Exploration of symptom clusters during hemodialysis and symptom network analysis of older maintenance hemodialysis patients: a cross-sectional study.

BACKGROUND: Symptom networks can provide empirical evidence for the development of personalized and precise symptom management strategies. However, few studies have established networks of symptoms experienced by older patients on maintenance hemodialysis. Our goal was to examine the type of symptom clusters of older maintenance hemodialysis patients during dialysis and construct a symptom network to understand the symptom characteristics of this population. METHODS: The modified Dialysis Symptom Index was used for a cross-sectional survey. Network analysis was used to analyze the symptom network and node characteristics, and factor analysis was used to examine symptom clusters. RESULTS: A total of 167 participants were included in this study. The participants included 111 men and 56 women with a mean age of 70.05 ± 7.40. The symptom burdens with the highest scores were dry skin, dry mouth, itching, and trouble staying asleep. Five symptom clusters were obtained from exploratory factor analysis, of which the clusters with the most severe symptom burdens were the gastrointestinal discomfort symptom cluster, sleep disorder symptom cluster, skin discomfort symptom cluster, and mood symptom cluster. Based on centrality markers, it could be seen that feeling nervous and trouble staying asleep had the highest strength, and feeling nervous and feeling irritable had the highest closeness and betweenness. CONCLUSIONS: Hemodialysis patients have a severe symptom burden and multiple symptom clusters. Dry skin, itching, and dry mouth are sentinel symptoms in the network model; feeling nervous and trouble staying asleep are core symptoms of patients; feeling nervous and feeling irritable are bridge symptoms in this symptom network model. Clinical staff can formulate precise and efficient symptom management protocols for patients by using the synergistic effects of symptoms in the symptom clusters based on sentinel symptoms, core symptoms, and bridge symptoms.

CDC42EP3 promotes colorectal cancer through regulating cell proliferation, cell apoptosis and cell migration.

BACKGROUND: Nowadays, colorectal cancer (CRC) is one of the most commonly diagnosed malignant tumors worldwide, the incidence rate of which is still increasing year by year. Herein, the objective of this study is to investigate whether CDC42EP3 has regulatory effects in CRC. METHODS: First, CDC42EP3 knockdown cell model based on HCT116 and RKO cell lines was successfully constructed, which was further used for constructing mouse xenotransplantation models. Importantly, effects of CDC42EP3 knockdown on proliferation, colony formation, apoptosis, and migration of CRC were accessed by MTT assay, EdU staining assay, colony formation assay, Flow cytometry, and Transwell assay. RESULTS: As the results, we showed that CDC42EP3 was significantly upregulated in CRC, and its high expression was associated with tumor progression. Furthermore, knockdown of CDC42EP3 could inhibit proliferation, colony formation and migration, and promote apoptosis of CRC cells in vitro. In vivo results further confirmed knockdown of CDC42EP3 attenuated tumor growth in CRC. Interestingly, the regulation of CRC by CDC42EP3 involved not only the change of a variety of apoptosis-related proteins, but also the regulation of downstream signaling pathway. CONCLUSION: In conclusion, the role of CDC42EP3 in CRC was clarified and showed its potential as a target of innovative therapeutic approaches for CRC.

Preparation and cellular targeting study of VEGF-conjugated PLGA nanoparticles.

Vascular endothelial growth factor receptor (VEGFR) is over-expressed on a variety of tumour cells and tumour neovasculature, and so becomes well-documented target for cancer treatment. This study was designed to evaluate the cellular targeting and anti-tumor potency of VEGF-conjugated nanoparticles (VEGF-NPs). The poly-lactic-co-glycolic acid nanoparticles were prepared using the emulsion-solvent evaporation method and the VEGF was conjugated on surface of nanoparticles by covalent coupling method. The obtained particles were found to be of spherical shape exhibiting a size of 710 nm and VEGF conjugation efficiency was 16.6%. The results in vitro test showed that VEGF-NPs were more associated to Human Umbilical Vein Endothelial Cells by binding to VEGFR. In vitro cell proliferation test, IC50 showed the superior antiproliferative activity of paclitaxel-loaded VEGF-NPs over unconjugated nanoparticles and native paclitaxel due to higher cellular association on tumour cells. So, the VEGF-NPs offer a promising active targeting carrier for tumour selective treatment.

Regulatory mechanisms of long non-coding RNAs on mitochondrial function in congestive heart failure.

