Tumor perfusion enhancement by focus ultrasound-induced blood-brain barrier opening to potentiate anti-PD-1 immunotherapy of glioma.

OBJECTIVE: To demonstrate the feasibility of using focused ultrasound to enhance delivery of PD-1 inhibitors in glioma rats and determine if such an approach increases treatment efficacy. METHODS: C6 glioma in situ rat model was used in this study. Transcranial irradiation with FUS combined with microbubbles was administered to open the blood-brain barrier (BBB). The efficacy of BBB opening was evaluated in normal rats. The rats with glioma were grouped to evaluate the role of PD-1 inhibitors combined with FUS-induced immune responses in suppressing glioma when the BBB opens. Flow cytometry was used to examine the changes of immune cell populations of lymphocytes in peripheral blood, tumor tissue and spleen tissue of the rats. A section of rat brain tissue was also used for histological and immunohistochemical analysis. The survival of the rats was then monitored; the tumor progression and changes in blood perfusion of tumor were dynamically observed in vivo using multimodal MRI. RESULTS: FUS combined with microbubbles could enhance the blood perfusion of tumors by increasing the permeability of BBB (p < 0.0001), thus promoting the infiltration of CD4+ T lymphocytes (p < 0.01). Compared with the control group, the combination treatment group had increased in the infiltration number of CD4+(p < 0.05) and CD8+ T (p < 0.05); the tumor volume of the combined treatment group was smaller than that of the control group (p < 0.01) and the survival rate of the rats was prolonged (p < 0.05). CONCLUSIONS: In this study, we demonstrated that the transient opening of the BBB induced by FUS enhanced tumor vascular perfusion and facilitated the delivery of PD-1 inhibitors, ultimately improving the therapeutic efficacy for glioblastoma.

Baicalin inhibits PANoptosis by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly in macrophages.

PANoptosis is an emerging form of regulated cell death (RCD) characterized by simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling that not only participates in pathologies of inflammatory diseases but also has a critical role against pathogenic infections. Targeting PANoptosis represents a promising therapeutic strategy for related inflammatory diseases, but identification of inhibitors for PANoptosis remains an unmet demand. Baicalin () is an active flavonoid isolated from Scutellaria baicalensis Georgi (Huangqin), a traditional Chinese medicinal herb used for heat-clearing and detoxifying. Numerous studies suggest that baicalin possesses inhibitory activities on various forms of RCD including apoptosis/secondary necrosis, pyroptosis, and necroptosis, thereby mitigating inflammatory responses. In this study we investigated the effects of baicalin on PANoptosis in macrophage cellular models. Primary macrophages (BMDMs) or J774A.1 macrophage cells were treated with 5Z-7-oxozeaenol (OXO, an inhibitor for TAK1) in combination with TNF-α or LPS. We showed that OXO plus TNF-α or LPS induced robust lytic cell death, which was dose-dependently inhibited by baicalin (50-200 µM). We demonstrated that PANoptosis induction was accompanied by overt mitochondrial injury, mitochondrial DNA (mtDNA) release and Z-DNA formation. Z-DNA was formed from cytosolic oxidized mtDNA. Both oxidized mtDNA and mitochondrial Z-DNA puncta were co-localized with the PANoptosome (including ZBP1, RIPK3, ASC, and caspase-8), a platform for mediating PANoptosis. Intriguingly, baicalin not only prevented mitochondrial injury but also blocked mtDNA release, Z-DNA formation and PANoptosome assembly. Knockdown of ZBP1 markedly decreased PANoptotic cell death. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), administration of baicalin (200 mg/kg, i.g., for 4 times) significantly mitigated lung and liver injury and reduced levels of serum TNF-α and IFN-γ, concomitant with decreased levels of PANoptosis hallmarks in these organs. Baicalin also abrogated the hallmarks of PANoptosis in liver-resident macrophages (Kupffer cells) in HLH mice. Collectively, our results demonstrate that baicalin inhibits PANoptosis in macrophages by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly, thus conferring protection against inflammatory diseases. PANoptosis is a form of regulated cell death displaying simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling. This study shows that induction of PANoptosis is linked to mitochondrial dysfunction and mitochondrial Z-DNA formation. Baicalin inhibits PANoptosis in macrophages in vitro via blocking mitochondrial dysfunction and the mitochondrial Z-DNA formation and thereby impeding the assembly of ZBP1-associated PANoptosome. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), baicalin inhibits the activation of PANoptotic signaling in liver-resident macrophages (Kupffer cells) in vivo, thus mitigating systemic inflammation and multiple organ injury in mice.

