2D copper-iron bimetallic metal-organic frameworks for reduction of nitrate with boosted efficiency and ammonia selectivity.

Electrocatalytic reduction of nitrate to ammonia has been considered a promising and sustainable pathway for pollutant treatment and ammonia has significant potential as a clean energy. Therefore, the method has received much attention. In this work, Cu/Fe 2D bimetallic metal-organic frameworks were synthesized by a facile method applied as cathode materials without high-temperature carbonization. Bimetallic centers (Cu, Fe) with enhanced intrinsic activity demonstrated higher removal efficiency. Meanwhile, the 2D nanosheet reduced the mass transfer barrier between the catalyst and nitrate and increased the reaction kinetics. Therefore, the catalysts with a 2D structure showed much better removal efficiency than other structures (3D MOFs and Bulk MOFs). Under optimal conditions, Cu/Fe-2D MOF exhibited high nitrate removal efficiency (87.8%) and ammonium selectivity (89.3%) simultaneously. The ammonium yielded up to significantly 907.2 µg/(hr·mgcat) (7793.8 µg/(hr·mgmetal)) with Faradaic efficiency of 62.8% at an initial 100 mg N/L. The catalyst was proved to have good stability and was recycled 15 times with excellent effect. DFT simulations confirm the reduced Gibbs free energy of Cu/Fe-2D MOF. This study demonstrates the promising application of Cu/Fe-2D MOF in nitrate reduction to ammonia and provides new insights for the design of efficient electrode materials.

[Emission Characteristics and Environmental Impact of VOCs from Wooden Furniture-manufacturing Industry in China].

Volatile organic compounds （VOCs） from the wooden furniture-manufacturing industry are an important emission source. To study the emission characteristics of VOCs from the wooden furniture-manufacturing industry and associated environmental impacts, nine typical wooden furniture manufacturers in China were selected to carry out sample collection and VOCs detection. The maximum incremental reactivity （MIR） method and secondary organic aerosol （SOA） formation potential method were used to quantify the corresponding contributions to the generation of O3 and SOA. The results showed that： ① The concentrations of VOCs emitted from different types of coating exhaust gas were different. The emission concentration of VOCs in solvent-based coating exhaust gas was significantly higher than that in water-based coating exhaust gas and ultra-violet （UV） coating exhaust gas, and the VOCs emission concentrations ranged between 2.82 - 155.37, 1.13 - 104.45, and 0.57 - 1.15 mg·m-3, respectively. ② The main organic group in solvent-based coating exhaust gas was esters, accounting for 45.88%, and butyl acetate （31.07%） was the main VOCs species. The main organic group in water-based coating exhaust gas and UV coating exhaust gas was alcohols, and the main VOCs species in water-based coating exhaust gas and UV coating exhaust gas were both ethanol, accounting for 46.63% and 34.32%, respectively. ③ The OFP of VOCs emitted by solvent-based coating, water-based coating, and UV coating were 149.23, 50.90, and 1.87 mg·m-3, respectively, and the primary contributing components of OFP of different types of coating were m/p-xylene （26.61%）, ethanol （36.35%）, and ethanol （23.98%）, respectively. ④ The SOA of VOCs emitted by solvent-based coating, water-based coating, and UV coating were 0.76, 0.25, and 0.01 mg·m-3, respectively. The SOA generation of various types of coating was dominated by aromatics（96.35%-98.96%）, and the main active compounds were toluene, ethylbenzene, and xylene. ⑤ Comparing the environmental impact of exhaust gas from solvent-based coating, water-based coating, and UV coating, it was found that the OFP and SOA generated by the VOCs emitted from solvent-based coating were much higher than those for water-based coating and UV coating. Therefore, the implementation of water-based coating and UV coating substitution strategy from the source could effectively reduce VOCs emissions and abate OFP and SOA productions.

The beginning of iron corrosion - high-resolution visualization with 3D electron tomography.

