anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The investigators are recruiting individuals with hypertension and LVH, as defined by echocardiography, who are on chronic angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blockade (ARB). Participants will be transitioned to enalapril, ACEi, with washout of all other anti-hypertensives and then randomized to add-on treatment for 9 months with eplerenone (MR antagonist) or chlorthalidone (thiazide-like diuretic) + potassium. The investigators will use cardiac PET to quantify changes in coronary microvascular function and cardiac efficiency; echocardiography to assess changes in cardiac function and structure. The investigators will define the impact of eplerenone as compared with chlorthalidone on coronary microvascular function (Aim 1) and cardiac efficiency (Aim 2) and determine the relationship between coronary microvascular function and cardiac efficiency. Additionally, the investigators will determine whether improvements in coronary microvascular function and/or cardiac efficiency correlate with improvements in myocardial structure and function (chamber dimensions, diastolic function, and global longitudinal strain) in individuals with hypertension and LVH.

Participants be placed on enalapril 10 mg and weaned off their other anti-hypertensives prior to the Pre-Treatment Assessment. After the Pre-Treatment Assessment, participants will be randomized to the following daily medications: 50 mg eplerenone or 12.5 mg chlorthalidone + 10 mEq potassium. At 2 weeks, eplerenone will be increased to 100 mg and chlorthalidone to 25 mg + 20 mEq potassium. Amlodipine (5 to 10 mg) will be added at 6 weeks or later if needed to achieve the BP target of \<135/85 mmHg. Study outcomes will be assessed at baseline and 9 months after randomization. The primary outcome measures will be: 1) myocardial flow reserve (MFR, ratio of stress over rest myocardial blood flow); and 2) myocardial external efficiency (MEE, ratio of myocardial work over myocardial oxygen consumption and LV mass). The investigators will also measure: 1) myocardial oxygen consumption (MVO2); 2) myocardial function (peak global longitudinal strain, tissue Doppler mitral annular early diastolic relaxation velocity \[e'\], and the ratio of mitral E velocity to e' \[E/e'\]) as measured by 2D echocardiography; 3) markers of cardiovascular injury and remodeling, including high sensitivity troponin and procollagen III amino terminal propeptide (PIIINP); and 4) measures of renin-angiotensin-aldosterone system under resting conditions, with upright posture, and with angiotensin-II stimulation.
Major depressive disorder (MDD) is a common complication of diabetes and is often observed alongside diabetic neuropathic pain (DNP) as a comorbidity in diabetic patients. Long non-coding RNA (lncRNA) plays an important role in various pathophysiological processes. The P2X7 receptor is responsible for triggering inflammatory responses, such as pyroptosis, linked to pain and depression. The aim of this study was to investigate the effect of lncRNA MSTRG.81401 on hippocampal pyroptosis induced by the P2X7 receptor in diabetic rats with DNP combined with MDD (DNP + MDD). Our results showed that the expression of lncRNA MSTRG.81401 was significantly elevated in the hippocampus of DNP + MDD rats compared with the control group. Following the administration of shRNA targeting lncRNA MSTRG.81401, a notable elevation in mechanical and thermal pain thresholds was observed in rats with comorbid DNP and MDD. Additionally, significant improvements in depression-like behaviors were evident in the open-field test (OFT), sucrose preference test (SPT), and forced swim test (FST). In the DNP + MDD rats, elevated levels in hippocampal P2X7 receptor mRNA and protein were observed, along with increased co-expression of P2X7 and the astrocytic marker glial fibrillary acidic protein (GFAP). Meanwhile, in DNP + MDD rats, the heightened mRNA expression of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), pyroptosis-related protein Gasdermin D (GSDMD), caspase-1, IL-1β, IL-18, and TNF-α was detected, in addition to increased serum levels of IL-1β, IL-18 and TNF-α. After shRNA treatment with lncRNA MSTRG.81401, the above abnormal changes in indicators for pyroptosis and inflammation were improved. Therefore, our study demonstrates that shRNA of lncRNA MSTRG.81401 can alleviate the pain and depression-like behaviors in diabetic rats associated with the comorbidity of DNP and MDD by inhibiting the hippocampal P2X7 receptor-mediated pyroptosis pathway and pro-inflammatory responses. This suggests that the P2X7R/NLRP3/caspase-1 implicated pyroptosis and inflammatory scenario may serve as a potential target for the management of comorbid DNP and MDD in diabetes.
Enrolled from January 1996. Patients to be included were those attending the out-patient clinic for a scheduled visit (i.e. appointment made more than 2 weeks before time of visit). For patients included in the study from 1994-1997, it was requested that the patients had a cluster of differentiation 4 (CD4) count \< 500 cells/µL within the last 5 months before inclusion. For all HIV patients enrolled and under follow up, laboratory, therapeutic and clinical data are collected twice annually. Demographic data, date on pregnancy and serological evidence for infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) are collected once annually.
