Plasma cell-free DNA promise monitoring and tissue injury assessment of COVID-19.

Coronavirus 2019 (COVID-19) is a complex disease that affects billions of people worldwide. Currently, effective etiological treatment of COVID-19 is still lacking; COVID-19 also causes damages to various organs that affects therapeutics and mortality of the patients. Surveillance of the treatment responses and organ injury assessment of COVID-19 patients are of high clinical value. In this study, we investigated the characteristic fragmentation patterns and explored the potential in tissue injury assessment of plasma cell-free DNA in COVID-19 patients. Through recruitment of 37 COVID-19 patients, 32 controls and analysis of 208 blood samples upon diagnosis and during treatment, we report gross abnormalities in cfDNA of COVID-19 patients, including elevated GC content, altered molecule size and end motif patterns. More importantly, such cfDNA fragmentation characteristics reflect patient-specific physiological changes during treatment. Further analysis on cfDNA tissue-of-origin tracing reveals frequent tissue injuries in COVID-19 patients, which is supported by clinical diagnoses. Hence, our work demonstrates and extends the translational merit of cfDNA fragmentation pattern as valuable analyte for effective treatment monitoring, as well as tissue injury assessment in COVID-19.

Stem cell like memory T cells: A new paradigm in cancer immunotherapy.

Stem cell like memory T (TSCM) cells have emerged as the apex of memory T cell differentiation for their properties of self-renewal and replenishing progenies. With potent long-term persistence, proliferative capacity and antitumor activity, TSCM cells were thought to be the ideal candidate for cancer immunotherapies. Several strategies have been proposed, such as manipulations of cytokines, metabolic factors, signal pathways, and T cell receptor signal intensity, to induce more TSCM cells in vitro, in the hope that they could reach a clinical order of magnitude to provide more long-lasting and effective anti-tumor effects in vivo. In this review, we summarized the differentiation characteristics of TSCM cells and strategies to generate more TSCM cells. We focused on their roles and application in the cancer immunotherapy especially in adoptive cell transfer therapy and cancer therapeutic vaccines, and hopefully provided clues for future understanding and researches.

Prevalence and associated factors for workplace violence among general practitioners in China: a national cross-sectional study.

BACKGROUND: General practitioners (GPs) were at risk of violence in their everyday working lives. Workplace violence (WPV) among GPs is a global public health concern. This study aimed to investigate the prevalence and factors associated with WPV among GPs in China. METHODS: A cross-sectional study was conducted among 4376 GPs in eastern, central, and western China between March and May 2021 using a structured self-administered questionnaire. The multivariable stepwise logistic regression model was used to examine the factors associated with WPV among GPs in China. RESULTS: Among these respondents, 14.26% of them reported exposure to WPV in the past 12 months. GPs who were female, practised in a rural area, made home visits occasionally, worked in a fair or good practice environment or work environment, and had a fair or good relationship with patients were less likely to encounter any type of WPV. In addition, GPs who served patients over 20 per day and worked overtime occasionally or frequently were more likely to be exposed to WPV. The determinants of WPV varied in different types of WPV and sexes. CONCLUSIONS: The prevalence of WPV among GPs is low in China. Our findings could inform the measures to reduce the WPV among GPs.

Mobile isolation wards in a fever clinic: a novel operation model during the COVID-19 pandemic.

A fever clinic within a hospital plays a vital role in pandemic control because it serves as an outpost for pandemic discovery, monitoring and handling. As the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan was gradually brought under control, the fever clinic in the West Campus of Wuhan Union Hospital introduced a new model for construction and management of temporary mobile isolation wards. A traditional battlefield hospital model was combined with pandemic control regulations, to build a complex of mobile isolation wards that used adaptive design and construction for medical operational, medical waste management and water drainage systems. The mobile isolation wards allowed for the sharing of medical resources with the fever clinic. This increased the capacity and efficiency of receiving, screening, triaging and isolation and observation of patients with fever. The innovative mobile isolation wards also controlled new sudden outbreaks of COVID-19. We document the adaptive design and construction model of the novel complex of mobile isolation wards and explain its characteristics, functions and use.

