BACKGROUND:U937 cells can be used as a cell model for studying the biological characteristics,signaling pathways,and therapeutic targets of acute myeloid leukemia.Although it has been reported that long non-coding RNA KIAA0125 is highly expressed in acute myeloid leukemia,its biological function in U937 cells remains unclear,and its mechanism of action in the occurrence and development of acute myeloid leukemia needs to be further clarified. OBJECTIVE:To investigate the expression level of long non-coding RNA KIAA0125 in peripheral blood of patients with acute myeloid leukemia and its effect on the proliferation and apoptosis of U937 cells. METHODS:RNA-sequencing was used to analyze the bone marrow monocyte samples from acute myeloid leukemia patients,and the differentially expressed gene long non-coding RNA KIAA0125 was screened.The expression of long non-coding RNA KIAA0125 in peripheral blood of patients with acute myeloid leukemia was detected by qRT-PCR.The relationship between long non-coding RNA KIAA0125 mRNA expression and prognosis in bone marrow cells of 173 acute myeloid leukemia patients and 70 healthy people was statistically analyzed by GEPIA database.Subsequently,recombinant lentivirus technology and CRISPR/Cas9-SAM technology were used to construct U937 cell lines with knockdown/overexpression of long non-coding RNA KIAA0125.qRT-PCR was used to detect the knockdown/overexpression efficiency of long non-coding RNA KIAA0125.Next,CCK-8 assay,flow cytometry,and western blot assay were used to detect the effects of knockdown/overexpression of long non-coding RNA KIAA0125 on the proliferation and apoptosis of U937 cells.Finally,western blot assay was used to detect the effect of knockdown/overexpressed long non-coding RNA KIAA0125 on Wnt/β-catenin signaling pathway-related proteins. RESULTS AND CONCLUSION:(1)The results of qRT-PCR showed that long non-coding RNA KIAA0125 was highly expressed in peripheral blood of acute myeloid leukemia patients.The results of GEPIA database showed that long non-coding RNA KIAA0125 was highly expressed in bone marrow cells of acute myeloid leukemia patients,and the high expression group had worse overall survival.(2)The knockdown efficiency of long non-coding RNA KIAA0125 in knockdown group was 70%,and the U937 cells that stably down-regulated long non-coding RNA KIAA0125 expression were successfully constructed.The expression of long non-coding RNA KIAA0125 in overexpression group was four times that of vector group,and stable U937 cells were successfully constructed.(3)Knockdown of long non-coding RNA KIAA0125 inhibited the proliferation of U937 cells and promoted their apoptosis.Overexpression of long non-coding RNA KIAA0125 promoted the proliferation of U937 cells but had no significant effect on the apoptosis of U937 cells.(4)Knockdown of long non-coding RNA KIAA0125 inhibited the activity of Wnt/β-catenin signaling pathway,while overexpression of long non-coding RNA KIAA0125 activated Wnt/β-catenin signaling pathway.These results confirm that long non-coding RNA KIAA0125 is highly expressed in acute myeloid leukemia peripheral blood.Long non-coding RNA KIAA0125 may affect the proliferation and apoptosis of U937 cells by regulating the Wnt/β-catenin signaling pathway,and may be a potential prognostic marker for acute myeloid leukemia.

Immune checkpoint blockade (ICB) therapy has demonstrated significant efficacy in the treatment of various cancers. However, a subset of patients develops hyper-progressive disease (HPD) following ICB, which is characterized by accelerated tumor growth and poor clinical outcomes. This review outlines the clinical features, potential mechanisms, and possible intervention strategies of HPD, with the aim of informing clinical practice and providing relevant recommendations.
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Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Neoplasms/therapy* ; Disease Progression ; Animals ; Immunotherapy