The invention discloses an antagonist of micro non-coding RNA and application thereof. The antagonist of the micro non-coding RNA is antisense oligonucleotide (AMO-153-3p) of miR-153-3p seed sequence, and the sequence of the antagonist is shown in SEQ ID NO. 1. Compared with the prior art, the method has the advantages that a large number of experiments prove that miR-153-3p is over-expressed in a hippocampal cortical brain region in the constructed long-term cerebral ischemia and hypoxia rat model induced by long-term cerebral hypoperfusion, and the method can regulate and control the expression of a plurality of proteins related to neurotransmitter release through multiple target points, inhibit the release process of the neurotransmitter and further promote the occurrence of cerebral cognitive injury. The targeted inhibition of the expression of miR-153-3p can specifically block the inhibition effect of miR-153-3p on neurotransmitter release. Therefore, AMO-153-3p can be applied to the prevention and treatment of various mental and nervous system diseases caused by neurotransmitter release disorder induced by long-term cerebral ischemia and hypoxia.
The invention discloses radix tetrastigme toothpaste and a preparation method thereof. The toothpaste is prepared from, by weight, 3.4-17.8 parts of mixed wall breaking stock solution, xanthan gum, carrageenan and other toothpaste body matrixes. The mixed wall breaking stock solution is prepared from, by weight, 3-15 parts of fresh radix tetrastigme, 0.3-2 parts of green tea leaves and 0.1-0.8 part of pseudo-ginseng. Spectral sterilization, ultralow constant temperature vibration type wall breaking micro smashing and other modes are adopted in the toothpaste for obtaining the mixed wall breaking stock solution, and the cell wall breaking rate reaches 98.5 or above. Meanwhile, under the condition of temperature control, the toothpaste is prepared by combing the stock solution and the toothpaste body matrixes. The ultralow constant temperature vibration type wall breaking micro smashing mode is adopted, and the mixed wall breaking stock solution with the optimal drug property can be obtained under the condition of temperature control and can be fully fused into the toothpaste, so that the utilization rate of medicinal materials is increased, the additional value of the medicine materials is improved, the effects of the toothpaste on dental ulcers, periodontitis, bleeding gums and other oral diseases are better than those of common medicine toothpaste, and tooth health is benefited better.
In patients with hepatic cirrhosis and ascites, LASIX therapy is best initiated in the hospital. In hepatic coma and in states of electrolyte depletion, therapy should not be instituted until the basic condition is improved. Sudden alterations of fluid and electrolyte balance in patients with cirrhosis may precipitate hepatic coma; therefore, strict observation is necessary during the period of diuresis. Supplemental potassium chloride and, if required, an aldosterone antagonist are helpful in preventing hypokalemia and metabolic alkalosis.

If increasing azotemia and oliguria occur during treatment of severe progressive renal disease, LASIX should be discontinued.

Cases of tinnitus and reversible or irreversible hearing impairment and deafness have been reported. Reports usually indicate that LASIX ototoxicity is associated with rapid injection, severe renal impairment, the use of higher than recommended doses, hypoproteinemia or concomitant therapy with aminoglycoside antibiotics, ethacrynic acid, or other ototoxic drugs. If the physician elects to use high dose parenteral therapy, controlled intravenous infusion is advisable (for adults, an infusion rate not exceeding 4mg LASIX per minute has been used) (see PRECAUTIONS: Drug Interactions).
INTRODUCTION: The burden of defunctioning ileostomy is significant with up to two thirds of patients reporting stoma-related morbidity. While timely reversal is safe and cost-effective, the time to reversal in regional Australian hospitals is not well described in professional publications. We aim to assess the current timeliness of ileostomy closure and identify possible reasons for delaying closure.
METHODS: A retrospective analysis of loop ileostomies created and reversed in Launceston General Hospital for both rectal cancer surgery and other benign indications was undertaken. Patients with loop ileostomy created between 2010 and 2020 were included. Clinical data of timing of events, complications, readmission and stoma follow-up were recorded; and analysed using multivariate regression analyses to identify clinically relevant risk factors for delayed closure.
RESULTS: A total of 123 patients underwent loop-ileostomy formation during the study period, of which 106 patients (86.2%) were reversed. Median time to closure was 8.5 months (IQR 5.2-12.4) for patients with rectal cancers, compared to 5.2 months (IQR 3.6-9.3) for patients who did not have rectal cancer, with a difference of 3.4 months (95% CI 0.9, 5.9; P = 0.008). Adjuvant chemotherapy and unexpected readmission to hospital were associated with delayed reversal (P = 0.0081 and P = 0.0005, respectively).
