A novel two-step administration of XPO-1 inhibitor may enhance the effect of anti-BCMA CAR-T in relapsed/refractory extramedullary multiple myeloma.

BACKGROUND: Extramedullary disease usually implies a dismal outcome in relapsed/refractory multiple myeloma patients, and requires novel treatment approaches. We designed a trial using Selinexor, a nuclear export protein 1 inhibitor, together with anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell product CT103A to treat these patients, and describe the first two cases in this report. METHODS: Selinexor was administered with a novel two-step schedule in bridging therapy and in maintenance. The clinical responses and adverse events were recorded after CAR-T infusion and Selinexor administration. In vitro analysis of the influence of Selinexor on CAR-T cell function was performed using myeloma cell lines. RESULTS: After infusion, both patients achieved stringent complete remission (sCR), and were maintained in sCR at data-cutoff, with survival over 13 and 10 months, respectively. Neither immune effector cell-associated neurotoxicity syndrome nor over grade 2 cytokine release syndrome was observed. Meanwhile, the patients showed good tolerance to the combination. In addition, we demonstrated that low dose of Selinexor could upregulate the expression of BCMA on plasma cell lines and subsequently enhance the function of CAR-T cell in vitro. CONCLUSIONS: The combination of Selinexor and CT103A exerts preliminary synergistic effect, and can be developed as a promising strategy for relapsed/refractory extramedullary myeloma.

The exploration of B cell maturation antigen expression in plasma cell dyscrasias beyond multiple myeloma.

BACKGROUND: B cell maturation antigen (BCMA) targeted immunotherapies have demonstrated remarkable clinical efficacy in multiple myeloma (MM). Here, we evaluated the BCMA expression in MM and other plasma cell dyscrasias (PCDs), hoping to provide a potential treatment strategy for the relapsed/refractory PCDs besides MM. METHODS: From January 2018 to August 2021, 377 patients with PCDs were enrolled in this study, including 334 MM, 21 systemic light chain amyloidosis (AL), 5 POEMS syndrome, 14 monoclonal gammopathy of undetermined significance (MGUS), and three monoclonal gammopathy of renal significance (MGRS). The membrane-bound BCMA expression measured by multiparameter flow cytometry was defined by BCMA positivity rate and the mean fluorescence intensity (MFI). RESULTS: The patients with MM had a median BCMA positive rate of 88.55% (range, 0.2% - 99.9%) and median BCMA MFI of 1281 (range, 109 - 48586). While the median BCMA positive rate in other PCDs was 55.8% (6.2% -98.9%), and the median BCMA MFI was 553 (182- 5930). BCMA expression level was negatively associated with hemoglobin concentration in multivariate analysis in terms of BCMA positive rate and MFI. CONCLUSIONS: In conclusion, BCMA has the potential to be a therapeutic target for other PCDs besides MM.

Mutations in immunodeficiency-related genes may increase the risk of infection after CAR-T-cell therapy: a report of two cases.

BACKGROUND: Chimeric antigen receptor T-cell therapy (CAR-T) has yielded unprecedented efficacy in B-cell malignancies. With the increasing use of CAR-T-cell therapy, infection has become one of the major concerns after CAR-T-cell infusion. Some patients even develop refractory or recurrent infections, posing challenges in treatment, prophylactic, and monitoring strategies. However, the mechanisms underlying the development of these infections were not clear. CASE PRESENTATION: We report two cases of infection after CAR-T-cell therapy. Patient 1, diagnosed with multiple myeloma, received anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T)-cell therapy. He developed a refractory urinary infection lasting for over 5 weeks, which was caused by Candida albicans. Whole-exome sequencing revealed that he had an IL-17RA gene mutation. Patient 2, diagnosed with acute lymphoblastic B-cell leukaemia, received anti-CD19 and anti-CD22 CAR-T-cell cocktail therapy and remained in complete remission for over 4 years. The patient had pneumonia five times during the 4 years. Whole-exon sequencing revealed that he had a CX3CR1 gene mutation. CONCLUSION: For patients who develop persistent or recurrent infections after CAR-T-cell therapy, it is recommended to screen for immunodeficiency-related gene mutations, and the results may contribute to the management of infections post-CAR-T treatment.

