Association between exposure to particulate matter and incidence of Parkinson's disease: A nationwide cohort study in Taiwan.

Objective: Emerging evidence suggests that air pollution exposure may increase the risk of Parkinson's disease (PD). We aimed to investigate the association between exposure to fine particulate matter (PM2.5) and the risk of incident PD nationwide. Methods: We utilized data from the Taiwan National Health Insurance Research Database, which was spatiotemporally linked with air quality data from the Taiwan Environmental Protection Administration website. The study population consisted of participants who were followed from the index date (January 1st, 2005) until the occurrence of PD or the end of the study period (December 31st, 2017). Participants who had a prior diagnosis of PD before the index date were excluded. To evaluate the association between exposure to PM2.5 and incident PD, we employed a Cox regression to estimate the hazard ratio with a 95% confidence interval (CI). Results: A total of 454,583 participants were included, with a mean (SD) age of 63.1 (9.9) years and a male proportion of 50%. Over a mean follow-up period of 11.1 (3.6) years, 4% of the participants (n = 18,862) developed PD. We observed a significant positive association between PM2.5 exposure and the risk of PD, with a hazard ratio of 1.22 (95% CI, 1.20-1.23) per interquartile range increase in exposure (10.17 µg/m3) when adjusting for both SO2 and NO2. Conclusion: We provide further evidence of an association between PM2.5 exposure and risk of PD. These findings underscore the urgent need for public health policies aimed at reducing ambient air pollution and its potential impact on PD.

Super-enhancer-driven IRF2BP2 enhances ALK activity and promotes neuroblastoma cell proliferation.

BACKGROUND: Super-enhancers (SEs) typically govern the expression of critical oncogenes and play a fundamental role in the initiation and progression of cancer. Focusing on genes that are abnormally regulated by SE in cancer may be a new strategy for understanding pathogenesis. In the context of this investigation, we have identified a previously unreported SE-driven gene IRF2BP2 in neuroblastoma (NB). METHODS: The expression and prognostic value of IRF2BP2 were detected in public databases and clinical samples. The effect of IRF2BP2 on NB cell growth and apoptosis was evaluated through in vivo and in vitro functional loss experiments. The molecular mechanism of IRF2BP2 was investigated by the study of chromatin regulatory regions and transcriptome sequencing. RESULTS: The sustained high expression of IRF2BP2 results from the activation of a novel SE established by NB master transcription factors MYCN, MEIS2 and HAND2, and they form a new complex that regulates the gene network associated with the proliferation of NB cell populations. We also observed a significant enrichment of the AP-1 family at the binding sites of IRF2BP2. Remarkably, within NB cells, AP-1 plays a pivotal role in shaping the chromatin accessibility landscape, thereby exposing the binding site for IRF2BP2. This orchestrated action enables AP-1 and IRF2BP2 to collaboratively stimulate the expression of the NB susceptibility gene ALK, thereby upholding the highly proliferative phenotype characteristic of NB. CONCLUSION: Our findings indicate that SE-driven IRF2BP2 can bind to AP-1 to maintain the survival of tumor cells via regulating chromatin accessibility of NB susceptibility gene ALK.

Light Therapy in Chronic Migraine.

PURPOSE OF REVIEW: This review assesses the effectiveness and safety of light therapy, particularly green light therapy, as an emerging non-pharmacological treatment for chronic migraine (CM). It aims to highlight alternative or complementary approaches to traditional pharmacological remedies, focusing the need for diverse treatment options. RECENT FINDINGS: Despite sensitivity to light being a defining feature of migraine, light therapy has shown promising signs in providing substantial symptom relief. Studies have provided insights into green light therapy's role in managing CM. These studies consistently demonstrate its efficacy in reducing the frequency, severity, and symptoms of migraines. Additional benefits observed include improvements in sleep quality and reductions in anxiety. Importantly, green light therapy has been associated with minimal side effects, indicating its potential as a suitable option for migraine sufferers. In addition to green light, other forms of light therapy, such as infrared polarized light, low-level laser therapy (LLLT), and intravascular irradiation of blood (ILIB), are also being explored with potential therapeutic effects. Light therapies, especially green light therapy, are recognized as promising, safe, and non-pharmacological interventions for treating CM. They have been shown to be effective in decreasing headache frequency and enhancing the overall quality of life. However, current studies, often limited by small sample sizes, prompt more extensive clinical trials to better understand the full impact of light therapies. The exploration of other light-based treatments, such as LLLT and ILIB, warrants further research to broaden the scope of effective migraine management strategies.

