Construction of a prognostic model for breast cancer based on moonlighting genes.

Breast cancer (BRCA) is a highly heterogeneous disease, with significant differences in prognosis among patients. Existing biomarkers and prognostic models have limited ability to predict BRCA prognosis. Moonlighting genes regulate tumor progression and are associated with cancer prognosis. This study aimed to construct a moonlighting gene-based prognostic model for BRCA. We obtained differentially expressed genes (DEGs) in BRCA from The Cancer Genome Atlas and intersected them with moonlighting genes from MoonProt to acquire differential moonlighting genes. GO and KEGG results showed main enrichment of these genes in the response of BRCA cells to environmental stimuli and pentose phosphate pathway. Based on moonlighting genes, we conducted drug prediction and validated results through cellular experiments. After ABCB1 knockdown, viability and proliferation of BRCA cells were significantly enhanced. Based on differential moonlighting genes, BRCA was divided into three subgroups, among which cluster2 had the highest survival rate and immunophenoscore and relatively low tumor mutation burden. TP53 had the highest mutation frequency in cluster2 and cluster3, while PIK3CA had a higher mutation frequency in cluster1, with the majority being missense mutations. Subsequently, we established an 11-gene prognostic model in the training set based on DEGs among subgroups using univariate Cox regression, LASSO regression, and multivariable Cox regression analyses. Model prognostic performance was verified in GEO, METABRIC and ICGC validation sets. In summary, this study obtained three BRCA moonlighting gene-related subtypes and constructed an 11-gene prognostic model. The 11-gene BRCA prognostic model has good predictive performance, guiding BRCA prognosis for clinical doctors.

Functional connectivity characteristics of the brain network involved in prickle perception of single fiber stimulation.

BACKGROUND: The complex network connections, information transmission and organization play key roles in brain cognition on sensory stimulation. Previous studies showed that several brain regions of somatosensory, motor, emotional, cognitive, etc. are linked to fabric-evoked prickle. But the functional connectivity characteristics of the brain network involved in prickle perception is still unclear. MATERIALS AND METHODS: In the present study, resting state fMRI (functional magnetic resonance imaging) with functional connectivity analysis was adopted to build the initial brain functional network, and task fMRI with psychophysiological interaction analysis was employed to investigate modulation features of prickling task to functional connections in the brain network. RESULTS: The results showed that, in resting state, six groups or sub-networks can be identified in the prickle network, and when the subjects performed the prickling task, functional connectivity strength between some seed regions (e.g., somatosensory regions and precuneus, emotional regions and the prefrontal cortex, etc.) in the network increased. CONCLUSION: Combining resting-state fMRI with task fMRI is a feasible and promising method to study functional connectivity characteristics of the brain network involved in prickle perception. It is inferred that the "itch" ingredient of prickle sensation was transmitted from somatosensory cortices to precuneus, and emotional attribute (e.g., pain) from somatosensory cortices to the prefrontal cortex and at last to emotional regions.

Effect of different retention doses of ultrasound-guided polidocanol chemical ablation for benign cystic-solid thyroid nodules.