Effect of Different Types of Ossification of the Posterior Longitudinal Ligament on the Dynamic Biomechanical Response of the Spinal Cord: A Finite Element Analysis.

Ossification of the posterior longitudinal ligament (OPLL) has been identified as an important cause of cervical myelopathy. However, the biomechanical mechanism between the OPLL type and the clinical characteristics of myelopathy remains unclear. The aim of this study was to evaluate the effect of different types of OPLL on the dynamic biomechanical response of the spinal cord. A three-dimensional finite element model of the fluid-structure interaction of the cervical spine with spinal cord was established and validated. The spinal cord stress and strain, cervical range of motion (ROM) in different types of OPLL models were predicted during dynamic flexion and extension activity. Different types of OPLL models showed varying degrees of increase in stress and strain under the process of flexion and extension, and there was a surge toward the end of extension. Larger spinal cord stress was observed in segmental OPLL. For continuous and mixed types of OPLL, the adjacent segments of OPLL showed a dramatic increase in ROM, while the ROM of affected segments was limited. As a dynamic factor, flexion and extension of the cervical spine play an amplifying role in OPLL-related myelopathy, while appropriate spine motion is safe and permitted. Segmental OPLL patients are more concerned about the spinal cord injury induced by large stress, and patients with continuous OPLL should be noted to progressive injuries of adjacent level.

Preliminary Study on Insecticidal Potential and Chemical Composition of Five Rutaceae Essential Oils against Thrips flavus (Thysanoptera: Thripidae).

To meet the demand for novel pest management strategies to combat the development of insecticide resistance, plant essential oils may be a promising alternative source. This study investigated the insecticidal activity of five essential oils from the Rutaceae plant family against Thrips flavus Schrank (Thysanoptera: Thripidae) under laboratory conditions. The plant essential oils were citrus oil (Citrus reticulata Blanco), Chuan-shan pepper oil (Zanthoxylum piasezkii Maxim.), zanthoxylum oil (Zanthoxylum bungeanum Maxim.), pomelo peel oil (Citrus maxima (Burm.) Merr.) and orange leaf oil (Citrus sinensis (L.) Osbeck). Among the essential oils evaluated, orange leaf oil (LC50 = 0.26 g/L), zanthoxylum oil (LC50 = 0.27 g/L), and pomelo peel oil (LC50 = 0.44 g/L) resulted in a higher gastric toxicity under laboratory conditions. The results of the pot experiment also showed that orange leaf oil (93.06 ± 3.67% at 540.00 g a.i.·hm-2, 97.22 ± 1.39% at 720 g a.i.·hm-2, 100.00% at 900.00 g a.i.·hm-2) zanthoxylum oil (98.73 ± 1.27% at 900 g a.i.·hm-2), and pomelo peel oil (100.00% at 900 g a.i.·hm-2) exhibited a higher control efficacy, being the most effective against T. flavus after 7 days of treatment. The essential oil components were then identified by gas chromatography-mass spectrometry (GC-MS). The insecticidal activity of orange leaf oil, pomelo peel oil, and zanthoxylum oil could be attributed to their main constituents, such as methyl jasmonate (50.92%), D-limonene (76.96%), and linalool (52.32%), respectively. In the olfactory test, adult T. flavus were attracted by zanthoxylum oil and Chuan-shan pepper oil. We speculated that linalool might be the key signaling compound that attracts T. flavus. These results showed that orange leaf oil, zanthoxylum oil, and pomelo peel oil exhibited insecticidal activities under controlled conditions. They can be implemented as effective and low-toxicity botanical insecticides and synergistic agents against T. flavus.

Exosomes derived from miR-155-5p-overexpressing synovial mesenchymal stem cells prevent osteoarthritis via enhancing proliferation and migration, attenuating apoptosis, and modulating extracellular matrix secretion in chondrocytes.

