CD19-CAR-DNT cells (RJMty19) in patients with relapsed or refractory large B-cell lymphoma: a phase 1, first-in-human study.

Background: Current approved chimeric antigen receptor (CAR) T-cell products are autologous cell therapies that are costly and poorly accessible to patients. We aimed to evaluate the safety and antitumor activity of a novel off-the-shelf anti-CD19 CAR-engineered allogeneic double-negative T cells (RJMty19) in patients with relapsed/refractory large B-cell lymphoma. We report the results from a first-in-human, open-label, single-dose, phase 1 study of allogeneic CD19-specific CAR double-negative T (CAR-DNT) cells. Methods: Eligibility criteria included the presence of measurable lesions, at least 2 lines of prior immunochemotherapy, and an ECOG score of 0-1. We evaluated four dose levels (DL) of RJMty19 in a 3 + 3 dose-escalation scheme: 1 × 106, 3 × 106, 9 × 106 and 2 × 107 CAR-DNT cells per kilogram of body weight. All patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide. The primary endpoints were dose-limiting toxicities (DLTs), incidence of adverse events (AEs), and clinically significant laboratory abnormalities. Secondary endpoints included evaluation of standard cellular pharmacokinetic parameters, immunogenicity, objective response rates (ORR), and disease control rate (DCR) per Lugano 2014 criteria. Findings: A total of 12 patients were enrolled between 22 July 2022 and 27 July 2023. Among these patients, 66% were classified as stage IV, 75% had an IPI score of 3 or higher, representing an intermediate risk or worse. The maximum tolerated dose was not reached because no DLT was observed. Four patient experienced grade 1 or 2 cytokine release syndrome and dizziness. The most common AEs were hematologic toxicities, including neutropenia (N = 12, 100%), leukopenia (N = 12, 100%), lymphopenia (N = 10, 83%), thrombocytopenia (N = 6, 50%), febrile neutropenia (N = 3, 25%), and anemia (N = 3, 25%). Seven subjects died till the cut-off date, five of them died of disease progression and two of them died of COVID 19. In all patients (N = 12), the ORR was 25% and CRR was 8.3%. DL1 and DL2 patients benefited less from the therapy (ORR: 17%, N = 1; DCR: 33%, N = 2). However, all DL3 patients achieved disease control (N = 3, 100%), and all DL4 patients achieved objective response (N = 3, 100%). Interpretation: Our results demonstrate that CD19-CAR-DNT cells appear to be well tolerated with promising antitumor activity in LBCL patients. Further study of this product with a larger sample size is warranted. This phase 1 study is registered on clinicaltrials.gov (NCT05453669). Funding: Wyze Biotech. Co., Ltd.

Comparison of long-term outcomes between imatinib and dasatinib prophylaxis after allogeneic stem cell transplantation in patients with Philadelphia-positive acute lymphoblastic leukemia: A multicenter retrospective study.

BACKGROUND: Although the prognosis of Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) has improved with the introduction of tyrosine kinase inhibitors (TKIs) and stem cell transplantation, prevention of relapse after transplantation remains a concern. The aim of this study was to compare the impact of TKI prophylaxis with imatinib and dasatinib on long-term outcomes after transplantation. METHODS: Patients with Ph+ ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at first complete remission (CR1) and received TKI prophylaxis after allo-HSCT were included in this retrospective analysis. Two cohorts were established based on the choice of TKI prophylaxis: the imatinib (Ima) and dasatinib (Das) cohorts. The survival and safety outcomes of these cohorts were compared. RESULTS: Ninety-one patients in the Ima cohort and 50 in the Das cohort were included. After a median follow-up of 50.6 months, the 5-year cumulative incidence of relapse, nonrelapse mortality rate, and overall survival in the Ima and Das cohorts were 16.1% and 12.5%, 5.2% and 9.8%, and 86.5% and 77.6%, respectively, with no statistical differences. The cumulative incidence of mild chronic graft-versus-host disease was higher in the Das cohort. The most common adverse event was neutropenia (64.7% vs. 69.5%). The Das cohort had a higher incidence of gastrointestinal bleeding (25.5% vs. 2.3%) and gastrointestinal reaction (48.9% vs. 31.4%) than the Ima cohort. The proportion of patients treated on schedule was significantly lower in the Das cohort than in the Ima cohort, and drug intolerance was the main reason for protocol violation. CONCLUSIONS: For patients with Ph+ ALL undergoing allo-HSCT in CR1, imatinib prophylaxis achieved long-term outcomes similar to those of dasatinib.