OBJECTIVE: To assess the influence of varying retention doses of ultrasound-guided polidocanol chemical ablation for benign cystic-solid thyroid nodules. METHODS: A retrospective study was conducted from December 2019 to January 2022, including 78 patients with benign cystic-solid thyroid nodules, of which 31 received polidocanol chemical ablation alone, 23 received polidocanol chemical plus thermal ablation, and 24 received open surgery. Patients who received polidocanol chemical ablation were assigned into groups based on the retention dose of polidocanol: 0 %, 10 %, 20 %, 30 %, and 50 %. Follow-ups were done at 1, 3, 6, and 12 months postoperatively. The volume of the nodules, postoperative complications, and recurrence of the nodules were examined before treatment and during follow-up visits. RESULTS: Total operation time and intraoperative bleeding volume for patients who received ablation were substantially lower than those for patients who received open surgery (P < 0.001). Among patients in the polidocanol chemical ablation group, volume shrinkage rate of thyroid nodules in the 10 % retention dose group was significantly lower than that in the 0 % retention dose group at 1, 3, and 6 months postoperatively (P < 0.05). The 30 % retention dose group had the highest nodule shrinkage rate (98.46 ± 1.55 %) at 12 months postoperatively, which was significantly higher than that in the 50 % retention dose group (P < 0.05). Among patients in the polidocanol chemical and thermal ablation group, the volume shrinkage rate of thyroid nodules in the 10 % and 30 % retention dose groups at 1 month postoperatively was significantly lower than that in the 0 % retention dose group (P < 0.05). Although volume shrinkage rate in the 20 % retention dose group after thermal ablation was higher than that in the 0 % retention dose group, the difference was not statistically significant (P > 0.05). In terms of adverse reactions, the incidence of hoarseness and coughing was higher in the open surgery group than in the polidocanol chemical ablation and polidocanol chemical and thermal ablation groups, but there was no significant difference (P > 0.05). CONCLUSION: Chemical ablation with polidocanol was safe and effective for therapy of benign cystic-solid thyroid nodules, and the optimal retention dose may be between 20 % and 30 %. Patients with poor efficacy from chemical ablation alone can receive safe and effective treatment through thermal ablation.

Analysis of brain signal change response in amygdala evoked by skin pressure stimulus.

BACKGROUND: It was well known that the human body would produce an uncomfortable sensation when the fabric exerted a certain amount of pressure irritation on the skin. The amygdala had long been thought to be the source of negative emotion perception. However, up to now, the brain signal changes in the amygdala evoked by skin exposure pressure had not been known. MATERIALS AND METHODS: In this work, a series of gradually increasing contact pressure stimulus from boneless corsets was repeatedly applied to the body's waist and abdomen, and the technology of functional magnetic resonance imaging (fMRI) was adopted to detect the brain response synchronously. RESULTS: The results shown that both subjective comfort score and percent signal changes (PSCs) of amygdala decreased with the increase of skin contact pressure. When the skin pressure applied to the waist and abdomen of the human body exceeded about 1 kPa, blood oxygen level dependent signal in the amygdala was negatively activated. Besides, the degree of response of PSCs was intense than subjective evaluation, and the standard deviations of PSCs between individuals were much smaller than subjective evaluations. CONCLUSION: It was suggested that skin contact pressure stimulus caused the attention of the amygdala brain area. The greater the stimulus, the higher the attention, but such attention was caused by negative activation of the amygdala induced by skin discomfort. In addition, skin comfort representation based on brain perception was superior to subjective representation due to its higher response sensitivity and antipsychological interference ability.

Comparison of brain functional response to mechanical prickling stimuli to the glabrous and hairy skin.

BACKGROUND: A kind of prickle sensation, which is a composite feeling of pain and itch, can be evoked by mechanical stimulation of fiber ends from fabric surface against to human hairy skin, rather than glabrous skin. Now, a functional magnetic resonance imaging (fMRI) study was conducted to investigate the cognitive differences in the brain for mechanical prickling stimuli to the two types of skin. MATERIALS AND METHODS: A nylon filament with the diameter of 205 µm and the length of 8 mm was used to deliver mechanical prickling stimuli respectively to two skin sites, fingertip (glabrous skin) and volar forearm (hairy skin), of eight healthy male subjects. Simultaneously, the technology of fMRI was adopted to acquire BOLD (Blood Oxygen Level-Dependent) signals of brain functional response of the subjects. RESULTS: Somatosensory areas, emotional areas, and the posterior parietal cortex (especially the precuneus) are important brain regions that distinguish between the two conditions. The representation of mechanical prickling stimulation to glabrous skin in the brain favors much more the tactile information of the stimulation and contains no itch, while the key brain area, precuneus, involved in itch was activated by the same mechanical prickling stimulation to hairy skin, and brain response for the condition of hairy skin contains more emotional information, which plays an important role in pain processing. CONCLUSION: Therefore, it can be inferred that a kind of stronger prickle sensation, which contains both pain and itch, was evoked by mechanical stimulation to hairy skin than glabrous skin.

