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Programmed cell death protein 1 (PD-1) is an immune checkpoint modulator and a major target of immunotherapy as anti-PD-1 monoclonal antibodies have demonstrated remarkable efficacy in cancer treatment. Accumulating evidence suggests an important role of PD-1 in the central nervous system (CNS). PD-1 has been implicated in CNS disorders such as brain tumors, Alzheimer’s disease, ischemic stroke, spinal cord injury, multiple sclerosis, cognitive function, and pain. PD-1 signaling suppresses the CNS immune response via resident microglia and infiltrating peripheral immune cells. Notably, PD-1 is also widely expressed in neurons and suppresses neuronal activity via downstream Src homology 2 domain-containing protein tyrosine phosphatase 1 and modulation of ion channel function. An improved understanding of PD-1 signaling in the cross-talk between glial cells, neurons, and peripheral immune cells in the CNS will shed light on immunomodulation, neuromodulation, and novel strategies for treating brain diseases.
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【Objective】 To develop an assay to determine β-lactam antibiotics using microcolumn gels and to study the β-lactam antibiotics present in the blood of patients and their clinical significances. 【Methods】 446 patients with a history of taking β-lactam antibiotics from January 2019 to June 2019 were randomly selected from Trauma Emergency Center, Department of Arthrosis, Department of Spine and Department of Bone Oncology of our hospital, and 4 mL(per capita) venous blood was collected. Irregular antibody screening, anti-globulin detection and drug antibody determination were performed by microcolumn gel method. The data of gender, age, disease, blood transfusion history and medication were collected. The test results and clinical data were retrospective analyzed. 【Results】 The yielding rate of antibody was 0.45%(2/446) in patients with a history of taking β -lactam antibiotics. 16.38%(73/446) of the samples were positive in direct antiglobulin test, and 64.38%(47/73) of them did not agglutinate with RBCs treated with drugs. The yielding rate of specific antibodies against drug was 4.93%(22/446), and the titer ranged from 2 to 128(8). 1 case of auto-IgM antibody, 1 case of blood group related antibody and 2 cases of non-specific protein adsorption were detected. The yielding rate of drug antibody in patients with blood transfusion history reached to 12.10 %(22/124), so it was also high in patients with bone tumor. 【Conclusion】 Direct antiglobulin assay is helpful for the detection of β-lactam antibodies. The negative results of antibody screening cannot completely exclude the presence of drug antibodies. The yielding rate of drug antibody can be greatly improved by specific drug antibody detection, and it was higher in transfused patients relative to non-transfused one.
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BACKGROUND@#In previous studies, we succeeded in repairing a long bone defect with tissue-engineered periosteum (TEP), fabricated by incorporating rabbit mesenchymal stem cells with small intestinal submucosa. In this study, we investigated the feasibility of allogeneic irregular bone defect repair using TEP. @*METHODS@#We performed a subtotal resection of the scapula in 36 rabbits to establish a large irregular bone defect model. The rabbits were then randomly divided into three groups (n = 12 per group) and the defects were treated with TEP (Group 1), allogeneic deproteinized bone (DPB) (Group 2) or a hybrid of TEP and DPB (Group 3). At 4, 8, and 12 weeks after surgery, the rabbits were sacrificed, and the implants were harvested. X-ray radiographic and histological examinations were performed to detect bone healing. Ink-formaldehyde perfusion was introduced to qualitatively analyze vascularization in TEP engineered new bone. @*RESULTS@#The repair of scapular defects was diverse in all groups, shown by radiographic and histological tests. The radiographic scores in Group 1 and Group 3 were significantly higher than Group 2 at 8 and 12 weeks (p < 0.05).Histological scores further proved that Group 1 had significantly greater new bone formation compared to Group 3 (p < 0.05), while Group 2 had the lowest osteogenesis at all time-points (p < 0.001). Ink-formaldehyde perfusion revealed aboundant microvessels in TEP engineered new bone. @*CONCLUSION@#We conclude that TEP is promising for the repair of large irregular bone defects. As a 3D scaffold, DPB could provide mechanical support and a shaping guide when combined with TEP. TEP engineered new bone has aboundant microvessels.