Impact of positive CD4 cells on event-free survival in follicular lymphoma patients.

OBJECTIVE: Previous results about prognostic value of CD4+ T cells in follicular lymphoma (FL) remain controversial. METHODS: Immunohistochemistry was used to examine expression of positive CD4 cells in 103 patients with FL 1-3A. Early failure was described as failing to achieve event-free survival (EFS) at 12 or 24 months. RESULTS: There were 49 (47.6%) male and 54 (52.4%) females, with a median age of 54 years. Compared to patients with <20% of positive CD4 cells, patients with ≥20% of positive CD4 cells exhibited a significant lower risk of early failure (2-year EFS rate: 56.7% vs 73.5%, p = 0.047). When patients were stratified based on positive CD4 cell combined with FLIPI, the median EFS (p = 0.002) and median OS (p = 0.007) were significantly different. CONCLUSIONS: This study demonstrated that higher expression of positive CD4 cells predicts lower risk of early failure in follicular lymphoma, and combination analysis of CD4 and FLIPI could better predict disease relapse and survival outcome.

A QuEChERS method based on octadecyl-bonded hectorite for the determination of ten mycotoxins in yak ghee.

To develop a clean-up material suitable for high-fat food matrices for detecting mycotoxins in yak ghee, an octadecyl-bonded hectorite (Hectorite@NHCO(CH2)17CH3) was synthesized through multi-step chemical reactions. A modified QuEChERS-HPLC-MS/MS method for detecting ten mycotoxins in sesame oil in yak ghee was established using Hectorite@NHCO(CH2)17CH3 as clean-up agent. It involved extracting mycotoxin contaminants using acidified acetonitrile and employing the Hectorite@NHCO(CH2)17CH3 to remove interfering substances from the extract. The purified samples were then analyzed using HPLC-MS/MS. Within a linear range of 1.0-500 µg/kg, there was a good linear relationship between the quantification ion peak area of the target analytes and the corresponding concentrations (R2 ≥ 0.9991). The limit of detection (LOD) ranged from 0.10 µg/kg to 18.62 µg/kg and the limit of quantitation (LOQ) ranged 0.32-62.07 µg/kg. The recoveries at low, medium and high concentrations (25, 100 and 500 µg/kg) ranged from 72.2% to 113.9%, with relative standard deviations (RSD) between 3.2% and 17.5%. The intra-day and inter-day precision met experimental requirements. The proposed method was characterized by a high accuracy and precision, and it could cater to the current demand for detecting ten mycotoxins in yak ghee.

Recent advances in the use of resveratrol against Staphylococcus aureus infections (Review).

As a notorious bacterial pathogen, Staphylococcus aureus (S. aureus) can readily induce infections in the community and hospital, causing significant morbidity and mortality. With the extensive rise of multiple resistance, conventional antibiotic therapy has rapidly become ineffective for related infections. Resveratrol is a naturally occurring polyphenolic substance that has been demonstrated to have effective antimicrobial activity against S. aureus. Resveratrol at sub-inhibitory doses can suppress the expression of virulence factors, contributing to attenuated biofilm formation, interference with quorum sensing and the inhibition of the production of toxins. As a promising efflux pump inhibitor, resveratrol enhances antibiotic susceptibility to a certain extent. In conjunction with conventional antibiotics, resveratrol displays unique synergistic effects with norfloxacin and aminoglycoside on S. aureus, yet antagonizes the lethal effects of daptomycin, oxacillin, moxifloxacin and levofloxacin. Nevertheless, given the low oral bioavailability of resveratrol, advanced formulations need to be developed to delay the rapid metabolism conversion to low or inactive conjugates. The present review discusses the antibacterial properties of resveratrol against S. aureus, in an aim to provide in-depth insight for researchers to address the challenges of antimicrobial resistance.

