Evaluation of risk factors related to sleep disorders in patients undergoing hemodialysis using a nomogram model.

This study aimed to investigate the risk factors related to sleep disorders in patients undergoing hemodialysis using a nomogram model. A cross-sectional survey was conducted in a hospital in Zhejiang province, China from January 1, 2020, to November 31, 2022 among patients undergoing hemodialysis. Dietary intake was assessed applying a Food Frequency Questionnaire. Sleep quality was evaluated by the Pittsburgh Sleep Quality Index. Evaluation of risk factors related to sleep disorders in patients undergoing hemodialysis was using a nomogram model. This study included 201 patients and 87 individuals (43.3%, 87/201) exhibited sleep disorders. The average age of included patients was 51.1 ±â€…9.0 years, with males accounting for 55.7% (112/201). Results from nomogram model exhibited that potential risk factors for sleep disorders in patients undergoing hemodialysis included female, advanced age, increased creatinine and alanine aminotransferase levels, as well as higher red meat consumption. Inversely, protective factors against sleep disorders in these patients included higher consumption of poultry, fish, vegetables, and dietary fiber. The C-index demonstrated a high level of discriminative ability (0.922). This study found that age, sex, and dietary factors were associated with sleep disorders in hemodialysis patients. Hemodialysis patients with sleep disorders require urgent dietary guidance.

Increased retinoic acid signaling decreases lung metastasis in salivary adenoid cystic carcinoma by inhibiting the noncanonical Notch1 pathway.

MYB-NFIB fusion and NOTCH1 mutation are common hallmark genetic events in salivary gland adenoid cystic carcinoma (SACC). However, abnormal expression of MYB and NOTCH1 is also observed in patients without MYB-NFIB fusion and NOTCH1 mutation. Here, we explore in-depth the molecular mechanisms of lung metastasis through single-cell RNA sequencing (scRNA-seq) and exome target capture sequencing in two SACC patients without MYB-NFIB fusion and NOTCH1 mutation. Twenty-five types of cells in primary and metastatic tissues were identified via Seurat clustering and categorized into four main stages ranging from near-normal to cancer-based on the abundance of each cell cluster in normal tissue. In this context, we identified the Notch signaling pathway enrichment in almost all cancer cells; RNA velocity, trajectory, and sub-clustering analyses were performed to deeply investigate cancer progenitor-like cell clusters in primary tumor-associated lung metastases, and signature genes of progenitor-like cells were enriched in the "MYC_TARGETS_V2" gene set. In vitro, we detected the NICD1-MYB-MYC complex by co-immunoprecipitation (Co-IP) and incidentally identified retinoic acid (RA) as an endogenous antagonist of genes in the "MYC_TARGETS_V2" gene set. Following this, we confirmed that all-trans retinoic acid (ATRA) suppresses the lung metastasis of SACC by correcting erroneous cell differentiation mainly caused by aberrant NOTCH1 or MYB expression. Bioinformatic, RNA-seq, and immunohistochemical (IHC) analyses of primary tissues and metastatic lung tissues from patients with SACC suggested that RA system insufficiency partially promotes lung metastasis. These findings imply the value of the RA system in diagnosis and treatment.

Loss of Mature Lamin A/C Triggers a Shift in Intracellular Metabolic Homeostasis via AMPKα Activation.

The roles of lamin A/C in adipocyte differentiation and skeletal muscle lipid metabolism are associated with familial partial lipodystrophy of Dunnigan (FPLD). We confirmed that LMNA knockdown (KD) in mouse adipose-derived mesenchymal stem cells (AD-MSCs) prevented adipocyte maturation. Importantly, in in vitro experiments, we discovered a significant increase in phosphorylated lamin A/C levels at serine 22 or 392 sites (pLamin A/C-S22/392) accompanying increased lipid synthesis in a liver cell line (7701 cells) and two hepatocellular carcinoma (HCC) cell lines (HepG2 and MHCC97-H cells). Moreover, HCC cells did not survive after LMNA knockout (KO) or even KD. Evidently, the functions of lamin A/C differ between the liver and adipose tissue. To date, the mechanism of hepatocyte lipid metabolism mediated by nuclear lamin A/C remains unclear. Our in-depth study aimed to identify the molecular connection between lamin A/C and pLamin A/C, hepatic lipid metabolism and liver cancer. Gain- and loss-of-function experiments were performed to investigate functional changes and the related molecular pathways in 7701 cells. Adenosine 5' monophosphate-activated protein kinase α (AMPKα) was activated when abnormalities in functional lamin A/C were observed following lamin A/C depletion or farnesyltransferase inhibitor (FTI) treatment. Active AMPKα directly phosphorylated acetyl-CoA-carboxylase 1 (ACC1) and subsequently inhibited lipid synthesis but induced glycolysis in both HCC cells and normal cells. According to the mass spectrometry analysis, lamin A/C potentially regulated AMPKα activation through its chaperone proteins, ATPase or ADP/ATP transporter 2. Lonafarnib (an FTI) combined with low-glucose conditions significantly decreased the proliferation of the two HCC cell lines more efficiently than lonafarnib alone by inhibiting glycolysis or the maturation of prelamin A.

