Gut microbiota and serum metabolomic alterations in modulating the impact of fecal microbiota transplantation on ciprofloxacin-induced seizure susceptibility.

Introduction: The gut microbiota and the microbiota-gut-brain axis have gained considerable attention in recent years, emerging as key players in the mechanisms that mediate the occurrence and progression of many central nervous system-related diseases, including epilepsy. In clinical practice, one of the side effects of quinolone antibiotics is a lower seizure threshold or aggravation. However, the underlying mechanism remains unclear. Methods: We aimed to unravel the intrinsic mechanisms through 16S rRNA sequencing and serum untargeted metabolomic analysis to shed light on the effects of gut microbiota in ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. Results: We observed that ciprofloxacin treatment increased seizure susceptibility and caused gut dysbiosis. We also found similar changes in the gut microbiota of rats with lithium pilocarpine-induced epilepsy. Notably, the levels of Akkermansia and Bacteroides significantly increased in both the ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. However, Marvinbryantia, Oscillibacter, and Ruminococcaceae_NK4A214_group showed a coincidental reduction. Additionally, the serum untargeted metabolomic analysis revealed decreased levels of indole-3-propionic acid, a product of tryptophan-indole metabolism, after ciprofloxacin treatment, similar to those in the plasma of lithium pilocarpine-induced epilepsy in rats. Importantly, alterations in the gut microbiota, seizure susceptibility, and indole-3-propionic acid levels can be restored by fecal microbiota transplantation. Conclusion: In summary, our findings provide evidence that ciprofloxacin-induced seizure susceptibility is partially mediated by the gut microbiota and tryptophan-indole metabolism. These associations may play a role in epileptogenesis, and impacting the development progression and treatment outcomes of epilepsy.

Resolved magnetohydrodynamic wave lensing in the solar corona.

Electromagnetic wave lensing, a common physical phenomenon recognized in visible light for centuries, finds extensive applications in manipulating light in optical systems such as telescopes and cameras. Magnetohydrodynamic wave is a common perturbation phenomenon in the corona. By using high spatio-temporal resolution observations from the Solar Dynamics Observatory, here, we report the observation of a magnetohydrodynamic wave lensing in the highly ionized and magnetized coronal plasma, where quasi-periodic wavefronts emanated from a flare converged at a specific point after traversing a coronal hole. The entire process resembles an electromagnetic wave lensing from the source to the focus. Meanwhile, the magnetohydrodynamic wave lensing is well reproduced through a magnetohydrodynamic numerical simulation with full spatio-temporal resolution. We further investigate potential applications for coronal seismology, as the lensing process encodes information on the Alfvén speed, in conjunction with favorable geometric and density variations.

Development of Ru-polypyridyl complexes for real-time monitoring of Aß oligomers and inhibition of Aß fibril formation.

The aggregation of amyloid-ß (Aß) is one of the important pathological markers of Alzheimer's disease. Ruthenium(II) complexes have good stability, low cytotoxicity, a high fluorescence quantum yield, and a good Stokes shift as fluorescent probes. Based on this, we constructed a fluorescent probe for in vivo real-time imaging and inhibition of Aß-fibril formation using a complex of Ru polypyridine with organic fluorophores (N,N-dimethylaniline) and hydrophobic peptides (KLVFF). DLS and TEM studies have shown that Ru-YH has an inhibitory effect on the fibrotic aggregation of Aß. Both in vivo and in vitro studies have shown that Ru-WJ and Ru-YH can quickly cross the blood-brain barrier and successfully detect Aß in early (2.5-month old) transgenic mouse models. In summary, we have explored the potential of Ru complex based biological probes for early diagnosis and inhibition of AD.

Local and Remote Chemogenetic Suppression of Hippocampal Seizures in Rats.

