The comorbid network characteristics of anxiety and depressive symptoms among Chinese college freshmen.

BACKGROUND: This study aimed to investigate the interplay between anxiety and depressive symptoms in Chinese college freshmen using the causal system perspective (CSP), which differs from the traditional common cause perspective (CCP) by providing an alternative explanation by attributing comorbidity to direct interactions among symptoms. METHODS: A convenience sample of 2,082 Chinese college freshmen (39.51% male, Mage = 18.61) from a normal university completed the Generalized Anxiety Disorder 7-Item Scale (GAD-7) and the Patient Health Questionnaire (PHQ-9). Network analysis was conducted and evaluated as to centrality, stability, node predictability, and bridging features. Moreover, the moderated network model (MNM) was utilized to detect the moderation effects of gender in the comorbidity network. RESULTS: The network of anxiety and depressive symptoms exhibited stability, characterized by the core symptoms of "restlessness", "lack of energy", and "excessive worry about control", as well as the bridging symptoms of "fearfulness", "sad mood", and "irritability". Notably, the nodes representing "uncontrollable worry" and "difficulty in relaxation" demonstrated the highest predictive power. Gender did not exert any moderating effects on the anxiety and depressive symptom network. CONCLUSION: These results reinforce that certain anxiety or depressive symptoms are more central than others, and thus play a more vital role in the comorbid network. These findings highlight underlying potential targeting symptoms to consider in future interventions.

NSCLC extracellular vesicles containing miR-374a-5p promote leptomeningeal metastasis by influencing blood‒brain barrier permeability.

Leptomeningeal metastasis (LM) is a devastating complication of advanced non-small cell lung cancer (NSCLC). Diagnosis and monitoring of LM can be challenging. Extracellular vesicles (EVs) microRNAs (miRNAs) have become a new noninvasive diagnostic biomarker. The purpose of this study was to examine the clinical value and role of EVs miRNAs in NSCLC-LM. According to next-generation sequencing (NGS), miRNAs with differential expression of EVs in serum of NSCLC patients with LM and non-LM were detected to find biological markers for the diagnosis of LM. Cellular and in vivo experiments were conducted to explore the pathogenesis of EVs miRNA promoting LM in NSCLC. In the present study, we first demonstrated the serum level of EV-associated miR-374a-5p in patients with LM of lung cancer was much higher than that in patients without LM and was correlated with the survival time of patients with LM. Further studies showed that EVs miR-374a-5p efficiently destroys tight junctions and the integrity of the cerebral microvascular endothelial cell barrier, resulting in increased blood-brain barrier (BBB) permeability. Mechanistically, miR-374a-5p regulates the distribution of ZO-1 and occludin in endothelial cells by targeting ADD3, increasing vascular permeability and promoting LM. Implications: These results suggest that serum NSCLC-derived EVs miR-374a-5p is involved in premetastatic niche formation by regulating the permeability of BBB to promote NSCLC-LM, and can be used as a blood biomarker for the diagnosis and prognosis of NSCLC-LM.

Sample self-selection using dual teacher networks for pathological image classification with noisy labels.

Deep neural networks (DNNs) involve advanced image processing but depend on large quantities of high-quality labeled data. The presence of noisy data significantly degrades the DNN model performance. In the medical field, where model accuracy is crucial and labels for pathological images are scarce and expensive to obtain, the need to handle noisy data is even more urgent. Deep networks exhibit a memorization effect, they tend to prioritize remembering clean labels initially. Therefore, early stopping is highly effective in managing learning with noisy labels. Previous research has often concentrated on developing robust loss functions or implementing training constraints to mitigate the impact of noisy labels; however, such approaches have frequently resulted in underfitting. We propose using knowledge distillation to slow the learning process of the target network rather than preventing late-stage training from being affected by noisy labels. In this paper, we introduce a data sample self-selection strategy based on early stopping to filter out most of the noisy data. Additionally, we employ the distillation training method with dual teacher networks to ensure the steady learning of the student network. The experimental results show that our method outperforms current state-of-the-art methods for handling noisy labels on both synthetic and real-world noisy datasets. In particular, on the real-world pathological image dataset Chaoyang, the highest classification accuracy increased by 2.39 %. Our method leverages the model's predictions based on training history to select cleaner datasets and retrains them using these cleaner datasets, significantly mitigating the impact of noisy labels on model performance.