Gut microbiota-derived acetate attenuates lung injury induced by influenza infection via protecting airway tight junctions.

BACKGROUND: Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV) infection, suggesting the involvement of the gut-to-lung axis in a host's response to IAV. IAV primarily destroys airway epithelium tight junctions (TJs) and consequently causes acute respiratory disease syndrome. It is known that GM and their metabolism produce an anti-influenza effect, but their role in IAV-induced airway epithelial integrity remains unknown. METHODS: A mouse model of IAV infection was established. GM were analyzed using 16S rRNA gene sequencing, and short-chain fatty acids (SCFAs) levels were measured. GM depletion and fecal microbiota transplantation (FMT) were conducted to validate the role of GM in IAV infection. A pair-feeding experiment was conducted to reveal whether IAV-induced GM dysbiosis is attributed to impaired food intake. Furthermore, human bronchial epithelial (HBE) cells were cocultured with IAV in the presence or absence of acetate. TJs function was analyzed by paracellular permeability and transepithelial electronic resistance (TEER). The mechanism of how acetate affects TJs integrity was evaluated in HBE cells transfected with G protein-coupled receptor 43 (GPR43) short hairpin RNA (shRNA). RESULTS: IAV-infected mice exhibited lower relative abundance of acetate-producing bacteria (Bacteroides, Bifidobacterium, and Akkermansia) and decreased acetate levels in gut and serum. These changes were partly caused by a decrease in food consumption (due to anorexia). GM depletion exacerbated and FMT restored IAV-induced lung inflammatory injury. IAV infection suppressed expressions of TJs (occludin, ZO-1) leading to disrupted airway epithelial barrier function as evidenced by decreased TEER and increased permeability. Acetate pretreatment activated GPR43, partially restored IAV-induced airway epithelial barrier function, and reduced inflammatory cytokines levels (TNF-α, IL-6, and IL-1ß). Such protective effects of acetate were absent in HBE cells transfected with GPR43 shRNA. Acetate and GPR43 improved TJs in an AMP-activated protein kinase (AMPK)-dependent manner. CONCLUSION: Collectively, our results demonstrated that GM protected airway TJs by modulating GPR43-AMPK signaling in IAV-induced lung injury. Therefore, improving GM dysbiosis may be a potential therapeutic target for patients with IAV infection.

Deep Learning-Based Approach for Identifying and Measuring Focal Liver Lesions on Contrast-Enhanced MRI.

