Drug-associated porphyria: a pharmacovigilance study.

BACKGROUND: The potentially fatal attacks experienced by porphyria carriers are triggered by various porphyrinogenic drugs. However, determining the safety of particular drugs is challenging. METHODS: We retrospectively used the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) to identify drugs associated with porphyria as an adverse event (AE) extracted from data from January 2004 to March 2022. The associated search terms included "Porphyria," "Porphyria screen," "Porphyria non-acute," "Porphyria acute," "Acquired porphyria," and "Pseudoporphyria." Signal mining analysis was performed to identify the association between drugs and AEs by four algorithms, namely the reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker. RESULTS: FAERS reported 1470 cases of porphyria-related AEs, and 406 drugs were screened after combining trade and generic names. All four algorithms identified 52 drugs with signals. The characteristics of all the reports and signaling drugs were analyzed. CONCLUSIONS: This is the first report of drug-associated porphyria that provides critical information on drug porphyrogenicity, facilitating rational and evidence-based drug prescription and improving the accuracy of porphyrogenicity prediction based on model algorithms. Moreover, this study serves a reference for clinicians to ensure that porphyrinogenic drugs are not prescribed to carriers of porphyria genetic mutations.

Umbilical Cord Blood-Derived Cells Can Reconstruct Hematopoiesis in an Aplastic Anemia Animal Model.

Objectives: To explore the efficacy and the mechanism of the umbilical cord-derived cells combined with cyclosporine A (CsA) in treating aplastic anemia (AA) in mice. Methods: Immune-mediated AA model mice were treated with CsA + UC mesenchymal stem cells (UC-MSC), CsA + umbilical cord blood regulatory T cells (UCB-Treg), UC-MSC, UCB-Treg, CsA alone, or blank control, respectively (n = 9 mice/group). CsA and the cell infusion was administered on d0. Routine peripheral blood testing was performed once weekly; bone marrow colony culture, bone marrow cell flow cytometry, peripheral blood T cell subsets, and serum inflammatory cytokines tests were performed on d14. Transcriptome sequencing was performed for cells from CsA + UC-MSC, CsA + UCB-Treg, and CsA groups to detect the possible related genes. Gene function cluster and signal pathway enrichment analysis were also performed. Results: Blank control mice died due to pancytopenia within 21 days, whereas mice in other groups survived for >28 days. On d14, the CsA + UC-MSC and CsA + UCB-Treg groups had higher white blood cell (WBC) counts than the other groups (p < 0.05), along with higher burst-forming unit (BFU) and colony-forming unit-granulocyte, macrophage (CFU-GM) counts (p < 0.01). The CsA + UC-MSC group had the highest BFU count (p < 0.01). The CsA + UC-MSC and CsA + UCB-Treg groups exhibited the highest bone marrow CD34+ cell proportion (9.68% ± 1.35% and 8.17% ± 0.53%, respectively; p < 0.01). Tumor necrosis factor (TNF)-α and interleukin (IL)-2 levels in the CsA + UC-MSC group (p < 0.05) and TNF-α, interleukin-2, and interferon (INF)-γ levels in the CsA + UC-Treg group (p < 0.01) were lower than those in the CsA group. Compared with CsA treatment, CsA + UC-MSC significantly downregulated the histone methylation pathway (p < 0.05), whereas CsA + UCB-Treg significantly upregulated energy metabolism processes (p < 0.05). Treatment with CsA + UC-MSC upregulated superoxide dismutase activity compared with CsA + UCB-Treg treatment. Conclusions: Adding UC-MSC or UCB-Treg to CsA markedly enhanced the reconstruction of hematopoiesis in AA mice, with UC-MSC eliciting greater efficiency than UCB-Treg. Accordingly, the addition of these cells could further improve immune abnormalities.

Sysmex XN-HPC: study of reference intervals and clinical decision limits in healthy allogeneic donors mobilised with G-CSF.

