Compromised Dynamic Cerebral Autoregulation in Patients with Restless Legs Syndrome.

Background: Restless legs syndrome (RLS) is a prevalent sensorimotor nervous system disorder in patients accompanied with insomnia, blood pressure fluctuation, and sympathetic dysfunction. These symptoms may disrupt cerebral hemodynamics. Dynamic cerebral autoregulation (dCA) describes the temporary response of cerebrovascular system to abrupt fluctuations in blood pressure, which keep cerebral blood flow stable and serve as a marker of cerebrovascular system ability. Objective: This research aimed to assess dCA in RLS patients. Methods: In this study, RLS patients were recruited and subsequently classified into four groups (mild, moderate, severe, and very severe) based on the International RLS Rating Scale (IRLS). Healthy controls matched for age and sex were enrolled. All participants were evaluated dCA by assessing phase difference (PD). A portion of patients with RLS was reassessed for dCA after one month of medication therapy (pramipexole [0.125 mg/day] and gabapentin [300 mg/day]). Results: There were altogether 120 patients with RLS and 30 controls completed the polysomnography and dCA assessment. PD was lower in the moderate, severe, and very severe RLS groups than that in the controls and mild RLS groups. Periodic limb movement index (PLMI), arousal index, and IRLS all showed a linear correlation with PD in RLS patients. Additionally, PD increased in RLS patients after therapy. Conclusion: The dCA was compromised in moderate, severe, and very severe RLS patients and was negatively correlated with the IRLS, arousal index, and PLMI. After 1 month of therapy, dCA improved in RLS patients.

Ultrahigh Energy Storage Density and Efficiency in Orthorhombic PLZST Antiferroelectric Ceramics via Composition Regulation.

PbZrO3-based antiferroelectric (AFE) ceramic materials have emerged as potential candidates for the next generation of high-energy multilayer ceramic capacitors (MLCCs) because of their distinctive characteristics of double hysteresis loops. The energy storage efficiency of orthorhombic AFE ceramics with ultrahigh storage density is relatively low, which hinders their practical application. In this study, the low efficiency limit of PLZST-based orthorhombic ceramics was overcome by precisely adjusting the Sn4+ content in the (Pb0.95Ca0.02La0.02)(Zr0.99-xSnxTi0.01)O3 AFE ceramics. On one hand, the addition of Sn4+ disrupts the original long-range dipole and improves the rapid response of polarization reversal under the applied voltage. As a result, the difference in electric hysteresis under an electric field is reduced, leading to a significant improvement in energy storage efficiency. On the other hand, increasing the Sn4+ content suppresses the formation of oxygen vacancies, inhibiting grain growth and strengthening grain bonding. This results in ceramics with a high breakdown field strength. Ultimately, the resulting PLCZST ceramics reveal an expressively improved recoverable energy density of 10.2 J cm-3 together with a high energy efficiency of 91.4% under a high applied electric field of 560 kV cm-1. The present study demonstrates the tunability of performance in orthorhombic PLZST AFE ceramics, thereby introducing a ceramic material with exceptional energy storage capabilities for MLCC applications.

Anxiety and depression among patients with insomnia during the first wave and the release of the COVID-19 in Northeast China: A cross-sectional survey.

