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Background: This study aimed to investigate the knowledge, attitudes, and practices (KAP) toward cardiovascular complications among end-stage renal disease patients undergoing maintenance hemodialysis. Methods: This web-based cross-sectional study was conducted at Guangdong Provincial People's Hospital between December 2022, and May 2023. Results: A total of 545 valid questionnaires were collected, with an average age of 57.72 ± 13.47 years. The mean knowledge, attitudes and practices scores were 8.17 ± 2.9 (possible range: 0–24), 37.63 ± 3.80 (possible range: 10–50), 33.07 ± 6.10 (possible range: 10–50) respectively. Multivariate logistic regression analysis showed that patients from non-urban area had lower knowledge compared to those from urban area (odds ratio (OR) = 0.411, 95% CI: 0.262–0.644, P < 0.001). Furthermore, higher levels of education were associated with better knowledge, as indicated by OR for college and above (OR = 4.858, 95% CI: 2.483–9.504), high school/vocational school (OR = 3.457, 95% CI: 1.930–6.192), junior high school (OR = 3.300, 95% CI: 1.945–5.598), with primary school and below as reference group (all P < 0.001). Besides, better knowledge (OR = 1.220, 95% CI: 1.132–1.316, P < 0.001) and higher educational levels were independently associated with positive attitudes. Specifically, individuals with a college degree and above (OR = 2.986, 95% CI: 1.411–6.321, P = 0.004) and those with high school/vocational school education (OR = 2.418, 95% CI: 1.314–4.451, P = 0.005) have more positive attitude, with primary school and below as reference group. Next, better attitude (OR = 1.174, 95% CI: 1.107–1.246, P < 0.001) and higher education were independently associated with proactive practices. Those with college and above (OR = 2.870, 95% CI: 1.359–6.059, P = 0.006), and those with high school/vocational school education (OR = 1.886, 95% CI: 1.032–3.447, P = 0.039) had more proactive practices, with primary school and below as reference group. Conclusions: End-stage renal disease patients undergoing maintenance hemodialysis demonstrated insufficient knowledge, positive attitudes, and moderate practices regarding cardiovascular complications. Targeted interventions should prioritize improving knowledge and attitudes, particularly among patients with lower educational levels and income, to enhance the management of cardiovascular complications in end-stage renal disease. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) remains a pressing public health issue, posing a significant threat to individuals' well-being and lives. This study delves into the TB incidence in Chinese mainland during 2014–2021, aiming to gain deeper insights into their epidemiological characteristics and explore macro-level factors to enhance control and prevention. Methods: TB incidence data in Chinese mainland from 2014 to 2021 were sourced from the National Notifiable Disease Reporting System (NNDRS). A two-stage distributed lag nonlinear model (DLNM) was constructed to evaluate the lag and non-linearity of daily average temperature (℃, Atemp), average relative humidity (%, ARH), average wind speed (m/s, AWS), sunshine duration (h, SD) and precipitation (mm, PRE) on the TB incidence. A spatial panel data model was used to assess the impact of demographic, medical and health resource, and economic factors on TB incidence. Results: A total of 6,587,439 TB cases were reported in Chinese mainland during 2014–2021, with an average annual incidence rate of 59.17/100,000. The TB incidence decreased from 67.05/100,000 in 2014 to 46.40/100,000 in 2021, notably declining from 2018 to 2021 (APC = -8.87%, 95% CI: -11.97, -6.85%). TB incidence rates were higher among males, farmers, and individuals aged 65 years and older. Spatiotemporal analysis revealed a significant cluster in Xinjiang, Qinghai, and Xizang from March 2017 to June 2019 (RR = 3.94, P < 0.001). From 2014 to 2021, the proportion of etiologically confirmed cases increased from 31.31% to 56.98%, and the time interval from TB onset to diagnosis shortened from 26 days (IQR: 10–56 days) to 19 days (IQR: 7–44 days). Specific meteorological conditions, including low temperature (< 16.69℃), high relative humidity (> 71.73%), low sunshine duration (< 6.18 h) increased the risk of TB incidence, while extreme low wind speed (< 2.79 m/s) decreased the risk. The spatial Durbin model showed positive associations between TB incidence rates and sex ratio (β = 1.98), number of beds in medical and health institutions per 10,000 population (β = 0.90), and total