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@# Objective To explore the predictive value of a simplified signs scoring system for the severity and prognosis of patients with coronavirus disease 2019 (COVID-19). Methods Clinical data of 1 605 confirmed patients with COVID-19 from January to May 2020 in 45 hospitals of Sichuan and Hubei Provinces were retrospectively analyzed. The patients were divided into a mild group (n=1 150, 508 males, average age of 51.32±16.26 years) and a severe group (n=455, 248 males, average age of 57.63±16.16 years). Results Age, male proportion, respiratory rate, systolic blood pressure and mean arterial pressure in the severe group were higher than those in the mild group (P<0.05). Peripheral oxygen saturation (SpO2) and Glasgow coma scale (GCS) were lower than those in the mild group (P<0.05). Multivariate logistic regression analysis showed that age, respiratory rate, SpO2, and GCS were independent risk factors for severe patients with COVID-19. Based on the above indicators, the receiver operating characteristic (ROC) curve analysis showed that the area under the curve of the simplified signs scoring system for predicting severe patients was 0.822, which was higher than that of the quick sequential organ failure assessment (qSOFA) score and modified early warning score (MEWS, 0.629 and 0.631, P<0.001). The ROC analysis showed that the area under the curve of the simplified signs scoring system for predicting death was 0.796, higher than that of qSOFA score and MEWS score (0.710 and 0.706, P<0.001). Conclusion Age, respiratory rate, SpO2 and GCS are independent risk factors for severe patients with COVID-19. The simplified signs scoring system based on these four indicators may be used to predict patient's risk of severe illness or early death.
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To study the chemical constituents and their biological activities in the rhizomes of Curcuma phaeocaulis, silica gel column chromatography, reverse medium pressure liquid chromatography, preparative thin layer chromatography, and semi-preparative high performance liquid chromatography were used for isolation and purification and modern spectroscopic methods were used to determine the structure of the isolated compound. Moreover, the effect of the compound on the proliferation of HUVECs was determined by the MTT assay. A new elemane-type sesquiterpenoid glycoside was isolated from the n-butanol soluble fraction of 95% ethanolic extract of the rhizomes of Curcuma phaeocaulis. Its structure was identified as (1Z)-2-hydroxy-curzerenone 2-O-β-D-glucoside. It showed no inhibitory effect on the proliferation of HUVECs.
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ObjectiveTo conduct a visualized analysis of the research related to the use of brain-computer interface technology for stroke rehabilitation in the past ten years, and identify and predict the hot spots and hot trends in order to promote the further development of this field. MethodsThe Web of Science Core Collection database was searched for literature related to brain-computer interface technology for stroke rehabilitation from January, 2011 to October, 2022. CiteSpace 5.8.R3 was used to analyze the number of publications, countries, institutions, authors, keywords, co-citations, and grant support. Results and ConclusionA total of 592 papers were included, and the annual number of publications in this field of research showed a rapid growth trend, and the research enthusiasm continued to increase. The United States was in the leading position in this field, with the highest number of cooperative publications and the highest intermediary centrality; China had certain advantages in this field, but still needed to strengthen the exchange and cooperation with other countries/regions. Foreign institutions and authors had formed a network of close cooperative relationships, and formed a high-impact team represented by Niels Birbaumer, Cuntai Guan, Kai Keng Ang, etc.; there were poor cooperative relationships among domestic authors and institutions, and there were geographical restrictions and lack of high-impact academic groups. The keywords "motor imagery" and "recovery" formed ten major clusters and 15 prominent words with high variation rates, showing a trend of diversification in research directions. The study of the efficacy of upper limb motor rehabilitation and central mechanisms has been the hot topics in this field and will continue for some time in the future; the use of lower limb brain-computer interface systems for improving foot drop, gait and balance in stroke patients and the application of multimodal brain-computer interfaces will probably become a hot topic in the future. Finally, the use of brain-computer interface-guided neurofeedback training for cognitive and language rehabilitation in stroke also needs attention.