Understanding the genesis and early-phase reactions of iron corrosion is essential for the early detection, mitigation and prevention of metal degradation. In this work, high-resolution 3D tomography of metallic iron oxidation was acquired using high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM). In particular, dendritic capillaries (<0.5 nm) were observed during the initial oxidation of fresh nanoscale zero-valent iron due to the differential oxygen diffusion and iron atoms migration. This observation led to the proposal of a nanoscale "pothole" model for early-phase corrosion, wherein hollowing out of the metal nanoparticle and formation of nanovoids beneath the iron/oxide interface through Kirkendall effect. Coalescence of the nanocapillaries results in the ultimate collapse of metal structure and/or functional failure. Using nanoscale zero-valent iron as a research model, this work provides unprecedented insights into the nano- and atomic-scale mechanisms of iron oxidation, paving the way for advanced detection and prevention strategies for iron corrosion.

Determining the optimum high-flow nasal cannula flow rate to achieve the desired fraction of inspired oxygen: A bench study.

BACKGROUND: Purpose: High-flow nasal cannula (HFNC) has many benefits in various clinical conditions. The original hypothesis suggests that the high and constant fraction of inspired oxygen (FiO2) is one of the main physiological effects. However, increasing evidence shows that there is a gap between the actual FiO2 and administered FiO2. We aimed to determine the actual FiO2 under different respiratory conditions and develop a regression model using a spontaneous breathing lung model. METHODS: A spontaneous breathing simulation model was built using an airway manikin and a model lung. The FiO2 was measured under different respiratory conditions with varying tidal volumes and respiratory and HFNC flow rates. The relationships between the respiratory parameters and actual FiO2 were determined and used to build the predictive model. RESULTS: The actual FiO2 was negatively correlated with respiratory rate and tidal volume and positively correlated with HFNC flow. The regression model could not be developed using simple respiratory parameters. Therefore, we introduced a new variable, defined as flow ratio, which equaled the HFNC flow divided by inspiratory flow. Our equation demonstrated that the actual FiO2 was mainly determined by the flow ratio in a non-linear relationship. Accordingly, a flow ratio greater than 1 did not ensure a constant high FiO2, whereas a flow ratio >1.435 could produce FiO2 >0.9. CONCLUSION: The FiO2 during HFNC was not constant even at sufficiently high oxygen flow compared with inspiratory flow. The predictive model showed that the actual FiO2 was mainly determined by the flow ratio.

Enzymatic acylation of cyanidin-3-O-glucoside with aromatic and aliphatic acid methyl ester: Structure-stability relationships of acylated derivatives.

Anthocyanins are water-soluble pigments, but they tend to be unstable in aqueous solutions. Modification of their molecular structure offers a viable approach to alter their intrinsic properties and enhance stability. Aromatic and aliphatic acid methyl esters were used as acyl donors in the enzymatic acylation of cyanidin-3-O-glucoside (C3G), and their analysis was conducted using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). The highest conversion rate achieved was 96.41 % for cyanidin-3-O-(6″-feruloyl) glucoside. Comparative evaluations of stability revealed that aromatic acyl group-conjugated C3G exhibited superior stability enhancement compared with aliphatic acyl group derivatives. The stability of aliphatic C3G decreased with increasing carbon chain length. The molecular geometries of different anthocyanins were optimized, and energy level calculations using density functional theory (DFT) identified their sites with antioxidant activities. Computational calculations aligned with the in vitro antioxidant assay results. This study provided theoretical support for stabilizing anthocyanins and broadened the application of acylated anthocyanins as food colorants and nutrient supplements.

Chinese Rural Kindergarten Teachers' Work-Family Conflict and Their Turnover Intention: The Role of Emotional Exhaustion and Professional Identity.

The loss of rural kindergarten teachers has become a common social concern in China, which is of great importance to the development of preschool education. This study conducted a survey of 2944 kindergarten teachers in mainland China, to explore the relationship between work-family conflict and turnover intention, the mediating effect of emotional exhaustion, and the moderating effect of professional identity. The study used the work-family conflict questionnaire, the emotional exhaustion scale, the turnover intention questionnaire, and the professional identity questionnaire. The results showed that (1) work-family conflict significantly predicted turnover intention; (2) emotional exhaustion played a mediating role between work-family conflict and turnover intention; and (3) professional identity moderated the latter half path of the mediation model, that is, strong professional identity alleviated the indirect predicting effect of work-family conflict on turnover intention through emotional exhaustion. The results clarified the influencing mechanism of work-family conflict on turnover intention, which could help improve rural preschool teachers' positive emotions and reducing turnover.

