Safety and efficacy of interventional embolization in cirrhotic patients with refractory hepatic encephalopathy associated with spontaneous portosystemic shunts.

This study aimed to assess the safety and efficacy of interventional embolization in cirrhotic patients with refractory hepatic encephalopathy (HE) associated with large spontaneous portosystemic shunts (SPSS). Inverse probability of treatment weighting (IPTW) was employed to minimize potential bias. A total of 123 patients were included in this study (34 in the embolization group and 89 in the control group). In the unadjusted cohort, the embolization group demonstrated significantly better liver function, a larger total area of SPSS, and a higher percentage of patients with serum ammonia levels > 60 µmol/L and the presence of hepatocellular carcinoma (HCC) (all P < 0.05). In the IPTW cohort, baseline characteristics were comparable between the two groups (all P > 0.05). Patients in the embolization group exhibited significantly longer HE-free survival compared to the control group in both the unadjusted and IPTW cohorts (both P < 0.05). Subsequent subgroup analyses indicated that patients with serum ammonia level > 60 µmol/L, hepatopetal flow within the portal trunk, the presence of solitary SPSS, a baseline HE grade of II, and the absence of HCC at baseline showed statistically significant benefit from embolization treatment (all P < 0.05). No early procedural complications were observed in the embolization group. The incidence of long-term postoperative complications was comparable to that in the control group (all P > 0.05). Hence, interventional embolization appears to be a safe and effective treatment modality for cirrhotic patients with refractory HE associated with large SPSS. However, the benefits of embolization were discernible only in a specific subset of patients.

Integrated Analysis of scRNA-Seq and Bulk RNA-Seq Reveals Metabolic Reprogramming of Liver Cancer and Establishes a Prognostic Risk Model.

Liver cancer manifests as a profoundly heterogeneous malignancy, posing significant challenges in terms of both therapeutic intervention and prognostic evaluation. Given that the liver is the largest metabolic organ, a prognostic risk model grounded in single-cell transcriptome analysis and a metabolic perspective can facilitate precise prevention and treatment strategies for liver cancer. Hence, we identified 11 cell types in a scRNA-seq profile comprising 105,829 cells and found that the metabolic activity of malignant cells increased significantly. Subsequently, a prognostic risk model incorporating tumor heterogeneity, cell interactions, tumor cell metabolism, and differentially expressed genes was established based on eight genes; this model can accurately distinguish the survival outcomes of liver cancer patients and predict the response to immunotherapy. Analyzing the immune status and drug sensitivity of the high- and low-risk groups identified by the model revealed that the high-risk group had more active immune cell status and greater expression of immune checkpoints, indicating potential risks associated with liver cancer-targeted drugs. In summary, this study provides direct evidence for the stratification and precise treatment of liver cancer patients, and is an important step in establishing reliable predictors of treatment efficacy in liver cancer patients.

CRISPR/Cas12b assisted loop-mediated isothermal amplification for easy, rapid and sensitive quantification of chronic HBV DNA in one-pot.

BACKGROUND: Currently, millions of people suffer from undiagnosed chronic hepatitis B (CHB) infection each year, which leads to high mortality rates attributed to cirrhosis and hepatocellular carcinoma. Previously reported assays, such as PCR-based assays, have limitations in terms of convenient for CHB screening in high-burden regions and resource-limited settings. Recently, diagnosis based on CRISPR/Cas, which has been considered as a potential method of point-of-care test (POCT) in resource-limited settings, offers a significant advantage in terms of high sensitivity and specificity. Therefore, there is an urgent need for the hepatitis B virus (HBV) detection utilizing CRISPR/Cas system. RESULTS: We have proposed a one-pot of one-step method for CRISPR/Cas12b assisted loop-mediated isothermal amplification (LAMP) to facilitate the quick, sensitive, and precise quantification of HBV DNA. This method is designed for point-of-care testing following genomic extraction or sample heat treatment. We have optimized several critical factors, such as the reaction buffer, AapCas12b-gRNA concentration, reporter and its concentration, reaction temperature, and chemical additives, to significantly enhance the performance of the one-pot assay for HBV. Importantly, it exhibited no cross-reactivity between HBV and blood-borne pathogens. Moreover, the assay is capable of quantifying HBV DNA within 1 h with a limit of detection (LOD) of 25 copies per milliliter. Additionally, when tested on 236 clinical samples, the assay demonstrated a sensitivity of 99.00 % (198/200) and a specificity of 100.00 % (36/36) at the 99 % confidence level compared to real-time quantitative PCR. SIGNIFICANCE: The utilization of convenient and reliable point-of-care diagnostic methods is crucial for reducing the burden of CHB globally. The assay we developed was helpful to improve the ability of HBV diagnosis for practical clinical translation, especially in high-burden regions and resource-limited settings. It has great advantages for rapid screening of CHB as well as evaluation of therapeutic efficacy as a companion diagnostic method.

