MUC20 regulated by extrachromosomal circular DNA attenuates proteasome inhibitor resistance of multiple myeloma by modulating cuproptosis.

BACKGROUND: Proteasome inhibitors (PIs) are one of the most important classes of drugs for the treatment of multiple myeloma (MM). However, almost all patients with MM develop PI resistance, resulting in therapeutic failure. Therefore, the mechanisms underlying PI resistance in MM require further investigation. METHODS: We used several MM cell lines to establish PI-resistant MM cell lines. We performed RNA microarray and EccDNA-seq in MM cell lines and collected human primary MM samples to explore gene profiles. We evaluated the effect of MUC20 on cuproptosis of PI-resistant MM cells using Co-immunoprecipitation (Co-IP), Seahorse bioenergetic profiling and in vivo assay. RESULTS: This study revealed that the downregulation of Mucin 20 (MUC20) could predict PI sensitivity and outcomes in MM patients. Besides, MUC20 attenuated PI resistance in MM cells by inducing cuproptosis via the inhibition of cyclin-dependent kinase inhibitor 2 A expression (CDKN2A), which was achieved by hindering MET proto-oncogene, receptor tyrosine kinase (MET) activation. Moreover, MUC20 suppressed MET activation by repressing insulin-like growth factor receptor-1 (IGF-1R) lactylation in PI-resistant MM cells. This study is the first to perform extrachromosomal circular DNA (eccDNA) sequencing for MM, and it revealed that eccDNA induced PI resistance by amplifying kinesin family member 3 C (KIF3C) to reduce MUC20 expression in MM. CONCLUSION: Our findings indicated that MUC20 regulated by eccDNA alleviates PI resistance of MM by modulating cuproptosis, which would provide novel strategies for the treatment of PI-resistant MM.

Coenzyme Q10 Protects Against Hyperlipidemia-Induced Osteoporosis by Improving Mitochondrial Function via Modulating miR-130b-3p/PGC-1α Pathway.

In hyperlipidemia-induced osteoporosis, bone marrow mesenchymal stem cells (BMSCs) differentiate into more adipocytes than osteoblasts, leading to decreased bone formation. It is vital to elucidate the effects of hyperlipidemia on bone metabolism and seek new agents that regulate adipocyte-osteoblast lineage allocation. CoQ10, a rate-limiting coenzyme of the mitochondrial respiratory chain, has been reported to decrease oxidative stress and lipid peroxidation by functioning as a mitochondrial antioxidant. However, its effect on hyperlipidemia-induced osteoporosis remains unknown. Here, we analyzed the therapeutic mechanisms of CoQ10 on hyperlipidemia-induced osteoporosis by using high-fat diet (HFD)-treated ApoE-/- mice or oxidized low-density lipoprotein (ox-LDL)-treated BMSCs. The serum lipid levels were elevated and bone formation-related markers were decreased in HFD-treated ApoE-/- mice and ox-LDL-treated BMSCs, which could be reversed by CoQ10. Additionally, PGC-1α protein expression was decreased in HFD-treated ApoE-/- mice and ox-LDL-treated BMSCs, accompanied by mitochondrial dysfunction, decreased ATP content and overgeneration of reactive oxygen species (ROS), which could also be antagonized by CoQ10. Furthermore, PGC-1α knockdown in vitro promoted ROS generation, BMSC apoptosis, and adipogenic differentiation while attenuating osteogenic differentiation in BMSCs. Mechanistically, it suggested that the expression of PGC1-α protein was increased with miR-130b-3p inhibitor treatment in osteoporosis under hyperlipidemia conditions to improve mitochondrial function. Collectively, CoQ10 alleviates hyperlipidemia-induced osteoporosis in ApoE-/- mice and regulates adipocyte-osteoblast lineage allocation. The possible underlying mechanism may involve the improvement of mitochondrial function by modulating the miR-130b-3p/PGC-1α pathway.

