Effect of l-oxiracetam and oxiracetam on memory and cognitive impairment in mild-to-moderate traumatic brain injury patients: Study protocol for a randomized controlled trial.

Objectives: Patients with traumatic brain injury (TBI) often suffer memory and cognitive impairments, and oxiracetam-like drugs are considered to have a positive impact on these symptoms potentially. However, the efficacy and safety of l-oxiracetam and oxiracetam in TBI patients have not been sufficiently investigated. Methods: The study adopts a multicenter, randomized, double-blind, parallel-group, phase 3 clinical trial design in 74 centers across 51 hospitals in China. A total of 590 TBI patients meeting criteria will be randomly allocated into three groups in a 2:2:1 ratio: l-oxiracetam group, oxiracetam group, and placebo group. The treatment period is 14 days, with a follow-up period of 90 days. The primary outcome measure is the change in the Loewenstein Occupational Therapy Cognitive Assessment score at 90 days after treatment. Secondary outcomes include changes in other cognitive assessments, neurological function, activities of daily living, and safety assessments. Discussion: There is no robust evidence to suggest that l-oxiracetam and oxiracetam can enhance memory and cognitive function in patients with mild to moderate TBI. This study has the potential to answer this crucial clinical question. Trial registration: chinadrugtrials.org.cn, identifier CTR20192539; ClinicalTrials.gov, identifier NCT04205565.

A dual-prodrug nanogel combining Vorinostat and Pyropheophorbide a for a high efficient photochemotherapy.

The challenges posed by intractable relapse and metastasis in cancer treatment have led to the development of various forms of photodynamic therapy (PDT). However, traditional drug delivery systems, such as virus vectors, liposomes, and polymers, often suffer from issues like desynchronized drug release, carrier instability, and drug leakage during circulation. To address these problems, we have developed a dual-prodrug nanogel (PVBN) consisting of Pyro (Pyropheophorbide a) and SAHA (Vorinostat) bound to BSA (Bovine Serum Albumin), which facilitates synchronous and spontaneous drug release in situ within the lysosome. Detailed results indicate that PVBN-treated tumor cells exhibit elevated levels of ROS and Acetyl-H3, leading to necrosis, apoptosis, and cell cycle arrest, with PDT playing a dominant role in the synergistic therapeutic effect. Furthermore, the anti-tumor efficacy of PVBN was validated in melanoma-bearing mice, where it significantly inhibited tumor growth and pulmonary metastasis. Overall, our dual-prodrug nanogel, formed by the binding of SAHA and Pyro to BSA and releasing drugs within the lysosome, represents a novel and promising strategy for enhancing the clinical efficacy of photochemotherapy.

Utilizing a suture-constrained covered stent for shunt reduction to treat transjugular intrahepatic portosystemic shunt-related refractory hepatic encephalopathy: a retrospective study.

PURPOSE: Refractory hepatic encephalopathy (RHE) can occur as a consequence of excessive shunting following the creation of a transjugular intrahepatic portosystemic shunt (TIPS). We describe a technique that utilizes a suture-constrained covered stent for shunt reduction to treat TIPS-related RHE. MATERIALS AND METHODS: Between January 2017 and September 2023, 25 patients with TIPS-related RHE who underwent shunt reduction utilizing a suture-constrained covered stent were reviewed. The procedure involved reducing the diameter of a polytetrafluoroethylene-covered stent from 8 to 5 mm with a non-absorbable suture and inserting it into the existing TIPS stent to reduce shunt flow. RESULTS: Twelve of the 25 patients were evaluated. Shunt reduction was technically successful in all patients and no immediate complications related to the procedures were observed. Varying degrees of improvement in HE symptoms were observed after shunt reduction, with a mean increase in portosystemic gradient of 5 mmHg compared to pre-procedure, and complete disappearance of symptoms was observed in seven (58.3%) individuals. After a median follow-up of 8.3 months, HE recurred in 4 patients (33.3%) and TIPS indication recurred in 2 patients (16.7%) in the form of ascites and variceal bleeding, respectively. One patient (8.3%) developed shunt dysfunction detected by Doppler ultrasound and was accompanied by the presence of hepatic hydrothorax and ascites. At the end of the study, 5 patients (41.7%) were alive, 5 (41.7%) succumbed to liver failure, and 2 (16.7%) succumbed to pneumonia. CONCLUSIONS: Constraining the stent diameter with a suture is feasible, and using this suture-constrained covered stent for shunt reduction can effectively improve TIPS-related RHE. Further investigations are warranted to precisely delineate the impact of the increased portosystemic gradient and to optimize patient survival.