BACKGROUND: The global coronavirus disease 2019 (COVID-19) pandemic seriously affected people's lives. We evaluated anxiety and depression among patients with insomnia in northeast China during the first wave and release of COVID-19, providing a basis for the clinical diagnosis and treatment of insomnia. METHODS: We enrolled 4211 patients with insomnia from January 2016 to February 2020, August 2020 to February 2022, August 2022 to December 2022, and January 2023 to February 2023, from our institution. Sleep quality was evaluated using the Athens Insomnia Scale, Insomnia Severity Index (ISI), and Pittsburgh sleep quality index (PSQI), while mood disorder and fatigue were evaluated using the Hhospital anxiety and depression scale (HAD), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder (GAD-7), and Fatigue Scale-14 (FS-14). RESULTS: Insomnia with depression increased in prevalence after COVID-19 compared with before (12.8 % vs. 15.3 %, P < 0.05), while the age of patients decreased [(50.2 ± 15.2) vs. (47.5 ± 16.8), P < 0.05]. The number of patients with insomnia and severe depression increased compared with before COVID-19 (20.3 % vs. 25.3 %, P < 0.05). A higher proportion of patients with insomnia for >2 years had depression (P < 0.05). As the epidemic subsided, insomnia increased among young and male patients (young patients: 55.2 % vs. 37.0 %; male patients: 41 % vs. 27.4 %, respectively; P < 0.05). The proportion of patients with insomnia with anxiety and depression increased (53.8 % vs. 51.8 %，P < 0.05), the proportion with moderate to severe anxiety increased (7.6 % vs. 13.5 %, P < 0.05), and moderate and severe depression decreased (moderate: 25.6 % vs. 19.1 %, severe: 25.8 % vs. 20.3 %, P < 0.05, respectively). Middle-aged and elderly patients had higher PQSI scores in sleep latency, habitual sleep efficiency, subjective sleep quality, and use of sleep medications than young patients (P < 0.05). The PSQI score was positively correlated with the PHQ-9 score (r = 0.526), GAD-7 score (r = 0.563), and FS-14 score (r = 0.316) (P < 0.05). LIMITATIONS: The study was single-center, the sample size was small, and assessment data were lacking from early in the epidemic. The scale is subjective, which may affect the accuracy. CONCLUSION: Insomnia with depression increased during COVID-19. The patients were younger than before the epidemic, and a higher proportion with insomnia for >2 years had depression. The proportion of patients with insomnia with anxiety and depression was higher after the epidemic period, and the degree worsened. The proportion of insomnia with depression decreased after the epidemic period, and the degree alleviated. The proportion of young male patients with insomnia increased. Middle aged and elderly patients with insomnia had poor sleep quality, which was positively correlated with anxiety, depression, and fatigue.

Oral microbiota disorder in GC patients revealed by 2b-RAD-M.

BACKGROUND: Microbiota alterations are linked with gastric cancer (GC). However, the relationship between the oral microbiota (especially oral fungi) and GC is not known. In this study, we aimed to apply 2b-RAD sequencing for Microbiome (2b-RAD-M) to characterize the oral microbiota in patients with GC. METHODS: We performed 2b-RAD-M analysis on the saliva and tongue coating of GC patients and healthy controls. We carried out diversity, relative abundance, and composition analyses of saliva and tongue coating bacteria and fungi in the two groups. In addition, indicator analysis, the Gini index, and the mean decrease accuracy were used to identify oral fungal indicators of GC. RESULTS: In this study, fungal imbalance in the saliva and tongue coating was observed in the GC group. At the species level, enriched Malassezia globosa (M. globosa) and decreased Saccharomyces cerevisiae (S. cerevisiae) were observed in saliva and tongue coating samples of the GC group. Random forest analysis indicated that M. globosa in saliva and tongue coating samples could serve as biomarkers to diagnose GC. The Gini index and mean decreases in accuracy for M. globosa in saliva and tongue coating samples were the largest. In addition, M. globosa in saliva and tongue coating samples classified GC from the control with areas under the receiver operating curve (AUCs) of 0.976 and 0.846, respectively. Further ecological analysis revealed correlations between oral bacteria and fungi. CONCLUSION: For the first time, our data suggested that changes in oral fungi between GC patients and controls may help deepen our understanding of the complex spectrum of the different microbiotas involved in GC development. Although the cohort size was small, this study is the first to use 2b-RAD-M to reveal that oral M. globosa can be a fungal biomarker for detecting GC.

A Blind Source Separation Method Based on Bounded Component Analysis Optimized by the Improved Beetle Antennae Search.

