Near-Infrared-II Imaging Revealed Hypothermia Regulates Neuroinflammation Following Brain Injury by Increasing the Glymphatic Influx.

Advanced in vivo imaging techniques have facilitated the comprehensive visual exploration of animal biological processes, leading to groundbreaking discoveries such as the glymphatic system. However, current limitations of macroscopic imaging techniques impede the precise investigation of physiological parameters regulating this specialized lymphatic transport system. While NIR-II fluorescence imaging has demonstrated advantages in peripheral lymphatic imaging, there are few reports regarding its utilization in the glymphatic system. To address this, a noninvasive transcranial macroscopic NIR-II fluorescence imaging model is developed using a cyanine dye-protein coupled nanoprobe. NIR-II imaging with high temporal and spatial resolution reveals that hypothermia can increase the glymphatic influx by reducing the flow rate of cerebrospinal fluid. In addition, respiratory rate, respiratory amplitude, and heart rate all play a role in regulating the glymphatic influx. Thus, targeting the glymphatic influx may alter the trajectory of immune inflammation following brain injury, providing therapeutic prospects for treating brain injury with mild hypothermia.

Development of postoperative bronchopleural fistula after neoadjuvant immunochemotherapy in non-small cell lung cancer: case reports and review of the literature.

BACKGROUND: The advent of immune checkpoint inhibitors has dramatically changed the treatment paradigm for advanced non-small-cell lung cancer (NSCLC). Due to the complexity and diversity of stage III disease, the inclusion of immune checkpoint inhibitors (ICIs) in neoadjuvant treatment regimens is also required. However, immune-related adverse events (irAEs) limit the application of ICIs to a certain extent. Bronchopleural fistula (BPF) is a serious and fatal complication after pneumonectomy that is rarely reported, especially in patients who accept neoadjuvant immunotherapy or chemoimmunotherapy. CASE PRESENTATION: Herein, we reported four patients with postoperative BPF who received a neoadjuvant regimen of sintilimab plus chemotherapy. Postoperative BPF occurred in the late stage in three patients; one patient underwent bronchoscopic fistula repair, and the fistula was closed well after surgery, and the other two patients gradually recovered within 1-2 months after symptomatic treatment with antibiotics. One patient with BPF after left pneumonectomy died of respiratory failure due to pulmonary infection. We also reviewed the literature on the development of postoperative BPF in patients receiving immuno-neoadjuvant therapy to discuss the clinical process further, postoperative pathological changes, as well as risk factors of BPF patients. CONCLUSIONS: Central type lung cancer with stage III may be the risk factors of BPF in cases of neoadjuvant immunochemotherapy for lung cancers patients.

[Process Approach in Memory Assessment of Patients With Alzheimer's Disease and Mild Cognitive Impairment:A Review].

The process approach,a set of analytical methods used in neuropsychology,quantifies the word-list learning tests and conventional analytical methods and fully reflects the memory profile of the subject.Therefore,it is widely used in the memory assessment of patients with Alzheimer's disease(AD)and mild cognitive impairment(MCI).The common indices of process approach,such as learning slope,semantic clustering,serial position effects,discriminability,and response bias,are key components of memory assessment.This article reviews the application of common indices of process approach in memory assessment of AD and MCI patients and discusses the shortcomings and future research directions of process approach.

Efficacy and safety of Wuhu oral liquid in treating acute soft tissue injuries: a multicenter, randomized, double-blind, double-dummy, parallel-controlled trial.

