BACKGROUND:The mechanisms underlying the occurrence of pressure injuries are complex,and it is not entirely clear which factors play a central role in the development of pressure injuries and how these factors operate. OBJECTIVE:To investigate the relationship between Piezo-type mechanosensitive ion channel component 1(Piezo1)and the occurrence of pressure injuries. METHODS:(1)Cellular experiment:Human immortalized keratinocytes(HaCaT)were treated with Yoda1,a Piezo1 agonist,at different concentrations.Cell viability,calcium ion influx,Piezo1,and apoptosis-related protein expression were detected.(2)Animal experiment:Twelve Sprague-Dawley rats were randomly divided into a control group and three experimental groups,with three rats in each group.The control group was not subjected to pressure,while in the three experimental groups,magnets with a thickness of 1,2,and 3 mm were used to press on both sides of the rats'back for 1 hour,respectively,to establish the animal models of pressure injuries.After modeling,all traumatic tissues were excised and subjected to hematoxylin-eosin,Masson,immunofluorescence staining and western blot assay. RESULTS AND CONCLUSION:Cellular experiments:The results of live/dead cell staining showed that HaCaT cell apoptosis increased with the increase of Yoda1 concentration(0,2.5,5,and 10 μmol/L),and calcium ion influx increased with the increase of Yoda1 concentration(0,5,and 10 μmol/L),as well as with the prolongation of treatment time.Western blot assay results showed an increase in the expression of BAX,TG2,and PIEZO1 and a decrease in the expression of the expression of Bcl-2 protein in HaCaT cells in 5 and 10 μmol/L Yoda1 groups compared with the control group(0 μmol/L Yoda1).Animal experiments:The results of hematoxylin-eosin and Masson staining showed that the skin structure of the three experimental groups was damaged at the compression site,there was subcutaneous fat liquefaction and necrosis,and collagen was sparse and disorganized,and damage to the skin structure at the compression site was aggravated with the increase of magnet thickness.Immunofluorescence staining and western blot results showed that compared with the control group,the expression of BAX,TG2,Yap1 and PIEZO1 proteins was elevated,and the expression of Bcl-2 proteins was lowered in the three experimental groups.Moreover,the expression of related proteins showed more significant changes with the increase of magnet thickness(pressure).To conclude,skin compression activates PIEZO1,leading to a significant influx of calcium ions.As the pressure increases,this ultimately results in cell apoptosis due to calcium overload.

BACKGROUND:Although researchers have noted that fibroblast growth factor receptor 1 shows great potential in rheumatoid arthritis bone destruction,there is a lack of reviews related to the potential mechanisms of fibroblast growth factor receptor 1 in rheumatoid arthritis bone destruction. OBJECTIVE:To comprehensively analyze the mechanism of fibroblast growth factor receptor 1 in bone destruction in rheumatoid arthritis by reviewing the relevant literature at both home and abroad. METHODS:We searched the CNKI database using the Chinese search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,bone cells,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,vascular endothelial cells."PubMed database was searched using the English search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,osteocytes,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,endothelial cells."The search period focused on April 1992 to January 2024.After screening the literature by reading titles,abstracts,and full texts,a total of 82 articles were finally included for review according to inclusion and exclusion criteria. RESULTS AND CONCLUSION:Fibroblast growth factor receptor 1 was found to be widely expressed in bone tissue-associated cells,including osteoblasts,osteoclasts,and osteoclasts.Fibroblast growth factor receptor 1 affects bone remodeling and homeostasis by regulating the function of these cells,as well as promoting the onset and progression of bone destruction in rheumatoid arthritis.Fibroblast growth factor receptor 1 is involved in the inflammatory response of synovial fibroblasts and macrophages and regulates angiogenesis of endothelial cells in synovial tissues.Fibroblast growth factor receptor 1 promotes bone destruction in several ways.Fibroblast growth factor receptor 1 may be a potential causative agent of bone destruction in rheumatoid arthritis and provides a reference for further research on its therapeutic targets.