Helicobacter pylori infection alters gastric microbiota structure and biological functions in patients with gastric ulcer or duodenal ulcer.

BACKGROUND: Helicobacter pylori (H. pylori) infection is closely associated with gastrointestinal diseases. Our preliminary studies have indicated that H. pylori infection had a significant impact on the mucosal microbiome structure in patients with gastric ulcer (GU) or duodenal ulcer (DU). AIM: To investigate the contributions of H. pylori infection and the mucosal microbiome to the pathogenesis and progression of ulcerative diseases. METHODS: Patients with H. pylori infection and either GU or DU, and healthy individuals without H. pylori infection were included. Gastric or duodenal mucosal samples was obtained and subjected to metagenomic sequencing. The compositions of the microbial communities and their metabolic functions in the mucosal tissues were analyzed. RESULTS: Compared with that in the healthy individuals, the gastric mucosal microbiota in the H. pylori-positive patients with GU was dominated by H. pylori, with significantly reduced biodiversity. The intergroup differential functions, which were enriched in the H. pylori-positive GU patients, were all derived from H. pylori, particularly those concerning transfer RNA queuosine-modification and the synthesis of demethylmenaquinones or menaquinones. A significant enrichment of the uibE gene was detected in the synthesis pathway. There was no significant difference in microbial diversity between the H. pylori-positive DU patients and healthy controls. CONCLUSION: H. pylori infection significantly alters the gastric microbiota structure, diversity, and biological functions, which may be important contributing factors for GU.

Heterogenous liver parenchymal enhancement in CT is a favorable prognosis of HCC after hepatic resection.

This study aimed to define the role of heterogeneity of liver parenchymal enhancement on computed tomography (CT) in the survival of patients with hepatocellular carcinoma (HCC) after hepatic resection. The medical records of patients with HCCs and who had undergone hepatic resection were retrospectively reviewed. The standard deviation (SD) of three different enhanced CT scan images was used to estimate the heterogeneity of liver parenchymal enhancement: SD of > 5.6, heterogenous enhancement, and SD of ≤ 5.6, homogeneous enhancement. A total of 57 patients had heterogenous enhancement, and 143 patients had homogeneous enhancement. The patients with heterogenous enhancement had longer disease-free and overall survivals than those with other enhancements (log-rank test, P < 0.001 and P = 0.036). The pathologic exam showed that heterogenous enhancement tended to develop septa in the peritumoral liver tissues. The prevalence of CD8+ cells was significantly higher in the peritumor liver tissues with septa than in those without (0.83% vs. 0.26%, P < 0.001). The peritumoral CD8/Foxp3 ratio was higher in the liver tissues with septa than in those without (1.22 vs. 0.47, P = 0.001), and patients with CD8/Foxp3 of > 0.8 had better overall survival than those with CD8/Foxp3 of ≤ 0.8 (log-rank test, P = 0.028). In conclusion, patients who had undergone hepatic resection with a heterogenous liver parenchymal enhancement tended to develop hepatic septa, which was associated with a higher CD8/Foxp3 ratio and longer survival. Therefore, contrast-enhanced CT scans might be a useful tool to predict the outcome of HCC.

Intervention with fructooligosaccharides, Saccharomyces boulardii, and their combination in a colitis mouse model.