BACKGROUND: Innovative treatments of refractory epilepsy are widely desired, for which chemogenetic technology can provide region- and cell-type-specific modulation with relative noninvasiveness. OBJECTIVES: We aimed to explore the specific applications of chemogenetics for locally and remotely networks controlling hippocampal seizures. METHODS: A virus coding for a modified human Gi-coupled M4 muscarinic receptor (hM4Di) on pyramidal cells was injected into either the right hippocampal CA3 or the bilateral anterior nucleus of the thalamus (ANT) in rats. After one month, seizures were induced by 4-aminopyridine (4-AP) injection into the right CA3. Simultaneously, clozapine-N-oxide (CNO) (2.5 mg/kg) or clozapine (0.1 mg/kg), the specific ligands acting on hM4Di, were injected intraperitoneally. We also set up hM4Di control and clozapine control groups to eliminate the influence of viral transfection and the ligand alone on the experimental results. RESULTS: For both local and remote controls, the mean seizure duration was significantly reduced upon ligand application in the experimental groups. Seizure frequency, on the other hand, only showed a significant decrease in local control, with a lower frequency in the clozapine group than in the CNO group. Both the effects of CNO and clozapine were time-dependent, and clozapine was faster than CNO in local seizure control. CONCLUSION: This study shows the potency of chemogenetics to attenuate hippocampal seizures locally or remotely by activating the transfected hM4Di receptor with CNO or clozapine. ANT is suggested as a potentially safe chemogenetic application target in the epileptic network for focal hippocampal seizures.

Inconsistency between Human Observation and Deep Learning Models: Assessing Validity of Postmortem Computed Tomography Diagnosis of Drowning.

Drowning diagnosis is a complicated process in the autopsy, even with the assistance of autopsy imaging and the on-site information from where the body was found. Previous studies have developed well-performed deep learning (DL) models for drowning diagnosis. However, the validity of the DL models was not assessed, raising doubts about whether the learned features accurately represented the medical findings observed by human experts. In this paper, we assessed the medical validity of DL models that had achieved high classification performance for drowning diagnosis. This retrospective study included autopsy cases aged 8-91 years who underwent postmortem computed tomography between 2012 and 2021 (153 drowning and 160 non-drowning cases). We first trained three deep learning models from a previous work and generated saliency maps that highlight important features in the input. To assess the validity of models, pixel-level annotations were created by four radiological technologists and further quantitatively compared with the saliency maps. All the three models demonstrated high classification performance with areas under the receiver operating characteristic curves of 0.94, 0.97, and 0.98, respectively. On the other hand, the assessment results revealed unexpected inconsistency between annotations and models' saliency maps. In fact, each model had, respectively, around 30%, 40%, and 80% of irrelevant areas in the saliency maps, suggesting the predictions of the DL models might be unreliable. The result alerts us in the careful assessment of DL tools, even those with high classification performance.

DNA Nanobarrel-Based Drug Delivery for Paclitaxel and Doxorubicin.

Co-delivery of anticancer drugs and target agents by endogenous materials is an inevitable approach towards targeted and synergistic therapy. Employing DNA base pair complementarities, DNA nanotechnology exploits a unique nanostructuring method and has demonstrated its capacity for nanoscale positioning and templated assembly. Moreover, the water solubility, biocompatibility, and modifiability render DNA structure suitable candidate for drug delivery applications. We here report single-stranded DNA tail conjugated antitumor drug paclitaxel (PTX), and the co-delivery of PTX, doxorubicin and targeting agent mucin 1 (MUC-1) aptamer on a DNA nanobarrel carrier. We investigated the effect of tail lengths on drug release efficiencies and dual drug codelivery-enabled cytotoxicity. Owing to the rapidly developing field of structural DNA nanotechnology, functional DNA-based drug delivery is promising to achieve clinical therapeutic applications.

Ameliorative effects of the Coptis inflorescence extract against lung injury in diabetic mice by regulating AMPK/NEU1 signaling.