Construction and validation of a metabolism-related prognostic model for thyroid cancer.

Metabolic reprogramming is a common pathological process of cancer. Expression of metabolism-related genes differs in thyroid cancer (TC) patients with different prognoses. This work committed to constructing a prognostic model for TC through identifying metabolism-related signatures. Expression profiles of mRNAs and clinical data of TC, were acquired from The Cancer Genome Atlas. Differential analysis was performed on mRNA expression profiles. The obtained differentially expressed genes (DEGs) were overlapped with metabolism-related genes from MSigDB database to acquire metabolism-related DEGs. Cox regression and Least Absolute Shrinkage and Selection Operator analyses were performed to ascertain feature genes and to build a prognostic model for TC. The model was evaluated comprehensively through survival curve, time-dependent receiver operating characteristic (ROC) curve, gene set enrichment analysis (GSEA), and Cox regression analyses combining varying clinical information. 7 key genes related to metabolism, including AWAT2, GGT6, ENTPD1, PAPSS2, CYP26A, ACY3 and PLA2G10, were identified, based on which a prognostic model was constructed. The survival analysis indicated that high-risk group presented shorter survival time than low-risk group. ROC curve results exhibited that AUC values of 3-year and 5-year survival of TC patients were both >0.70. Besides, GSEA on high/low-risk groups revealed that DEGs were mainly gathered in biological functions and signaling pathways linked with keratan sulfate catabolism and triglyceride catabolism. Combined with clinical information, Cox regression analyses unveiled that the 7-gene prognostic model can be an independent predictor. In conclusion, this model can effectively predict prognoses of TC patients, and also offer guidance for clinical treatment of TC.

Analysis of brain functional response to cutaneous prickling stimulation by single fiber.

BACKGROUND: It is now well understood that, as an uncomfortable sensation evoked by special fabric, prickle derives from the mechanical stimulation of protruding hairiness from fabric surface against the human skin, in which some nociceptors are easy to be triggered by stiff fiber ends. However, up to now, the neural mechanism of the brain for perceiving fabric-evoked prickle is still unclear. MATERIALS AND METHODS: In this work, A type of single-fiber stimulus made from nylon filament was used to repetitively prick the skin of volar forearm at a specific frequency, and the technology of functional magnetic resonance imaging (fMRI) was adopted to detect the brain response synchronously. RESULTS: The results show that repetitive prickling stimulation from the single fiber applied to the volar forearm aroused distributed activation in several brain regions, such as primary somatosensory cortex, secondary somatosensory cortex, motor cortex, bilateral occipital lobe, insular cortex, and ipsilateral limbic lobe. Although the brain activation distribution is similar to pain, the single fiber-evoked prickle sensation possesses unique activation characteristics in several brain regions. CONCLUSION: It is suggested that the sensation evoked by cutaneous prickling stimulation from single fiber belongs to a kind of multidimensional experience involving somatosensory, motor, emotional, cognitive, etc Our study constitutes an important step toward identifying the brain mechanism of fabric-evoked prickle.

Integrated analysis reveals potential long non-coding RNA biomarkers and their potential biological functions for disease free survival in gastric cancer patients.

