The circRNA circSCAF8 promotes tumor growth and metastasis of gastric cancer via miR-1293/TIMP1signaling.

SR-like CTD-associated factor 8 (SCAF8) can regulate transcriptional termination, but the function of circSCAF8 remains unclear. In our study, we observed a significant increase in circSCAF8 expression in gastric cancer, particularly in tissues with lymph node metastasis. The Kaplan-Meier curve revealed that high circSCAF8 expression was associated with a low overall survival time in gastric cancer patients. Moreover, circSCAF8 shRNA effectively decreased gastric cancer proliferation, invasion, and migration in vitro. Additionally, using bioluminescence imaging (BLI) technology in vivo, we found that circSCAF8 shRNA viruses inhibited the growth of xenograft tumors and gastric cancer lung metastasis. RNA immunoprecipitation (RIP) and circRNA pulldown assays confirmed the direct binding of circSCAF8 to miR-1293, but circSCAF8 could not regulate the expression of miR-1293 in gastric cancer. Interestingly, circSCAF8 regulated the downstream gene tissue inhibitor of metalloproteinases 1 (TIMP1) of miR-1293, and this observation was further verified in gastric cancer tissues. Moreover, we confirmed that miR-1293 directly suppressed TIMP1 expression. Subsequent rescue experiments revealed that TIMP1 overexpression reversed the impact of circSCAF8 shRNA viruses on gastric cancer. In conclusion, circSCAF8 expression was elevated in gastric cancer, and circSCAF8 shRNA viruses inhibited gastric cancer growth and metastasis by upregulating TIMP1 expression via miR-1293.

Activating astrocytic α2A adrenoceptors in hippocampus reduces glutamate toxicity to attenuate sepsis-associated encephalopathy in mice.

BACKGROUND: Glutamate metabolism disorder is an important mechanism of sepsis-associated encephalopathy (SAE). Astrocytes regulate glutamate metabolism. In septic mice, α2A adrenoceptor (α2A-AR) activation in the central nervous system provides neuroprotection. α2A-ARs are expressed abundantly in hippocampal astrocytes. This study was performed to determine whether hippocampal astrocytic α2A-AR activation confers neuroprotection against SAE and whether this protective effect is astrocyte specific and achieved by the modulation of glutamate metabolism. METHODS: Male C57BL/6 mice with and without α2A-AR knockdown were subjected to cecal ligation and puncture (CLP). They were treated with intrahippocampal guanfacine (an α2A-AR agonist) or intraperitoneal dexmedetomidine in the presence or absence of dihydrokainic acid [DHK; a glutamate transporter 1 (GLT-1) antagonist] and/or UCPH-101 [a glutamate/aspartate transporter (GLAST) antagonist]. Hippocampal tissue was collected for the measurement of astrocyte reactivity, GLT-1 and GLAST expression, and glutamate receptor subunit 2B (GluN2B) phosphorylation. In vivo real-time extracellular glutamate concentrations in the hippocampus were measured by ultra-performance liquid chromatography tandem mass spectrometry combined with microdialysis, and in vivo real-time hippocampal glutamatergic neuron excitability was assessed by calcium imaging. The mice were subjected to the Barnes maze and fear conditioning tests to assess their learning and memory. Golgi staining was performed to assess changes in the hippocampal synaptic structure. In vitro, primary astrocytes with and without α2A-AR knockdown were stimulated with lipopolysaccharide (LPS) and treated with guanfacine or dexmedetomidine in the presence or absence of 8-bromo- cyclic adenosine monophosphate (8-Br-cAMP, a cAMP analog). LPS-treated primary and BV2 microglia were also treated with guanfacine or dexmedetomidine. Astrocyte reactivity, PKA catalytic subunit, GLT-1 an GLAST expression were determined in primary astrocytes. Interleukin-1ß, interleukin-6 and tumor necrosis factor-alpha in the medium of microglia culture were measured. RESULTS: CLP induced synaptic injury, impaired neurocognitive function, increased astrocyte reactivity and reduced GLT-1 and GLAST expression in the hippocampus of mice. The extracellular glutamate concentration, phosphorylation of GluN2B at Tyr-1472 and glutamatergic neuron excitability in the hippocampus were increased in the hippocampus of septic mice. Intraperitoneal dexmedetomidine or intrahippocampal guanfacine administration attenuated these effects. Hippocampal astrocytes expressed abundant α2A-ARs; expression was also detected in neurons but not microglia. Specific knockdown of α2A-ARs in hippocampal astrocytes and simultaneous intrahippocampal DHK and UCPH-101 administration blocked the neuroprotective effects of dexmedetomidine and guanfacine. Intrahippocampal administration of DHK or UCPH-101 alone had no such effect. In vitro, guanfacine or dexmedetomidine inhibited astrocyte reactivity, reduced PKA catalytic subunit expression, and increased GLT-1 and GLAST expression in primary astrocytes but not in primary astrocytes that received α2A-AR knockdown or were treated with 8-Br-cAMP. Guanfacine or dexmedetomidine inhibited microglial reactivity in BV2 but not primary microglia. CONCLUSIONS: Our results suggest that neurocognitive protection against SAE after hippocampal α2A-AR activation is astrocyte specific. This protection may involve the inhibition of astrocyte reactivity and alleviation of glutamate neurotoxicity, thereby reducing synaptic injury. The cAMP/protein kinase A (PKA) signaling pathway is a potential cellular mechanism by which activating α2A-AR modulates astrocytic function.