Currently, the widely used blind source separation algorithm is typically associated with issues such as a sluggish rate of convergence and unstable accuracy, and it is mostly suitable for the separation of independent source signals. Nevertheless, source signals are not always independent of one another in practical applications. This paper suggests a blind source separation algorithm based on the bounded component analysis of the enhanced Beetle Antennae Search algorithm (BAS). Firstly, the restrictive assumptions of the bounded component analysis method are more relaxed and do not require the signal sources to be independent of each other, broadening the applicability of this blind source separation algorithm. Second, the objective function of bounded component analysis is optimized using the improved Beetle Antennae Search optimization algorithm. A step decay factor is introduced to ensure that the beetle does not miss the optimal point when approaching the target, improving the optimization accuracy. At the same time, since only one beetle is required, the optimization speed is also improved. Finally, simulation experiments show that the algorithm can effectively separate independent and dependent source signals and can be applied to blind source separation of images. Compared to traditional blind source separation algorithms, it has stronger universality and has faster convergence speed and higher accuracy compared to the original independent component analysis algorithm.

Simultaneously Achieving Large Piezoelectricity and Low Dielectric Loss in High-Temperature BiScO3-PbTiO3-Based Ceramics.

High-temperature piezoelectric materials are pivotal to technology applications fields including defense, aerospace, nuclear energy, and oil well logging. However, the acquisition of excellent piezoelectric properties is usually at the cost of temperature stability (reduced Curie temperature and increased high-temperature dielectric loss), which hinders the application of piezoelectric ceramics in harsh environments. In this study, we investigated the effect of Nb5+ donor and Mn2+/3+ acceptor doping on the dielectric and piezoelectric properties of BiScO3-PbTiO3 (BS-PT)-based ceramics. In contrast to the acceptor doping, it was found that the donor doping not only enhances the piezoelectric properties but also effectively suppresses the dielectric loss at a high temperature by reducing the oxygen vacancy concentration. Eventually, we simultaneously attained an excellent piezoelectric performance (d33 is 553 pC/N at room temperature and 1528 pC/N at 400 °C, respectively) and a low dielectric loss (less than 2% in the temperature range of 150-300 °C) but still with a high Curie temperature (TC ∼ 445 °C) in Nb5+-doped BS-PT ceramics. Furthermore, different in situ measurements were used to demonstrate the remarkable temperature stability up to a high depolarization temperature of ∼400 °C. This work represents significant progress in high-temperature piezoelectric materials and provides a guideline for future efforts on enhancing the piezoelectricity and suppressing the dielectric loss at high temperature.

Combining WGCNA and machine learning to construct immune-related EMT patterns to predict HCC prognosis and immune microenvironment.

Hepatocellular carcinoma (HCC) is a malignancy with a very high mortality rate. Because of its high heterogeneity, there is an urgent need to find biomarkers that accurately predict prognosis. Epithelial-mesenchymal transition (EMT) is closely associated with frequent recurrence and high mortality of HCC. Therefore, it is necessary to comprehensively analyze the prognostic value and immunological properties of EMT gene in HCC. In our study, we performed bioinformatics analysis of the TCGA and ICGC liver cancer cohorts and identified the module genes of immune-associated EMTs (iEMT) by Weighted Gene Co-Expression Network Analysis (WGCNA). Further we used machine learning (support vector machines-recursive feature elimination and Lasso) to identify three central iEMT genes (ARMC9, ADAM15 and STC2) and construct iEMT_score. Subsequently, in the training and validation cohorts, it was demonstrated that the overall survival (OS) of patients in the high iEMT_score group was worse than that of patients in the low iEMT_score group. Based on this, we have constructed a nomogram that is easy for clinicians to use. In addition, our study explored differences in pathway enrichment, immunological properties, and sensitivity to common chemotherapy and targeted drugs in different subgroups of iEMT_score. Finally, we showed through in vitro experiments that knockdown of ARMC9 could significantly inhibit the proliferation, migration and invasion of HCC cells BEL7402. Taken together, our findings suggest that iEMT_score is an excellent biomarker for predicting prognosis and provide some new insights for personalized treatment of HCC patients.

Circadian rhythm in restless legs syndrome.