Objective: To examine the effects of an intervention with fructooligosaccharides (FOS), Saccharomyces boulardii, and their combination in a mouse model of colitis and to explore the mechanisms underlying these effects. Methods: The effects of FOS, S. boulardii, and their combination were evaluated in a DSS-induced mouse model of colitis. To this end, parameters such as body weight, the disease activity index (DAI), and colon length were examined in model mice. Subsequently, ELISA was employed to detect the serum levels of proinflammatory cytokines. Histopathological analysis was performed to estimate the progression of inflammation in the colon. Gas chromatography was used to determine the content of short-chain fatty acids (SCFAs) in the feces of model mice. Finally, 16S rRNA sequencing technology was used to analyze the gut microbiota composition. Results: FOS was slight effective in treating colitis and colitis-induced intestinal dysbiosis in mice. Meanwhile, S. boulardii could significantly reduced the DAI, inhibited the production of IL-1ß, and prevented colon shortening. Nevertheless, S. boulardii treatment alone failed to effectively regulate the gut microbiota. In contrast, the combined administration of FOS/S. boulardii resulted in better anti-inflammatory effects and enabled microbiota regulation. The FOS/S. boulardii combination (109 CFU/ml and 107 CFU/ml) significantly reduced the DAI, inhibited colitis, lowered IL-1ß and TNF-α production, and significantly improved the levels of butyric acid and isobutyric acid. However, FOS/S. boulardii 109 CFU/ml exerted stronger anti-inflammatory effects, inhibited IL-6 production and attenuated colon shortening. Meanwhile, FOS/S. boulardii 107 CFU/ml improved microbial regulation and alleviated the colitis-induced decrease in microbial diversity. The combination of FOS and S. boulardii significantly increased the abundance of Parabacteroides and decreased the abundance of Escherichia-Shigella. Additionally, it promoted the production of acetic acid and propionic acid. Conclusion: Compared with single administration, the combination can significantly increase the abundance of beneficial bacteria such as lactobacilli and Bifidobacteria and effectively regulate the gut microbiota composition. These results provide a scientific rationale for the prevention and treatment of colitis using a FOS/S. boulardii combination. They also offer a theoretical basis for the development of nutraceutical preparations containing FOS and S. boulardii.

Intrathecal Fumagillin Alleviates Chronic Neuropathy-Induced Nociceptive Sensitization and Modulates Spinal Astrocyte-Neuronal Glycolytic and Angiogenic Proteins.

Nociceptive sensitization is accompanied by the upregulation of glycolysis in the central nervous system in neuropathic pain. Growing evidence has demonstrated glycolysis and angiogenesis to be related to the inflammatory processes. This study investigated whether fumagillin inhibits neuropathic pain by regulating glycolysis and angiogenesis. Fumagillin was administered through an intrathecal catheter implanted in rats with chronic constriction injury (CCI) of the sciatic nerve. Nociceptive, behavioral, and immunohistochemical analyses were performed to evaluate the effects of the inhibition of spinal glycolysis-related enzymes and angiogenic factors on CCI-induced neuropathic pain. Fumagillin reduced CCI-induced thermal hyperalgesia and mechanical allodynia from postoperative days (POD) 7 to 14. The expression of angiogenic factors, vascular endothelial growth factor (VEGF) and angiopoietin 2 (ANG2), increased in the ipsilateral lumbar spinal cord dorsal horn (SCDH) following CCI. The glycolysis-related enzymes, pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA) significantly increased in the ipsilateral lumbar SCDH following CCI on POD 7 and 14 compared to those in the control rats. Double immunofluorescence staining indicated that VEGF and PKM2 were predominantly expressed in the astrocytes, whereas ANG2 and LDHA were predominantly expressed in the neurons. Intrathecal infusion of fumagillin significantly reduced the expression of angiogenic factors and glycolytic enzymes upregulated by CCI. The expression of hypoxia-inducible factor-1α (HIF-1α), a crucial transcription factor that regulates angiogenesis and glycolysis, was also upregulated after CCI and inhibited by fumagillin. We concluded that intrathecal fumagillin may reduce the expression of ANG2 and LDHA in neurons and VEGF and PKM2 in the astrocytes of the SCDH, further attenuating spinal angiogenesis in neuropathy-induced nociceptive sensitization. Hence, fumagillin may play a role in the inhibition of peripheral neuropathy-induced neuropathic pain by modulating glycolysis and angiogenesis.

Mitochondrial RNA modification-based signature to predict prognosis of lower grade glioma: a multi-omics exploration and verification study.