Case Report: Radiation necrosis mimicking tumor progression in a patient with extranodal natural killer/T-cell lymphoma.

Radiation-induced cerebral necrosis, also known as radiation encephalopathy, is a debilitating condition that significantly impacts the quality of life for affected patients. Secondary central nervous system lymphoma (SCNSL) typically arises from highly aggressive mature B-cell lymphoma, but rarely from extranodal natural killer T-cell lymphoma (ENKTL). Treatment will be guided by differentiation between lymphoma progression from brain necrosis, and is particularly important for critically ill patients in an acute setting. However, differential diagnosis remains challenging because they share similar clinical manifestations and have no specific imaging features. We present the case of a 52-year-old man with ENKTL who suffered an emergency brain herniation secondary to massive radiation necrosis. The diagnosis established by brain biopsy ultimately led to appropriate treatment. The importance of the diagnostic biopsy is highlighted in this case for distinguishing between radiation necrosis and SCNSL.

Effect of Lactylated Gluten and Freeze-Thaw Cycles on Frozen Dough: From Water State and Microstructure.

The influence of lactylated gluten and Freeze-Thaw Cycles on the water state, microstructure, and quality of frozen steamed bread dough was investigated. After three freeze-thaw cycles (3F/T), the specific volume of steamed bread with sodium lactate-treated gluten increased by 18.34% compared with the blank group and 5.73% compared with the wheat gluten (WG) group. Compared with wheat gluten, the texture properties of steamed bread with lactylated gluten increased significantly. Changes in rheological properties demonstrated that the frozen dough's viscoelasticity increased significantly. The lactylated gluten could reduce water mobility and decrease the content of freezable water in frozen dough. Moreover, the free sulfhydryl (SH) content increased, revealing that the protein was depolymerized. Based on the microstructure and corresponding protein network analysis (PNA), the total area and the number of protein network connection points of the dough adding lactylated gluten were significantly higher than those of the blank group and the WG group. In conclusion, lactylated gluten enhanced the freeze-thaw tolerance of frozen dough.

Ssa1-targeted antibody prevents host invasion by Candida albicans.

Introduction: Candida albicans is a commensal fungus that colonizes most healthy individuals' skin and mucosal surfaces but can also cause life-threatening invasive infections, particularly in immunocompromised patients. Despite antifungal treatment availability, drug resistance is increasing, and mortality rates remain unacceptably high. Heat shock protein Ssa1, a conserved member of the Hsp70 family in yeast, is a novel invasin that binds to host cell cadherins, induces host cell endocytosis, and enables C. albicans to cause maximal damage to host cells and induces disseminated and oropharyngeal disease. Result: Here we discovered a mouse monoclonal antibody (mAb 13F4) that targeting C. albicans Ssa1 with high affinity (EC50 = 39.78 ng/mL). mAb 13F4 prevented C. albicans from adhering to and invading human epithelial cells, displayed antifungal activity, and synergized with fluconazole in proof of concept in vivo studies. mAb 13F4 significantly prolonged the survival rate of the hematogenous disseminated candidiasis mice to 75%. We constructed a mAb 13F4 three-dimensional structure using homology modeling methods and found that the antigen-binding fragment (Fab) interacts with the Ssa1 N-terminus. Discussion: These results suggest that blocking Ssa1 cell surface function may effectively control invasive C. albicans infections and provide a potential new treatment strategy for invasive fungal infections.

Mechanism of Action for an All-in-One Monoclonal Antibody Against Staphylococcus aureus Infection.