Dexmedetomidine Inhibits Paraventricular Corticotropin-releasing Hormone Neurons that Attenuate Acute Stress-induced Anxiety-like Behavior in Mice.

BACKGROUND: Dexmedetomidine has repeatedly shown to improve anxiety, but the precise neural mechanisms underlying this effect remain incompletely understood. This study aims to explore the role of corticotropin-releasing hormone-producing hypothalamic paraventricular nucleus (CRHPVN) neurons in mediating the anxiolytic effects of dexmedetomidine. METHODS: A social defeat stress mouse model was used to evaluate the anxiolytic effects induced by dexmedetomidine through the elevated plus maze, open-field test, and measurement of serum stress hormone levels. In vivo Ca2+ signal fiber photometry and ex vivo patch-clamp recordings were used to determine the excitability of CRHPVN neurons and investigate the specific mechanism involved. CRHPVN neuron modulation was achieved through chemogenetic activation or inhibition. RESULTS: Compared with saline, dexmedetomidine (40 µg/kg) alleviated anxiety-like behaviors. Additionally, dexmedetomidine reduced CRHPVN neuronal excitability. Chemogenetic activation of CRHPVN neurons decreased the time spent in the open arms of the elevated plus maze and in the central area of the open-field test. Conversely, chemogenetic inhibition of CRHPVN neurons had the opposite effect. Moreover, the suppressive impact of dexmedetomidine on CRHPVN neurons was attenuated by the α2-receptor antagonist yohimbine. CONCLUSIONS: The results indicate that the anxiety-like effects of dexmedetomidine are mediated via α2-adrenergic receptor-triggered inhibition of CRHPVN neuronal excitability in the hypothalamus.

The Association of Preoperative Diabetes With Postoperative Delirium in Older Patients Undergoing Major Orthopedic Surgery: A Prospective Matched Cohort Study.