Advances in antibacterial activity of zinc oxide nanoparticles against Staphylococcus aureus (Review).

Nanoparticles (NPs) are one of the promising strategies to deal with bacterial infections. As the main subset of NPs, metal and metal oxide NPs show destructive power against bacteria by releasing metal ions, direct contact of cell membranes and antibiotic delivery. Recently, a number of researchers have focused on the antibacterial activity of zinc oxide nanoparticles (ZnO NPs) against Staphylococcus aureus (S. aureus). Currently, there is a lack of a comprehensive review on ZnO NPs against S. aureus. Therefore, in this review, the antibacterial activity against S. aureus of ZnO NPs made by various synthetic methods was summarized, particularly the green synthetic ZnO NPs. The synergistic antibacterial effect against S. aureus of ZnO NPs with antibiotics was also summarized. Furthermore, the present review also emphasized the enhanced activities against S. aureus of ZnO nanocomposites, nano-hybrids and functional ZnO NPs.

Superior Circularly Polarized Luminescence Brightness Achieved with Chiral Heteroleptic Nine-Coordinate Coumarin-Based Tb3+ Complexes.

In order to facilitate the practical application of circularly polarized luminescence (CPL) active molecules, the CPL brightness (BCPL) must be optimized. We have applied a binary modular strategy to synthesize two chiral organo-Tb3+ complexes, [Tb(Coum)3(1R,2R-Ph-PyBox)] (2) and [Tb(Coum)3(1S,2S-Ph-PyBox)] (5), combining 3-acetyl-4-hydroxy-coumarin (Coum) and enantiopure 2,6-bis(4-phenyl-2-oxazolin-2-yl) pyridine (1R,2R/1S,2S-Ph-PyBox). The photophysical properties of these novel complexes have been fully characterized. The combined point-chiral induction capability of chiral bis(oxazoline) derivatives and the outstanding photophysical properties of the coumarin-derived ligand have resulted in an intense excited-state chiroptical activity (|glum| = 0.097-0.103) for both Tb3+ enantiomers, with a bright Tb3+-centered high-purity green emission (ΦPL = 74%) and enhanced antenna-centered absorption behavior (ε320 nm = 47820-47940 M-1 cm-1). A superior BCPL (1132.7-1205.8 M-1 cm-1 at 5D4 → 7F5) has been established for complexes 2 and 5. The strategy adopted in this work provides a new route to chiroptical organo-Tb3+ luminophores with outstanding comprehensive performance.

Enhancement of Synergistic Photocatalytic Performance by Anchoring Cadmium Sulfide on Nanosphere Structured Coordination Polymers.

Precisely tuning how and where a reaction occurs in a one-step selective system is important but challenging owing to the similar electronic environments in multiple active sites. In this work, highly selective and effective reaction sites were obtained by generating copper coordination polymers (Cu-CP) of a range of sizes and morphologies, from bulk solid crystals (1) to uniform nanosphere structures (1a), by controlling the amount of surfactant hexadecyl trimethylammonium bromide (CTAB). The results indicated that the morphology and size of the uniform nanosphere structures were affected by the proportion of CTAB; uniform distribution of nanosphere structures was achieved with a premade building carrier when the content of CTAB was 0.005 mmol, generating a well-established platform. Photocatalytic cadmium sulfide (CdS) was then immobilized on the surface of the premade platform unit 1a through an in situ process to generate CdS@1a composites with well-dispersed catalytic CdS active sites. Furthermore, the well-defined CdS@1a composite platform was utilized as photocatalysts to explore the selective one-step depolymerization reaction under blue-light irradiation. Notably, the CdS0.149@1a composite, which featured a unique structure with evenly dispersed, closely spaced catalytic sites, exhibiting remarkable photoelectrochemical behaviors for selective one-step depolymerization of lignin model substances to aromatic monomer phenol and acetophenone framework products. This work demonstrates the use of an inherently morphological process to construct outstanding photocatalysts that could enable a wide range of photocatalytic reactions.