Staphylococcus aureus is a major human pathogen associated with high mortality rates. The extensive use of antibiotics is associated with the rise of drug resistance, and exotoxins are not targeted by antibiotics. Therefore, monoclonal antibody (mAb) therapy has emerged as a promising solution to solve the clinical problems caused by refractory S aureus. Recent research suggests that the synergistic effects of several cytotoxins, including bicomponent toxins, are critical to the pathogenesis of S aureus. By comparing the amino acid sequences, researchers found that α-toxin and bicomponent toxins have high homology. Therefore, we aimed to screen an antibody, designated an all-in-one mAb, that could neutralize α-toxin and bicomponent toxins through hybridoma fusion. We found that this mAb has a significant pharmacodynamic effect within in vivo mouse models and in vitro experiments.

Long-term survival in a patient with primary refractory AML after salvage allogeneic hematopoietic transplantation and post-transplant localized irradiation and venetoclax maintenance: a case report.

For patients with primary refractory AML, allogeneic hematopoietic cell transplantation (allo-HCT) is considered the only curative approach. However, the therapeutic efficacy of salvage transplantation in the non-remission (NR) state remains controversial. We present a patient with primary refractory AML and concomitant central nervous system (CNS) leukemia, who received salvage allo-HCT, localized radiotherapy and venetoclax maintenance. Although he experienced systemic chronic graft-versus-host disease (cGVHD), he remained disease-free for 2 years. We propose that salvage transplantation is a feasible for primary refractory AML and discuss strategies to prevent relapse after allo-HCT, including maintenance therapy and donor lymphocyte infusion (DLI). Finally, we highlight the importance of radiotherapy, which can exert immunomodulatory effects to enhance immune responses against leukemia.

Case report: Successful treatment of a patient with relapsed/refractory primary central nervous system lymphoma with thiotepa-based induction, autologous stem cell transplantation and maintenance.

Despite significant improvements in prognosis, a subset of patients with primary central nervous system lymphoma (PCNSL) remains at high risk for relapse. The treatment of relapsed and refractory (R/R) PCNSL remains a major clinical challenge. Herein, we present a 24-year-old patient with PCNSL who relapsed 4 years after initial diagnosis and subsequently became refractory to high-dose methotrexate (HD-MTX), temozolomide, whole brain radiation therapy (WBRT), ibrutinib, and lenalidomide. She received thiotepa with anti-programmed cell death protein 1 (PD-1) antibody and achieved partial remission and then underwent autologous stem cell transplantation (ASCT) with thiotepa-based conditioning. Post-transplant maintenance with thiotepa and anti-PD-1 at 3-month intervals resulted in a durable complete response (CR) in this case of R/R PCNSL. Our report highlights the important role of thiotepa in the treatment of patients with R/R PCNSL.

Corrosion behavior of 316 stainless steel arc parts in liquid lead at 650 °C under high oxygen concentrations.

The corrosion of 316SS in contact with lead complicates the realization of high coolant temperature. To explore the corrosion behavior at high temperature, the corrosion test of 316SS was performed in liquid lead at a high temperature of 650 °C under Ar with oxygen levels of 10-2 wt% and 10-5 wt% by the static corrosion method. The mass changes after corrosion were determined; then, the corrosion depth and the oxide product formed were further characterized. A multi-oxide layer was formed on the 316SS alloy surface, and the thickness reached 17.5 µm over a period of 100 h at the oxygen level of ∼10-2 wt%. Fe oxide was the main product in the outer layer; the dense Fe-Cr oxide was formed in the inner layer and lead was isolated from the metal substrate. When the oxygen content was 10-5 wt%, corrosion by dissolution at a rather high rate was dominant, and the corrosion depth was as high as 50 µm for 100 h. It is speculated that the oxide layer is also formed at the initial stage but gets dissociated when there is no oxygen supply to sustain the oxide layer with prolonged exposure time. The oxygen content in the cover gas greatly influences the corrosion behavior of 316SS, thus directly affecting the application of 316SS immersed in liquid lead at high temperature.

Corrosion Behavior of Ti3SiC2 in Flowing Liquid Lead-Bismuth Eutectic at 500 °C.