Beta 2-microglobulin is an independent risk marker of acute kidney injury in adult patients with hemophagocytic lymphohistiocytosis.

BACKGROUND AND AIMS: The role of beta2-microglobulin (ß2-MG) in predicting acute kidney injury (AKI) in hemophagocytic lymphohistiocytosis patients has been poorly studied. This study aimed to analyze the clinical characteristics of hemophagocytic lymphohistiocytosis patients and identify risk factors that predict AKI development. METHODS: This retrospective observational cohort study conducted at a single-center involved 938 patients diagnosed with hemophagocytic lymphohistiocytosis, who were divided into AKI  group and non-AKI group. Patient data were collected and analyzed using univariate and multivariate binary logistic regression to identify potiential risk factors associated with AKI occurrence.   RESULTS: Among the enrolled patients, 486 were male (51.9%), the median age was 37 years (interquartile range, 28.0, 52.0), 58.4% experienced AKI. Mechanical ventilation (8.0% vs. 0.8%) and vasopressor support (21.7% vs. 4.1%) occurred at significantly higher rates in the AKI group compared to the non-AKI group, with significantly higher in-hospital mortality (5.5% vs. 1.3%) and 28-day mortality (12.8% vs. 5.4%). When ß2-MG was used as a continuous variable, multifactorial analysis showed that ß2-MG, transplantation, and vasopressor support were independently associated with risk for the development of AKI. CONCLUSIONS: The incidence of morbidity and mortality in patients with hemophagocytic lymphohistiocytosis complicated by AKI remains high. Monitoring levels of ß2-MG may provide clinicians with timely indicators of changes in renal function,  facilitating adjustments to treatment strategies.

Deterministic positioning and alignment of a single-molecule exciton in plasmonic nanodimer for strong coupling.

Experimental realization of strong coupling between a single exciton and plasmons remains challenging as it requires deterministic positioning of the single exciton and alignment of its dipole moment with the plasmonic fields. This study aims to combine the host-guest chemistry approach with the cucurbit[7]uril-mediated active self-assembly to precisely integrate a single methylene blue molecule in an Au nanodimer at the deterministic position (gap center of the nanodimer) with the maximum electric field (EFmax) and perfectly align its transition dipole moment with the EFmax, yielding a large spectral Rabi splitting of 116 meV for a single-molecule exciton-matching the analytical model and numerical simulations. Statistical analysis of vibrational spectroscopy and dark-field scattering spectra confirm the realization of the single exciton strong coupling at room temperature. Our work may suggest an approach for achieving the strong coupling between a deterministic single exciton and plasmons, contributing to the development of room-temperature single-qubit quantum devices.

TLR3 activation enhances abscopal effect of radiotherapy in HCC by promoting tumor ferroptosis.

Radiotherapy (RT) has been reported to induce abscopal effect in advanced hepatocellular carcinoma (HCC), but such phenomenon was only observed in sporadic cases. Here, we demonstrated that subcutaneous administration of Toll-like receptor 3 (TLR3) agonist poly(I:C) could strengthen the abscopal effect during RT through activating tumor cell ferroptosis signals in bilateral HCC subcutaneous tumor mouse models, which could be significantly abolished by TLR3 knock-out or ferroptosis inhibitor ferrostatin-1. Moreover, poly(I:C) could promote the presentation of tumor neoantigens by dendritic cells to enhance the recruitment of activated CD8+ T cells into distant tumor tissues for inducing tumor cell ferroptosis during RT treatment. Finally, the safety and feasibility of combining poly(I:C) with RT for treating advanced HCC patients were further verified in a prospective clinical trial. Thus, enhancing TLR3 signaling activation during RT could provide a novel strategy for strengthening abscopal effect to improve the clinical benefits of advanced HCC patients.