BACKGROUND: In diabetic patients, complications are the leading cause of death and disability, while diabetic lung damage has received little research. The Coptis inflorescence extract (CE) has hypoglycemic properties, but the mechanism of its protective role on diabetic lung injury is understood. PURPOSE: This study aims to explore the protective actions and molecular mechanism of CE and its active ingredients in diabetic lung disease. METHOD: Twenty-nine metabolites were identified in the metabolomic profile of CE using HPLC-ESI/MS, and high-content substances of berberine (BBR) and linarin (LIN) were isolated from CE using column chromatography. The potential targets and molecular mechanisms of CE against diabetic lung damage were systematically investigated by network pharmacology and in vitro experimental validation. RESULTS: CE significantly improved lung function and pathology. CE (360 mg/kg) or metformin treatment significantly improved lipid metabolism disorders, including decreased HDL-C and elevated serum TG, TC, and LDL-C levels. Furthermore, CE's chemical composition was determined using the HPLC-QTOF-MS method. CE identified five compounds as candidate active compounds (Berberine, Linarin, Palmatine, Worenine, and Coptisine). Network pharmacology analysis predicted CE contained five active compounds and target proteins, that AMPK, TGFß1, and Smad might be the key targets in treating diabetic lung injury. Then we investigated the therapeutic effect of bioactive compounds of CE on diabetic lung damage through in vivo and in vitro experiments. Intragastric administration with BBR (50 mg/kg) or LIN (20 mg/kg) suppressed weight loss, hyperglycemia, and dyslipidemia, significantly alleviating lung inflammation in diabetic mice. Further mechanism research revealed that LIN or BBR inhibited alveolar epithelial-mesenchymal transition induced by high glucose by regulating AMPK/NEU-mediated signaling pathway. CONCLUSION: In conclusion, the administration of CE can effectively alleviate diabetic lung damage, providing a scientific basis for lowering blood sugar to moisturize lung function. BBR and LIN, the main components of CE, can effectively alleviate diabetic lung damage by regulating AMPK/NEU1 Signaling and inhibiting the TGF-ß1 level, which may be a critical mechanism of its effects.

Textbook outcomes in liver surgery for gallbladder cancer patients treated with curative-intent resection: a multicenter observational study.

BACKGROUND: Cholecystectomy, hepatectomy, and lymphadenectomy are recommended as the curative treatment for resectable gallbladder cancer (GBC). Textbook outcomes in liver surgery (TOLS) is a novel composite measure that has been defined by expert consensus to represent the optimal postoperative course after hepatectomy. This study aimed to determine the incidence of TOLS and the independent predictors associated with TOLS after curative-intent resection in GBC patients. METHODS: All consecutive GBC patients who underwent curative-intent resection between 2014 and 2020 were enrolled from a multicenter database from 11 hospitals as the training and the internal testing cohorts, and Southwest Hospital as the external testing cohort. TOLS was defined as no intraoperative grade greater than or equal to 2 incidents, no grade B/C postoperative bile leaks, no postoperative grade B/C liver failure, no 90-day postoperative major morbidity, no 90-day readmission, no 90-day mortality after hospital discharge, and R0 resection. Independent predictors of TOLS were identified using logistic regression and were used to construct the nomogram. The predictive performance was assessed using the area under the curve and calibration curves. RESULTS: TOLS was achieved in 168 patients (54.4%) and 74 patients (57.8%) from the training and internal testing cohorts, and the external testing cohort, respectively. On multivariate analyses, age less than or equal to 70 years, absence of preoperative jaundice (total bilirubin≤3 mg/dl), T1 stage, N0 stage, wedge hepatectomy, and no neoadjuvant therapy were independently associated with TOLS. The nomogram that incorporated these predictors demonstrated excellent calibration and good performance in both the training and external testing cohorts (area under the curve: 0.741 and 0.726). CONCLUSIONS: TOLS was only achieved in approximately half of GBC patients treated with curative-intent resection, and the constructed nomogram predicted TOLS accurately.

Scalp ripple rates for rapid epilepsy differentiation and seizure activity assessment: Applicability and influential factors.