The Sysmex XN series haematopoietic progenitor cell (XN-HPC) is a novel tool for assessing stem cell yield before allogeneic haematopoietic stem cell transplantation. This study aimed to establish a reference interval (RI) for XN-HPC in peripheral blood allogeneic transplant donors following granulocyte colony-stimulating factor (G-CSF) stimulation and determine its clinical significance. All specimens were analysed using Sysmex XN-20. Samples were collected and analysed using non-parametric percentile methods to define the RIs. Quantile regression was used to explore the dependency of the RIs on sex and age. Samples were included in clinical decision limits for apheresis based on receiver operating characteristic curve analysis. The non-parametrically estimated RI for XN-HPC was 623.50 (90% confidence interval [CI90%] 510.00-657.00) to 4,144.28 (CI90% 3,761.00-4,547.00). The RIs for the XN-HPC were not age-dependent but were sex-dependent. The RI for males was 648.40 (CI90% 582.00-709.00)-4,502.60 (CI90% 4,046.00-5,219.00) and for females was 490.90 (CI90% 311.00-652.00)-3,096.90 (CI90% 2,749.00-3,782.00). Comparisons based on XN-HPC values between the poor and less-than-optimal groups, good and less-than-optimal groups, and good and non-good groups had areas under the curve of 0.794 (P < 0.001), 0.768 (P < 0.001), and 0.806 (P < 0.001), respectively, indicating a good predictive value for mobilisation effectiveness. XN-HPC data exceeding 3974 × 106/L suggested that a sufficient number of stem cells could be collected clinically. Values > 5318 < 106/L indicated 100% mobilisation effectiveness. We established an RI for XN-HPC in peripheral blood allogeneic transplant donors following G-CSF stimulation and determined clinical decision thresholds for mobilisation efficiency.

Immediate and long-term efficacy of transcranial direct current stimulation (tCDS) in obsessive-compulsive disorder, posttraumatic stress disorder and anxiety disorders: a systematic review and meta-analysis.

Currently, there is still debate over the effectiveness of transcranial direct current stimulation (tDCS) in treating obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD) and anxiety disorders (ADs). To investigate the immediate and long-term effectiveness of tDCS in these diseases, we conducted a systematic review and quantitative analysis of existing literature on the treatment of OCD, PTSD, and ADs with tDCS. Following the PRISMA guidelines, we searched seven electronic databases and systematically retrieved articles published from May 2012 to June 2024 that compared the effects of active tDCS with sham stimulation in the treatment of these disorders. We included primary outcome measures such as the change scores in disorder-specific and general anxiety symptoms before and after treatment, as well as secondary outcomes such as changes in disorder-specific and general anxiety symptoms at follow-up. We also assessed the impact of tDCS on depressive symptoms. Fifteen papers met the eligibility criteria. Overall, the results of meta-analysis indicated that tDCS had a high effect in improving specific symptoms (SMD = -0.73, 95% CI: -1.09 to -0.37) and general anxiety symptoms (SMD = -0.75; 95% CI: -1.23 to -0.26) in OCD, PTSD and ADs, with effects lasting up to 1 month and showing a moderate effect size. Furthermore, tDCS demonstrated immediate and significant alleviation of depressive symptoms in these diseases. This study concludes that tDCS can serve as a non-invasive brain stimulation technology for treating these disorders, and the therapeutic effects can be maintained for a period of time.

CYLD/HDAC6 signaling regulates the interplay between epithelial-mesenchymal transition and ciliary homeostasis during pulmonary fibrosis.

The primary cilium behaves as a platform for sensing and integrating extracellular cues to control a plethora of cellular activities. However, the functional interaction of this sensory organelle with epithelial-mesenchymal transition (EMT) during pulmonary fibrosis remains unclear. Here, we reveal a critical role for cylindromatosis (CYLD) in reciprocally linking the EMT program and ciliary homeostasis during pulmonary fibrosis. A close correlation between the EMT program and primary cilia is observed in bleomycin-induced pulmonary fibrosis as well as TGF-ß-induced EMT model. Mechanistic study reveals that downregulation of CYLD underlies the crosstalk between EMT and ciliary homeostasis by inactivating histone deacetylase 6 (HDAC6) during pulmonary fibrosis. Moreover, manipulation of primary cilia is an effective means to modulate the EMT program. Collectively, these results identify a pivotal role for the CYLD/HDAC6 signaling in regulating the reciprocal interplay between the EMT program and ciliary homeostasis during pulmonary fibrosis.