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BACKGROUND@#In previous studies, we succeeded in repairing a long bone defect with tissue-engineered periosteum (TEP), fabricated by incorporating rabbit mesenchymal stem cells with small intestinal submucosa. In this study, we investigated the feasibility of allogeneic irregular bone defect repair using TEP. @*METHODS@#We performed a subtotal resection of the scapula in 36 rabbits to establish a large irregular bone defect model. The rabbits were then randomly divided into three groups (n = 12 per group) and the defects were treated with TEP (Group 1), allogeneic deproteinized bone (DPB) (Group 2) or a hybrid of TEP and DPB (Group 3). At 4, 8, and 12 weeks after surgery, the rabbits were sacrificed, and the implants were harvested. X-ray radiographic and histological examinations were performed to detect bone healing. Ink-formaldehyde perfusion was introduced to qualitatively analyze vascularization in TEP engineered new bone. @*RESULTS@#The repair of scapular defects was diverse in all groups, shown by radiographic and histological tests. The radiographic scores in Group 1 and Group 3 were significantly higher than Group 2 at 8 and 12 weeks (p < 0.05).Histological scores further proved that Group 1 had significantly greater new bone formation compared to Group 3 (p < 0.05), while Group 2 had the lowest osteogenesis at all time-points (p < 0.001). Ink-formaldehyde perfusion revealed aboundant microvessels in TEP engineered new bone. @*CONCLUSION@#We conclude that TEP is promising for the repair of large irregular bone defects. As a 3D scaffold, DPB could provide mechanical support and a shaping guide when combined with TEP. TEP engineered new bone has aboundant microvessels.
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OBJECTIVE@#To explore the genetic basis for a pedigree affected with Charcot-Marie-Tooth (CMT) disease through high-throughput sequencing.@*METHODS@#Potential variants of the genes associated with CMT were screened by next-generation sequencing (NGS) of the members of the pedigree.@*RESULTS@#NGS has revealed that the two affected sisters both harbored homozygous c.1A>G variant of the GDAP1 gene, which caused replacement of the first amino acid Methionine by Valine (p.Met1Val). Their parents were both carriers of the heterozygous c.1A>G variant. The variant was unreported previously and has an extremely low frequency in the population. Meanwhile, one of the sisters and the mother also carried heterozygous c.710A>T variant of the BAG3 gene.@*CONCLUSION@#The homozygous c.1A>G variant of the GDAP1 gene probably underlay the CMT in both children. Above result has enabled clinical diagnosis and genetic counseling for this pedigree.
Subject(s)
Child , Female , Humans , Adaptor Proteins, Signal Transducing/genetics , Apoptosis Regulatory Proteins/genetics , Charcot-Marie-Tooth Disease/genetics , Fibula/abnormalities , Homozygote , Mutation , Nerve Tissue Proteins/genetics , PedigreeABSTRACT
Objective To analyze the role of telehealth?based dialysis registration systems in real?time and dynamic reflection of renal anemia in hemodialysis (HD) patients, and discuss the prospect of its application in dialysis registration management. Methods The Red China project was to build up a dialysis registration system based on the WeChat mobile terminal platform. Demographic and baseline laboratory parameters such as age, gender, primary disease, dialysis age, creatinine were recorded in this system. Hemoglobin (Hb) level was monthly recorded. The platform generated Hb statistics report for each HD center monthly, including the detection rate, target rate and the distribution level of Hb, and released it to physicians through the WeChat terminal of mobile phone. After that, physicians could change the treatment of anemia individually on basis of this report. Here the demographic and baseline laboratory parameters, the detection rate, target rate, the average level and the distribution of Hb from June 2015 to October 2017 after the project launched were analyzed. Results From June 2015 to October 2017, 8392 maintenance HD patients from 28 HD centers in Shanghai were enrolled, of whom 5059(60.3％) were male.The average rate age was (60.5 ± 13.7) years old. Baseline average Hb was (108.3±16.0) g/L. Baseline detection rate and target rate were 54.2％and 47.5％, respectively. After 28 months follow?up, the detection rate of Hb increased from 54.2％ to 73.6％ (P<0.001), the target rate of Hb increased from 47.5％ to 56.1％ (P<0.001), and the level of average Hb rose from (108.3±16.0) g/L to (110.7±16.0) g/L. The difference between average Hb in two consecutive months was less than 1.3 g/L. Conclusions The telehealth?based dialysis registration system can timely report the anemia situation of HD patients, which may improve the awareness rate of anemia, the degree of attention and the compliance of anemia monitoring, so as to improve the detection rate and target rate of Hb and reduce the fluctuation of Hb, which helps to maintain the HD patients to correct anemia in a timely, stable and long?term way. The telehealth?based dialysis registration system, as an improved mode of dialysis registration is a promising way for long?term management of renal anemia in dialysis patients.