OBJECTIVE: We aim to determine whether automatically detected ripple rate (ADRR) of 10-min scalp electroencephalography (EEG) during slow-wave sleep can be a useful tool for rapid epilepsy differentiation and seizure activity assessment, and we analyze the clinical factors that may affect the scalp ripple rates. METHODS: We retrospectively included 336 patients who underwent long-term video-EEG with a sampling rate ≥1000 Hz, and three groups were established based on their final clinical diagnosis (non-epilepsy; non-active epilepsy [epilepsy being seizure-free for at least 1 year]; and active epilepsy [epilepsy with one or more seizures in the past year]). ADRRs between groups were compared and diagnostic thresholds set according to the maximum of Youden index with the receiver-operating characteristic curve. RESULTS: The 336 patients comprised 49 non-epilepsy and 287 epilepsy patients (95 non-active epilepsy and 192 active epilepsy). The median ADRR of the epilepsy group was significantly greater than in the non-epilepsy group, with a diagnostic threshold of 4.25 /min (specificity 89.8%, sensitivity 47.74%, p<.001). Following stratification by age, the area under the curve was greatest in the 0-20 year subgroup, threshold 4.10 /min (specificity 100%, sensitivity 52.47%, p<.001). Regarding distinguishing active epilepsy from non-active epilepsy patients, the area under the curve was also greatest in patients 0-20 years of age, threshold 13.05/min (specificity 98.36%, sensitivity 35.64%, p<.001). Following stratification by epilepsy type, the diagnostic efficiency was best in children with developmental and epileptic encephalopathies/epileptic encephalopathies (DEEs/EEs) (threshold 5.20/min, specificity 100%, sensitivity 100%) and self-limited focal epilepsies (SeLFEs) (threshold 5.45/min, specificity 80%, sensitivity 100%). Multivariate analysis revealed that the influential factors of ADRRs were age, depth of epileptogenic lesion, and seizure frequency. SIGNIFICANCE: ADRR of scalp EEG can be a rapid and specific method to differentiate epilepsy and evaluate seizure activity. This method is especially suitable for young patients.

The ability of long non-coding RNA RP11-284N8.3 to predict the risk, the severity and 28-day mortality of adults with sepsis.

In a prior study, we identified a novel sepsis specific long noncoding RNAs (lncRNA) RP11-284N8.3, which may primarily participate in T cell activation and immune response during sepsis. However, the clinical significance of lncRNA RP11-284N8.3 in sepsis remains entirely unknown. This single-center prospective cohort study enrolled 147 adults with sepsis and 74 healthy controls (HCs) with matched age and sex between January 2021 and November 2022 at our hospital. Blood samples and clinical data were collected from HCs at enrollment and from adults with sepsis within 24 hours after admission. lncRNA RP11-284N8.3 expression was detected by RT-qPCR. The relative expression of lncRNA RP11-284N8.3 was significantly decreased in adults with sepsis compared to HCs (P < .0001), in adults with septic shock compared to adults without shock (P = .0012), and in 28-day deaths compared to 28-day survivors (P = .0006). receiver operating characteristic curves of lncRNA RP11-284N8.3 in predicting sepsis severity and 28-day mortality showed an area under the curve of 0.6570 (95% confidence interval [CI]: 0.5701-0.7440) and an area under the curve of 0.6765 (95% CI: 0.5809-0.7721), respectively. Multivariate logistic regression analysis revealed that lncRNA RP11-284N8.3 was an independent risk factor for 28-day mortality in adults with sepsis (odds ratio: 0.1057, 95% CI: 0.0115-0.7746, P = .0328). Low expression of lncRNA RP11-284N8.3 is correlated with increased risk, severity and 28-day mortality in adults with sepsis, and it may function as a potential biomarker to facilitate the diagnosis and management of sepsis.

Analysis of bulk RNA-seq data from sepsis patients reveals sepsis-associated lncRNAs and targeted cell death-related genes contributing to immune microenvironment regulation.