The 10-m cotton maps in Xinjiang, China during 2018-2021.

Cotton maps (10 m) of Xinjiang (XJ_COTTON10), which is the largest cotton production region of China, were produced from 2018 to 2021 through supervised classification. A two-step mapping strategy, i.e., cropland mapping followed by cotton extraction, was employed to improve the accuracy and efficiency of cotton mapping for a large region of about 1.66 million km2 with high heterogeneity. Additionally, the time-series satellite data related to spectral, textural, structural, and phenological features were combined and used in a supervised random forest classifier. The cotton/non-cotton classification model achieved overall accuracies of about 95% and 90% on the test samples of the same and adjacent years, respectively. The proposed two-step cotton mapping strategy proved promising and effective in producing multi-year and consistent cotton maps. XJ_COTTON10 agreed well with the statistical areas of cotton at the county level (R2 = 0.84-0.94). This is the first cotton mapping for the entire Xinjiang at 10-meter resolution, which can provide a basis for high-precision cotton monitoring and policymaking in China.

A national, multicenter, retrospective study of Castleman disease in China implementing CDCN criteria.

Background: Castleman disease (CD) is a group of rare and heterogenous lymphoproliferative disorders including unicentric CD (UCD), human herpesvirus-8(HHV-8)-associated multicentric CD (HHV8-MCD), and HHV-8-negative/idiopathic multicentric CD (iMCD). Knowledge of CD mainly comes from case series or retrospective studies, but the inclusion criteria of these studies vary because the Castleman Disease Collaborative Network (CDCN) diagnostic criteria for iMCD and UCD were not available until 2017 and 2020, respectively. Further, these criteria and guidelines have not been systematically evaluated. Methods: In this national, multicenter, retrospective study implementing CDCN criteria, we enrolled 1634 CD patients (UCD, n = 903; MCD, n = 731) from 2000 to 2021 at 40 Chinese institutions to depict clinical features, treatment options, and prognostic factors of CD. Findings: Among UCD, there were 162 (17.9%) patients with an MCD-like inflammatory state. Among MCD, there were 12 HHV8-MCD patients and 719 HHV-8-negative MCD patients, which included 139 asymptomatic MCD (aMCD) and 580 iMCD meeting clinical criteria. Of 580 iMCD patients, 41 (7.1%) met iMCD-TAFRO criteria, the others were iMCD-NOS. iMCD-NOS were further divided into iMCD-IPL (n = 97) and iMCD-NOS without IPL (n = 442). Among iMCD patients with first-line treatment data, a trend from pulse combination chemotherapy toward continuous treatment was observed. Survival analysis revealed significant differences between subtypes and severe iMCD (HR = 3.747; 95% CI: 2.112-6.649, p < 0.001) had worse outcome. Interpretation: This study depicts a broad picture of CD, treatment options and survival information in China and validates the association between the CDCN's definition of severe iMCD and worse outcomes, requiring more intensive treatment. Fundings: Beijing Municipal Commission of Science and Technology, CAMS Innovation Fund and National High Level Hospital Clinical Research Funding.

MicroRNA Let-7i Regulates Innate TLR4 Pathways in Peripheral Blood Mononuclear Cells of Patients with Ankylosing Spondylitis.