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ObjectiveTo observe the effect of brain-computer interface (BCI) training based on motor imagery on hand function in hemiplegic patients with subacute stroke. MethodsFrom June, 2020 to December, 2021, 40 patients with hemiplegia in subacute stroke from Department of Rehabilitation Medicine, Fifth Affiliated Hospital of Zhengzhou University were divided into control group (n = 20) and experimental group (n = 20) using random number table. Both groups accepted medication and routine comprehensive rehabilitation, while the control group accepted hand rehabilitation robot training, and the experimental group accepted the robot training using motor imagery-based BCI, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), modified Barthel Index, modified Ashworth scale, and measured integrated electromyogram of the superficial finger flexors, finger extensors and short thumb extensors of the affected forearm during maximum isometric voluntary contraction with surface electromyography. ResultsTwo patients in the control group and one in the experimental group dropped off. All the indexes improved in both groups after treatment (t > 2.322, Z > 2.631, P < 0.05), and they were better in the experimental group than in the control group (t > 2.227, Z > 2.078, P < 0.05), except the FMA-UE score of wrist. ConclusionMotor imagery-based BCI training is more effective on hand function and activities of daily living in hemiplegic patients with subacute stroke.
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Objective:To investigate the effect and mechanism of histone methyltransferase enhancer of zeste homolog 2 (EZH2) on sepsis-induced T cell dysfunction.Methods:Twenty-four male C57BL/6 mice were divided into three groups randomly: sham operated group, sepsis model group [cecum ligation and puncture (CLP)+dimethyl sulfoxide (DMSO) group] and EZH2 selective inhibitor treated group (CLP+GSK126 group), with 8 mice in each group. Sepsis murine model was reproduced by CLP. CLP+DMSO group and CLP+GSK126 group were treated with DMSO or GSK126 (10 mg/kg) respectively right after surgery through intraperitoneal injection. The mice were sacrificed 24 hours after operation, and the mesenteric lymph nodes were collected. The expression of EZH2, apoptosis rates, cell proliferation marker ki-67 antigen positive T lymphocytes (ki-67 + cell), interferon-γ positive T lymphocytes (IFN-γ + cell), programmed death receptor-1 positive T lymphocytes (PD-1 + cell) and programmed death-ligand 1 positive T lymphocytes (PD-L1 + cell) were determined by flow cytometry. Results:Compared with sham operated group, the expression of EZH2 in T lymphocytes was up-regulated on mesenteric lymph nodes of CLP+DMSO group. Compared with CLP+DMSO group, the ratio of CD3 + T lymphocytes in CLP+GSK126 group was up-regulated (0.70±0.02 vs. 0.50±0.07, P < 0.01), indicating that the EZH2 inhibitor could increase the number of T lymphocytes in lymph nodes of septic mice; the ratio of ki-67 + cells in CD4 + and CD8 + T lymphocytes in CLP+GSK126 group was increased (CD4 +: 0.74±0.05 vs. 0.63±0.04, CD8 +: 0.82±0.06 vs. 0.70±0.04, both P < 0.05), indicating that the EZH2 inhibitor could increase the ratio of T lymphocytes with high proliferative activity in lymph nodes of septic mice. However, no significant difference was found on both CD4 + and CD8 + T lymphocytes apoptosis rates in the mesenteric lymph nodes of mice between CLP+GSK126 group and CLP+DMSO group [CD4 +: (21.53±2.87)% vs. (20.48±3.21)%, CD8 +: (8.34±1.02)% vs. (7.71±1.38)%, both P > 0.05], indicating that no extra T lymphocytes apoptosis was induced by EZH2 inhibitor. Compared with CLP+DMSO group, the ratios of IFN-γ + CD4 + and IFN-γ + CD8 + T lymphocytes were increased in CLP+GSK126 group (IFN-γ +CD4 +: 0.31±0.11 vs. 0.14±0.06, IFN-γ +CD8 +: 0.30±0.10 vs. 0.13±0.06, both P < 0.05), suggesting that secretion of IFN-γ in lymph nodes by sepsis T lymphocytes was augmented after EZH2 inhibitor administration. Furthermore, compared with CLP+DMSO group, the ratio of PD-1 + cell in CD8 + T lymphocyte was down-regulated in CLP+GSK126 group (0.092±0.006 vs. 0.135±0.004, P < 0.01), suggesting that EZH2 inhibitor restrained the PD-1 expression on sepsis lymphoid node CD8 + T lymphocytes, however, it had no significant effect on PD-L1 + cells. Conclusion:EZH2, regulates sepsis-induced T lymphocyte dysfunction, possibly through modulating the expression of PD-1.