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Objective: To analyze the electrocardiographic (ECG) characteristics for the ifrst diagonal branch of infarction related artery (IRA) in patients with acute ST-segment elevation myocardial infarction (STEMI) in order to ifnd the rule for physician to make quick diagnosis. Methods: A total of 28 STEMI patients with coronary angiography (CAG) confirmed first diagonal branch of IRA were retrospectively analyzed. The patients were treated in our hospital from 2005-01 to 2014-06 and their ECG changes at admission were studied for ST-segment elevation/depression and q wave, Q wave changes during the period of evolution at different leads in all patients. Results: CAG presented that there were 19/28 (67.9%) patients with single vessel disease, 13 (46.4%) with isolated diagonal lesion. From onset of chest pain to AMI graph shown on ECG was about 240 (252 ± 71) min in all patients. All 28 (100%) patients were with ST-segment elevation in lead aVL, 27 (96.4%) in lead I, and 15 (55.6%) patients with ST-segment elevation by (0.5-1.0) mm. The incidence of ST-segment elevation in the chest lead was, in turn as 21 (75.0%) patients in lead V2, 16 (57.1%) in lead V3 and 12 (42.9%) in lead V1respectively; while ST-segment depression was as 28 (100%) patients in lead III, 27 (96.4%) in lead aVF and 22 (78.6%) in lead II respectively. During the period of evolution, the most q wave or Q wave formation were, in turn as 22 (88.0%) patients in lead aVL, 10 (40.0%) in lead V2, 9 (36.0%) in lead V3 and 7 (28.0%) in lead I respectively. Conclusion: The ECG changes in STEMI patients with diagonal branch of IRA have the high prevalence of ST-segment elevation in lead aVL and lead I, while there is an important feature that the ST-segment elevation < 1 mm in about half amount of relevant patients.
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Objective To investigate the effect of hyperbaric oxygen treatment on course of different intervention time,cognitive impairment in patients with traumatic brain injury.Methods Ninety cases of cognitive dysfunction in patients with traumatic brain injury after hyperbaric oxygen in different intervention time were divided into group A,group B and group C,with 30 cases in each group.In 7-14 d,15-28 d,＞ 28 d after injury starting hyperbaric oxygen therapy,treatment 1 time a day,12 times for a course.The cognitive function of patients in three groups before and after 1,2,3 courses of treatment was evaluated by U.S.RLA cognition level classification standard evaluation form.Results Three groups after 1 course of treatment there was no statistically significant difference compared with before treatment RLA grading (P ＞ 0.05).Three groups after 2,3 courses of treatment compared with after 1 course of treatment RLA grading difference was statistically significant (P ＜ 0.05),three groups after 3 courses of treatment compared with after 2 courses of treatment RLA grading difference was statistically significant (P ＜ 0.05).Three groups after 1 course of treatment total effectiveness rate was no statistically significant difference(P ＞ 0.05).Group A and group B after 2,3 courses of treatment total effective rate was significantly higher than that in group C [73.33％ (22/30) and 66.67％ (20/30) vs.46.67 ％(14/30),93.33％ (28/30) and 86.67 ％(26/30) vs.60.00 ％ (18/30),P ＜ 0.05],group A was higher than group B,but there was no statistical significance (P ＞ 0.05).Conclusions Hyperbaric oxygen comprehensive therapy can effectively improve cognitive function in patients with traumatic brain injury cognitive impairment.After the injury,the earlier to start the hyperbaric oxygen therapy,the better effect it has,and the longer the course the better curative effect it has.
