XCR1: A promising prognostic marker that pinpoints targeted and immune-based therapy in hepatocellular carcinoma.

Objectives: The lymphotactin receptor X-C motif chemokine receptor 1 (XCR1) is an essential member of the chemokine receptor family and is related to tumor development and progression. Nevertheless, further investigation is required to explore its expression patterns, prognostic values, and functions related to target or immune therapies in patients with hepatocellular carcinoma (HCC). Materials and methods: The differential expression patterns of XCR1 and its prognostic influences were performed through The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Subsequently, immunohistochemistry (IHC) staining and univariate and multivariate Cox regressions were performed to validate the prognostic values in different subgroups. Furthermore, the potential roles of XCR1 in predicting target and immune therapeutic responses were also investigated. Results: Increased expression level of XCR1 was associated with favorable overall survival (OS) and recurrence-free survival (RFS). Subgroup analysis revealed that a high expression level of XCR1 or positive immune cell proportion score (iCPS) were associated with favorable OS in the HCC patients with favorable tumor characteristics. In addition, the enhanced XCR1 expression was associated with the tumor environment scores, immune cell infiltration levels, and the expression levels of immune checkpoint genes. Further analysis revealed that improved expression of XCR1 was linked to better OS and RFS in HCC patients who received sorafenib. Conclusion: This study identified that XCR1 is a valuable prognostic biomarker in the HCC population, especially in those with favorable tumor characteristics. The combination of iCPS status and BCLC status has a synergistic effect on stratifying patients' OS and RFS. Further analyses showed that XCR1 has the potential ability to predict treatment responses to sorafenib and immune-based therapies.

[Design and application of a drainage tube dredging umbrella and anti-retrograde infection kit].

The consensus has been reached on the benefits of surgical drainage. However, catheter-related blockage and retrograde infection remain bottleneck problems in the treatment process. To this end, with Huashan Hospital, Fudan University, as the main inventors, a drainage tube dredging umbrella and anti-retrograde infection kit have been designed and applied for the national utility model patent (patent number: ZL 2023 2 1300036.2). The main body of the kit consists of a catheter dredging umbrella, drainage tube, and drainage bag. Several isolation layers are installed in the drainage bag to form a maze structure and a reflux valve is added, thereby increasing the distance and resistance of liquid reflux, greatly reducing the possibility of liquid reflux entering the drainage tube, so as to reduce the risk of retrograde infection through physical means. When the drainage tube is blocked, the drainage tube and joint tube of the drainage bag can be separated, the unblocking umbrella can be inserted into the blockage through the guide wire, the cannula can be inserted along the guide wire, the guide wire is pulled to release the dredging umbrella in the contraction state, and the dredging umbrella can be pulled back in the expansion state until the blockage is removed from the drainage tube. The operating procedure is standardized and simple. While preventing retrograde infection (anti-retrograde infection kit), the catheter dredging umbrella could effectively address the issue of catheter blockage. It has certain clinical promotion and application value.

Oral administration of lysozyme protects against injury of ileum via modulating gut microbiota dysbiosis after severe traumatic brain injury.

Objective: The current study sought to clarify the role of lysozyme-regulated gut microbiota and explored the potential therapeutic effects of lysozyme on ileum injury induced by severe traumatic brain injury (sTBI) and bacterial pneumonia in vivo and in vitro experiments. Methods: Male 6-8-week-old specific pathogen-free (SPF) C57BL/6 mice were randomly divided into Normal group (N), Sham group (S), sTBI group (T), sTBI + or Lysozyme-treated group (L), Normal + Lysozyme group (NL) and Sham group + Lysozyme group (SL). At the day 7 after establishment of the model, mice were anesthetized and the samples were collected. The microbiota in lungs and fresh contents of the ileocecum were analyzed. Lungs and distal ileum were used to detect the degree of injury. The number of Paneth cells and the expression level of lysozyme were assessed. The bacterial translocation was determined. Intestinal organoids culture and co-coculture system was used to test whether lysozyme remodels the intestinal barrier through the gut microbiota. Results: After oral administration of lysozyme, the intestinal microbiota is rebalanced, the composition of lung microbiota is restored, and translocation of intestinal bacteria is mitigated. Lysozyme administration reinstates lysozyme expression in Paneth cells, thereby reducing intestinal permeability, pathological score, apoptosis rate, and inflammation levels. The gut microbiota, including Oscillospira, Ruminococcus, Alistipes, Butyricicoccus, and Lactobacillus, play a crucial role in regulating and improving intestinal barrier damage and modulating Paneth cells in lysozyme-treated mice. A co-culture system comprising intestinal organoids and brain-derived proteins (BP), which demonstrated that the BP effectively downregulated the expression of lysozyme in intestinal organoids. However, supplementation of lysozyme to this co-culture system failed to restore its expression in intestinal organoids. Conclusion: The present study unveiled a virtuous cycle whereby oral administration of lysozyme restores Paneth cell's function, mitigates intestinal injury and bacterial translocation through the remodeling of gut microbiota.

