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Objective:To evaluate the predictive values of the Status Epilepticus in Pediatric Patients Severity Score (STEPSS) and END-IT score in the short-term prognosis of children with status epilepticus (SE).Methods:It was a retrospective study involving 103 children with SE who were admitted to the Qingdao Women and Children′s Hospital Affiliated to Qingdao University from January 1, 2012 to January 1, 2022.Glasgow Outcome Scale was used to evaluate the prognosis at discharge, and the children were divided into good prognosis group ( n=78) and poor prognosis group ( n=25). Risk factors for poor prognosis of SE in children were analyzed by Logistic regression.Receiver operating characteristic (ROC) curve was used to evaluate the prognostic values of STEPSS and END-IT score in children with SE. Results:Compared with those of the good prognosis group, significantly younger age [16 (9, 58) months vs.56 (21, 84) months, Z=-3.068, P=0.002], higher blood lactic acid levels [3.16 (2.43, 4.01) mmol/L vs.1.67 (1.32, 2.10) mmol/L, Z=-6.085, P<0.001], STEPSS scores [3.0(3.0, 4.0) points vs.1.0(1.0, 2.0) points, Z=-6.956, P<0.001], END-IT scores [3.0(1.5, 4.0) points vs.1.0(0, 1.0) points, Z=-5.502, P<0.001], proportion of developmental delay ( χ2=16.756, P<0.001), abnormal brain magnetic resonance imagine examination ( χ2=5.860, P=0.015), use of ventilator and multiple drugs (all P<0.001), and longer duration of anti-SE therapy time( Z=1.488, P=0.024) were detected in the poor prognosis group. Logistic regression analysis indicated that increased blood lactic acid ( OR=7.975, 95% CI: 2.705-23.518), increased drug types ( OR=14.562, 95% CI: 2.035-104.173), STEPSS scores( OR=8.914, 95% CI: 2.824-28.140) and END-IT scores ( OR=2.209, 95% CI: 1.046-4.667) were risk factors for the poor prognosis of SE in children.The area under the curve (AUC) of STEPSS in predicting the poor prognosis of SE in children was 0.939, with the cut-off value, sensitivity, specificity and Youden index of 2.5 points, 96.0%, 85.9% and 0.82, respectively.AUC of END-IT scores in predicting the poor prognosis of SE in children was 0.853, with the cut-off value, sensitivity, specificity and Youden index of 1.5 points, 76.0%, 75.6% and 0.52, respectively.AUC of STEPSS in predicting the poor prognosis of SE in children was significantly higher than that of END-IT scores ( U=36.91, P<0.05). The predictive value of STEPSS combined with END-IT was higher, and the sensitivity and negative predictive value of parallel test were 100.0%, while the specificity and positive predictive value of series test were 94.9% and 81.8%, respectively. Conclusions:STEPSS and END-IT scores may be used as predictors for the poor prognosis of SE in children.Their combination provides a better prediction.
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Efforts have been made to establish various human pluripotent stem cell lines. However, such methods have not yet been duplicated in non-human primate cells. Here, we introduce a multiplexed single-cell sequencing technique to profile the molecular features of monkey pluripotent stem cells in published culture conditions. The results demonstrate suboptimized maintenance of pluripotency and show that the selected signaling pathways for resetting human stem cells can also be interpreted for establishing monkey cell lines. Overall, this work legitimates the translation of novel human cell line culture conditions to monkey cells and provides guidance for exploring chemical cocktails for monkey stem cell line derivation.
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Animals , Haplorhini , Single-Cell Gene Expression Analysis , Pluripotent Stem Cells/metabolism , Cell Line , Signal Transduction , Cell Differentiation , TranscriptomeABSTRACT
Parkinson′s disease (PD) is a widely heterogeneous disorder with a broad list of motor and nonmotor manifestations. PD varies in clinical features, dominant symptoms, and rate of progression from case to case, suggesting the existence of distinct subtypes. Research on PD subtypes aims to understand this heterogeneity. This review summarized the commonly used PD subtyping solutions and discussed the challenges and future perspectives of subtyping. In future study, by designing a more standardized research and comparing the differences of these subtypes in terms of a number of putative biomarkers, that might help to better understand the underlying disease mechanisms, predict prognosis, and eventually design more efficient personalized management strategies.