Mitochondrial RNA modification (MRM) plays a crucial role in regulating the expression of key mitochondrial genes and promoting tumor metastasis. Despite its significance, comprehensive studies on MRM in lower grade gliomas (LGGs) remain unknown. Single-cell RNA-seq data (GSE89567) was used to evaluate the distribution functional status, and correlation of MRM-related genes in different cell types of LGG microenvironment. We developed an MRM scoring system by selecting potential MRM-related genes using LASSO regression analysis and the Random Survival Forest algorithm, based on multiple bulk RNA-seq datasets from TCGA, CGGA, GSE16011, and E-MTAB-3892. Analysis was performed on prognostic and immunological features, signaling pathways, metabolism, somatic mutations and copy number variations (CNVs), treatment responses, and forecasting of potential small-molecule agents. A total of 35 MRM-related genes were selected from the literature. Differential expression analysis of 1120 normal brain tissues and 529 LGGs revealed that 22 and 10 genes were upregulated and downregulated, respectively. Most genes were associated with prognosis of LGG. METLL8, METLL2A, TRMT112, and METTL2B were extensively expressed in all cell types and different cell cycle of each cell type. Almost all cell types had clusters related to mitochondrial RNA processing, ribosome biogenesis, or oxidative phosphorylation. Cell-cell communication and Pearson correlation analyses indicated that MRM may promoting the development of microenvironment beneficial to malignant progression via modulating NCMA signaling pathway and ICP expression. A total of 11 and 9 MRM-related genes were observed by LASSO and the RSF algorithm, respectively, and finally 6 MRM-related genes were used to establish MRM scoring system (TRMT2B, TRMT11, METTL6, METTL8, TRMT6, and TRUB2). The six MRM-related genes were then validated by qPCR in glioma and normal tissues. MRM score can predict the malignant clinical characteristics, abundance of immune infiltration, gene variation, clinical outcome, the enrichment of signaling pathways and metabolism. In vitro experiments demonstrated that silencing METTL8 significantly curbs glioma cell proliferation and enhances apoptosis. Patients with a high MRM score showed a better response to immunotherapies and small-molecule agents such as arachidonyl trifluoromethyl ketone, MS.275, AH.6809, tacrolimus, and TTNPB. These novel insights into the biological impacts of MRM within the glioma microenvironment underscore its potential as a target for developing precise therapies, including immunotherapeutic approaches.

Ectopic MYBL2-Mediated Regulation of Androglobin Gene Expression.

Androglobin (ADGB) is a highly conserved and recently identified member of the globin superfamily. Although previous studies revealed a link to ciliogenesis and an involvement in murine spermatogenesis, its physiological function remains mostly unknown. Apart from FOXJ1-dependent regulation, the transcriptional landscape of the ADGB gene remains unexplored. We, therefore, aimed to obtain further insights into regulatory mechanisms governing ADGB expression. To this end, changes in ADGB promoter activity were examined using luciferase reporter gene assays in the presence of a set of more than 475 different exogenous transcription factors. MYBL2 and PITX2 resulted in the most pronounced increase in ADGB promoter-dependent luciferase activity. Subsequent truncation strategies of the ADGB promoter fragment narrowed down the potential MYBL2 and PITX2 binding sites within the proximal ADGB promoter. Furthermore, MYBL2 binding sites on the ADGB promoter were further validated via a guide RNA-mediated interference strategy using reporter assays. Chromatin immunoprecipitation (ChIP)-qPCR experiments illustrated enrichment of the endogenous ADGB promoter region upon MYBL2 and PITX2 overexpression. Consistently, ectopic MYBL2 expression induced endogenous ADGB mRNA levels. Collectively, our data indicate that ADGB is strongly regulated at the transcriptional level and might have functions beyond ciliogenesis.

Prevention and management of cytomegalovirus infection and disease in kidney transplant: A consensus statement of the Transplantation Society of Taiwan.