Background: Wuhu Oral Liquid (WHOL) is a modified preparation derived from the famous Wuhu Powder, which has a long history of use in treating traumatic injuries. This preparation has anti-inflammatory and analgesic properties and accelerates recovery following acute soft tissue injuries. Aims: To evaluate the efficacy and safety of WHOL in treating acute soft tissue injury associated with qi stagnation and blood stasis syndrome and to provide a basis for applying for the protection of varieties of Chinese medicine for WHOL. Methods: This study was a randomized, controlled, double-blind, multicenter clinical trial in which Fufang Shang Tong Capsule (FFSTC) was selected as the control drug. A total of 480 subjects with acute soft tissue injury associated with qi stagnation and blood stasis syndrome were randomly divided into a test and control group in a 3:1 ratio. The duration of drug treatment was 10 days. The primary outcome was Visual Analogue Scale (VAS) score for pain (including pain at rest and pain on activity). Secondary outcomes included the disappearance time of the pain at rest and on activity; the curative effect of TCM syndrome and improvement in the individual symptoms of TCM (swelling, ecchymosis, and dysfunction); and changes in C-reactive protein (CRP) and interleukin-6 (IL-6) levels. Safety was assessed using vital signs, laboratory examinations, electrocardiograms, and physical examinations. Results: Patient compliance was satisfactory in both groups (all between 80% and 120%). After 4 days of treatment, the WHOL group was superior to the FFSTC group in decreasing the VAS scores for pain at rest (-1.88 ± 1.13 vs. -1.60 ± 0.93, p < 0.05) and on activity (-2.16 ± 1.18 vs. -1.80 ± 1.07, p < 0.05). After 7 days of treatment, the WHOL group was superior to the FFSTC group in decreasing the VAS scores for pain on activity (-3.87 ± 1.60 vs. -3.35 ± 1.30, p < 0.01) and improving swelling (cure rate: 60.4% vs. 46.2%, p < 0.05; obvious effective rate: 60.7% vs. 47.0%, p < 0.05). After 10 days of treatment, the WHOL group was superior to the FFSTC group in decreasing the levels of CRP (-0.13 ± 2.85 vs. 0.25 ± 2.09, p < 0.05) and improving the TCM syndrome (cure rate: 44.1% vs. 30.8%, p < 0.05) and swelling (cure rate: 75.6% vs. 67.5%, p < 0.01; obvious effective rate: 75.6% vs. 68.4%, p < 0.05; effective rate: 77.0% vs. 71.8%, p < 0.05). The disappearance time of pain at rest was 8 days in both groups and 9 days on activity in both groups. In addition, there was no statistical difference between the incidence of adverse events (4.5% vs. 2.6%, p > 0.05) and adverse reactions (0.3% vs. 0%, p > 0.05) between the WHOL group and the FFSTC group. No serious adverse events occurred in either group, and no subjects were withdrawn because of adverse events. Conclusion: WHOL relieves the symptoms caused by acute soft tissue injury associated with qi stagnation and blood stasis syndrome more rapidly than FFSTC, and it is effective and safe in the treatment of acute soft tissue injury. Future studies still need a larger sample size to verify its efficacy and safety. Clinical Trial Registration: https:// www.chictr.org.cn/showproj.html?proj=149531, Identifier ChiCTR2200056411.

Parthenolide induces ROS-dependent cell death in human gastric cancer cell.

BACKGROUND: Parthenolide (PN), a key active ingredient of feverfew, has been used to treat gastrointestinal disorders. However, the mechanism of the cytotoxic effect exerted by PN on tumor cells has not been elucidated. OBJECTIVES: To study the cytotoxic effect of PN on human gastric cancer cells, the specific death mode, and gene expression changes induced by PN. MATERIAL AND METHODS: In this study, MGC-803 cells were used to study PN-induced cytotoxicity as a gastric cancer cell line. Assays of cell proliferation, cell cycle distribution, apoptosis, and reactive oxygen species (ROS) were performed using a Cell Counting Kit-8 (CCK-8) assay and a flow cytometer. MGC-803 cells treated with and without PN were separately subjected to high-throughput RNA sequencing. Western blotting was used to investigate the expression of some important proteins. RESULTS: Parthenolide exposure elicited cell proliferation inhibition in a doseand time-dependent manner. Parthenolide induced cell cycle arrest at the G1 and S stages. Parthenolide-induced caspase-dependent apoptosis and necroptosis were caused by the activation of RIP, RIP3 and MLKL. MGC-803 cells showed a response to ROS and oxidative stress after PN treatment. Moreover, ROS and cytotoxicity induced by PN were significantly attenuated by a ROS scavenger catalase. CONCLUSIONS: Parthenolide-induced gastric cancer cell death is a complex ROS-dependent process different from ordinary apoptosis and necrosis, suggesting that PN is a potential treatment option for gastric cancer.