PPM1F regulates ovarian cancer progression by affecting the dephosphorylation of ITGB1.

PPM1F has been shown to play diverse biological functions in the progression of multiple tumors. PPM1F controls the T788/T789 phosphorylation switch of ITGB1 and regulates integrin activity. However, the impacts of PPM1F and ITGB1 on ovarian cancer (OV) progression remain unclear. Whether there is such a regulatory relationship between PPM1F and ITGB1 in ovarian cancer has not been studied. Therefore, the purpose of this study is to elucidate the function and the mechanism of PPM1F in ovarian cancer. The expression level and the survival curve of PPM1F were analyzed by databases. Gain of function and loss of function were applied to explore the function of PPM1F in ovarian cancer. A tumor formation assay in nude mice showed that knockdown of PPM1F inhibited tumor formation. We tested the effect of PPM1F on ITGB1 dephosphorylation in ovarian cancer cells by co-immunoprecipitation and western blotting. Loss of function was applied to investigate the function of ITGB1 in ovarian cancer. ITGB1-mut overexpression promotes the progression of ovarian cancer. Rescue assays showed the promoting effect of ITGB1-wt on ovarian cancer is attenuated due to the dephosphorylation of ITGB1-wt by PPM1F. PPM1F and ITGB1 play an oncogene function in ovarian cancer. PPM1F regulates the phosphorylation of ITGB1, which affects the occurrence and development of ovarian cancer.

The safety and efficacy of neoadjuvant PD-1 inhibitor plus chemotherapy for patients with locally advanced gastric cancer: A systematic review and meta-analysis.

BACKGROUND: The extensive utilization of immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) has achieved significant advancements in the treatment of diverse solid tumors. The present meta-analysis aims to evaluate the safety and efficacy of neoadjuvant chemotherapy (NCT) plus PD-1 inhibitor for patients with locally advanced gastric cancer (LAGC). METHODS: An electronic search of PubMed, EmBase, and the Cochrane Library was performed to identify the clinical trials of NCT + PD-1 inhibitor vs. NCT in patients with LAGC. The retrieval period extended from the establishment of the corresponding database until April 2024, and meta-analysis was conducted using Stata (version 15) software. Subsequently, direct comparative analysis was used to compare pooled results of neoadjuvant immunochemotherapy (NICT) with NCT. RESULTS: After screening, 6 phase II/III randomized controlled trials (RCTs) and 9 retrospective studies with 2,953 patients were included. In meta-analysis, NICT group demonstrated a significantly higher rate of pathological complete response (pCR) (P<0.001) and R0 resection (P=0.001), and a lower 2-year recurrence rate (P=0.001) compared to the NCT group. The NICT group, however, exhibited a higher incidence of severe treatment-related adverse events (TRAEs) (P=0.044). Additionally, the NICT and NCT groups exhibited no statistical differences in terms of the number of harvested lymph nodes, the occurrence of total TRAEs and postoperative complications, as well as the duration of postoperative hospitalization. CONCLUSIONS: The combination of PD-1 inhibitor + NCT in LAGC patients enhances the likelihood of achieving radical surgery and improves prognosis, albeit to some extent increasing the risk of severe TRAEs. NICT is anticipated to emerge as the preferred neoadjuvant therapy option for patients diagnosed with LAGC.

Role of sodium pyrophosphate and catechin in the enzymatic hydrolysis of oxidatively damaged myofibrillar protein gels in vitro: Mechanistic insights.