MAX phases are promising candidate structural materials for lead-cooled fast reactors (LFRs) and accelerator-driven sub-critical systems (ADSs) due to their excellent corrosion resistance in liquid LBE. In this work, one of the typical MAX phases, Ti3SiC2, was exposed to the flowing LBE with a saturated oxygen concentration at 500 °C for up to 3000 h. The corrosion behaviors, including the evolution of the corrosion layer, mechanical properties and wettability, were evaluated via X-ray diffraction, a scanning electron microscope equipped with an energy-dispersive X-ray, a microhardness test and contact angle measurement. The results reveal that a corrosion structure with a duplex layer was formed on the sample surfaces. The outer layer was a diffusion layer, which always remained thin (<3 µm) during the whole test due to the erosion effect caused by the flowing LBE. The inner layer was the stable protective oxide layer, and its thickness increased with exposure time. The growth of the corrosion structure improved the microhardness and reduced the wettability with regard to LBE, which was beneficial to inhibiting further surface corrosion of Ti3SiC2.

Case Report: Primary Cardiac T-Cell Lymphoma With Complete Atrio-Ventricular Block Diagnosed by Endomyocardial Biopsy.

Primary cardiac lymphoma (PCL) is a rare disease, the definite diagnosis of which is sometimes difficult and mainly relies on endomyocardial biopsy. Primary cardiac T-cell lymphoma (PCTL) is an extremely rare sub-type of PCL. Here, we report on a 47-year-old female with PCTL who presented with fever, syncope, palpitations, and a third-degree atrioventricular block (AVB) on electrocardiogram. Chemotherapy was administered with two courses of methotrexate, cyclophosphamide, liposomal doxorubicin, vincristine, and dexamethasone (MTX-CHOP). As the tumor vanished, AVB changed from third degree to second degree and finally to sinus rhythm. In conclusion, endomyocardial biopsy is valuable in the diagnosis of primary cardiac lymphoma. It is worth noting that alterations in the electrocardiogram may indicate an attack on the heart by PCTL.

Potential of Polyethyleneimine as an Adjuvant To Prepare Long-Term and Potent Antifungal Nanovaccine.

Background: Candida albicans infections are particularly prevalent in immunocompromised patients. Even with appropriate treatment with current antifungal drugs, the mortality rate of invasive candidiasis remains high. Many positive results have been achieved in the current vaccine development. There are also issues such as the vaccine's protective effect is not persistent. Considering the functionality and cost of the vaccine, it is important to develop safe and efficient new vaccines with long-term effects. In this paper, an antifungal nanovaccine with Polyethyleneimine (PEI) as adjuvant was constructed, which could elicit more effective and long-term immunity via stimulating B cells to differentiate into long-lived plasma cells. Materials and Methods: Hsp90-CTD is an important target for protective antibodies during disseminated candidiasis. Hsp90-CTD was used as the antigen, then introduced SDS to "charge" the protein and added PEI to form the nanovaccine. Dynamic light scattering and transmission electron microscope were conducted to identify the size distribution, zeta potential, and morphology of nanovaccine. The antibody titers in mice immunized with the nanovaccine were measured by ELISA. The activation and maturation of long-lived plasma cells in bone marrow by nanovaccine were also investigated via flow cytometry. Finally, the kidney of mice infected with Candida albicans was stained with H&E and PAS to evaluate the protective effect of antibody in serum produced by immunized mice. Results: Nanoparticles (NP) formed by Hsp90-CTD and PEI are small, uniform, and stable. NP had an average size of 116.2 nm with a PDI of 0.13. After immunizing mice with the nanovaccine, it was found that the nano-group produced antibodies faster and for a longer time. After 12 months of immunization, mice still had high and low levels of antibodies in their bodies. Results showed that the nanovaccine could promote the differentiation of B cells into long-lived plasma cells and maintain the long-term existence of antibodies in vivo. After immunization, the antibodies in mice could protect the mice infected by C. albicans. Conclusion: As an adjuvant, PEI can promote the differentiation of B cells into long-lived plasma cells to maintain long-term antibodies in vivo. This strategy can be adapted for the future design of vaccines.