3D Printing of Anisotropic Piezoresistive Pressure Sensors for Directional Force Perception.

Anisotropic pressure sensors are gaining increasing attention for next-generation wearable electronics and intelligent infrastructure owing to their sensitivity in identifying different directional forces. 3D printing technologies have unparalleled advantages in the design of anisotropic pressure sensors with customized 3D structures for realizing tunable anisotropy. 3D printing has demonstrated few successes in utilizing piezoelectric nanocomposites for anisotropic recognition. However, 3D-printed anisotropic piezoresistive pressure sensors (PPSs) remain unexplored despite their convenience in saving the poling process. This study pioneers the development of an aqueous printable ink containing waterborne polyurethane elastomer. An anisotropic PPS featuring tailorable flexibility in macroscopic 3D structures and microscopic pore morphologies is created by adopting direct ink writing 3D printing technology. Consequently, the desired directional force perception is achieved by programming the printing schemes. Notably, the printed PPS demonstrated excellent deformability, with a relative sensitivity of 1.22 (kPa*wt. %)-1 over a substantial pressure range (2.8 to 8.1 kPa), approximately fivefold than that of a state-of-the-art carbon-based PPS. This study underscores the versatility of 3D printing in customizing highly sensitive anisotropic pressure sensors for advanced sensing applications that are difficult to achieve using conventional measures.

Human embryonic stem cell-derived mesenchymal stromal cells suppress inflammation in mouse models of rheumatoid arthritis and lung fibrosis by regulating T-cell function.

BACKGROUND AIMS: Rheumatoid arthritis (RA) is characterized by an overactive immune system, with limited treatment options beyond immunosuppressive drugs or biological response modifiers. Human embryonic stem cell-derived mesenchymal stromal cells (hESC-MSCs) represent a novel alternative, possessing diverse immunomodulatory effects. In this study, we aimed to elucidate the therapeutic effects and underlying mechanisms of hESC-MSCs in treating RA. METHODS: MSC-like cells were differentiated from hESC (hESC-MSCs) and cultured in vitro. Cell proliferation was assessed using Cell Counting Kit-8 assay and Ki-67 staining. Flow cytometry was used to analyze cell surface markers, T-cell proliferation and immune cell infiltration. The collagen-induced arthritis (CIA) mouse model and bleomycin-induced model of lung fibrosis (BLE) were established and treated with hESC-MSCs intravenously for in vivo assessment. Pathological analyses, reverse transcription-quantitative polymerase chain reaction and Western blotting were conducted to evaluate the efficacy of hESC-MSCs treatment. RESULTS: Intravenous transplantation of hESC-MSCs effectively reduced inflammation in CIA mice in this study. Furthermore, hESC-MSC administration enhanced regulatory T cell infiltration and activation. Additional findings suggest that hESC-MSCs may reduce lung fibrosis in BLE mouse models, indicating their potential to mitigate complications associated with RA progression. In vitro experiments revealed a significant inhibition of T-cell activation and proliferation during co-culture with hESC-MSCs. In addition, hESC-MSCs demonstrated enhanced proliferative capacity compared with traditional primary MSCs. CONCLUSIONS: Transplantation of hESC-MSCs represents a promising therapeutic strategy for RA, potentially regulating T-cell proliferation and differentiation.

Biomimetic Responsive Nanoconverters with Immune Checkpoint Blockade Plus Antiangiogenesis for Advanced Hepatocellular Carcinoma Treatment.