Restless legs syndrome (RLS) is a sensorimotor disorder with a obvious circadian rhythm, as its symptoms often occur or worsen only in the evening or at night. The mechanisms behind the rhythms of RLS have not yet been fully elucidated. This review explores possible causes for the circadian fluctuations of the symptomatology, including the levels of iron, dopamine, melatonin, melanocortin, and thyroid-stimulating hormone in the brain, as well as conditions such as peripheral hypoxia and microvascular function disorders. The metabolic disturbances of the substances above can create a pathological imbalance, which is further aggravated by physiological fluctuations of circadian rhythms, and results in the worsening of RLS symptoms at night. The review concludes with the suggestions for RLS treatment and research directions in the future.

Progress of autonomic disturbances in narcolepsy type 1.

Narcolepsy type 1 is a kind of sleep disorder characterized by a specific loss of hypocretin neurons in the lateral hypothalamus and reduced levels of hypocretin-1 in the cerebrospinal fluid. Hypocretin deficiency is associated with autonomic disorders. This article summarizes the autonomic disorders and possible mechanisms associated with narcolepsy type 1. Patients with narcolepsy type 1 often have various systemic autonomic symptoms, including non-dipping blood pressure, reduced heart rate variability, dynamic cerebral autoregulation impairment, reduced gastric motility and emptying, sleep-related erectile dysfunction, skin temperature abnormalities, and blunted pupillary light reflex. Similar findings should strengthen the recognition and intervention of these disturbances in clinical practice. In addition to hypocretin deficiency, current evidence also indicates that pharmacological therapy (including psychostimulants and anti-cataplectic drugs) and comorbidities may contribute to the alterations of autonomic system observed in narcolepsy type 1.

Variation in pollution status, sources, and risks of soil heavy metals in regions with different levels of urbanization.

Soil heavy metal (HM) pollution is an increasing threat to ecosystem integrity and human health with rapid urbanization. Nevertheless, how soil HMs vary with the process of urbanization remains unclear. Here we used index evaluation, spatial analysis, and a positive matrix factorization (PMF) model to determine the pollution characteristics and sources of eight soil HMs (Mn, Cr, Cu, Zn, As, Cd, Pb, and Ni) among regions with different urbanization levels (urban area, suburb, and ecoregion) in Baoding City, Northern China. We also assessed the risks posed to the ecosystem and human health using risk assessment models. The results indicated that the mean levels of Cu, Zn, As, Cd, and Pb in the study area exceeded the soil environmental quality standards by 10.7 %, 10.7 %, 12.5 %, 23.2 %, and 3.57 %, respectively. A pronounced regional spatial distribution was discovered with high levels in suburban areas. Both the geo-accumulation index and potential ecological risk index revealed significantly higher HM contamination in suburban areas than in urban or ecoregion areas. Source apportionment based on the PMF model and correlation analysis showed that soil HMs in suburban areas primarily originated from agricultural activity, industrial sources, and natural sources. Those in urban soils originated from industrial sources, urban traffic, and natural sources, whereas those in ecoregions derived from natural sources and agricultural activity. The complex sources of soil HMs in suburban areas resulted in the highest carcinogenic risks to children health, followed by the ecoregion, but not in urban areas. This study identified the differences in pollution levels, sources, and risks of soil HMs among regions with different urbanization levels and can guide future efforts to mitigate and manage soil HM pollution during urbanization.

Serum biomarker panel for disease severity and prognosis in patients with COVID-19.