Synovial mesenchymal stem cells (SMSCs) have the potential to attenuate osteoarthritis (OA)-induced injury. The role and mechanism of SMSC-derived exosomes (SMSC-Exos), pivotal paracrine factors of stem cells, in OA-associated injury remain unclear. We aimed to confirm the effect of SMSC-Exos with specific modifications on OA-induced damage and to investigate the potential molecular mechanisms. Exosomes derived from miR-155-5p-overexpressing SMSCs (SMSC-155-5p-Exos) and SMSCs (SMSC-Exos) were isolated and characterized. CCK-8, Transwell, and Western blot analyses were used to detect proliferation, migration, extracellular matrix (ECM) secretion, and apoptosis of osteoarthritic chondrocytes. The therapeutic effect of exosomes in a mouse model of OA was examined using immunohistochemical staining and OARSI scores. SPSS 17.0 and GraphPad software were used for all statistical analyses in this study. The SMSC-Exos enhanced the proliferation and migration and inhibited the apoptosis of osteoarthritic chondrocytes but had no effect on ECM secretion. The miR-155-5p-overexpressing exosomes showed common characteristics of exosomes in vitro and further promoted ECM secretion by targeting Runx2. Thus, the SMSC-155-5p-Exos promoted proliferation and migration, suppressed apoptosis and enhanced ECM secretion of osteoarthritic chondrocytes, and effectively prevented OA in a mouse model. In addition, overexpression of Runx2 partially reversed the effect of the SMSC-155-5p-Exos on osteoarthritic chondrocytes. Given the insufficient effect of the SMSC-Exos on the ECM secretion of osteoarthritic chondrocytes, we modified the SMSM-Exos and demonstrated that the SMSC-155-5p-Exos could prevent OA. Exosomes derived from modified SMSCs may be a new treatment strategy to prevent OA. Graphical abstract.

Relaxin inhibits patellar tendon healing in rats: a histological and biochemical evaluation.

BACKGROUND: Female patients are more likely to have tendon injuries than males, especially those who has a higher concentration of relaxin. Previous studies have demonstrated that relaxin attenuates extracellular matrix (ECM) formation. However, the mechanism of relaxin on tendon repair remains unclear. We hypothesize that relaxin inhibits tendon healing by disrupting collagen synthesis. METHODS: A patellar tendon window defect model was established using Sprague-Dawley rats. The center of the patellar tendon was removed from the patella distal apex and inserted to the tibia tuberosity in width of 1 mm. Then, the rats were injected with saline (0.2 µg/kg/day) or relaxin (0.2 µg/kg/day) for two and four weeks, which was followed by biomechanical analysis and histological and histochemical examination. RESULTS: Mechanical results indicated that relaxin induces a significant decrease in tear resistance, stiffness, and Young's modulus compared to those rats without relaxin treatment. In addition, it was shown that relaxin activates relaxin family peptide receptor 1(RXFP1), disturbs the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteases (TIMPs), and reduces the deposition of collagen in injury areas. CONCLUSIONS: Relaxin impairs tendon healing in rats. Also, relaxin might lead to tendon injury more commonly for females than males.

Raman and SERS spectra of thiamethoxam and the Ag3-thiamethoxam complex: an experimental and theoretical investigation.

The insecticide thiamethoxam (TMX) is one of the most important neonicotinoid pesticides. The chromatographic methods currently employed to detect TMX require multiple operational steps. This study proposes a simple method that detects TMX via surface-enhanced Raman scattering (SERS) spectroscopy with Ag nanoparticles (NPs) as the SERS active substrate. Density functional theory (DFT) was used to calculate the structures and vibrational modes of the Ag- and Ag3-TMX complexes at the B3LYP/6-311++G(d,p)(C,H,N)/LanL2DZ(Ag) level of theory. The results reveal that the atoms in the thiazole ring all lie in the same plane, while the six-membered ring is perpendicular to the thiazole ring. Data from both Ultraviolet-visible and Raman spectroscopy indicated that TMX bonds to Ag through its nitro group, vertically. A weak intramolecular (N22-O23…H26) hydrogen bonding and Ag-O bands shift N-O symmetrical vibration to down to lower wavenumber. This was supported by the appearance of a strong 866 cm-1 band in the SERS spectrum assigned to the N-O symmetrical vibration coupled with the N-N stretching vibrational mode of different excitation wavelength. Notably, a good linear relationship was observed in the TMX concentration range 1.0 × 10-6-1.0 × 10-4 mol·L-1 (R2 = 0.9667). SERS is an extremely simple and rapid technique that requires little sample for analysis.