Crafting Docetaxel-Loaded Albumin Nanoparticles Through a Novel Thermal-Driven Self-Assembly/Microfluidic Combination Technology: Formulation, Process Optimization, Stability, and Bioavailability.

Background: The commercial docetaxel (DTX) formulation causes severe side effects due to polysorbate 80 and ethanol. Novel surfactant-free nanoparticle (NP) systems are needed to improve bioavailability and reduce side effects. However, controlling the particle size and stability of NPs and improving the batch-to-batch variation are the major challenges. Methods: DTX-loaded bovine serum albumin nanoparticles (DTX-BSA-NPs) were prepared by a novel thermal-driven self-assembly/microfluidic technology. Single-factor analysis and orthogonal test were conducted to obtain the optimal formulation of DTX-BSA-NPs in terms of particle size, encapsulation efficiency (EE), and drug loading (DL). The effects of oil/water flow rate and pump pressure on the particle size, EE, and DL were investigated to optimize the preparation process of DTX-BSA-NPs. The drug release, physicochemical properties, stability, and pharmacokinetics of NPs were evaluated. Results: The optimized DTX-BSA-NPs were uniform, with a particle size of 118.30 nm, EE of 89.04%, and DL of 8.27%. They showed a sustained release of 70% over 96 hours and an increased stability. There were some interactions between the drug and excipients in DTX-BSA-NPs. The half-life, mean residence time, and area under the curve (AUC) of DTX-BSA-NPs increased, but plasma clearance decreased when compared with DTX. Conclusion: The thermal-driven self-assembly/microfluidic combination method effectively produces BSA-based NPs that improve the bioavailability and stability of DTX, offering a promising alternative to traditional formulations.

FTO is Associated with Patient Prognosis and Immune Infiltrates in Gastric Cancer and Regulates TGF-ß Expression.

AIMS: This study aimed to examine the associations of FTO expression with prognosis, tumor microenvironment (TME), immune cell infiltration, immune checkpoint genes, and relevant signaling pathways in GC. Furthermore, the relationship between FTO and TGF-ß was studied in GC. METHODS: The mRNA expression and clinical survival data of GC samples were obtained from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD). TIMER2, TNM plot, and GEPIA database were used to analyze FTO expression. The associations of FTO with prognosis and clinicopathologic features were assessed using the Kaplan-Meier plotter and UALCAN database, respectively. The R software was employed to analyze its related signaling pathways and the associations with TME, immune cell infiltration, and immune checkpoint genes. GEPIA and ENCORI were used to examine the association of FTO with TGF-ß expression. The SRAMP website was utilized to predict m6A modification of TGF-ß. IHC, Western blot, and qPCR were used to analyze the expression levels of FTO and TGF-ß in clinical gastric cancer tissue samples or gastric cancer cell lines. In addition, a m6A RNA methylation assay kit was used to determine m6A levels in gastric cancer cells. RESULTS: FTO mRNA and protein levels were significantly elevated in GC compared to normal gastric tissues. Kaplan-Meier survival analysis suggested that upregulated FTO was associated with a worse prognosis in GC. Upregulated FTO was markedly correlated with differentiation degree, lymph node metastasis, and clinical TNM stage. GO and KEGG pathway analyses revealed that FTO-associated molecules were enriched in neuroactive ligand-receptor interaction, calcium signaling, PI3k-Akt signaling, cAMP signaling pathways, and TGF-ß signaling pathways, among others. The TME score was remarkably higher in the high-FTO group than in the low-FTO group. Furthermore, FTO expression had positive correlations with different types of immune cells and immune checkpoint genes. Moreover, FTO may regulate TGF-ß in an m6A RNA modification manner in GC. CONCLUSION: FTO may become an independent predictive prognostic biomarker correlating with TME, immune cell infiltration, and immune checkpoint genes in gastric cancer and might influence GC progression by regulating TGF-ß expression.