Apnea Testing Practice to Increase Baseline PaCO2 and Frequency of Blood Gas Analyses.

OBJECTIVE: To study the influence of the initial partial pressure of carbon dioxide (PaCO2) and frequency of blood gas analyses on the positivity rate and safety of apnea testing (AT). DESIGN: A prospective multicenter cohort study. SETTING: Seven teaching hospitals. PARTICIPANTS: A total of 55 patients who underwent AT. INTERVENTIONS: Patients were divided into 2 groups according to their initial PaCO2-the experimental group (≥40 mmHg, 27 patients) and the control group (<40 mmHg, 28 patients). Blood gas analysis was performed at 3, 5, and 8 minutes, and vital signs were taken. AT results and complications were compared between the groups. RESULTS: The initial PaCO2 of the experimental group was 42.8 ± 2.2 mmHg v 36.4 ± 2.9 mmHg in the controls. The AT positivity rate was 100%. The experimental group needed less time to reach the target PaCO2 than the control group (4.07 ± 1.27 minutes v 5.68 ± 2.06 minutes; p = 0.001). Twenty-six patients (96.3%) in the experimental group reached the target PaCO2 in 5 minutes v 17 in the control group (60.7%) (p = 0.001). Seven patients (12.7%) were unable to complete 8-minute disconnection due to hypotension. The experimental group had a slightly lower incidence of hypotension than the control group, but there was no statistical difference (7.4% v 17.9%, p = 0.245). CONCLUSION: Increasing the baseline PaCO2 and doing more blood gas analyses can significantly shorten the time needed for AT and improve the AT positivity rate.

MSS-UNet: A Multi-Spatial-Shift MLP-based UNet for skin lesion segmentation.

Multilayer perceptron (MLP) networks have become a popular alternative to convolutional neural networks and transformers because of fewer parameters. However, existing MLP-based models improve performance by increasing model depth, which adds computational complexity when processing local features of images. To meet this challenge, we propose MSS-UNet, a lightweight convolutional neural network (CNN) and MLP model for the automated segmentation of skin lesions from dermoscopic images. Specifically, MSS-UNet first uses the convolutional module to extract local information, which is essential for precisely segmenting the skin lesion. We propose an efficient double-spatial-shift MLP module, named DSS-MLP, which enhances the vanilla MLP by enabling communication between different spatial locations through double spatial shifts. We also propose a module named MSSEA with multiple spatial shifts of different strides and lighter external attention to enlarge the local receptive field and capture the boundary continuity of skin lesions. We extensively evaluated the MSS-UNet on ISIC 2017, 2018, and PH2 skin lesion datasets. On three datasets, the method achieves IoU metrics of 85.01%±0.65, 83.65%±1.05, and 92.71%±1.03, with a parameter size and computational complexity of 0.33M and 15.98G, respectively, outperforming most state-of-the-art methods.The code is publicly available at https://github.com/AirZWH/MSS-UNet.

Flow diverter tail malapposition after implantation in the internal carotid artery for aneurysm treatment: a preliminary study.