Structure information analysis and relative content determination of protein and chitin from yellow mealworm larvae using Raman spectroscopy.

Insect protein extract is one of the high-quality protein sources and is frequently viewed as a potential nutrition alternative. However, a more precise method for protein measurement is still needed due to protein overestimation by the Kjeldahl method due to the presence of a large amount of chitin in insects. Therefore, we demonstrated the monitoring of chitin and protein extracted from yellow mealworm larvae through the information on molecular vibration obtained using Raman spectroscopy and infrared (IR) spectroscopy. The NH vibration at 3475 cm-1 is the characteristic peak of chitin in defatted product observed in the Raman spectra. The nitrogen-to-protein conversion factor in protein extracted from larvae by the Raman method was determined based on the NH vibration and found to be 5.66 ± 0.01. We also compared these experimental data to theoretical Raman and IR spectra and determined the possible reasons for why nitrogen elements in chitin affect the determination of protein content. The method of sequentially removing fat and protein could provide more accurate quantification of protein and chitin. Raman spectroscopy is feasible for various types of insects with high chitin content. Compared with the Kjeldahl method, the Raman method is a faster and more accurate measurement method. Moreover, it provides the content of impurities, purity, and structural information.

Se site targeted-two circles antioxidant in GPx4-like catalytic peroxide degradation by polyphenols (-)-epigallocatechin gallate and genistein using SERS.

A Se site targeted-two circles antioxidant of polyphenols EGCG and genistein in glutathione peroxidase 4 (GPx4)-like catalytic peroxide H2O2 and cumene hydroperoxide degradation was demonstrated by surface-enhanced Raman scattering (SERS). Se atom's active center is presenting a 'low-oxidation' and a 'high-oxidation' catalytic cycle. The former is oxidized to selenenic acid (SeO-) with a Raman bond at 619/ 610 cm-1 assigned to the νO - Se by the hydroperoxide substrate at 544/ 551 cm-1 assigned to ωHSeC decreased. Under oxidative stress, the enzyme shifted to 'high-oxidation' catalytic cycle, in which GPx4 shuttles between R-SeO- and R-SeOO- with a Raman intensity of bond at 840/ 860 cm-1 assigned to νO[bond, double bond]Se. EGCG could act as a reducing agent both in H2O2 and Cu-OOH degradation, while, genistein can only reduce Cu-OOH, because it binds more readily to the selenium site in GPx4 than EGCG with a closer proximity, therefore may affect its simultaneous binding to coenzymes.

Egg White Peptides Accelerating the Wound Healing Process Through Modulating the PI3K-AKT Pathway: A Joint Analysis of Transcriptomic and Proteomic.

Wound healing is a multiphase process with a complex repair mechanism; trauma-repairing products with safety and high efficiency have a great market demand. Egg white peptides (EWP) have various physiological regulatory functions and have been proven efficient in ameliorating skin damage. However, their underlying regulation mechanism has not been revealed. This study further evaluated the EWP ameliorating mechanism by conducting a full-thickness skin wound model. Results demonstrated that EWP administration significantly inhibited the expression of pro-inflammatory and shortened the inflammatory phase. Besides, EWP can accelerate the secretion of growth factors (PDGF, VEGF, and TGF-ß1) in skin tissue, significantly increasing the regeneration of granulation tissue and endothelium in the proliferation phase, thereby promoting wound healing. After 400 mg/kg EWP interventions for 13 days postoperation, the wound healing rate reached 90%. The combination of transcriptomic and proteomic analyses demonstrated the ameliorating efficiency effects of EWP on wound healing. EWP mainly participates in the functional network with the PI3K-AKT signaling pathway as the core to accelerate wound healing. These findings suggest a promising EWP-based strategy for accelerating wound healing.