BACKGROUND: The number of focal liver lesions (FLLs) detected by imaging has increased worldwide, highlighting the need to develop a robust, objective system for automatically detecting FLLs. PURPOSE: To assess the performance of the deep learning-based artificial intelligence (AI) software in identifying and measuring lesions on contrast-enhanced magnetic resonance imaging (MRI) images in patients with FLLs. STUDY TYPE: Retrospective. SUBJECTS: 395 patients with 1149 FLLs. FIELD STRENGTH/SEQUENCE: The 1.5 T and 3 T scanners, including T1-, T2-, diffusion-weighted imaging, in/out-phase imaging, and dynamic contrast-enhanced imaging. ASSESSMENT: The diagnostic performance of AI, radiologist, and their combination was compared. Using 20 mm as the cut-off value, the lesions were divided into two groups, and then divided into four subgroups: <10, 10-20, 20-40, and ≥40 mm, to evaluate the sensitivity of radiologists and AI in the detection of lesions of different sizes. We compared the pathologic sizes of 122 surgically resected lesions with measurements obtained using AI and those made by radiologists. STATISTICAL TESTS: McNemar test, Bland-Altman analyses, Friedman test, Pearson's chi-squared test, Fisher's exact test, Dice coefficient, and intraclass correlation coefficients. A P-value <0.05 was considered statistically significant. RESULTS: The average Dice coefficient of AI in segmentation of liver lesions was 0.62. The combination of AI and radiologist outperformed the radiologist alone, with a significantly higher detection rate (0.894 vs. 0.825) and sensitivity (0.883 vs. 0.806). The AI showed significantly sensitivity than radiologists in detecting all lesions <20 mm (0.848 vs. 0.788). Both AI and radiologists achieved excellent detection performance for lesions ≥20 mm (0.867 vs. 0.881, P = 0.671). A remarkable agreement existed in the average tumor sizes among the three measurements (P = 0.174). DATA CONCLUSION: AI software based on deep learning exhibited practical value in automatically identifying and measuring liver lesions. TECHNICAL EFFICACY: Stage 2.

Comparative effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies and onabotulinumtoxinA in chronic migraine: A multicenter, real-world study in Taiwan.

OBJECTIVE: To compare the real-world effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and onabotulinumtoxinA in chronic migraine (CM) patients. METHODS: This multicenter study involved retrospective analysis of prospectively collected data of CM patients treated with CGRP mAbs or onabotulinumtoxinA, including difficult-to-treat (DTT) patients (i.e., ≥3 preventive failures). Treatment outcomes were determined at 6 months based on prospective headache diaries and Migraine Disability Assessment (MIDAS). RESULTS: The study included 316 (55 M/261F, mean age 44.4 ± 13.5 years) and 333 (61 M/272F, mean age 47.9 ± 13.4 years) CM patients treated with CGRP mAbs or onabotulinbumtoxinA, respectively. At 6 months, CGRP mAb treatment was associated with a greater decrease in monthly migraine days (MMDs) (-13.0 vs. -8.7 days/month, p < 0.001) and a higher ≥50% responder rate (RR) (74.7% vs. 50.7%, p < 0.001) compared with onabotulinumtoxinA injections. The findings were consistent in DTT patients (-13.0 vs. -9.1 MMDs, p < 0.001; ≥50% RR: 73.9% vs. 50.3%, p < 0.001) or those with medication-overuse headache (MOH) (-13.3 vs. -9.0 MMDs, p < 0.001; ≥50% RR: 79.0% vs. 51.6%, p < 0.001). Besides, patients receiving CGRP mAbs had greater improvement (-42.2 vs. -11.8, p < 0.001) and a higher ≥50% RR (62.0% vs. 40.0%, p = 0.001) in MIDAS scores and a lower rate of adverse events (AEs) (6.0% vs. 21.0%, p < 0.001). However, none of the patients discontinued treatment due to AEs. CONCLUSIONS: In this multicenter, real-world study, CGRP mAbs were more effective than onabotulinumtoxinA in CM patients, even in DTT or MOH patients. All of these injectables were well tolerated. Further prospective studies are needed to verify these findings.

Maintaining calcium homeostasis as a strategy to alleviate nephrotoxicity caused by evodiamine.