Background and purpose: Favorable wall apposition of a flow diverter (FD) is essential for the treatment of intracranial aneurysms. The irretrievability and final drop point uncertainty of the proximal tail of the FD increase the difficulty of achieving good tail apposition. Therefore, understanding the factors associated with FD tail malapposition would be helpful for clinical practice. Methods: A total of 153 patients with 161 FD deployments in the carotid artery between 2020 and 2023 were retrospectively collected from our center's database for this study. Patient demographics, aneurysm characteristics, FDs, carotid artery anatomy, periprocedural complications, discharge modified Rankin scale (MRS) scores, and follow-up outcomes were investigated by comparing patients with and without FD tail malapposition. Comparisons were made with t tests or Kruskal-Wallis tests for continuous variables and the Pearson χ2 or Fisher exact test for categorical variables. Logistic regression was conducted to determine the predictors of malapposition. Results: Tail malapposition occurred for 41 out of the 161 FDs (25.5%). Univariate analysis revealed that the FD brand, FD length, FD distal to proximal vessel diameter ratio, FD tail position (straight or curved), and curvature of the vessel curve were significantly associated with FD tail malapposition (p < 0.05). Further multivariate analysis demonstrated that the application of a surpass FD (p = 0.04), the FD distal to proximal vessel diameter ratio (p = 0.022), the FD tail position (straight or curved) (p < 0.001) and the curvature of the vessel curve (p < 0.001) were factors significantly associated with FD tail malapposition. No significant difference was found in periprocedural or follow-up outcomes. The classification of FD tail malapposition was determined from imaging. The two major patterns of FD tail malapposition are unattached tails and protrusive tails. Conclusion: FD tail malapposition might be associated with a larger FD distal to the proximal vessel diameter difference, a curved vessel where the FD tail is located, and a larger curvature of the vessel curve. FD tail malapposition can be classified into unattached tails and protrusive tails, which have their own characteristics and should be noted in clinical practice.

Causal associations between genetically determined common psychiatric disorders and the risk of falls: evidence from Mendelian randomization.

BACKGROUND: The causal associations between psychiatric disorders and falls risk remains uncertain. Consequently, this study aimed to explore the causal relationship between genetically determined three common psychiatric disorders and the risk of falls based on Mendelian randomization (MR). METHODS: The genome-wide association study (GWAS) data for schizophrenia (SCZ) (N = 320,404), major depressive disorder (MDD) (N = 480,359), and Alzheimer's disease (AD) (N = 63,926) were obtained as exposures. The GWAS data for falls risk (N = 451,179) was obtained as outcome. Univariate Mendelian randomization (UVMR) was used to evaluate the direct causal relationship between SCZ, MDD, AD, and risk of falls. Inverse variance weighting (IVW) was used as the primary analysis method. Sensitivity analysis was performed to assess the validity of the casualty. Multivariate Mendelian randomization (MVMR) analysis was conducted after adjusting body mass index and smoking initiation. Mediating MR was conducted to calculate the mediating effects of potential intermediaries. RESULTS: UVMR analysis showed that SCZ (OR 1.02, 95% CI 1.01-1.04, p = 8.03E-03) and MDD (OR 1.15, 95% CI 1.08-1.22, p = 1.38E-05) were positively associated with the risk of falls. Sensitivity analysis results were reliable and robust. MVMR results indicated that the relationship between MDD and SCZ and falls risk remained significant. Mediating MR results demonstrated that smoking initiation mediated partial causal effect of SCZ (0.65%, P = 0.03) and MDD (14.82%, P = 2.02E-03) on risk of falls. CONCLUSIONS: This study provides genetic evidence for a causal relationship of individuals with SCZ and MDD on an increased risk of falls. Healthcare providers should be aware of the risk of falls in MDD and SCZ patients and develop strategies accordingly.

Comparison of anesthetic effects of different doses of alfentanil combined with ciprofol in elderly patients undergoing ERCP: a randomized controlled trial.