Comparison of chronic myeloid leukemia stem cells and hematopoietic stem cells by global proteomic analysis.

Tyrosine kinase inhibitors (TKIs) that target BCR-ABL are the standard first-line therapy for patients with chronic-phase CML. However, TKIs cannot eliminate quiescent leukemia stem cells (LSCs) which persist in all patients on long-term therapy and provides a reservoir for disease progression and recurrence. Many researches have confirmed that TKI-resistant LSCs compartment can be captured within CD26 + fraction. In order to analyze distinctive biological characteristics of TKI-resistant LSCs, we isolated the CD34 + CD38-CD26+, CD34 + CD38-CD26-and CD34 + CD38 + cells from 8 CML patients utilizing magnetic and flow sorting, and analyzed the global proteomic expression through high-resolution LC-MS/MS analysis. In the work, we discovered that a list of dysregulated proteins involved in energy metabolism and carcinogenesis, including PPARD, IL1-RAP, HNF, S15A2, PCLO, VA0D1, CKLF5, were extremely upregulated in the CD26 + LSCs while some majoring in DNA mismatch repair or related to cell senescence, such as MLH3, NOLC1, were downregulated. Additionally, we verified the upregulation of PPARD in both CML patients-derived CD26 + LSCs and donor-derived BCR-ABL1 overexpressed HSCs. These results open in turn new therapeutic avenues for targeting TKI-insensitive LSCs.

T cells expressing CD26-specific chimeric antigen receptors exhibit extensive self-antigen-driven fratricide.

Background: Immunotherapy utilizing T cells genetically modified to express chimeric antigen receptors (CARs) is rapidly emerging as a promising novel treatment for hematological and nonhematological malignancies. In order to target the TKI-insensitive leukemia stem cells (LSCs) in chronic myeloid leukemia (CML) by CAR T cells, we chose CD26 as a cell surface tumor-associated antigen due to preferentially expression on LSCs. Additionally, CD26 has also been suggested to be a multipurpose therapeutic target for other cancer. Therefore, developing the CD26-targeting CAR T cells may be a promising therapy for not only LSCs but also other CD26+ cancer cells. Methods: We designed the second-generation CD26-targeting CAR utilizing 4-1BB (CD137) as costimulatory domain, and transduced T cells with CD26-CAR containing lentiviral. Then we evaluated the transduction efficiency and expansion ability, and demonstrated the existence of self-antigen-driven fratricide by cytokine assay and cytotoxicity assay. Results: Anti-CD26-4-1BB-CAR T cells exhibited poor viability, multiple cytokine secretion, down-regulation of CD26 and direct cytotoxicity against themselves, indicating self-antigen-driven fratricide. Conclusion: Eradicating CML-LSCs via anti-CD26-4-1BB-CAR T cells is not applicable, and optimized design or alternative target is needed.

Disulfiram/copper targets stem cell-like ALDH+ population of multiple myeloma by inhibition of ALDH1A1 and Hedgehog pathway.

Multiple myeloma stem cells (MMSCs) have been considered as the major cause resulting in relapse. Eradicating MMSCs may be an effective strategy to improve the outcome of multiple myeloma (MM). Increased activity of aldehyde dehydrogenase (ALDH) has been found in MMSCs, but whether inhibiting ALDH activity can eliminate MMSCs remains unknown. Disulfiram (DS) has been reported as an inhibitor of ALDH, and increasing studies showed it has anti-cancer effects in a copper (Cu)-dependent manner. In this study, we isolated ALDH+ cells of MM by Aldefluor assay and demonstrated they possessed tumorigenesis capacities in vitro and in vivo. Next, we investigated the effects of DS with or without Cu on suppressing the stemness of MM both in vitro and in vivo. We found that DS/Cu eliminated the stem cell-like ALDH+ cells. Furthermore, we demonstrated that DS/Cu inhibited the expression of stem cell transcription factors NANOG and OCT4, and abolished the clonogenicity of MM. We also showed that DS/Cu reduced the tumor growth and inhibited stemness of MM in xenograft model. We further found the specific target of DS/Cu is ALDH1A1 and DS/Cu inhibited the Hedgehog (Hh) pathway transcription factors Gli1 and Gli2 regulated by ALDH1A1 at least in part. Our data suggest that DS/Cu can inhibit the ALDH+ stem cell-like cells through ALDH1A1 and Hh pathway, which may be a promising therapeutic agent in eradicating stem cell-like cells of MM.