Effective Management of Polycythemia Vera With Ropeginterferon Alfa-2b Treatment.

Background: Polycythemia vera (PV) is a myeloproliferative neoplasm. Ropeginterferon alfa-2b is a new-generation polyethylene glycol-conjugated proline-interferon. It is approved for the treatment of PV at a starting dose of 100 µg (50 µg for patients receiving hydroxyurea (HU)) and dose titrations up to 500 µg by 50 µg increments. The study was aimed at assessing its efficacy and safety at a higher starting dose and simpler intra-patient dose escalation. Methods: Forty-nine patients with PV having HU intolerance from major hospitals in China were treated biweekly with an initial dose of 250 µg, followed by 350 µg and 500 µg thereafter if tolerated. Complete hematological response (CHR) was assessed every 12 weeks based on the European LeukemiaNet criteria. The primary endpoint was the CHR rate at week 24. The secondary endpoints included CHR rates at weeks 12, 36 and 52, changes of JAK2V617F allelic burden, time to first CHR, and safety assessments. Results: The CHR rates were 61.2%, 69.4% and 71.4% at weeks 24, 36, and 52, respectively. Mean allele burden of the driver mutation JAK2V617F declined from 58.5% at baseline to 30.1% at 52 weeks. Both CHR and JAK2V617F allele burden reduction showed consistent increases over the 52 weeks of the treatment. Twenty-nine patients (63.0%) achieved partial molecular response (PMR) and two achieved complete molecular response (CMR). The time to CHR was rapid and median time was 5.6 months according to central lab results. The CHRs were durable and median CHR duration time was not reached at week 52. Mean spleen index reduced from 55.6 cm2 at baseline to 50.2 cm2 at week 52. Adverse events (AEs) were mostly mild or moderate. Most common AEs were reversible alanine aminotransferase and aspartate aminotransferase increases, which were not associated with significant elevations in bilirubin levels or jaundice. There were no grade 4 or 5 AEs. Grade 3 AEs were reversible and manageable. Only one AE led to discontinuation. No incidence of thromboembolic events was observed. Conclusion: The 250-350-500 µg dosing regimen was well tolerated and effectively induced CHR and MR and managed spleen size increase. Our findings demonstrate that ropeginterferon alfa-2b at this dosing regimen can provide an effective management of PV and support using this dosing regimen as a treatment option.

m6A-dependent upregulation of DDX21 by super-enhancer-driven IGF2BP2 and IGF2BP3 facilitates progression of acute myeloid leukaemia.

BACKGROUND: Acute myeloid leukaemia (AML) is a haematological malignancy with unfavourable prognosis. Despite the effectiveness of chemotherapy and targeted therapy, relapse or drug resistance remains a major threat to AML patients. N6-methyladenosine (m6A) RNA methylation and super-enhancers (SEs) are extensively involved in the leukaemogenesis of AML. However, the potential relationship between m6A and SEs in AML has not been elaborated. METHODS: Chromatin immunoprecipitation (ChIP) sequencing data from Gene Expression Omnibus (GEO) cohort were analysed to search SE-related genes. The mechanisms of m6 A-binding proteins IGF2BP2 and IGF2BP3 on DDX21 were explored via methylated RNA immunoprecipitation (MeRIP) assays, RNA immunoprecipitation (RIP) assays and luciferase reporter assays. Then we elucidated the roles of DDX21 in AML through functional assays in vitro and in vivo. Finally, co-immunoprecipitation (Co-IP) assays, RNA sequencing and ChIP assays were performed to investigate the downstream mechanisms of DDX21. RESULTS: We identified two SE-associated transcripts IGF2BP2 and IGF2BP3 in AML. High enrichment of H3K27ac, H3K4me1 and BRD4 was observed in IGF2BP2 and IGF2BP3, whose expression were driven by SE machinery. Then IGF2BP2 and IGF2BP3 enhanced the stability of DDX21 mRNA in an m6A-dependent manner. DDX21 was highly expressed in AML patients, which indicated a poor survival. Functionally, knockdown of DDX21 inhibited cell proliferation, promoted cell apoptosis and led to cell cycle arrest. Mechanistically, DDX21 recruited transcription factor YBX1 to cooperatively trigger ULK1 expression. Moreover, silencing of ULK1 could reverse the promoting effects of DDX21 overexpression in AML cells. CONCLUSIONS: Dysregulation of SE-IGF2BP2/IGF2BP3-DDX21 axis facilitated the progression of AML. Our findings provide new insights into the link between SEs and m6A modification, elucidate the regulatory mechanisms of IGF2BP2 and IGF2BP3 on DDX21, and reveal the underlying roles of DDX21 in AML.