BACKGROUND AND OBJECTS: Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) are often old and poor in physical fitness. The purpose of this study was to investigate the anesthetic effect of different doses of alfentanil combined with ciprofol in elderly patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). METHODS: In this clinical trial, 137 patients, who were candidates for ERCP were randomly divided into three groups. Group A were given 0.15 µg/kg/min of alfentanil in maintenance stage, Group B were given 0.25 µg/kg/min and Group C were given 0.35 µg/kg/min. Mean arterial pressure (MAP), heart rate (HR), oxygen saturation (SpO2) of the patients at each time point including the entry into the operation room (T0), at the beginning of surgery(T1), 10 min after surgery(T2), 20 min after surgery(T3), 30 min after surgery(T4),endoscopy withdrawal (T5) were recorded. Adverse events(including respiratory depression, body movement and hypoxemia),the dosage of ciprofol, the time of operation time and awakening were recorded. RESULTS: Compared with Group A, MAP and HR in Group B and Group C was decreased during T1-T5 (P < 0.05). Compared with group B, MAP and HR in group C was decreased during T1-T5 (P < 0.05). Compared with Group A and Group C,the number of adverse reactions of Group B was decreased(P < 0.05). There was no statistical difference in surgical time among the three groups(P > 0.05),but a statistically significant difference in recovery time (P < 0.05). CONCLUSION: The adverse events of alfentanil 0.25µg/kg/min combined with ciprofol were low, and the anesthetic effect was the best.

The effect of different sources of mesenchymal stem cells on microglia states.

Microglial reaction plays a key role in the prognosis of traumatic CNS injuries (TBI and SCI). A growing number of studies have shown that mesenchymal stem cells (MSCs) play an important role in regulating microglial states. This review summarizes the effects and mechanisms of different sources of MSCs on microglial states in the last 5 years. In general, bone marrow-derived mesenchymal stem cells are the most accessible and widely used, and can produce immunosuppressive effects on a variety of brain injuries including TBI through tissue engineering in situ implantation; MSCs mainly regulate inflammatory pathways and promote the states of microglia in the anti-inflammatory direction, which also secrete certain cytokines or extracellular vesicles to affect apoptotic pathways, such as the extracellular vesicles miR-21-5p, acting as a neuronal protector.

[Changes in Plasma Amyloid-ß Level and Their Relationship With White Matter Microstructure in Patients With Mild Cognitive Impairment].

Objective To investigate the changes in plasma amyloid-ß (Aß) level and their relationship with white matter microstructure in the patients with amnesic mild cognitive impairment(aMCI) and vascular mild cognitive impairment (vMCI).Methods A total of 36 aMCI patients,20 vMCI patients,and 34 sex and age matched healthy controls (HC) in the outpatient and inpatient departments of the First Affiliated Hospital of Anhui Medical University were enrolled in this study.Neuropsychological scales,including the Mini-Mental State Examination,the Montreal Cognitive Assessment,and the Activity of Daily Living Scale,were employed to assess the participants.Plasma samples of all the participants were collected for the measurement of Aß42 and Aß40 levels.All the participants underwent magnetic resonance scanning to obtain diffusion tensor imaging (DTI) data.The DTI indexes of 48 white matter regions of each individual were measured (based on the ICBM-DTI-81 white-matter labels atlas developed by Johns Hopkins University),including fractional anisotropy (FA) and mean diffusivity (MD).The cognitive function,plasma Aß42,Aß40,and Aß42/40 levels,and DTI index were compared among the three groups.The correlations between the plasma Aß42/40 levels and DTI index of aMCI and vMCI patients were analyzed.Results The Mini-Mental State Examination and the Montreal Cognitive Assessment scores of aMCI and vMCI groups were lower than those of the HC group (all P<0.001).There was no significant difference in the Activity of Daily Living Scale score among the three groups (P=0.654).The plasma Aß42 level showed no significant difference among the three groups (P=0.227).The plasma Aß40 level in the vMCI group was higher than that in the HC group (P=0.014),while it showed no significant difference between aMCI and HC groups (P=1.000).The plasma Aß42/40 levels in aMCI and vMCI groups showed no significant differences from that in the HC group (P=1.000,P=0.105),while the plasma Aß42/40 level was lower in the vMCI group than in the aMCI group (P=0.016).The FA value of the left anterior limb of internal capsule in the vMCI group was lower than those in HC and aMCI groups (all P=0.001).The MD values of the left superior corona radiata,left external capsule,left cingulum (cingulate gyrus),and left superior fronto-occipital fasciculus in the vMCI group were higher than those in HC (P=0.024,P=0.001,P=0.003,P<0.001) and aMCI (P=0.015,P=0.004,P=0.019,P=0.001) groups,while the MD values of the right posterior limb of internal capsule (P=0.005,P=0.001) and left cingulum (hippocampus) (P=0.017,P=0.031) in the aMCI and vMCI groups were higher than those in the HC group.In the aMCI group,plasma Aß42/40 level was positively correlated with FA of left posterior limb of internal capsule (r=0.403,P=0.015) and negatively correlated with MD of the right fonix (r=-0.395,P=0.017).In the vMCI group,plasma Aß42/40 level was positively correlated with FA of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=0.575,P=0.008;r=0.639,P=0.002),while it was negatively correlated with MD of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=-0.558,P=0.011;r=-0.626,P=0.003).Conclusions Plasma Aß levels vary differently in the patients with aMCI and vMCI.The white matter regions of impaired microstructural integrity differ in the patients with different dementia types in the early stage.The plasma Aß levels in the patients with aMCI and vMCI are associated with the structural integrity of white matter,and there is regional specificity between them.