Dosimetric advantages of volumetric modulated arc therapy (VMAT) with deep inspiration breath hold (DIBH) technique in Halcyon Linac for left breast cancer treatment.

To evaluate the dosimetric advantages of incorporating the deep inspiration breath hold (DIBH) technique into left breast cancer volumetric modulated arc therapy (VMAT) treatment under Halcyon Linac and to investigate the correlation between mean heart dose (MHD) and distance from the heart to target volumes in left breast cancer VMAT treatment. Fifteen Post-lumpectomy, left-sided breast patients treated between January 2017 and October 2020 were selected. Two plans were generated for each patient using Eclipse treatment planning system (TPS) with the prescription of 50.4 Gy to planning target volume (PTV) breast and 58.8 Gy to PTV boost in 28 fractions. For each patient, DIBH and free breathing (FB) VMAT treatment plans under Halcyon Linac were generated. Dosimetric parameters, monitor unit and beam-on time of both DIBH and FB groups were compared. Three-dimensional distances from heart surface to each target volume were measured on computed tomography images using the TPS contouring tool and their correlation with MHD was evaluated by Pearson's correlation coefficient (r). Comparable target coverage was shown in both groups. Mean dose to heart, left anterior descending artery, and left ventricle in Halcyon-DIBH-VMAT group were significantly reduced by 0.49 Gy, 1.19 Gy, and 0.57 Gy, respectively, compared to Halcyon-FB-VMAT (p < 0.001). A significant lung dose reduction was also achieved in Halcyon-DIBH-VMAT group. There was also a strong negative correlation between MHD and distance from heart surface to PTV boost in both FB and DIBH group (r = -0.741, p < 0.001), but not observed for distance from heart surface to PTV breast. Incorporating DIBH into left breast cancer VMAT treatment under Halcyon Linac demonstrated significant cardiac and lung dose reduction. It was also demonstrated that MHD had a strong negative correlation with distance from heart surface to PTV boost but relatively independent of distance from heart surface to PTV breast. Recognizing the distance from the heart surface to PTV boost as the main factor in affecting MHD could potentially facilitate clinical treatment planning workflow and decision.

(-)-Epigallocatechin-3-gallate plays an antagonistic role in the antitumor effect of bortezomib in myeloma cells via activating Wnt/ß-catenin signaling pathway.

BACKGROUND: (-)-Epigallocatechin-3-gallate (EGCG) is an active constituent of green tea, whose efficacy on chemoprevention and chemotherapy has been extensively researched. Its anticancer potency with low toxicity and easy administration allows for its widespread use. Bortezomib, a proteasome inhibitor, has a significant influence on multiple myeloma (MM) in chemotherapy. Previous studies about the role of EGCG in the antitumor effect induced by bortezomib remain controversial. OBJECTIVES: In our study, the effect of EGCG on the antitumor activity of bortezomib was investigated in myeloma cell lines U266 and RPMI8226, and the underlying mechanism was explored. MATERIAL AND METHODS: The effect of EGCG on the antiproliferative and pro-apoptotic activities of bortezomib were investigated in myeloma cells using MTT assay and cell cycle analysis, respectively. The Wnt/ß-catenin signaling pathway and related proteins were involved in this antagonistic effect and measured with western blot assay. RESULTS: Our results showed the inhibitory activity of EGCG on myeloma cells in a timeand dose-dependent manner. The EGCG neutralized the antiproliferative and pro-apoptotic effect induced by bortezomib by activating Wnt/ß-catenin signaling pathway with the accumulation of ß-catenin. An increase of the downstream target proteins as c-Myc and cyclin D1 was also observed. was also observed. These findings demonstrated the antagonistic role of EGCG in the antitumor effect of bortezomib likely through the activated Wnt/ß-catenin signaling pathway and the upregulated target proteins. CONCLUSIONS: When bortezomib is involved in the MM chemotherapy, the consumption of green tea should be avoided in order to maintain the biological efficacy of bortezomib.

Design, synthesis and preclinical evaluation of bio-conjugated amylinomimetic peptides as long-acting amylin receptor agonists.