Kidney transplant recipients have an increased risk of cytomegalovirus (CMV) infection and disease. A strategy for mitigating the risk of CMV infection in kidney transplant recipients has not yet been established in Taiwan. The Transplantation Society of Taiwan aimed to develop a consensus by expert opinion on the prevention and management of CMV infection. Based on the results of Consensus Conference, we suggested low-dose valganciclovir prophylaxis (450 mg once daily) for kidney transplant recipients. The prophylaxis duration was ≥6 months for high-risk (D+/R-) patients and 3 months for moderate-risk (R+) patients. Even for low-risk (D-/R-) patients, prophylaxis for at least 3 months is recommended because of the high seroprevalence of CMV in Taiwan. CMV prophylaxis was suggested after anti-thymocyte globulin treatment but not after methylprednisolone pulse therapy. Routine surveillance after prophylaxis, secondary prophylaxis after CMV disease treatment, and mTOR inhibitors for primary CMV prophylaxis were not recommended. Letermovir and marabavir are emerging CMV agents used for prophylaxis and refractory CMV disease. CMV immunoglobulins have been used to treat refractory CMV disease in Taiwan. We hope this consensus will help professionals manage patients with CMV in Taiwan to improve the quality of care.

Effect of "Tiaoshen" acupuncture technique on mild depression and its underlying mechanism: A randomized controlled trial study protocol.

Background: Mild depression is not just a mental disease, but also a serious and long-term public health issue. It affects the quality of life of patients and can quickly develop into major depression. There are currently no effective drug treatments with high efficacy and few adverse reactions. Acupuncture may be an alternative treatment option. Preliminary experiments and practices have demonstrated that "Tiaoshen" acupuncture improves symptoms in patients who have depression, however the underlying data and method remain unclear at present. Methods: This is a prospective, single-center, single-blind, randomized controlled trial. We plan to recruit 70 participants and randomly assign them to receive "Tiaoshen" acupuncture or traditional acupuncture at a ratio of 1:1. Then, all the participants will receive the appropriate acupuncture treatment for four weeks. The results of the Hamilton Depression Rating Scale (HDSR-24) will serve as the primary outcome, while the results of the Patient Health Questionnaire-9 (PHQ-9) and the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) will serve as secondary outcomes. Evaluations will be conducted at baseline, 1, 2, and 4 weeks after treatment initiation, and 1 and 3 months after treatment completion. The safety of the intervention will be evaluated every week using the Columbia-Suicide Severity Rating Scale (C-SSRS) and the Treatment Emergent Symptoms Scale (TESS). Serum levels of oxidative stress markers 8-iso-prostaglandin F2α (8-iso-PGF2α), superoxide dismutase (SOD), uric acid (UA), and total bilirubin (TBIL) will be measured at baseline and the end of the treatment. We will conduct a statistical analysis of intention to treat (ITT) and conformance to protocol set (PPS) data. Discussion: This research aims to provide high-quality evidence for the efficacy and safety of "Tiaoshen" acupuncture as a treatment for mild depression. In addition, the mechanism through which acupuncture heals mild depression will be investigated.

Erector spinae plane block level does not impact analgesic efficacy in enhanced recovery for lumbar spine surgery.