A Phase 1a/1b Dose Escalation/Expansion Study of the Anti-PD-1 Monoclonal Antibody Nofazinlimab in Chinese Patients with Solid Tumors or Lymphoma.

BACKGROUND: Immune checkpoint blockade with anti-programmed cell death 1 (PD-1) antibodies has demonstrated efficacy in multiple tumor types. Nofazinlimab is a humanized rat antibody targeting PD-1. A first-in-human study of nofazinlimab conducted in Australia found no dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) was not reached in the range of 1-10 mg/kg. OBJECTIVE: We evaluated nofazinlimab for multiple advanced malignancies in Chinese patients. PATIENTS AND METHODS: This was a phase 1a/1b, open-label, multicenter, dose-escalation/expansion trial. In phase 1a, patients received an abbreviated dose escalation of nofazinlimab at 60 mg and 200 mg every 3 weeks (Q3W) to determine DLTs and the recommended phase 2 dose (RP2D). In phase 1b, patients received the RP2D (monotherapy/combination) in six arms by tumor type; DLTs were evaluated for nofazinlimab plus lenvatinib in the unresectable hepatocellular carcinoma (uHCC) arm. Safety (continuously monitored in patients who received nofazinlimab) and efficacy (patients with measurable baseline disease) were assessed. RESULTS: Overall, 107 patients were eligible and received nofazinlimab. In phase 1a, no DLTs were observed; the RP2D was 200mg Q3W. In phase 1b, no DLTs were observed with nofazinlimab plus lenvatinib. The safety profile was consistent with that observed in the first-in-human study (NCT03475251). In phase 1b, 21/88 (23.9%) patients achieved confirmed objective responses, 26 (29.5%) had stable disease, and 9/20 (45.0%) patients with uHCC achieved confirmed objective responses to nofazinlimab plus lenvatinib. CONCLUSIONS: Nofazinlimab was well tolerated in Chinese patients. Preliminary efficacy was encouraging, particularly for nofazinlimab plus lenvatinib in uHCC, which is being studied in an ongoing phase 3 trial. CLINICAL TRIAL REGISTRATION: NCT03809767; registered 18 January 2019.

Loncastuximab tesirine in Chinese patients with relapsed or refractory diffuse large B-cell lymphoma: a multicenter, open-label, single-arm, phase II trial.

Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Loncastuximab tesirine (Lonca), an antibody conjugate targeting CD19, has demonstrated significant clinical benefit in R/R DLBCL in a global phase 2 LOTIS-2 study. In the China bridging pivotal phase 2 OL-ADCT-402-001 study, eligible patients aged ≥18 years with R/R DLBCL who had failed ≥ 2 lines of systemic therapies were enrolled and treated with Lonca every 3 week with 150 µg/kg for 2 cycles; then 75 µg/kg for subsequent cycles (up to 1 year). The primary endpoint was overall response rate (ORR) assessed by independent review committee. Primary analyses for efficacy and safety were performed on the patients who received at least one treatment and had at least 6 months of follow-up following an initial documented response. As of data-cutoff, 64 patients received Lonca (median: 4.0 cycles [range: 1 to 17]). The median number of prior lines of therapies was 3.0 (range: 2 to 12). The ORR was 51.6% (95% CI: 38.7% to 64.2%), and the complete response rate was 23.4%. Hematological events accounted for the majority of the most common (≥15%) Grade ≥3 treatment-emergent adverse events (TEAEs), in which increased gamma glutamyltransferase (25.0%), and hypokalaemia (18.8%) also were reported. Serious TEAEs were reported in 35 of 64 patients with 4 fatal TEAEs. In conclusion, Lonca monotherapy demonstrated clinically meaningful efficacy and was well-tolerated in heavily pretreated Chinese patients with R/R DLBCL, which was consistent with the results of the LOTIS-2 study in Caucasian patients.