BACKGROUND: Postoperative delirium (POD) is a common form of postoperative brain dysfunction, especially in the elderly. However, its risk factors remain largely to be determined. This study aimed to investigate whether (1) preoperative diabetes is associated with POD after elective orthopedic surgery and (2) intraoperative frontal alpha power is a mediator of the association between preoperative diabetes and POD. METHODS: This was a prospective matched cohort study of patients aged 60 years or more, with a preoperative diabetes who underwent elective orthopedic surgery. Nondiabetic patients were matched 1:1 to diabetic patients in terms of age, sex, and type of surgery. Primary outcome was occurrence of POD, assessed using the 3-minute Diagnostic Confusion Assessment Method (3D-CAM) once daily from 6 pm to 8 pm during the postoperative days 1-7 or until discharge. Secondary outcome was the severity of POD which was assessed for all participants using the short form of the CAM-Severity. Frontal electroencephalogram (EEG) was recorded starting before induction of anesthesia and lasting until discharge from the operating room. Intraoperative alpha power was calculated using multitaper spectral analyses. Mediation analysis was used to estimate the proportion of the association between preoperative diabetes and POD that could be explained by intraoperative alpha power. RESULTS: A total of 138 pairs of eligible patients successfully matched 1:1. After enrollment, 6 patients in the diabetes group and 4 patients in the nondiabetes group were excluded due to unavailability of raw EEG data. The final analysis included 132 participants with preoperative diabetes and 134 participants without preoperative diabetes, with a median age of 68 years and 72.6% of patients were female. The incidence of POD was 16.7% (22/132) in patients with preoperative diabetes vs 6.0% (8/134) in patients without preoperative diabetes. Preoperative diabetes was associated with increased odds of POD after adjustment of age, sex, body mass index, education level, hypertension, arrhythmia, coronary heart disease, and history of stroke (odds ratio, 3.2; 95% confidence interval [CI], 1.4-8.0; P = .009). The intraoperative alpha power accounted for an estimated 20% (95% CI, 2.6-60%; P = .021) of the association between diabetes and POD. CONCLUSIONS: This study suggests that preoperative diabetes is associated with an increased risk of POD in older patients undergoing major orthopedic surgery, and that low intraoperative alpha power partially mediates such association.

Prognosis and Prediction of Asymptomatic Intracranial Hemorrhage After Endovascular Thrombectomy: A Multi-Center Study.

PURPOSE: The impact of asymptomatic intracranial hemorrhage (aICH) on functional outcomes after endovascular thrombectomy (EVT) remains unclear, and tools for forecasting this complication are lacking. We aim to evaluate the clinical relevance of aICH and establish a prediction model. METHODS: Data of patients who received EVT for acute anterior-circulation large vessel occlusion in 3 comprehensive hospitals were retrospectively analyzed. Asymptomatic intracranial hemorrhage was defined as any hemorrhage detected after EVT that did not fulfill the definition of symptomatic intracranial hemorrhage in the European Cooperative Acute Stroke Study. Logistic regression models were performed to assess the impact of aICH on 90-day functional outcomes and identify the predictors of aICH, which were then used to establish a prediction model. The discrimination, calibration, and clinical utility of the model were evaluated. RESULTS: This study included 460 patients, among whom 152 (33.0%) developed aICH after EVT. Asymptomatic intracranial hemorrhage was negatively associated with 90-day excellent outcomes (adjusted odds ratio [OR]: 0.414, 95% confidence interval [CI]: 0.230-0.745, p=0.003) and good outcome (adjusted OR: 0.603, 95% CI: 0.374-0.971, p=0.037), but not with mortality (adjusted OR: 1.110, 95% CI: 0.611-2.017, p=0.732) after adjusted for other predictors of functional outcome. Pre-stroke anticoagulant therapy (OR: 2.233, 95% CI: 1.073-4.647, p=0.032), Alberta stroke program early CT score (OR: 0.842, 95% CI: 0.754-0.939, p=0.002), site of occlusion (internal carotid artery occlusion as the reference; M1 segment of middle cerebral artery occlusion, OR: 2.827, 95% CI: 1.409-5.674, p=0.003; tandem occlusion, OR: 3.928, 95% CI: 1.752-8.806, p=0.001), intravenous thrombolysis (OR: 2.091, 95% CI: 1.362-3.209, p=0.001), and successful recanalization (OR: 0.383, 95% CI: 0.213-0.689, p=0.001) were identified as the predictors of aICH, which were incorporated into a nomogram model. The area under the receiver operating characteristic curve of the model was 0.707 (95% CI: 0.657-0.757), and the calibration plot demonstrated good consistency between actual observed and predicted probability of aICH. Decision curve analysis showed that patients might benefit from the model. CONCLUSION: Asymptomatic intracranial hemorrhage was negatively associated with favorable functional outcome after EVT. We established a nomogram model for predicting aICH, which requires external clinical validation. CLINICAL IMPACT: The impact of asymptomatic intracranial hemorrhage after endovascular thrombectomy on mid-term functional outcome has been controversial. We found that asymptomatic intracranial hemorrhage may also decreased the likelihood of 90-day favourable functional outcome after endovascular thrombectomy, supporting the notion that asymptomatic intracranial hemorrhage at the acute stage may not be benign. Moreover, we established a prediction model for this complication, which may improve clinical evaluation and management of patients who would receive endovascular thrombectomy for large vessel occlusion.

