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.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K _D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

AIM:To compare the differences of ocular biometric parameters of age-related cataract between Tibetan and Han ethnic groups, and to analyze the distribution characteristics of ocular biometric parameters in Tibetan cataract patients.METHODS:Retrospective cohort study. A total of 661 patients(1 030 eyes)with age-related cataract confirmed in the hospital between January 2019 and December 2020 were enrolled. The parameters of axial length, anterior chamber depth, keratometry, corneal astigmatism and astigmatic axis were measured by IOL Master 500 in 483 cases(739 eyes)of Tibetan age-related cataract patients and 178 cases(291 eyes)of Han patients.RESULTS:The axial length, anterior chamber depth and corneal astigmatism of the Tibetan patients with age-related cataract were 23.33(22.81, 23.86)mm, 3.04(2.79, 3.30)mm and 0.73(0.47, 1.07)D. The mean keratometry was 43.89±1.35 D. The results indicated that Tibetan cataract patients had shorter axial lengths and smaller keratometry compared to Han patients(all P<0.05). Age in Tibetan patients was negatively correlated with axial length and anterior chamber depth, and positively correlated with keratometry(all P<0.05). Tibetan male patients had longer axial lengths, deeper anterior chambers, and flatter corneas compared to female patients(all P<0.05).CONCLUSION:There were differences in ocular biometric parameters between age-related cataract patients of Tibetan and Han ethnicities. The distribution of ocular biometric parameters in Tibetan cataract patients varied across different age groups and gender groups.

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.

Objective:To elucidate the pathophysiological mechanisms of idiopathic inflammatory myopathy subtypes by analyzing the gene expression profiles of peripheral blood mononuclear cells (PBMCs) from anti-MDA5 antibody-positive and anti-Jo-1 antibody-positive myositis patients.Methods:Gene expression profiling screening and analysis of PBMCs from 12 anti-MDA5 positive, 16 anti-Jo-1 positive myositis patients and 43 healthy controls were performed using Illumina HT-12 v4 expression profiling microarrays. Applying the unpaired t test with Benjamini-Hochberg correction, the genes with the absolute value of fold change (FC) in gene expression signal ≥2 and adjusted P<0.05 were selected as differentially expressed genes. Differential gene sets were subjected to Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, with P<0.05 as the threshold for being significantly enriched. Validation of differentially expressed genes by real time-PCR. The Kolmogorov-Smirnov test was used to test the normality of continuous variables. If the distribution was normal and the variance was homogeneous, analysis of variance (one-way ANOVA) was used.If the distribution was not normal, Kruskal-Wallis test was used, and P<0.05 was regarded as statistically significant difference. Results:Analysis of gene expression profiles of PBMCs from patients with positive anti-MDA5 and anti-Jo-1 antibody revealed significant differences in gene expression of PBMCs from patients with the two myositis subtypes. The number of differentially expressed genes that specifically up-regulated in anti-MDA5 antibody positive patients was 407, and the GO functional enrichment analysis was mainly enriched in biological processes such as innate immune response ( P<0.001), response to virus ( P<0.001) and type Ⅰ interferon signaling pathway ( P<0.001), and the KEGG pathway enrichment analysis was mainly enriched in the viral infection-associated pathway ( P<0.001), RIG-Ⅰ like receptor signaling pathway ( P<0.001) and Toll-like receptor signaling pathway ( P=0.002), etc. The 259 differential genes specifically down-regulated in the anti-MDA5 antibody positive group were mainly enriched in biological processes such as immune response ( P=0.006), TGF-β receptor signaling pathway ( P=0.010) and natural killer cell mediated immunity ( P=0.015) in GO functional enrichment analysis. There were 162 differentially expressed genes up-regulated specifically in anti-Jo-1 antibody positive patients, and GO functional enrichment analysis was mainly enriched in biological processes such as nucleosome assembly ( P<0.001), negative regulation of cell growth ( P=0.001), negative regulation of apoptotic process P=0.004), and innate immune response in mucosa ( P=0.012), and the KEGG pathway enrichment analysis mainly enriched in metabolic-related signaling pathways ( P<0.001) and immune-related pathways ( P<0.001), etc. Real-time PCR confirmed that IFIH1 ( P=0.037), ISG15 ( P=0.003), and DDX58 ( P=0.032) in the RIG-Ⅰ-like receptor pathway as well as chemokines MCP-1 ( P=0.003), MCP-2 ( P<0.001), and transcription factor BATF2 ( P=0.002), and inflammatory signaling pathway-associated MYD88 ( P<0.001) were highly expressed in PBMCs from anti-MDA5 antibody-positive myositis patients. Conclusion:The gene expression profile of PBMCs in anti-MDA5 antibody-positive patients suggests that the pathogenesis of patients with anti-MDA 5 antibody positive is closely related to biological processes such as innate immune response, viral infection, and interferon response.