CS1 Expression Pattern in NK Cells and Correlated Factors in Plasma Cell dyscrasias: Implications for Elotuzumab Therapy and CAR-T Efficacy.

Treatment with elotuzumab alone has no discernible antitumor effect and progress in chimeric antigen receptor T cells (CAR-T) therapy targeting CS1 is relatively slow. A retrospective analysis was performed on 236 patients with multiple myeloma (MM) and 30 patients with other plasma cell dyscrasias (PCDs). CS1 expression in NK cells, lymphocytes, and monoclonal plasma cells was assessed using multiparameter flow cytometry. Furthermore, new explorations were undertaken regarding the antitumor applications of elotuzumab. Patients with MM had significantly higher CS1 expression levels in plasma cells than other patients with PCDs, with no significant differences between lymphocytes and NK cells. In both patients with MM and other PCDs, CS1 expression was significantly higher in plasma cells than in NK cells and lymphocytes. Univariate and multivariate analyses revealed a significant correlation between CS1 expression in plasma (r = 0.60; P < 0.001) and NK (r = 0.79; P < 0.001) cells. Factors such as cytogenetic abnormalities, disease progression, and survival were not associated with CS1 expression in NK cells. Moreover, this study showed that elotuzumab strongly increases the cytotoxicity of NK cells against non-plasma and plasma tumor cells independent of their CS1 expression level. This underscores the potential of elotuzumab in combination with NK cells as an effective therapeutic strategy against a broad spectrum of tumor types.

Finite element modeling and analysis of effect of preexisting cervical degenerative disease on the spinal cord during flexion and extension.

Recent studies have emphasized the importance of dynamic activity in the development of myelopathy. However, current knowledge of how degenerative factors affect the spinal cord during motion is still limited. This study aimed to investigate the effect of various types of preexisting herniated cervical disc and the ligamentum flavum ossification on the spinal cord during cervical flexion and extension. A detailed dynamic fluid-structure interaction finite element model of the cervical spine with the spinal cord was developed and validated. The changes of von Mises stress and maximum principal strain within the spinal cord in the period of normal, hyperflexion, and hyperextension were investigated, considering various types and grades of disc herniation and ossification of the ligamentum flavum. The flexion and extension of the cervical spine with spinal canal encroachment induced high stress and strain inside the spinal cord, and this effect was also amplified by increased canal encroachments and cervical hypermobility. The spinal cord might evade lateral encroachment, leading to a reduction in the maximum stress and principal strain within the spinal cord in local-type herniation. Although the impact was limited in the case of diffuse type, the maximum stress tended to appear in the white matter near the encroachment site while compression from both ventral and dorsal was essential to make maximum stress appear in the grey matter. The existence of canal encroachment can reduce the safe range for spinal cord activities, and hypermobility activities may induce spinal cord injury. Besides, the ligamentum flavum plays an important role in the development of central canal syndrome.Significance. This model will enable researchers to have a better understanding of the influence of cervical degenerative diseases on the spinal cord during extension and flexion.

PtbNet: Based on Local Few-Shot Classes and Small Objects to accurately detect PTB.