DrLLPS: a data resource of liquid-liquid phase separation in eukaryotes.

Here, we presented an integrative database named DrLLPS (http://llps.biocuckoo.cn/) for proteins involved in liquid-liquid phase separation (LLPS), which is a ubiquitous and crucial mechanism for spatiotemporal organization of various biochemical reactions, by creating membraneless organelles (MLOs) in eukaryotic cells. From the literature, we manually collected 150 scaffold proteins that are drivers of LLPS, 987 regulators that contribute in modulating LLPS, and 8148 potential client proteins that might be dispensable for the formation of MLOs, which were then categorized into 40 biomolecular condensates. We searched potential orthologs of these known proteins, and in total DrLLPS contained 437 887 known and potential LLPS-associated proteins in 164 eukaryotes. Furthermore, we carefully annotated LLPS-associated proteins in eight model organisms, by using the knowledge integrated from 110 widely used resources that covered 16 aspects, including protein disordered regions, domain annotations, post-translational modifications (PTMs), genetic variations, cancer mutations, molecular interactions, disease-associated information, drug-target relations, physicochemical property, protein functional annotations, protein expressions/proteomics, protein 3D structures, subcellular localizations, mRNA expressions, DNA & RNA elements, and DNA methylations. We anticipate DrLLPS can serve as a helpful resource for further analysis of LLPS.

A small nucleolar RNA, SNORD126, promotes adipogenesis in cells and rats by activating the PI3K-AKT pathway.

Small nucleolar RNA (snoRNA) plays important role in various histogenesis. Whether snoRNA plays a role in adipogenesis is unknown. SNORD126 is a C/D box snoRNA. We previously demonstrated that SNORD126 promoted hepatocellular carcinoma cell growth by activating the phosphoinositide 3-kinase-protein kinase B (Akt) pathway through upregulating fibroblast growth factor receptor 2 expression. In the present study, we found that the expression of SNORD126 was downregulated in the obesity-related tissues in high-fat diet-fed rats. Overexpression of SNORD126 in 3T3-L1 cells promoted adipocytes differentiation. SNORD126 significantly increased the expression of CCAAT/enhancer-binding protein α, fatty acid-binding protein 4, peroxisome proliferative-activated receptor-γ, and the phosphorylation of Akt and p70S6K. Overexpression of SNORD126 in human adipose-derived stem cells stimulated adipogenesis and increased phosphorylation of Akt. Meanwhile, SNORD126 increased the messenger RNA and protein levels of cyclin D1 and cyclin-dependent kinase 2, which promoted mitotic clonal expansion progression during the early stage of 3T3-L1 cell differentiation. We further found that SNORD126 accelerated the growth of the groin fat pad and increased phosphorylation of Akt and p70S6K in rats. Overall, our results suggested that SNORD126 promoted adipocyte differentiation through increasing phosphorylation of Akt and p70S6K both in vitro and in vivo.

Dexmedetomidine attenuates sepsis-associated inflammation and encephalopathy via central α2A adrenoceptor.