The dual ECL signal enhancement strategy of Pd nanoparticles attached covalent organic frameworks and exonuclease cycling reaction for the ultrasensitive detection of progesterone.

Nowadays, novel and efficient signal amplification strategy in electrochemiluminescence (ECL) platform is urgently needed to enhance the sensitivity of biosensor. In this work, the dual ECL signal enhancement strategy was constructed by the interactions of Pd nanoparticles attached covalent organic frameworks (Pd NPs@COFs) with tris (bipyridine) ruthenium (RuP) and Exonuclease III (Exo.III) cycle reaction. Within this strategy, the COFs composite was generated from the covalent reaction between 2-nitro-1,4-phenylenediamine (NPD) and trialdehyde phloroglucinol (Tp), and then animated by glutamate (Glu) to attach the Pd NPs. Next, the "signal on" ECL biosensor was constructed by the coordination assembly of thiolation capture DNA (cDNA) onto the Pd NPs@COFs modified electrode. After the aptamer recognition of progesterone (P4) with hairpin DNA 1 (HP1), the Exo. III cycle reaction was initiated with HP2 to generate free DNA, which hybridized with cDNA to form double-stranded DNA (dsDNA). For that, the RuP was embedded into the groove of dsDNA and achieved the ultrasensitive detection of P4 with a lower limit of detection (LOD) down to 0.45 pM, as well as the excellent selectivity and stability. This work expands the COFs-based materials application in ECL signal amplification and valuable DNA cyclic reaction in biochemical testing field.

[A Real-World Single-Center Study of Adult Hodgkin's Lymphoma].

OBJECTIVE: To summarize the clinical characteristics, therapeutic effect and prognostic factors of patients with Hodgkin's lymphoma (HL). METHODS: A total of 129 patients with HL diagnosed in Peking University Third Hospital from January 2010 to March 2021 who were given at least one efficacy assessment after treatment were enrolled, and their clinical data, including sex, age, pathological type, Ann Arbor stage, ECOG score, blood test, ß2-microglobulin, lactate dehydrogenase level, albumin level were collected. The clinical characteristics, therapeutic effect and long-term prognosis of the patients were summarized and analyzed. RESULTS: In classical HL, nodular sclerosis HL accounted for the highest proportion of 51.6%, followed by mixed cellularity HL (36.5%), lymphocyte-rich classical HL (3.2%), and lymphocyte depletion HL (0.7%), while nodular lymphocyte predominant HL accounted for 4.8%. The 3-year overall survival (OS) rate of HL patients was 89.8%, and 5-year OS was 85.0%. The 3-year progression-free survival (PFS) rate was 73.4%, and 5-year PFS was 63.1%. Multivariate regression analysis indicated that IPI score was an independent negative factor, while hemoglobin (Hb) level was an independent positive factor for OS in HL patients. When the mediastinal mass size was 9.2 cm, it was most significant to judge the survival status of HL patients. 5-year OS and 5-year PFS were 97.4% and 76.0% in early-stage HL patients without large mass, respectively, while in patients with advanced-stage HL was 83.4% and 55.9% (both P < 0.05). After 2-4 courses of treatment, the overall response rate (ORR) of patients who received chemotherapy combined with radiotherapy was 95.0%, while that was 89.6% in those with chemotherapy alone. CONCLUSIONS: The overall prognosis of patients with HL is satisfactory, especially those in early-stage without large mass. IPI score and Hb level are independent risk factors for the prognosis of HL patients. A 9.2 cm mediastinal mass can be used as the cut-off value for the prognosis of Chinese HL patients.

The effect of cognitive rehabilitation on daily functioning of patients with Alzheimer's disease: a systematic review and meta-analysis of clinical trials.