Pramlintide is an equipotent amylin analogue that reduces food intake and body weight in obese subjects and has been clinically approved as an adjunctive therapy for the treatment of adult diabetic patients. However, due to its extremely short half-life in vivo, a regimen of multiple daily administrations is required for achieving clinical effectiveness. Herein is described the development of prototypical long-acting pramlintide bioconjugates, in which pramlintide's disulfide-linked macrocycle was replaced by a cyclic thioether motif. This modification enabled stable chemical conjugation to a half-life extending antibody. In contrast to pramlintide (t1/2 < 0.75 h), bioconjugates 35 and 38 have terminal half-lives of ∼2 days in mice and attain significant exposure levels that are maintained up to 7 days. Single dose subcutaneous administration of 35 in lean mice, given 18-20 h prior to oral acetaminophen (AAP) administration, significantly reduced gastric emptying (as determined by plasma AAP levels). In a separate study, similar administration of 35 in fasted lean mice effected a reduction in food intake for up to 48 h. These data are consistent with durable amylinomimetic responses and provide the basis for further development of such long-acting amylinomimetic conjugates for the potential treatment of obesity and associated pathologies.

Estimating the Neovascularity of Human Finger Tendon Through High-Frequency Ultrasound Micro-Doppler Imaging.

OBJECTIVE: Neovascularization of injured tendons prolongs the proliferative phase of healing, but prolonged neovascularization may cause improper healing and pain. Currently, ultrasound Doppler imaging is used for measuring the neovascularization of injured tendons (e.g., Achilles tendon). However, the resolution of state-of-the-art clinical ultrasound machines is insufficient for visualizing the neovascularization in finger tendons. In this study, a high-frequency micro-Doppler imaging (HFµDI) based on 40-MHz ultrafast ultrasound imaging was proposed for visualizing the neovascularization in injured finger tendons during multiple rehabilitation phases. METHOD: The vessel visibility was enhanced through a block-wise singular value decomposition filter and several curvilinear structure enhancement strategies, including the bowler-hat transform and Hessian-based vessel enhancement filtering. HFµDI was verified through small animal kidney and spleen imaging because the related vessel structure patterns of mice are well studied. Five patients with finger tendon injuries underwent HFµDI examination at various rehabilitation phases after surgery (weeks 11-56), and finger function evaluations were performed for comparisons. RESULTS: The results of small animal experiments revealed that the proposed HFµDI provides excellent microvasculature imaging performance; the contrast-to-noise ratio of HFµDI was approximately 15 dB higher than that of the conventional singular value decomposition filter, and the minimum detectable vessel size for mouse kidney was 35 µm without the use of contrast agent. In the human study, neovascularization was clearly observed in injured finger tendons during the early phase of healing (weeks 11-21), but it regressed from week 52 to 56. Finger rehabilitation appears to help reduce neovascularization; neovascular density decreased by approximately 1.8%-8.0% in participants after 4 weeks of rehabilitation. CONCLUSION: The experimental results verified the performance of HFµDI for microvasculature imaging and its potential for injured finger tendon evaluations.

miR-223-3p carried by cancer-associated fibroblast microvesicles targets SORBS1 to modulate the progression of gastric cancer.

BACKGROUND: Cancer-associated fibroblasts (CAFs) aggravate gastric cancer (GC) development. METHODS: Combined with bioinformatics analysis and literature review, miR-223-3p had high expression in microvesicles (MVs) derived from GC CAFs, and it could modulate SORBS1. miR-223-3p and SORBS1 mRNA levels were assessed by qRT-PCR. The levels of CAFs markers, MVs markers, epithelial-mesenchymal transition (EMT)-associated proteins, and SORBS1 protein were assessed by western blot. MVs isolated from fibroblasts were observed by transmission electron microscopy. Combined with immunofluorescence and co-culture experiments, GC cells were determined to absorb MVs carrying miR-223-3p. Cell functions were measured using CCK-8, transwell, flow cytometry and colony formation assays. The binding of miR-223-3p and SORBS1 was determined by dual-luciferase assay and RNA immunoprecipitation. The cancer-promoting effect of MVs carrying miR-223-3p on experimental animals was verified in vivo by tumor-bearing experiment in nude mice. RESULTS: miR-223-3p was upregulated in the MVs secreted by GC CAFs and could be transmitted to GC cells through MVs, to boost the malignant progression of tumor cells. Additionally, it was also revealed that miR-223-3p targeted SORBS1 and accelerated progression along with EMT in GC. CONCLUSIONS: CAFs-derived MVs could carry miR-223-3p to GC cells to target SORBS1, thereby promoting the malignant progression of GC.