Obeticholic acid attenuates the intestinal barrier disruption in a rat model of short bowel syndrome.

BACKGROUND: Short bowel syndrome (SBS) features nutrients malabsorption and impaired intestinal barrier. Patients with SBS are prone to sepsis, intestinal flora dysbiosis and intestinal failure associated liver disease. Protecting intestinal barrier and preventing complications are potential strategies for SBS treatment. This study aims to investigate the effects of farnesoid X receptor (FXR) agonist, obeticholic acid (OCA), have on intestinal barrier and ecological environment in SBS. METHODS AND RESULTS: Through testing the small intestine and serum samples of patients with SBS, impaired intestinal barrier was verified, as evidenced by reduced expressions of intestinal tight junction proteins (TJPs), increased levels of apoptosis and epithelial cell damage. The intestinal expressions of FXR and related downstream molecules were decreased in SBS patients. Then, global FXR activator OCA was used to further dissect the potential role of the FXR in a rat model of SBS. Low expressions of FXR-related molecules were observed on the small intestine of SBS rats, along with increased proinflammatory factors and damaged barrier function. Furthermore, SBS rats possessed significantly decreased body weight and elevated death rate. Supplementation with OCA mitigated the damaged intestinal barrier and increased proinflammatory factors in SBS rats, accompanied by activated FXR-related molecules. Using 16S rDNA sequencing, the regulatory role of OCA on gut microbiota in SBS rats was witnessed. LPS stimulation to Caco-2 cells induced apoptosis and overexpression of proinflammatory factors in vitro. OCA incubation of LPS-pretreated Caco-2 cells activated FXR-related molecules, increased the expressions of TJPs, ameliorated apoptosis and inhibited overexpression of proinflammatory factors. CONCLUSIONS: OCA supplementation could effectively ameliorate the intestinal barrier disruption and inhibit overexpression of proinflammatory factors in a rat model of SBS and LPS-pretreated Caco-2 cells. As a selective activator of FXR, OCA might realize its protective function through FXR activation.

Comprehensive review of emerging contaminants: Detection technologies, environmental impact, and management strategies.

Emerging contaminants (ECs) are a diverse group of unregulated pollutants increasingly present in the environment. These contaminants, including pharmaceuticals, personal care products, endocrine disruptors, and industrial chemicals, can enter the environment through various pathways and persist, accumulating in the food chain and posing risks to ecosystems and human health. This comprehensive review examines the chemical characteristics, sources, and varieties of ECs. It critically evaluates the current understanding of their environmental and health impacts, highlighting recent advancements and challenges in detection and analysis. The review also assesses existing regulations and policies, identifying shortcomings and proposing potential enhancements. ECs pose significant risks to wildlife and ecosystems by disrupting animal hormones, causing genetic alterations that diminish diversity and resilience, and altering soil nutrient dynamics and the physical environment. Furthermore, ECs present increasing risks to human health, including hormonal disruptions, antibiotic resistance, endocrine disruption, neurological effects, carcinogenic effects, and other long-term impacts. To address these critical issues, the review offers recommendations for future research, emphasizing areas requiring further investigation to comprehend the full implications of these contaminants. It also suggests increased funding and support for research, development of advanced detection technologies, establishment of standardized methods, adoption of precautionary regulations, enhanced public awareness and education, cross-sectoral collaboration, and integration of scientific research into policy-making. By implementing these solutions, we can improve our ability to detect, monitor, and manage ECs, reducing environmental and public health risks.

Phaeohyphomycosis caused by Corynespora cassiicola, a plant pathogen worldwide.