This study investigated the effects of sodium pyrophosphate (SPP) and catechin (C) on the in vitro enzymatic digestion of oxidatively damaged myofibrillar protein (MP) gel. The results indicated that SPP increased the ß-sheet content and the gastric digestibility of the MP gel, while C hindered the transition from α-helix to ß-sheet structure, leading to decreased digestibility. Notably, neither compound significantly affected intestinal digestibility. Furthermore, SPP and C significantly enhanced the antioxidant activity of MP gel digestion products. Notably, their synergistic hydrolysis products, simulating both gastric and gastrointestinal stages, chelated 91.4 % and 89.1 % of Fe2+ and scavenged 59.4 % and 77.6 % of hydroxyl radicals, respectively. Moreover, the final digestion products of the MP gel treated with SPP and C exhibited the highest content of negatively charged amino acids and absolute Zeta potential values. Overall, this study demonstrated that incorporating SPP and C could positively impact the digestion of oxidatively damaged MP gels.

Fully automated classification of pulmonary nodules in positron emission tomography-computed tomography imaging using a two-stage multimodal learning approach.

Background: Lung cancer is a malignant tumor, for which pulmonary nodules are considered to be significant indicators. Early recognition and timely treatment of pulmonary nodules can contribute to improving the survival rate of patients with cancer. Positron emission tomography-computed tomography (PET/CT) is a noninvasive, fusion imaging technique that can obtain both functional and structural information of lung regions. However, studies of pulmonary nodules based on computer-aided diagnosis have primarily focused on the nodule level due to a reliance on the annotation of nodules, which is superficial and unable to contribute to the actual clinical diagnosis. The aim of this study was thus to develop a fully automated classification framework for a more comprehensive assessment of pulmonary nodules in PET/CT imaging data. Methods: We developed a two-stage multimodal learning framework for the diagnosis of pulmonary nodules in PET/CT imaging. In this framework, Stage I focuses on pulmonary parenchyma segmentation using a pretrained U-Net and PET/CT registration. Stage II aims to extract, integrate, and recognize image-level and feature-level features by employing the three-dimensional (3D) Inception-residual net (ResNet) convolutional block attention module architecture and a dense-voting fusion mechanism. Results: In the experiments, the proposed model's performance was comprehensively validated using a set of real clinical data, achieving mean scores of 89.98%, 89.21%, 84.75%, 93.38%, 86.83%, and 0.9227 for accuracy, precision, recall, specificity, F1 score, and area under curve values, respectively. Conclusions: This paper presents a two-stage multimodal learning approach for the automatic diagnosis of pulmonary nodules. The findings reveal that the main reason for limiting model performance is the nonsolitary property of nodules in pulmonary nodule diagnosis, providing direction for future research.

Research Progress on the Association between Schizophrenia and Toxoplasma gondii Infection.

Toxoplasma gondii( T. gondii or Tg), is an obligatory intracellular parasite with humans as its intermediate hosts. In recent years, significant correlations between T. gondii infection and schizophrenia have been reported, including the possible mediating mechanisms. Currently, mechanisms and hypotheses focus on central neurotransmitters, immunity, neuroinflammation, and epigenetics; however, the exact underlying mechanisms remain unclear. In this article, we review the studies related to T. gondii infection and schizophrenia, particularly the latest research progress. Research on dopamine (DA) and other neurotransmitters, the blood-brain barrier, inflammatory factors, disease heterogeneity, and other confounders is also discussed. In addition, we also summarized the results of some new epidemiological investigations.

Targeting the AMPK/Nrf2 Pathway: A Novel Therapeutic Approach for Acute Lung Injury.