health expenses (β = 0.55). There were negative associations between TB incidence rates and population (β = -1.14), population density (β = -0.19), urbanization rate (β = -0.62), number of medical and health institutions (β = -0.23), and number of health technicians per 10,000 population (β = -0.70). Conclusions: Significant progress has been made in TB control and prevention in China, but challenges persist among some populations and areas. Varied relationships were observed between TB incidence and factors from meteorological, demographic, medical and health resource, and economic aspects. These findings underscore the importance of ongoing efforts to strengthen TB control and implement digital/intelligent surveillance for early risk detection and comprehensive interventions. [ABSTRACT FROM AUTHOR]

Objective: Duchenne muscular dystrophy (DMD) is a devastating X-linked neuromuscular disorder caused by various defects in the dystrophin gene and still no universal therapy. This study aims to identify the hub genes unrelated to excessive immune response but responsible for DMD progression and explore therapeutic siRNAs, thereby providing a novel treatment. Methods: Top ten hub genes for DMD were identified from GSE38417 dataset by using GEO2R and PPI networks based on Cytoscape analysis. The hub genes unrelated to excessive immune response were identified by GeneCards, and their expression was further verified in mdx and C57 mice at 2 and 4 months (M) by (RT-q) PCR and western blotting. Therapeutic siRNAs were deemed as those that could normalize the expression of the validated hub genes in transfected C2C12 cells. Results: 855 up-regulated and 324 down-regulated DEGs were screened from GSE38417 dataset. Five of the top 10 hub genes were considered as the candidate genes unrelated to excessive immune response, and three of these candidates were consistently and significantly up-regulated in mdx mice at 2 M and 4 M when compared with age-matched C57 mice, including Col1a2, Fbn1 and Fn1. Furthermore, the three validated up-regulated candidate genes can be significantly down-regulated by three rational designed siRNA (p < 0.0001), respectively. Conclusion: COL1A2, FBN1 and FN1 may be novel biomarkers for DMD, and the siRNAs designed in our study were help to develop adjunctive therapy for Duchenne muscular dystrophy. [ABSTRACT FROM AUTHOR]

Background: Residential mobility is believed to influence the occurrence and development of cancer; however, the results are inconclusive. Furthermore, limited studies have been conducted on Asian populations. This study aimed to evaluate the relationship between residential mobility and liver cancer risk among Chinese women. Methods: We enrolled 72,818 women from urban Shanghai between 1996 and 2000, and then followed them until the end of 2016. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the association between residential mobility and liver cancer risk. A linear trend test was conducted by ranking variables. A sensitivity analysis was also conducted, excluding participants with follow-up times of less than 2 years, to prevent potential bias. Results: During the 1,269,765 person-years of follow-up, liver cancer was newly diagnosed in 259 patients. Domestic migration (HR = 1.47, 95% CI, 1.44–1.50), especially immigration to Shanghai (HR = 1.47, 95% CI, 1.44–1.50) was associated with an increased risk of liver cancer. In addition, migration frequency, age at initial migration and first immigration to Shanghai had linear trends with an increased liver cancer risk (Ptrend <0.001). The results were similar when excluding participants with less than two years of follow-up. Conclusions: The possible association between residential mobility and a higher risk of liver cancer in women could suggest the need for effective interventions to reduce adverse environmental exposures and enhance people's health. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) ranks as the third most common cause of cancer related death globally, representing a substantial challenge to global healthcare systems. In China, the primary risk factor for HCC is the hepatitis B virus (HBV). Aberrant serum glycoconjugate levels have long been linked to the progression of HBV-associated HCC (HBV-HCC). Nevertheless, few study systematically explored the dysregulation of glycoconjugates in the progression of HBV-associated HCC and their potency as the diagnostic and prognostic biomarker. Methods: An integrated strategy that combined transcriptomics, glycomics, and glycoproteomics was employed to comprehensively investigate the dynamic