Background and aims: Dietary diversity change is associated with cognitive function, however, whether the effect still exists among the oldest-old (80+) is unclear. Our aim was to examine the effect ...of dietary diversity changes on cognitive impairment for the oldest-old in a large prospective cohort. Methods: Within the Chinese Longitudinal Healthy Longevity Study, 6237 adults older than 80 years were included. The dietary diversity score (DDS) was assessed by a simplified food frequency questionnaire (FFQ). Cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score lower than 18 points. Cognitive decline was defined as a reduction of total MMSE score ≥3 points, and cognitive decline of different subdomains was defined as a reduction of ≥15% in the corresponding cognitive domain. The multivariate-adjusted Cox proportional hazard model evaluated the effects of DDS change on cognitive decline. The linear mixed-effect model was used to test subsequent changes in MMSE over the years. Results: During 32,813 person-years of follow-up, 1829 participants developed cognitive impairment. Relative to the high–high DDS change pattern, participants in the low–low and high–low patterns were associated with an increased risk of cognitive impairment with a hazard ratio (95% confidential interval, CI) of 1.43 (1.25, 1.63) and 1.44 (1.24, 1.67), and a faster decline in the MMSE score over the follow-up year. Participants with the low–high pattern had a similar incidence of cognitive impairment with HRs (95% CI) of 1.03 (0.88, 1.20). Compared with the stable DDS status group (−1–1), the risk of cognitive impairment was higher for those with large declines in DDS (≤−5) and the HR was 1.70 (95% CI: 1.44, 2.01). Conclusions: Even for people older than 80, dietary diversity change is a simple method to identify those who had a high risk of cognitive decline. Keeping high dietary diversity is beneficial for cognitive function and its subdomain even in the final phase of life, especially for females and the illiterate oldest-old.
Emerging evidence has shown that epigenetic changes in DNA methylation, an important regulator of long non-coding RNA (lncRNA) expression, can disturb the expression patterns of lncRNAs and ...contribute to carcinogenesis. However, knowledge about crosstalk effects between DNA methylation and lncRNA regulation in thyroid cancer (THCA) remain largely unknown. In this study, we performed an integrated analysis of methylation and the transcriptome and identified 483 epigenetically regulated lncRNAs (EpilncRNAs) associated with the development and progression of THCA. These EpilncRNAs can be divided into two categories based on their methylation and expression patterns: 228 HyperLncRNAs and 255 HypoLncRNAs. Then, we identified a methylation-driven 5-lncRNA-based signature (EpiLncPM) to improve prognosis prediction using the random survival forest and multivariate Cox analysis, which were then validated using the training dataset Hazard ratio (HR) = 50.097, 95% confidence interval (CI): 10.231-245.312,
< 0.001 and testing dataset (HR = 4.395, 95% CI: 0.981-19.686,
= 0.053). Multivariate analysis suggested that the EpiLncPM is an independent prognostic factor. By performing a functional enrichment analysis of GO and KEGG for mRNAs co-expressed with the EpiLncPM, we found that the EpiLncPM was involved in immune and inflammatory-related biological processes. Finally,
hybridization analysis in 119 papillary thyroid carcinoma (PTC) tissues and paired adjacent normal tissues revealed that selected candidate lncRNA
has significantly higher expression of PTC compared to adjacent non-neoplastic tissues, and was closely related to the tumor size, lymph node metastasis, and extrathyroidal extension. In summary, our study characterized the crosstalk between DNA methylation and lncRNA, and provided novel biomarkers for the prognosis of THCA.
Abstract
Considering the issue of significant total harmonic distortion in the no-load back electromotive force (EMF) and torque ripple of a brushless excitation synchronous motor (BESM) used in a ...compressor, a multiobjective optimization design method of a BESM based on the Taguchi method was proposed. By selecting the polar arc coefficient, stator slot width, damping winding pitch, and air gap length as the optimization parameters, the maximum no-load back EMF, minimum back EMF total harmonic distortion rate, and minimum torque ripple are selected as the optimization objectives. Then, the Taguchi method was employed to construct an orthogonal table to enhance the performance of the optimization objectives. This approach facilitated the determination of the optimal parameter combination for optimization. Finally, the simulation results indicate significant enhancements in each optimized aspect of the motor’s performance following the optimization process. This outcome serves as validation for the efficacy of the Taguchi method in achieving an optimal design for the BESM.