BACKGROUND: Coronavirus disease-2019 (COVID-19) has become a worldwide emergency and has had a severe impact on human health. Inflammatory factors have the potential to either enhance the efficiency of host immune responses or damage the host organs with immune overreaction in COVID-19. Therefore, there is an urgent need to investigate the functions of inflammatory factors and serum markers that participate in disease progression. METHODS: In total, 54 COVID-19 patients were enrolled in this study. Disease severity was evaluated by clinical evaluation, laboratory tests, and computed tomography (CT) scans. Data were collected at: admission, 3-5 days after admission, when severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA detection became negative, and composite endpoint. RESULTS: We found that the positive rate in sputum was three times higher than that in throat swabs. Higher levels of C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer (D-D), interleukin-6 (IL-6) and neutrophil-to-lymphocyte ratio (NLR) or lower lymphocyte counts suggested more severe disease, and the levels of cytokines and serum markers were intrinsically correlated with disease progression. When SARS-CoV-2 RNA detection became negative, the receiver operating characteristic (ROC) curve demonstrated that LDH had the highest sensitivity independently, and four indicators (NLR, CRP, LDH, and D-D) when combined had the highest sensitivity in distinguishing critically ill patients from mild ones. CONCLUSIONS: Monitoring dynamic changes in NLR, CRP, LDH, IL-6, and D-D levels, combined with CT imaging and viral RNA detection in sputum, could aid in severity evaluation and prognosis prediction and facilitate COVID-19 treatment.

Case report: Excessive daytime sleepiness as a presenting manifestation of autoimmune glial fibrillary acidic protein astrocytopathy.

Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a recently discovered autoimmune inflammatory disease of the central nervous system. It presents with a variety of clinical symptoms, including fever, seizures, psychiatric symptoms, limber weakness, and sensory symptoms. However, the symptoms of sleep disorders have not been sufficiently addressed. Here, we report a case of GFAP-A in which the patient complained of excessive daytime sleepiness and an excessive need for sleep. Our patient was a 58-year-old male who experienced excessive daytime sleepiness for 50 days following SARS-CoV-2 infection. He was diagnosed with coronavirus disease 2019 on June 1st. On the 7th of June, he experienced excessive daytime sleepiness, nausea, reduced food intake, lower limb weakness, and dysuria. Subsequently, his sleepiness significantly deteriorated on July 21st. Five months prior, the patient underwent laparoscopic partial right nephrectomy for clear-cell renal cell carcinoma. Brain MRI revealed abnormal hyperintense lesions in the pontine brain and around the mesencephalic aqueduct on T2 and T2-fluid attenuated inversion recovery (T2-FLAIR) sequences However, these lesions did not exhibit any pathological enhancement. Spinal cord MRI revealed lesions in the C6-C7 and T2-T3 segments on the T2 sequence. His Epworth Sleepiness Scale (ESS) score was 16 (reference range, <10), and 24-hour polysomnography supported the diagnosis of rapid-eye-movement sleep disorder and severe sleep apnea-hypopnea syndrome. Glial fibrillary acidic protein IgG antibodies were detected in the cerebrospinal fluid (1:32, cell-based assay) but not in the serum. The level of hypocretin in the cerebrospinal fluid was 29.92 pg/mL (reference range ≥110 pg/mL), suggesting narcolepsy type 1. After treatment with corticosteroids for approximately 1 month, the patient showed considerable clinical and radiological improvement, as well as an increase in hypocretin levels. Although repeated polysomnography and multiple sleep latency tests suggested narcolepsy, his ESS score decreased to 8. Our findings broaden the range of clinical manifestations associated with GFAP-A, thereby enhancing diagnostic and therapeutic strategies for this disease. Additionally, our results indicate a potential common autoimmune mechanism involving GFAP-A and orexin system dysregulation, warranting further investigation.

[Distribution Characteristics and Ecological Risk Assessment of Soil Heavy Metals in Baiyangdian Lake].