Background: Alzheimer's disease (AD) is the most prevalent type of dementia and represents 60-80% of dementia cases. AD affects over 32 million people globally, and 8.1% of affected females and 5.4% of affected males were older than 65 years. Cognitive rehabilitation focuses on helping patients develop individualized strategies to obtain or maintain optimal functioning. As of now, there is no complete and systematic meta-analysis on the effects of cognitive rehabilitation on cognitive functioning in AD patients. Objectives: To provide the most recent and extensive pooled analysis and evidence and explore the influence of cognitive rehabilitation on overall cognitive functioning in patients with AD. Methods: We searched articles through several databases such as PubMed, Cochrane Library, Embase, and Web of Science, from the inception to June 2023. Studies on cognitive stimulation, cognitive training, and cognitive interventions, and non-English articles were excluded. The outcome measures encompassed the effects of cognitive rehabilitation on the overall cognitive functioning of people with AD (e.g., verbal fluency, behavioral memory, neuropsychiatric status and occupational performance levels). Results: A total of 14 clinical trials were included in this analysis. The meta-analysis showed that cognitive rehabilitation significantly improved quality of life (WMD: 2.87; 95% CI: 0.79, 4.95; p = 0.007) and occupational performance levels (WMD: 1.53; 95% CI: 0.43, 2.63; p = 0.007) in patients with AD. However, it did not show a significant effect on other domains of specific cognitive functions in patients with AD. Conclusion: Cognitive rehabilitation exhibited a moderate to large impact on both quality of life and occupational performance levels in people with AD. Future studies are required to explore the potential of various cognitive interventions across specific domains, so as to provide more insights into the management of AD. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023444390.

Efficacy of the combination of BRII-196/BRII-198 in the treatment of COVID-19 vaccine breakthrough infections.

BACKGROUND: BRII-196 and BRII-198 are two recombinant human immunoglobulin (Ig) G1 monoclonal antibodies (mAbs) that non-competitively target distinct epitope regions within the receptor-binding domain (RBD) of the coronavirus spike glycoproteins. These antibodies are derived directly from human B cells of individuals who recovered from COVID-19. OBJECTIVE: To analyze the efficacy of BRII-196/BRII-198 in the treatment of coronavirus disease 2019 (COVID-19) vaccine breakthrough infections. METHODS: COVID-19 patients at high risk of progressing to severe and critical illness, with an initial SARS-CoV-2 immunoglobulin (Ig) G antibody level < 1.0 S/CO (detected within 24-48 hours post COVID-19 diagnosis), were treated with BRII-196/BRII-198 within three days of symptom onset. Treatment continued until the antibody level exceeded 1.0 S/CO. Patients whose absolute lymphocyte count (ALC) at first detection (within 24-48 h post-diagnosis) was < 0.8 × 109/L received thymalfasin therapy within three days of symptom onset, continuing until the ALC level surpassed 0.8 × 109/L. We determined the correlation of SARS-CoV-2 IgG antibody level and ALC with the condition of COVID-19 patients. Additionally, we analyzed the effects of BRII-196/BRII-198 on SARS-CoV-2 nucleic acid (NA) negative conversion, lymphocyte count recovery, and the change in SARS-CoV-2 IgG antibody level from the first positive NA test for SARS-CoV-2 to negative conversion in COVID-19 patients. RESULTS: A total of 61 cases of breakthrough infections were observed, classified as 10 mild cases, 31 ordinary cases, and 20 severe cases. Among these, 20%, 48.4% and 75% of the patients with mild, ordinary, and severe COVID-19, respectively, had initial SARS-CoV-2 IgG antibody level < 1.0 S/CO. Additionally, 0%, 35% and 70% had initial ALC < 0.8 × 109/L, respectively. Fifteen ordinary and 15 severe COVID-19 patients were treated with BRII-196/BRII-198. In severely infected patients, BRII-196/BRII-198 treatment showed statistically significant differences in NA negative conversion time and changes in SARS-CoV-2 IgG antibody levels (P < 0.05). However, in patients classified with ordinary severity, BRII-196/BRII-198 treatment did not lead to notable differences in NA negative conversion time or changes in SARS-CoV-2 IgG antibody level (P > 0.05). BRII-196/BRII-198 therapy was not associated with lymphocyte count recovery time in patients with either ordinary and/or severe COVID-19 (P > 0.05). CONCLUSIONS: The initial levels of SARS-CoV-2 IgG antibody and lymphocytes in fully vaccinated patients with breakthrough infections are inversely correlated with the severity of the disease. Early treatment with BRII-196/BRII-198 can shorten NA negative conversion time in severe COVID-19 patients and increase in vivo neutralizing antibody levels post-conversion, providing lasting protection. However, BRII-196/BRII-198 does not influence lymphocyte count recovery in patients with either ordinary and/or severe COVID-19.