Sepsis-associated encephalopathy (SAE) is a significant clinical issue that is associated with increased mortality and cost of health care. Dexmedetomidine, an α2 adrenoceptor agonist that is used to provide sedation, has been shown to induce neuroprotection under various conditions. This study was designed to determine whether dexmedetomidine protects against SAE and whether α2 adrenoceptor plays a role in this protection. Six- to eight-week old CD-1 male mice were subjected to cecal ligation and puncture (CLP). They were treated with intraperitoneal injection of dexmedetomidine in the presence or absence of α2 adrenoceptor antagonists, atipamezole or yohimbine, or an α2A adrenoceptor antagonist, BRL-44408. Hippocampus and blood were harvested for measuring cytokines. Mice were subjected to Barnes maze and fear conditioning 14 days after CLP to evaluate their learning and memory. CLP significantly increased the proinflammatory cytokines including tumor necrosis factor α, interleukin (IL)-6 and IL-1ß in the blood and hippocampus. CLP also increased the permeability of blood-brain barrier (BBB) and impaired learning and memory. These CLP detrimental effects were attenuated by dexmedetomidine. Intracerebroventricular application of atipamezole, yohimbine or BRL-44408 blocked the protection of dexmedetomidine on the brain but not on the systemic inflammation. Astrocytes but not microglia expressed α2A adrenoceptors. Microglial depletion did not abolish the protective effects of dexmedetomidine. These results suggest that dexmedetomidine reduces systemic inflammation, neuroinflammation, injury of BBB and cognitive dysfunction in septic mice. The protective effects of dexmedetomidine on the brain may be mediated by α2A adrenoceptors in the astrocytes.

GC-MS metabolomics identifies novel biomarkers to distinguish tuberculosis pleural effusion from malignant pleural effusion.

BACKGROUND: Tuberculous pleural effusions (TBPEs) and malignant pleural effusions (MPEs) are two of the most common and severe forms of exudative effusions. Clinical differentiation is challenging; however, metabolomics is a collection of powerful tools currently being used to screen for disease-specific biomarkers. METHODS: 17 TBPE and 17 MPE patients were enrolled according to the inclusion criteria. The normalization gas chromatography-mass spectrometry (GC-MS) data were imported into the SIMCA-P + 14.1 software for multivariate analysis. The principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used to analyze the data, and the top 50 metabolites of variable importance projection (VIP) were obtained. Metabolites were qualitatively analyzed using the National Institute of Standards and Technology (NIST) databases. Pathway analysis was performed by MetaboAnalyst 4.0. The detection of biochemical indexes such as urea and free fatty acids in these pleural effusions was also verified, and significant differences were found between these two groups. RESULTS: 1319 metabolites were screened by non-targeted metabonomics of GC-MS. 9 small molecules (urea, L-5-oxoproline, L-valine, DL-ornithine, glycine, L-cystine, citric acid, stearic acid, and oleamide) were found to be significantly different (p < 0.05 for all). In OPLS-DA, 9 variables were considered significant for biological interpretation (VIP≥1). However, after the ROC curve was performed, it was found that the metabolites with better diagnostic value were stearic acid, L-cystine, citric acid, free fatty acid, and creatinine (AUC > 0.8), with good sensitivity and specificity. CONCLUSION: Stearic acid, L-cystine, and citric acid may be potential biomarkers, which can be used to distinguish between the TBPE and the MPE.

Hemobilia due to Hepatic artery pseudoaneurysm secondary to collateral circulation formation after liver trauma: a case report.

BACKGROUND: Hemobilia due to rupture of hepatic artery pseudoaneurysm and recurrent hemorrhage caused by hepatic artery collateral circulation are both rare complications after liver trauma. There have been a number of separate reports of both complications, but no cases have been reported in which the two events occurred in the same patient. Here we report a recurrent hemorrhage in the bile duct due to hepatic artery pseudoaneurysm secondary to collateral circulation formation after hepatic artery ligation in a patient with liver trauma. CASE PRESENTATION: A 52-year-old male patient was admitted to our hospital for liver trauma (Grade IV according to the American Association for the Surgery of Trauma (AAST) grading system) with active bleeding after a traffic accident. Hepatic artery ligation was performed for hemostasis. Three months after the surgery, the patient was readmitted for melena and subsequent hematemesis. Selective angiography examination revealed the formation of collateral circulation between the superior mesenteric artery and right hepatic artery. Moreover, a ruptured hepatic artery pseudoaneurysm was observed and transcatheter arterial embolization (TAE) was performed for hemostasis at the same time. After the treatment, the patient recovered very well and had an uneventful prognosis until the last follow-up. CONCLUSION: For patients with hepatic trauma, the selection of the site of hepatic artery ligation and the diagnosis and treatment methods of postoperative biliary hemorrhage are crucial for the prognosis of the disease.