ALI(acute lung injury) is a severe respiratory dysfunction caused by various intrapulmonary and extrapulmonary factors. It is primarily characterized by oxidative stress and affects the integrity of the pulmonary barrier. In severe cases, ALI can progress to ARDS(acute respiratory distress syndrome), a condition that poses a serious threat to the lives of affected patients. To date, the etiological mechanisms underlying ALI remain elusive, and available therapeutic options are quite limited. AMPK(AMP-activated protein kinase), an essential serine/threonine protein kinase, performs a pivotal function in the regulation of cellular energy levels and cellular regulatory mechanisms, including the detection of redox signals and mitigating oxidative stress. Meanwhile, Nrf2(nuclear factor erythroid 2-related factor 2), a critical transcription factor, alleviates inflammation and oxidative responses by interacting with multiple signaling pathways and contributing to the modulation of oxidative enzymes associated with inflammation and programmed cell death. Indeed, AMPK induces the dissociation of Nrf2 from Keap1(kelch-like ECH-associated protein-1) and facilitates its translocation into the nucleus to trigger the transcription of downstream antioxidant genes, ultimately suppressing the expression of inflammatory cells in the lungs. Given their roles, AMPK and Nrf2 hold promise as novel treatment targets for ALI. This study aimed to summarise the current status of research on the AMPK/Nrf2 signaling pathway in ALI, encompassing recently reported natural compounds and drugs that can activate the AMPK/Nrf2 signaling pathway to alleviate lung injury, and provide a theoretical reference for early intervention in lung injury and future research on lung protection.

Effectiveness of a Mobile Health Application for Educating Outpatients about Bowel Preparation.

Colonoscopy is an essential method for diagnosing and treating colorectal cancer, relying on effective bowel preparation to thoroughly examine the large intestinal mucosa. Traditional education involves printed instructions and verbal explanations but does not guarantee clear patient understanding. Poor bowel preparation can obscure mucosal visibility, delaying cancer diagnosis and treatment. A mobile medical model using Android devices for bowel preparation education was tested in a single-blind, randomized trial. This trial enrolled outpatients undergoing colonoscopy at the Endoscopy Center for Diagnostic and Treatment between 27 October 2021 and 31 December 2022. This study introduced the ColonClean app alongside traditional methods. After examination, endoscopists rated the preparation quality using the Aronchick scale. A data analysis was conducted using SPSS 25.0 to determine if there was a significant improvement in bowel preparation quality between the control group (traditional method) and the experimental group (traditional method plus the ColonClean app). Forty patients were recruited in each group. In the experimental group, all ratings were "fair", with 75% receiving an "excellent" or "good" rating, showing statistical significance (p = 0.016). The ColonClean app improves bowel preparation quality more effectively than traditional care instructions.

Astragalin from Thesium chinense: A Novel Anti-Aging and Antioxidant Agent Targeting IGFR/CD38/Sirtuins.

Astragalin (AG), a typical flavonoid found in Thesium chinense Turcz (T. chinense), is abundant in various edible plants and possesses high nutritional value, as well as antioxidant and antibacterial effects. In this study, we initially predicted the mechanism of action of AG with two anti-aging and antioxidant-related protein targets (CD38 and IGFR) by molecular docking and molecular dynamics simulation techniques. Subsequently, we examined the anti-aging effects of AG in Caenorhabditis elegans (C. elegans), the antioxidant effects in zebrafish, and verified the related molecular mechanisms. In C. elegans, AG synergistically extended the lifespan of C. elegans by up-regulating the expression of daf-16 through inhibiting the expression of daf-2/IGFR and also activating the AMPK and MAPK pathways to up-regulate the expression of sir-2.1, sir-2.4, and skn-1. In oxidatively damaged zebrafish embryos, AG demonstrated a synergistic effect in augmenting the resistance of zebrafish embryos to oxidative stress by up-regulating the expression levels of SIRT1 and SIRT6 within the zebrafish embryos system via the suppression of CD38 enzymatic activity and then inhibiting the expression of IGFR through high levels of SIRT6. These findings highlight the antioxidant and anti-aging properties of AG and indicate its potential application as a supplementary ingredient in aquaculture for enhancing fish health and growth.

Long-Term Follow-Up of Eltrombopag Treatment for Patients with Cyclosporin A Refractory/Relapsed Transfusion-Dependent Non-Severe Aplastic Anemia: A Report from a Single Center in China.