To understand the spatial distribution characteristics and potential ecological risk of heavy metals in soil of Baiyangdian Lake, 55 soil samples were collected and the contents of eight heavy metals (Mn, Cr, Cu, Zn, As, Cd, Pb, and Ni) were detected. The spatial variation structure and distribution pattern were analyzed using geostatistical methods (Moran index and semi-variance model). The degree of heavy metal pollution and its risk were assessed using the geoaccumulation index (Igeo) and potential ecological risk index (Eri and RI). The results showed that the average of ω(Mn), ω(Cr), ω(Cu), ω(Zn), ω(As), ω(Cd), ω(Pb), and ω(Ni) were 467.75, 43.59, 28.57, 89.04, 12.32, 0.18, 19.26, and 30.56 mg·kg-1, respectively, all of which were lower than the screening values of soil pollution risk in agricultural land. However, the contents of Cu, Zn, and Cd were significantly higher than their background values, with two highly variable elements of Cu (48.65%) and Cd (37.52%). The Moran index indicated that Mn, Cu, Cd, and Pb showed weak spatial autocorrelation. Nugget coefficients of both of Cd and Pb shown by the semi-variance model were 100%, suggesting random variation as a main spatial variation driven by anthropogenic factors. High values of soil heavy metals were mainly distributed in the southwest of Baiyangdian Lake with a significant correlation between the heavy metals. The Igeo of soil heavy metals from high to low was Cd>Cu>Zn>Ni>As>Pb>Mn>Cr. Cd pollution was the most common, in which 67.27% of the samples were lightly polluted. Ecological risk assessment revealed that the average Eri of Cd was 58.81, belonging to the middle ecological risk level, and the rest were at light ecological risk. As a whole, the RI of soil heavy metal pollution in Baiyangdian Lake was at a light ecological risk level (87.81), with the highest contribution rate of Cd to RI (66.39%). Thus, it is necessary to strengthen the control of soil heavy metal Cd pollution in Baiyangdian Lake in the future.

A comprehensive pancancer analysis reveals the potential value of RAR-related orphan receptor C (RORC) for cancer immunotherapy.

Background: RAR-related orphan receptor C (RORC) plays an important role in autoimmune responses and inflammation. However, its function in cancer immunity is still unclear. Its potential value in cancer immunotherapy (CIT) needs to be further studied. Methods: Expression and clinical data for 33 cancers were obtained from UCSC-Xena. The correlation between RORC expression and clinical parameters was analyzed using the limma software package to assess the prognostic value of RORC. Timer2.0 and DriverDBv3 were used to analyze the RORC mutation and methylation profiles. RORC-associated signaling pathways were identified by GSEA. The correlations of RORC expression with tumor microenvironment factors were further assessed, including immune cell infiltration (obtained by CIBERSORT) and immunomodulators (in pancancer datasets from the Tumor-Immune System Interactions and Drug Bank [TISIDB] database). In addition, the correlations of RORC with four CIT biomarkers (tumor mutational burden, microsatellite instability, programmed death ligand-1, and mismatch repair) were explored. Furthermore, three CIT cohorts (GSE67501, GSE168204, and IMvigor210) from the Gene Expression Omnibus database and a previously published study were used to determine the association between RORC expression and CIT response. Results: RORC was differentially expressed in many tumor tissues relative to normal tissues (20/33). In a small number of cancers, RORC expression was correlated with age (7/33), sex (4/33), and tumor stage (9/33). Furthermore, RORC expression showed prognostic value in many cancers, especially in kidney renal clear cell carcinoma (KIRC), brain lower grade glioma (LGG), and mesothelioma (MESO). The mutation rate of RORC in most cancer types was low, while RORC was hypermethylated or hypomethylated in multiple cancers. RORC was associated with a variety of biological processes and signal transduction pathways in various cancers. Furthermore, RORC was strongly correlated with immune cell infiltration, immunomodulators, and CIT biomarkers. However, no significant association was found between RORC and CIT response in the three CIT cohorts. Conclusion Our findings revealed the potential immunotherapeutic value of RORC for various cancers and provides preliminary evidence for the application of RORC in CIT.

Oral iron supplementation in patients with heart failure: a systematic review and meta-analysis.