BACKGROUND: Increasing evidences supported the association between long non-coding RNA (lncRNA) and disease free survival in gastric cancer (GC) patients. The purpose of the current study was to construct and verify a noninvasive preoperative predictive tool for disease free survival in GC patients. METHODS: There were 265 and 300 GC patients in model dataset and validation dataset respectively. The associations between the lncRNA biomarkers and disease free survival were evaluated by univariate and multivariate Cox regression. RESULTS: Thirteen lncRNA biomarkers (GAS5-AS1, AL109615.3, KDM7A-DT, AP000866.2, KCNJ2-AS1, LINC00656, LINC01777, AC046185.3, TTTY14, LINC01526, LINC02523, LINC00592, and C5orf66) were identified as prognostic biomarkers with disease free survival. These thirteen lncRNA biomarkers were combined to construct a prognostic signature for disease free survival. The C-indexes of the current predictive signature in model cohort were 0.849 (95% CI 0.803-0.895), 0.859 (95% CI 0.813-0.905) and 0.888 (95% CI 0.842-0.934) for 1-year, 3-year and 5-year disease free survival respectively. Based on thirteen-lncRNA prognostic signature, patients in model cohort could be stratified into high risk group and low risk group with significant different disease free survival rate (hazard ratio [HR] = 7.355, 95% confidence interval [CI] 4.378-12.356). Good reproducibility of thirteen-lncRNA prognostic signature was confirmed in an external validation cohort (GSE62254) with HR 3.919 and 95% CI 2.817-5.453. Further analysis demonstrated that the prognostic significance of thirteen-lncRNA prognostic signature was independent of other clinical characteristics. CONCLUSIONS: In conclusion, a simple noninvasive prognostic signature was established for preoperative prediction of disease free survival in GC patients. This prognostic signature might predict the individual mortality risk of disease free survival without pathological information and facilitate individual treatment decision-making.

Association between BCL2 interacting protein 3 like (BNIP3L) genetic polymorphisms and the risk of multiple myeloma in China.

BACKGROUND: The BCL2 interacting protein 3-like (BNIP3L) protein is involved in multiple myeloma (MM) development and progression. This study aims to explore the connection between BNIP3L single-nucleotide polymorphisms (SNPs) and MM. METHODS: SNaPshot was used to examine six SNP loci of the BNIP3L gene in enrolled subjects. The relationship between these loci and MM susceptibility and prognosis was explored. Survival analysis was used to evaluate the impact of different factors on patient survival. RESULTS: The rs2874670 AA genotype and A allele were associated with increased MM risk (P < 0.05). The CCACAC haplotype had a higher frequency in MM, while CCGCAC had a higher frequency in normal patients (all P < 0.05). Patients with R-ISS stage I and II had higher survival rates than those with stage III (P < 0.05). Patients, who received chemotherapy followed by autologous stem cell transplantation, had longer survival time than those who only received chemotherapy (P < 0.05). Low levels of LDH and ß2-MG were associated with better survival rates (P < 0.05). Cox regression identified that LDH levels, ß2-MG levels, and R-ISS staging were the risk factors for the death of MM. Mann-Whitney U test found a significant difference in survival time between MM patients with different BNIP3L rs2874670 genotypes after BD chemotherapy (P < 0.05). CONCLUSION: To our knowledge, this is the first study to find that BNIP3L rs2874670 could increase MM susceptibility in China. Different BNIP3L rs2874670 genotypes may affect the prognosis of MM patients receiving BD chemotherapy.

Investigating the Impact of Fly Ash on the Strength and Micro-Structure of Concrete during Steam Curing and Subsequent Stages.

Steam curing, a common way of curing precast concrete, can greatly improve its 1-day strength. However, the thermal effect of prolonged high-temperature curing can negatively impact the concrete's performance, thus compromising production of precast products in cold regions. Fly ash (FA) is used as a supplementary cementitious material to improve part of the properties of concrete. In this paper, we investigated the effect of FA (10~30%) on the compressive strength and microstructure of manufactured sand concrete at the steam curing and later stages. Specifically, we analyzed the behavior of FA in the constant temperature phase under steam curing. Results indicated that the pozzolanic reaction of FA started to occur at 24 h of constant temperature curing. Early hydration under steam curing produces a large amount of Ca(OH)2, causing the pozzolanic reaction of FA to occur significantly earlier, and the high pH value of the solution and the fibrous mesh structure of the FA surface promote the pozzolanic reaction. The addition of 30% FA to manufactured sand concrete causes a significant reduction in early strength under steam curing, which is not beneficial to the formwork removal and tensioning of precast members. Notably, manufactured sand concrete with 20% FA under steam curing had the highest late strength. The filling effect of FA and the additional gel produced by the pozzolanic reaction would result in the reduction in large pore content, refinement of pore size, improvement of microstructural compactness, and increase in gel system strength. Therefore, the addition of 20% FA to the manufactured sand concrete can improve the long-term strength, which is beneficial to the production of precast beams in cold regions.