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Our previous study demonstrated that phosphodiesterase 8 (PDE8) could work as a potential target for vascular dementia (VaD) using a chemical probe 3a. However, compound 3a is a chiral compound which was obtained by chiral resolution on HPLC, restricting its usage in clinic. Herein, a series of non-chiral 9-benzyl-2-chloro-adenine derivatives were discovered as novel PDE8 inhibitors. Lead 15 exhibited potent inhibitory activity against PDE8A (IC50 = 11 nmol/L), high selectivity over other PDEs, and remarkable drug-like properties (worthy to mention is that its bioavailability was up to 100%). Oral administration of 15 significantly improved the cAMP level of the right brain and exhibited dose-dependent effects on cognitive improvement in a VaD mouse model. Notably, the X-ray crystal structure of the PDE8A-15 complex showed that the potent affinity and high selectivity of 15 might come from the distinctive interactions with H-pocket including T-shaped π-π interactions with Phe785 as well as a unique H-bond network, which have never been observed in other PDE-inhibitor complex before, providing new strategies for the further rational design of novel selective inhibitors against PDE8.
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A total of 15 batches of the substance reference of Guizhi Jia Gegen Decoction(GZGGD) were prepared and the characteristic fingerprints of them were established. Furthermore, the similarity of the fingerprints and peak attributes were explored. The extraction rate, and the content and the transfer rate ranges of the index components, puerarin, paeoniflorin, liquiritin, and ammonium glycyrrhizate were determined for the analysis of the quality value transfer. The result demonstrated that the fingerprints of the 15 batches of the samples showed high similarity(>0.99). A total of 15 characteristic peaks were identified from the fingerprints, with 10 for Puerariae Lobatae Radix, 1 for Cinnamomi Ramulus, 2 for Paeoniae Radix Alba, and 2 for Glycyrrhizae Radix et Rhizoma. The content of puerarin was 11.05-18.35 mg·g~(-1) and the average transfer rate was 21.27%-39.49%. The corresponding figures were 7.95-10.90 mg·g~(-1) and 23.28%-43.23% for paeoniflorin, 3.25-4.95 mg·g~(-1) and 32.31%-61.27% for ammonium glycyrrhizate, and 3.65-5.80 mg·g~(-1) and 14.57%-27.05% for liquiritin. The extraction rate of the 15 batches of samples was in the range of 16.85%-21.78%. In this paper, the quality value transfer of the substance reference of GZGGD was analyzed based on characteristic fingerprint, content of index components, and the extraction rate. This study is expected to lay a basis for the quality control and further development of GZGGD.