An eco-friendly extraction and purification method of nuciferine from Folium nelumbinis with p-sulfonatocalix[6]arenes.

INTRODUCTION: Folium nelumbinis is used as vegetable, functional food and herbal medicine in Asia. p-Sulfonatocalix[6]arene (SC6A) is a water-soluble supramolecular macrocycle and has never been applied to the extraction of herbal products. OBJECTIVE: In this study, SC6A-assisted extraction of nuciferine from Folium nelumbinis has been carried out to develop an eco-friendly extraction process with high extraction efficacy and easy operation. METHODS: Single-factor experiments were adopted to obtain the optimal conditions for the SC6A-assisted extraction of nuciferine from Folium nelumbinis, and then nuciferine and SC6A were separated easily by one-step alkalization. The host-guest complexes between nuciferine and SC6A were analyzed by competitive fluorescence titration, DSC, FT-IR and 1 H-NMR. RESULTS: The optimal SC6A/Folium nelumbinis/solution ratio for extraction was 0.4:1:20 (g/g/mL), with a granulometric fraction below 180 µm and an extraction time of 1 h with soaking. The purity and recovery of nuciferine extracted with SC6A were increased 29.24 and 35.73 times compared with extraction with aqueous solution, respectively. Moreover, a good reusability of SC6A in the extraction of nuciferine was demonstrated. Competitive fluorescence titration, DSC, FT-IR and 1 H-NMR characterization indicated that SC6A could form host-guest complexes with nuciferine at a ratio of 1:1. CONCLUSION: The study provided an eco-friendly, safe and effective nuciferine extraction method, which can be used for the development of nutrition supplements containing nuciferine.

Effectiveness of methylprednisolone therapy in patients with a high-risk common type of COVID-19 pneumonia: a retrospective cohort study.

The optimal timing of glucocorticoid treatment for coronavirus disease 2019 (COVID-19) pneumonia is uncertain. We evaluated the clinical outcomes of methylprednisolone therapy (MPT) for patients with a high-risk common type (HRCT) COVID-19 pneumonia. We conducted a multicenter retrospective cohort study in Northeast China. A comparison was performed between the standard treatment (SDT) group and the SDT + MPT group to determine the efficacy of methylprednisolone in treating HRCT COVID-19 pneumonia. We collected the medical records of 403 patients with HRCT COVID-19 pneumonia (127 in the SDT + MPT group and 276 in the SDT group). None of the patients had received mechanical ventilation or died. Furthermore, there were no side effects associated with MPT. Patients in the SDT + MPT group treated with methylprednisolone received an intravenous injection for a median interval of five days (interquartile range of 3 to 7 days). The trends in lymphocyte count, C-reactive protein, interleukin 6, lactic acid dehydrogenase, respiratory rate, SpO2, PaO2, D-dimer and body temperature were similar between the SDT + MPT and SDT groups. The results for the SDT + MPT group seemed to improve faster than those for the SDT group; however, the results were not statistically significant. Clinical outcomes revealed that the average hospitalized days and the rate of progression to severe type COVID-19 pneumonia in both the SDT + MPT group and the SDT group were 14.56 ± 0.57 days versus 16.55 ± 0.3 days (p = 0.0009) and 21.26% (27/127) versus 32.4% (89/276) (p = 0.0247), respectively. The 16-day nucleic acid negative rate was higher in the SDT + MPT group than in the SDT group, 81.73% (104/127) versus 65.27% (180/276) (p = 0.0006). MPT effectively prevents patients with HRCT COVID-19 pneumonia from progressing to the severe stage.