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Programmed cell death 1 (PD-1) blockade is considered contraindicated in liver transplant (LT) recipients due to potentially lethal consequences of graft rejection and loss. Though post-transplant PD-1 blockade had already been reported, pre-transplant use of PD-1 blockade has not been thoroughly investigated. This study explores the safety and efficacy of neoadjuvant PD-1 blockade in patients with hepatocellular carcinoma (HCC) after registration on the waiting list. Seven transplant recipients who underwent neoadjuvant PD-1 blockade combined with lenvatinib and subsequent LT were evaluated. The objective response rate (ORR) and disease control rate (DCR) was 71% and 85% according to the mRECIST criteria. Additionally, a literature review contained 29 patients were conducted to summarize the PD-1 blockade in LT for HCC. Twenty-two LT recipients used PD-1 inhibitors for recurrent HCC. 9.1% (2/22) and 4.5% (1/22) recipients achieved complete remission (CR) and partial remission (PR), respectively; 40.9% (9/22) recipients had progressive disease (PD). Allograft rejection occurred in 45% of patients. In total, seven patients from our center and three from the literature used pretransplant anti-PD-1 antibodies, eight patients (80%) had a PR, and the disease control rate was 100%. Biopsy-proven acute rejection (BPAR) incidence was 30% (3 in 10 patients), two patients died because of BPAR. This indicated that neoadjuvant PD-1-targeted immunotherapy plus tyrosine kinase inhibitors (TKI) exhibited promising efficacy with tolerable mortality in transplant recipients under close clinical monitoring.

Seven lanthanide–organic frameworks [(CeCl2L(phen))2(μ-Cl)2]·CH3CN (1) (L = tetrakis(O-isopropyl)methylenediphosphonate, phen = 1,10-phenanthroline) and [LnCl(H2O)3L(phen)]·nCH3CN (n = 0 for 2, n = 2 for 3, n = 1.5 for 4, n = 0 for 5, n = 1.5 for 6, n = 1.5 for 7) (Ln = Dy, Ho, Er, Tm, Yb, Lu for 2–7, respectively) have been synthesized by the reaction of lanthanide chlorides, the ligand L and phen in acetonitrile at room temperature. These title complexes were characterized by IR, elemental analyses, single-crystal X-ray diffraction analysis, luminescence, thermal analysis, 1H NMR and 31P NMR spectroscopy. The complex [(CeCl2Lphen)2(μ-Cl)2]·CH3CN (1) is a dinuclear compound and displays a two-dimensional mesh 63 topology formed by π–π interactions. Complexes 2–7 can be simplified as having a two-dimensional mesh 4.82 topology formed by hydrogen bonds (C–H⋯Cl and O–H⋯Cl). These interesting structures are rarely found. We found a fluorescence quenching phenomenon which may be due to the presence of crystalline water molecules and solvent. Their terahertz (THz) time-domain spectroscopy was also studied.

Background The worsening problems of antibiotic resistance prompt the need for alternative strategies. Baicalin, which is isolated from Scutellaria baicalensisi, has been demonstrated to exhibit anti-inflammatory, anti-virulence and antimicrobial effects. Salmonella typhimurium is an important foodborne pathogenic bacteriaum that causes gastrointestinal disease in humans and many animals. Purpose The aim of this study was to investigate the effects of baicalin on S. typhimurium infection in mice and its possible mechanism in vitro. Study design To evaluate the effect of baicalin in vivo, mice were orally administered of baicalin, and then were infected by an intragastric administration of S. typhimurium. The minimal inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of baicalin, baicalein, and oroxylin A against S. typhimurium were detected under the guides of the Clinical and Laboratory Standards Institute. In vitro, Caco-2 cells were infected with S. typhimurium in the presence or absence of baicalin, baicalein, and oroxylin A at sub-MICs. Methods In the in vivo experiment, the body weight loss, the serum levels of TNFα, IL-6, and lactic dehydrogenase (LDH), the pathological changes of the caecum and the caecum bacterial burdens were examined. The MICs and MBCs of baicalin, baicalein, and oroxylin A against S. typhimurium were detected by two-fold serial dilutions. In vitro, Caco-2 cells were infected with S. typhimurium, and the invasion capacity, TNFα, nitrate, and LDH were analysed. The transcription levels of Salmonella pathogenicity island 1 virulence associated genes (sopB, sopE, sopE2) of S. typhimurium in the presence of baicalin, baicalein, and oroxylin A were detected by qRT-PCR. Results Our results showed that baicalin significantly decreased the body weight loss, the serum levels of TNFα, IL-6, and LDH, and the caecum bacterial burdens of mice challenged with S. typhimurium. Histological examination showed that baicalin decreased the lesion in the caecum of S. typhimurium-infected mice. MICs and MBCs of baicalin, and oroxylin A. against S. typhimurium were > 128 µg/ml. MICs and MBCs of baicalein against S. typhimurium were 64 µg/ml, and > 128 µg/ml, respectively. Pretreatment of Caco-2 cells or S. typhimurium with baicalin, baicalein, and oroxylin A significantly inhibited the invasion of Caco-2 cells by S. typhimurium in a dose-dependent manner. Sub-MICs of baicalin, baicalein, and oroxylin A also significantly decreased the levels of TNFα, nitrate, and LDH from S. typhimurium-infected Caco-2 cells. Moreover, the transcription levels of sopB, sopE, and sopE2 were significantly suppressed by baicalin, baicalein, and oroxylin A. Conclusions These results demonstrated that baicalin is a promising agent for the prevention of S. typhimurium infection via the modulation of both bacterial virulence and host response.