Congestive heart failure (CHF) is a multifaceted cardiovascular condition that imposes significant economic and social burdens on society, while also presenting a dearth of efficacious treatment modalities. Long non-coding RNAs (lncRNAs) possess the ability to influence the pathophysiological mechanisms underlying cardiac disease through their regulation of gene transcription, translation, and post-translational modifications. Additionally, certain lncRNAs can be encoded by the mitochondrial genome, hence impacting mitochondrial function. The heart relies heavily on mitochondrial oxidative phosphorylation for approximately 95 % of its ATP production. Consequently, the primary determinant linking mitochondrial dysfunction to heart failure is the impairment of cardiac energy supply resulting from mitochondrial injury. Cardiac dysfunction can arise as a result of various factors, including metabolic disease, disturbances in calcium homeostasis, oxidative stress, apoptosis, and mitochondrial phagocytosis, all of which are facilitated by mitochondrial damage. Currently, an increasing body of research indicates that lncRNA plays a significant role in the regulation of mitochondrial activity, hence impacting heart failure. As a result, the goal of this paper is to propose new ideas and targets for clinical research and therapy of heart failure by reviewing recent research on the regulatory mechanism of mitochondrial function by novel lncRNAs.

In vivo distribution of 5-Fluorouracil after peritumoral implantation using a biodegradable micro-device in tumor-bearing mice.

A novel implantable micro-device was used for delivery of 5-Fluorouracil (5-Fu), which was often used in the treatment of various human malignancies. The biodegradable poly(lactic-co-glycolic) acid (PLGA) was used as material. The purpose of this study was to investigate the efficiency of delivery of 5-Fu to the tumor via this delivery system. The distribution characters of the 5-Fu in tumor, plasma, peritumoral tissue, liver and kidney were compared after peritumoral implantation of micro-device and intraperitoneal injection of solution. After administration of micro-device, the 5-Fu was absorbed into the tumor on Day 1, and Cmax (4.14 µg/g) was reached on Day 6. The half life for the elimination was 4.48 d and the AUC was 46.78 µg × d/g. Similar pharmacokinetic behaviors were observed in plasma, peritumoral tissue, kidney and liver, while the Cmax and the AUC of plasma and these tissues were lower than those of tumor. When administered the solution, 5-Fu was rapidly absorbed into plasma, liver, kidney, spleen and tumor, and rapidly cleared from these tissues after 2 or 4 h. And the AUC in tumor of 5-Fu solution was significantly lower than that of the micro-device. These results indicated that 5-Fu loaded biodegradable micro-device offered a relatively high concentration and long-term delivery of the drug to the tumor site.

Wide QRS complex tachycardia with a mysterious mask-Tricuspid isthmus-dependent atrial flutter with preexcitation syndrome and dual atrioventricular nodal pathway conduction.

Key Clinical Message: Atrial flutter (AFL) and supraventricular tachycardia (SVT) are common arrhythmias in clinic. However, some AFL cases may present additional complexities, such as both accessory pathways (AP) and dual atrioventricular node pathways, putting on a mysterious mask and making it challenging to distinguish on electrocardiograms (ECGs). Abstract: A 60-year-old male patient had a sudden syncope, and an ECG showed wide QRS complex tachycardia. This diagnostic ambiguity is further compounded by the fact that SVT via AP conduction can exhibit wide QRS complex tachycardia characteristics resembling ventricular tachycardia (VT). Consequently, a definitive diagnosis through electrophysiological (EP) examination becomes imperative, as it dictates subsequent ablation strategies. In this article, we present a rare case involving three distinct arrhythmias including AFL, AP, and dual atrioventricular node pathways, and successfully treated through ablation.

Clostridium butyricum inhibits the progression of colorectal cancer and alleviates intestinal inflammation via the myeloid differentiation factor 88 (MyD88)-nuclear factor-kappa B (NF-κB) signaling pathway.