CONCLUSION: Stoma reversal is often scheduled 3-6 months after creation. More than two-thirds of patients experienced delays due to changing clinical concerns and non-clinical factors, such as unexpected delays at each stage of surgical planning. Early placement on the waiting list and better-coordinated follow-ups may expedite reversal surgery and reduce associated morbidities.
BACKGROUND: Circular RNAs (circRNAs) are highly stable regulators, often accumulated in mammalian brains and thought to serve as "memory molecules" that govern the long process of aging. Mounting evidence demonstrated circRNA dysregulation in the brains of Alzheimer's disease (AD) patients. However, whether and how circRNA dysregulation underlies AD progression remains unexplored.
METHODS: We combined Poly(A)-tailing/RNase R digestion experimental approach with CARP, our published computational framework using pseudo-reference alignment for more sensitive and accurate circRNA detection to identify genome-wide circRNA dysregulation and their downstream pathways in the 5xFAD mouse cerebral cortex between 5 and 7 months of age, a critical window marks the transition from reversible to irreversible pathogenic progression. Dysregulated circRNAs and pathways associated with disease progression in 5xFAD cortex were systematically compared with circRNAs affected in postmortem subcortical areas of a large human AD cohort. A top-ranked circRNA conserved and commonly affected in AD patients and 5xFAD mice was depleted in cultured cells to examine AD-relevant molecular and cellular changes.
RESULTS: We discovered genome-wide circRNA alterations specifically in 5xFAD cortex associated with AD progression, many of which are commonly dysregulated in the subcortical areas of AD patients. Among these circRNAs, circGigyf2 is highly conserved and showed the highest net reduction specifically in the 7-month 5xFAD cortex. CircGIGYF2 level in AD patients' cortices negatively correlated with dementia severity. Mechanistically, we found multiple AD-affected splicing factors that are essential for circGigyf2 biogenesis. Functionally, we identified and experimentally validated the conserved roles of circGigyf2 in sponging AD-relevant miRNAs and AD-associated RNA binding proteins (RBPs), including the cleavage and polyadenylation factor 6 (CPSF6). Moreover, circGigyf2 downregulation in AD promoted silencing activities of its sponged miRNAs and enhanced polyadenylation site processing efficiency of CPSF6 targets. Furthermore, circGigyf2 depletion in a mouse neuronal cell line dysregulated circGigyf2-miRNA and circGigyf2-CPSF6 axes and potentiated apoptotic responses upon insults, which strongly support the causative roles of circGigyf2 deficiency in AD neurodegeneration.
CONCLUSIONS: Together, our results unveiled brain circRNAs associated with irreversible disease progression in an AD mouse model that is also affected in AD patients and identified novel molecular mechanisms underlying the dysregulation of conserved circRNA pathways contributing to AD pathogenesis.
The present invention discloses a formula of bezoar tea helpful for recovering from toothache and a production method thereof. The formula uses the as the main raw material. The main process flow for the production method includes: selecting materials, drying, pulverizing, blending ingredients, quantifying and packaging, thereby obtaining finished products. The tea has combined effects of nourishing heart and tranquilizing mind, clearing away heat and detoxifying body, diminishing inflammation, stopping pain and bleeding, etc. The tea is fresh and delicious in taste, easy to use and pure natural in raw materials, and has no toxin or any side effects. The tea is suitable for restaurant and household consumption.
Aging is the primary risk factor for cardiovascular disease (CVD). One critical process that links aging to CVD is the development of vascular dysfunction, characterized by endothelial dysfunction and arterial stiffness. Both endothelial dysfunction and arterial stiffness predict cardiovascular events in older individuals. Aging often coincides with obesity, another independent risk factor for CVD. Although vascular function is well characterized in both aging and obesity, it's unclear how these two conditions interact to modulate vascular function, and whether the combination of aging and obesity has additive or compounding effects on endothelial dysfunction and arterial stiffness.

Currently, it is unknown whether vascular dysfunction is driven by the same underlying cellular mechanisms in aging and obesity. Accumulating data in experimental animals suggest that ER stress may be an important factor in aging- and obesity-related vascular dysfunction. Additionally, middle-aged and older obese adults with endothelial dysfunction display evidence of ER stress within biopsied endothelial cells. In light of these data, the overall goal of this proposal is to test the hypothesis that ER stress is associated with human vascular dysfunction in the settings of aging and obesity, and to determine the efficacy of the chemical chaperone tauroursodeoxycholic acid (TUDCA), an established inhibitor of ER stress, to reduce endothelial cell ER stress and improve vascular function in these at-risk individuals. Results from this study have the potential to identify a novel, safe, and clinically relevant intervention strategy for the treatment of vascular dysfunction in an aging population at high-risk for the development of CVD.