AIMS: This review aimed to assess whether oral iron supplementation in a chronic heart failure (HF) population with iron deficiency (ID) or mild anaemia is safe and effective according to evidence-based medicine. METHODS: We retrieved 1803 records from the PubMed, Embase, and the Cochrane Library databases from 1 January 1991 to 15 September 2021. The clinical outcome of oral iron supplementation for ID anaemia in patients with HF was the primary endpoint. The primary safety measures included adverse events and all-cause mortality, and efficacy measures included transferrin saturation (Tsat), ferritin levels, and the 6-min walk test (6MWT). The rate ratio (RR) was used to pool the efficacy measures. RESULTS: Five randomized controlled trials that compared oral iron treatment for patients with the placebo group and included a combined total of 590 participants were analysed. No significant difference was found in all-cause death between oral iron treatment and placebo groups (RR = 0.77; 95% confidence intervals (CI), 0.46-1.29, Z = 0.98; P = 0.33). However, adverse events were not significantly higher in the iron treatment group (RR = 0.83; 95% CI, 0.60-1.16, Z = 1.07; P = 0.28). In addition, ferritin levels and Tsat were slightly increased after iron complex administration in patients with HF but were not statistically significant (ferritin: mean difference [MD] = 2.70, 95% CI, -2.41 to 7.81, Z = 1.04; P = 0.30; Tsat: MD = 27.42, 95% CI, -4.93 to 59.78, Z = 1.66; P = 0.10). No significant difference was found in exercise capacity, as indicated by the 6MWT results (MD = 59.60, 95% CI, -17.89 to 137.08, Z = 1.51; P = 0.13). We also analysed two non-randomized controlled trials with follow-up results showing that oral iron supplementation increased serum iron levels (MD = 28.87, 95% CI, 1.62-56.12, Z = 2.08; P = 0.04). CONCLUSIONS: Based on the current findings, oral iron supplementation can increase serum iron levels in patients with HF and ID or mild anaemia but does not improve Tsat and 6MWT. In addition, oral iron supplementation is relatively safe.

SPOP Inhibition of Endometrial Carcinoma and Its Clinicopathological Relationship.

Objective: Endometrial carcinoma (EC) ranks first in the incidence of female genital malignancies in developed countries. SPOP (speckle-type POZ protein) has changed in EC with a statistically high frequency. This research may play a crucial role in the initiation and progression of EC, ultimately leading to fresh therapeutic targets. Explore the expression of SPOP in EC; observe its effect on the proliferation, invasion, and migration of EC cells after upregulating the expression of SPOP through RNA activation. Methods: The expression levels of SPOP protein in 150 EC tissues and 45 normal endometrial tissues were detected by immunohistochemistry and Western blotting. Analyze the relationship between SPOP expression and clinicopathological characteristics. The differences of the proliferation, migration, and invasion abilities between before and after transfection were analyzed using CCK-8 and Transwell assays. Results: The results of immunohistochemistry and Western blotting showed the expression level of SPOP in EC tissue significantly reduced or even missed compared with normal endometrial tissue. The results of CCK-8 showed that the growth of EC significantly slowed down after the upregulating of SPOP expression. The results of the Transwell assay showed the migration and invasion abilities of EC cells were weakened after the level of SPOP was upregulated. Conclusions: The expression level of SPOP in EC tissues is lower and related to the clinicopathological features compared with normal endometrial tissues. After upregulating the SPOP expression by RNA activation in EC cell lines, the abilities of proliferation, migration, and invasion of cells were significantly inhibited.

The value of erlotinib related target molecules in kidney renal cell carcinoma via bioinformatics analysis.

OBJECTIVE: Erlotinib was found to be an effective treatment for metastatic kidney renal cell carcinoma (KIRC). This study employed bioinformatics to explore the value of erlotinib's target molecules in KIRC. METHODS: We screened GSE25698 dataset for differentially expressed genes (DEGs) following erlotinib treatment, followed by analyzing their underlying functional mechanisms. The value of DEGs was identified in TCGA database to construct risk model and nomogram, and possible mechanisms underlying model factors and their relationship with KIRC immune infiltration were analyzed. RESULTS: Following erlotinib treatment, DEGs were involved in antigen binding, myeloid leukocyte activation, JAK-STAT signaling pathway, etc. COL11A1, EMCN, GLYATL1, HHLA2, IGFN1, LIPA, LRRC19, PANK1, PRAME, and TNFSF14 were independent factors influencing poor prognosis in KIRC patients. Age, grade, and risk score were independent risk factors influencing poor prognosis of KIRC patients. The risk score was associated with immune cells such as T cells regulatory, T cells follicular helper, macrophages M0, etc., and participated signaling mechanisms such as ERBB, insulin, mTOR, PPAR, apoptosis, MAPK, T cell receptor, etc. CONCLUSIONS: The expression levels of COL11A1, EMCN, GLYATL1, HHLA2, IGFN1 LIPA, LRRC19, PANK1, PRAME, and TNFSF14 were associated with KIRC prognosis and immune cell infiltration. The risk model and nomogram based on erlotinib's target molecules were expected to be a tool for evaluating the prognosis of KIRC patients.