Evodiamine (EVO), the main active alkaloid in Evodia rutaecarpa, was shown to exert various pharmacological activities, especially anti-tumor. Currently, it is considered a potential anti-cancer drug due to its excellent anti-tumor activity, which unfortunately has adverse reactions, such as the risk of liver and kidney injury, when Evodia rutaecarpa containing EVO is used clinically. In the present study, we aim to clarify the potential toxic target organs and toxicity mechanism of EVO, an active monomer in Evodia rutaecarpa, and to develop mitigation strategies for its toxicity mechanism. Transcriptome analysis and related experiments showed that the PI3K/Akt pathway induced by calcium overload was an important step in EVO-induced apoptosis of renal cells. Specifically, intracellular calcium ions were increased, and mitochondrial calcium ions were decreased. In addition, EVO-induced calcium overload was associated with TRPV1 receptor activation. In vivo TRPV1 antagonist and calcium chelator effects were observed to significantly reduce body weight loss and renal damage in mice due to EVO toxicity. The potential nephrotoxicity of EVO was further confirmed by an in vivo test. In conclusion, TRPV1-mediated calcium overload-induced apoptosis is one of the mechanisms contributing to the nephrotoxicity of EVO due to its toxicity, whereas maintaining body calcium homeostasis is an effective measure to reduce toxicity. These studies suggest that the clinical use of EVO-containing herbal medicines should pay due attention to the changes in renal function of patients as well as the off-target effects of the drugs.

Evaluating the clinical impact of resuscitative endovascular balloon occlusion of the aorta in patients with blunt trauma with hemorrhagic shock and coexisting traumatic brain injuries: a retrospective cohort study.

BACKGROUND: The impact of resuscitative endovascular balloon occlusion of the aorta (REBOA) on traumatic brain injuries remains uncertain, with potential outcomes ranging from neuroprotection to exacerbation of the injury. The study aimed to evaluate consciousness recovery in patients with blunt trauma with shock and traumatic brain injuries. MATERIAL AND METHODS: Data were obtained from the American College of Surgeons Trauma Quality Improvement Program from 2017-2019. During the study period, 3,138,896 trauma registries were examined, and 16,016 adult patients with blunt trauma, shock, and traumatic brain injuries were included. Among these, 172 (1.1%) underwent REBOA. Comparisons were conducted between patients with and without REBOA after implementing 1:3 propensity score matching to mitigate disparities. The primary outcome was the highest Glasgow Coma Scale score during admission. The secondary outcomes encompassed the volume of blood transfusion, the necessity for hemostatic interventions and therapeutic neurosurgery, and mortality rate. RESULTS: Through well-balanced propensity score matching, a notable difference in mortality rate was observed, with 59.7% in the REBOA group and 48.7% in the non-REBOA group (P=0.015). In the REBOA group, the median 4-hour red blood cell transfusion was significantly higher (2800 mL [1500, 4908] vs. 1300 mL [600, 2500], P<0.001). The REBOA group required lesser hemorrhagic control surgeries (31.8% vs. 47.7%, P<0.001) but needed more transarterial embolization interventions (22.2% vs 15.9%, P=0.076). The incidence of therapeutic neurosurgery was 5.1% in the REBOA group and 8.7% in the non-REBOA group (P=0.168). Among survivors in the REBOA group, the median highest Glasgow Coma Scale score during admission was significantly greater for both total (11 [8, 14] vs. 9 [6, 12], P=0.036) and motor components (6 [4, 6] vs. 5 [3, 6], P=0.037). The highest GCS score among the survivors with predominant pelvic injuries was not different between the two groups (11 [8, 13] vs. 11 [7, 14], P=0.750). CONCLUSIONS: Patients experiencing shock and traumatic brain injury have high mortality rates, necessitating swift resuscitation and prompt hemorrhagic control. The use of REBOA as an adjunct for bridging definitive hemorrhagic control may correlate with enhanced consciousness recovery.

The Association Between Sleep Problems and Attentional Network Functions in Patients with Self-Limited Epilepsy with Centrotemporal Spikes.