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Objective:To investigate the prognosis value of the Child-Turcotte-Pugh (CTP), pediatrics end-stage liver disease/model for end-stage liver disease(PELD/MELD) and sequential organ failure assessment (SOFA) scores in pediatric acute liver failure (PALF) at 28 th day. Methods:Fifty-four PALF patients admitted in the Pediatric Intensive Care Unit (PICU) and Infection Department of Pediatrics, Qingdao Women′s and Children′s Hospital from June 1, 2012 to June 1, 2019 were included in the study.According to the survival of PALF patients on the 28 th day, they were divided into the survival group (28 cases) and the death group (26 cases). Baseline characte-ristics and laboratory examination data of PALF patients in both groups were collected and compared.Receiver operating characteristic (ROC) curve was used to evaluate the prognostic value of CTP, PELD/MELD and SOFA scores in PALF. Results:The mortality rate of 54 PALF patients was 48.1%.Compared with the survival group, PALF patients in the death group were significantly younger than those in survival group [11.0(3.8-39.0) months vs.14.5(7.3-84.0) months]( Z=-2.145, P=0.020). In addition, CTP, PELD/MELD and SOFA scores were significantly higher in the death group than those in survival group [14.0(11.7-15.0) vs.9.0(7.0-10.0), 32.0(29.0-36.0) vs.25.0(22.0-26.0), 13.0(11.0-16.0) vs.6.0(4.0-7.0)]( Z=-5.095, -4.894, -5.502, all P<0.05). Serum lactate level, blood ammonia level, total bilirubin, direct bilirubin and international normalized ratio were significantly higher in the death group than those in survival group [3.4(2.1-5.3) mmol/L vs.1.5(0.8-2.3) mmol/L, 69.5(46.9-102.9) μmol/L vs.41.7(27.3-50.3) μmol/L, 173.0(97.0-237.2) μmol/L vs.71.9(62.0-136.9) μmol/L, 132.3(53.6-206.2)μmol/L vs.59.3(62.0-99.7) μmol/L, 2.6(1.8-3.5) vs.1.7(1.5-1.9)]( Z=-4.027, -3.220, -2.649, -2.648, -3.807, all P<0.05). Prothrombin time (PT) was significantly prolonged in the death group than that of survival group [27.5(19.2-41.9)s vs.17.8(16.9-22.2)s]( Z=-3.489, P<0.05). Compared with those of survival group, serum albumin, alanine transaminase (ALT) and alpha fetoprotein (AFP) levels were significantly lower in the death group [(30.9±1.0) g/L vs.(33.6±0.9) g/L, 379.2(163.3-880.3) U/L vs.962.5(457.0-1 657.3) U/L, 7.5(0.7-115.8) μg/L vs.22.1(7.9-91.3) μg/L]( t=2.049, Z=-2.510, -2.342, respectively, all P<0.05). The incidence of alimentary tract hemorrhage was significantly higher in the death group than that of survival group (22/26 cases vs.11/28 cases)( χ2=13.340, P<0.05). The cut-off value of CTP, PELD/MELD and SOFA scores in predicting the prognosis of PALF were 11.5, 28.5 and 10.0, respectively.Among the three scoring systems, the specificity and positive predictive value of SOFA scores remained the highest.The sensitivity and specific of a combination of three scoring systems in predicting the prognosis of PALF were 92.3% and 89.3%, respectively, and its Youden index was the highest than that of a single scoring of either CTP, PELD/MELD or SOFA ( Z=2.19, P<0.05). Conclusions:CTP, PELD/MELD and SOFA scores have high predictive value for the short-term prognosis of PALF.The combined detection of the three scoring systems can improve the forecasting efficiency of PALD.
