER stress via the TSP 1-PERK pathway, thereby leading to thyroid damage, and suggest that TSP-1 may be a potential therapeutic target for DU-induced thyroid damage.

Mannosylated polydopamine nanoparticles alleviate radiation- induced pulmonary fibrosis by targeting M2 macrophages and inhibiting the TGF-ß1/Smad3 signaling pathway.

Radiation-induced pulmonary fibrosis (RIPF), one type of pulmonary interstitial diseases, is frequently observed following radiation therapy for chest cancer or accidental radiation exposure. Current treatments against RIPF frequently fail to target lung effectively and the inhalation therapy is hard to penetrate airway mucus. Therefore, this study synthesized mannosylated polydopamine nanoparticles (MPDA NPs) through one-pot method to treat RIPF. Mannose was devised to target M2 macrophages in the lung through CD 206 receptor. MPDA NPs showed higher efficiency of penetrating mucus, cellular uptake and ROS-scavenging than original polydopamine nanoparticles (PDA NPs) in vitro. In RIPF mice, aerosol administration of MPDA NPs significantly alleviated the inflammatory, collagen deposition and fibrosis. The western blot analysis demonstrated that MPDA NPs inhibited TGF-ß1/Smad3 signaling pathway against pulmonary fibrosis. Taken together this study provide a novel M2 macrophages-targeting nanodrugs through aerosol delivery for the prevention and targeted treatment for RIPF.

Depleted uranium causes renal mitochondrial dysfunction through the ETHE1/Nrf2 pathway.

The kidney is the main organ affected by acute depleted uranium (DU) toxicity. The mechanism of nephrotoxicity induced by DU is complex and needs to be further explored. This study aimed to elucidate the function of mitochondrial dysfunction in nephrotoxicity generated by DU and confirm the latent mechanism. We verified that DU (2.5-10 mg/kg) caused mitochondrial dysfunction in male rat kidneys and decreased ATP content and the mitochondrial membrane potential. In addition, melatonin (20 mg/kg), as an antioxidant, alleviated DU-induced oxidative stress and mitochondrial dysfunction in male rats, further reducing kidney damage caused by DU. These results indicate that mitochondrial dysfunction plays a vital role in DU nephrotoxicity. When ethylmalonic encephalopathy 1 (ETHE1) was knocked down, DU-induced oxidative stress and mitochondrial dysfunction were increased, and renal injury was aggravated. When exogenous ETHE1 protein was applied to renal cells, the opposite changes were observed. We also found that ETHE1 knockdown increased the expression of NF-E2-related factor 2 (Nrf2), a vital oxidative stress regulator, and its downstream molecules heme oxygenase-1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1). Nrf2 knockout also aggravated DU-induced oxidative stress, mitochondrial dysfunction, and kidney damage. In conclusion, DU causes oxidative stress and antioxidant defense imbalance in renal cells through the ETHE1/Nrf2 pathway, further causing mitochondrial dysfunction and ultimately leading to nephrotoxicity.

Perineural invasion confers poorer clinical outcomes in patients with T1/T2 intrahepatic cholangiocarcinoma: a single center, retrospective cohort study.

Background: Intrahepatic cholangiocarcinoma (ICC) poses a significant clinical challenge, demanding a thorough understanding of prognostic indicators for effective patient management. Despite reports suggesting the impact of perineural invasion (PNI) on the prognosis of early-stage ICC patients, there has been a dearth of comprehensive research specifically targeting this subgroup. This study seeks to investigate the influence of PNI on survival outcomes in early-stage ICC patients and aims to enhance the prognostic value of the American Joint Committee on Cancer (AJCC) T category. Methods: A cohort of 268 early-stage (T1-T2N0M0) ICC patients, who underwent curative-intent resection (R0) between 2011 and 2015 at the Eastern Hepatobiliary Surgery Hospital, were enrolled in this study. Lasso and Cox regression analyses were employed to explore differences in clinical and prognostic data. Kaplan-Meier curves were generated to illustrate the clinical significance of the combination of PNI and T category. Results: Among the 268 patients, 24.6% exhibited PNI. Patients with PNI demonstrated shorter recurrence-free survival (RFS) [median RFS: 16 months (interquartile range, 9.5-19 months)] and overall survival (OS) [median OS: 16.53 months (interquartile range, 10-25 months)]. PNI emerged as an independent risk factor for both RFS and OS in T1- and T2-stage patients (all P<0.05), whereas tumor size was only an independent risk factor for OS (P=0.004). PNI was associated with all prognostic markers for ICC patients, including gender, jaundice, cholangitis, hepatitis B virus (HBV) infection, cancer antigen 199 (CA199), preoperative serum albumin, and preoperative platelet count (all P<0.05). However, there was no significant difference in RFS (P=0.270) and OS (P=0.360) between T2 patients without PNI and T1 patients with PNI. Conclusions: This study underscores PNI as a robust prognostic factor in early-stage ICC, emphasizing the necessity of incorporating PNI into the AJCC T category for precise risk stratification. Clinically, understanding the impact of PNI on survival outcomes can guide tailored treatment strategies for early ICC patients.