Background: Sepsis is a life-threatening organ dysfunction syndrome that leads to the massive death of immune cells. Long non-coding RNAs (lncRNAs) have been reported to exert key regulatory roles in cells. However, it is unclear how lncRNAs regulate the survival of immune cells in the occurrence and development of sepsis. Methods: In this study, we used blood whole transcriptome sequencing data (RNA-seq) from normal controls (Hlty) and patients with uncomplicated infection (Inf1 P), sepsis (Seps P), and septic shock (Shock P), to investigate the fraction changes of immune cell types, expression pattern of cell death-related genes, as well as differentially expressed lncRNAs. Association network among these factors was constructed to screen out essential immune cell types, lncRNAs and their potential targets. Finally, the expression of lncRNAs and cell death genes in sepsis patients were validated by qRT-PCR. Results: In this study, we found fifteen immune cell types showed significant fraction difference between Hlty and three patient groups. The expression pattern of cell death-related genes was also dysregulated in Hlty compared with patient groups. Co-expression network analysis identified a key turquoise module that was associated with the fraction changes of immune cells. We then identified differentially expressed lncRNAs and their potential targets that were tightly associated with the immune cell dysregulation in sepsis. Seven lncRNAs, including LINC00861, LINC01278, RARA-AS1, RP11-156P1.3, RP11-264B17.3, RP11-284N8.3 and XLOC_011309, as well as their co-expressed cell death genes, were finally identified, and we validated two lncRNAs (LINC00861 and LINC01278) and four mRNA targets using qRT-PCR in sepsis samples. Conclusion: The global analysis of cell death-related genes in the occurrence and development of sepsis was carried out for the first time, and its expression regulation mode was displayed. The expression pattern of sepsis-associated lncRNAs were analyzed and identified, and the lncRNAs were significantly related to the change of immune cell proportion. We highlight the important roles of lncRNAs and their potential targets in the regulation of immune cell fraction changes during sepsis progression. The identified lncRNAs and their target genes may become new biomarkers and therapeutic targets of sepsis.

Heterophyllin B an Active Cyclopeptide Alleviates Dextran Sulfate Sodium-Induced Colitis by Modulating Gut Microbiota and Repairing Intestinal Mucosal Barrier via AMPK Activation.

SCOPE: Advances in pathology broaden the perception of the intimate interaction between gut microbiota dysbiosis and the pathogenesis of ulcerative colitis (UC), but the potential modulating roles remain to be elucidated. METHODS AND RESULTS: DSS-induced colitis is used to investigate the effect of Heterophyllin B (HB), a typical active cyclopeptide extracted from Pseudostellaria heterophylla, on colitis and gut microbiota. Administration of HB substantially mitigates the symptoms of UC as evidenced by increasing body weight and colon length, as well as decreased macrophages infiltration in the colon. Meanwhile, HB significantly alleviates intestinal mucosal barrier dysfunction by reducing the production of inflammatory cytokines, while all the mentioned beneficial effects are significantly eliminated by co-treatment with compound C, a selective AMPK inhibitor. In addition, 16S rDNA gene analyses and fecal microbiota transplantation also reveal that HB dramatically prevents against UC by reshaping intestinal dysbiosis, especially elevates the relative abundance of Akkermansia muciniphila. CONCLUSION: These findings illustrate that HB prominently improves intestinal epithelial homeostasis via activating AMPK and ameliorates the colonic inflammation in a gut microbiota-dependent manner, which provide evidence for microbial contribution to UC pathogenesis and suggesting a novel approach for colitis prevention.

Dinuclear Organoruthenium Complex for Mitochondria-Targeted Near-Infrared Imaging and Anticancer Therapy to Overcome Platinum Resistance.

New mononuclear and dinuclear Ru(II) coordination compounds with the 2,7-bisbenzoimidazolyl-naphthyridine ligand have been synthesized and characterized by UV-vis, NMR, and MALDI-TOF. The molecular structures for Ru(II) compounds were determined by single-crystal X-ray diffraction. With the expansion of ligand π-conjugation and the increase in the complexed Ru number, the maximum emission wavelength red-shifted from 696 to 786 nm. The binding mode between complexes and DNA was predicted by molecular docking, which is intercalations and π-π stacking interactions with the surrounding bases. The intercalation mode of DNA binding was then determined by DNA titration and ethidium bromide (EB) displacement experiments. The antigrowth effects of complexes RuY, RuY1, and RuY2 were tested in HaCat (normal cells), HeLa (cervical cancer), A549 (lung cancer), and A549/DDP (cisplatin-resistant lung cancer) through the MTT assay. The dinuclear complex RuY2 was superior to mononuclear complexes and cisplatin in the cisplatin-resistant cell line. Confocal imaging proved that the subcellular localization of Ru(II) complexes was mitochondria; moreover, apoptosis was detected by flow cytometry. All three complexes showed a dose-dependent manner in all four cell lines. All Ru(II) complexes were found to have reactive oxygen species (ROS). The finding indicated that these Ru(II) complexes caused cell death by both DNA disruption and ROS. This study helps to explore the potential of the polynuclear Ru(II) complexes for the combination of NIR imaging and Pt-resistant cancer therapy.