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OBJECTIVE@#To investigate the effects of restrictive fluid management in patients with severe traumatic brain injury (sTBI).@*METHODS@#Between January, 2019 and June, 2020, we randomly assigned 51 postoperative patients (stay in the ICU of no less than 7 days) with sTBI into treatment group (@*RESULTS@#The cumulative fluid balance of the two groups were positive on day 1 and negative on days 3 and 7 after ICU admission; at the same time points, the patients in the treatment group had significantly greater negative fluid balance than those in the control group (@*CONCLUSIONS@#Restrictive fluid management can reduce cerebral edema and improve the prognosis but does not affect the 28-day mortality of patients with sTBI.
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Humans , Brain Injuries, Traumatic/therapy , Fluid Therapy , Prognosis , Respiration, Artificial , Treatment OutcomeABSTRACT
Objective To evaluate the effects of different solubilizing techniques on the in vitro dissolution and in vivo pharmacokinetics of Sirolimus (SRL). Methods Solid dispersions (SD), inclusion complex (IC), self-micro emulsifying drug delivery system (SMEDDS) and nano-structured lipid carrier (NLC) were selected as the solubilization technology for SRL. SRL-SMEDDS and SRL-NLC have obtained the optimal prescription in the previous studies. Additionally, the formulation process of SRL-SD and SRL-IC was screened by using inclusion rate and dissolution profiles as indicators. 0.4% SDS, water and buffer solutions with pH 1.2, 4.5, 6.8, 7.4 were used as dissolution media. The dissolution profile of the commercially available formulation Rapamune® and the lab-made solubilized preparations were investigated. The in vivo absorption of the above preparations was examined using a pharmacokinetic test in Beagle dogs. Results In 0.4% SDS, the dissolution of each preparation exceeded 80% in 2 h. In the medium of pH 1.2, the dissolution of SRL-SD could not be measured while the dissolution of IC, SMEDDS and NLC increased first and then decreased. In other media, the dissolution of the SRL was reduced. The SRL-IC showed the best dissolution without a significant decrease. The relative bioavailability of APIs, SRL-SD, SRL-IC, SRL-NLC and SRL-SMEDDS were 9.1%, 18.7%, 33.2%, 78.0%, and 97.6% respectively in vivo pharmacokinetic tests. Conclusion SD, SMEDDS, NLC, and IC can improve the in vitro dissolution and in vivo absorption of SRL. Among them, SMEDDS has the most significant improvement in the bioavailability of SRL.
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Objective To avoid the accumulation of copper sulfide (CuS) nanoparticles, prepare and optimize CuS nanoparticles, analyze the factors affecting the particle size and evaluate their photothermal properties. Methods Based on the single factor study, central composite design-response surface methodology was used to optimize the CuS nanoparticle formulation process. The morphology, particle size stability, photothermal conversion efficiency, photothermal stability of optimized CuS nanoparticles were characterized. The toxicity of CuS nanoparticles on 4T1 breast cancer cells and HK2 kidney cells was evaluated by CCK-8 method. In vitro photothermal experiment was used to investigate the ability of CuS nanoparticles on killing 4T1 breast cancer cells. Results The average hydration dynamic diameter of optimized CuS nanoparticles was (10.53±1.63)nm, the actual particle size of CuS nanoparticles showed by TEM image was (3.10±0.81)nm. It had good particle size stability, good photothermal conversion efficiency and photothermal stability. Within the concentration range of 100 μg/ml and 150 μg/ml，it showed no significant toxicity on 4T1 breast cancer cells and HK2 kidney cells, indicating the good stability of CuS nanoparticles. In vitro photothermal therapy showed that CuS nanoparticles had good ability to kill 4T1 breast cancer cells by photothermal. Conclusion The prepared CuS nanoparticles have a small particle size (less than 6nm) and a good photothermal effect, which is expected to solve the problem of CuS nanoparticles accumulation in vivo and make it better for tumor treatment.