Full-Scale Maneuvering Trials Correction and Motion Modelling Based on Actual Sea and Weather Conditions.

Aiming at the poor accuracy and difficult verification of maneuver modeling induced by the wind, waves and sea surface currents in the actual sea, a novel sea trials correction method for ship maneuvering is proposed. The wind and wave drift forces are calculated according to the measurement data. Based on the steady turning hypothesis and pattern search algorithm, the adjustment parameters of wind, wave and sea surface currents were solved, the drift distances and drift velocities of wind, waves and sea surface currents were calculated and the track and velocity data of the experiment were corrected. The hydrodynamic coefficients were identified by the test data and the ship maneuvering motion model was established. The results show that the corrected data were more accurate than log data, the hydrodynamic coefficients can be completely identified, the prediction accuracy of the advance and tactical diameters were 93% and 97% and the prediction of the maneuvering model was accurate. Numerical cases verify the correction method and full-scale maneuvering model. The turning circle advance and tactical diameter satisfy the standards of the ship maneuverability of International Maritime Organization (IMO).

[Design and Implementation of Remote Firmware Update System Based on IAP Technology].

This paper introduces a network remote firmware update system based on IAP technology, which aims to solve the problems of low efficiency and high cost in the traditional upgraded medical device firmware (lower computer program) mode, and to improve the portability of the lower computer program upgrade maintenance. In order to better cope with market changes, customer needs, and solve software failures in medical devices, it is necessary to update and upgrade medical device software in a timely manner. Through the IAP technology and Internet communication technology of STM32 platform, this solution can complete the update of all instrument firmware in a short time, which not only saves a lot of travel expenses, mailing costs and labor costs, but also greatly shortens the update time.

Adiponectin Attenuates Streptozotocin-Induced Tau Hyperphosphorylation and Cognitive Deficits by Rescuing PI3K/Akt/GSK-3ß Pathway.

Clinical studies have demonstrated that decreased adiponectin is associated with the development of Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD). We focused on determining the neuroprotective effect offered by adiponectin against streptozotocin-induced brain damage in ICV-STZ rat model. We found that adiponectin supplements significantly restored the cognitive deficits in ICV-STZ rat model including shorter escape latency, more crossing times and increased time spent in the target quadrant. Adiponectin supplements also increased number of dendritic branches and mushroom percentage. In addition, adiponectin supplements attenuated tau hyperphosphorylation at multiple AD-related sites through activation of protein Ser9-phosphorylated glycogen synthase kinase-3ß (Ser9-GSK-3ß) with increased the Akt and PI3K activity. Our data suggest that adiponectin supplements have neuroprotective effects on the ICV-STZ rat model, which may be mediated by the activation of the PI3K/Akt/GSK-3ß signaling pathway.

Ultrasound-guided left lateral transversus abdominis plane block combined with rectus sheath block in peritoneal dialysis catheter placement.

This study assessed the utility of ultrasound-guided lateral transversus abdominis plane (TAP) block combined with rectus sheath (RS) block for peritoneal dialysis catheter placement surgery. Thirty consecutive patients with end-stage renal disease scheduled to have peritoneal dialysis catheter placement received a left lateral TAP block combined with RS block performed under ultrasound guidance. The TAP and RS blocks were, respectively, conducted with 15 ml of 0.5% ropivacaine and 10 ml of 0.5% ropivacaine. Pain intensity was evaluated by verbal rating scale during operation, and the degree of patient and surgeon satisfaction was qualified by a categorical scale. Twenty-nine patients received successful blocks without any other adjuvant anesthetic drugs. One patient required rescue analgesia with lidocaine infiltration. No complications related to regional anesthesia were noted. Ultrasound-guided left lateral TAP block combined with RS block can serve as the primary anesthetic modality for peritoneal dialysis catheter placement surgery.

Perioperative risk factors and cumulative duration of "triple-low" state associated with worse 30-day mortality of cardiac valvular surgery.