Thiotepa-busulfan-fludarabine-based conditioning as a promising approach prior to allogeneic hematopoietic stem cell transplantation in patients with blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive myeloid malignancy associated with a poor prognosis. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) has emerged as a potential treatment strategy for BPDCN, standardized conditioning regimens remain lacking. In this manuscript, we present two cases of BPDCN that were treated with a thiotepa-busulfan-fludarabine (TBF)-based conditioning regimen prior to allo-HSCT. Both cases demonstrated complete remission post-transplantation, sustained donor chimerism, and remission maintenance, suggesting the potential efficacy of the TBF conditioning regimen for BPDCN transplantation. Given the small sample size in our study, we emphasize caution and advocate for larger studies to confirm the efficacy of TBF in the treatment of BPDCN.

Sociodemographic, clinical and treatment characteristics of current rapid-cycling bipolar disorder: a multicenter Chinese study.

BACKGROUND: Rapid cycling bipolar disorder (RCBD), characterized by four or more episodes per year, is a complex subtype of bipolar disorder (BD) with poorly understood characteristics. METHOD: This multicenter, observational, longitudinal cohort study enrolled 520 BD patients across seven psychiatric institutions in China from January 2013 to January 2014. Participants were divided into RCBD and non-RCBD (NRCBD) groups based on the frequency of mood episodes in the preceding year. Data collection utilized a standardized form, supplemented by a medical record review, focusing on sociodemographic, clinical, and treatment characteristics. Statistical analysis involved independent samples t-tests, Kruskal-Wallis H tests, Chi-square or Fisher's exact tests, with Bonferroni correction applied to account for multiple comparisons, and multivariable logistic regression to identify characteristics associated with RCBD. RESULTS: Among the BD cohort, 9.4% were identified as current RCBD. Compared to NRCBD, RCBD patients had a shorter duration from the first psychiatric consultation to the diagnosis of BD, a reduced duration of their longest period of euthymia, a lower proportion of lifetime hospitalization history due to BD, and less use of electroconvulsive therapy (ECT) within the last 12 months. Additionally, they presented higher baseline scores on the Mood Disorder Questionnaire (MDQ) and the Brief 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). However, after applying the Bonferroni correction, these differences were not statistically significant. Multivariable logistic regression analysis identified three factors that were independently associated with RCBD: time from first psychiatric consultation to BD diagnosis (Odds Ratio [OR] = 0.512, P = 0.0416), lifetime hospitalization history due to BD (OR = 0.516, P = 0.0476), and ECT treatment within the past 12 months (OR = 0.293, P = 0.0472). CONCLUSION: This study revealed that the duration from first psychiatric consultation to BD diagnosis, lifetime hospitalization history due to BD, and ECT treatment in the past year were associated with RCBD. Recognizing these factors could contribute to enhance the early identification and clinical outcomes of RCBD. Trial Registration Number Registry ClinicalTrials.gov NCT01770704. Date of Registration: First posted on January 18, 2013.

Venetoclax plus cytarabine and azacitidine in relapsed/refractory AML: An open-label, single-arm, phase 2 study.