Although rare, trans-kingdom infection features an interesting infection biology concept, in which highly versatile pathogenic attributes allow successful infections in evolutionarily highly divergent species. Corynespora cassiicola is a phytopathogenic fungus and occasionally causes human infections. Herein, we report a phaeohyphomycosis case caused by C. cassiicola. Given that sporadic reports may contribute to a lack of awareness of the transmission route, clinical manifestations, and diagnostic and clinical management, we systematically reviewed the cases reported thus far. Nine patients were identified and included in the pooled analysis, 88.9% (8/9) of whom were reported after 2010. All patients were from Asian, African, and Latin American countries, among whom 77.8% (7/9) were farmers or lived in areas with active agriculture. Exposed body parts were the major affected infection area, and clinical manifestations were mainly non-specific inflammatory reactions. Although biochemical and morphological examinations confirmed the presence of fungal infection, molecular analysis was used for the final diagnosis, with 77.8% (7/9) being identified by internal transcribed spacer sequencing. Whereas voriconazole, terbinafine, and AmB, either alone or in combination, resulted in successful infection resolution in most cases (5/9; 55.5%), those suffering from invasive facial infections and CARD9 deficiency showed poor outcomes. Our patient is the third case of invasive facial infection caused by C. cassiicola and was successfully treated with intravenous LAmB followed by oral voriconazole combined with topical antifungal irrigation. Molecular identification of fungus and prompt antifungal treatment is pivotal in the clinical success of patients suspected to have phaeohyphomycosis. Moreover, as evidenced by our data, itraconazole treatment is not recommended.

Correlation between congenital pelvic floor muscle development assessed by magnetic resonance imaging and postoperative defecation.

OBJECTIVE: Children with congenital anorectal malformation (CAM) experience challenges with defecation. This study aims to assess defecation in preschool-age children with CAM and to evaluate the correlation between pelvic floor muscle developed assessed by magnetic resonance imaging (MRI) and postoperative defecation. METHODS: We collected clinical data and MRI results from 89 male children with CAM. The bowel function scores for children with Perineal (cutaneous) fistula, Rectourethral fistula(Prostatic or Bulbar), and Rectovesical fistula were computed. MRI scans were subjected to image analysis of the striated muscle complex (SMC). The association between pelvic floor muscle score and bowel function score was examined using the Cochran-Armitage Trend Test. RESULTS: We observed that 77.4% of the SMC scores by MRI for Perineal fistula were good. The Rectourethral fistula SMC score was 40.6% for moderate and 59.4% for poor. The SMC score for Rectovesical fistula was 100% for moderate. Furthermore, 77.4% of patients with Perineal fistula had bowel function scores (BFS) ≥ 17 points. Among those with Rectourethral fistula and Rectovesical fistula, 12.5% and 0 had BFS ≥ 17 points, respectively. An analysis of muscle development and bowel function in patients with Rectovesical fistula, Rectourethral fistula, and Perineal fistula revealed a correlation between SMC development and BFS. Subgroup analysis showed that the Perineal fistula had statistical significance; however, the Rectourethral fistula and Rectovesical fistula were not statistically significant. CONCLUSION: A correlation exists between pelvic floor muscle development and postoperative defecation in children with Perineal fistula.

Differences in nature killer cell response and interference with mitochondrial DNA induced apoptosis in moxifloxacin environment.

OBJECTIVES: As antibiotics become more prevalent, accuracy and safety are critical. Moxifloxacin (MXF) have been reported to have immunomodulatory effects on a variety of immune cells and even anti-proliferative and pro-apoptotic effects, but the mechanism of action is not fully clear. METHODS: Peripheral blood mononuclear cells (PBMC) from experimental groups of healthy adults (n = 3) were treated with MXF (10ug/ml) in vitro for 24 h. Single-cell sequencing was performed to investigate differences in the response of each immune cell to MXF. Flow cytometry determined differential gene expression in subsets of most damaged NK cells. Pseudo-time analysis identified drivers that influence MXF-stimulated cell differentiation. Detection of mitochondrial DNA and its involvement in the mitochondrial respiratory chain pathway clarifies the origin of MXF-induced stress injury. RESULTS: Moxifloxacin-environmental NK cells are markedly reduced: a new subset of NK cells emerges, and immediate-early-response genes in this subset indicate the presence of an early activation response. The inhibitory receptor-dominant subset shows enhanced activation, leading to increased expression of cytokines and chemokines. The near-mature subset showed greater cytotoxicity and the most pronounced cellular damage. CD56bright cells responded by antagonizing the regulation of activation and inhibitory signals, demonstrating a strong cleavage capacity. The severe depletion of mitochondrial genes was focused on apoptosis induced by the mitochondrial respiratory chain complex. CONCLUSION: NK cells exhibit heightened sensitivity to the MXF environment. Different NK subsets upregulate the expression of cytokines and chemokines through different activation pathways. Concurrently, MXF induces impairment of the mitochondrial oxidative phosphorylation system, culminating in apoptosis.