Decreased CXCR2 expression on circulating monocytes of colorectal cancer impairs recruitment and induces Re-education of tumor-associated macrophages.

Though circulating monocytes are the main source of tumour-associated macrophages (TAMs), the regulatory mechanisms of their recruitment to tumours and further differentiation remain unclear. In the present study, we observed a significant decrease in CXCR2 expression in classical circulating monocytes of patients with colorectal cancer (CRC), particularly those in the late TNM stage. The percentage of CXCR2+ monocytes was negatively associated with systemic inflammatory markers and positively associated with intratumoural immunocyte infiltration. The pro-inflammatory cytokine IFN-γ, which was overexpressed in patients with CRC, down-regulated CXCR2 expression of monocytes/TAMs by promoting GRK-2 expression. In vitro, inhibition of CXCR2 signalling in monocytes led to impaired chemotaxis to the tumour cell line supernatant and lower responsiveness to lipopolysaccharide (LPS) stimulation. Finally, monocytes from patients with CRC with decreased CXCR2 expression showed distinct phenotypes and functions after differentiating into CRC cell line-educated TAMs, including expression of co-stimulatory factors and secretion profile, than those from healthy controls. GRK-2 inhibitor altered the functional characteristics of TAMs. In summary, our findings suggest that CXCR2 expression on circulating monocytes reflects CRC stages and is an important factor determining TAM composition in the tumour microenvironment.

High-Frequency Oscillations and Epileptogenic Network.

Epilepsy is a network disease caused by aberrant neocortical large-scale connectivity spanning regions on the scale of several centimeters. High-frequency oscillations, characterized by the 80-600 Hz signals in electroencephalography, have been proven to be a promising biomarker of epilepsy that can be used in assessing the severity and susceptibility of epilepsy as well as the location of the epileptogenic zone. However, the presence of a high-frequency oscillation network remains a topic of debate as high-frequency oscillations have been previously thought to be incapable of propagation, and the relationship between high-frequency oscillations and the epileptogenic network has rarely been discussed. Some recent studies reported that high-frequency oscillations may behave like networks that are closely relevant to the epileptogenic network. Pathological highfrequency oscillations are network-driven phenomena and elucidate epileptogenic network development; high-frequency oscillations show different characteristics coincident with the epileptogenic network dynamics, and cross-frequency coupling between high-frequency oscillations and other signals may mediate the generation and propagation of abnormal discharges across the network.

Mechanistic Analysis of Micro-Neurocircuits Underlying the Epileptogenic Zone in Focal Cortical Dysplasia Patients.

We aim to explore the microscopic neurophysiology of focal cortical dysplasia (FCD) induced epileptogenesis in specific macroscopic brain regions, therefore mapping a micro-macro neuronal network that potentially indicates the epileptogenic mechanism. Epileptic and relatively non-epileptic temporal neocortex specimens were resected from FCD and mesial temporal lobe epilepsy (mTLE) patients, respectively. Whole-cell patch-clamping was performed on cells from the seizure onset zone (SOZ) and non-SOZ inside the epileptogenic zone (EZ) of FCD patients, as well as the non-epileptic neocortex of mTLE patients. Microscopic data were recorded, including membrane characteristics, spontaneous synaptic activities, and evoked action potentials. Immunohistochemistry was also performed on parvalbumin-positive (PV+) interneurons. We found that SOZ interneurons exhibited abnormal neuronal expression and distribution as well as reduced overall function compared with non-SOZ and mTLE interneurons. The SOZ pyramidal cells experienced higher excitation but lower inhibition than the mTLE controls, whereas the non-SOZ pyramidal cells exhibited intermediate excitability. Action potential properties of both types of neurons also suggested more synchronized neuronal activity inside the EZ, particularly inside the SOZ. Together, our research provides evidence for a potential neurocircuit underlying SOZ epileptogenesis and non-SOZ seizure susceptibility. Further investigation of this microscopic network may promote understanding of the mechanism of FCD-induced epileptogenesis.