Objective:To explore the current status of cognitive function of the older adults in Beijing,and to analyze the factors affecting their cognitive function.Methods:It was a cross-sectional study.A questionnaire survy was conducted in 2023 among the older adults in Beijing.The cognitive function of the older adults was assessed with the Hong Kong brief cognitive test(HKBC)scale,a simple cognitive assessment tool.Using SPSS 27.0 to perform the descriptive analysis and multiple linear regression analy-sis of factors,which affect cognitive function among the older adults.Results:Totally 349 older adults were recruited,with the highest percentage of respondents aged 60-69 years(41.3％),of whom 58.7％were female,88.0％of the respondents had a junior high school or above education level.Most of the older adults(68.8％)worked 35-48 h/week before they retired,and 14.0％of the older adults had a family history of dementia.After controlling age and gender,the linear regression analysis showed that marital status married(β=0.501,95％CI:0.144-0.859)and 3-4 times physical activity per week(β=0.617,95％CI:0.087-1.148)were protective factors of cognitive function in the older adults,and depressive symptoms were a risk factor(β=-0.723,95％CI:-1.198 to-0.247)of cognitive function for the older adults.Conclusion:In this study,the factors influencing cognitive function among the older adults was analyzed based on a life-cycle perspective.Lack of physical activity and depressive symptoms were risk factors for cognitive function among the older adults.It was suggested that strengthening physical activity,improving mental health of the older adults,as well as conducting preventive intervention in early stages of the life-cycle will be benefit for preventing and slowing cognitive decline in the older adults.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Cartilage is solid connective tissue that recovers slowly from injury, and pain and dysfunction from cartilage damage affect many people. The treatment of cartilage injury is clinically challenging and there is no optimal solution, which is a hot research topic at present. With the rapid development of 3D printing technology in recent years, 3D bioprinting can better mimic the complex microstructure of cartilage tissue and thus enabling the anatomy and functional regeneration of damaged cartilage. This article reviews the methods of 3D printing used to mimic cartilage structures, the selection of cells and biological factors, and the development of bioinks and advances in scaffold structures, with an emphasis on how 3D printing structure provides bioactive cargos in each stage to enhance the effect. Finally, clinical applications and future development of simulated cartilage printing are introduced, which are expected to provide new insights into this field and guide other researchers who are engaged in cartilage repair.

Objective:To correlate peripheral blood neutrophil-to-lymphocyte ratio with the occurrence of restless legs syndrome (RLS) in patients undergoing maintenance hemodialysis (MHD).Methods:This is a cross-sectional study. A total of 203 patients who underwent long-term MHD at the Blood Purification Center, Department of Nephrology, The First Affiliated Hospital of Xiamen University from May to June 2021 were included in this study. The counts of peripheral blood neutrophils and lymphocytes were determined and the neutrophil-to-lymphocyte ratio was calculated. These patients were divided into a RLS group and a non-RLS group according to whether they developed RLS. RLS-related factors were evaluated using face-to-face interview questionnaires. Various clinical and laboratory parameters were analyzed. The influential factors of RLS in patients undergoing MHD were analyzed through univariate regression analysis and multivariate logistic regression analysis.Results:A total of 203 patients undergoing MHD were enrolled, 30 individuals were determined as current RLS cases (14.78%). The levels of NLR and PTH in the RLS group were 4.86 (3.39, 5.82) L/L and 244.50 (143.25, 406.50) ng/L, respectively, which were significantly higher than those in the normal group [3.51 (2.60, 5.24) L/L, 147.00 (94.80, 263.50) ng/L, Z = -3.38, -2.64, both P < 0.05]. Univariate logistic regression analysis showed that NLR, PTH, uric acid, and neutrophil count were correlated with RLS (Wald χ2 = 7.96, 4.99, 4.76, 8.33, all P < 0.05). NLR was the independent risk factor of RLS (Wald χ2 = 6.14, P < 0.05) in multivariate models adjusting for confounding factor. Conclusion:The prevalence of RLS is high in patients undergoing MHD. RLS is assicuated with NLR among patients undergoing MHD after adjusting for confounding factor. RLS is likely associated with systemic inflammatory diseases.