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Ammonium Compounds , Benchmarking , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , PaeoniaABSTRACT
This study aimed to analyze aflatoxins content and fungal community distribution in the harvesting and processing of Platycladi Semen, and explore the key link that affects aflatoxins contamination. The related Platycladi Semen samples of different maturity periods(cone non-rupture period, early rupture, and complete rupture period) and different processing periods(before drying, during 2-d drying, during 7-d drying, before and after seed scale removal, before and after peeling, 1 d after color sorting, and 7 d after color sorting) were collected for identifying the fungal community composition on sample surface by ITS amplicon sequencing. Then the content of aflatoxins B_1, B_2, G_1 and G_2 was determined by HPLC-MS/MS. The results showed that during the harvesting of Platycladi Semen from cone non-rupture to complete rupture, aflatoxins were only detected in the seed scale and seed coat, with aflatoxin G_2 in the seed scale and aflatoxin B_1 in the seed coat. During the drying, with the prolongation of drying time, aflatoxins B_1 and G_2 were detected simultaneously in the seed scale, aflatoxin B_1 in the seed coat, and low-content aflatoxin B_1 in the seed kernel. During subsequent processing, the aflatoxin content in seed kernel during subsequent processing was slighted increased. As demonstrated by fungal detection, Aspergillus flavus was not present during the harvesting of Platycladi Semen, but present during the drying and processing. Its content in the seed coat during the drying process was relatively higher. In short, Platycladi Semen should be harvested as soon as possible after it becomes fully mature. Drying process is the key link of preventing aflatoxin contamination. It is advised to build a sunlight room or adopt similar settings, standardize the operations in other processes, and keep the surrounding environment clean to minimize aflatoxin contamination.
Subject(s)
Aflatoxins/analysis , Aspergillus flavus , Food Contamination/prevention & control , Mycobiome , Semen/chemistry , Tandem Mass SpectrometryABSTRACT
Objective:To explore the clinical effect of the middle facial rejuvenation by cutting off the tear trough ligament and the orbicularis retaining ligament complex, opening the soft tissue spaces, combined with the lower eyelid muscle flap lateral canthus periosteum suspension and the orbital septum fat release.Methods:The clinical data of 39 patients with pouch and lacrimal groove, eyelid buccal groove depression in the Department of Cosmetic Surgery, Chongqing Chengshang Medical Beauty Clinic from June 2018 to June 2019 were retrospectively analyzed, including 2 males and 37 females, aged 30-58 (39±7) years. Through the incision of lower eyelid margin, the tear trough ligament and the orbicularis retaining ligament were completely severed. Up on the periosteum blunt, the preseptal, premaxillary and the prezygomatic spaces were dissected, and thus the fat of orbital diaphragmatic was fully expanded, by moving down and fixing on the inside, midside and outside periosteum of the inferior edge of the orbital bone. The lower eyelid muscle flap was suspended on the lateral canthus periosteum at the same time.Results:The patients were followed up for 12 months, the pouch, lacrimal groove and eyelid buccal groove depression were solved, the ptosis tissue of middle face was restored well and the effect was lasting. 3 patients felt the external eye angle traction after operation, and the symptoms disappeared 3-4 weeks later. 1 patient had mild eyelid ball separation due to hematoma organization after operation, and symptoms disappeared 3 months after anti scar treatment.Conclusions:For patients with pouch, lacrimal groove depression, eyelid buccal groove depression and midface tissue ptosis, the operation can safely and effectively solve the above problems and achieve the purpose of rejuvenation of the middle face, which is worthy of clinical application.