The first-line treatment for advanced hepatocellular carcinoma (HCC) combines immune checkpoint inhibitors and antiangiogenesis agents to prolong patient survival. Nonetheless, this approach has several limitations, including stringent inclusion criteria and suboptimal response rates that stem from the severe off-tumor side effects and the unfavorable pharmacodynamics and pharmacokinetics of different drugs delivered systemically. Herein, we propose a single-agent smart nanomedicine-based approach that mimics the therapeutic schedule in a targeted and biocompatible manner to elicit robust antitumor immunity in advanced HCC. Our strategy employed pH-responsive carriers, poly(ethylene glycol)-poly(ß-amino esters) amphiphilic block copolymer (PEG-PAEs), for delivering apatinib (an angiogenesis inhibitor), that were surface-coated with plasma membrane derived from engineered cells overexpressing PD-1 proteins (an immune checkpoint inhibitor to block PD-L1). In an advanced HCC mouse model with metastasis, these biomimetic responsive nanoconverters induced significant tumor regression (5/9), liver function recovery, and complete suppression of lung metastasis. Examination of the tumor microenvironment revealed an increased infiltration of immune effector cells (CD8+ and CD4+ T cells) and reduced immunosuppressive cells (myeloid-derived suppressor cells and T regulatory cells) in treated tumors. Importantly, our nanomedicine selectively accumulated in both small and large HCC occupying >50% of the liver volume to exert therapeutic effects with minimal systemic side effects. Overall, these findings highlight the potential of such multifunctional nanoconverters to effectively reshape the tumor microenvironment for advanced HCC treatment.

Serum IL-31 is related to the severity and 3-month prognosis of patients with Intracerebral hemorrhage.

Interleukin (IL)-31/IL-33 axis has been proved to play an important role in the regulation of inflammation, and serum IL-33 was found to be a novel serum prognostic marker of intracerebral hemorrhage (ICH), while the value of serum IL-31 levels on prognosis in patients with ICH remains unknown. The present study was designed to study the value of serum IL-31 levels on prognosis in ICH patients. A total of 200 ICH patients and 50 healthy people were included in this study. We collected clinical data such as demographic data, laboratory data, admission disease scores and medical histories of these participants. We measured serum IL-31 levels using enzyme-linked immunosorbent assay, and assessed the prognosis of ICH patients 3 months after onset by mRS scale, and mRS > 2 was defined as a 3-month poor outcome. The level of IL-31 in ICH patients were significantly higher than that in healthy control people (211.91 ± 61.61 vs 167.64 ± 27.45 pg/mL, P < .001), and levels of IL-31 in ICH patients with 3-month good outcome were significantly lower than that in ICH patients with 3-month poor outcome (196.09 ± 50.84 vs 248.05 ± 41.41 pg/mL, P < .001). Results of correlation analysis suggested that the level of serum IL-31 was positively related to admission NIHSS score (r = 0.627, P < .001), hematoma volume (r = 0.352, P < .001), mRS score (r = 0.515, P < .001), high-density lipoprotein-cholesterol (r = 0.177, P = .012), serum C-reactive protein levels (r = 0.483, P < .001), and serum tumor necrosis factor α levels (r = 0.389, P < .001) in ICH patients, while the level of serum IL-31 was negatively related to the admission GCS score (r = -0.518, P < .001) and triglycerides (r = -0.147, P = .038). Results of multivariate regression analysis shows that serum IL-31 levels are an independent risk factor affecting NIHSS scores (OR = 1.023, 95% CI = 1.010-2.036) and 3-month prognosis (OR = 1.023, 95% CI = 0.982-1.747) in ICH patients. The receiver operating characteristic curve analysis showed that the sensitivity and specificity of serum IL-31 level in evaluating the prognosis of ICH were 85.2% and 76.7%, respectively. A cutoff value of serum IL-31 level > 185.30 pg/mL may indicate a poor prognosis for ICH. Serum IL-31 levels on admission in ICH patients are associated with patient prognosis, and higher serum IL-31 levels are associated with a higher risk of poor prognosis in ICH patients.

Imaging Features and Misdiagnosis of Giant Cerebral Cavernous Malformations.