Early Intraventricular Antibiotic Therapy Improved In-Hospital-Mortality in Neurocritical Patients with Multidrug-Resistant Bacterial Nosocomial Meningitis and Ventriculitis.

BACKGROUND: Hospital-acquired multidrug-resistant (MDR) bacterial meningitis and/or ventriculitis (MEN) is a severe condition associated with high mortality. The risk factors related to in-hospital mortality of patients with MDR bacterial MEN are unknown. We aimed to examine factors related to in-hospital mortality and evaluate their prognostic value in patients with MDR bacterial MEN treated in the neurointensive care unit. METHODS: This was a single-center retrospective cohort study of critically ill neurosurgical patients with MDR bacterial MEN admitted to our hospital between January 2003 and March 2021. Data on demographics, admission variables, treatment, time to start of intraventricular (IVT) therapy, and in-hospital mortality were analyzed. Both univariate and multivariable analyses were performed to identify determinants of in-hospital mortality. RESULTS: All 142 included patients received systemic antibiotic therapy, and 102 of them received concomitant IVT treatment. The median time to start of IVT treatment was 2 days (interquartile range 1-5 days). The time to start of IVT treatment had an effect on in-hospital mortality (hazard ratio 1.17; 95% confidence interval 1.02-1.34; adjusted p = 0.030). The cutoff time to initiate IVT treatment was identified at 3 days: patients treated within 3 days had a higher cerebrospinal fluid (CSF) sterilization rate (81.5%) and a shorter median time to CSF sterilization (7 days) compared with patients who received delayed IVT treatment (> 3 days) (48.6% and 11.5 days, respectively) and those who received intravenous antibiotics alone (42.5% and 10 days, respectively). CONCLUSIONS: Early IVT antibiotics were associated with superior outcomes in terms of the in-hospital mortality rate, time to CSF sterilization, and CSF sterilization rate compared with delayed IVT antibiotics and intravenous antibiotics alone.

Predicting the progression of chronic subdural hematoma based on skull density.

Objective: The objective of this study was to investigate potential correlations between skull density and the progression of chronic subdural hematoma (CSDH). Methods: Patients with unilateral CSDH were retrospectively enrolled between January 2018 and December 2022. Demographic and clinical characteristics, as well as hematoma and skull density (Hounsfield unit, Hu), were collected and analyzed. Results: The study enrolled 830 patients with unilateral CSDH until the resolution of the CDSH or progressed with surgical treatment. Of the total, 488 patients (58.80%) necessitated surgical treatment. The study identified a significant correlation between the progression of CSDH and three variables: minimum skull density (MiSD), maximum skull density (MaSD), and skull density difference (SDD) (p < 0.001). Additionally, in the multivariable regression analysis, MiSD, MaSD, and SDD were independent predictors of CSDH progression. The MiSD + SDD model exhibited an accuracy of 0.88, as determined by the area under the receiver operating characteristic curve, with a sensitivity of 0.77 and specificity of 0.88. The model's accuracy was validated through additional analysis. Conclusion: The findings suggest a significant correlation between skull density and the CSDH progression.

Recovering fetal signals transabdominally through interferometric near-infrared spectroscopy (iNIRS).

Noninvasive transabdominal fetal pulse oximetry can provide clinicians critical assessment of fetal health and potentially contribute to improved management of childbirth. Conventional pulse oximetry through continuous wave (CW) light has challenges measuring the signals from deep tissue and separating the weak fetal signal from the strong maternal signal. Here, we propose a new approach for transabdominal fetal pulse oximetry through interferometric near-infrared spectroscopy (iNIRS). This approach provides pathlengths of photons traversing the tissue, which facilitates the extraction of fetal signals by rejecting the very strong maternal signal from superficial layers. We use a multimode fiber combined with a mode-field converter at the detection arm to boost the signal of iNIRS. Together, we can detect signals from deep tissue (>∼1.6 cm in sheep abdomen and in human forearm) at merely 1.1 cm distance from the source. Using a pregnant sheep model, we experimentally measured and extracted the fetal heartbeat signals originating from deep tissue. This validated a key step towards transabdominal fetal pulse oximetry through iNIRS and set a foundation for further development of this method to measure the fetal oxygen saturation.

Prevalence and Clinical Characteristics of Bacterial Pneumonia in Neurosurgical Emergency Center Patients: A Retrospective Study Spanning 13 Years at a Tertiary Center.