Pulmonary Tuberculosis (PTB) is one of the world's most infectious illnesses, and its early detection is critical for preventing PTB. Digital Radiography (DR) has been the most common and effective technique to examine PTB. However, due to the variety and weak specificity of phenotypes on DR chest X-ray (DCR), it is difficult to make reliable diagnoses for radiologists. Although artificial intelligence technology has made considerable gains in assisting the diagnosis of PTB, it lacks methods to identify the lesions of PTB with few-shot classes and small objects. To solve these problems, geometric data augmentation was used to increase the size of the DCRs. For this purpose, a diffusion probability model was implemented for six few-shot classes. Importantly, we propose a new multi-lesion detector PtbNet based on RetinaNet, which was constructed to detect small objects of PTB lesions. The results showed that by two data augmentations, the number of DCRs increased by 80% from 570 to 2,859. In the pre-evaluation experiments with the baseline, RetinaNet, the AP improved by 9.9 for six few-shot classes. Our extensive empirical evaluation showed that the AP of PtbNet achieved 28.2, outperforming the other 9 state-of-the-art methods. In the ablation study, combined with BiFPN+ and PSPD-Conv, the AP increased by 2.1, APs increased by 5.0, and grew by an average of 9.8 in APm and APl. In summary, PtbNet not only improves the detection of small-object lesions but also enhances the ability to detect different types of PTB uniformly, which helps physicians diagnose PTB lesions accurately. The code is available at https://github.com/Wenhui-person/PtbNet/tree/master.

Improving the performance of perovskite solar cells using a dual-hole transport layer.

The energy loss (Eloss) caused by inefficient charge transfer and large energy level offset at the buried interface can easily restrict the performance of p-i-n perovskite solar cells (PVSCs). In this study, the utilization of poly-TPD and P3CT-N as a dual-hole transporting layer (HTLs) was implemented in a sequential manner. This approach aimed to improve the charge transfer efficiency of the HTL and mitigate charge recombination at the interface between the HTL and PVK. The results showed that this strategy also could achieve more suitable energy levels, improve the quality of the perovskite film layer, and ultimately enhance the device's stability. IPVSCs employing the dual-HTLs approach exhibited the highest power conversion efficiency of 19.85%, and the open-circuit voltage increased to 1.09 V from 1.00 V. This study offers a straightforward and efficient approach to boost the device performance by minimizing Eloss and reducing the buried interfacial defects. The findings underscore the potential of employing a dual-HTL strategy as a promising pathway for further advancements in PVSCs.

Case report: Light-chain amyloidosis responsive to selinexor in combination with daratumumab and dexamethasone (SDd) therapy.

The outcome of AL amyloidosis remains poor, particularly in patients with advanced organ involvement which takes long time to recovery. We conducted an observational study of two patients with AL amyloidosis treated with SDd regimen. Both patients successfully achieved significant hematological and organ responses without severe adverse events, and the time to organ response was remarkably shorter than previously reported. Notably, an over 15% reduction in interventricular septal thickness (IVST) was observed in patient#2 within 6 months. Up to now, SDd therapy has not been previously reported in AL amyloidosis and may be a promising option for these patients.

Quality characteristic of spray-drying egg white powders.

Spray drying is a useful method for developing egg process and utilization. The objective of this study was to evaluate effects on spray drying condition of egg white. The optimized conditions were spraying flow 22 mL/min, feeding temperature 39.8 °C and inlet-air temperature 178.2 °C. Results of sulfydryl (SH) groups measurement indicated conformation structure have changed resulting in protein molecule occur S-S crosslinking phenomenon when heating. It led to free SH content decreased during spray drying process. There was almost no change of differential scanning calorimetry between fresh egg white and spray-drying egg white powder (EWP). For a given protein, the apparent SH reactivity is in turn influenced by the physico-chemical characteristics of the reactant. The phenomenon illustrated the thermal denaturation of these proteins was unrelated to their free SH contents. Color measurement was used to study browning level. EWP in optimized conditions revealed insignificant brown stain. Swelling capacity and scanning electron micrograph both proved well quality characteristic of spray-drying EWP. Results suggested spray drying under the optimized conditions present suitable and alternative method for egg processing industrial implementation. Egg food industrialization needs new drying method to extend shelf-life. The purpose of the study was to provide optimal process of healthy and nutritional instant spray-drying EWP and study quality characteristic of spray-drying EWP.

U-MLP: MLP-based ultralight refinement network for medical image segmentation.