alterations in glyco-genes, N-glycans, and glycoproteins in the progression of HBV- HCC. Results: Bioinformatic analysis of Gene Expression Omnibus (GEO) datasets uncovered dysregulation of fucosyltransferases (FUTs) in liver tissues from HCC patients compared to adjacent tissues. Glycomic analysis indicated an elevated level of fucosylated N-glycans, especially a progressive increase in fucosylation levels on IgA1 and IgG2 determined by glycoproteomic analysis. Conclusions: The findings indicate that the abnormal fucosylation plays a pivotal role in the progression of HBV-HCC. Systematic and integrative multi-omic analysis is anticipated to facilitate the discovery of aberrant glycoconjugates in tumor progression. [ABSTRACT FROM AUTHOR]

Background: Patients with spondyloarthritis (SpA)/HLA-B27-associated acute anterior uveitis (AAU) experience recurring acute flares, which pose significant visual and financial challenges. Despite established links between SpA and HLA-B27-associated AAU, the exact mechanism involved remains unclear, and further understanding is needed for effective prevention and treatment. Methods: To investigate the acute pathogenesis of SpA/HLA-B27-associated AAU, Mendelian randomization (MR) and single-cell transcriptomic analyses were employed. The MR incorporated publicly available protein quantitative trait locus data from previous studies, along with genome-wide association study data from public databases. Causal relationships between plasma proteins and anterior uveitis were assessed using two-sample MR. Additionally, colocalization analysis was performed using Bayesian colocalization. Single-cell transcriptome analysis utilized the anterior uveitis dataset from the Gene Expression Omnibus (GEO) database. Dimensionality reduction, clustering, transcription factor analysis, pseudotime analysis, and cell communication analysis were subsequently conducted to explore the underlying mechanisms involved. Results: Mendelian randomization analysis revealed that circulating levels of AIF1 and VARS were significantly associated with a reduced risk of developing SpA/HLA-B27-associated AAU, with AIF1 showing a robust correlation with anterior uveitis onset. Colocalization analysis supported these findings. Single-cell transcriptome analysis showed predominant AIF1 expression in myeloid cells, which was notably lower in the HLA-B27-positive group. Pseudotime analysis revealed dendritic cell terminal positions in differentiation branches, accompanied by gradual decreases in AIF1 expression. Based on cell communication analysis, CD141+CLEC9A+ classic dendritic cells (cDCs) and the APP pathway play crucial roles in cellular communication in the Spa/HLA-B27 group. Conclusions: AIF1 is essential for the pathogenesis of SpA/HLA-B27-associated AAU. Myeloid cell differentiation into DCs and decreased AIF1 levels are also pivotal in this process. [ABSTRACT FROM AUTHOR]

Background: Tubular biomarkers have been regarded as emerging and promising markers for early diagnosis of diabetic kidney disease (DKD). The study was to determine the diagnostic capabilities of tubular biomarkers (urinary neutrophil gelatinase-associated lipocalin [NGAL], clusterin, and cystatin C) for DKD and diabetic microalbuminuria, and whether or not the tubular biomarkers appear earlier than microalbuminuria.Methods: In this consecutive cohort study, 146 type 2 diabetes mellitus (T2DM) patients with a disease duration of ≥6 years were enrolled. Thirty age- and gender-matched subjects without any systemic diseases were recruited as the control group. Urinary samples collected before treatment were tested for NGAL, clusterin, and cystatin C.Results: The levels of biomarkers were higher in patients with DKD (p < 0.001); and positively correlated with the urinary albumin creatinine ratio (UACR; p < 0.001). With respect to the diagnosis of DKD, the areas under the receiver operating characteristic curve (AUCs) for urinary NGAL, clusterin, and cystatin C were 0.816 (95% confidence interval [CI], 0.741-0.891), 0.775 (95% CI: 0.694-0.857), and 0.803 (95% CI: 0.722-0.884), respectively. The levels of urinary NGAL and cystatin C in the normoalbuminuria group (UACR <30 mg /g•Cr) were elevated compared with the control group, unlike urinary clusterin. There was no statistical difference in the levels of the three biomarkers between groups with different levels of haemoglobin A1C (HbA1c). The diagnostic AUCs for urinary NGAL, clusterin, and cystatin C in patients with diabetic microalbuminuria were 0.841 (95% CI: 0.775-0.907), 0.783(95% CI: 0.710-0.856), and 0.805 (95% CI: 0.733-0.877), respectively.Conclusions: Urinary NGAL, clusterin, and cystatin C may be promising biomarkers for diagnosing DKD and diabetic microalbuminuria. It is possible that urinary NGAL and cystatin C increase before the onset of microalbuminuria in T2DM patients. [ABSTRACT FROM AUTHOR]