Chemical composition and antioxidant activity of Polygonatum kingianum processed by the traditional method of "Nine Cycles of Steaming and Sun-Drying".

Polygonatum kingianum Coll. et (Hemsl) is a famous Chinese traditional food and medicine analogous plant. The rhizome of P. kingianum showed a decrease in levels of alkaloids, amino acids and derivatives, terpenoids, and an increase in organic acid and saccharides when it was processed by the traditional method of "Nine Cycles of Steaming and Sun-Drying". The relative content of 341 metabolites were increased (fold change, FC > 2; variable importance in projection, VIP > 1 and P-value, P < 0.05); while 456 metabolites were decreased (FC < 0.5, VIP > 1, and P < 0.05). The changes in chemical components result in a decrease in numb taste and an increase in sweetness. The increased antioxidant activity was observed in the processed samples. Together, this work has advanced the mechanism of reducing numb taste and enhancing antioxidant activity in the resource plants, such as P. kingianum, processed by the traditional method.

Enhancing assisted diagnostic accuracy in scalp psoriasis: A Multi-Network Fusion Object Detection Framework for dermoscopic pattern diagnosis.

BACKGROUND: Dermoscopy is a common method of scalp psoriasis diagnosis, and several artificial intelligence techniques have been used to assist dermoscopy in the diagnosis of nail fungus disease, the most commonly used being the convolutional neural network algorithm; however, convolutional neural networks are only the most basic algorithm, and the use of object detection algorithms to assist dermoscopy in the diagnosis of scalp psoriasis has not been reported. OBJECTIVES: Establishment of a dermoscopic modality diagnostic framework for scalp psoriasis based on object detection technology and image enhancement to improve diagnostic efficiency and accuracy. METHODS: We analyzed the dermoscopic patterns of scalp psoriasis diagnosed at 72nd Group army hospital of PLA from January 1, 2020 to December 31, 2021, and selected scalp seborrheic dermatitis as a control group. Based on dermoscopic images and major dermoscopic patterns of scalp psoriasis and scalp seborrheic dermatitis, we investigated a multi-network fusion object detection framework based on the object detection technique Faster R-CNN and the image enhancement technique contrast limited adaptive histogram equalization (CLAHE), for assisting in the diagnosis of scalp psoriasis and scalp seborrheic dermatitis, as well as to differentiate the major dermoscopic patterns of the two diseases. The diagnostic performance of the multi-network fusion object detection framework was compared with that between dermatologists. RESULTS: A total of 1876 dermoscopic images were collected, including 1218 for scalp psoriasis versus 658 for scalp seborrheic dermatitis. Based on these images, training and testing are performed using a multi-network fusion object detection framework. The results showed that the test accuracy, specificity, sensitivity, and Youden index for the diagnosis of scalp psoriasis was: 91.0%, 89.5%, 91.0%, and 0.805, and for the main dermoscopic patterns of scalp psoriasis and scalp seborrheic dermatitis, the diagnostic results were: 89.9%, 97.7%, 89.9%, and 0.876. Comparing the diagnostic results with those of five dermatologists, the fusion framework performs better than the dermatologists' diagnoses. CONCLUSIONS: Studies have shown some differences in dermoscopic patterns between scalp psoriasis and scalp seborrheic dermatitis. The proposed multi-network fusion object detection framework has higher diagnostic performance for scalp psoriasis than for dermatologists.

COVID-19 Rebound After VV116 vs Nirmatrelvir-Ritonavir Treatment: A Randomized Clinical Trial.