BACKGROUND: While cerebral cavernous malformations (CCMs) have been extensively described, few reports have described the imaging appearance of giant CCMs (GCCMs). OBJECTIVE: To describe the imaging characteristics of GCCMs and study the reasons for preoperative misdiagnosis. METHODS: We retrospectively analyzed the data of 12 patients (5 men, 7 women; mean age, 35.23 ± 12.64 years) with histopathologically confirmed GCCMs. Two radiologists analyzed the CT (n = 12) and MRI (n = 10) features: location, number, size, shape, boundary, signal intensity, and enhancement. RESULTS: The sellar region, cerebral hemisphere, skull bone, and ventricle were involved in 5, 4, 2, and 1 patients, respectively. Three tumors were irregularly shaped, while nine were oval. Eleven lesions showed slightly high- and/or high-density on CT; 1 lesion appeared as a low-density cyst. Calcifications were found in 11 lesions. Four tumors showed uniform hypointensity on T1-weighted imaging (T1WI) and hyperintense signals on T2-weighted imaging (T2WI). Six tumors showed mixed low-, equal-, and high-intensity signals on T1WI and T2WI. Noticeable contrast enhancement and gradual strengthening were noted on T1WI. Ten lesions showed hemorrhage and hemosiderin deposition. The GCCMs were wrongly diagnosed as cartilage-derived tumors/ meningioma (3 patients); tumor and hematoma (2 patients each); and pituitary tumor/ meningioma, chondroma, chordoma, ependymoma, and macroadenoma (1 patient each). CONCLUSIONS: GCCMs present as an oval mass with slightly high- and/or high-density calcifications on CT and show hemorrhage and hemosiderin accumulation on MRI. Therefore, slightly high- and/or high-density calcification and hemosiderin accumulation are critical clinical characteristics of GCCMs.

Topological Engineering Electrodes with Ultrafast Oxygen Transport for Super-Power Sodium-Oxygen Batteries.

Sodium-oxygen battery has attracted tremendous interest due to its extraordinary theoretical specific energy (1605 Wh kg-1 NaO2) and appealing element abundance. However, definite mechanistic factors governing efficient oxygen diffusion and consumption inside electrolyte-flooded air cathodes remain elusive thus precluding a true gas diffusion electrode capable of high discharge current (i.e., several mA cm-2) and superior output power. Herein, 3D-printing technology is adopted to create gas channels with tailored channel size and structure to demystify the diffusion-limited oxygen delivery process. It is revealed that as the clogging discharging products increase, large channel size, and interconnected channel structure are essential to guaranteeing fast O2 diffusion. Moreover, to further encourage O2 diffusion, a bio-inspired breathable cathode with progressively branching channels that balances between O2 passage and reaction is 3D printed. This elaborated 3D electrode allows a sodium-oxygen cell to deliver an impressive discharging current density of up to 4 mA cm-2 and an output power of 8.4 mW cm-2, giving rise to an outstanding capacity of 18.4 mAh cm-2. The unraveled mystery of oxygen delivery enabled by 3D printing points to a valuable roadmap for the rational design of metal-air batteries toward practical applications.

Impact of three-dimensional reconstruction visualization technology on short-term and long-term outcomes after hepatectomy in patients with hepatocellular carcinoma: a propensity-score-matched and inverse probability of treatment-weighted multicenter study.

BACKGROUND: Three-dimensional reconstruction visualization technology (3D-RVT) is an important tool in the preoperative assessment of patients undergoing liver resection. However, it is not clear whether this technique can improve short-term and long-term outcomes in patients with hepatocellular carcinoma (HCC) compared with two-dimensional (2D) imaging. METHOD: A total of 3402 patients from five centers were consecutively enrolled from January 2016 to December 2020, and grouped based on the use of 3D-RVT or 2D imaging for preoperative assessment. Baseline characteristics were balanced using propensity score matching (PSM, 1:1) and stabilized inverse probability of treatment-weighting (IPTW) to reduce potential selection bias. The perioperative outcomes, long-term overall survival (OS), and recurrence-free survival (RFS) were compared between the two groups. Cox-regression analysis was used to identify the risk factors associated with RFS. RESULTS: A total of 1681 patients underwent 3D-RVT assessment before hepatectomy (3D group), while 1721 patients used 2D assessment (2D group). The PSM cohort included 892 patient pairs. In the IPTW cohort, there were 1608.3 patients in the 3D group and 1777.9 patients in the 2D group. In both cohorts, the 3D group had shorter operation times, lower morbidity and liver failure rates, as well as shorter postoperative hospital stays. The 3D group had more margins ≥10 mm and better RFS than the 2D group. The presence of tumors with a diameter ≥5 cm, intraoperative blood transfusion and multiple tumors were identified as independent risk factors for RFS, while 3D assessment and anatomical resection were independent protective factors. CONCLUSION: In this multicenter study, perioperative outcomes and RFS of HCC patients following 3D-RVT assessment were significantly different from those following 2D imaging assessment. Thus, 3D-RVT may be a feasible alternative assessment method before hepatectomy for these patients.