OBJECTIVES: To evaluate the impact of HBV infection on pre- and postpartum health-related quality of life (HRQoL) in pregnant women. METHODS: A prospective matched cohort consisting of 70 HBV-infected and 70 healthy pregnant women was recruited from the Fifth Affiliated Hospital of Guangzhou Medical University between April 17 and September 25, 2023. HRQoL of the participants was assessed at 16-24 weeks of gestation, between 32 weeks and delivery, and 5-13 weeks postpartum. Mixed linear models were used for evaluating temporal trends of HRQoL changes, and univariate ANOVA with multiple linear regression was used to identify the predictors of HRQoL. RESULTS: Compared with healthy pregnant women, HBV-infected pregnant women had consistently lower total HRQoL scores across all the 3 intervals, with the lowest scores observed between 32 weeks of gestation and delivery, during which these women had significantly reduced mental component scores (74.27±13.43 vs 80.21±12.9, P=0.009) and postpartum mental (76.52±16.19 vs 85.02±6.51, P<0.001) and physical component scale scores (77.17±14.71 vs 83.09±10.1, P=0.009). HBV infection was identified as an independent risk factor affecting HRQoL during late pregnancy and postpartum periods. Additional independent risk factors for postpartum HRQoL reduction included self-pay medical expenses, spouse's neutral attitude toward the current pregnancy, and preexisting comorbidities (all P<0.05). CONCLUSIONS HRQoL of pregnant women deteriorates progressively in late pregnancy, and HBV infection exacerbates reductions of physical function and role emotion in late pregnancy and after delivery, suggesting the importance of targeted interventions for financial burdens, partner support and comorbid conditions to improve HRQoL of pregnant women with HBV infection.
Humans ; Female ; Pregnancy ; Quality of Life ; Prospective Studies ; Postpartum Period ; Hepatitis B, Chronic/psychology* ; Adult ; Pregnancy Trimester, Third ; Pregnancy Trimester, Second ; Pregnancy Complications, Infectious

Repetitive transcranial magnetic stimulation (rTMS) is a rapid and effective therapy for major depressive disorder; however, there is significant variability in therapeutic outcomes both within and across individuals, with approximately 50% of patients showing no response to rTMS treatment. Many studies have personalized the stimulation parameters of rTMS (e.g., location and intensity of stimulation) according to the anatomical and functional structure of the brain. In addition to these parameters, the internal states of the individual, such as circadian rhythm, behavior/cognition, neural oscillation, and neuroplasticity, also contribute to the variation in rTMS effects. In this review, we summarize the current literature on the interaction between rTMS and internal states. We propose two possible methods, multimodal treatment, and adaptive closed-loop treatment, to integrate patients' internal states to achieve better rTMS treatment for depression.
Humans ; Transcranial Magnetic Stimulation/methods* ; Depressive Disorder, Major/physiopathology* ; Neuronal Plasticity/physiology* ; Brain/physiopathology*