Purpose: To investigate sleep problems in children with self-limited epilepsy with central temporal spiking (SeLECTS) and to assess the relationship between sleep problems and attention network dysfunction. Patients and methods: 107 children 6-14 years of age with SeLECTS and 90 age- and sex-matched healthy controls were recruited for this study. The sleep status of these participants was evaluated using the Children's Sleep Habits Questionnaire (CSHQ), while attentional network function was assessed with the attention network function test (ANT). Results: Together, these analyses revealed that children with SeLECTS exhibited higher total CSHQ scores and sleep disorder incidence relative to healthy controls (P< 0.001). Children with SeLECTS had higher scores in delayed sleep onset, sleep duration, night awakenings, parasomnias, daytime sleepiness and sleep anxiety (P<0.01). Total CSHQ scores were negatively correlated with average ANT correct rates (ρ= -0.253, P<0.01), while they were positively correlated with total reaction time (ρ=0.367, P<0.01) and negatively correlated with the efficiency of the alerting and executive control networks (ρ=-0.344 P<0.01; ρ=-0.418 P<0.01). Conclusion: Children with SeLECTS face a higher risk of experiencing sleep disorders relative to age-matched healthy children, while also demonstrating that the magnitude of the impairment of attentional network function in these children is positively correlated with sleep disorder severity. Thus, the prognosis and quality of life of children with SeLECTS can be improved by interventions addressing sleep disorders.

PDIA3 orchestrates effector T cell program by serving as a chaperone to facilitate the non-canonical nuclear import of STAT1 and PKM2.

Dysregulated T cell activation underpins the immunopathology of rheumatoid arthritis (RA), yet the machineries that orchestrate T cell effector program remain incompletely understood. Herein, we leveraged bulk and single-cell RNA sequencing data from RA patients and validated protein disulfide isomerase family A member 3 (PDIA3) as a potential therapeutic target. PDIA3 is remarkably upregulated in pathogenic CD4 T cells derived from RA patients and positively correlates with C-reactive protein level and disease activity score 28. Pharmacological inhibition or genetic ablation of PDIA3 alleviates RA-associated articular pathology and autoimmune responses. Mechanistically, T cell receptor signaling triggers intracellular calcium flux to activate NFAT1, a process that is further potentiated by Wnt5a under RA settings. Activated NFAT1 then directly binds to the Pdia3 promoter to enhance the expression of PDIA3, which complexes with STAT1 or PKM2 to facilitate their nuclear import for transcribing T helper 1 (Th1) and Th17 lineage-related genes, respectively. This non-canonical regulatory mechanism likely occurs under pathological conditions, as PDIA3 could only be highly induced following aberrant external stimuli. Together, our data support that targeting PDIA3 is a vital strategy to mitigate autoimmune diseases, such as RA, in clinical settings.

The potential of glycinin basic peptide derived from soybean as a promising candidate for the natural food additive and preservative: A review.

Glycinin basic peptide (GBP) is the basic polypeptide of soybean glycinin that is isolated using cheap and readily available raw materials (soybean meals). GBP can bear high-temperature processing and has good functional properties, such as emulsification and adhesion properties et al. GBP exhibits broad-spectrum antimicrobial activities against Gram-positive and Gram-negative bacteria as well as fungi. Beyond that, GBP shows enormous application potential to improve the quality and extend the shelf life of food products. This review will systematically provide information on the purification, physicochemical and functional properties of GBP. Moreover, the antimicrobial activities and multi-target antimicrobial mechanism of GBP as well as the applications of GBP in different food products are also reviewed and discussed in detail. This review aims to offer valuable insights for the applications of GBP in the food industry as a promising natural food additive and preservative.

Determination of the variations in the metabolic profiles and bacterial communities during traditional craftsmanship Liupao tea processing.

In this study, the metabolic profiles of traditional craftsmanship (TC) Liupao tea presented great changes at different processing stages. The contents of flavonoids and their glycosides generally exhibited a continuing downward trend, resulting in the sensory quality of TC-Liupao tea gradually improved. However, the taste of TC-Liupao tea faded when piling exceeded 12 h, as a result of the excessive degradation of some key flavor substances. Therefore, it could be deduced that piling for 10 h might be optimum for the quality formation of TC-Liupao tea. Sphingomonas, Acrobacter, Microbacterium, and Methylobacterium were the dominant bacteria during piling. The correlation analysis between differential metabolites and bacteria showed that only Sphingomonas and Massilia were significantly correlated to metabolites, demonstrating that the bacteria had less effect on the transformation of metabolites. Thus, the metabolic structure change during the process of TC-Liupao tea might be mainly attributed to the high temperature and humidity environment.

