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objective To investigate the quality of life in old patients with dysphagia and the related factors. Methods:From January to December, 2019, 523 old inpatients were selected and investigated with Swallowing-Quality of Life Questionnaire (SWAL-QOL), Eating Assessment Tool-10 (EAT-10), videofluoroscopic swallowing study (VFSS), Nutritional Risk Screening 2002 (NRS-2002) and FRIED scale. Results:There were 160 inpatients diagnosed dysphagia (30.59%). The total score of SWAL-QOL in the inpatients with dysphagia was (45.15±13.31), and the dimension scores from low to high were appetite, social function, swallowing symptoms, mental health, sleep, eating fear, eating time, fatigue, swallowing burden and communication. For the total score of SWAL-QOL, EAT-10 score ≥ 19 was the risk factor, while good health condition and accepting swallowing treatment were the protective factors. Conclusion:The quality of life is poor for the old inpatients with dysphagia, and early screening and intervention for dysphagia are needed.
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OBJECTIVE@#To investigate the role of endoplasmic reticulum (ER)-stress of Kupffer cells (KCs) and KCs-derived tumor necrosis factor- (TNF-) in medicating apoptosis of hepatic stellate cell (HSC).@*METHODS@#Sixty male SD rats were randomized into control group, model group, ER- stress group, depletion group and KCs block group (=15). The 4 groups of rats were given intraperitoneal injections (twice a week for 8 weeks) of normal saline (2 mg/kg); 40% CCl4 solution (in peanut oil, 2 mg/kg); 40% CCl4 solution (2 mg/kg) and tunicamycin (1 mg/kg); and 40% CCl4 solution (2 mg/kg) and tunicamycin (1 mg/kg) followed by clodronate liposomes (50 mg/kg), respectively. After the treatments, samples of the liver tissue and serum were collected from the rats from the 4 groups to isolate KC cells, which were co-cultured with LX2 cells. In the depletion group, the rats were injected with anti-rat TNFR mAb (0.35 mg/kg) via the portal vein before isolating the KCs. Liver function examination, Eirius red staining, ELISA, immuno- histochemical staining, and RT-PCR were performed to assess the liver function, liver fibrosis, KC phenotypes, expression of the in fl ammatory factors, and the number of active HSC was detected. The isolated KCs were treated with tunicamycin before co-culture with LX2 cells, and ELISA, RT-PCR and Western blot were performed to examine KC phenotypes, in fl ammatory factors, LX2 cell apoptosis and TNFR/caspase8 pathway activity.@*RESULTS@#Compared with the rats in the control group, the rats in the model group had significantly increased ALT and AST levels, Sirius red staining-positive area, and Desmin-positive cells (activated HSCs) ( < 0.05) with significantly lowered number of CD16-positive KCs (M1), and TNF- protein and mRNA expression ( < 0.05). Compared with those in the model group, the rats in ER-stress group showed significantly decreased ALT and AST levels, Sirius red staining positivity and Desmin-positive cells ( < 0.05) and increased number of CD16-positive KCs and TNF- expressions ( < 0.05). In the depletion group, compared with the ER-stress group, the rats had significantly increased ALT and AST levels of, Sirius red staining positivity and Desmin-positive cells ( < 0.05) and reduced CD16- positive KCs and TNF-expressions ( < 0.05). In the cell co-culture experiment, the model group showed significantly reduced TUNEL-positive LX2 cells, CD16-positive cells, and expressions of TNFR1, cleaved caspase- 8 and cleaved caspase- 3 in the KCs ( < 0.05) with increased Desmin-positive LX2 cells ( < 0.05). Compared with the model group, the ER- stress group exhibited significantly increased TUNEL-positive LX2 cells, CD16-positive cells and expressions of TNFR, cleaved caspase-8 and cleaved caspase-3 in the KCs ( < 0.05) and decreased Desmin-positive LX2 cells ( < 0.05). In the depletion group, blocking TNFR resulted in significantly decreased expressions of cleaved caspase-8 and cleaved caspase-3 compared with those in ER- stress group ( < 0.05) although there was no significant changed in TNFR expression.@*CONCLUSIONS@#ER stress of KCs promotes the transformation of KCs towards M1 phenotype and increases the expression of TNF-, which triggers the apoptosis of HSCs through the TNFR/caspase-8 pathway.
Subject(s)
Animals , Male , Rats , Apoptosis , Caspase 8 , Endoplasmic Reticulum Stress , Hepatic Stellate Cells , Kupffer Cells , Rats, Sprague-Dawley , Tumor Necrosis Factor-alphaABSTRACT
Objective • To engineer a light-induced size-switchable (large to small) nanosystem for doxorubicin (DOX) delivery and characterize its light-induced size change and cytotoxicity. Methods • The poly(ethylene glycol)-polylactide nanoparticles loading DOX (PEG-PLA-DOX) were fabricated with the dropwise addition method. Then the nanoparticles were encapsulated into the inner cavity of liposome (LP), and a photosensitizer (verteporfin, VP) was loaded in the bilayers of the LP to engineer the near-infrared light-sensitive core-shell nanoparticles (PEG-PLA-DOX@LP). The morphology of the nanoparticles was observed under a transmission electron microscope. Dynamic light scattering was used to examine the particle size at each stage. The size-switchable property of the nanoparticles and its influence on viability of murine melanoma B16F10 cells under near-infrared light were evaluated. The stability of the nanoparticles was also investigated. Results • PEG-PLA-DOX@LP, the light-sensitive nanoparticles, were successfully developed. The nanoparticles had a particle size of (194.83±5.70) nm and Zeta potential of (-1.43±0.32) mV. The drug loading was 2.82% for DOX, and 1.16% for VP. The small-sized PEG-PLA-DOX [(37.42±8.67) nm] was quickly released from the nanoparticles upon light for enhanced toxicity to B16F10 murine melanoma cells. Conclusion • The particle size of the novel DOX delivery nanosystem rapidly changes from large size to small size upon the irradiation of near-infrared light, and thus the cytotoxic effect on tumor cells can be enhanced.