BACKGROUND: The outcome of relapsed/refractory (R/R) acute myeloid leukemia (AML) remains extremely poor. Venetoclax (VEN)-based regimens have shown promise in treating R/R AML. OBJECTIVE: This phase 2 study aimed to systematically evaluate the efficacy and safety of the VAA regimen (VEN plus Cytarabine and Azacitidine) in R/R AML patients. METHODS: Thirty R/R AML patients were enrolled. The study adopted a stepwise ramp-up of VEN dosing, starting with 100 mg on day 1, escalating to 200 mg on day 2, and reaching 400 mg from day 3 to day 9. Cytarabine (10 mg/m2, q12h) was administered intravenously twice daily from days 1 to 10, and Azacitidine (75 mg/m2) was administered via subcutaneous injection once daily from days 1-7. The primary efficacy endpoint was the composite complete remission rate (CRc), including complete response (CR) and complete response with incomplete blood count recovery (CRi). Secondary endpoints included overall survival (OS), duration of response (DOR), and safety analysis. RESULTS: The CRc rate was 63.3% (19/30), with CR in 36.7% of patients and CRi in 26.7%. Notably, 14 (73.7%) of 19 patients achieving CRc showed undetectable measurable residual disease by flow cytometry. With a median follow-up of 10.7 months, the median OS had not been reached, and the median DOR was 18.3 months. The most common grade 3-4 adverse events (AEs) were neutropenia (100%), anemia (96.7%), thrombocytopenia (90.0%), and leukopenia (90.0%). Infections, with pneumonia being the most prevalent (43.3%), were observed, including one fatal case of Pseudomonas aeruginosa septicemia. There were no treatment-related deaths. CONCLUSION: The VAA regimen is an effective and safe option for patients with R/R AML, demonstrating a high CRc rate and manageable safety profile.

Comparative analysis of CRASH and IMPACT in predicting the outcome of 340 patients with traumatic brain injury.

Background: Both the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) and the Corticosteroid randomization after significant head injury (CRASH) models are globally acknowledged prognostic algorithms for assessing traumatic brain injury (TBI) outcomes. The aim of this study is to externalize the validation process and juxtapose the prognostic accuracy of the CRASH and IMPACT models in moderate-to-severe TBI patients in the Chinese population. Methods: We conducted a retrospective study encompassing a cohort of 340 adult TBI patients (aged > 18 years), presenting with Glasgow Coma Scale (GCS) scores ranging from 3 to 12. The data were accrued over 2 years (2020-2022). The primary endpoints were 14-day mortality rates and 6-month Glasgow Outcome Scale (GOS) scores. Analytical metrics, including the area under the receiver operating characteristic curve for discrimination and the Brier score for predictive precision were employed to quantitatively evaluate the model performance. Results: Mortality rates at the 14-day and 6-month intervals, as well as the 6-month unfavorable GOS outcomes, were established to be 22.06, 40.29, and 65.59%, respectively. The IMPACT models had area under the curves (AUCs) of 0.873, 0.912, and 0.927 for the 6-month unfavorable GOS outcomes, with respective Brier scores of 0.14, 0.12, and 0.11. On the other hand, the AUCs associated with the six-month mortality were 0.883, 0.909, and 0.912, and the corresponding Brier scores were 0.15, 0.14, and 0.13, respectively. The CRASH models exhibited AUCs of 0.862 and 0.878 for the 6-month adverse outcomes, with uniform Brier scores of 0.18. The 14-day mortality rates had AUCs of 0.867 and 0.87, and corresponding Brier scores of 0.21 and 0.22, respectively. Conclusion: Both the CRASH and IMPACT algorithms offer reliable prognostic estimations for patients suffering from craniocerebral injuries. However, compared to the CRASH model, the IMPACT model has superior predictive accuracy, albeit at the cost of increased computational intricacy.

CFL1 is Implicated in Chronic Myeloid Leukemia Response during Imatinib Therapy.

Cofilin (CFL1) is one critical member of the actin deploy family (ADF). Overexpression of CFL1 is associated with aggressive features and poor prognosis in malignancies. We evaluated the expression of CFL1 in patients with chronic myeloid leukemia in the chronic phase (CML-CP), acute myelocytic leukemia (AML) and healthy controls. The role of CFL1 in imatinib therapy was also investigated using cell line. We found that the expression of CFL1 was lower in CML patients than that in healthy controls, and was significantly upregulated after imatinib therapy (p<0.05). CML patients with lower CFL1 achieved higher Major molecular response (MMR) rate after 6 months of imatinib therapy (p<0.05). Cofilin, P-cofilin and F-actin, especially branched F-actin were all upregulated after imatinib therapy. The lower CFL1 expression before treatment may predicts a better response to imatinib. Imatinib affects F-actin remodeling in CML patients by regulating CFL1 expression and activity.