Psoriasis vulgaris is notoriously difficult to treat and prone to recurrence. Traditional Chinese medicine （TCM）， however， has shown considerable efficacy in mitigating or suppressing such recurrence. The underlying reason lies in the TCM concept of "latent pathogens"， which are prone to be reactivated by external pathogenic factors， thereby triggering relapse. At the early stage of recurrence， manifestations of "latent fire" often appear externally. If treatment is not thorough， the condition may shift into a state of "stalemate between healthy Qi and pathogenic factors"， in which the disease appears on the skin but is rooted in deeper pathological layers， remaining unresolved and accumulating internally. Over time， blood stasis arises from fire， and the fire further congeals due to stasis， leading ultimately to recurrent flare-ups. This aligns with the modern immunological concept of "immunological memory" mediated by tissue-resident memory T cells （T_RM） in the skin， which corroborates the TCM view of "latent fire inducing blood stasis". The interaction between T_RM and keratinocytes （KC） parallels the entanglement of latent fire and latent stasis， both of which are deeply entrenched and difficult to resolve. The core pathogenesis of recurrent psoriasis vulgaris lies in "latent fire causing blood stasis". The hallmark is the deep concealment and persistence of latent fire and stasis， which linger and await an opportunity to reemerge. Based on this understanding， Xijiao Dihuangtang is employed to cool the blood， resolve stasis， and eliminate latent pathogens， and treatment is tailored according to the disease stage through three-phase syndrome differentiation. In the progressive stage， both exterior and interior are treated， with emphasis on clearing latent fire. In the stationary stage， the focus shifts to dispelling latent stasis and simultaneously regulating the Zang-fu organs. In the regressive stage， efforts are made to prevent the retention of latent pathogens and to strengthen healthy Qi. Accordingly， drugs effective in dispersing wind and clearing heat， pungent-moistening and dredging the collaterals， and tonifying deficiency and moistening dryness are often employed to achieve optimal outcomes. The precise mechanisms by which Xijiao Dihuangtang treats recurrent psoriasis vulgaris remain to be fully elucidated. Current research suggests it may intervene in the recurrence process through inhibiting KC proliferation via the PI3K/Akt/mTOR signaling pathway and glycolysis， regulating the Th1/Th2 and Th17/Treg cell balances to restore immune homeostasis， suppressing inflammatory cytokine production to alleviate the inflammatory response， modulating angiogenesis-related factors， such as vascular endothelial growth factor A （VEGF-A） and matrix metalloproteinase-9 （MMP-9）， to control disease progression， and restructuring the gut microbiota to modulate systemic immunity and thereby influence the course of disease recurrence.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

OBJECTIVE: To investigate the clinical characteristics, curative effect and prognostic factors of patients with multiple myeloma (MM) complicated with light chain myocardial amyloidosis (AL-CA). METHODS: The data of 38 patients diagnosed with MM complicated with AL-CA in our hospital from January 2018 to December 2023 were retrospectively analyzed, and the data were comprehensively screened by multiple methods such as positive two-dimensional spot tracking echocardiography (2D-STE). Survival analysis was performed using the Kaplan-Meier method. Cox regression models were used to screen for independent prognostic factors. RESULTS: Among the 38 MM patients with AL-CA, 23 were male and 15 were female, with a median age of 60(50,75) years. The 1-year survival rate was 71.05%. Patients who underwent transplantation had significantly better survival outcomes than those who did not (P < 0.01). Additionally, the median survival time of patients with all-negative FISH results at the first visit was statistically different compared to patients with other mutations (P < 0.05). Multivariate Cox regression analysis showed that all negative FISH results at the first visit and the absence of autologous hematopoietic stem cell transplantation (ASCT) were not independent risk factor for the prognosis of patients with MM and AL-CA (P >0.05). CONCLUSION ASCT may improve the prognosis of MM patients with AL-CA, and negative FISH results may indicate poor prognosis, but the results still need to be verified by larger samples.
Humans ; Multiple Myeloma/complications* ; Retrospective Studies ; Aged ; Female ; Male ; Middle Aged ; Prognosis ; Hematopoietic Stem Cell Transplantation ; Amyloidosis/complications* ; Survival Rate ; Proportional Hazards Models

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Aim To explore the improvement effect of Bazi Bushen capsule on thymic degeneration in SAMP6 mice and the possible mechanism.Methods Twenty 12 week old male SAMP6 mice were randomly divided into the model group(SAMP6)and the Bazi Busheng capsule treatment group(SAMP6+BZBS).Ten SAMR1 mice were assigned to a homologous control group(SAMR1).The SAMP6+BZBS group was oral-ly administered Bazi Bushen capsule suspension(2.8 g·kg-1)daily,while the other two groups were orally administered an equal amount of distilled water.After nine weeks of administration,the morphology of the thymus in each group was observed and the thymus in-dex was calculated;HE staining was used to observe the structural changes of thymus tissue;SA-β-gal stai-ning was used to detect thymic aging;flow cytometry was used to detect the proportion of thymic CD3+T cells in each group;Western blot was used to detect the levels of p16,Bax,Bcl-2,and cleaved caspase-3 proteins in thymus;immunofluorescence was applied to detect the proportion of cortical thymic epithelial cells in each group;ELISA was employed to detect IL-7 lev-els in thymus.Results Compared with the SAMP6 group,the thymic index of the SAMP6+BZBS group significantly increased(P＜0.05);the disordered thy-mic structure was significantly improved;the positive proportion of SA-β-gal staining significantly decreased(P＜0.01);the proportion of CD3+T cells apparently increased(P＜0.05);the level of p16 protein signifi-cantly decreased(P＜0.05);the level of Bcl-2 pro-tein significantly increased(P＜0.05),while the lev-el of cleaved caspase-3 protein markedly decreased(P＜0.05);the proportion of cortical thymic epithelial cells evidently increased;the level of IL-7 significantly increased(P＜0.01).Conclusions Bazi Bushen capsule can delay thymic degeneration,inhibit cell ap-optosis in thymus and promote thymic cell development in SAMP6 mice,which may be related to increasing the proportion of cortical thymic epithelial cells and promoting IL-7 secretion.