Effect of shape on the transport and retention of nanoplastics in saturated quartz sand.

Nanoplastics (NPs) pose great challenges to soil-groundwater systems. This study investigated the transport and retention of self-synthesized 0.5-µm polystyrene NPs with different shapes using column experiments. The regular NPs were with spherical shapes, while the irregular NPs were with toroid-like shapes. The toroid-like shapes were the irregular shapes (with low aspect ratio) which have not been studied yet. The explorations were carried out in both 5-25 mM NaNO3 and 1-10 mM Ca(NO3)2 solutions. Both breakthrough curves (BTCs) and retained profiles (RPs) were monitored. Our findings uncovered a clear disparity in the transport of irregular and regular NPs, with irregular particles exhibiting lower transport ability compared to the regular ones. For example, the average breakthrough plateaus of the regular and irregular NPs were ∼0.9 and ∼0.5, respectively, in 10 mM NaNO3. In-depth theoretical analysis indicated that the lower XDLVO interaction energy barrier between the irregular NPs and quartz sand was one factor, and the greater margination of irregular NPs on quartz sand, as verified by the numerical simulation, was another factor leading to the decreased transport and increased retention of the irregular NPs. The obtained results highlighted the significance of considering particle shape in future modelling and predicting the fate of NPs in real environmental circumstances.

A Novel m.1636A > G Variant in Mitochondrial TV Gene Might Cause New Phenotype of Mitochondrial Disease in a 2-Year Old Chinese Boy.

Pathogenic variants of mitochondrial DNA (mtDNA) are associated with a large number of heterogeneous diseases involving multiple systems with which patients may present with a wide range of clinical phenotypes. Clinical data of the proband and his family members were gathered in a retrospective study. Whole-exome sequencing and full-length sequencing of the mitochondrial genome that was performed on peripheral blood, urine, and oral mucosa cells were applied for genetic analysis. In this study, we describe a 2-year-old Chinese boy with global developmental delay, Charcot-Marie-Tooth (CMT) disease, progressive myoclonic epilepsy, paroxysmal arrhythmia, and brain atrophy with elevated blood lactate levels. The clinical manifestations of the patient were improved after metabolic therapy, but the development regressed after infection. The molecular finding of whole-exome sequencing is unremarkable, but the mtDNA genome sequencing of the proband and his monther revealed a de novo novel heteroplasmic variant, m.1636A > G, located next to the highly conserved anticodon loop of tRNA Val (MT-TV) gene. Moreover, the higher levels of mutational load in urinary epithelial cells (19.05%) and oral mucosa cells (20.8%) were detected than that in blood (17.4%). Combined with the phenotypic and molecular genetics analysis of this family, this novel variation was currently considered to be a likely pathogenic variant. Our results added evidence that the de novo m.1636A > G variation in the highly conserved sequence of MT-TV appears to suggest a childhood-onset mitochondrial phenotype of a 2-year-old patient, thus broaden the genotypic interpretation of mitochondrial DNA-related disease.

The longitudinal trend and influential factors exploring of global antimicrobial resistance in Klebsiella pneumoniae.