Child inflammatory myofibroblastic tumor of the kidney misdiagnosed as Wilms' tumor: case report.

Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor with recurrent potential, most commonly occurring in the lung but rarely in the kidney with nonspecific clinical symptoms and radiographic features, thus may be misdiagnosed as primary malignant lesions. We described a 6-year-old boy with renal IMT misdiagnosed as Wilms' tumor and then treated with right nephrectomy. It should be emphasized that in addition to the most common renal tumors in children, IMT should also be taken as a differential diagnosis. It is therefore mandatory to carry out clinical interpretation, careful histologic examination, and immunohistochemical studies collectively to make solid diagnosis.

A Noncoding Regulatory RNAs Network Driven by Circ-CDYL Acts Specifically in the Early Stages Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the fastest-rising causes of cancer-related death worldwide, but its deficiency of specific biomarkers and therapeutic targets in the early stages lead to severe inadequacy in the early diagnosis and treatment of HCC. Covalently closed circular RNA (circRNA), which was once considered an aberrant splicing by-product, is now drawing new interest in cancer research because of its remarkable functionality. Beneath the surface of the dominant functional proteins events, a hidden circRNA-centric noncoding regulatory RNAs network active in the very early stage of HCC is here revealed by a genome-wide analysis of mRNA, circRNA, and microRNA (miRNA) expression profiles. Circ-CDYL (chromodomain Y like) is specifically up-regulated in the early stages of HCC and therefore contributes to the properties of epithelial cell adhesion molecule (EPCAM)-positive liver tumor-initiating cells. Circ-CDYL interacts with mRNAs encoding hepatoma-derived growth factor (HDGF) and hypoxia-inducible factor asparagine hydroxylase (HIF1AN) by acting as the sponge of miR-892a and miR-328-3p, respectively. Subsequently, activation of the phosphoinositide 3-kinase (PI3K)-AKT serine/threonine kinase-mechanistic target of rapamycin kinase complex 1/ß-catenin and NOTCH2 pathways, which promote the expression of the effect proteins, baculoviral IAP repeat containing 5 (BIRC5 or SURVIVIN) and MYC proto-oncogene, is influenced by circ-CDYL. A treatment incorporating circ-CDYL interference and traditional enzyme inhibitors targeting PI3K and HIF1AN demonstrated highly effective inhibition of stem-like characteristics and tumor growth in HCC. Finally, we demonstrated that circ-CDYL expression or which combined with HDGF and HIF1AN are both independent markers for discrimination of early stages of HCC with the odds ratios of 1.09 (95% confidence interval [CI], 1.02-1.17) and 124.58 (95% CI, 13.26-1170.56), respectively. Conclusion: These findings uncover a circRNA-centric noncoding regulatory RNAs network in the early stages of HCC and thus provide a possibility for surveillance and early treatment of HCC.

Hydrogen-rich saline protects against renal ischemia/reperfusion injury in rats.

BACKGROUND: Recently it has been demonstrated that hydrogen, as a novel antioxidant, can selectively reduce hydroxyl radicals (·OH) and peroxynitrite anion (ONOO-) in vitro and exert therapeutic antioxidant activity in many diseases. This study was designed to investigate the effect of hydrogen-rich saline on renal ischemia/reperfusion (I/R) injury in rats. METHODS: A rat model of renal I/R injury was induced by 45-min occlusion of the bilateral renal pedicles and 24-h reperfusion. Physiologic saline, hydrogen-rich saline, or nitrogen-rich saline (8 mL/kg) were administered intraperitoneally at 5 min before reperfusion, respectively. RESULTS: After I/R injury, serum blood urea nitrogen (BUN), creatinine (Cr), tissue malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OhdG), TNF-α, IL-1ß, IL-6 levels, and myeloperoxidase (MPO) activity were all increased significantly, while tissue superoxide dismutase (SOD) and catalase (CAT) activities were all decreased significantly. Hydrogen-rich saline reversed these changes and relieved morphological renal injury and I/R-induced apoptosis, while no significant changes were observed in the nitrogen-rich saline-treated group compared with physiologic saline-treated group. CONCLUSIONS: Hydrogen-rich saline is able to attenuate the renal I/R injury, which is possibly by reduction of oxidative stress and inflammation.