Cell-free DNA testing for early hepatocellular carcinoma surveillance.

BACKGROUND: Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. METHODS: A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort. FINDINGS: PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%-62.84%] at 95.53% [95% CI: 94.62%-96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%-35.07%] at 99.37% [95% CI: 98.91%-99.64%] specificity for US) (P < 0.01, Fisher's exact test). PreCar Score plus US further achieved a higher sensitivity of 60.53% at 95.08% specificity for early/very early HCC screening. INTERPRETATION: Our study developed and validated a cfDNA-based screening tool (PreCar Score) for HCC in cohorts at high risk. The combination of PreCar Score and US can serve as a promising and practical strategy for routine HCC care. FUNDING: A full list of funding bodies that contributed to this study can be found in Acknowledgments section.

Proteomics-driven noninvasive screening of circulating serum protein panels for the early diagnosis of hepatocellular carcinoma.

Early diagnosis of hepatocellular carcinoma (HCC) lacks highly sensitive and specific protein biomarkers. Here, we describe a staged mass spectrometry (MS)-based discovery-verification-validation proteomics workflow to explore serum proteomic biomarkers for HCC early diagnosis in 1002 individuals. Machine learning model determined as P4 panel (HABP2, CD163, AFP and PIVKA-II) clearly distinguish HCC from liver cirrhosis (LC, AUC 0.979, sensitivity 0.925, specificity 0.915) and healthy individuals (HC, AUC 0.992, sensitivity 0.975, specificity 1.000) in an independent validation cohort, outperforming existing clinical prediction strategies. Furthermore, the P4 panel can accurately predict LC to HCC conversion (AUC 0.890, sensitivity 0.909, specificity 0.877) with predicting HCC at a median of 11.4 months prior to imaging in prospective external validation cohorts (No.: Keshen 2018_005_02 and NCT03588442). These results suggest that proteomics-driven serum biomarker discovery provides a valuable reference for the liquid biopsy, and has great potential to improve early diagnosis of HCC.

Risk factors for acute ischemic stroke in patients with type 2 diabetes mellitus.

To investigate the risk factors for acute ischemic stroke (AIS) in patients with type 2 diabetes mellitus (T2DM) patients. a total of 120 T2DM patients who met the inclusion and exclusion criteria, from between January 2021 to June 2022, were randomly selected and divided into T2DM and T2DM + AIS groups based on the presence or absence of a history of AIS. Blood samples were collected by fasting, 24 hours after admission, and levels of serum uric acid (UA), serum homocysteine (Hcy), serum creatinine (SCR), blood urea nitrogen (BUN), fasting blood glucose (FBG), glycated hemoglobin A1c (HbA1c), serum total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, high-sensitivity C-reactive protein (hs-CRP), and lipoprotein-associated phospholipase A2 (Lp-PLA2) were measured. Multivariate logistic regression analysis was performed for the significantly associated indicators to analyze the risk factors for AIS, and finally ROC curve analysis was carried out to explore the predictive value of the above risk factors for AIS in T2DM patients. the levels of FBG, Hcy, Hs-CRP and Lp-PLA2 were significantly higher in the T2DM + AIS group than those in T2DM group (P < .05). Multivariate logistic regression analysis revealed that hs-CRP and Lp-PLA2 were independent risk factors for the development of AIS in patients with T2DM with an OR of 2.85 (95% CI: 1.26-6.43, P = .012) and 3.64 (95% CI: 1.63-8.12, P = .002), respectively. ROC curve analysis showed that plasma hs-CRP and Lp-PLA2 showed good performance to predict AIS occurrence in T2DM patients (AUC = 0.749, 95% CI: 0.663, 0.835; and 0.791, 95% CI: 0.712, 0.870), with a sensitivity of 58.1% and 83.9%, and a specificity of 84.5% and 60.3%, respectively. The optimal concentration cutoff points of hs-CRP and Lp-PLA2 were 3.38 mg/L and 204.2 ng/mL. our findings suggested that plasma hs-CRP and Lp-PLA2 were independent risk factors for developing AIS in T2DM patients. Hs-CRP and Lp-PLA2 are potential biomarker for risk for AIS in patients with T2DM.

Customizing Three-Dimensional Elastic Barium Titanate Sponge for Intelligent Piezoelectric Sensing.