INTRODUCTION: Aplastic anemia (AA) is characterized by bone marrow failure and cytopenia. Eltrombopag (ELT) is effective and safe for treating refractory/relapsed AA; however, reports on the long-term outcomes of transfusion-dependent non-severe AA (TD-NSAA) are limited. METHODS: Patients with TD-NSAA refractory to immunosuppressive therapy (IST) or relapsed after IST, treated with ELT alone, and followed up for at least 12 months were retrospectively enrolled. The baseline characteristics of patients, efficacy and adverse effects of ELT, and relapse and clone evolution rates after ELT were documented. RESULTS: Of the 55 patients with TD-NSAA included, 24 (43.6%) were men. Median age at diagnosis was 46 (19-80) years. Twenty-four patients had relapsed TD-NSAA, and 31 patients had refractory TD-NSAA. During the median follow-up period of 28 (12-48) months, the overall and complete response rates at 3, 6, and 12 months of ELT treatment were 38.2, 60.0, and 52.7 and 9.1, 14.6, and 9.1%, respectively. After a median follow-up of 28 (12-48) months, 21.2% (7/33) of patients experienced relapse, with a median duration from ELT treatment to relapse of 14 (6-45) months. CONCLUSION: ELT was effective in patients with relapsed/refractory TD-NSAA, with tolerable adverse effects.

UK5099 Inhibits the NLRP3 Inflammasome Independently of its Long-Established Target Mitochondrial Pyruvate Carrier.

Targeting NLRP3 inflammasome has been recognized as a promising therapeutic strategy for the treatment of numerous common diseases. UK5099, a long-established inhibitor of mitochondrial pyruvate carrier (MPC), is previously found to inhibit macrophage inflammatory responses independent of MPC expression. However, the mechanisms by which UK5099 inhibit inflammatory responses remain unclear. Here, it is shown that UK5099 is a potent inhibitor of the NLRP3 inflammasome in both mouse and human primary macrophages. UK5099 selectively suppresses the activation of the NLRP3 but not the NLRC4 or AIM2 inflammasomes. Of note, UK5099 retains activities on NLRP3 in macrophages devoid of MPC expression, indicating this inhibitory effect is MPC-independent. Mechanistically, UK5099 abrogates mitochondria-NLRP3 interaction and in turn inhibits the assembly of the NLRP3 inflammasome. Further, a single dose of UK5099 persistently reduces IL-1ß production in an endotoxemia mouse model. Importantly, structure modification reveals that the inhibitory activities of UK5099 on NLRP3 are unrelated to the existence of the activated double bond within the UK5099 molecule. Thus, this study uncovers a previously unknown molecular target for UK5099, which not only offers a new candidate for the treatment of NLRP3-driven diseases but also confounds its use as an MPC inhibitor in immunometabolism studies.

α-Lipoic acid treatment regulates enzymatic browning and nutritional quality of fresh-cut pear fruit by affecting phenolic and carbohydrate metabolism.

Fresh-cut pear fruit is greatly impacted by enzymatic browning, and maintaining quality remains a challenge. This study examined the impact of exogenous α-lipoic acid (α-LA) treatment on enzymatic browning and nutritional quality of fresh-cut pears. Results revealed that 0.5 g/L α-LA treatment effectively maintained color and firmness, and inhibited the increase in microbial number. The α-LA treatment also reduced MDA and H2O2 contents, decreased PPO activity, and enhanced SOD, CAT, and PAL activities. The α-LA treatment notably upregulated phenolic metabolism-related gene expression, including PbPAL, Pb4CL, PbC4H, PbCHI and PbCHS, and then increasing total phenols and flavonoids contents. Furthermore, it also influenced carbohydrate metabolism-related gene expression, including PbSS, PbSPS, PbAI and PbNI, maintaining a high level of sucrose content. These findings indicated that α-LA treatment showed promise in reducing browning and enhancing fresh-cut pears quality, offering a potential postharvest method to prolong the lifespan and maintain nutritional quality.

Chlorella pyrenoidosa polysaccharides supplementation increases Drosophila melanogaster longevity at high temperature.