Importance: With the widespread use of anti-SARS-CoV-2 drugs, accumulating data have revealed potential viral load rebound after treatment. Objective: To compare COVID-19 rebound after a standard 5-day course of antiviral treatment with VV116 vs nirmatrelvir-ritonavir. Design, Setting, and Participants: This is a single-center, investigator-blinded, randomized clinical trial conducted in Shanghai, China. Adult patients with mild-to-moderate COVID-19 and within 5 days of SARS-CoV-2 infection were enrolled between December 20, 2022, and January 19, 2023, and randomly allocated to receive either VV116 or nirmatrelvir-ritonavir. Interventions: Participants in the VV116 treatment group received oral 600-mg VV116 tablets every 12 hours on day 1 and 300 mg every 12 hours on days 2 through 5. Participants in the nirmatrelvir-ritonavir treatment group received oral nirmatrelvir-ritonavir tablets with 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 hours for 5 days. Participants were followed up every other day until day 28 and every week until day 60. Main Outcomes and Measures: The primary outcome was viral load rebound (VLR), defined as a half-log increase in viral RNA copies per milliliter compared with treatment completion. Secondary outcomes included a reduction in the cycle threshold value of 1.5 or more, time until VLR, and symptom rebound, defined as an increase of more than 2 points in symptom score compared with treatment completion. The primary outcome and secondary outcomes were analyzed using the full analysis set. Sensitivity analyses were conducted using the per protocol set. Adverse events were analyzed using the safety analysis set. Results: The full analysis set included 345 participants (mean [SD] age, 53.2 [16.8] years; 175 [50.7%] were men) who received VV116 (n = 165) or nirmatrelvir-ritonavir (n = 180). Viral load rebound occurred in 33 patients (20.0%) in the VV116 group and 39 patients (21.7%) in the nirmatrelvir-ritonavir group (P = .70). Symptom rebound occurred in 41 of 160 patients (25.6%) in the VV116 group and 40 of 163 patients (24.5%) in the nirmatrelvir-ritonavir group (P = .82). Viral whole-genome sequencing of 24 rebound cases revealed the same lineage at baseline and at viral load rebound in each case. Conclusions and Relevance: In this randomized clinical trial of patients with mild-to-moderate COVID-19, viral load rebound and symptom rebound were both common after a standard 5-day course of treatment with either VV116 or nirmatrelvir-ritonavir. Prolongation of treatment duration might be investigated to reduce COVID-19 rebound. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200066811.

Cannabidiol Alleviates Neurological Deficits After Traumatic Brain Injury by Improving Intracranial Lymphatic Drainage.

Traumatic brain injury (TBI) persists as a substantial clinical dilemma, largely because of the absence of effective treatments. This challenge is exacerbated by the hindered clearance of intracranial metabolic byproducts and the continual accrual of deleterious proteins. The glymphatic system (GS) and meningeal lymphatic vessels (MLVs), key elements of the intracranial lymphatic network, play critical roles in the clearance of harmful substances. Cannabidiol (CBD) has shown promise in reducing metabolite overload and bolstering cognitive performance in various neurodegenerative diseases. The precise mechanisms attributing to its beneficial effects in TBI scenarios, however, are yet to be distinctly understood. Utilizing a fluid percussion injury paradigm, our research adopted a multifaceted approach, encompassing behavioral testing, immunofluorescence and immunohistochemical analyses, laser speckle imaging, western blot techniques, and bilateral cervical efferent lymphatic ligation. This methodology aimed to discern the influence of CBD on both neurological outcomes and intracranial lymphatic clearance in a murine TBI model. We observed that CBD administration notably ameliorated motor, memory, and cognitive functions, concurrently with a significant reduction in the concentration of phosphorylated tau protein and amyloid-ß. In addition, CBD expedited the turnover and elimination of intracranial tracers, increased cerebral blood flow, and enhanced the efficacy of fluorescent tracer migration from MLVs to deep cervical lymph nodes (dCLNs). Remarkably, CBD treatment also induced a reversion in aquaporin-4 (AQP-4) polarization and curtailed neuroinflammatory indices. A pivotal discovery was that the surgical interruption of efferent lymphatic conduits in the neck nullified CBD's positive contributions to intracranial waste disposal and cognitive improvement, yet the anti-neuroinflammatory actions remained unaffected. These insights suggest that CBD may enhance intracranial metabolite clearance, potentially via the regulation of the intracranial lymphatic system, thereby offering neurofunctional prognostic improvement in TBI models. Our findings underscore the potential therapeutic applicability of CBD in TBI interventions, necessitating further comprehensive investigations and clinical validations to substantiate these initial conclusions.