Background: Clostridium butyricum (C. butyricum, CB) is a probiotic to modulate the intestinal disorders and CB supplement has been found to have a great impact on inflammation and cancer treatment. However, the effects and mechanisms of CB on colorectal cancer (CRC) are not clear. We performed this study to investigate the influence of CB on the progression of CRC and the potential mechanisms in vivo and in vitro. Methods: We established azoxymethane (AOM)/dextran sulfate sodium salt (DSS) model mice (male, 6-week-old C57BL/6J) and divided them into the control (Ctrl) and CB groups at the end of the second DSS cycle. Mice in the CB group received treatment with CB [1×108 colony forming unit (CFU) in 100 µL phosphate buffered saline (PBS)] 3 times a week for 40 days by gavage administration. The apoptotic cells in tumor tissues were assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. IL-6 and IL-10 were detected using enzyme linked immunosorbent assay (ELISA) assayes. Microbiota was analyzed through 16S rDNA sequencing. The location of CB was detected by the fluorescence in situ hybridization (FISH) assay. The function of CB on the proliferation of cell lines, HT-29 and CT-26, was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assayes. The expression of myeloid differentiation factor 88 (MyD88) and nuclear factor-kappa B (NF-κB) in cells and tissues was evaluated by real time quantitative PCR (RT-qPCR) and western blot. Results: Mice in the CB group showed a lower incidence and total volume of CRC, more apoptotic cells in the tumor tissue, a lower level of IL-6, and a higher level of IL-10 compared with those in the Ctrl group. CB altered the composition of the gut microbiota and was enriched in the small intestine and tumor tissue. Moreover, CB restrained the proliferation and the expression of MyD88 and NF-κB in CRC cell lines and colon tissue. Conclusions: CB restrained the progression of CRC, improved the inflammation of AOM/DSS mice, altered the composition of their gut microbiota, and regulated the expression of MyD88 and NF-κB. We concluded that CB plays its role in CRC via MyD88 and the NF-κB signaling pathway.

Dispersion of daidzein with polyvinylpyrrolidone effects on dissolution rate and bioavailability.

OBJECTIVE: To study on the dispersion of daidzein with polyvinylpyrrolidone (PVP) and its effects on the aqueous solubility, dissolution rate and bioavailability of daidzein. METHODS: The solid dispersion of daidzein at various daidzein to PVP ratios were obtained via the solvent evaporation method and characterized by differential scanning calorimetry and fourier transform infrared spectroscopy. In addition,the bioavailability of free daidzein as well as its solid dispersion were studied in mice. RESULTS: It was found that the daidzein solubility in the solid dispersion form was 8 times greater than that of the free drug in water at (37 +/- 0.1) degrees C. Meanwhile,the daidzein dissolution rate was significantly increased after dispersing with PVP. The results of the bioavailability showed that both Cmax and AUC value of daidzein solid dispersion were about 5 times larger than unprocessed daidzein, implying that the rate-limiting step in daidzein absorption may be the dissolution process. CONCLUSIONS: The results in this work reveal the substantial advantages of adopting polyvinylpyrrolidone dispersion as an oral preparation to improve daidzein bioavailability.

The Impact of Immune Microenvironment on the Prognosis of Pancreatic Ductal Adenocarcinoma Based on Multi-Omics Analysis.

Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor characterized by rapid progression, early metastasis, high recurrence, and limited responsiveness to conventional therapies. The 5-year survival rate of PDAC is extremely low (<8%), which lacks effective prognostic evaluation indicators. In this study, we used xCell to analyze infiltrating immune cells in a tumor and through the univariate and multivariate Cox analyses screened out two prognosis-related immune cells, CD4+TN and common lymphoid progenitor (CLP), which were used to construct a Cox model and figure out the risk-score. It was found that the constructed model could greatly improve the sensitivity of prognostic evaluation, that the higher the risk-score, the worse the prognosis. In addition, the risk-score could also identify molecular subtypes with poor prognosis and immunotherapy sensitivity. Through transcriptome and whole-exome sequencing analysis of PDAC dataset from The Cancer Genome Atlas (TCGA), it was found that copy number deletion and low expression of CCL19 might be crucial factors to affect the risk-score. Lastly, validation of the above findings was confirmed not only in Gene Expression Omnibus (GEO) datasets but also in our PDAC patient samples, Peking2020 cohort.

Imperatorin derivative OW1 inhibits the upregulation of TGF-ß and MMP-2 in renovascular hypertension-induced cardiac remodeling.

Chronic hypertension induces vascular and cardiac remodeling. OW1 is a novel imperatorin derivative that was previously reported to inhibit vascular remodeling and improve kidney function affected by hypertension. In the present study, the effect of OW1 on the cardiac remodeling induced by hypertension was investigated. OW1 inhibited vascular smooth muscle cell (VSMC) proliferation and the phenotypic modulation of VSMCs induced by angiotensin II (Ang II). The OW1-induced vasodilatation of rat cardiac arteries was evaluated in vitro. Renovascular hypertensive rats were developed using the two-kidney one-clip method and treated with OW1 (40 or 80 mg/kg/day) or nifedipine (30 mg/kg per day) for 5 weeks. OW1 markedly reduced the systolic and diastolic blood pressure compared with that in the hypertension group or the respective baseline value during the first week. OW1 also reduced cardiac weight, and the concentrations of Ang II, aldosterone and transforming growth factor-ß1 (TGF-ß1). Histological examination demonstrated that OW1 exerted an inhibitory effect on vascular and cardiac remodeling. These inhibitory effects were associated with decreased cardiac levels of Ang II, matrix metalloproteinase-2 and TGF-ß1 in the hypertensive rats. In summary, OW1 exhibited a clear antihypertensive effect. More importantly, it inhibited vascular and cardiovascular remodeling, which may reduce the risk of hypertension-induced cardiovascular diseases. These results have potential implications in the development of new antihypertensive drugs.