The long-term efficacy of eltrombopag in children with immune thrombocytopenia.

Immune thrombocytopenia (ITP) is the most common autoimmune disorder characterized by decreased platelet counts and impaired platelet production. Eltrombopag has been demonstrated to be safe and effective for children with ITP. It is reported eltrombopag can achieve a sustained response off treatment. However, data on its overall efficacy and safety profile are scarce in children. This study aimed to investigate the long-term efficacy of eltrombopag in children with ITP. Treatment overall response (OR), complete response (CR), response (R), durable response (DR), no response (NR), treatment free remission (TFR), and relapse rate, were assessed in 103 children with ITP during eltrombopag therapy. The OR rate, CR rate, R rate, DR rate, NR rate, TFR rate, and relapse rate were 67.0%, 55.3%, 11.7%, 56.3%, 33.0%, 60%, 36.2%, respectively. Importantly, we discovered that newly diagnosed ITP patients showed a higher DR rate, TFR rate and lower relapse rate compared to persistent and chronic ITP patients. Furthermore, the CR rate, DR rate, and TFR rate of 5 patients under six months were 100%. None of them suffered relapse. The most common adverse event (AEs) was hepatotoxicity (7.77%). Our study highlighted the critical role of eltrombopag as the second-line treatment in children with ITP who were intolerant to first-line therapy.

DTI-ALPS index decreased in patients with Type 2 Diabetes Mellitus.

Backgrounds: Type 2 Diabetes Mellitus (T2DM) has become a significant global public health issue, characterized by a rising prevalence and associated deficits across multiple organ systems. Our study aims to utilize the DTI-ALPS technique to assess the change of ALPS index in T2DM patients, and to explore whether such changes are correlated with cognition level and diffusion parameters. Methods: The study involved 41 patients with T2DM (mean age, 60.49 ± 8.88 years) and 27 healthy controls (mean age, 58.00 ± 7.63 years). All subjects underwent MRI examination, cognitive assessment, and laboratory tests. Tract-based spatial statistics (TBSS) was used to evaluate white matter changes. GLM was performed to check the DTI-ALPS index difference between T2DM and HC groups. Spearman correlation analysis and partial correlation analysis were used to analyze the correlation between the DTI-ALPS index and diffusion properties & cognitive scores. Results: The results show that the ALPS index was lower in T2DM patients. MoCA score was significantly correlated with the ALPS index. Patients with T2DM had a significant increase in both mean diffusivity (MD) and radial diffusivity (RD) and decrease in fractional anisotropy (FA) compared to the HC group. Conclusion: The results suggest that the ALPS index is decreased in T2DM patients and associates with cognitive level.

Value of magnetic resonance imaging for diagnosis of LR­3 and LR-4 lesions coexisting with hepatocellular carcinoma.

PURPOSE: To explore which preoperative clinical data and conventional magnetic resonance imaging (MRI) features may indicate the presence of hepatocellular carcinoma (HCC) in HCC patients coexisting with LR-3 and LR-4 lesions. METHODS: HCC Patients coexisting with LR-3 and LR-4 lesions who participated in a prospective clinical trial (XX) were included in this study. Two radiologists independently assessed the preoperative MRI features and each lesion was assigned according to the liver imaging reporting and data system (LI-RADS). The preoperative clinical data were also evaluated. The relative values of these parameters were assessed as potential predictors of HCC for coexisting LR-3 and LR-4 lesions. RESULTS: We enrolled 102 HCC patients (58.1 ± 11.5 years; 84.3% males) coexisting with 110 LR-3 and LR-4 lesions (HCCs group [n = 66]; non-HCCs group [n = 44]). The presence of restricted diffusion (OR: 18.590, p < 0.001), delayed enhancement (OR: 0.113, p < 0.001), and mild-moderate T2 hyperintensity (OR: 3.084, p = 0.048) were found to be independent predictors of HCC diagnosis. The sensitivity and specificity of the above independent variables for the diagnosis of HCC ranged from 66.7 to 80.3% and 56.8 to 88.6%, respectively. ROC analysis showed that, in discriminating HCC, the AUCs of the above factors were 0.777, 0.686, and 0.670, respectively. Combining these three findings for the prediction of HCC resulted in a specificity greater than 97%, and the AUC further increased to 0.874. CONCLUSION: The presence of restricted diffusion, delayed enhancement, and mild-moderate T2 hyperintensity can be useful features for risk stratification of coexisting LR-3 and LR-4 lesions in HCC patients. Trial registration a prospective clinical trial (ChiCTR2000036201).