Purpose: This study aimed to compare the changes in the expression of microRNA Let-7i in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS) and the correlation between Let-7i and innate pro-inflammatory factors. It is necessary to search for a new biomarker to guide the prognosis of AS. Methods: A total of 10 patients with AS and 10 healthy volunteers were selected as AS and control groups, respectively. The expression levels of Let-7i, Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), and interferon-gamma (IFN-γ) in PBMCs were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB) to explore the relationship between Let-7i and pro-inflammatory factors. Furthermore, the relationship between Let-7i and TLR4 was determined by the luciferase reporter technology. Results: The expression level of Let-7i in PBMCs of patients with AS was significantly lower than that of healthy control. The expression levels of TLR4, NF-κB, and IFN-γ in PBMCs derived from patients with AS were significantly higher than those of healthy control. The results show that Let-7i manipulation can regulate lipopolysaccharide (LPS)-induced TLR4 and IFN-γ expression in CD4+ T cells of patients with AS. The overexpression of Let-7i in T cells of patients with AS can suppress TLR4 and IFN-γ LPS-induced expression levels of cellular mRNA and protein. Let-7i can directly interfere TLR4-3'untranslated region (UTR) sequence and regulate the expression of the TLR4 gene in Jurkat T cells. Conclusion: Let-7i may be involved in the pathogenesis of AS, and Let-7i expression in PBMCs may be helpful for the diagnosis and treatment of AS in the future.

Three-dimensional-printed MPBI@ß-TCP scaffold promotes bone regeneration and impedes osteosarcoma under near-infrared laser irradiation.

Beta-tricalcium phosphate (ß-TCP) is considered as one of the most promising biomaterials for bone reconstruction. This study generated a functional molybdenum disulfide (MoS2 )/polydopamine (PDA)/-bone morphogenetic protein 2 (BMP2)-insulin-like growth factor-1 (IGF-1) coating on the ß-TCP scaffold and analyzed the outcomes. The MoS2 /PDA-BMP2-IGF-1@ß-TCP (MPBI@ß-TCP) scaffold was prepared by 3D printing and physical adsorption, followed by characterization to validate its successful construction. The in vitro osteogenic effect of the MPBI@ß-TCP scaffold was evaluated. It was found that MPBI@ß-TCP augmented the adhesion, diffusion and proliferation of mesenchymal stem cells (MSCs). The alkaline phosphatase (ALP) activity, collagen secretion and extracellular matrix (ECM) mineralization along with the expression of Runx2, ALP and OCN were also enhanced in the presence of MPBI@ß-TCP. Additionally, MPBI@ß-TCP stimulated endothelial cells to secrete VEGF and promoted capillary-like tubule formation. We then confirmed the biocompatibility of MPBI@ß-TCP to macrophages and its anti-inflammatory effects. Furthermore, under near-infrared (NIR) laser irradiation, MPBI@ß-TCP produced photothermal effect to not only kill MG-63 osteosarcoma cells, but also enhance bone regeneration in vivo with biosafety. Overall, this work demonstrates that 3D-printed MPBI@ß-TCP with enhanced osteogenic activity under NIR laser irradiation has a vast potential in the field of tissue defects.

Tislelizumab with gemcitabine and oxaliplatin in patients with relapsed or refractory classic Hodgkin lymphoma: a multicenter phase II trial.

Although classic Hodgkin lymphoma (cHL) is highly curable with current treatment paradigms, therapy fails in 10-25% of patients. This prospective multicenter phase II study attempted to investigate the efficacy and safety of the combination of tislelizumab with gemcitabine and oxaliplatin (T-GemOx) in relapsed or refractory cHL. Participants received six to eight courses of gemcitabine (1 g/m2 on day 1) and oxaliplatin (100 mg/m2 on day 1) combined with tislelizumab (200 mg on day 2) at 21-day intervals, followed by tislelizumab maintenance (every 2 months for 2 years). The main outcome measure was the best complete remission rate. As of August 2022, a total of 30 patients had been consecutively enrolled and given induction therapy. The best overall response rate and complete remission rate were 100% (95% confidence interval [CI]: 88.4-100%) and 96.7% (95% CI: 82.8-99.9%), respectively. The median duration of follow-up after initiation of T-GemOx was 15.8 months. The 12-month progression-free survival rate without autologous stem cell transplant was 96% (95% CI: 74.8-99.4%). There were 122 adverse events recorded, of which 93.4% were grade 1 or 2. Thrombocytopenia (10%) and anemia (6.7%) were the most common grade 3 or 4 adverse events. Overall, T-GemOx demonstrated promising antitumor activity with manageable toxicities as a salvage treatment for relapsed or refractory cHL. A longer follow-up duration is required to determine whether maintenance therapy with tislelizumab rather than transplantation can be curative following such a highly active regimen. This trial was registered with the Chinese Clinical Trials Registry (http://www.chictr.org.cn) on June 1, 2020, identifier ChiCTR2000033441.