Gastrodin facilitates recovery of neurological function of MCAO rats through upregulating miR-20a-5p/XIAP pathway via exosome.

Cerebral infarction (CI) is characterised by high morbidity, mortality, and disability rates. Recently, Chinese medicine has been widely used and has gained satisfactory results in the treatment of CI. Our previous study showed that gastrodin could facilitate the recovery of neurological function in middle cerebral artery occlusion (MCAO) rats. This study explores this mechanism. SD rats were separated into control, sham, model, and gastrodin groups. After MCAO surgery, the gastrodin group was administered gastrodin (100 mg/kg), and after 1/3/7 days, the ischaemic hemisphere and serum was collected, and then we extracted the circulating exosomes from the serum. We then tested the levels of XIAP (x-linked inhibitor of apoptosis protein), IAP binding proteins (SMAC, HtrA2, ARTs), and miR-20a-5p (a gastrodin potential effect target) in the brain tissues, circulating exosomes, and serum using various methods. Our results showed that circulating exosomes can penetrate the blood-brain barrier (BBB) and that gastrodin can upregulate the amount of miR-20a-5p in circulating exosomes. The circulating exosomes penetrate the BBB and upregulate the expression of XIAP in the ischaemic hemisphere. Gastrodin can also decrease the amount of IAP binding proteins (SMAC, HtrA2, ARTs). Gastrodin can increase the amount of miR-20a-5p in circulating exosomes, which penetrates the BBB and upregulates XIAP expression in the ischaemic hemisphere. By inhibiting apoptosis of neurones, it can facilitate the recovery of neurological function in MCAO rats.

The emerging roles and mechanism of N6-methyladenosine (m6A) modifications in urologic tumours progression.

Prostate cancer (PCa), bladder cancer (BC), and renal cell cancer (RCC) are the most common urologic tumours in males. N6-methyladenosine (m6A), adenosine N6 methylation, is the most prevalent RNA modification in mammals. Increasing evidence suggests that m6A plays a crucial role in cancer development. In this review, we comprehensively analyzed the influence of m6A methylation on Prostate cancer, bladder cancer, and renal cell cancer and the relationship between the expression of relevant regulatory factors and their development and occurrence, which provides new insights and approaches for the early clinical diagnosis and targeted therapy of urologic malignancies.

A systematic review and bibliometric study of Bertolotti's syndrome: clinical characteristics and global trends.