Heat inactivation does not alter host plasma cell-free DNA characteristics in infectious disease research.

BACKGROUND: Cell-free DNA (cfDNA) is a promising analyte for non-invasive liquid biopsy, carrying abundant signatures for disease diagnosis and monitoring. In infectious disease researches, blood plasma samples are routinely heat-inactivated before proceeding with downstream analyses. However, the effects of heat inactivation on cfDNA fragmentomic analysis remain largely unclear, potentially introducing biases or altering the characteristics of cfDNA. METHODS: We performed a comprehensive investigation of cfDNA concentrations and fragmentomics in 21 plasma samples from 7 healthy individuals, by comparing the sample group without the heat inactivation to those exposed to once or twice heat-inactivation at 56 °C for 30 min and following freeze-thaw. RESULTS: Plasma samples with once and twice heat inactivation displayed no significant deviations in primary characteristics, including cfDNA concentrations, size profiles, end motif features, and genome-wide distributions, compared to samples without heat treatment. CONCLUSIONS: Heat-inactivated cfDNA can be utilized for liquid biopsy in infectious disease researches, without substantial impact on cfDNA concentrations and fragmentomic properties. This study provides essential insights into the effects of heat inactivation on cfDNA properties and will contribute to the development of reliable non-invasive biomarkers for infectious disease.

Bioinformatic-based genetic characterizations of neural regulation in skin cutaneous melanoma.

Background: Recent discoveries uncovered the complex cancer-nerve interactions in several cancer types including skin cutaneous melanoma (SKCM). However, the genetic characterization of neural regulation in SKCM is unclear. Methods: Transcriptomic expression data were collected from the TCGA and GTEx portal, and the differences in cancer-nerve crosstalk-associated gene expressions between normal skin and SKCM tissues were analyzed. The cBioPortal dataset was utilized to implement the gene mutation analysis. PPI analysis was performed using the STRING database. Functional enrichment analysis was analyzed by the R package clusterProfiler. K-M plotter, univariate, multivariate, and LASSO regression were used for prognostic analysis and verification. The GEPIA dataset was performed to analyze the association of gene expression with SKCM clinical stage. ssGSEA and GSCA datasets were used for immune cell infiltration analysis. GSEA was used to elucidate the significant function and pathway differences. Results: A total of 66 cancer-nerve crosstalk-associated genes were identified, 60 of which were up- or downregulated in SKCM and KEGG analysis suggested that they are mainly enriched in the calcium signaling pathway, Ras signaling pathway, PI3K-Akt signaling pathway, and so on. A gene prognostic model including eight genes (GRIN3A, CCR2, CHRNA4, CSF1, NTN1, ADRB1, CHRNB4, and CHRNG) was built and verified by independent cohorts GSE59455 and GSE19234. A nomogram was constructed containing clinical characteristics and the above eight genes, and the AUCs of the 1-, 3-, and 5-year ROC were 0.850, 0.811, and 0.792, respectively. Expression of CCR2, GRIN3A, and CSF1 was associated with SKCM clinical stages. There existed broad and strong correlations of the prognostic gene set with immune infiltration and immune checkpoint genes. CHRNA4 and CHRNG were independent poor prognostic genes, and multiple metabolic pathways were enriched in high CHRNA4 expression cells. Conclusion: Comprehensive bioinformatics analysis of cancer-nerve crosstalk-associated genes in SKCM was performed, and an effective prognostic model was constructed based on clinical characteristics and eight genes (GRIN3A, CCR2, CHRNA4, CSF1, NTN1, ADRB1, CHRNB4, and CHRNG), which were widely related to clinical stages and immunological features. Our work may be helpful for further investigation in the molecular mechanisms correlated with neural regulation in SKCM, and in searching new therapeutic targets.

Factors associated with the incidence and the expenditure of self-medication among middle-aged and older adults in China: A cross-sectional study.