Anti-Postmenopausal osteoporosis effects of Isopsoralen: A bioinformatics-integrated experimental study.

Isopsoralen (IPRN), which comes from the fruit of Psoralea corylifolia, has been identified as a kind of phytoestrogen and has been proven to be effective for the treatment of osteoporosis (OP). However, the mechanisms underlying IPRN's anti-OP effects, especially the anti-postmenopausal osteoporosis (PMOP) effects, remain indistinct. Thus, this study aimed to investigate the effects and mechanisms of IPRN's anti-PMOP activity. In this study, the bioinformatics results predicted that IPRN could resist PMOP by targeting EGFR, AKT1, SRC, CCND1, ESR1 (ER-α), AR, PGR, BRCA1, PTGS2, and IGF1R. An ovariectomized (OVX) mice model and a H2 O2 -induced bone marrow mesenchyml stem cells (BMSCs) model confirmed that IPRN could inhibit the bone loss induced by OVX in mice and promote the osteogenic differentiation in H2 O2 -induced BMSCs by inhibiting oxidative stress and apoptosis. Moreover, IPRN could significantly produce the above effects by upregulating ESR1. IPRN might be a therapeutic agent for PMOP by acting as an estrogen replacement agent and a natural antioxidant.

Palbociclib regulates the expression of dihydrofolate reductase and the cell cycle to inhibit t (11;14) multiple myeloma.

Background: Multiple myeloma (MM) with t (11;14) has a unique biology. New combinations of novel agents are needed to improve the prognosis of patients with t (11;14) MM. As a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), palbociclib (PAL) has been used to treat various malignancies, including breast cancer, ovarian cancer, and so on. However, the effects of PAL on MM remain unclear, and thus, further investigations are warranted. Methods: Two t (11;14) MM cell lines, U266 and KMS27, were used in this study. The cell viability and cell cycle were detected to evaluate the anti-myeloma effect of the combination of pralatrexate (PTX) and methotrexate (MTX) with PAL. Three-dimensional (3D) spheroid and mouse models were built to verify the effect of the combination treatment. Western blot was used to detect the expressions of Minichromosome Maintenance Complex Component 2 (MCM2), Minichromosome Maintenance Complex Component 3 (MCM3), and dihydrofolate reductase (DHFR). Results: It was observed that PAL had obvious anticancer effects on U266 and KMS27 cells, which had synergistic effects together with PTX and MTX. Importantly, it was found that PAL could promote cell cycle genes including MCM2 and MCM3, and increase the number of MM cells in the G1 phase. Moreover, PAL reduced the expression level of DHFR and exerted its anticancer effects on MM cells by targeting DHFR. It was also determined that PAL exerted anticancer effects on MM in the spheroid and mouse models. Conclusions: PAL exerted obvious anticancer effects on t (11;14) MM cells, which had synergistic effects together with PTX and MTX. PAL could promote cell cycle genes and the G1 phase of MM cells. Moreover, PAL reduced the expression level of DHFR and exerted its anticancer effects on t (11;14) MM cells by targeting DHFR.

Association between dietary acid load and cancer risk and prognosis: An updated systematic review and meta-analysis of observational studies.