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Objective:To observe the multimodal imaging characteristics of the eyes in patients with presumed tuberculous retinal vasculitis.Methods:A retrospective case series study. A total of 15 patients (22 eyes) diagnosed with presumed tuberculous retinal vasculitis and receiving anti-tuberculosis treatment (ATT) effectively in Department of Ophthalmology, Subei People's Hospital Affiliated to Yangzhou University from January 2018 to April 2021 were included. Among them, there were 5 males and 10 females. Seven had bilateral involvement and 8 had unilateral involvement. The age was 49.3±11.1 years old. The best corrected visual acuity (BCVA), fundus colour photography, wide-angle fundus fluorescein angiography (FFA), and optical coherence tomography (OCT) were performed in all patients. Indocyanine green angiography (ICGA) was performed in 7 eyes. The BCVA examination was performed with the international standard visual acuity chart, which was converted into the logarithm of minimal angel resolution vision (logMAR). Systemic tuberculosis-related examinations included chest CT, serum T-spot, purified protein derivative and other tuberculosis-related tests. All patients were treated with systemic anti-tuberculosis therapy. The follow-up time was >12 months. The multimodal imaging characteristics for affected eyes. Nonparametric test was used to compare BCVA before and after treatment.Results:The retinal vessels of all the affected eyes were tortuously dilated, including 3 eyes with vascular white scabbard, 5 eyes with scattered bleeding point at the retina inculding 3 eyes walking along the vessels. The lesions were mainly distributed in the middle and periphery of the retina, and some of them involved the posterior pole; 12 eyes (54.5%, 12/22) with simple retinal vasculitis and 10 eyes (45.5%, 10/22) with retinal vasculitis complicated with choroiditis. Tuberculous retinal vasculitis showed different degrees of retinal vascular leakage on FFA, mainly retinal vein and capillary leakage, not involving arteries; 16 eyes (72.7%, 16/22) of retinal vasculitis showed peripheral occlusive retinal vasculitis and 4 eyes (18.2%, 4/22) were associated with retinal neovascularization. In 10 eyes with choroiditis, there were multiple focal choroiditis lesions of different sizes under the retina. Of the 7 eyes examined by ICGA, the choroidal inflammatory lesions showed hypofluorescent dark dots (HDD) in 5 eyes (71.4%,5/7), showing HDDs of different sizes, most of which were distributed in the posterior pole and middle periphery. In 10 eyes with retinal vasculitis complicated with choroiditis after ATT, the accumulation of hyper-reflective substances above and below the retinal pigment epithelium layer of the retina was gradually absorbed, but not completely disappeared, and most of the disorders of retinal structure could not be recovered. The average logMAR visual acuity was 0.61±0.57 before treatment and 0.36±0.55 after treatment. The BCVA after treatment was significantly higher than that before treatment ( Z=-3.102, P<0.01). Conclusions:Peripheral occlusive retinal vasculitis is the most common manifestation of tuberculous retinal vasculitis in FFA, which may be accompanied by focal choroidal inflammatory lesions. Wide-angle FFA and ICGA are more important in the diagnosis of tuberculous retinal vasculitis. OCT can be used for monitoring the changes of inflammation.
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Objective: To evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation (auto-HSCT) in elderly patients (≥65 years old) with multiple myeloma (MM) . Methods: From June 1, 2006 to July 31, 2020, 22 MM patients (≥65 years old) who were diagnosed in the First Affiliated Hospital, Sun Yat-sen University and received novel drug induction followed by auto-HSCT were analyzed retrospectively. These patients were evaluated for important organ functions before transplantation, and the International Myeloma Working Group frail score was used in 2016 to screen out transplant-eligible patients. Results: The median (interquartile range, IQR) age at the time of transplantation of the 22 patients was 66.75 (IQR 4.50) years. A total of 20 patients received stem cell mobilization. The median number of mononuclear cells collected was 4.53×10(8)/kg, that of CD34(+) cells was 3.37×10(6)/kg, and the median number of apheresis procedures performed was 2. After stem cell transfusion, the median time of neutrophil implantation was 11 days, that of platelet implantation was 13 days, and the treatment-related mortality was 0 at 100 days after transplantation. The median follow-up was 48.7 months. The median time to progression time was not reached, and the median overall survival time was 111.8 months. Conclusion: Auto-HSCT is a safe and effective treatment for selected elderly patients of 65 years or older with MM.