Can Sound Health Insurance Increase the Internal Circulation in the Economy of China?

In 2020, President Xi Jinping put forward a constructing cycle that has been given priority in this study. This particular cycle, when considered within the inner loop and outer loop, promotes the guiding ideology of the new development pattern of the binary economy that exists in recent times. Therefore, to gauge the extent of the promotion of domestic production and consumption, from the perspectives of medical expenses, this study refers to the bootstrap rolling window causality method, which considers the evidence-based medical spending on the consumption Granger causality. The results show that the Granger causality exists between medical expenditure and consumption expenditure at different time interval endpoints. In contrast, however, the variable of consumption does not produce Granger causality between medical expenditure and consumption. In this regard, a series of measures, such as increasing medical insurance expenditure, improvement of the medical insurance system, reduction of the housing price rise, and increasing government investment have been proposed to promote the development of the domestic circular economy.

Noncoding RNA 886 alleviates tumor cellular immunological rejection in host C57BL/C mice.

Non-coding RNA 886 (nc886/VTRNA2-1) is a Pol III transcript and an atypical imprinted gene. Its exact function as a negative regulator of protein kinase R establishes its connection with innate immunity. Studies have shown that nc886 silencing is closely associated with prostate cancer progression. Previous work has constructed a cell model of stable nc886 overexpression ("mimic" or "nc886+ ") in PC-3M-1E8 cell lines (1E8), which are highly bone-metastatic human prostate cancer cells with low expression of nc886, and cells expressing the mimic were validated to have lower invasive and metastatic abilities than cells expressing the scramble transcript in vitro and in vivo. In this study, we directly injected mimic or scramble cells into the left ventricle of C57BL/C mice, an immunocompetent animal model, to elucidate the immune mechanisms of tumor-host interactions. Interestingly, we found that tumor cells induced the inflammation of many important organs due to xenogeneic antigen rejection; this inflammation was ultimately repaired by tissue fibrosis after 28 days, except for in the spleen. The reason is that mimic cells, as heterogeneous antigens, are mostly directly recognized by macrophages or T cells in blood, and few mimic cells enter the spleen compared with scramble cells. The induction of splenic macrophage polarization to M2 macrophages by scramble cells is a critical factor in maintaining chronic splenic inflammation. In addition, we recognize that nc886 broadly decreases the expression of some human leukocyte antigen molecules and antigen transporters. This evidence reveals the interesting role of nc886 in regulating tumor cell antigens.

Identification of reciprocal microRNA-mRNA pairs associated with metastatic potential disparities in human prostate cancer cells and signaling pathway analysis.

The major cause of mortality for prostate cancer (PCa) is metastasis; however, the metastatic mechanism remains unclear. MicroRNAs (miRNAs) alter the expression patterns of essential genes through posttranscriptional regulation during cancer development. The study was mainly aimed at identifying specific miRNA-messenger RNA (mRNA) interactions and signaling pathways associated with PCa distant metastasis. New analytical approaches were applied, combining miRNA and gene expression microarray, to screen differentially expressed miRNA-mRNA pairs in the normal prostate epithelial cell line RWPE-1, the highly-metastatic human PCa cell line PC-3M-1E8 (H-1E8 or 1E8) and the lowly metastatic cell line PC-3M-2B4 (L-2B4 or 2B4). Eight differentially expressed candidate miRNAs and their targets closely related to PCa metastasis were identified and validated in patients by using the Gene Expression Omnibus database. Among them, overexpression of hsa-miR-92b-3p and hsa-let-7a-5p and underexpression of their targets, such as glutathione-S-transferase M3 (GSTM3), baculoviral IAP repeat-containing 3, and cyclin-dependent kinase inhibitor 1 (CDKN1A), were also validated in H-1E8 cells compared with L-2B4 cells. Bioinformatics suggested that hsa-miR-92b-3p and hsa-let-7a-5p and their targets might promote PCa metastasis through platinum-based drug resistance and the JAK-STAT signaling pathway. H-1E8 and L-2B4 cells treated by cisplatin showed the greatly decreased levels of hsa-miR-92b-3p and hsa-let-7a-5p; however, in contrast to 2B4 cells, 1E8 cells did not negatively regulate the increase in the expression levels of the targets GSTM3 and CDKN1A. This finding suggests that the dysregulation between hsa-let-7a-5p/CDKN1A and hsa-miR-92b-3p/GSTM3 pairs is associated with platinum-based chemoresistance of metastatic cancer cells.