Background: With the accelerated ageing of population and the growing prevalence of various chronic diseases in China, self-medication plays an increasingly important role in complementing the health care system due to its convenience and economy. Objective: This study aimed to investigate the incidence of self-medication and the amount of self-medication expenditure among middle-aged and older adults in China, and to explore factors associated with them. Methods: A total of 10,841 respondents aged 45 years and older from the China Health and Retirement Longitudinal Study (CHARLS) wave 4 which conducted in 2018 were included as the sample of this study. The two-part model was adopted to identify the association between the incidence of self-medication and the amount of self-medication expenditure and specific factors, respectively. Results: The incidence of self-medication among Chinese middle-aged and older adults was 62.30%, and the average total and out-of-pocket (OOP) pharmaceutical expenditure of self-medication of the self-medicated individuals were 290.50 and 264.38 Chinese yuan (CNY) respectively. Participants who took traditional Chinese medicine (TCM), self-reported fair, and poor health status, suffered from one and multiple chronic diseases had strongly higher incidence of self-medication. Older age and multiple chronic diseases were strongly associated with higher expenditure of self-medication. Those who took TCM had more self-medication expenditure, while those who drank alcohol had less. Conclusion: Our study demonstrated the great prevalence of self-medication among middle-aged and older adults in China and the large pharmaceutical expenditure that come with it, especially in the high-risk groups of self-medication identified in this paper. These findings enhanced our understanding of self-medication behaviors among Chinese middle-aged and older adults and may contribute to the formulation of targeted public health policy.

Successful treatment discontinuation in CML patients with full-dose and low-dose TKI: Results from real-world practice.

Background: In clinical studies, some patients who achieve deep molecular response (DMR) can successfully discontinue tyrosine kinase inhibitor (TKI). TKI dose reduction is also an important aspect of alleviating adverse effects and improving quality of life. This study aimed to explore the outcome after drug withdrawal in Chinese CML patients. Methods: We conducted a retrospective analysis of the outcome of 190 patients who stopped TKI. 27 patients experienced dose reduction before TKI discontinuation. The median duration of TKI treatment and MR4 before discontinuation was 82 months and 61 months. Results: With median follow-up after stopping TKI treatment of 17 months, the estimated TFR (Treatment Free Remission) were 76.9% (95%CI, 70.2%-82.4%), 68.8% (95%CI, 61.3%-75.2%), and 65.5% (95%CI, 57.4%-72.5%) at 6, 12 and 24 months. For full-dose and low-dose TKI groups, the TFR at 24 months was 66.7% and 55.8% (p = 0.320, log-rank). Most patients (56/57) quickly achieved MMR after restarting TKI treatment. Multivariable analysis showed that patients with TKI resistance had a higher risk of molecular relapse than patients without TKI resistance (p < 0.001). Conclusion: TFR rates were not impaired in patients experiencing dose reduction before TKI discontinuation compared to patients with full-dose TKI. Our data on Chinese population may provide a basis for the safety and feasibility of TKI discontinuation, including discontinuation after dose reduction, in clinical practice.

Quality-of-life, mental health, and perspective on TKI dose reduction as a prelude to discontinuation in chronic phase chronic myeloid leukemia.