Patients with brain injuries are at a heightened susceptibility to bacterial pneumonia, and the timely initiation of empiric antibiotic treatment has been shown to substantially reduce mortality rates. Nevertheless, there is a need for knowledge regarding the resistance and prevalence of pulmonary bacterial infections in this patient population. To address this gap, a retrospective study was conducted at a neurosurgical emergency center, focusing on patients with brain injuries. Among the entire patient population, a total of 739 individuals (18.23%) were identified as having bacterial pneumonia, consisting of 1489 strains of Gram-negative bacteria and 205 strains of Gram-positive bacteria. The resistance of Klebsiella pneumoniae to imipenem exhibited a significant increase, rising from 21.74% in 2009 to 96.67% in 2018, and subsequently reaching 48.47% in 2021. Acinetobacter baumannii displayed resistance rates exceeding 80.0% against multiple antibiotics. The resistance profile of Pseudomonas aeruginosa was relatively low. The proportion of Staphylococcus aureus reached its peak at 18.70% in 2016, but experienced a decline to 7.83% in 2021. The abundance of Gram-negative bacteria exceeded that of Gram-positive bacteria by a factor of 5.96. Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococcus aureus are prominent pathogens characterized by limited antibiotic choices and scarce treatment alternatives for the isolated strains.

Intensity-dependent gamma electrical stimulation regulates microglial activation, reduces beta-amyloid load, and facilitates memory in a mouse model of Alzheimer's disease.

BACKGROUND: Gamma sensory stimulation may reduce AD-specific pathology. Yet, the efficacy of alternating electrical current stimulation in animal models of AD is unknown, and prior research has not addressed intensity-dependent effects. METHODS: The intensity-dependent effect of gamma electrical stimulation (GES) with a sinusoidal alternating current at 40 Hz on Aß clearance and microglia modulation were assessed in 5xFAD mouse hippocampus and cortex, as well as the behavioral performance of the animals with the Morris Water Maze. RESULTS: One hour of epidural GES delivered over a month significantly (1) reduced Aß load in the AD brain, (2) increased microglia cell counts, decreased cell body size, increased length of cellular processes of the Iba1 + cells, and (3) improved behavioral performance (learning & memory). All these effects were most pronounced when a higher stimulation current was applied. CONCLUSION: The efficacy of GES on the reduction of AD pathology and the intensity-dependent feature provide guidance for the development of this promising therapeutic approach.

Overexpression of GPX4 attenuates cognitive dysfunction through inhibiting hippocampus ferroptosis and neuroinflammation after traumatic brain injury.

Ferroptosis is a newly discovered form of regulated cell death that is triggered primarily by lipid peroxidation. A growing body of evidence has implicated ferroptosis in the pathophysiology of traumatic brain injury (TBI). However, none of these studies focused its role on TBI-induced hippocampal injury. Here, we demonstrated that the distinct ferroptotic signature was detected in the injured hippocampus at the early stage of TBI. Besides, a prominent pro-ferroptosis environment was detected in the ipsilateral hippocampus after TBI, including elevated levels of arachidonic acid (AA), ACLS4, and ALXO15, and deficiency of GPX4. Subsequently, we used AAV-mediated Gpx4 overexpression to counteract ferroptosis in the hippocampus, and found that TBI-induced cognitive deficits were significantly alleviated after Gpx4 overexpression. Biochemical results also confirmed that TBI-induced hippocampal ferroptosis and synaptic damage were partially reversed by Gpx4 overexpression. In addition, Gpx4 overexpression inhibited TBI-induced neuroinflammation and peripheral macrophage infiltration. Interestingly, the results of transwell migration assay showed that ferroptotic neurons increased CCL2 expression and promoted iBMDM cell migration. However, this effect was inhibited by CCL2 antagonist, RS102895. These data suggested that inhibition of ferroptosis may be as a potential strategy to ameliorate TBI-induced cognitive deficits through blockade of hippocampal ferroptosis and neuroinflammation.

Deep remediation of As(III) in water by La-Ce bimetal oxide modified carbon framework.

Arsenic contamination of groundwater harms the health of millions of people, especially As(III), which is extremely toxic and difficult to remediate. Herein, we fabricated a reliable La-Ce binary oxide-anchored carbon framework foam (La-Ce/CFF) adsorbent for As(III) deep removal. Its open 3D macroporous structure ensures fast adsorption kinetic. The incorporation of an appropriate amount of La could enhance the affinity of La-Ce/CFF for As(III). The adsorption capacity of La-Ce10/CFF reached 40.01 mg/g. It could purify the As(III) concentrations to drinking standard level (< 10 µg/L) over the pH ranges 3-10. It also possessed excellent anti-interference ability to the interfering ions. In addition, it worked reliably in the simulated As(III)-contaminated groundwater and river water. La-Ce10/CFF could easily apply in fixed-bed, and La-Ce10/CFF (1 g) packed column could purify 4580 BV (36.0 L) of As(III)-contaminated groundwater. When further considering the excellent reusability of La-Ce10/CFF, it is a promising and reliable adsorbent for As(III) deep remediation.