OBJECTIVE: To investigate the association between fluid balance trajectories within the first 3 days of intensive care unit (ICU) admission and 28-day mortality as well as the incidence of continuous renal replacement therapy (CRRT) in patients with severe acute pancreatitis (SAP). METHODS: Clinical data of SAP patients were extracted from the Medical Information Mart of Intensive Care-IV (MIMIC-IV). Group-based trajectory modeling (GBTM) was used to analyze the daily fluid balance of patients within 3 days of ICU admission, and grouping them accordingly. Univariate and multivariate Logistic regression analyses were performed to assess the association between fluid balance trajectory and 28-day mortality and ICU CRRT in SAP patients. RESULTS: A total of 251 SAP patients were included, with 33 deaths within 28 days, and a 28-day mortality of 13.15%; 49 patients (19.52%) continued to receive bedside CRRT after 3 days of ICU admission. The fluid balance on the 3rd day, cumulative fluid balance within 3 days of ICU admission, and incidence of CRRT in the death group were significantly higher than those in the survival group. According to GBTM groups, there were 127 cases in the moderate fluid resuscitation with rapid reduction (MF group), 44 cases in the large fluid resuscitation with rapid reduction (LF group), 20 cases in the moderate fluid resuscitation with slow reduction (MS group), and 60 cases in the small fluid resuscitation with slow reduction (SS group). The cumulative fluid balance within 3 days of ICU admission of the MF group, LF group, MS group, and SS group were 8.60% (5.15%, 11.70%), 16.70% (13.00%, 21.02%), 23.40% (19.38%, 25.45%), and 0.65% (-2.35%, 2.20%), respectively, and the incidence of CRRT during ICU hospitalization were 11.02%, 29.55%, 85.00%, and 8.33%, respectively, with statistically significant differences among the groups (both P < 0.05); the 28-day mortality were 11.02%, 18.18%, 20.00%, and 11.67%, respectively, with no statistically significant difference among the groups (P > 0.05). Kaplan-Meier survival curve analysis showed there was no statistically significant difference in 28-day cumulative survival rate among groups with different fluid balance trajectories (Log-rank test: χ ² = 2.31, P = 0.509). Multivariate Logistic regression analysis showed that cumulative fluid balance within 3 days of ICU admission was an independent risk factor for 28-day mortality [odds ratio (OR) = 1.071, 95% confidence interval (95%CI) was 1.005-1.144, P = 0.040] and CRRT requirement (OR = 1.233, 95%CI was 1.125-1.372, P < 0.001); early aggressive fluid resuscitation on day 1 reduced CRRT risk (OR = 0.866, 95%CI was 0.756-0.978, P = 0.030). CONCLUSIONS Dynamic fluid management is essential in SAP patients. While early aggressive fluid resuscitation may reduce CRRT demand, excessive cumulative fluid balance is associated with increased 28-day mortality and CRRT incidence.
Humans ; Male ; Female ; Middle Aged ; Water-Electrolyte Balance ; Continuous Renal Replacement Therapy ; Intensive Care Units ; Aged ; Adult ; Pancreatitis/mortality* ; Logistic Models ; Retrospective Studies ; Renal Replacement Therapy

Background Chrysotile is widely used in construction and industry. Research has shown that it is associated with lung fibrosis in occupational groups, but the involvement of microRNAs (miRNAs) in chrysotile-induced lung fibrosis has been less well studied, and the specific mechanism is still unclear. Objective Using next-generation sequencing technology to analyze the effects of chrysotile exposure on the miRNAs expression profiles of human lung epithelial cells (BEAS-2B cells), to explore the variations of differentially expressed miRNAs and related signaling pathways, and to identify potential targets and molecular mechanisms of chrysotile-induced lung fibrosis. Methods Chrysotile was analyzed with a laser particle size analyzer and an X-ray diffractometer for particle size and physical phase. BEAS-2B cells were exposed to chrysotile for designed time sessions (12, 24, and 48 h) and doses (0, 50, 100, and 200 μg·mL⁻¹). Cell viability was detected with a cell viability assay kit (CCK8); expression levels of Fibronectin, Collagen-Ⅰ, and α-smooth muscle actin (α-SMA) were detected by Western blot after exposure to 200 μg·mL⁻¹ chrysotile for 24 h. Sample correlation and changes in miRNAs expression profiles between the chrysotile-exposed and the control groups were analyzed by next-generation sequencing technology. The target genes of differentially expressed miRNAs were predicted and subjected to Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results The average particle size of the chrysotile dust sample used in this study was 3.58 μm, and the results of X-ray diffraction analysis confirmed the characteristic peaks of chrysotile. Compared with the control group, the chrysotile gradually inhibited the survival rate of BEAS-2B cells with increasing concentration and exposure time (P<0.01). The survival rates of the 50, 100, and 200 μg·mL⁻¹ chrysotile-exposed cells after 12 h exposure were 83.88%±1.86%, 78.07%±3.97%, and 71.95%±2.99%, respectively; the survival rates after 24 h exposure were 77.41%±1.58%, 69.57%±2.23%, and 62.79%±3.65%, respectively; the survival rates after 48 h exposure were 74.31%±4.93%, 65.84%±2.71%, and 52.74%±6.31%, respectively. The Fibronectin, Collagen-Ⅰ, and α-SMA protein expression levels were elevated in the 200 μg·mL⁻¹ chrysotile-exposed BEAS-2B cells (P <0.05). The results of principal component analysis showed that there were differences in the composition of the samples between the chrysotile exposure group and the control group, and a total of 163 differential miRNAs were screened, of which 79 were up-regulated and 84 were down-regulated. The results of GO analysis showed that the differential miRNAs were mainly associated with biological processes such as regulation of transcription by RNA polymerase II, regulation of DNA templated transcription, cellular differentiation, protein phosphorylation, lipid metabolism, and cell cycle, cellular components such as nucleus, cytomembrane, cytoskeleton, mitochondria, and endoplasmic reticulum, as well as molecular functions such as protein binding, metal ion binding, transferase activity, and DNA binding. The results of KEGG analysis revealed that the differential miRNAs were mainly enriched in cancer pathway, phosphatidylinositol 3-kinase/ protein kinase B (PI3K/AKT) pathway, Ras-associated protein 1 (Rap1) pathway, calcium pathway, cyclic guanosine monophosphate/ protein kinase G (cGMP-PKG) pathway, Hippo pathway, cyclic adenosine monophosphate (cAMP) pathway, and Ras pathway. Conclusion Chrysotile exposure could significantly inhibit BEAS-2B cell survival, elevate the expression of lung fibrosis-associated proteins, and induce differential miRNAs expression, affecting biological processes (such as lipid metabolism, protein phosphorylation, and cell cycle) and cell components (such as mitochondria and endoplasmic reticulum), and interfering with PI3K/AKT pathway, Hippo pathway, cAMP pathway, Rap1 pathway, and Ras pathway.