ABSRACT: Hospital stay and mortality in high-risk patients after noncardiac surgery has been associated with a triple low anesthesia. However, the association between anesthesia-related factors and perioperative outcome after cardiac surgery remains unclear.We tested the effect of a novel triple low state: low mean arterial pressure (MAP) <65 mmHg and low bispectral index (BIS) <45 during a low target effect-site concentration (Ce) <1.5 µg ml-1 of propofol anesthesia on postoperative duration of hospitalization and 30-day mortality in cardiac valvular patients. In this prospective observational study, univariable and multivariable logistic regression analyses were used to determine whether perioperative factors, in particular, cumulative duration of triple low state were independently associated with duration of hospitalization and 30-day mortality among patients who underwent elective valvular replacement. 489 patients were included in the final analysis. After adjusting for related covariates, cumulative duration of the triple-low state was not associated with prolonged hospitalization (multivariable odds ratio: 1.007; 95 % confidence interval 0.997-1.017; P = 0.564), but was a significant predictor of 30-day mortality (multivariable odds ratio: 1.016; 95 % confidence interval 1.002-1.031; P = 0.030). Compared to a triple-low duration of <15 min, a duration >60 min increased the 30-day mortality rate by 8 times. After adjusting for patient- and procedure-related characteristics, the cumulative duration of a triple-low state (intraoperative low MAP, low BIS, and low Ce) was associated with poorer 30-day mortality, but not with prolonged duration of hospital stay.The mortality risk was even greater when a cumulative time >60 min.

Adjuvant Transarterial Chemoembolization Plus Immunotherapy for Huge Hepatocellular Carcinoma: A Propensity Score Matching Cohort Study.

Purpose: The prognosis of patients with huge hepatocellular carcinoma (huge HCC, diameter ≥10 cm) is poor owing to the high early recurrence rate. This study aimed to explore the clinical value of postoperative adjuvant transarterial chemoembolization (PA-TACE) plus programmed cell death-1 (PD-1) inhibitors for huge HCC. Patients and Methods: Data from consecutive huge HCC patients treated with hepatectomy during June 2017 and July 2022 were retrospectively collected. Baseline differences were balanced between huge HCC patients who underwent PA-TACE with (AIT group) or without PD-1 inhibitors (AT group) by propensity-score matching (PSM). We compared recurrence-free survival (RFS), overall survival (OS) and recurrence patterns between the two groups. Independent risk factors for RFS and OS were confirmed by Cox regression analysis, and subgroup analysis was also conducted. Results: A total of 294 patients were enrolled, and 77 pairs of patients in the AIT and AT groups were matched by PSM. The 1-year and 2-year RFS were 49.9% and 35.7% in the AIT group compared to 24.7% and 15.5% in the AT group respectively (p<0.001). The 1-year and 2-year OS were 83.6% and 66.9% in the AIT group compared to 50.6% and 36.8% in the AT group respectively (p<0.001). There were no significant differences in recurrence patterns between the two groups. Multivariable analysis demonstrated that combined therapy of PA-TACE plus PD-1 inhibitors was a protective factor related to both RFS and OS. Conclusion: PA-TACE plus PD-1 inhibitors could improve survival outcomes for huge HCC patients.

Improvements in advanced hepatocellular carcinoma to repeat implementation of primary protocol after cancer progression occurs following sequential systemic therapy and a clinical trial: A case report.

INTRODUCTION: Systemic therapy is recommended for patients with advanced hepatocellular carcinoma (aHCC). However, drug resistance occurs over time when patients receive systemic therapy, resulting in cancer progression. Due to the lack of relevant clinical trials, optimizing subsequent treatments after cancer progression remains elusive. PATIENT CONCERNS: A 52-year-old male patient presented with epigastric discomfort and fatigue for almost 1 month with a past history of chronic hepatitis B virus infection for 30 years. DIAGNOSIS: Based on the patient's performance status, tumor status assessed by computed tomography, liver function, he was diagnosed with HCC at BCLC stage C. INTERVENTIONS AND OUTCOMES: He first received transarterial chemoembolization (TACE) combined with sintilimab and lenvatinib as first-line treatment and experienced 10-month progression-free survival. After cancer progression, the patient participated in a clinical trial of ABSK-011, a novel fibroblast growth factor receptor 4 inhibitor, with a frustrating result. Then, the patient underwent TACE and received sintilimab plus lenvatinib again. Surprisingly, the tumor had a partial response, and the patient's serum alpha-fetoprotein returned to normal. LESSONS: The combined treatment of TACE plus systemic therapy might be an appropriate subsequent treatment.