Effect of therapeutic ultrasound on brain angiogenesis following intracerebral hemorrhage in rats.

Intracerebral hemorrhage (ICH) can produce severe neurological deficits in stroke survivors. However, few effective approaches are available to improve the recovery from ICH. Given that therapeutic ultrasound exposure can enhance on angiogenesis in peripheral tissues, the present study was designed to examine the effects of therapeutic ultrasound exposure on the brain angiogenesis following ICH. To this end, we applied once daily therapeutic ultrasound treatment to rats for 7 consecutive days after intracranial infusion of vehicle (Sham control) or collagenase (ICH). Repeated exposure to the low intensity of therapeutic ultrasound decreased behavioral scores in ICH rats, but not in sham control rats. Such an effect was correlated with an increased number of vessel-like structures and microvessels and PCNA positive cells in vWF-positive blood vessels in perihematomal brain tissues at post-ICH day 7. Furthermore, immunohistochemistry and western blotting results showed that ICH trigged the expression of extracellular matrix (ECM)-related molecules, including collagen Is, III, and IV, as well as integrins αvß3 and α5ß1, and exposure to therapeutic ultrasound increased the expression of these molecules. Therefore, our results indicated that repeated exposure to a low intensity of therapeutic ultrasound can increase the expression of collagen and integrins of ECM-related molecules, promote the formation of a large number of vessel-like structure and capillaries around the hematoma, and accelerate the recovery of neurological function impaired by ICH.

[Application of partial internal sphincter myomectomy in patients with Hirschsprung disease undergoing transanal one-stage pull-through operation].

OBJECTIVE: To investigate the effect of partial internal sphincter myomectomy on transanal one-stage pull-through operation for Hirschsprung disease (HD). METHODS: A prospective group of 153 pediatric patients with HD in Guangdong Dongguan People's Hospital between 2003-2012 were enrolled, who underwent transanal one-stage pull-through operation. Children were divided into partial resection group (77 cases) undergoing partial internal sphincter myomectomy and simple incision group (76 cases) undergoing simply internal sphincter dissection, respectively. Differences of postoperative complications and continence between two groups were compared. RESULTS: Postoperative complications such as rectal muscularis infection [1.3% (1/77) vs. 11.8% (9/76), P<0.05], enterocolitis [2.6% (2/77) vs. 13.2% (10/76), P<0.05], anastomosis stenosis[3.9% (3/77) vs. 22.4% (17/76), P<0.01] and abdominal distension [10.4% (8/77) vs. 25.0% (19/76), P<0.05] were lower in partial resection group as compared to simple incision group. The time of antibiotics administration was also lower in partial resection group [(3.9±1.1) d vs. (4.6±1.1) d, P<0.01]. Difference in the continence between the two groups was not statistically significant (kelly score, 5.1±0.5 vs. 5.2±0.6, P>0.05). CONCLUSIONS: Compared with simply internal sphincter dissection in operation, partial internal sphincter myomectomy with transanal one-stage pull-through operation for HD can reduce the postoperative complications and does not increase the damage of the continence.

Correlation between DNase I hypersensitive site distribution and gene expression in HeLa S3 cells.