More than 80% of the world’s populations are at risk of vector-borne diseases, with mosquito-borne diseases as a significant global public health problem. Mosquito populations control is critical to interrupting the transmission of mosquito-borne diseases. This review summarizes the physical attributes, smell, vision, touch, and hearing of mosquitoes to unravel the preferences of female mosquitoes, and describes the mechanisms underlying the best male mating by female mosquitoes, so as to provide new insights into management of mosquito-borne diseases.

AIM: To observe the early retinal degeneration and activation of microglia in C57BL/6N(Crb1rd8/rd8)mice.METHODS:Totally 15 male SPF C57BL/6N mice and 15 male SPF C57BL/6J mice were raised normally, and fundus photography examinations were performed by Micron-Ⅲ at the time of 0, 4, 8, 12 wk of enrollment to calculate the number and area of retinopathy. At the end of experiment, all mice were sacrificed and the right eyeballs were removed to prepare retinal tissue slices. After HE staining, the retinal tissue morphology was observed under optical microscope while the location and level of CX3CR1 expression were detected in immunohistochemical staining. The left eyeballs were removed to isolate retina, then Western-Blot was used to analyze the expression of CD86 and CD206 proteins in retina, and the concentration of IL-1β, IL-6, TNF-α, IL-4 and IL-10 in retina was detected by electrochemiluminescence.RESULTS:The result of fundus photography examinations showed that the number of retinopathy in the C57BL/6N significantly increased at 4, 8, and 12 wk, and there were differences in variations compared with the C57BL/6J at the same time point(all P<0.05). In the changes in area of retinopathy, there was a difference between two groups at 12 wk(P<0.05), but no difference in variations within groups(both P>0.05). HE staining of retinal tissue showed that the retinal structure of C57BL/6N mice was abnormal, with loose and disordered cell arrangement, and the photoreceptor layer was obviously protruding to the inner side of retina with a drusen-like protrusion. The retinal structure of C57BL/6J mice was clearer, with orderly cell arrangement and no obvious abnormality. Immunohistochemical results showed that CX3CR1 was highly expressed in ganglion cell layer, inner and outer plexiform layer, photoreceptor cell layer and lesion in the retina of C57BL/6N mice, with a mean density of 0.285±0.056 in C57BL/6N and 0.189±0.084 in C57BL/6J mice(P<0.05). The results of Western-Blot showed that the expression of CD86 and CD206 in retina of C57BL/6N increased compared with that in C57BL/6J to varying degrees, and the difference of CD86 was statistically significant(P<0.05). The results of cytokine detection showed that the level of IL-1β, TNF-α in C57BL/6N was significantly higher than that of C57BL/6J, while IL-10 was significantly lower(all P<0.05).CONCLUSION: The retinal degeneration of C57BL/6N(Crb1rd8/rd8)mice progressed slowly and gradually aggravated with age. The retinal structure of the lesion was disordered and accompanied by microglial infiltration dominated by M1 polarization.