Epidemiological studies have suggested that dietary acid load (DAL) might be related to the risk and prognosis of cancer, whereas the evidence is contentious. Several high-quality observational studies have been published following a prior systematic review with only one study included. Consequently, we conducted an updated systematic review and meta-analysis to comprehensively investigate the relationship between DAL and cancer risk and prognosis. A systematic literature search was conducted in the PubMed, Embase, and Web of Science databases from inception to 26 October 2021. Summary relative risks (RRs) with 95% CIs were calculated using a random-effects model. Publication bias, subgroup, meta-regression, and sensitivity analyses were also conducted. Ten observational studies (six cohorts and four case-control studies) with 227,253 participants were included in this systematic review and meta-analysis. The summary RRs revealed a statistically significant associations between DAL and cancer risk (RR = 1.58, 95% CI = 1.23-2.05, I 2 = 71.9%, n = 7) and prognosis (RR = 1.53, 95% CI = 1.10-2.13, I 2 = 77.1%, n = 3). No evidence of publication bias was observed in the current analysis. Positive associations were observed in most subgroup analyses stratified by predefined factors, including region, study design, study quality, study population, participants' gender, age of participants, cancer type, DAL assessment indicator, and adjustment of potential confounding parameters. No evidence of heterogeneity between subgroups was indicated by meta-regression analyses. The high DAL might be associated with an increased risk of cancer, as well as a poor prognosis of cancer. More high-quality prospective studies are warranted to further determine the associations between DAL and risk and prognosis for specific cancers.

DNMT3a promotes osteoblast differentiation and alleviates osteoporosis via the PPARγ/SCD1/GLUT1 axis.

Background: This study was designed to elucidate the role of DNMT3a and PPARγ functions in postmenopausal osteoporosis. Materials & methods: Mice were ovariectomized to establish an in vivo osteoporosis model and MC3T3-E1-14 osteoblasts were induced to differentiate. Gain- or loss-of-function approaches were used to manipulate the expression of PPARγ, DNMT3a and SCD1, followed by an evaluation of their role in postmenopausal osteoporosis both in vivo and in vitro. Results: DNMT3a induced methylation of the PPARγ promoter region, consequently stimulating osteoblast differentiation. PPARγ elevated SCD1, which decreased GLUT1 and inhibited osteoblast differentiation. Inhibition of PPARγ reduced SCD1 while increasing GLUT1 expression, thus alleviating postmenopausal osteoporosis in mice. Conclusion: DNMT3a promotes osteoblast differentiation and prevents postmenopausal osteoporosis by regulating the PPARγ/SCD1/GLUT1 axis.

Aberrant SPOP-CHAF1A ubiquitination axis triggers tumor autophagy that endows a therapeutical vulnerability in diffuse large B cell lymphoma.

PURPOSE: Aberrant epigenetic changes, like DNA methylation, histone modifications, or ubiquitination, could trigger metabolic disorders in human cancer cells. This study planed to uncover the biological roles of epigenetic SPOP/CHAF1A axis in modulating tumor autophagy during Diffuse large B-cell lymphoma (DLBCL) tumorigenesis. MATERIALS AND METHODS: The Immunohistochemistry (IHC) was performed to assess the CHAF1A expressions. The expression data of CHAF1A was derived from The Cancer Genome Atlas (TCGA), GSE32918 and GSE83632 datasets. Bioinformatic assays contain differential analysis, functional enrichment analysis and Kaplan-Meier survival curve analysis. The colony generation assay, Transwell assay and CCK-8 assays were conducted for the in vitro assays. The in vivo ubiquitination assays were used to assess regulations of SPOP on CHAF1A. The Chromatin immunoprecipitation (ChIP) assays were used to uncover epigenetic regulations of CHAF1A on TFEB. The relevant DLBCL cells were subcutaneously injected to SCID beige mice to establish the xenograft models. RESULTS: Bioinformatic results revealed that CHAF1A expressed highly in DLBCL that were validated in patients samples. Patients with high CHAF1A suffered from inferior prognosis with shorter survival months relative to those with low CHAF1A. High CHAF1A enhanced DLBCL aggressiveness, including cell proliferation, migration and in vivo growth. Mechanistically, E3 ubiquitin ligase SPOP binds to and induces the degradative ubiquitination of CHAF1A via recognizing a consensus SPOP-binding motif in CHAF1A. SPOP is down-regulated in DLBCL and habours two DLBCL-associated mutations. Deficient SPOP leads to accumulated CHAF1A proteins that promote malignant features of DLBCL. Subsequently, ChIP-qPCR assay revealed that CHAF1A directly binds to TFEB promoters to activate the expressions. High CHAF1A could enhance the transcriptional activity of TFEB and downstream genes. The SPOP/CHAF1A axis modulates TFEB-dependent transactivation to regulate the lysosomal biogenesis and autophagy. The in vivo models suggested that TFEB inhibition is effective to suppress growth of SPOP-deficient DLBCLs. CONCLUSIONS: CHAF1A is aberrantly elevated in SPOP-deficient DLBCL. The in-depth mechanism understanding of SPOP/CHAF1A/TFEB axis endows novel targets for DLBCL treatment.