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Objective To prepare, investigate and optimize the drug stability of compound adapalene ointment.Methods The ointment containing adapalene and mupirocin were prepared with PEG400and PEG3350as matrix.Stress test was usedto evaluate and optimize the stability of drugs in the ointment.The drug stability was further tested by the acceleration test and long-term test.Results The raw adapalene was stable under high temperature, high humidity and strong light irradiation.The raw mupirocin was stable under high humidity and strong light irradiation, but was highly unstable under high temperature condition.Degradation of adapalene and mupirocin was found with pH≤7.At pH 7.5, the best stability was achieved, with over95％of the drugs remaining at day 10.Favorable ointment was prepared with PEG400∶PEG3350=2∶1.The drug stability was promoted by addition of 0.2％triethanolamine significantly.In the acceleration test and long-term test, the percentages of adapalene and mupirocin were above 95％.Conclusion The compound adapalene ointment was successfully prepared and the drug stability was excellent.
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Objective@#To characterize the gut microbial community structure of two-kidney-one-clip (2K1C) hypertensive rats, provide new evidences for prevention and treatment of hypertension.@*Methods@#Adult male SD rats were divided into 2K1C hypertensive model group and sham operation group (n=8 each). Blood pressure was recorded by tail-cuff technique weekly for 4 weeks. Then, the total fecal DNA of rats in 2K1C model group and sham operation group were extracted. The structure and principal components of intestinal flora in 2K1C model rats and sham operated rats were analyzed using Hiseq3000 sequencing platform. Additionally, real time fluorescent quantitative polymerase chain reaction technology was used to detect the content of predominant bacteria, including Escherichia, Bifidobacterium, Lactobacillus and Bacteroides.@*Results@#Compared with sham operation group, significant reduction in the relative abundance of Firmicutes (31.72 (30.06, 32.18) vs. 40.99 (38.78, 44.41), U=0.00, P<0.05) and increase in Bacteroidetes (48.13(41.16,50.25) vs. 27.81(25.84,31.38),U=0.00, P<0.05) were observed in the fecal samples from model group. The relative abundance of Escherichia coli (0.08(0.07,0.11) vs. 0.07(0.06,0.08),U=12.50, P<0.05) was increased and the short chain fatty acid producing strains such as Coprococcus, Roseburia, Blautia, Clostridium and Bacteroides was reduced in 2K1C model group than in sham operation group (all P<0.05). Moreover, the relative abundance of Prevotella (Bacteroidetes) was also significantly higher in 2K1C model group than in sham operation group (18.14(17.78,18.75) vs.1.83(1.50,5.19), U=0.00, P<0.05). Moreover, the relative abundance of Ruminococcus (Firmicutes) was significant higher in 2K1C model group than in sham operation group (7.73(6.04,9.34) vs. 3.68(2.46,4.67),U=0.00, P<0.05). Principal coordinate analysis showed that there was significant difference in the gut microbial community structure between 2K1C model group and sham operation group.@*Conclusion@#There are significant changes in the gut microbial community structure in 2K1C model group as compared to sham operation group, indicating renovascular hypertension might affect gut microbial community structure in this rat model.
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Objective:In oder to investigate the effect of Chuanmingshen violaceum polysaccharides ( CVP) and Solfated Chua-nmingshen violaceum polysaccharides ( SCVP) on immunosuppression induced by cyclophosphamide ( CY) in mice.Methods: CY were used to induce immunosuppression in mice;Spleen and thymus indexes were used to evaluate the immune organs indexes;the [3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltet-razolium bromide,MTT] method was used to detect the proliferation of spleen lymphocytes of each group;the concentrations of IFN-γand IL-2 were assayed by ELISA kit.Results: SCVP and CVP could resist immunosuppression by promoting lymphocyte proliferation, increasing the contents of IFN-γ and IL-2, promoting immune organs development in immunosuppressive mice induced by CY.Conclusion:SCVP and CVP exhibited the potential to used as immunopotentiator.