A Streptococcus suis LysM domain surface protein contributes to bacterial virulence.

Streptococcus suis (SS) is a major swine pathogen, as well as a zoonotic agent for humans. Numerous factors contribute to SS virulence, but the pathogenesis of SS infection is poorly understood. Here, we show that a novel SS surface protein containing a LysM at the N-terminus (SS9-LysM) contributes to SS virulence. Homology analysis revealed that the amino acid sequence of SS9-LysM from the SS strain GZ0565 shares 99.8-68.7% identity with homologous proteins from other SS strains and 41.2% identity with Group B Streptococcal protective antigen Sip. Immunization experiments showed that 7 out of 30 mice immunized with recombinant SS9-LysM were protected against challenge with the virulent GZ0565 strain, while all of the control mice died within 48h following bacterial challenge. In mouse infection model, the virulence of the SS9-LysM deletion mutant (ΔSS9-LysM) was reduced compared with the wild-type (WT) strain GZ0565 and SS9-LysM complemented strain. In addition, ΔSS9-LysM was significantly more sensitive to killing by pig blood ex vivo and mouse blood in vivo compared with the WT strain and SS9-LysM complemented strain. In vivo transcriptome analysis in mouse blood showed that the WT strain reduced the expression of host genes related to iron-binding by SS9-LysM. Moreover, the total free iron concentration in blood from infected mice was significantly lower for the ΔSS9-LysM strain compared with the WT strain. Together, our data reveal that SS9-LysM facilitates SS survival within blood by releasing more free iron from the host. This represents a new mechanism of SS pathogenesis.

Short-term complete submergence of rice at the tillering stage increases yield.

Flooding is a major threat to agricultural production. Most studies have focused on the lower water storage limit in rice fields, whereas few studies have examined the upper water storage limit. This study aimed to explore the effect of waterlogging at the rice tillering stage on rice growth and yield. The early-ripening late japonica variety Yangjing 4227 was selected for this study. The treatments included different submergence depths (submergence depth/plant height: 1/2 (waist submergence), 2/3 (neck submergence), and 1/1 (complete submergence)) and durations (1, 3, and 5 d). The control group was treated with the conventional alternation of drying and wetting. The effects of waterlogging at the tillering stage on root characteristics, dry matter production, nitrogen and phosphorus accumulation, yield, yield components, and 1-aminocyclopropane-1-carboxylic acid synthase (ACS) gene expression were explored. Compared with the control group, the 1/1 group showed significant increases in yield, seed-setting rate, photosynthetically efficient leaf area, and OS-ACS3 gene expression after 1 d of submergence. The grain number per panicle, dry weight of the aboveground and belowground parts, and number of adventitious roots also increased. Correlation analysis revealed a significant positive correlation between the panicle number and nitrogen content; however, no significant correlation was found for phosphorus content. If a decrease in rice yield of less than 10% is acceptable, half, 2/3, and complete submergence of the plants can be performed at the tillering stage for 1-3 d; this treatment will increase the space available for rice field water management/control and will improve rainfall resource utilization.

5-Fluorouracil delivery from a novel three-dimensional micro-device: in vitro and in vivo evaluation.

A novel three-dimensional biodegradable micro-device using microelectromechanical systems technology was developed for implantable controlled drug delivery. In order to evaluate the effect of monomer composition and molecular weight of poly(lactic-co-glycolic acid) (PLGA) on the drug release, three 5-Fluorouracil loaded micro-devices, made of 50/50, 27 kDa; 50/50, 40 kDa and 75/25 27 kDa PLGA, were prepared and characterized by in vitro and in vivo methods. The in vitro drug release from three micro-devices followed zero-order kinetics, and PLGA micro-device with the higher molecular weight and lactide/glycolide ratio tended to a longer sustained release period. The in vivo release results agreed with the in vitro results and drug release in vivo was faster than that in vitro for each of micro-devices. And three micro-devices showed different tumor inhibition effect in the tumor bearing mice. In addition, the SEM and weight loss experiments showed that PLGA micro-devices with lower molecular weight and lactide/glycolide ratio had faster degradation. These data provided the information for the optimization of the novel three-dimensional biodegradable micro-device to obtain more suitable systems for controlled release and to meet release requirements of different drugs.