Epilepsy is one of the most common serious chronic brain disorders, affecting up to 70 million people worldwide. Vascular disruption, including blood-brain barrier impairment and pathological angiogenesis, exacerbates its occurrence. However, its underlying mechanisms remain elusive. MCC950 is a specific small-molecule inhibitor that selectively blocks NLRP3 inflammatory vesicle activation across the blood-brain barrier, limits downstream IL-1β maturation and release, and exerts therapeutic effects across multiple diseases. In the present study, an epilepsy model was established by intraperitoneal administration of Kainic acid to adult male C57BL/6J wild-type mice. The results revealed that the epilepsy susceptibility of MCC950-treated mice was decreased, and neural damage following seizure episodes was reduced. In addition, immunofluorescence staining, RT-qPCR, and Western blot demonstrated that MCC950 inhibited the expression of the NLRP3 inflammasome and its related proteins in microglia, whereas microangiogenesis was found to be increased in the cerebral cortex and hippocampus of epileptic mice, and these effects could be reversed by MCC950. Furthermore, neurobehavioral impairment was observed in the epileptic mouse model, and MCC950 similarly alleviated the aforementioned pathological process. To the best of our knowledge, this is the first study to establish that pathological microangiogenesis is associated with NLRP3/IL-1β signaling pathway activation in a Kainic acid-induced epilepsy mouse model and that MCC950 administration attenuates the above-mentioned pathological changes and exerts neuroprotective effects. Therefore, MCC950 is a promising therapeutic agent for the treatment of epilepsy.
Metabolic disorders and gut microbiota dysbiosis contribute to the complicated pathology of chronic obstructive pulmonary disease (COPD). Qi-Huo-Yi-Fei formula (QHYFF) is a Chinese medicine prescription for COPD treatment and has showed beneficial clinical effects, but the underlying mechanism remains elusive. This study integrated metabolomics and gut microbiota analysis to explore potential mechanism of QHYFF against COPD. The therapeutic effects of QHYFF were evaluated using a murine model of COPD induced by cigarette smoke and lipopolysaccharide. QHYFF effectively improved pulmonary function, suppressed inflammation, and relieved lung pathological changes. Serum and urine metabolomics analysis identified 19 differential metabolites, such as L-tyrosine, epinephrine, dopamine, hypotaurine, citric acid, L-tryptophan and indoleacrylic acid, involving tyrosine metabolism, taurine and hypotaurine metabolism, citrate cycle and tryptophan metabolism. QHYFF also enriched Bifidobacterium, Blautia, Faecalibaculum and Parasutterella. Moreover, Spearman's correlation analysis showed that discriminative metabolites and bacteria were closely correlated with efficacy indices. The findings indicated that QHYFF could be an effective therapeutic measure against COPD by regulating metabolism and gut microbiota.
Questionnaire items will be created in two stages. First, 5 experts will independently review the literature on "telerehabilitation" and "usability". In addition, these experts will be asked to create a pool of questions based on their experiences in telerehabilitation and by taking the opinions of patients receiving telerehabilitation about usability. Then, 5 experts will come together and obtain a single question pool containing the questions they deem important in their question pool. The second step will involve scaling the elements. In this study, scale items will be scored on a five-point Likert scale, ranging from 1, strongly disagree to 5, strongly agree. Then, it will be applied to a pilot group of 10 people and it will be evaluated whether the items prepared by the experts are understood by the patients. In line with the expert opinion and the result of the pilot study, the final version of the scale will be decided and applied to MS, PD, and stroke patients who make up the study group. Finally, the validity and reliability of the questionnaire will be calculated.
The present invention relates to novel retinol derivatives, the methods of preparation and the uses thereof. According to the present invention, retinol derivatives comprise carboester linkage between di-, tri-, polypeptide having functional group of COOH and retinol. Retinol derivatives in the present invention comprise carboester linkage between amino acid having functional group of di-COOH and retinol. Retinol derivatives comprise carboester linkage between retinol and the compounds having the function group of COOH and multiple double bonds on carbon chain. Retinol derivatives in the present invention comprise carboester linkage between retinol and the compounds having the functional group of di-COOH and one double bond. Retinol derivatives in the present invention comprise ether linkage between the compounds with OH functional group and retinol.
We tested the hypothesis, generated from the Gradient Order Directions Into Velocities of Articulators (GODIVA) model, that adults who stutter (AWS) may comprise subtypes based on differing connectivity within the cortico-basal ganglia planning or motor loop. Resting state functional connectivity from 91 AWS and 79 controls was measured for all GODIVA model connections. Based on a principal components analysis, two connections accounted for most of the connectivity variability in AWS: left thalamus - left posterior inferior frontal sulcus (planning loop component) and left supplementary motor area - left ventral premotor cortex (motor loop component). A k-means clustering algorithm using the two connections revealed three clusters of AWS. Cluster 1 was significantly different from controls in both connections; Cluster 2 was significantly different in only the planning loop; and Cluster 3 was significantly different in only the motor loop. These findings suggest the presence of planning and motor subtypes of stuttering.