Assessment of the prognostic value of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in perihilar cholangiocarcinoma patients following curative resection: A multicenter study of 333 patients.

Background & Aims: Tumor-associated chronic inflammation has been determined to play a crucial role in tumor progression, angiogenesis and immunosuppression. The objective of this study was to assess the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in perihilar cholangiocarcinoma (pCCA) patients following curative resection. Methods: Consecutive pCCA patients following curative resection at 3 Chinese hospitals between 2014 and 2018 were included. The NLR was defined as the ratio of neutrophil count to lymphocyte count. PLR was defined as the ratio of platelet count to lymphocyte count. The optimal cutoff values of preoperative NLR and PLR were determined according to receiver operating characteristic (ROC) curves for the prediction of 1-year overall survival (OS), and all patients were divided into high- and low-risk groups. Kaplan-Meier curves and Cox regression models were used to investigate the relationship between values of NLR and PLR and values of OS and recurrence-free survival (RFS) in pCCA patients. The usefulness of NLR and PLR in predicting OS and RFS was evaluated by time-dependent ROC curves. Results: A total of 333 patients were included. According to the ROC curve for the prediction of 1-year OS, the optimal cutoff values of preoperative NLR and PLR were 1.68 and 113.1, respectively, and all patients were divided into high- and low-risk groups. The 5-year survival rates in the low-NLR (<1.68) and low-PLR groups (<113.1) were 30.1% and 29.4%, respectively, which were significantly higher than the rates of 14.9% and 3.3% in the high-NLR group (≥1.68) and high-PLR group (≥113.1), respectively. In multivariate analysis, high NLR and high PLR were independently associated with poor OS and RFS for pCCA patients. The time-dependent ROC curve revealed that both NLR and PLR were ideally useful in predicting OS and RFS for pCCA patients. Conclusions: This study found that both NLR and PLR could be used to effectively predict long-term survival in patients with pCCA who underwent curative resection.

Case report: Recurrent hemobilia due to hepatic artery pseudoaneurysm mimicking gastrointestinal tract bleeding.

Hemobilia, a rare form of upper gastrointestinal bleeding (UGIB), is a potentially fatal complication that usually occurs after iatrogenic hepatobiliary trauma. However, hemobilia is clinically challenging to diagnose and often gets too late to diagnose. We herein report a case of recurrent hemobilia due to hepatic artery pseudoaneurysm (HAP) that was initially misdiagnosed as gastrointestinal tract bleeding. However, the patient was treated successfully with percutaneous coil occlusion of the pseudoaneurysm. This case illustrates that hemobilia can present as a mimic of gastrointestinal tract bleeding, but this is often difficult to diagnose at first glance and often misleads clinicians, especially emergency physicians, into making an incorrect diagnosis. Familiarity with the clinical features of hemobilia can help raise clinical suspicion and facilitate the early diagnosis and treatment of hemobilia.

Automatic detection of interictal ripples on scalp EEG to evaluate the effect and prognosis of ACTH therapy in patients with infantile spasms.

OBJECTIVE: We aimed to explore the feasibility of using scalp-recorded high-frequency oscillations (HFOs) to evaluate the efficacy and prognosis of adrenocorticotropic hormone (ACTH) treatment in patients with infantile spasms. METHODS: Thirty-nine children with infantile spasms were enrolled and divided into seizure-free and non-seizure-free groups after ACTH treatment. Patients who were seizure-free were further divided into relapse and non-relapse subgroups based on the observations made during a 6-month follow-up period. Scalp ripples were detected and compared during the interictal periods before and after 2 weeks of treatment. RESULTS: After ACTH treatment, the number and channels of ripples were significantly lower, whereas the percentage decrease in the number, spectral power, and channels of ripples was significantly higher in the seizure-free group than in the non-seizure-free group. In addition, the relapse subgroup showed higher number and spectral power and wider distribution of ripples than did the non-relapse subgroup. Changes in HFOs in terms of number, spectral power, and channel of ripples were closely related to the severity of epilepsy and can indicate disease susceptibility. SIGNIFICANCE: Scalp HFOs can be used as an effective biomarker to monitor the effect and evaluate the prognosis of ACTH therapy in patients with infantile spasms.