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Objective · To engineer a light-induced size-switchable (large to small) nanosystem for doxorubicin (DOX) delivery and characterize its light-induced size change and cytotoxicity. Methods · The poly (ethylene glycol) -polylactide nanoparticles loading DOX (PEG-PLA-DOX) were fabricated with the dropwise addition method. Then the nanoparticles were encapsulated into the inner cavity of liposome (LP), and a photosensitizer (verteporfin, VP) was loaded in the bilayers of the LP to engineer the near-infrared light-sensitive core-shell nanoparticles (PEG-PLA-DOX@LP). The morphology of the nanoparticles was observed under a transmission electron microscope. Dynamic light scattering was used to examine the particle size at each stage. The size-switchable property of the nanoparticles and its influence on viability of murine melanoma B16F10 cells under near-infrared light were evaluated. The stability of the nanoparticles was also investigated. Results · PEG-PLA-DOX@LP, the light-sensitive nanoparticles, were successfully developed. The nanoparticles had a particle size of (194.83±5.70) nm and Zeta potential of (-1.43±0.32) mV. The drug loading was 2.82％ for DOX, and 1.16％ for VP. The small-sized PEG-PLA-DOX [ (37.42±8.67) nm] was quickly released from the nanoparticles upon light for enhanced toxicity to B16F10 murine melanoma cells. Conclusion · The particle size of the novel DOX delivery nanosystem rapidly changes from large size to small size upon the irradiation of near-infrared light, and thus the cytotoxic effect on tumor cells can be enhanced.
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N-methyl-D-aspartate receptors (NMDARs), a subtype of glutamate-gated ion channels, play a central role in epileptogenesis. Recent studies have identified an increasing number of GRIN2A (a gene encoding the NMDAR GluN2A subunit) mutations in patients with epilepsy. Phenotypes of GRIN2A mutations include epilepsy-aphasia disorders and other epileptic encephalopathies, which pose challenges in clinical treatment. Here we identified a heterozygous GRIN2A mutation (c.1341T>A, p.N447K) from a boy with Rolandic epilepsy by whole-exome sequencing. The patient became seizure-free with a combination of valproate and lamotrigine. Functional investigation was carried out using recombinant NMDARs containing a GluN2A-N447K mutant that is located in the ligand-binding domain of the GluN2A subunit. Whole-cell current recordings in HEK 293T cells revealed that the N447K mutation increased the NMDAR current density by ~1.2-fold, enhanced the glutamate potency by 2-fold, and reduced the sensitivity to Mg inhibition. These results indicated that N447K is a gain-of-function mutation. Interestingly, alternative substitutions by alanine and glutamic acid at the same residue (N447A and N447E) did not change NMDAR function, suggesting a residual dependence of this mutation in altering NMDAR function. Taken together, this study identified human GluN2A N447K as a novel mutation associated with epilepsy and validated its functional consequences in vitro. Identification of this mutation is also helpful for advancing our understanding of the role of NMDARs in epilepsy and provides new insights for precision therapeutics in epilepsy.
Subject(s)
Adolescent , Humans , Male , Epilepsy, Rolandic , Genetics , Mutation , Receptors, N-Methyl-D-Aspartate , GeneticsABSTRACT
Objective To study the effect and mechanism of Akt during Islet -1 inducing the mesenchymal stem cells of C3H10T 1/2 cells to differentiate specifically into cardiomyocytes.Methods Developing a model of Islet-1 over-expression cells, Lentivirus infection efficiency of cells was detected by flow cytometry detection tech-nology.Cell proliferation was tested by CCK-8.The protein expression of Islet-1, cTnT and p-Akt/T-Akt was measured by Western blot.The mRNA expression of GATA4,Nkx2.5 and Mef2c were tested by real-time PCR. Results With the increasing of MK-2206 concentration, the inhibition rate of cell proliferation increased ( P<0.05) ,and the best inhibition concentration of Akt was 8nmol /L; With prolongation of Islet-1 inducing time,the protein expression of p-Akt/TA-kt reduced ( P<0.05 );The gene expression of myocardial specific transcription factor GATA4, Nkx2.5 andMe f2c increased( P<0.05); treated with MK-2206, the geneexpres-sion of GATA4, Nkx2.5 and Mef2cincreased significantly at the first week and then reduced ( P<0.05) . Conclu isons Akt plays different effects in different differentiation stages during the Islet-1 inducing the cells into cardiacs-pecific differentiation process .
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To further evaluate the safety of ginkgo diterpene lactone meglumine injection in the clinical use in ischemic stroke patients. Clinical safety study was conducted in 82 clinical units and 6 300 cases were completed and included from June 2013 to December 2014 by using multicenter, prospective, open and uncontrolled design methods for clinical research. A total of 29 cases of adverse reactions were observed in the experiment. Adverse reaction ratio (ADR) was 0.46%, and about 86.21% (25 cases) of them was mild with transient response which could be alleviated or disappeared without intervention; about 13.79% (4 cases) was moderate, including 2 cases of headache, 1 case of dizziness and 1 case of rash; no serious adverse reactions were found. The adverse reactions occurred in this study were pre-known adverse reactions or common adverse reactions of Chinese medicine injection. The overall incidence of adverse reactions was low, and the risk was controllable.