To investigate the effect of HBV markers on HBV-GN.
The immunohistochemistry was used to detect HBsAg and HBcAg in frozen sections of renal biopsy, the changes in HBV serum markers, renal functional ...parameters and clinical manifestations or symptoms were observed to analyze renal damage.
Using renal biopsy data from 329 cases, this study found that the most common pathological subtype in HBV-GN was mesangioproliferative glomerulonephritis (MsPGN) (24.9%, P <0.05), and 29.4% of patients who show serological HBsAg, HBeAg and anti-HBc positive developed membranoproliferative glomerulonephritis (MPGN) (P <0.05). The immunohistochemistry was used to detect HBsAg and HBcAg in frozen sections.50% of HBsAg and HBcAg deposits was observed in the glomeruli of MPGN patients, while 36.6% of HBsAg and 43.9% of HBcAg deposited in the glomeruli of MsPGN patients. The deposits of HBsAg and HBcAg in glomeruli were directly correlated with IgA, IgG, IgM and C3 deposits. In addition, cases with a moderate to severe decrease as reflected by the glomerular filtration rate (GFR) were predominantly patients with MPGN (31.6%, P <0.05) or MsPGN (21.1%, P <0.05). Patients who were serological HBsAg, HBeAg and anti-HBc positive or HBsAg, anti-HBe and anti-HBc positive mainly exhibited urine and renal parameter changes.
Examination of HBV markers in serum and renal biopsy will be useful for clinicians to predict the renal damage in early stage when it is reversible in HBV-GN.
The purpose of this study was to investigate the HOX gene expression profile in laryngeal squamous cell carcinoma (LSCC) and assess whether some genes are associated with the clinicopathological ...features and prognosis in LSCC patients. The HOX gene levels were tested by microarray and validated by qRT-PCR in paired cancerous and adjacent noncancerous LSCC tissue samples. The microarray testing data of 39 HOX genes revealed 15 HOX genes that were at least 2-fold upregulated and 2 that were downregulated. After qRT-PCR evaluation, the three most upregulated genes (HOXB9, HOXB13, and HOXD13) were selected for tissue microarray (TMA) analysis. The correlations between the HOXB9, HOXB13, and HOXD13 expression levels and both clinicopathological features and prognosis were analyzed. Three HOX gene expression levels were markedly increased in LSCC tissues compared with adjacent noncancerous tissues (P<0.001). HOXB9 was found to correlate with histological grade (P<0.01) and prognosis (P<0.01) in LSCC. In conclusion, this study revealed that HOXB9, HOXB13, and HOXD13 were upregulated and may play important roles in LSCC. Moreover, HOXB9 may serve as a novel marker of poor prognosis and a potential therapeutic target in LSCC patients.
Transcriptional factor
HOXB9
, a part of the HOX gene family, plays a crucial role in the development of diverse cancer types. This study aimed to elucidate the regulatory mechanism of HOXB9 on the ...proliferation and invasion of laryngeal squamous cell carcinoma (LSCC) cells to provide guidance for the development and prognosis of LSCC. The CRISPR/Cas9 method was employed in LSCC cell lines to knock out the
HOXB9
gene and validate its effects on the proliferation, migration, invasion, and regulation of LSCC cells. CCK-8 and flow cytometry were used to detect cell viability and proliferation; Tunnel was used to detect cell apoptosis, and transwell was used to detect cell migration and invasion. The effect of HOXB9 on tumor growth was tested in nude mice. The downstream target genes regulated by HOXB9 were screened by microarray analysis and verified by Western blotting, immunohistochemistry, chromatin immunoprecipitation, and double-luciferase reporter assays. The current research investigated molecular pathways governed by HOXB9 in the development of LSCC. Additionally, both laboratory- and living-organism-based investigations revealed that disrupting the
HOXB9
gene through the CRISPR/CAS9 mechanism restrained cellular growth, movement, and infiltration, while enhancing cellular apoptosis. Detailed analyses of LSCC cell strains and human LSCC samples revealed that HOXB9 promoted LSCC progression by directly elevating the transcriptional activity of MMP12.