Klebsiella pneumoniae (Kp) is a human symbiotic opportunistic pathogen capable of causing severe hospital-based infections and community-acquired infections. The problem of antimicrobial resistance (AMR) has become increasing serious over time, posing a major threat to socio-economic and human development. In this study, we explored the global trend of AMR in 1786 strains of Kp isolated between 1982 and 2023. The number of antibiotic resistance genes (ARGs) in Kp increased significantly from 24.29 ± 5.44 to 32.42 ± 8.52 over time. Mobile genetic elements (MGEs) were responsible for the ARGs horizontal transfer of Kp strains. The results of structural equation modeling (SEM) indicated a strong association between the human development index and the increase of antibiotic consumption, which indirectly affected the occurrence and development of antibiotic resistance in Kp. The results of Generalized Linear Models (GLM) indicated that the influence of environmental factors such as temperature on the development of Kp resistance could not be ignored. Overall, this study monitored the longitudinal trend of antimicrobial resistance in Kp, explored the factors influencing antibiotic resistance, and provided insights for mitigating the threat of antimicrobial resistance.

The application of CRISPR-Cas system in Staphylococcus aureus infection.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated nuclease (Cas) system has been proven to play an irreplaceable role in bacteria immunity activity against exogenous genetic elements. In recent years, this system has emerged as a valid gene engineering method and could be used to detect and treat various microorganisms such as bacteria and viruses, etc. Staphylococcus aureus, as a Gram-positive, opportunistic human and animal pathogen, can cause a variety of diseases greatly threatening human health. Here, we mainly reviewed the applications of the CRISPR-Cas system in Staphylococcus aureus infections in detail. Furthermore, the prospects and drawbacks of the CRISPR-Cas system were also discussed.

Docetaxel-Encapsulated Catalytic Pt/Au Nanotubes for Synergistic Chemo-Photothermal Therapy of Triple-Negative Breast Cancer.

The combination of photothermal therapy with chemotherapy has emerged as a promising therapeutic modality for addressing triple-negative breast cancer (TNBC). This manuscript describes a novel hybrid nanoplatform comprising ultrathin catalytic platinum/gold (Pt/Au) nanotubes encapsulated with docetaxel and phase-change materials (PCMs) for the photoacoustic imaging-guided synergistic chemo-photothermal therapy of TNBC. Upon irradiation of near-infrared laser, the photothermal heating of nanotubes converts solid-state PCM into liquid, triggering the controlled release of the encapsulated docetaxel. The thin Pt layer within nanotubes enhances the nanotube's thermal stability, thus prolonging the photothermal ablation of tumors. Furthermore, platinum effectively mitigates tumor hypoxia by catalyzing the decomposition of hydrogen peroxides to generate oxygen in the tumor microenvironment, thus improving the efficiency of chemotherapy. It is demonstrated that the drug-loaded nanotubes achieve significant tumor inhibition rates of 75.4% in vivo on 4T1 tumor-bearing mice, significantly surpassing control groups. These nanotubes also notably extend survival, attributable to the synergistic effects of prolonged photothermal therapy facilitated by platinum and oxygenation-enhanced chemotherapy. This combination leverages the unique properties of the Pt/Au NTs-DTX/PCM nanoplatform, optimizing therapeutic outcomes. It is envisioned that this nanoplatform may find important applications in managing superficial malignant solid tumors in general.

Polysulfone membranes decorated with Fe-Mn binary oxide nanoparticles and polydopamine for enhanced arsenate/arsenite adsorptive removal.