Combination regimen of granulocyte colony-stimulating factor and recombinant human thrombopoietin improves the curative effect on elderly patients with leukemia through inducing pyroptosis and ferroptosis of leukemia cells.

Leukemia ranks as the one of most common causes of death from tumor. 51.4% of patients with leukemia are over 65 years old. However, the median overall survival (OS) of elderly leukemia patients is less than one year. It is urgent to explore more effective treatments for elderly patients with leukemia. Our recent prospective phase II single-arm study has revealed that combination regimen of granulocyte colony-stimulating factor (G-CSF) and recombinant human thrombopoietin (rhTPO) could improve the curative effect on elderly patients with leukemia, yet the precise mechanism remains unknown. This study demonstrated that combination of G-CSF and rhTPO showed greater effect on suppressing leukemia growth than G-CSF or rhTPO alone in vitro and in vivo. Mechanistically, G-CSF induced pyroptosis through ELANE in leukemia cells. Besides, rhTPO triggered ferroptosis by EP300 in leukemia cells. Moreover, rhTPO suppressed glutathione peroxidase 4 (GPX4) expression to induce ferroptosis through blocking the interaction between EP300 and GPX4 gene promoter via associating with EP300. In summary, this study illuminated that combination regimen of G-CSF and rhTPO improved the curative effect on elderly patients with leukemia through inducing pyroptosis and ferroptosis of leukemia cells. Therefore, our results provided a theoretical basis for combination regimen of G-CSF and rhTPO treating leukemia and potential therapeutic targets for leukemia.

[Intraoperative IPC combined with 3M warming instrument to prevent lower extremity deep venous thrombosis in patients undergoing proximal femoral anti rotation intramedullary nailing].

OBJECTIVE: To explore the effect of intermittent pneumatic compression(IPC) combined with 3M thermometer on the prevention of deep venous thrombosis(DVT) in patients with femoral intertrochanteric fracture. METHODS: From March 2016 to August 2019, 127 patients with femoral intertrochanteric fractures who underwent proximal femoral nail antirotation(PFNA) were retrospectively analyzed. They were divided into two groups according to different methods of thrombus prevention and treatment. Among them, 63 patients in group A did not use IPC and 3M thermometer;64 cases in group B were treated with IPC combined with 3M thermometer. Color Doppler ultrasound was used to dynamically monitor the DVT and changes of lower limbs during perioperative period. The venous thrombosis of lower limbs was monitored at 0, 24, 72 h and > 72 h after operation(recheck every 3 days until discharge). RESULTS: Occurrence of DVT of lower limbs after PFNA operation in two groups:there were 5 cases (7.8%) in group B and 20 cases (31.7%) in group A, there was significant difference between two groups (P=0.001). There was no significant difference in lower limb DVT between two groups at 0, 72 and > 72 h after operation(P>0.05), but the formation rate of group A was significantly higher than that of group B at 24 h after operation (P=0.049). There was no significant difference in DVT formation between group A and group B(P>0.05). However, the formation of DVT in group A was significantly higher than that in group B(P=0.012). CONCLUSION: Intraoperative IPC combined with 3M thermostat can effectively prevent DVT of lower limbs in patients undergoing PFNA surgery.