Preoperative prediction of lymphovascular invasion and T-staging of rectal cancer via a dual-energy computed tomography iodine map: a feasibility study.

PURPOSE: To investigate the value of dual-energy computed tomography (DECT) in predicting lymphovascular invasion (LVI) and the accuracy of preoperative T-staging of rectal cancer (RC). METHODS: Forty-nine patients with RC who had not received radiotherapy were enrolled to undergo a DECT scan. All patients underwent surgical tumor resection within 3-5 days after the DECT scan. Preoperative T-staging of RC based on images was performed by experienced radiologists. The normalized iodine concentrations (NIC) of the tumor and the perirectal adipose tissue (PAT) from the arterial phase (AP) and venous phase (VP) were measured using DECT. The tumor LVI and T-staging confirmed by pathology were used as the gold standard for grouping (group A, LVI-; group B, LVI+; group C, T1-2; and group D, T3-4a). The NIC values between two groups were compared using the Mann-Whitney U test, with P < 0.05 indicating a statistically significant difference. The accuracy of NIC in predicting LVI and distinguishing T1-2 RC from T3-4a RC were determined via receiver operating characteristic curve analysis, and the optimal cut-off of NIC was determined using the area under the curve. RESULTS: The tumor NIC values were significantly higher in the LV+ group than in the LVI- group in the VP (0.728 ± 0.031 vs. 0.669 ± 0.034, P < 0.001). The NIC values of PAT were significantly higher in the T3-4a group than in the T1-2 group in both the AP (4.034 ± 0.991 vs. 3.115 ± 0.581, P < 0.05) and the VP (5.481 ± 1.054 vs. 3.450 ± 0.980, P < 0.001). The accuracy of using NIC values to distinguish between the LVI+ group and the LVI- group and to diagnose the T3-4a group were 85.7% and 89.8%, respectively. However, there was no statistically significant difference between the NIC value in the LVI+ group and in the LVI- group in the AP. There was also no statistical difference in the tumor NIC value between the T1-2 group and the T3-4a group. CONCLUSION: The tumor and PAT NIC are valuable indicators in RC that can preoperatively predict LVI and improve the accuracy of preoperative RC T-staging. CLINICAL SIGNIFICANCE: The use of DECT improves the T-staging and LVI prediction of RC, which is helpful in guiding the clinical selection of appropriate treatment modalities and improving prognostic outcomes.

Myasthenia gravis with tongue muscle atrophy: A case series.

Here, we presented 6 patients who were admitted to our institution and diagnosed as myasthenia gravis (MG) with tongue muscle atrophy. All these 6 patients developed symptoms of bulbar muscle weakness in acetylcholine receptor antibodies positive MG (AChR-MG) (3/6), muscle-specific receptor tyrosine kinase antibodies positive MG (MuSK-MG) (1/6), and sero-negative MG (2/6). Most of patients had "triple-furrowed" tongue except for patient 2 with irregular atrophy of tongue muscle. Tongue muscle atrophy occurs in patients with MuSK-MG, AChR-MG, and sero-negative MG. Atrophied tongue muscles of five patients with MG were reversible after immunotherapy.