BACKGROUND: Treatment-free remission (TFR) has become the main target for chronic myeloid leukemia (CML). Tyrosine kinase inhibitors (TKI) dose optimization is crucial in managing adverse events, and improving adherence in clinical practice. In persons achieving a deep molecular response (DMR), some data suggest TKI dose reduction before discontinuation does not change success rate of achieving TFR, but this is controversial. However, data on quality-of-life (QoL) and mental health in CML patients with full-dose TKI, low-dose TKI, and TKI discontinuation are limited. Moreover, recent evidence indicating the feasibility of TKI dose reduction and discontinuation after dose reduction, which may change CML patients' perspectives on TKI discontinuation. METHODS: We conducted a cross-sectional study using online questionnaires to explore the QoL, mental health in patients with diverse TKI dose, and perspective on TKI dose reduction as a prelude to discontinuation. RESULTS: 1450 responses were included in the analysis. 44.3% of respondents reported a moderate-to-severe impact of TKI treatment on their QoL. 17% of respondents had moderate-to-severe anxiety. 24.4% of respondents had moderate-to-severe depression. In 1326 patients who had not discontinued their medication, 1055 (79.6%) patients reported they would try TKI discontinuation because of concerns over side effects of long-term medication (67.9%), financial burden (68.7%), poor QoL (77.9%), pregnancy needs (11.6%), anxiety and depression while taking TKI (20.8%), inconvenience of TKI treatment (22.2%). 613 of 817 (75.0%) patients on full-dose TKI therapy indicated they preferred trying a dose reduction before discontinuing TKI therapy after dose reduction compared with 31 (3.8%) preferring no dose reduction before stopping. CONCLUSIONS: TKI dose reduction showed a significant improvement of patients' QoL and mental health, comparable to the effect of TKI discontinuation. Most patients indicated they preferred dose reduction before stopping TKI therapy. In clinical practice, TKI dose reduction can be considered as a bridge from full-dose treatment to discontinuation. Our results showed that tyrosine kinase inhibitors (TKI) dose reduction showed a significant improvement of patients' quality-of-life and mental health, comparable to the effect of TKI discontinuation. Most patients desire to discontinue TKI in the future. TKI discontinuation after dose reduction is more acceptable compared to discontinuing it directly. In clinical practice, TKI dose reduction can be considered as a bridge from full-dose treatment to discontinuation. Please do not hesitate to contact me in case further clarification is needed with this submission.

The function of myeloid-derived suppressor cells in COVID-19 lymphopenia.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic and presents a significant danger to public health. Lymphopenia is considered to be the defining characteristic of severe COVID-19, especially in elderly people. Lymphopenia has been suggested as a pivotal factor in disease severity. To minimize mortality in COVID-19 patients, it is essential to have a deeper understanding of the processes behind lymphocytopenia. Recently, myeloid-derived suppressor cells (MDSCs) have been confirmed as a key mediator of lymphopenia. MDSCs are characterized by their powerful capacity to suppress T cells and eventually contribute to the course of illness. Targeting these cells may improve the disease prognosis. In this article, we analyze the available research on MDSCs in lymphopenia and discuss their immunopathologic changes and prospective therapeutic targets in patients with COVID-19 lymphocytopenia.

Bidirectional regulation between tumor cell-intrinsic PD-L1 and TGF-ß1 in epithelial-to-mesenchymal transition in melanoma.

Background: Transforming growth factor-ß1 (TGF-ß1) is the predominant form of TGF-ß and induces epithelial-to-mesenchymal transition (EMT) in melanoma. Tumor cell-intrinsic programmed death ligand-1 (PD-L1) plays a crucial role in maintenance of the EMT in melanoma. However, the relationship among tumor cell-intrinsic PD-L1, TGF-ß1 and EMT is very complicated. Methods: We investigated the bidirectional regulation between cell-intrinsic PD-L1 and TGF-ß1 in melanoma, and explored the role of PD-L1 in TGF-ß1-induced EMT and tumor progression. Results: We found that TGF-ß1 upregulated PD-L1 expression in B16-F0 and B16-F10 melanoma cells. Interestingly, PD-L1 also enhanced the intracellular TGF-ß1 mRNA levels and induced the secretion of TGF-ß1. Immunohistochemical staining revealed that PD-L1 protein expression was co-localized with α-smooth muscle actin (SMA) protein expression in melanoma, suggesting that PD-L1 was associated with EMT. By using shRNA lentivirus to knockdown PD-L1 (PD-L1-shRNA) in melanoma cell lines, we showed that TGF-ß1-induced EMT was significantly inhibited in PD-L1-shRNA melanoma cells, which was characterized by the lower fibronectin (FN1) mRNA and higher E-cadherin (CDH1) mRNA levels (both are EMT markers) than that in control. TGF-ß1-induced melanoma cell proliferation and migration were also markedly inhibited in PD-L1-shRNA cells. Consistent with the observation in vitro, PD-L1 knockdown inhibited tumor growth and repressed TGF-ß1-induced EMT characterized by reduction of FN1 and increase of CDH1 in mouse model. Conclusions: The present study demonstrated a bidirectional regulation between cell-intrinsic PD-L1 and TGF-ß1 in melanoma, which may help in designing promising combinations which include targeting TGF-ß1 signaling along with PD-L1.