The convolutional neural network (CNN) and Transformer play an important role in computer-aided diagnosis and intelligent medicine. However, CNN cannot obtain long-range dependence, and Transformer has shortcomings in computational complexity and a large number of parameters. Recently, compared with CNN and Transformer, the Multi-Layer Perceptron (MLP)-based medical image processing network can achieve higher accuracy with smaller computational and parametric quantities. Hence, in this work, we propose an encoder-decoder network, U-MLP, based on the ReMLP block. The ReMLP block contains an overlapping sliding window mechanism and a Multi-head Gate Self-Attention (MGSA) module, where the overlapping sliding window can extract local features of the image like convolution, then combines MGSA to fuse the information extracted from multiple dimensions to obtain more contextual semantic information. Meanwhile, to increase the generalization ability of the model, we design the Vague Region Refinement (VRRE) module, which uses the primary features generated by network inference to create local reference features, thus determining the pixel class by inferring the proximity between local features and labeled features. Extensive experimental evaluation shows U-MLP boosts the performance of segmentation. In the skin lesions, spleen, and left atrium segmentation on three benchmark datasets, our U-MLP method achieved a dice similarity coefficient of 88.27%, 97.61%, and 95.91% on the test set, respectively, outperforming 7 state-of-the-art methods.

Potential Benefits of Egg White Proteins and Their Derived Peptides in the Regulation of the Intestinal Barrier and Gut Microbiota: A Comprehensive Review.

Impaired intestinal barrier function can impede the digestion and absorption of nutrients and cause a range of metabolic disorders, which are the main causes of intestinal disease. Evidence suggests that proper dietary protein intake can prevent and alleviate intestinal diseases. Egg white protein (EWP) has received considerable attention, because of its high protein digestibility and rich amino acid composition. Furthermore, bioactive peptides may have an increased repair effect due to their high degradation efficiency in the gut. In this study, we aimed to review the effects of EWP and its bioactive peptides on intestinal structural repair. The potential modulation mechanisms by which EWP and their peptides regulate the gut microbiota and intestinal barrier can be summarized as follows: (1) restoring the structure of the intestinal barrier to its intact form, (2) enhancing the intestinal immune system and alleviating the inflammatory response and oxidative damage, and (3) increasing the relative abundance of beneficial bacteria and metabolites. Further in-depth analysis of the coregulation of multiple signaling pathways by EWP is required, and the combined effects of these multiple mechanisms requires further evaluation in experimental models. Human trials can be considered to understand new directions for development.

Recovery-model: A model for CAR T-cell-related thrombocytopenia in relapsed/refractory multiple myeloma.

BACKGROUND: Patients with multiple myeloma (MM) treated with anti-B cell maturation antigen (BCMA) and chimeric antigen receptor (CAR) T-cell therapy tend to show delayed platelet recovery. PATIENTS AND METHODS: This single-center retrospective observational study included a cohort of patients with MM treated with anti-BCMA CAR-T cells in ChiCTR-OPC-16009113, ChiCTR1800018137, and ChiCTR1900021153. RESULTS: Fifty-eight patients with MM treated with anti-BCMA CAR-T cells were included. Delayed platelet recovery (platelet count not recovering to 50 × 109/L within 28 days) was observed in 36 % of patients. Regression analysis identified several factors that influenced platelet recovery, and accordingly, a Recovery-Model was developed. A high Recovery-Model score indicates a greater risk of delayed platelet recovery after CAR-T cell infusion and reflects the risk of hematologic toxicity. The model's predictive biomarkers included baseline platelet count, baseline hemoglobin level, logarithm of baseline Ferritin level, and cytokine release syndrome grade. Finally, survival analysis showed a significant relationship between overall survival, delayed platelet recovery (p = 0.0457), and a high Recovery-Model score (p = 0.0011). CONCLUSIONS: Inflammation-related factors and bone marrow reserves are associated with delayed platelet recovery. Therefore, we developed a model to predict the risk of delayed platelet recovery and hematological toxicity in relapsed/refractory patients with MM after anti-BCMA CAR-T cell treatment.