Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

The pain-evoked potential electroencephalogram (EEG) is an effective electrophysiological indicator for pain assessment, yet its extraction is challenging due to interference from background activity and involuntary blinks. Although existing blink artifact-removal methods show efficacy, they face limitations such as the need for reference signals, neglect of individual differences, and reliance on user input, hindering their practical application in clinical pain assessments. In this paper, we propose a novel framework applying adaptive quadrature mirror filter banks (AQMFB) with discrete wavelet transform (DWT) to remove blink artifacts in pain EEG. Unlike traditional DWT methods that apply fixed wavelets across subjects, our method adapts wavelet construction based on the characteristics of EEG. Experimental results demonstrate that AQMFB-DWT outperforms four leading methods in removing blink artifacts with minimal distortion of pain information, all within an acceptable processing time. This technique is a valuable preprocessing step for enhancing the extraction of pain-evoked potentials.
Humans ; Artifacts ; Blinking/physiology* ; Electroencephalography/methods* ; Pain/diagnosis* ; Male ; Wavelet Analysis ; Adult ; Female ; Evoked Potentials/physiology* ; Young Adult ; Brain/physiopathology* ; Pain Measurement/methods* ; Signal Processing, Computer-Assisted

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 measure the Young's modulus values of the quadriceps muscles(rectus femoris,vastus intermedius,vastus lateralis,vastus medialis)and tendons in Parkinson's disease(PD)patients using real-time shear wave elastography(SWE)technology,and to analyze the changes in muscle and tendon tone.Methods A total of 60 clinically diagnosed PD patients from Yunnan University Affiliated Hospital between April 2023 and April 2024 were included in the study group.Based on the scores and ratings of PD rating scale,patients were divided into Group A(symptomatic side,n=60)and Group B(less symptomatic side,n=60).An additional 60 healthy subjects were selected as the control group.The shear wave elastography function of the ACUSON Sequoia ultrasound diagnostic device from Siemens USA was used to measure the Young's modulus values(kPa)of the quadriceps muscles and tendons in a relaxed state,and to analyze and compare the changes in muscle and tendon tone.Results The Young's modulus values of quadriceps muscles(rectus femoris,intermedius femoris,vastus lateralis,vastus medialis)in groups A and B were higher than those in control group(P<0.05).The Young's modulus values of the intermediate and lateral femoris muscles in group A were higher than that in group B(all P<0.05).The Young's modulus values of quadriceps tendon in groups A and B were higher than that in control group.(P<0.05).The Young modulus value of quadriceps tendon in group A was higher than that in group B(P<0.05).Conclusion Patients with Parkinson's disease exhibit increased muscle and tendon tone in the quadriceps.Notably,the muscle tone of the vastus intermedius and vastus lateralis on the symptomatic side is higher than that on the less symptomatic side,while there is no significant difference in muscle tone between the rectus femoris and vastus medialis on the symptomatic and less symptomatic sides.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

Objective Endothelial injury plays a crucial role in forming deep vein thrombosis.This study aims to compare the effectiveness of various methods for creating rabbit femoral vein thrombotic models after the endothelial injuryso as to provide a solid experimental foundation for further research on the endothelial injury and deep vein thrombosis.Methods Forty-five rabbits were randomly divided into three groups(A,B,C),with 15 cases in each group and subjected to the endothelial injury using the methods of simple clamping,combined complete ligation,and combined incomplete ligation,respectively.The intravascular ultrasonic manifestations and local endothelial pathological changes were compared at 1,3,and 7 days after modeling.Results Significant differences in vascular diameter and Young's modulus values were observed after 7 days of modeling(P<0.05).In pairwise comparisons between the groups,the Young's modulus values in group C were significantly higher than those in groups A and B after 7 days of modeling(P<0.05).Pathological examination confirmed the presence of fibr-inoid thrombus in the blood vessels of group C on the seventh day of modeling.Conclusion Combining simple clam-ping and incomplete ligation can produce a relatively stable endothelial injury and thrombus formation.This method provides a robust experimental model for further investigation into deep vein thrombosis after the endothelial injury.