Lineage-specific positive selection on ACE2 contributes to the genetic susceptibility of COVID-19.

The Angiotensin-Converting Enzyme-2 (ACE2) gene, located on Xp22.2, attracts a great deal of attention because the protein it encodes is believed to be the functional cellular receptor for the new coronavirus (SARS-CoV-2). However, recent studies are controversial, especially concerning the intrinsic link between ACE2 diversity and COVID-19 susceptibility. Here, we conduct a population genetic study on ACE2 in 6354 individuals representing 210 present-day populations and 5329 individuals of ancient or archaic groups. We dissected the genetic architecture of ACE2 and identified two major haplogroups (hg) in East Asians, i.e. ACE2-hg1 (43%) and ACE2-hg2 (53%), while other populations harbor more diverse ACE2-hgs. Accordingly, there was a significant loss of ACE2 common variations in East Asians in contrast to the X-chromosome-wide and genome-wide patterns. Notably, association analysis between ACE2-hgs and COVID-19 severity in 1229 Han Chinese individuals with various levels of COVID-19 severity showed a higher risk of ACE2-hg1 (odds ratio = 1.56, P < 0.01) and a lower risk of ACE2-hg2 (odds ratio = 0.65, P < 0.01). Interestingly, ACE2-hg1 is in strong linkage disequilibrium with rs1849863-C, which is an assumed risk factor of elevated plasma ACE2 level and is related to a higher risk of COVID-19 severity, hospitalization and infection. Strikingly, remarkable signatures of positive selection were detected, especially on ACE2-hg2, and were traced back to 100 000 years ago (but rose to a strong level during the Bronze Age, 5000∼3000 years ago, in East Asians). The selection pressures could have stemmed from multiple sources, but pre-COVID-19 viral epidemics and pandemics might have been potential driving forces, which consequently contributed to the genetic susceptibility to COVID-19 within and between populations.

Rare Variants in Inborn Errors of Immunity Genes Associated With Covid-19 Severity.

Host genetic factors have been shown to play an important role in SARS-CoV-2 infection and the course of Covid-19 disease. The genetic contributions of common variants influencing Covid-19 susceptibility and severity have been extensively studied in diverse populations. However, the studies of rare genetic defects arising from inborn errors of immunity (IEI) are relatively few, especially in the Chinese population. To fill this gap, we used a deeply sequenced dataset of nearly 500 patients, all of Chinese descent, to investigate putative functional rare variants. Specifically, we annotated rare variants in our call set and selected likely deleterious missense (LDM) and high-confidence predicted loss-of-function (HC-pLoF) variants. Further, we analyzed LDM and HC-pLoF variants between non-severe and severe Covid-19 patients by (a) performing gene- and pathway-level association analyses, (b) testing the number of mutations in previously reported genes mapped from LDM and HC-pLoF variants, and (c) uncovering candidate genes via protein-protein interaction (PPI) network analysis of Covid-19-related genes and genes defined from LDM and HC-pLoF variants. From our analyses, we found that (a) pathways Tuberculosis (hsa:05152), Primary Immunodeficiency (hsa:05340), and Influenza A (hsa:05164) showed significant enrichment in severe patients compared to the non-severe ones, (b) HC-pLoF mutations were enriched in Covid-19-related genes in severe patients, and (c) several candidate genes, such as IL12RB1, TBK1, TLR3, and IFNGR2, are uncovered by PPI network analysis and worth further investigation. These regions generally play an essential role in regulating antiviral innate immunity responses to foreign pathogens and in responding to many inflammatory diseases. We believe that our identified candidate genes/pathways can be potentially used as Covid-19 diagnostic markers and help distinguish patients at higher risk.

ACSL1 promotes imatinib-induced chronic myeloid leukemia cell senescence by regulating SIRT1/p53/p21 pathway.