Septic arthritis caused by gout progressed to sepsis and hemophagocytic syndrome.

Gouty stone ulcers inducing bloodstream infections leading to chest wall and mediastinal abscesses and progression to sepsis and hemophagocytic syndrome are extremely rare in clinical practice. Keep in mind the possibility of coexistence of gout and septic arthritis. Prompt and accurate diagnosis and treatment of hemophagocytic syndrome (HPS), a highly fatal disease with acquired immunoregulatory abnormalities and release of large amounts of inflammatory factors, are important to save the patient's life.

Berberine improves cognitive impairment by alleviating brain atrophy and promoting white matter reorganization in diabetic db/db mice: a magnetic resonance imaging-based study.

Diabetic cognitive impairment is a common complication in type 2 diabetes. Berberine (BBR) is an isoquinoline alkaloid that has been shown to have neuroprotective effects against diabetes. This study aimed to investigate the effect of BBR on the gray and white matter of the brain by using magnetic resonance imaging (MRI) and to explore the underlying mechanisms. The study used diabetic db/db mice and administered BBR (50 and 100 mg/kg) intragastrically for twelve weeks. Morris water maze was applied to examine cognitive function. T2-weighted imaging (T2WI) was performed to assess brain atrophy, and diffusion tensor imaging (DTI) combined with fiber tracking was conducted to monitor the structural integrity of the white matter, followed by histological immunostaining. Furthermore, the protein expressions of the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT)/ glycogen synthase kinase-3ß (GSK-3ß) were detected. The results revealed that BBR significantly improved the spatial learning and memory of the db/db mice. T2WI exhibited ameliorated brain atrophy in the BBR-treated db/db mice, as evidenced by reduced ventricular volume accompanied by increased hippocampal volumes. DTI combined with fiber tracking revealed that BBR increased FA, fiber density and length in the corpus callosum/external capsule of the db/db mice. These imaging findings were confirmed by histological immunostaining. Notably, BBR significantly enhanced the protein levels of phosphorylated AKT at Ser473 and GSK-3ß at Ser9. Collectively, this study demonstrated that BBR significantly improved the cognitive function of the diabetic db/db mice through ameliorating brain atrophy and promoting white matter reorganization via AKT/GSK-3ß pathway.

Inhibition of mTORC2 promotes natriuresis in Dahl salt-sensitive rats via the decrease of NCC and ENaC activity.

We have previously observed that prolonged administration of rapamycin, an inhibitor targeting the mammalian target of rapamycin 1 (mTORC1), partially reduced hypertension and alleviated kidney inflammation in Dahl salt-sensitive (SS) rats. In contrast, treatment with PP242, an inhibitor affecting both mTORC1/mTORC2, not only completely prevented hypertension but also provided substantial protection against kidney injury. Notably, PP242 exhibited potent natriuretic effects that were not evident with rapamycin. The primary objective of this study was to pinpoint the specific tubular sites responsible for the natriuretic effect of PP242 in SS rats subjected to either 0.4% NaCl (NS) or 4.0% NaCl (HS) diet. Acute effects of PP242 on natriuretic, diuretic, and kaliuretic responses were determined in unanesthetized SS rats utilizing benzamil, furosemide, or hydrochlorothiazide (inhibitors of ENaC, NKCC2, or NCC, respectively) either administered alone or in combination. The findings indicate that the natriuretic effects of PP242 in SS rats stem predominantly from the inhibition of NCC and a reduction of ENaC open probability. Molecular analysis revealed that mTORC2 regulates NCC activity through protein phosphorylation and ENaC activity through proteolytic cleavage in vivo. Evidence also indicated that PP242 also prevents the loss of K+ associated with the inhibition of NCC. These findings suggest that PP242 may represent an improved therapeutic approach for antihypertensive intervention, potentially controlling blood pressure and mitigating kidney injury in salt-sensitive human subjects.