HOXB9
could influence changes in LSCC cell functions, and the mechanism of action might be exerted through its downstream target gene,
MMP1
2.
Objective. The paper aimed to analyze the clinical, serological, and imaging features of autoimmune pancreatitis (AIP) and the prognostic factors affecting hormone therapy. Methods. A total of 106 ...patients with AIP enrolled in our hospital from March 2016 to August 2018 were treated with the hormone. The curative effect and recurrence were followed up. The patients were divided into relapse group (n = 42) and nonrelapse group (n = 64) according to the recurrence within 3 years after initial hormone therapy. The symptoms and signs, laboratory examination, and treatment were compared, and binary logistic regression was employed to explore the risk factors of AIP recurrence. Results. Among the 106 patients included in this study, there were 78 males and 28 females, with a male-to-female ratio of 3:1. The average age of onset was 56.25 ± 8.87 years; the minimum age was 39 years; and the maximum age was 7 years. The main clinical symptoms were jaundice (67.92%), abdominal pain (48.11%), and abdominal distension (33.96%). In addition, there were symptoms of weight loss, nausea, vomiting, itching, and gray stool. Previous complications included 27.35% diabetes (29/106), 22.64% hypertension (24/106), 35.84% smoking (38/106), and 28.30% alcohol consumption (30/106). The serological characteristics were mainly the increase in serum IgG4 level; 92.45% (98/106) level was higher compared to the upper limit of normal value; the median level was 11.65 g/L; and the highest level was 35.79 g/L. A total of 88.67% (94/106) had an abnormal liver function. The results of imaging examination indicated that 58.49% (62/106) of extrapancreatic organs were involved, of which 46.22% (49/106) were the most common bile duct involvement. All the patients in the group reached a state of remission after hormone treatment. After the disease was relieved, the patients were followed up for 3 years. The recurrence rate was 39.62% (42/106), and the median time of recurrence (month) was 9 (range 2–36). The recurrence rates within 1, 2, and 3 years were 20.75%, 31.13%, and 39.62%, respectively. Among the recurrent patients, 52.38% (22/42) relapsed within 1 year, 78.57% (33/42) within 2 years, and 100.00% (42/42) within 3 years. Multivariate analysis showed that the short duration of glucocorticoid therapy and involvement of extrapancreatic organs were risk factors for relapse after glucocorticoid therapy in patients with type I AIP. Conclusion. Type 1 AIP is more common in middle-aged and elderly men. The clinical symptoms of jaundice, abdominal pain, and abdominal distension are common, often accompanied by involvement of extrapancreatic organs, of which bile duct involvement is the most common. Type 1 AIP glucocorticoid treatment acceptance and disease remission are better, but the recurrence rate is higher after glucocorticoid treatment. Patients with a short time of glucocorticoid treatment and involvement of extrapancreatic organs may have a higher risk of recurrence.