BACKGROUND CONTEXT: Postoperative pain control following spine surgery can be difficult. The Enhanced Recovery After Surgery (ERAS) programs use multimodal approaches to manage postoperative pain. While an erector spinae plane block (ESPB) is commonly utilized, the ideal distance for injection from the incision, referred to as the ES (ESPB to mid-surgical level) distance, remains undetermined. PURPOSE: We evaluated the impact of varying ES distances for ESPB on Numerical Rating Scale (NRS) measures of postoperative pain within the ERAS protocol. STUDY DESIGN/SETTING: Retrospective observational study. PATIENT SAMPLE: Adult patients who underwent elective lumbar spine fusion surgery. OUTCOME MEASURES: Primary outcome measures include the comparative postoperative NRS scores across groups at immediate (T1), 24 (T2), 48 (T3), and 72 (T4) hours postsurgery. For secondary outcomes, a propensity matching analysis compared these outcomes between the ERAS and non-ERAS groups, with opioid-related recovery metrics also assessed. METHODS: All included patients were assigned to one of three ERAS groups according to the ES distance: Group 1 (G1, ES > 3 segments), Group 2 (G2, ES = 2-3 segments), and Group 3 (G3, ES<2 segments). Each patient underwent a bilateral ultrasound-guided ESPB with 60 mL of diluted ropivacaine or bupivacaine. RESULTS: Patients within the ERAS cohort reported mild pain (NRS < 3), with no significant NRS variation across G1 to G3 at any time. Sixty-five patients were matched across ERAS and non-ERAS groups. The ERAS group exhibited significantly lower NRS scores from T1 to T3 than the non-ERAS group. Total morphine consumption during hospitalization was 26.7 mg for ERAS and 41.5 mg for non-ERAS patients. The ERAS group resumed water and food intake sooner and had less postoperative nausea and vomiting. CONCLUSIONS: ESPBs can be effectively administered at or near the mid-surgical level to the low thoracic region for lumbar spine surgeries. Given challenges with sonovisualization, a lumbar ESPB may be preferred to minimize the risk of inadvertent pleural injury.

Locoregional treatment improves overall survival for liver cancer during second-line regorafenib or immune checkpoint inhibitor.

For advanced hepatocellular carcinoma (HCC), the best second-line treatment after first-line treatment with sorafenib is unclear. This study aimed to compared the efficacy of second-line regorafenib (a tyrosine kinase inhibitor) and immune checkpoint inhibitors (ICIs) in patients with advanced HCC after sorafenib therapy. This retrospective study included 89 patients with HCC treated with sorafenib, and then regorafenib (n = 58) or an ICI (n = 31). Treatment response, overall survival (OS) and progression-free survival (PFS) of the 2 groups were compared, and factors associated with post-treatment mortality or disease progression were evaluated. During follow-up period, compared to regorafenib, treatment with an ICI results in a slight increase in a 20% decrease of AFP (35.7% vs. 31.8%), complete response rate (6.5% vs. 0%), objective response rate (16.1% vs. 6.9%), median overall survival (13.3 vs. 5 months), and median PFS (3.0 vs. 2.6 months). Combined locoregional treatment (LRT) (hazard ratio [HR] = 0.40, 95% confidence interval [CI]: 0.15-0.99) during second-line treatment was associated with a decreased risk of post-treatment mortality. After propensity scoring matching, combined LRT during second-line treatment had longer post-treatment OS than patients without combined LRT. A 20% decrease of AFP (HR = 0.54, 95% CI: 0.31-0.94) was associated with a decreased risk of post-treatment disease progression. In conclusions, second-line treatment with regorafenib or ICI prolongs OS in patients with advanced HCC treated with sorafenib. Combined LRT during second-line treatment is associated with decreased post-treatment mortality. A 20% decrease of AFP level may be predictive of a lower rate of disease progression.

Analgesia-nociception index accurately predicts inadequate pectoralis muscle fascia block (PECS) in patients undergoing breast surgery: A prospective observational study.

BACKGROUND: Postoperative opioid administration has been largely replaced by regional anesthesia techniques. We aimed to determine whether intraoperative Analgesia-Nociception Index (ANI) can aid in early evaluation of the effectiveness of regional blocks such as the pectoralis muscle fascia block (PECS, pectoserratus and interpectoral plane blocks) and predicting the need for analgesics postoperatively. METHODS: This prospective observational study enrolled 30 women (age: 20-80 years) undergoing unilateral, non-intubated, breast tumor excision alone or in conjunction with sentinel lymph node biopsy. PECS block was performed following sedation. ANI readings were obtained at 1-min intervals, and polar coordinates were assigned to the distance from the nipple (0.5-cm intervals) and o'clock position (15-min intervals) for each reading. Pain scores were assessed using a numeric rating scale from 0 to 10, and analgesics were administered depending on pain score post-operatively. RESULTS: 8 (27%), 19 (63%), and 3 (10%) patients received morphine, tramadol, and no analgesics, respectively. In total, 954 ANI measurements were obtained. At the proposed cut-off of 50, the sensitivity and specificity of the ANI nadir for need of post-operative opioids were 0.875 and 0.932, respectively. Block effectiveness was most satisfactory in the upper lateral quadrant of the breast with nipple-areolar complex (NAC) sparing effect. Most average ANI measurements for the NAC were <50. No patient experienced postoperative nausea/vomiting, although one reported dizziness. CONCLUSIONS: The intraoperative ANI nadir <50 was strongly correlated with need for postoperative opioids. The ANI may aid in objectively evaluating the effectiveness of pectoralis muscle fascial blocks and predicting postoperative need for analgesics.