PURPOSE: Bertolotti's syndrome is a prevalent congenital deformity. However, many physicians fail to include it in their differential diagnosis for low back pain (LBP), which results in missed diagnosis or misdiagnosis. There is still a lack of standardized treatment and management strategies for Bertolotti's syndrome. This study aimed to review the clinical characteristics and management of Bertolotti's syndrome and reports bibliometric insights in advancements in Bertolotti's syndrome research. METHODS: Studies published until 30 September 2022 were systematically reviewed according to the PRISMA guidelines. Three independent reviewers extracted the data and assessed the quality and risk of bias of the studies based on the methodological index of non-randomized studies (MINORS). SPSS, VOS viewer, and the Citespace software were used for the systematic review, visual analysis, data mining, mapping, and clustering of the retrieved articles, which presented clear and visual presentations of the structural patterns of published research in graphs. RESULT: A total of 118 articles, describing a total of 419 patients with Bertolotti's syndrome, were included. There was an upward trend with a steady increase in the number of publications. The world map distribution showed that most publications were predominantly from North America and Asia. The most cited articles were published in the following journals: Spine, J Bone Joint Surg, and Radiology. The mean age of the patients was 47.7 years, and 49.6% of them were male. A total of 159 (96.4%) patients had LBP symptoms. The mean symptom duration was 41.4 months (74.8%), and most of the patients had Castellvi type II. Disc degeneration was the most reported comorbid spinal diseases. The mean methodological index of non-randomized studies score was 4.16±3.95 points (range, 1-21). A total of 265 (68.3%) patients underwent surgical treatments. Minimally invasive surgical techniques, prevalence, image classification, and disc degeneration were the current main research areas of Bertolotti's syndrome. CONCLUSIONS: The steady increase in the number of publications demonstrated the increased attention of researchers on this topic. Our results showed a significant prevalence of Bertolotti's syndrome in patients with LBP and a long symptom duration before the initiation of treatment. Surgical treatments were commonly used to treat patients with Bertolotti's syndrome after a non-effective conservative treatment. Minimally invasive surgical techniques, prevalence, image classification, and disc degeneration are the major research areas of Bertolotti's syndrome.

Natural Products for the Immunotherapy of Glioma.

Glioma immunotherapy has attracted increasing attention since the immune system plays a vital role in suppressing tumor growth. Immunotherapy strategies are already being tested in clinical trials, such as immune checkpoint inhibitors (ICIs), vaccines, chimeric antigen receptor T-cell (CAR-T cell) therapy, and virus therapy. However, the clinical application of these immunotherapies is limited due to their tremendous side effects and slight efficacy caused by glioma heterogeneity, antigen escape, and the presence of glioma immunosuppressive microenvironment (GIME). Natural products have emerged as a promising and safe strategy for glioma therapy since most of them possess excellent antitumor effects and immunoregulatory properties by reversing GIME. This review summarizes the status of current immunotherapy strategies for glioma, including their obstacles. Then we discuss the recent advancement of natural products for glioma immunotherapy. Additionally, perspectives on the challenges and opportunities of natural compounds for modulating the glioma microenvironment are also illustrated.

Prognostic Factors of Gliosarcoma in the Real World: A Retrospective Cohort Study.

Purpose: Gliosarcoma is a histopathological variant of glioblastoma, which is characterized by a biphasic growth pattern consisting of glial and sarcoma components. Owing to its scarcity, data regarding the impact of available treatments on the clinical outcomes of gliosarcoma are inadequate. The purpose of this retrospective cohort study was to analyze the prognostic factors of gliosarcoma. Methods: By screening the clinical database of neurosurgical cases at a single center, patients with gliosarcoma diagnosed histologically from 2013 to 2021 were identified. Clinical, pathological, and molecular data were gathered founded on medical records and follow-up interviews. Prognostic factors were derived using the Cox proportional hazards model with backward stepwise regression analysis. Results: Forty-five GSM patients were included. Median overall survival was 25.6 months (95% CI 8.0-43.1), and median relapse-free survival was 15.2 months (95% CI 9.7-20.8). In multivariable analysis, total resection (p = 0.023, HR = 0.192, 95% CI 0.046-0.797) indicated an improved prognosis. And low expression of Ki-67 (p = 0.059, HR = 2.803, 95% CI 0.963-8.162) would be likely to show statistical significance. However, there might be no statistically significant survival benefit from radiotherapy with concurrent temozolomide (n = 33, 73.3%, log-rank p = 0.99) or adjuvant temozolomide (n = 32, 71.1%, log-rank p = 0.74). Conclusion: This single-center retrospective study with a limited cohort size has demonstrated the treatment of gross total resection and low expression of Ki-67 which are beneficial for patients with GSM, while radiotherapy or temozolomide is not.