Objective:To investigate the hot topics and trends of implementation science in the transformation of clinical practice guidelines, in order to provide ideas and references for clinical managers to reasonably apply and implement scientific promotion guidelines.Methods:CiteSpace6.2.R3 software was used to visualize the literature, which retrieved from the core database of Web of Science, including the number of articles, countries and high-frequency keywords and keyword clustering and emergence for visual analysis, etc.Results:A total of 4 593 articles were included in the final analysis. Since 1993, the number of published papers had increased year by year. The hot topics focused on primary care, attitudes, knowledge translation, clinical trials, risk factors and machine learning. The research trends included older adults and artificial intelligence.Conclusions:The rapid development of implementation science in guideline translation research suggests that scholars from various countries, especially hospital administrators should reasonably apply implementation science framework to integrate evidence into clinical practice, and promote the implementation of clinical practice guidelines.

BACKGROUND:Myelodysplastic syndrome has worse hazards of acute myeloid leukemia transformation,and some studies have revealed that immune infiltration plays a vital part in the two.Nevertheless,more studies are required to confirm the relationship between immune infiltration and related differentially expressed gene regulation. OBJECTIVE:To screen the differentially expressed genes with prognostic significance between myelodysplastic syndrome and acute myeloid leukemia by bioinformatics analysis and explore the possible roles and mechanisms among these differentially expressed genes and immune infiltration mechanisms in the occurrence and progression of diseases. METHODS:The differentially expressed genes were screened for bioinformatics analysis using the GEO datasets,and analyzed by DO,GO,KEGG and GSEA.The TCGA prognostic database was used to plot the K-M curves of differentially expressed genes and receiver operating characteristic curve analysis was applied to evaluate the clinical diagnostic performance.Finally,CIBERSORT analysis was used to intuitively demonstrate the correlation between critical prognostic genes and the distribution of immuno-infiltrated cells.RT-qPCR was employed to detect peripheral blood samples from healthy controls,myelodysplastic syndrome and acute myeloid leukemia patients so as to verify the crucial genes preliminarily. RESULTS AND CONCLUSION:(1)A total of 150 differentially expressed genes were obtained between myelodysplastic syndrome and acute myeloid leukemia,among which 16 genes were up-regulated and 134 were down-regulated.(2)The results of DO,GO,KEGG and GSEA analysis suggested that differentially expressed genes might promote the development of myelodysplastic syndrome to acute myeloid leukemia by regulating the immune response.CIBERSORT revealed the differences in immune infiltration between myelodysplastic syndrome and acute myeloid leukemia.The distribution of CD4+ T cells,monocytes,neutrophils and M1 macrophages decreased in acute myeloid leukemia patients.In contrast,the distribution of inflammatory suppressor cells M2 macrophages increased,suggesting that it may be related to the immunosuppression of acute myeloid leukemia.(3)K-M curve and receiver operating characteristic curve analysis of 150 differentially expressed genes screened out four genes relevant to immunity and prognosis with good diagnostic performance:MANSC1,FLT3,BMX and CXCR2.(4)The results of RT-qPCR exhibited that MANSC1,BMX and CXCR2 were low expressed,while FLT3 was highly expressed in acute myeloid leukemia patients.These findings verify that the differential expression of MANSC1,FLT3,BMX and CXCR2 in patients with myelodysplastic syndrome and acute myeloid leukemia is not only significantly correlated with the prognosis of patients but may also affect the occurrence and development of myelodysplastic syndrome and acute myeloid leukemia by regulating the immune infiltration of patients.They can be used as potential biomarkers and therapeutic targets of the transformation from myelodysplastic syndrome to acute myeloid leukemia,providing a new direction for clinical diagnosis and treatment of the transformation of myelodysplastic syndrome.