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Objective:To establish the determination methods for 5-HMF during the processing of polygonatums by HPLC and GC-MS. Methods:The contents of 5-HMF during the processing of three species of polygonatum were determined by HPLC and GC-MS, and the correlation curve of the processing time and the contents was established to study the change regularity of 5-HMF during the processing. Results:The contents of 5-HMF in the three species of polygonatum processed by steamed and stewed methods reached the peak value in 16h or so. The 5-HMF contents in the three species of polygonatum showed significant difference in the order of Polygo-natum cyrtonema Hua>Polygonatum kingianum Coll. et Hemsl. >Polygonatum. sibiricum Red. After the processing, the content of 5-HMF was increased, and the increase in stewed method was more notable than that in steamed method. Conclusion: The study pro-vides theoretical basis for the further study on the processing of polygonatum.
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Objective To establish a high purity primary culture methods of human nasal epithelial cells (HNEC) in vitro and to provide a successful primary culture model for evaluation experiments of the nasal preparation .Methods Primary culture of human nasal epithelial cells were performed with enzymatic dissociation of isolated tissue and cultured in serum-free medium .HNEC were separated through magnetic field by immunomagnetic beads .We determined the purity of the separated cells by light microscopy and flow cytometry .The morphology of HNEC was observed with a scanning electron microscope .Results Under an inverted phase microscope ,the cells morphology was paving stone shaped .Under the scanning electron microscopy ,abundant microvilli and cilia differentiation were observed .Flow cytometry showed the epithelial cells accounted for 99% .Conclusion The highly purified HNEC can be directly isolated by the magnetic cell sorting system .The cell model can be used for the basic research of nasal cavity preparation .
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<p><b>OBJECTIVE</b>To investigate the mechanism of iridoid from Valeriana jatamansi treating irritable bowel syndrome.</p><p><b>METHOD</b>Sixty male SD rats were equally divided into 6 groups (2 controls, 1 model and 3 treatment doses) with 10 rats per group. The test groups were administered with iridoid (24.92, 12.46, 6. 23 mg x kg(-1)) while the control groups were administered with fluoxetine (2.5 mg x kg(-1), positive control) or distilled water (negative control). The model was established by chronic stress and independent feeding. The influence of iridoid from V. jatamansi on 5-HT and 5-HIAA in colon, serum and hypothalamic were observed in all groups.</p><p><b>RESULT</b>In the model group, the content of 5-HT in colon and serum increased significantly, but the content of 5-HT in hypothalamic decreased significantly. The content of 5-HIAA and the value of 5-HT/5-HIAA had no significant change. In three iridoid-treated groups, the content of 5-HT in colon and serum decreased, but the content of 5-HT in hypothalamic increased. The content of 5-HIAA had no significant change. The value of 5-HT/5-HIAA in colon and serum reduced.</p><p><b>CONCLUSION</b>The mechanism of iridoid from V. jatamansi treating irritable bowel syndrome may be related to the regulation effect to the levels of 5-HT from Gastrointestinal to central nervous system.</p>
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Animals , Male , Rats , Chromatography, High Pressure Liquid , Colon , Metabolism , Hydroxyindoleacetic Acid , Blood , Metabolism , Hypothalamus , Metabolism , Iridoids , Therapeutic Uses , Irritable Bowel Syndrome , Blood , Drug Therapy , Metabolism , Rats, Sprague-Dawley , Serotonin , Blood , Metabolism , Valerian , ChemistryABSTRACT
Thiols, which are components of many proteins and simple molecules, play an important role in the cellular antioxidant defense system. The quantitative determination of thiols is important in biochemistry and clinical chemistry. Fluorescent probes, which have its apparent advantages in sensitivity and, most importantly, in imaging thiols in vivo, even in single living cells, appear to be particularly attractive. In this review, we classify the fluorescent probes based on their different reaction mechanisms with thiols and summarize the recent progresses of thiols fluorescent probes with fifty-one