Mapping DNase I hypersensitive sites (DHSs) within nuclear chromatin is a traditional and powerful method of identifying genetic regulatory elements. DHSs have been mapped by capturing the ends of long DNase I-cut fragments (>100,000 bp), or 100-1200 bp DNase I-double cleavage fragments (also called double-hit fragments). But next generation sequencing requires a DNA library containing DNA fragments of 100-500 bp. Therefore, we used short DNA fragments released by DNase I digestion to generate DNA libraries for next generation sequencing. The short segments are 100-300 bp and can be directly cloned and used for high-throughput sequencing. We identified 83,897 DHSs in 2,343,479 tags across the human genome. Our results indicate that the DHSs identified by this DHS assay are consistent with those identified by longer fragments in previous studies. We also found: (1) the distribution of DHSs in promoter and other gene regions of similarly expressed genes differs among different chromosomes; (2) silenced genes had a more open chromatin structure than previously thought; (3) DHSs in 3'untranslated regions (3'UTRs) are negatively correlated with level of gene expression.

[Study on no-load running-in wear of power-shift steering transmission based on oil spectrum analysis].

The running-in process wear rule of power-shift steering transmission can be studied conveniently and timely by using spectral analysis of oil. The configuration characteristic and the running-in mechanism of power-shift steering transmission were introduced firstly in the present paper. According to the discussion of running-in wear factors such as load, rotation speed, time, oil temperature, shifting number and original concentration of running-in oil, the wear calculation mode was established. The no-load running-in experiments of two power-shift steering transmissions were done, with different rotation speed and time. Based on the spectrum analysis of experiment result, the function relation between running-in wear and the oil original concentration and running-in speed was obtained, so the no-load running-in process wear calculation mode of power-shift steering transmission was confirmed. Through the experiment of other two power-shift steering transmissions, it was validated that the Cu element concentration can be calculated accurately by the wear calculation mode, which included the parameters such as oil original concentration, running-in speed, running-in time and gear shift alternate time. So the reference to evaluate the running-in quality and to constitute running-in regulations was gained.

[Copper ion electrochemistry in treatment of bleeding and prolapse due to hemorrhoid, experimental and clinical studies].

OBJECTIVE: To observe the effect of copper ion electrochemistry (CIE) in treatment of bleeding and prolapse due to hemorrhoid. METHODS: Bleeding was caused at several points on the sacrospinal muscles of 26 rabbits. Routine hemostasis was used at one side (control side) and CIE was used on the opposite side (experimental side). The stanch times at the different sides were recorded. Then the rabbits were killed. Pathological examination was made to the lung, liver, and kidney to observe the amount of small thrombus and inflammation. CIE was performed at the right side of anus of 6 dogs and the right side was used as control side. Tissue specimens of rabbit muscle and dog anus mucosa were collected to examine the copper ion concentration. A copper needle was inserted into each pile to the depth of 10 - 15 mm for 4'40" (with the mean number of treated points of 9.8) upon 202 patients suffering from bleeding due to hemorrhoid, 79 with inner hemorrhoids and 123 patients with mixed hemorrhoids (experimental group). Another 171 patients suffering from bleeding due to hemorrhoid, 64 with inner hemorrhoids and 107 with mixed hemorrhoids were treated with suppository as controls. CEI was performed on 128 patients suffering from prolapse of hemorrhoid, 41 with inner hemorrhoids and 87 with mixed hemorrhoids (experimental group). Another 115 patients suffering from prolapse of hemorrhoid, 40 with inner hemorrhoids and 75 with mixed hemorrhoids were treated with suppository as controls. Biopsy specimens of anus mucosa were taken from 18 patients with mixed hemorrhoid who underwent CIE. The copper ion concentration was measured in 30 patients undergoing CIE. RESULTS: The stanch time in the experimental side of rabbit was (1.16 +/- 0.18) min, significantly shorter than that in the control side [(2.13 +/- 0.46) min, P = 0.0037]. Extensive small thrombi and edema of vascular wall were seen in the rabbit liver, lung, kidney, and muscle tissues in comparison with the tissues of the control side (P < 0.01). Copper ion complex was seen in the experimental rabbit tissues. The copper ion concentration was significantly higher in the experimental area of dog anus mucosa than in the control area. Clinical study showed that after CIE the curative rate for bleeding was 95.5%, significantly higher than that of the control group (8.8%, U = 44.6, P < 0.001). The curative rate for prolapse in the experimental group was 60.8%, significantly higher than that of the control group (20.9%, U = 313.2, P < 0.01). No patient felt pain while treated and later. After the CIE treatment, the patients only needed to take a rest for 4 hours. Pathology showed there were much more small thrombi in the treated tissues. The blood copper ion concentration in the trial group did not increase significantly after CIE in comparison with that before treatment. CONCLUSION: CIE is safe, effective and easy to perform in treatment of bleeding and prolapse due to hemorrhoid.