Diet Quality Scores and Asthenoteratozoospermia Risk: Finding From a Hospital-Based Case-Control Study in China.

Objective: We aimed to examine associations of diet quality scores, including the dietary approaches to stop hypertension (DASH), alternate Healthy Eating Index (AHEI), and Chinese Healthy Eating Index (CHEI) with asthenoteratozoospermia risk in China. Methods: Among 254 cases and 633 controls in a hospital-based case-control study in Shenyang, Liaoning Province, China, DASH, AHEI, and CHEI were calculated using a validated food frequency questionnaire. Asthenotetrazoospermia was evaluated according to World Health Organization guidelines. Unconditional multiple logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between quality diet scores and asthenoteratozoospermia risk. Results: We found that the CHEI score was inversely associated with asthenoteratozoospermia risk, with ORs of 0.59 (95% CI 0.39, 0.88) and 0.59 (95% CI 0.39, 0.88) for the 2nd and 3rd tertiles vs. the 1st tertile, respectively (P trend < 0.05). In addition, our data indicated that each standard deviation increase in CHEI, AHEI-2010, and DASH score was associated with 19, 13, and 17% decreased risk of asthenoteratozoospermia, respectively. Conclusion: Our findings suggest that higher adherence to the CHEI, AHEI-2010, and DASH diet quality scores may reduce the risk of asthenoteratozoospermia, especially for younger participants.

The impact of value co-creation on consumer citizenship behavior: Based on consumer perspective.

This research investigated the value co-creation behaviors in livestreaming platforms and the internal mechanism of perceived value on consumer value co-creation behavior on the short-video platform TikTok. This research selected the Tiktok platform as the research object, and uses structural equation model to analyze consumer data. The results indicated that consumer-perceived value mediates the relationship between consumer engagement and citizenship behaviors. In addition, short-video platforms exhibit significant community attributes, and interactive behavior forms the primary part of consumer engagement that enhances the perceived value. Consumers join short-video platforms to look for communities that interest them. Consumers' responses generate the perceived value. Thus, it enhances consumers' intentions to continue using a particular service, which then increases the likelihood of citizenship behavior. This study also found that consumers' creative behavior in short-video platforms embodies social and functional values. This suggested that consumers of livestreaming and short-video platforms such as TikTok tend to seek social recognition by sharing their opinions or daily lives. The examination of the mediating role of perceived value on the relationship between consumer engagement behavior and citizenship behavior revealed that perceived value significantly mediated the relationship between consumer engagement behavior and citizenship behavior. This provided evidence of the fact that consumers usually actively participate on the platform by uploading content and sharing their creations, with the motivation to generate significant social impact and gain the recognition of others. Firstly, TikTok's consumers deeply engage on platforms in which their cognitive messages are integrated into the platform through interacting with others, browsing, and creating short videos. Secondly, TikTok provides a channel with high level of interactivity that facilitates social interaction among strangers. Video uploaders and fans develop positive interactive relationships. Thirdly, TikTok viewers may become video providers at some point; the act of co-creation creates economic value for the platform and generates emotional, functional, and social values for its consumers.

Extracellular vesicles carrying miRNA-181b-5p affects the malignant progression of acute lymphoblastic leukemia.