Although tyrosine kinase inhibitors (TKIs) improve the prognosis of chronic myeloid leukemia (CML) patients, resistance to TKIs and residual leukemia stem cells (LSCs) inevitably become the bottleneck of cure. Therefore, we need to explore novel treatment strategies based on conventional treatment strategies. Our previous study found that CML cell senescence may be one of the main factors to achieve clinical cure of CML. Studies have shown that lipid metabolism plays a key role in cellular senescence. Here, we found that long-chain acyl-CoA synthetase 1 (ACSL1) was significantly up-regulated in senescent CML cells. Furthermore, we demonstrated that overexpression of ACSL1 induces senescence and inhibits cell growth in K562 cells by altering cell cycle progression, and enhances the proliferation-inhibiting effect of imatinib. Overexpression of ACSL1 enhances imatinib-induced tumorigenic decline in K562 cells in vivo. Knockdown of ACSL1 reverses imatinib-induced senescence in K562 cells. Mechanistically, overexpression of ACSL1 induced senescence in K562 cells via the SIRT1/p53/p21 axis. Collectively, our study showed that ACSL1 promotes imatinib-induced K562 cells senescence and tumor growth by regulating SIRT1/p53/p21 pathway. The ACSL1/SIRT1/p53 signal axis is a novel mechanism of cell senescence in CML and a new potential target for eradication of CML LSCs.

Changes in the medical-seeking pattern and daily behavior of hematopoietic stem-cell transplant recipients during the COVID-19 epidemic: An online survey in Hubei Province, China.

Background: To curb the spread of the coronavirus disease 2019 (COVID-19) epidemic, the Chinese government shut down Wuhan city from January 23rd to April 8th, 2020. The COVID-19 epidemic not only leads to widespread illness but also affects the diagnosis and treatment of hematopoietic stem-cell transplant (HSCT) recipients. Objective: To investigate the medical-seeking pattern and daily behavior changes in Hubei Province during the COVID-19 epidemic in Hubei Province during the lockdown. Methods: We conducted a multicenter, cross-sectional, web-based investigation among 325 HSCT recipients by online questionnaires in Hubei Province during the COVID-19 epidemic. Results: A total of 145 complete responses were collected both before and during the epidemic questionnaires. The participants from pre-epidemic group preferred to go to hospital (68.29%) when they experienced influenza-like symptoms. The majority of the patients elected to take oral drugs by themselves (40%) or consulted their attending physicians online or by telephone during the lockdown (23.33%). 64.83% had difficulties in purchasing drugs during the lockdown, which was significantly higher than the proportion of the pre-epidemic group (24.83%) (P < 0.05). The participants preferred to purchase drugs online (23.40%) and decrease or withdraw drugs (18.09%) during the epidemic. The number of participants received regular re-examinations during the epidemic decreased sharply. The proportion of wearing masks and isolating themselves at home increased significantly during the epidemic. No statistic difference was observed in the incidence of graft-versus-host disease (GVHD)complications in participants between the during the epidemic group and the pre-epidemic group. In our study, six patients were confirmed to have COVID-19, and half of them died due to COVID-19-related complications. Conclusion: The medical-seeking pattern and daily behavior of HSCT recipients changed during the lockdown; the methods of self-protection, online consultation and drug delivery can help patients receive necessary follow-up and reduce the occurrence of COVID-19.

Circular RNA circCRKL inhibits the proliferation of acute myeloid leukemia cells via the miR-196a-5p/miR-196b-5p/p27 axis.

As a new type of non-coding RNA, the role of circular RNA (circRNA) in various diseases and tumors has received considerable attention. Studies have shown that circRNAs play an important role in the progression of acute myeloid leukemia (AML) via different mechanisms. However, the specific underlying molecular mechanism of circRNAs in the proliferation of AML cells remians unclear. This study aimed to clarify the biological role and mechanism of circCRKL in AML. The results indicated low circCRKL expression in AML cell lines and samples. Moreover, the overexpression of circCRKL inhibited the proliferation and colony-forming ability of AML cells, while its silencing promoted them. In addition, bioinformatics tools and luciferase assays revealed that circCRKL could sponge miR-196a-5p and miR-196b-5p to promote the expression of p27. Furthermore, circCRKL inhibited AML cell proliferation via the miR-196a-5p/miR-196b-5p/p27 axis, suggesting a potential new target for AML therapy.