Arsenic contamination of water is a global environmental concern, and membrane technology combined with nanotechnology contributes to more efficient removal of arsenic. In this study, Fe-Mn oxide (FM), Polydopamine (PDA), and PDA-modified FM (PFM) were incorporated into polysulfone (PSF) to prepare adsorption membranes (PFMP) for arsenic removal. The prepared nanoparticles and membranes were characterized using TEM, SEM, FTIR, TGA, contact angle, and pure water flux. The introduction of particles enhanced the hydrophilicity of the membranes and significantly enhanced the pure water flux of the membranes. Adsorption experiments indicated that the PFMP membrane exhibited the best arsenic removal performance, with maximum adsorption capacities for As(III) and As(V) were 11.57 mg/g and 12.39 mg/g, respectively. The Langmuir model fitted the adsorption isotherms well, and the kinetics followed the pseudo-second-order model. The filtration experiment revealed that the PFMP membrane was capable of reducing As(III) solution (915 L/m2) and As(V) solution (1075 L/m2) from a concentration of 100 µg/L to the safe limit of As (＜10 µg/L). The As-loaded membrane was regenerated using NaOH solution (pH = 11), and the filtration experiment was repeated. FTIR and XPS demonstrated that the mechanism of the reaction between the membrane and arsenic was ligand exchange, where the arsenic ions were bonded to the oxygen ions to form Mn-O-As and Fe-O-As.

A prospective phase 2 study of combination epigenetic therapy against relapsed/refractory peripheral T cell lymphoma.

BACKGROUND: Peripheral T cell lymphomas (PTCLs) are prototypical epigenetic malignancies with invariably poor prognoses. Novel and effective therapeutic strategies are needed to improve clinical outcomes, particularly in relapsed/refractory patients. METHODS: We conducted a multicenter phase 2 study to evaluate the therapeutic efficacy of azacitidine and chidamide, alone or in combination with gemcitabine and oxaliplatin (GemOx), in patients with relapsed/refractory PTCLs (registration number: ChiCTR2000037232). The primary endpoint was the best overall response rate. FINDINGS: As of May 1st, 2024, thirty patients were evaluable for efficacy and toxicity. The best overall response rate was 53.3%, meeting its primary endpoint. Among the patients with angioimmunoblastic T cell lymphoma (AITL; N = 19), a numerically higher response rate was observed, regardless of whether chemotherapy was combined, compared to patients with non-AITL. After a median follow-up of 36.6 months, median progression-free survival and overall survival were 7.1 and 8.7 months, respectively. Patients with AITL who received combination chemotherapy (N = 12) achieved the most promising response rates (overall response rate, 91.7%; complete remission rate, 66.7%) and survival outcomes (median progression-free survival, 17.2 months; median overall survival, 38.8 months). The most common grade 3-4 toxicities were neutropenia (40.0%) and thrombocytopenia (30.0%). CONCLUSIONS: The combination of epigenetic therapy with GemOx was well tolerated and highly effective in patients with relapsed/refractory PTCLs. Patients with AITL, in particular, may benefit more from this combination treatment and should be the focus of future studies. FUNDING: This work was funded by the Natural Science Foundation of Jiangsu Province (BK20232039).

Laparoscopic anatomical right hepatectomy using a four-incision anterior approach: Technical details and surgical outcomes (with Video).

With the continuous advancements of laparoscopic techniques, many surgeons have enhanced the feasibility and safety of this approach for carefully selected patients. This study aims to offer a comprehensive account of the technical aspects and surgical outcomes associated with laparoscopic anatomical right hepatectomy, explicitly utilizing a four-incision anterior approach. The surgical procedure involved several maneuvers, including blocking the Glissonean pedicle, ligation of the right hepatic artery, right branch of the portal vein, and the right hepatic duct, removal of the liver parenchyma along the ischemic line, and determination of the liver section based on four anatomical landmarks: the right anterior Glissonian pedicle, middle hepatic vein, root of the right hepatic vein, and retrohepatic inferior vena cava. The article provides clear visualization of these anatomical landmarks following right hepatectomy. Proper patient positioning and precise incision placement are crucial factors for ensuring the success of the laparoscopic right anterior hepatectomy procedure. The separation of the extrahepatic Glissonean pedicle at the liver hilum to determine the hepatic resection ischemia line, as well as the identification of liver sections using four anatomical landmarks are essential steps in the liver resection process. The laparoscopic anatomical right hepatectomy using a four-incision anterior approach was performed smoothly, with standard intraoperative techniques completed. Measures are in place to address any complications that may arise during the surgery.