OBJECTIVE: To investigate how serum extracellular vesicles (EVs)-carried miRNA-181b-5p affected the proliferation, cell cycle and apoptosis of acute lymphoblastic leukemia (ALL) cells. METHODS: Differentially expressed miRNAs related to ALL were screened by bioinformatics analysis, and the localization of target miRNA was searched by its expression. qRT-PCR was adopted to confirm the expression of miRNA-181b-5p. Flow cytometry and fluorescence microscopy were applied to evaluate EVs internalization. MTT assay was employed to verify the proliferation of ALL cells. Cell cycle and apoptosis were analyzed by flow cytometry. Transwell assay was applied to evaluate migration and invasion abilities. RESULTS: High expression of miRNA-181b-5p was proved in ALL cell lines, and miRNA-181b-5p enriched in the exosomes and vesicles of blood cells. In the meantime, it was found that EVs carrying miRNA-181b-5p could be internalized by ALL cells and thus the expression of miRNA-181b-5p was up-regulated. Cell function assays showed that the proliferation, migration, invasion abilities of ALL cell lines were promoted in miRNA-181b-5p mimic group or the group co-culturing ALL-derived EVs and BALL-1 cell lines. The percentage of cells in G0/G1 phase was reduced and cell apoptosis was also inhibited. CONCLUSION: miRNA-181b-5p carried by EVs in peripheral blood of ALL patients can enter ALL cells and thus promote the malignancy of ALL cells.

Nomogram Model for Dynamic and Individual Prediction of Cardiac Response and Survival for Light Chain Amyloidosis in 737 Patients With Cardiac Involvement.

OBJECTIVE: Light chain amyloidosis (AL) with cardiac involvement is associated with poor prognosis. The existing prognostic assessment system does not consider treatment-related factors, and there is currently no effective system for predicting the response. The purpose of this study was to build an individualized, dynamic assessment model for cardiac response and overall survival (OS) for AL patients with cardiac involvement. METHODS: The records of 737 AL patients with cardiac involvement were collected through cooperation with 18 hospitals in the Chinese Registration Network for Light-chain Amyloidosis (CRENLA). We used univariate and multivariate analyses to evaluate the prognostic factors for OS and cardiac response. Then, two nomogram models were developed to predict OS and cardiac response in AL patients with cardiac involvement. RESULTS: A nomogram including four independent factors from the multivariate Cox proportional hazards analysis-Mayo staging, courses of treatment, hematologic response, and cardiac response-was constructed to calculate the possibility of achieving survival by adding all the points associated with four variables. The higher the score, the more likely death would occur. The other nomogram model included the courses of treatment, hematological response, and different treatment regimens, and was correlated with cardiac response. The higher the score, the more likely a cardiac response would occur. CONCLUSION: In conclusion, based on the large Chinese cohort of patients with AL and cardiac involvement, we identified nomogram models to predict cardiac response and OS. These models are more individualized and dynamic, and therefore, they have important clinical application value.

Case Report: Management of Primary Tracheobronchial Light Chain Amyloidosis in a Patient With Biclonal Gammopathy Using a Systemic Bortezomib-Based Regimen.

Primary tracheobronchial light chain (AL) amyloidosis is a rare and heterogeneous disease characterized by the buildup of amyloid deposits in the airway mucosa. Although its treatment remains challenging, the current view is that the localized form can be treated conservatively due to its slow progression. While radiotherapy has proven effective in treating localized form of the disease, some patients do not respond to local treatment and continue to experience poor quality of life, highlighting the need to explore additional treatment strategies. In this report, we discuss a case of primary tracheobronchial AL amyloidosis with biclonal gammopathy (IgA κ and IgG κ) in a 46-year-old man who was transferred to our hospital due to dyspnea progression over the preceding 3 years. Chest computed tomography revealed irregular tracheobronchial stenosis with wall thickening, and histological examination of the bronchial biopsies confirmed the diagnosis of endobronchial AL amyloidosis. Owing to the poor effect of radiation therapy and treatments for improving airway patency, he was treated with a systemic chemotherapy regimen [cyclophosphamide-bortezomib-dexamethasone (CyBorD)]. We observed substantial improvements in his dyspnea, highlighting the potential of systemic therapy to improve quality of life of patients with tracheobronchial AL amyloidosis. However, the long-term pathological changes associated with local bronchial lesions require further investigation.