Ivermectin, a potential anticancer drug derived from an antiparasitic drug.

Ivermectin is a macrolide antiparasitic drug with a 16-membered ring that is widely used for the treatment of many parasitic diseases such as river blindness, elephantiasis and scabies. Satoshi omura and William C. Campbell won the 2015 Nobel Prize in Physiology or Medicine for the discovery of the excellent efficacy of ivermectin against parasitic diseases. Recently, ivermectin has been reported to inhibit the proliferation of several tumor cells by regulating multiple signaling pathways. This suggests that ivermectin may be an anticancer drug with great potential. Here, we reviewed the related mechanisms by which ivermectin inhibited the development of different cancers and promoted programmed cell death and discussed the prospects for the clinical application of ivermectin as an anticancer drug for neoplasm therapy.

Upregulation of FHIT gene expression in endometrial carcinoma by RNA activation.

Endometrial carcinoma is the most common malignant tumors of the reproductive system, and fragile histidine triad (FHIT) plays an important role in multiple tumors. The purpose of this study was to investigate the expression of FHIT gene in endometrial carcinoma, and its effect on proliferation, invasion, and metastasis after upregulation. In vitro, the endometrial carcinoma cell lines were cultured. The FHIT-saRNA expression vector was constructed. The endometrial carcinoma cell line that upregulated the expression of FHIT was established, and whether the saRNA had a direct targeting regulation on the FHIT was verified. A difference of expression of FHIT in normal endometrial and endometrial carcinoma was detected. We detected the proliferation of endometrial carcinoma cell lines before and after activating FHIT. The endometrial carcinoma cell lines were compared with the corresponding transiently transfected cell lines in their capabilities of cell migration and invasion. The results showed that the expression of FHIT in endometrial carcinoma was significantly decreased or even deficient compared with normal endometrium. Upregulating the expression of FHIT is related to inhibiting the proliferation, invasion and metastasis of endometrial carcinoma. The possible mechanism is related to the regulation of cell cycle regulation, and plays a role in inhibiting tumor proliferation. The research on molecular mechanism in the development and progression of endometrial carcinoma has important theoretical significance for improving the diagnosis, treatment and prognosis of clinical tumors.

Clinicopathologic features of succinate dehydrogenase deficiencient renal cell carcinoma.

According to the WHO new renal tumor classification (2016), the clinical and pathologic characteristics, immunophenotype and molecular genetic characteristics of 2 cases of succinate dehydrogenase (SDH)-deficient renal cell carcinoma were retrospectively analyzed, and the relevant literature was reviewed. In 2 cases, there was 1 male and 1 female, the average age was 52.5 years old. The renal tumor average length was 4.2 cm. Tumor cut surface was solid, grayish yellow and soft. The tumor boundary was clear, and the cells were arranged in solid, nested, or small tubular growth. The cytoplasm was vacuolated or contained eosinophilic or light-stained flocculent substance, with a regular nucleus and no obvious nucleoli, showing low-grade nuclei. No atypical mitotic figures or necrosis were found. SDH-deficient renal cell carcinoma has a characteristic morphologic manifestation, and lack of SDHB expression in the immunophenotype. During the clinical diagnosis and treatment, the patient's condition and family genetic history should be asked for in detail, and genetic detection should be performed to confirm the diagnosis if necessary.