CD4+ CD11b+ T cells infiltrate and aggravate the traumatic brain injury depending on brain-to-cervical lymph node signaling.

AIM: We aim to identify the specific CD4+ T-cell subtype influenced by brain-to-CLN signaling and explore their role during the acute phase of traumatic brain injury (TBI). METHOD: Cervical lymphadenectomy or cervical afferent lymphatic ligation was performed before TBI. Cytokine array and western blot were used to detect cytokines, while the motor function was assessed using mNss and rotarod test. CD4+ T-cell subtypes in blood, brain, and CLNs were analyzed with Cytometry by time-of-flight analysis (CyTOF) or fluorescence-activated cell sorting (FACS). Brain edema and volume changes were measured by 9.4T MRI. Neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. RESULTS: Cervical lymphadenectomy and ligation of cervical lymphatic vessels resulted in a decreased infiltration of CD4+ T cells, specifically CD11b-positive CD4+ T cells, within the affected region. The population of CD4+ CD11b+ T cells increased in ligated CLNs, accompanied by a decrease in the average fluorescence intensity of sphingosine-1-phosphate receptor-1 (S1PR1) on these cells. Administration of CD4+ CD11b+ T cells sorted from CLNs into the lateral ventricle reversed the attenuated neurologic deficits, brain edema, and lesion volume following cervical lymphadenectomy. CONCLUSION: The infiltration of CD4+ CD11b+ T cells exacerbates secondary brain damage in TBI, and this process is modulated by brain-to-CLN signaling.

The value of computed tomography texture analysis in identifying chronic subdural hematoma patients with a good response to polytherapy.

This study aimed to investigate the predictive factors of therapeutic efficacy for chronic subdural hematoma (CSDH) patients receiving atorvastatin combined with dexamethasone therapy by using clinical imaging characteristics in conjunction with computed tomography (CT) texture analysis (CTTA). Clinical imaging characteristics and CT texture parameters at admission were retrospectively investigated in 141 CSDH patients who received atorvastatin combined with dexamethasone therapy from June 2019 to December 2022. The patients were divided into a training set (n = 81) and a validation set (n = 60). Patients in the training data were divided into two groups based on the effectiveness of the treatment. Univariate and multivariate analyses were performed to assess the potential factors that could indicate the prognosis of CSDH patients in the training set. The receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of the significant factors in predicting the prognosis of CSDH patients and was validated using a validation set. The multivariate analysis showed that the hematoma density to brain parenchyma density ratio, singal min (minimum) and singal standard deviation of the pixel distribution histogram, and inhomogeneity were independent predictors for the prognosis of CSDH patients based on atorvastatin and dexamethasone therapy. The area under the ROC curve between the two groups was between 0.716 and 0.806. As determined by significant factors, the validation's accuracy range was 0.816 to 0.952. Clinical imaging characteristics in conjunction with CTTA could aid in distinguishing patients with CSDH who responded well to atorvastatin combined with dexamethasone.

Trends by age and sex and projections of disease prevalence from studying hypertensive heart disease in China over the past three decades.