Concurrent Atezolizumab Plus Bevacizumab and High-Dose External Beam Radiotherapy for Highly Advanced Hepatocellular Carcinoma.

BACKGROUND: Atezolizumab plus bevacizumab (atezo-bev) has been recommended for advanced hepatocellular carcinoma (HCC). High-dose external beam radiotherapy (RT) is recognized for its excellent local tumor control. The efficacy and safety of concurrent atezo-bev with RT for highly advanced HCC has been minimally explored. METHODS: In this preliminary retrospective study, we assessed patients with highly advanced HCC, characterized by Vp4 portal vein thrombosis or tumors exceeding 50% of liver volume, who received concurrent atezo-bev and RT (group A). Group A included 13 patients who received proton radiation at a dose of 72.6 GyE in 22 fractions, and one patient who received photon radiation at a dose of 54 Gy in 18 fractions. This group was compared with 34 similar patients treated atezo-bev alone as a control (group B). The primary objectives were to evaluate the objective response rate (ORR), overall survival (OS), and safety. RESULTS: Baseline characteristics were similar between groups, except for a higher incidence of Vp4 portal vein thrombosis in group A (78.6% vs. 21.4%, P = .05). Group A achieved a higher ORR (50.0% vs. 11.8%, P < .01) and a longer OS (not reached vs. 5.5 months, P = .01) after a median follow-up of 5.2 months. Multivariate analysis indicated that concurrent RT independently favored longer OS (hazard ratio: 0.18; 95% CI, 0.05-0.63, P < .01). Group A did not increase any grade adverse events (78.6% vs. 58.8%, P = .19) or severe adverse events of grade ≥ 3 (14.3% vs. 14.7%, P = .97) compared to group B. CONCLUSIONS: The concurrent high-dose external beam radiotherapy appears to safely enhance the effectiveness of atezolizumab plus bevacizumab for highly advanced patients with HCC. Further studies are warranted to confirm these findings.

Clinical implications of hepatitis B virus core antigen-mediated immunopathologic T cell responses in chronic hepatitis B.

Hepatitis B virus (HBV) infection significantly impacts Asian populations. The influences of continuous HBV antigen and inflammatory stimulation to T cells in chronic hepatitis B (CHB) remain unclear. In this study, we first conducted bioinformatics analysis to assess T-cell signaling pathways in CHB patients. In a Taiwanese cohort, we examined the phenotypic features of HBVcore -specific T cells and their correlation with clinical parameters. We used core protein overlapping peptides from the Taiwan prevalent genotype B HBV to investigate the antiviral response and the functional implication of HBV-specific T cells. In line with Taiwanese dominant HLA-alleles, we also evaluated ex vivo HBVcore -specific T cells by pMHC-tetramers targeting epitopes within HBV core protein. Compared to healthy subjects, we disclosed CD8 T cells from CHB patients had higher activation marker CD38 levels but showed an upregulation in the inhibitory receptor PD-1. Our parallel study showed HBV-specific CD8 T cells were more activated with greater PD-1 expression than CMV-specific subset and bulk CD8 T cells. Moreover, our longitudinal study demonstrated a correlation between the PD-1 fluctuation pattern of HBVcore -specific CD8 T cells and liver inflammation in CHB patients. Our research reveals the HBV core antigen-mediated immunopathologic profile of CD8 T cells in chronic HBV infection. Our findings suggest the PD-1 levels of HBVcore -specific CD8 T cells can be used as a valuable indicator of personal immune response for clinical application in hepatitis management.