In traditional Chinese medicine (TCM), Yu-Ping-Feng powder (YPFP) has been used to treat allergic rhinitis (AR) for centuries. However, the mechanisms underlying its effects or its molecular targets ...in AR treatment are yet to be elucidated. Therefore, the active compounds of YPFP and their targets were collected and identified from the Traditional Chinese Medicine Systems Pharmacology database. Moreover, AR-associated targets were acquired from the GeneCards and Online Mendelian Inheritance in Man database. Proteins interactions network of YPFP presumed targets and AR-associated targets were examined and merged to reveal the candidate YPFP targets against AR.Cytoscape software and BisoGenet Database were employed to perform the Visualization and Integrated Discovery (Cluster Profiler R package, version: 3.8.1). Kyoto Encyclopedia of Genes and Genomes and genome pathway analyses. To identify the key target genes, a gene-pathway network has been constructed.We identified 44 effective active compounds and 622 YPFP targets. Also 1324 target genes related to AR were identified. Twenty pathways, including those of AGE-RAGE signaling, fluid shear stress, atherosclerosis, PI3K-Akt signaling, and tumor necrosis factor signaling was enriched significantly. MAPK1 was identified as the core gene, while others including RELA, AKT1, NFKBIA, IL6, and JUN, were also important in the gene-pathway network. Clearly, network pharmacology can be applied in revealing the molecular targets and mechanisms of action of complex herbal preparations.These findings suggested that YPFP could treat AR by regulating immunological functions, diminishing inflammation, and improving immunity through different pathways.
Long non‐coding RNAs (lncRNAs), which are longer than 200 nt, have been proved to play a role in promoting or inhibiting cancer progression. The following study investigated the role and underlying ...mechanisms of lncRNA RP11‐159K7.2 in laryngeal squamous cell carcinoma (LSCC) progression. Briefly, in situ hybridization (ISH) and real‐time quantitative PCR (RT‐qPCR) showed higher expression of RP11‐159K7.2 in LSCC tissues and cell lines. Patients with low expression level of RP11‐159K7.2 lived longer compared to those with high expression of RP11‐159K7.2 (χ2 = 39.111, ***P < 0.001). Multivariate Cox regression analysis suggested that lncRNA RP11‐159K7.2 was an independent prognostic factor for LSCC patients (HR = 2.961, ***P < 0.001). Furthermore, to investigate the potential involvement of RP11‐159K7.2 in the development of LSCC, we knocked out the expression of endogenous RP11‐159K7.2 in TU‐212 cells and AMC‐HN‐8 cells via CRISPR/Cas9 double vector lentiviral system. RP11‐159K7.2 knockout decreased LSCC cell growth and invasion both in vitro and in vivo. Mechanically, we found that RP11‐159K7.2 could positively regulate the expression of DNMT3A by sponging miR‐206. In addition, a feedback loop was also discovered between DNMT3A and miR‐206. To sum up, these findings suggest that lncRNA RP11‐159K7.2 could be used as a potential biomarker for prognosis and treatment of LSCC.
BACKGROUND Fractional exhaled nitric oxide (FeNO) participates in the local defense of the upper respiratory tract. Abnormal FeNO level is directly related to the occurrence of nasal diseases. ...However, the clinical value of FeNO in the upper airway is limited, which greatly impedes the diagnosis and treatment of nasal diseases. Here, we assessed the level of FeNO and evaluated the diagnostic accuracy of FeNO for chronic rhinosinusitis. MATERIAL AND METHODS We enrolled 35 patients with confirmed nasal inflammation and 30 healthy subjects from December 2016 and June 2017. The FeNO level was measured using a fractional exhaled nitric oxide detector. The level of FeNO in patients with different clinicopathological factors was compared. The diagnostic potential of FeNO for chronic rhinosinusitis was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS FeNO level was significantly lower in patients with nasal inflammation than in healthy subjects (P<0.05). For nasal inflammation diagnosis, FeNO had the highest area under the curve (AUC) at 0.760, with a sensitivity of 93.30% and a specificity of 68.60%. FeNO level was significantly downregulated in chronic rhinosinusitis patients relative to chronic rhinitis patients (P<0.05). FeNO had a good ability to discriminate between chronic rhinosinusitis patients and chronic rhinitis patients, with higher AUC, sensitivity, and specificity of 0.760, 93.30%, and 68.60%, respectively. However, FeNO levels were not significantly different between different histological types of chronic rhinosinusitis (P>0.05). CONCLUSIONS Our results show that FeNO is a useful marker for discriminating chronic rhinosinusitis, and has potential to provide valuable information in the early diagnosis of chronic rhinosinusitis.
PDF