Chlorella pyrenoidos polysaccharides (CPPs) are the main active components of Chlorella pyrenoidos. They possess beneficial health properties, such as antioxidant, anti-inflammatory, and immune-enhancing. This study aims to investigate the protective function and mechanism of CPPs against high-temperature stress injury. Results showed that supplementation with 20 mg/mL CPPs significantly extended the lifespan of Drosophila melanogaster under high-temperature stress, improved its motility, and enhanced its resistance to starvation and oxidative stress. These effects were mainly attributed to the activation of Nrf2 signaling and enhanced antioxidant capacity. Additionally, it has been discovered that CPPs supplementation enhanced Drosophila resilience by preventing the disruption of the intestinal barrier and accumulation of reactive oxygen species caused by heat stress. Overall, these studies suggest that CPPs could be a useful natural therapy for preventing heat stress-induced injury.

Impact of major hepatectomy on recurrence after resection of hepatocellular carcinoma at CNLC Ib stage: a propensity score matching study.

OBJECTIVE: Patients with hepatocellular carcinoma (HCC) who undergo curative hepatectomy may experience varying remnant liver volumes. Our study aimed to evaluate whether the extent of liver resection has an effect on postoperative recurrence in HCC patients at China Liver Cancer Staging (CNLC) Ib stage. METHODS: A retrospective analysis was conducted on 197 patients who underwent hepatectomy for a solitary HCC lesion measuring ≥5 cm (CNLC Ιb stage) between January 2019 and June 2022. Patients were divided into major hepatectomy (MAH) group (n=70) and minor hepatectomy (MIH) group (n=127) based on the extent of liver resection. Recurrence-free survival (RFS) was compared between the two groups. Propensity score matching (PSM) was employed to minimize bias in the retrospective analysis. RESULTS: Patients who underwent MAH had a greater total complication rate than did those who underwent MIH (35.7% vs. 11.8%, P<0.001). The median RFS was 14.6 months (95% CI: 11.1-18.1) for MAH group and 24.1 months (95% CI 21.2-27.1) for MIH group (P<0.001). After PSM, patients who underwent MAH still had a greater total complication rate than those who underwent MIH (36.7% vs. 16.3%, P=0.037). The median RFS was 13.2 months (95% CI: 15.1-21.7) for MAH group and 22.3 months (95% CI 18.1-26.5) for MIH group (P=0.0013). The Cox regression model identified MAH as an independent poor predictor for HCC recurrence (hazard ratios of 1.826 and 2.062 before and after PSM, respectively; both P<0.05). CONCLUSION: MIH can be performed with fewer postoperative complications and contributes to improved RFS in patients with HCC at CNLC Ιb stage compared to MAH. Parenchyma-sparing resection should be considered the first choice for these HCCs.

Phosphorus-Doping Enables the Superior Durability of a Palladium Electrocatalyst towards Alkaline Oxygen Reduction Reactions.

The sluggish kinetics of oxygen reduction reactions (ORRs) require considerable Pd in the cathode, hindering the widespread of alkaline fuel cells (AFCs). By alloying Pd with transition metals, the oxygen reduction reaction's catalytic properties can be substantially enhanced. Nevertheless, the utilization of Pd-transition metal alloys in fuel cells is significantly constrained by their inadequate long-term durability due to the propensity of transition metals to leach. In this study, a nonmetallic doping strategy was devised and implemented to produce a Pd catalyst doped with P that exhibited exceptional durability towards ORRs. Pd3P0.95 with an average size of 6.41 nm was synthesized by the heat-treatment phosphorization of Pd nanoparticles followed by acid etching. After P-doping, the size of the Pd nanoparticles increased from 5.37 nm to 6.41 nm, and the initial mass activity (MA) of Pd3P0.95/NC reached 0.175 A mgPd-1 at 0.9 V, slightly lower than that of Pd/C. However, after 40,000 cycles of accelerated durability testing, instead of decreasing, the MA of Pd3P0.95/NC increased by 6.3% while the MA loss of Pd/C was 38.3%. The durability was primarily ascribed to the electronic structure effect and the aggregation resistance of the Pd nanoparticles. This research also establishes a foundation for the development of Pd-based ORR catalysts and offers a direction for the future advancement of catalysts designed for practical applications in AFCs.