Bilateral Hippocampal Volume Mediated the Relationship Between Plasma BACE1 Concentration and Memory Function in the Early Stage of Alzheimer's Disease: A Cross-Sectional Study.

BACKGROUND: ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a key enzyme in the formation of amyloid-ß (Aß) protein. Increasing evidence suggests that BACE1 concentration is a potential biomarker for Alzheimer's disease (AD). OBJECTIVE: To evaluate the correlations between plasma BACE1 concentration, cognition, and hippocampal volume at different stages of the AD continuum. METHODS: Plasma BACE1 concentrations were measured in 32 patients with probable dementia due to AD (ADD), 48 patients with mild cognitive impairment (MCI) due to AD, and 40 cognitively unimpaired (CU) individuals. Memory function was evaluated using the auditory verbal learning test (AVLT), and voxel-based morphometry was used to analyze bilateral hippocampal volumes. Correlation and mediation analyses were performed to investigate the associations between plasma BACE1 concentration, cognition, and hippocampal atrophy. RESULTS: The MCI and ADD groups exhibited elevated BACE1 concentrations compared with the CU group after adjusting for age, sex, and apolipoprotein E (APOE) genotype. Increased BACE1 concentration was found in AD continuum patients who were APOE ɛ4 carriers (p < 0.05). BACE1 concentration was negatively associated with the scores of the subitems of the AVLT and hippocampal volume (p < 0.05, false discovery rate correction) in the MCI group. Moreover, bilateral hippocampal volume mediated the relationship between BACE1 concentration and recognition in the MCI group. CONCLUSION: BACE1 expression increased in the AD continuum, and bilateral hippocampal volume mediated the effect of BACE1 concentration on memory function in patients with MCI. Research has indicated that the plasma BACE1 concentration might be a biomarker at the early stage of AD.

WITHDRAWN: Characteristics, Treatment and Research Development of Bertolotti's Syndrome: A Bibliometric Analysis and Systematic Review.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause.

Brain Gray Matter Volume Mediated the Correlation Between Plasma P-Tau and Cognitive Function of Early Alzheimer's Disease in China: A Cross-Sectional Observational Study.

BACKGROUND: The primary manifestations of Alzheimer's disease (AD) include cognitive decline and brain gray matter volume (GMV) atrophy. Recent studies have found that plasma phosphorylated-tau (p-tau) concentrations perform better in diagnosing, differentiating, and monitoring the progression of AD. However, the correlation between plasma p-tau, GMV, and cognition remains unclear. OBJECTIVE: To investigate whether GMV plays a mediating role in the association between plasma p-tau concentrations and cognition. METHODS: In total, 99 participants (47 patients with AD and 52 cognitively unimpaired [CU] individuals) were included. All participants underwent neuropsychological assessments, laboratory examinations, and magnetic resonance imaging scans. Plasma p-tau217 and p-tau181 concentrations were measured using an enzyme-linked immunosorbent assay kit. Voxel-based morphometry was performed to assess participants' brain GMV. Partial correlation and mediation analyses were conducted in AD group. RESULTS: Plasma p-tau concentrations were significantly higher in the AD group than in the CU group. Patients with AD had significant brain GMV atrophy in the right hippocampus, bilateral middle temporal gyrus, and right inferior temporal gyrus. In the AD group, there were significant correlations between plasma p-tau217 concentrations, GMV, and Mini-Mental State Examination (MMSE) scores. Brain GMV of the right hippocampus mediated the association between plasma p-tau217 concentrations and MMSE scores. A significant correlation between plasma p-tau181 and MMSE scores was not identified. CONCLUSION: The findings indicate that p-tau217 is a promising biomarker for central processes affecting brain GMV and cognitive function. This may provide potential targets for future intervention and treatment of tau-targeting therapies in the early stages of AD.