Piezoelectric energy harvesters (PEHs) with porous structures, such as piezoelectric elastic sponges, exhibit high force-to-electricity conversion efficiencies owing to their excellent compression recovery properties. However, conventional preparation methods are limited to producing bulk-form sponge-like PEHs and fail to create more elaborate three-dimensional (3D) structures that could enhance conversion efficiency. Herein, we invent a composite ink consisting of waterborne polyurethane (WPU), barium titanate (BTO), and cellulose nanofibers (CNFs) that is suitable for direct ink writing (DIW) 3D printing. This ink, when coupled with freeze-drying, allows the customization of piezoelectric sponges with functional 3D structures. The printed lattice sponge exhibits remarkable compression recovery of 70% and a notably high relative sensitivity of 9.83 mV/kPa*wt % (where *wt % denotes the BTO content) across a wide pressure range of 2.98-37 kPa, which is approximately three times broader than those of other composite piezoelectric pressure sensors based on BTO or piezoceramic (PZT) materials. Furthermore, a customized 3D piezoelectric sponge with a "boomerang" configuration is utilized as an anisotropic bending sensor on the wrist for intelligently monitoring the stroke posture and programming scientific training for table tennis players. This study highlights a versatile strategy for constructing elastic sponges with high piezoelectricity and designing 3D PEH functional structures that can be applied to flexible self-powered intelligent sensing systems.

Therapeutic Drug Monitoring-Guided Vancomycin Therapy of a Pediatric Patient after Liver Transplantation: a Case Report.

BACKGROUND: Vancomycin administration is challenging in critically ill patients because of pharmacokinetic changes and requires careful therapeutic drug monitoring (TDM) to guide the appropriate dosing for an effective serum concentration and to avoid toxicity. METHODS: We reported a one-year-old female pediatric patient with a body mass index of 15.4 had successful TDM-guided vancomycin therapy after a living donor liver transplantation for biliary atresia. RESULTS: The patient was admitted to the Intensive Care Unit for sepsis after her second liver transplantation. Even with the administration of the maximum approved vancomycin dosage (40 mg/kg/day), the serum trough levels were less than the recommended therapeutic level. After several adjustments based on TDM, a continuous pump infusion of up to 800 mg/day was needed to reach the desired serum trough concentration of > 10 µg/mL. Sepsis was controlled, and the patient was transferred from the Intensive Care Unit to the general ward and finally discharged home on a regular follow-up plan. CONCLUSIONS: TDM-guided vancomycin continuous infusion may be an effective therapeutic option for pediatric patients after liver transplantation.

Development and validation a radiomics nomogram for predicting thymidylate synthase status in hepatocellular carcinoma based on Gd-DTPA contrast enhanced MRI.

OBJECTIVES: The purpose of this study was to develop and validate a radiomics nomogram for predicting thymidylate synthase (TYMS) status in hepatocellular carcinoma (HCC) by using Gd-DTPA contrast enhanced MRI. METHODS: We retrospectively enrolled 147 consecutive patients with surgically confirmed HCC and randomly allocated to training and validation set (7:3). The TYMS status was immunohistochemical determined and classified into low TYMS (positive cells ≤ 25%) and high TYMS (positive cells > 25%) groups. Radiomics features were extracted from the arterial phases and portal venous phase of Gd-DTPA contrast enhanced MRI. Least absolute shrinkage and selection operator (LASSO) were applied for generating the Rad score. Clinical data and MRI findings were assessed to build a clinical model. Rad score combined with clinical features was used to construct radiomics nomogram. RESULTS: A total of 2260 features were extracted and reduced to 7 features as the most important discriminators to build the Rad score. InAFP was identified as the only independent clinical factors for TYMS status. The radiomics nomogram showed good discrimination in training (AUC, 0.759; 95% CI 0.665-0.838) and validation set (AUC, 0.739; 95% CI 0.585-0.860), and showed better discrimination capability (P < 0.05) compared with clinical model in training (AUC, 0.656; 95% CI 0.555-0.746) and validation set (AUC, 0.622; 95% CI 0.463-0.764). CONCLUSIONS: The radiomics nomogram shows favorable predictive efficacy for TYMS status in HCC, which might be helpful for the personalized treatment of HCC.