Background: Apolipoprotein M (apoM) was the carrier of the biologically active lipid mediator sphingosine-1-phospate in high density lipoprotein cholesterol (HDL-C) and played a critical role in formation and maturation of prebeta-HDL-C particles. The plasma apoM levels were decreased obviously in patients with type 2 diabetes mellitus (T2DM). A new single-nucleotide polymorphism (SNP) C-724del in apoM promoter was associated with a higher risk for coronary artery diseases (CAD) and myocardial infarction, could reduce promoter activities and apoM expression in vitro. The primary aim of the present case-controls study was to investigate the effect of apoM SNP C-724del on apoM expression in vivo and its association with T2DM susceptibility in an eastern Han Chinese cohort. Methods: Two hundred and fifty-nine T2DM patients and seventy-six healthy controls were included in this study. Amplifying DNA of apoM proximal promoter region including SNP C-724del by Real-Time Polymerase Chain Reaction (RT-PCR) and amplicons sequencing. The plasma apoM concentrations were assayed by enzyme linked immunosorbentassay (ELISA). Results: Four polymorphic sites, rs805297 (C-1065A), rs9404941 (T-855C), rs805296 (T-778C), C-724del were confirmed. rs805297 (C-1065A) and rs9404941 (T-855C) showed no statistical difference in allele frequencies and genotype distributions between T2DM patients and healthy controls just as previous studies. It's worth noting that the difference of rs805296 (T-778C) between these two groups was not found in this study. In SNP C-724del, the frequency of del allele and mutant genotypes (del/del, C/del) were higher in T2DM patients compared with healthy controls (p = 0.035; P = 0.040, respectively), while the plasma apoM levels of C-724del mutant allele carriers compared with the wide-type homozygotes carriers were not statistically different in T2DM patients (18.20 ± 8.53 ng/uL vs 20.44 ± 10.21 ng/uL, P = 0.245). Conclusion: The polymorphism C-724del in the promoter region of the apoM gene could confer the risk of T2DM among eastern Han Chinese. Unfortunately, the lowing of plasma apoM levels of C-724del mutant allele carriers compared with the wide-type homozygotes carriers in T2DM patients was not statistically different in present study, so further researchs were needed by enlarging the sample. [ABSTRACT FROM AUTHOR]

Background: Tubular biomarkers have been regarded as emerging and promising markers for early diagnosis of diabetic kidney disease (DKD). The study was to determine the diagnostic capabilities of tubular biomarkers (urinary neutrophil gelatinase-associated lipocalin [NGAL], clusterin, and cystatin C) for DKD and diabetic microalbuminuria, and whether or not the tubular biomarkers appear earlier than microalbuminuria., Methods: In this consecutive cohort study, 146 type 2 diabetes mellitus (T2DM) patients with a disease duration of ≥6 years were enrolled. Thirty age- and gender-matched subjects without any systemic diseases were recruited as the control group. Urinary samples collected before treatment were tested for NGAL, clusterin, and cystatin C., Results: The levels of biomarkers were higher in patients with DKD (p < 0.001); and positively correlated with the urinary albumin creatinine ratio (UACR; p < 0.001). With respect to the diagnosis of DKD, the areas under the receiver operating characteristic curve (AUCs) for urinary NGAL, clusterin, and cystatin C were 0.816 (95% confidence interval [CI], 0.741-0.891), 0.775 (95% CI: 0.694-0.857), and 0.803 (95% CI: 0.722-0.884), respectively. The levels of urinary NGAL and cystatin C in the normoalbuminuria group (UACR <30 mg /g•Cr) were elevated compared with the control group, unlike urinary clusterin. There was no statistical difference in the levels of the three biomarkers between groups with different levels of haemoglobin A 1C (HbA 1c ). The diagnostic AUCs for urinary NGAL, clusterin, and cystatin C in patients with diabetic microalbuminuria were 0.841 (95% CI: 0.775-0.907), 0.783(95% CI: 0.710-0.856), and 0.805 (95% CI: 0.733-0.877), respectively., Conclusions: Urinary NGAL, clusterin, and cystatin C may be promising biomarkers for diagnosing DKD and diabetic microalbuminuria. It is possible that urinary NGAL and cystatin C increase before the onset of microalbuminuria in T2DM patients.