Objective:To observe the influence of NOD-like receptor thermal protein domain associated protein 6 (NLRP6) on hepatic ischemia-reperfusion injury (IRI), and elucidate the related mechanism.Methods:Thirty C57BL/6 mice with body weight of (18.80±1.99) g, were divided randomly into 5 groups, with 6 mice in each group: the mice that experienced only exploratory laparotomy were Sham group; that only underwent an operation to establish a hepatic IRI model were IRI group; that were treated with tail intravenous injection of clodronate (Clo) liposomes before the establishment of hepatic IRI model were Clo group; that received tail intravenous injection of clodronate liposomes and transfusion of bone marrow derived macrophages (BMDM) before the operation were Clo+ BMDM group; that received preoperative tail intravenous injection of clodronate liposomes and transfusion of BMDM with NLRP6 knockdown were Clo+ NLRP6-knockdown group. Real time quantitative polymerase chain reaction analysis (RT-PCR) and Western blot were performed to analyze the expressions of pyroptosis related proteins and factors. Simulate a hypoxia/reoxygenation (H/R) model in vitro, and set up experimental groups: lipopolysaccharide (LPS) + adenosine triphosphate (ATP), LPS+ ATP+ NLRP6-knockdown, H/R, and H/R+ NLRP6-knockdown. The changes of expressions of pyroptosis related proteins and factors were detected by RT-PCR and Western blot. Expression of NF-κB in vivo and in vitro was measured.Results:Compared with those in Sham group, protein expressions of NLRP6, NLRP3, Caspase-1, gasdermin D (GSDMD), IL-1β and IL-18 were remarkably increased in IRI group, but the levels of these proteins were dramatically decreased in Clo group with the exhaustion of macrophages in comparison with in IRI group, which were significantly different statistically (all P<0.05). The levels of these proteins were enhanced again in Clo+ BMDM group with the reconstruction of macrophages in contrast to those in Clo group, while the enhancements were more obvious in Clo+ NLRP6-knockdown group comparing to those in Clo+ BMDM group, with significant differences (all P<0.05). In vitro, pyroptosis rate for LPS+ ATP group was (16.39±1.06)%, which was lower than (27.34±2.79)% for LPS+ ATP+ NLRP6-knockdown group, with a statistical significance ( P<0.05). Meanwhile, pyroptosis rate for H/R group was (20.59±5.66)%, also much more reduced than (37.76±2.00)% for H/R+ NLRP6-knockdown group ( P<0.05). Expressions of NLRP3, Caspase-1, GSDMD, IL-1β, IL-18 and NF-κB p65 in LPS+ ATP+ NLRP6-knockdown group were more elevated than in LPS+ ATP group, and these indices were also more enhanced in H/R+ NLRP6-knockdown group than which in H/R group. Compared to the Sham group, expression of NF-κB p65 significantly increased in IRI group, which was reversed in Clo group, but enhanced again in Clo+ BMDM group and reached a peak in Clo+ NLRP6-knockdown group. Conclusions:Macrophage plays a critical role in immune response to hepatic IRI, wherein NLRP6 functions specifically. NLRP6 acts to suppress inflammation during hepatic IRI through regulating macrophage pyroptosis via inhibiting NF-κB.

OBJECTIVE To provide reference for quality control of Gentiana rhodantha. METHODS Taking 52 batches of G. rhodantha as subject， ultra-high performance liquid chromatography （UPLC） fingerprint was adopted. The similarity of 52 batches of medicinal materials samples was evaluated by the Similarity Evaluation System for Chromatographic Fingerprints of Traditional Chinese Medicine （2004A edition）； the content of mangiferin was determined； chemometric analyses [cluster analysis， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA）] were performed. RESULTS UPLC fingerprints of 52 batches of G. rhodantha were established， 17 common peaks were identified， and 6 of them were identified， which were loganic acid （peak 1）， neomangiferin （peak 3）， swertiamarin （peak 5）， dangyin （peak 6）， mangiferin （peak 7） and isoorientin （peak 9）. The similarities of 52 batches of medicinal materials samples were all greater than 0.9； cluster analysis showed that S1-S46， S48-S52 clustered into one class， and S47 alone； PCA results showed that the cumulative variance contribution rate of the first six principal components was 82.928%； OPLS-DA results showed that the corresponding components of swertiamarin， mangiferin and chemical composition represented by peak 4， 14， 15， 16 were the main iconic components affecting the quality differences of G. rhodantha medicinal materials. The contents of mangiferin in 52 batches of medicinal material samples ranged from 18.2 to 101.0 mg/g， mostly in accordance with 2020 edition of Chinese Pharmacopoeia. CONCLUSIONS The established UPLC fingerprint and chemometric analysis methods combined with content determination method of mangiferin can comprehensively evaluate the quality of G. rhodantha.

Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.
Humans ; Antineoplastic Agents/therapeutic use* ; Apoptosis ; beta Catenin/metabolism* ; Biomarkers, Tumor/metabolism* ; Cell Line, Tumor ; Coenzyme A Ligases/metabolism* ; Leukemia, Myeloid, Acute/metabolism* ; Lipoylation ; Prognosis ; Wnt Signaling Pathway

OBJECTIVE To establish comprehensive quality evaluation method based on multi-index components combined with multivariate statistical analysis， and to comprehensively evaluate the quality of Periploca forrestii. METHODS Taking 11 batches of P. forrestii medicinal materials from different areas in Guizhou as samples， the contents of neochlorogenic acid， cryptochlorogenic acid， chlorogenic acid， procyanidin A2， isochlorogenic acid A and isochlorogenic acid C were determined by HPLC. Clustering heat map analysis， grey correlation analysis（GRA） and technique for order preference by similarity to ideal solution（TOPSIS） were used to evaluate the quality of P. forrestii. RESULTS The results of methodological investigation of content determination were in accordance with the relevant regulations， and the linear relationship and accuracy of each component were good in their respective sampling range. The contents of chlorogenic acid， cryptochlorogenic acid， neochlorogenic acid， procyanidin A2， isochlorogenic acid A and isochlorogenic acid C in 11 batches of samples were 3.650-7.302， 0.888-2.575， 1.371- 2.386， 0.947-1.469， 0.084-0.169 and 0.725-1.067 mg/g， respectively. The content of each component was significantly different， with the highest content of chlorogenic acid and the lowest content of isochlorogenic acid A. The comprehensive results of cluster heat map， GRA and TOPSIS analysis showed that the comprehensive quality of S5 and S10 was relatively good. CONCLUSIONS The established method is accurate， stable and simple. Combined with multivariate statistical analysis method， it can be used for quality evaluation of P. forrestii. The quality of samples from Jiuzhou Town and Caiguan Town of Xixiu District in Anshun City of Guizhou Province are relatively good among 11 different origin samples.