Downregulation of miR-337-3p in hypoxia/reoxygenation neuroblastoma cells increases KCTD11 expression.

Neurodegeneration is linked to the progressive loss of neural function and is associated with several diseases. Hypoxia is a hallmark in many of these diseases, and several therapies have been developed to treat this disease, including gene expression therapies that should be tightly controlled to avoid side effects. Cells experiencing hypoxia undergo a series of physiological responses that are induced by the activation of various transcription factors. Modulation of microRNA (miRNA) expression to alter transcriptional regulation has been demonstrated to be beneficial in treating multiple diseases, and in this study, we therefore explored potential miRNA candidates that could influence hypoxia-induced nerve cell death. Our data suggest that in mouse neuroblasts Neuro-2a cells with hypoxia/reoxygenation (H/R), miR-337-3p is downregulated to increase the expression of Potassium channel tetramerization domain containing 11 (KCTD11) and subsequently promote apoptosis. Here, we demonstrate for the first time that KCTD11 plays a role in the cellular response to hypoxia, and we also provide a possible regulatory mechanism by identifying the axis of miR-337-3p/KCTD11 as a promising candidate modulator of nerve cell survival after H/R exposure.

A differential diagnosis method for systemic CAEBV and the prospect of EBV-related immune cell markers via flow cytometry.

Chronic active Epstein-Barr virus (CAEBV) infection of the T-cell or Natural killer (NK)-cell type, systemic form (systemic CAEBV or sCAEBV) was defined by the WHO in 2017 as an EBV-related lymphoproliferative disorder and is listed as an EBV-positive T-cell and NK-cell proliferation. The clinical manifestations and prognoses are heterogeneous. This makes systemic CAEBV indistinguishable from other EBV-positive T-cell and NK-cell proliferations. Early diagnosis of systemic CAEBV and early hematopoietic stem cell transplantation can improve patient prognosis. At present, the diagnosis of systemic CAEBV relies mainly on age, clinical manifestations, and cell lineage, incurring missed diagnosis, misdiagnosis, long diagnosis time, and inability to identify high-risk systemic CAEBV early. The diagnostic methods for systemic CAEBV are complicated and lack systematic description. The recent development of diagnostic procedures, including molecular biological and immunological techniques such as flow cytometry, has provided us with the ability to better understand the proliferation of other EBV-positive T cells and NK cells, but there is no definitive review of their value in diagnosing systemic CAEBV. This article summarizes the recent progress in systemic CAEBV differential diagnosis and the prospects of flow cytometry.

Prevalence and risk factors of fatigue and its association with quality of life among patients with chronic pancreatitis: A cross-sectional study.

BACKGROUND: Fatigue is a debilitating symptom found in various chronic diseases and is associated with more severe symptoms and worse quality of life (QoL). However, this symptom has not been adequately addressed in chronic pancreatitis (CP), and there have been no studies on fatigue in patients with CP. METHODS: This cross-sectional study was conducted at the Changhai Hospital in Shanghai, China. Data on the patients' sociodemographic, disease, and therapeutic characteristics were collected. Fatigue was assessed using the Multidimensional Fatigue Inventory-20. QoL was assessed utilizing the European Organization for the Research and Treatment of Cancer of QoL questionnaire (EORTC-QLQ-C30). Sleep quality, anxiety and depression, and pain was assessed using Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, and the Brief Pain Inventory, respectively. RESULTS: The prevalence of fatigue among Chinese patients with CP was 35.51 % (87/245). Multivariate analysis showed that steatorrhea (OR = 2.638, 95 % CI: 1.117-6.234), history of smoking (OR = 4.627, 95 % CI: 1.202-17.802), history of endoscopic treatment (OR = 0.419, 95 % CI: 0.185-0.950), depression (OR = 5.924, 95 % CI: 2.462-14.255), and sleep disorder (OR = 6.184, 95 % CI: 2.543-15.034) were influencing factors for the presence of fatigue. The scores for global health and all functional dimensions in the EORTC-QLQ-C30 significantly decreased, whereas the scores for all symptom dimensions significantly increased in patients with fatigue. CONCLUSIONS: This study indicated that Fatigue is a common symptom and has a negative impact on the QoL of patients with CP. Steatorrhea, smoking history, endoscopic treatment, depression, and sleep disorders were associated with fatigue.