Subject(s)
Aged , Hematopoietic Stem Cell Mobilization/methods , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Multiple Myeloma/drug therapy , Retrospective Studies , Transplantation, Autologous/methods , Treatment OutcomeABSTRACT
Particle design, based on the concept of "quality by design", combines the elements of microbiology, formulation science, heat and mass transfer, solid state physics, powder science, and nanotechnology. It is widely used to develop particles with excellent functional properties. Without affecting the active ingredients, the modification technology of traditional Chinese medicine (TCM) powder based on particle design theory, could improve the flowability, tabletability, disintegration and dissolution behavior, hygroscopicity, wettability, and other functional properties at the physical structure level. This greatly promotes the development of solid preparations of TCM. The present review aims to summarize and discuss the research progress of powder modification of TCM from the perspective of the theory of particle design, powder modification technology, equipment used for powder modification, application in TCM and modification mechanism mainly based on researches published in recent ten years. This review could provide ideas and theory basis for the development of particle design.
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Scaffold hopping refers to computer-aided screening for active compounds with different structures against the same receptor to enrich privileged scaffolds, which is a topic of high interest in organic and medicinal chemistry. However, most approaches cannot efficiently predict the potency level of candidates after scaffold hopping. Herein, we identified potent PDE5 inhibitors with a novel scaffold via a free energy perturbation (FEP)-guided scaffold-hopping strategy, and FEP shows great advantages to precisely predict the theoretical binding potencies ΔG FEP between ligands and their target, which were more consistent with the experimental binding potencies ΔG EXP (the mean absolute deviations | Δ G FEP - Δ G EXP | < 2 kcal/mol) than those ΔG MM-PBSA or ΔG MM-GBSA predicted by the MM-PBSA or MM-GBSA method. Lead L12 had an IC50 of 8.7 nmol/L and exhibited a different binding pattern in its crystal structure with PDE5 from the famous starting drug tadalafil. Our work provides the first report via the FEP-guided scaffold hopping strategy for potent inhibitor discovery with a novel scaffold, implying that it will have a variety of future applications in rational molecular design and drug discovery.
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OBJECTIVE@#In order to grasp the quality status of the first-aid ventilator in pre-hospital and field environment in time, the quality control and detection items of invasive ventilator were optimized to form a rapid detection operation process of first-aid ventilator and ensure the safety of patient treatment.@*METHODS@#Based on the quality control detection data of invasive ventilator in hospital in recent years, methods such as narrowing the range of qualified criteria and analyzing confidence interval were adopted to extract indicators prone to deviation and verify their correlation with similar indicators, so as to form an optimized rapid detection portfolio.@*RESULTS@#Compared with the original quality control detection procedures, the detection indicators of the rapid detection procedures were reduced from 5 categories of 24 indicators to 3 categories of 7 indicators. The detection time was shortened by 56.1% and the coincidence rate of the detection results was 100% after the actual measurement and verification.@*CONCLUSIONS@#Under the premise of ensuring the testing quality, the operating procedure for rapid detection of emergency ventilator can greatly reduce the detection time, and realize the rapid and high frequency quality control detection, so as to ensure the quality and safety of the equipment.
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Home Care Services , Humans , Quality Control , Ventilators, MechanicalABSTRACT
BACKGROUND@#SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator of Chromatin, Subfamily A, Member 2) is an important ATPase catalytic subunit in the switch-sucrose nonfermenting (SWI/SNF) complex. However, its relationship with the pathological features of NSCLC and its prognosis remain unclear.@*METHODS@#We retrospectively reviewed 2390 patients with surgically resected NSCLC, constructed tissue microarrays (TMAs) and performed immunohistochemical assays. We analyzed the correlation of SAMRCA2 with clinicopathological features and evaluated its prognostic value.@*RESULTS@#Among 2390 NSCLC cases, the negative expression ratios of SAMRCA2, SMARCA4, ARID1A, ARID1B and INI1 were 9.3%, 1.8%, 1.2%, 0.4% and 0%, respectively. In NSCLC, male sex, T3 and T4 stage, moderate and poor differentiation, tumor ≥ 2 cm, Ki67 ≥ 15%, SOX-2 negative expression, middle lobe lesion and adenocarcinoma were relative risk factors affecting SMARCA2-negative expression. In lung adenocarcinomas, high-grade nuclei, histological morphology of acinar and papillary, solid and micropapillary and TTF-1-negative expression were relative risk factors affecting SMARCA2-negative expression. Kaplan-Meier survival analysis showed that the OS was shorter in the SMARCA2-negative group. Multivariate survival analysis revealed that SMARCA2-negative expression was an independent factor correlated with a poor prognosis in NSCLC.@*CONCLUSION@#In conclusion, SMARCA2-negative expression is an independent predictor of a poor outcome of NSCLC and is a potential target for NSCLC treatment.