Difference between arterial and venous peak optical density after thrombectomy is associated with functional outcomes.

Background: The density of contrast medium in digital subtraction angiography (DSA) have been used to evaluate the cerebral circulation function. Our aim was to study the effect of difference in arteriovenous peak optical density (POD) after thrombectomy on functional outcomes. Methods: Consecutive patients with acute ischemic stroke due to large vessel occlusion who underwent thrombectomy were reviewed. We processed DSA images with ImageJ software to measure the POD of internal carotid artery (ICA) and cortical veins. The average POD of cortical veins (PODVA) and the POD difference between ICA and cortical veins (PODICA-CV) were calculated. Primary outcome was good functional outcome (modified Rankin scale score of 0-2 at 90 days). Results: One hundred sixty-six patients were finally included in the study. Patients with good functional outcome had lower ipsilateral PODVA (median [interquartile range (IQR)], 257.198 [216.623-296.631] vs. 290.944 [248.647-338.819], p < 0.001) and lower ipsilateral PODICA-CV (median [IQR], 128.463 [110.233-153.624] vs. 182.01 [146.621-211.331], p < 0.001). Multivariable logistic regression analyses showed that ipsilateral PODVA (odds ratio [OR] 0.991, 95% confidence interval [CI] 0.984-0.999, p = 0.019) and ipsilateral PODICA-CV (OR 0.975, 95% CI 0.963-0.986, p < 0.001) were associated with good functional outcome. The predictive ability was significantly enhanced in the model including ipsilateral PODICA-CV (0.893 vs. 0.842, p = 0.027). No correlation was found between ipsilateral PODICA-CV and expanded Thrombolysis in Cerebral Infarction grades (r = -0.133, p = 0.099). Conclusion: Ipsilateral PODICA-CV is an additional indicator of cerebral reperfusion status and predicts functional outcomes after thrombectomy.

Establishment and Validation of a Nomogram for Identifying False Positives in Xpert MTB/RIF Rifampicin Resistance Test.

Purpose: This study aimed to establish and validate a diagnostic nomogram for identifying false positives in the Xpert MTB/RIF (Xpert) for detection of rifampicin resistance (RIF-R). Patients and Methods: In this retrospective study, we collected basic patient characteristics and various clinical information from the electronic medical record database. Patients were randomly divided into training and validation groups in a 7:3 ratio. LASSO regression was used to screen variables and construct a diagnostic nomogram. The ROC curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the performance of the nomogram. Results: A total of 384 patients were included in the study, with 268 and 116 patients in the training and validation cohorts, respectively. Finally, probe mutations and probe delay were identified as the independent influencing factors. Using the mutation of probe E as a reference, probes A or C (OR = 51.07, P<0.001), probe D (OR = 7.48, P<0.001), and multiple probes (OR = 4.42, P=0.029) were identified as factors influencing false positives in Xpert for detection of RIF-R. Taking probe delay ΔCT <4 as a reference, ΔCT (4-5.9) (OR = 17.06, P=0.005) and ΔCT (6-7.9) (OR = 36.67, P<0.001) were noted to be the factors influencing false positives in Xpert for detection of RIF-R. Based on these two variables, we constructed a diagnostic nomogram. The area under the curve of the nomogram model was 0.847 and 0.850 for the training and validation groups, respectively. The calibration curves were consistent. The DCA revealed that the model achieved the greatest net benefit when the threshold probability was set between 6% and 71% in the training cohort and 6% and 70% in the validation cohort. Conclusion: The nomogram constructed can identify false positives in Xpert for detection of RIF-R and provides basis for clinicians to formulate diagnosis and treatment plans.