BACKGROUND: Hypertensive heart disease (HHD) is a common cause of cardiovascular disease and mortality worldwide, and its burden is increasing with aging populations. OBJECTIVES: This study aimed to estimate the prevalence and mortality rates of HHD in mainland China and Taiwan Province using data from the Global Burden of Disease Study 2019 (GBD 2019), and forecast the development trend of HHD from 2020 to 2024. METHODS: We obtained data on number of cases, deaths, crude prevalence rate, crude death rate, age-standardized prevalence rate (ASPR), and age-standardized death rate (ASDR) for mainland China and Taiwan Province from 1990 to 2019 from the GBD 2019. Joinpoint software was used to estimate average annual percentage change (AAPC) with 95% confidence intervals, and the number of HHD cases in China from 2022 to 2024 was predicted by the exponential smoothing method. RESULTS: Between 1990 and 2019, HHD cases and deaths increased in mainland China, but the ASPR and ASDR decreased by 5.96% and 48.72%, respectively. In Taiwan Province, ASPR and ASDR decreased by 7.66% and 52.14%, respectively. The number of HHD cases and death rates varied by region, age, and sex, with a higher number of cases in mainland China than in Taiwan Province. By 2024, the number of HHD cases in mainland China was projected to be over 9.6 million cases, and in Taiwan Province, it was projected to surpass 120,000 cases. CONCLUSION: The differences in HHD cases between mainland China and Taiwan Province in terms of age and sex indicated the need for effective prevention and control measures, especially targeting the elderly population. These findings can inform policymakers and health professionals in the development of targeted prevention and treatment strategies and resource allocation for HHD in China.

Delayed Administration of an Angiotensin II Type 2 Receptor Agonist Promotes Functional Recovery of the Brain and Heart After Traumatic Brain Injury.

Cardiac injury is a common complication following traumatic brain injury (TBI) that can lead to poor clinical outcomes. Angiotensin II type 2 receptor (AT2R) activation exerts protective roles in the brain and heart, yet its potential impact on TBI or TBI-induced cardiac deficits remains elusive. The goal of this study was to investigate the influence of AT2R activation on recovery after TBI-induced cognitive and cardiac injury using the selective nonpeptide AT2R agonist compound 21 (C21). TBI was induced by cortical impact injury in male adult C57BL/6J mice, and the mice received C21 (0.03 mg/kg, intraperitoneally) starting from 24 h after TBI and continuing once daily. C21 facilitated cognitive function recovery until 1 month after TBI. C21 alleviated blood-brain barrier leakage and brain edema and inhibited the expression of proinflammatory cytokines in the brain after 3 consecutive days of treatment. C21 improved cerebral blood flow after 1 month, although the lesion volume was not affected. C21 also reduced the expression of proinflammatory cytokines in the heart after a 3-day consecutive treatment. Meanwhile, C21 benefited cardiac function, as identified by increased left ventricular ejection fraction 1 month after TBI. In addition, C21 alleviated TBI-induced cardiac hypertrophy and fibrosis; however, blood pressure was not affected. Our results demonstrate that AT2R activation ameliorates TBI-induced neurological and cardiac deficits.

Inhibition of KDM5B participates in immune microenvironment remodeling in pancreatic cancer by inducing STING expression.

OBJECTIVE: This study aims to investigate the effect of lysine demethylase 5B (KDM5B)-mediated dimethyl-lysine 4 histone H3 (H3K4me2) demethylation on immune microenvironment remodeling in pancreatic cancer. METHODS: Pan 02 mouse pancreatic cancer cell lines were cultured and used to establish tumor model in vivo. RT-qPCR and Western blot were used to detect the expression of stimulator of interferon gene (STING) and KDM5B in pancreatic cancer tissues and Pan 02 cells. The specific demethylation domain of KDM5B was detected by isothermal titration calorimetry binding assay. The regulatory roles of KDM5B in cell apoptosis and remodeling of immune microenvironment in vitro and in vivo were explored after loss-of functions in KDM5B. RESULTS: KDM5B was highly expressed but STING was poorly expressed in pancreatic cancer tissues and Pan 02 cells. After knockdown of KDM5B, CD8+ T cells recognized and killed Pan 02 cells, which promoted the infiltration of CD8+ T cells in Pan 02 cells, thus improving the anti-tumor ability. The PHD domain in KDM5B specifically bound to H3K4me2 peptide and inhibition of KDM5B induced STING expression. Knockdown of KDM5B up-regulated STING expression to promote apoptosis, thus regulating the immune microenvironment and inhibiting the growth of tumor in mice. Meanwhile, knockdown of KDM5B and STING simultaneously counteracted the knockdown effect of KDM5B. CONCLUSION: Inhibition of KDM5B can promote the expression of STING through H3K4me2 demethylation, which promoted the recognition and killing of Pan 02 cells by CD8+ T cells, thus improving the anti-tumor ability and regulating the immune microenvironment.