Subject(s)
Adenosine Triphosphatases/metabolism , Carcinoma, Non-Small-Cell Lung/genetics , Humans , Male , Retrospective Studies , Transcription Factors/geneticsABSTRACT
In this study, dexamethasone (DXMS) and captopril (CAP) were co-loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles with a surface coating of a phospholipid bilayer, and then the core-shell nanoparticles were modified with polyethylene glycol and integrin α8 antibody to obtain immunoliposome-nanoparticle hybrids (DXMS/CAP@PLGA-ILs). The role of nanoparticles on the renal targeting, anti-inflammatory effects, and macrophage differentiation were investigated. The results showed that the particle size of the nanoparticles was 115.9 ± 2.89 nm, and the core-shell structure could be observed under an electron microscope. The drug loading capacity of DXMS and CAP was 5.72% ± 0.37% and 7.51% ± 0.07%, respectively. The results of in vitro experiments showed that DXMS/CAP@PLGA-ILs could reduce the secretion of specific cytokines and the mRNA expression of markers in M2-type macrophages, thus promoting the differentiation of M2-type macrophages in the direction of unpolarized macrophages. In vivo experiments in mice showed that DXMS/CAP@PLGA-ILs had a significant renal targeting effect, which could restore the renal index, serum creatinine, and urea nitrogen levels of mesangial proliferative glomerulonephritis in mice. Moreover, DXMS/CAP@PLGA-ILs could reduce both the secretion of inflammatory cytokines and the mRNA expression levels of M1 and M2 macrophage markers in the kidney. All the animal experiments were in accordance with the regulations of Animal Ethics Committee of Sichuan Agricultural University. In conclusion, renal-targeting DXMS/CAP@PLGA-ILs could effectively regulate the polarization of macrophages and had an "anti-inflammatory/anti-fibrosis" therapeutic effect, providing a new strategy and basis for the targeted therapy of glomerulonephritis.
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Objective: To analyze the effects of spvD gene on invasion and intracellular proliferation of Caco-2 cells and in order to provide insight into the function of that gene and the underlying mechanism of Salmonella caused infection. Methods: Functional verification of spvD gene deletion mutant and compensation strain. The deletion mutant strain was constructed through a suicide plasmid-mediated homologous recombination. The compensation plasmid constructed by cloning the coding sequence of spvD by PCR into plasmid pBAD33 was mobilized into the deletion mutant by conjugation and the pBAD33 was introduced into wild strains and deleted mutant strains as control. The relative expression of spvD mRNA was detected by quantitative reverse transcription PCR. In order to analyze the virulence of spvD against Caco-2 cells, Caco-2 cells was cocultured with wild type Salmonella enteritidis carrying spvD gene, the deletion mutant strain and compensation strain respectively. The expression level of spvD mRNA and the the number of Salmonella enteritidis after Caco-2 cells intervention were compared between the three groups by LSD-t test, and the invasion rate was compared by χ2 test. Results: The expression level of spvD mRNA in wild type Salmonella enteritidis was set as unit "1", the deletion mutant strain was "0.00", and the compensation strain was "2.60" (LSD-twild, deleted=1.11, P=0.31; LSD-twild, compensation=-1.77, P=0.13; LSD-t deleted, compensation=-2.88, P=0.03), which confirmed the successful construction of the deletion mutant strain and the compensation strain. The invasion experiment results of the above three Salmonella enteritidis strains on Caco-2 cells showed that the invasion rate of wild strain was 0.23%, the invasion rate of deleted mutant strain was 0.16%, and the invasion rate of compensation strain was 0.16%, with no statistical significance (χ2=1.13, P=0.570). By comparing the number of Salmonella enteritidis at different time points after Caco-2 cells intervention, it was discovered that the number of Salmonella enteritidis in wild strains (6.50×106 CFU/ml) and compensation strains (7.25×106 CFU/ml) was significantly increased than that in deletion mutant strain (1.90×106 CFU/ml) after 16 h coculture (LSD-twild, deleted=7.95, P=0.00; LSD-twild, compensation=-1.27, P=0.25; LSD-t deleted, compensation=-9.22, P=0.00). Conclusion: It is not considered that spvD gene can affect the invasion of Salmonella enteritidis on Caco-2 cells, but the gene can promote the reproduction of Salmonella enteritidis in Caco-2 cells.