Background: Apolipoprotein M (apoM) was the carrier of the biologically active lipid mediator sphingosine-1-phospate in high density lipoprotein cholesterol (HDL-C) and played a critical role in formation and maturation of prebeta-HDL-C particles. The plasma apoM levels were decreased obviously in patients with type 2 diabetes mellitus (T2DM). A new single-nucleotide polymorphism (SNP) C-724del in apoM promoter was associated with a higher risk for coronary artery diseases (CAD) and myocardial infarction, could reduce promoter activities and apoM expression in vitro. The primary aim of the present case-controls study was to investigate the effect of apoM SNP C-724del on apoM expression in vivo and its association with T2DM susceptibility in an eastern Han Chinese cohort., Methods: Two hundred and fifty-nine T2DM patients and seventy-six healthy controls were included in this study. Amplifying DNA of apoM proximal promoter region including SNP C-724del by Real-Time Polymerase Chain Reaction (RT-PCR) and amplicons sequencing. The plasma apoM concentrations were assayed by enzyme linked immunosorbentassay (ELISA)., Results: Four polymorphic sites, rs805297 (C-1065A), rs9404941 (T-855C), rs805296 (T-778C), C-724del were confirmed. rs805297 (C-1065A) and rs9404941 (T-855C) showed no statistical difference in allele frequencies and genotype distributions between T2DM patients and healthy controls just as previous studies. It's worth noting that the difference of rs805296 (T-778C) between these two groups was not found in this study. In SNP C-724del, the frequency of del allele and mutant genotypes (del/del, C/del) were higher in T2DM patients compared with healthy controls (p = 0.035; P = 0.040, respectively), while the plasma apoM levels of C-724del mutant allele carriers compared with the wide-type homozygotes carriers were not statistically different in T2DM patients (18.20 ± 8.53 ng/uL vs 20.44 ± 10.21 ng/uL, P = 0.245)., Conclusion: The polymorphism C-724del in the promoter region of the apoM gene could confer the risk of T2DM among eastern Han Chinese. Unfortunately, the lowing of plasma apoM levels of C-724del mutant allele carriers compared with the wide-type homozygotes carriers in T2DM patients was not statistically different in present study, so further researchs were needed by enlarging the sample.

Background: Podocyte apoptosis is a major mechanism that leads to proteinuria in many kidney diseases. However, the concert mechanisms that cause podocyte apoptosis in these kidney diseases are not fully understood. RhoA is one of Rho GTPases that has been well studied and plays a key role in regulating cytoskeletal architecture. Previous study showed that insufficient RhoA could result in rat aortic smooth muscle cell apoptosis. However, whether RhoA is involved in podocyte apoptosis remains unknown., Methods: Culture podocytes were treated with LPS, ADR or siRNA for 48 h before harvest. Subcellular immunoblotting, qRT-PCR, immunofluorescence and flow cytometry were used to exam the expression and function of RhoA or YAP in podocytes., Results: We found that the expression of RhoA and its activity were significantly decreased in LPS or ADR-injured podocytes, accompanying loss of stress fibers and increased cell apoptosis. Knocking down RhoA or its downstream effector mDia expression by siRNA also caused loss of stress fibers and podocyte apoptosis. Moreover, our results further demonstrated that RhoA deficiency could reduce the mRNA and protein expression of YAP, which had been regarded as an anti-apoptosis protein in podocyte. Silenced dendrin expression significantly abolished RhoA, mDia or YAP deficiency-induced podocyte apoptosis., Conclusion: RhoA deficiency could disrupt podocyte cytoskeleton and induce podocyte apoptosis by inhibiting YAP/dendrin signal. RhoA/mDia/YAP/dendrin signal pathway may potentially play an important role in regulating podocyte apoptosis. Maintaining necessary RhoA would be one potent way to prevent proteinuria kidney diseases.