Aim To investigate the effect of polyphyl-lin Ⅱ(PP Ⅱ)on autophagy of osteosarcoma(OS)cells and its related molecular mechanism.Methods U2OS and HOS cells were cultured in vitro and treated with different concentrations of PP Ⅱ(5,10,15,20 μmol·L-1)for 24 h.The changes of acid vesicles were detected by AO staining,the autophagosomes was ob-served by transmission electron microscopy,the ex-pressions of LC3B-Ⅱ/LC3B-Ⅰ,p62,caspase-3,cleaved caspase-3 were detected by Western blot,the intracellular reactive oxygen species(ROS)was detec-ted by DCFH-DA fluorescence probe,cell viability was detected by CCK-8,cell apoptosis rate was detected by Annexin V-FITC/PⅠ staining.Results PP Ⅱ signifi-cantly increased the number of acidic vesicles(P＜0.05,P＜0.01)and autophagosomes.PP Ⅱ signifi-cantly up-regulated the ratio of LC3B-Ⅱ/LC3B-Ⅰ,and down-regulated the expression level of p62 protein in a concentration-and time-dependent manner(P＜0.05,P＜0.01).PP Ⅱ significantly increased intra-cellular ROS levels(P＜0.01).Autophagy inhibitor 3-MA and CQ could reverse the regulation of cell via-bility,autophagy and apoptosis related proteins by PP Ⅱ in U2OS cells,endoplasmic reticulum stress inhibi-tor 4-PBA could also reverse the regulation of autoph-agy related proteins by PP Ⅱ in U2OS cells.Conclu-sion PP Ⅱ promotes OS cell autophagy by mediating ROS and endoplasmic reticulum stress.

To address the issue of peak loss when applying variational mode decomposition(VMD)to denoise spectra with sharp peaks,in this study,a method for spectral signal denoising of complex samples called peak extraction variational mode decomposition(PE-VMD)was introduced.Firstly,the spectral signal was subjected to a process of denoising utilising the VMD algorithm.Next,the first order derivatives of the spectral signals were calculated to determine the peak center.Subsequently,the second order derivatives of the spectral signal was calculated to extract the sharp peaks with high signal-to-noise ratio(SNR).Finally,the peak intercepted that lose information after VMD denoising were removed,and the remaining spectrum was sequentially connected with the extracted sharp peaks to obtain the final denoised spectrum.The effectiveness of the method was evaluated by one of simulated signals and X-ray diffraction(XRD)spectrum of MnCo-ISAs/CN catalysts.Furthermore,the method was compared with other denoising techniques,including Savitzky-Golay(SG)smoothing,empirical mode decomposition(EMD)and VMD.The efficacy of the denoising process was then assessed by analyzing the spectrograms and signal-to-noise ratio before and after denoising.The results demonstrated that PE-VMD denoising achieved the greatest SNR and effectively preserved the essential information of the spectral signals.Consequently,PE-VMD exhibited superior denoising capability for spectra with sharp peaks.

Objective To develop a portable,modular and multifunctional surgical instrument kit with intelligent recognition for disaster relief.Methods The surgical instrument kit had three variations for thorax and abdomen,limbs and cranium and brain,which was composed of a lip,partitions and drawers.A traceability code was pasted on each surgical instrument kit,and each instrument in the kit was equipped with a RF chip.Results The surgical instrument kit made the average time for operating table preparation and instrument arrangement and that for instrument counting both shortened effectively,and thus the efficiency of medical staffs were enhanced greatly.Conclusion The surgical instrument kit gains advantages in rational configuration and easy operation,and can be used for surgical operation in disaster conditions.[Chinese Medical Equipment Journal,2024,45(2):113-117]