Subject(s)
Caco-2 Cells , Gene Deletion , Humans , Lysergic Acid Diethylamide , RNA, Messenger/genetics , Salmonella enteritidis/geneticsABSTRACT
Genetic code expansion (GCE) allows the incorporation of unnatural amino acids into proteins via using stop codons. GCE may achieve site-specific labeling of proteins in combination with the click reaction. Compared with other labeling tools such as fluorescent proteins and tagged antibodies, the compound molecules used in protein labeling by GCE technology are smaller, and therefore, may less interfere the conformational structure of proteins. In addition, through click reaction, GCE allows a 1:1 stoichiometric ratio of the target protein molecule and the fluorescent dye, and the protein can be quantified based on the fluorescence intensity. Thus, GCE technology has great advantages in the researches that require the exposition of living cells under high laser power for longer time, for example, in the context of single molecule tracing and super-resolution microscopic imaging. Meanwhile, this technology lays the foundation for improving the accuracy of positioning and molecule counting in the imaging process of living cells. This review summarized the GCE technology and its recent applications in functionally characterizing, labeling and imaging of proteins.
Subject(s)
Amino Acids/chemistry , Fluorescent Dyes/chemistry , Genetic Code , Proteins/chemistryABSTRACT
@#Objective To explore the specialty system of special physical education at master's level.Methods Professional competency for special physical education was developed using the World Health Organization Rehabilitation Competency Framework (RCF), and was applied to the exploration of theoretical structure and methodological system for the construction of special physical education program at master's level.Results Based on the RCF, a competency framework for special physical education teachers was constructed, involving in five areas: practice, professionalism, learning and development, management and leadership, and research. The proficiency of competencies and activities should attain the corresponding level. The construction of special physical education program should be built to highlight the characteristics of RCF and focus on the training of competency in four areas: education objectives, instructional methods, the curriculum of the program and instructional assessment.Conclusion A competency-based program at the master's level in special physical education has been constructed using the RCF. The program uses the RCF to specify professional competency standards for special physical education teachers, and this can be transformed into the content of the competency-based program for special physical education at the master's level. The RCF is used to construct a competency-based special physical education system, which can be used to specify the educational objectives, instructional modalities, specialized core curriculum, and content and methods of instructional assessment in the design of a special physical education program at the master's level.
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Kidney transplantation can improve the quality of life of end-stage renal disease patients and is the most effective treatment.But renal transplantation is also a high risk factor for bladder cancer.Bladder cancer is a common malignant tumor in department of urology.Bacillus Calmette-Guerin intravesical instillation is a first-line therapy for high-risk non muscle invasive bladder cancer, which can directly kill bladder cancer cells.We reviewed the mechanism and clinical application of BCG in the treatment of bladder cancer after renal transplantation, in order to provide references for better utilization of Bacillus Calmette-Guerin in adjuvant treatment of bladder cancer after renal transplantation.