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Objective To assess the human β-defensin-2 ( hBD2 ) gene therapeutic efficacy in a rat urinary tract infection (UTI) model via intravesical liposome-mediated gene transfer.Methods Fifty-six female Wistar rats (class SPF) weighting 1 80 -220 were randomly divided into an experiment group and a control group ( each n =28 ).The animals were administered either 250 μl recombinant pCAGG-hBD2 or control vector pCAGG intravesically.After 48 h,rats in both groups were infected via intravesical inoculation with 200 μl of the bacterial suspension of UTI89 ( 1 × 108 CFU/ml).The rats were sacrificed at 4,24,48,and 72 h post-inoculation.The bladders were aseptically removed and bisected.One half was fixed in neutral buffered formalin for histological analysis.The remaining half-bladders were homogenized and titered for surviving bacteria.The clean-catch urine sample from each rat was collected in sterile before they were killed for bacterial titers determined and WBC counted.Results Numbers of bacterial colony-forming unit in urine and bladders from hBD2 gene treated UTI rats were significantly lower than those from the control vector administered UTI rats at 24,36,and 72 h after infection ( P ＜ 0.05 ).The amount of WBC in urine was significantly less in the defensin group than in the control group.In addition,in vivo expression of hBD2 could reduce mucosa damage,interstitium edema and inflammatory cells infiltration in UTI animals.Conclusions The successful inhibition of UTI progression could be obtained with hBD2 gene therapy.Recombinant beta-defensin-2 could kill UTI89 in vivo and suppress the subsequent infection-induced inflammatory responses.
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Objective To investigate the early comprehensive intervention on neonatal hypoxic ischemic encephalopathy (HIE) effects and the biological mechanisms.Methods 120 cases of HIE were randomly divided into intervention group and control group.Under the basis of drug treatment,the intervention group were given the different perceptual stimuli,audiovisual stimulation,active and passive limb training early comprehensive intervention,the control group only to normal drug treatment.The mental development index(MDI) and psychomotor develo pmental index (PDI) were applied after 3,6,12,and 18 months.S100B protein levels were detected using enzyme immunoassay.Results MDI score in the intervention group with HIE,from the beginning of the 12 month,was higher than that in the control group,there was significant differences (12th month:(96.6±9.4)vs (86.8±9.5),P0.05).From the beginning of the 3rd month,serum S100B protein levels in the intervention group were reduced significandy,compared with the control group at each time point level(3rd month:(1.29±0.15)ng/L vs(1.40±0.14)ns/L;6th month:(1.06±0.21)ng/L vs(1.26±0.22)ng/L,P<0.01).Conclusion Early intervention can improve the mental and motor development of children with HIE,and serum S100B protein is involved in the mechanisms.
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Objective To investigate characteristics of glucose metabolism of non-obese and obese women with polycystic ovary syndrome (PCOS). Methods From May 2006 to April 2009, 1928 PCOS patients treated in Reproductive Medicine Center of Shandong Provincial Hospital Affiliated to Shandong University were enrolled in this study, which were divided into 901 cases [body mass index (BMI) ≥25 kg/m2] in obese group and 1027 cases in non-obese (BMI < 25 kg/m2) group. The prevalence of type 2 diabetes mellitus (T2DM), oral glucose tolerance test, impaired fasting glucose (IFG), impaired glucose tolerance(IGT) were compared between the two groups. Results (1) Blood glucose levels: at the time of fasting, 30, 60, 120 and 180 minutes, the levels of glucose were (5. 3±1.1), (9. 0±2. 4), (9. 3±4. 4),(7.5±2.8) ,(5.3±1.8)mmol/L in obese group and (5.0±0. 8) ,(8.4±3.5),(8.0±4.2),(6.5±3.2) ,(4. 9±1.6) mmol/L in non-obese group, which all showed statistical difference at every time point (P < 0. 01). (2)The level of insulin: at the time of fasting, 30, 60, 120 min, the level of insulin were (13±7), (81±51), (102±65), (83±63) mU/L in obese group and (8±5) ,(57±35) ,(62±44),(46±39) mU/L in non-obese group, which all showed statistical differenceatevery time point (P <0. 01). However, at time point of 180 minutes, the level of insulin did not exhibit significantly difference between obese and non-obese group (P > 0. 05). (3) The prevalence of abnormal glucose metabolism: the rate of IFG was 4. 98% (96/1928). The rate of abnormal glucose tolerance was 23. 08% (445/1928). The rate of IGT were 13.05% (134/1027) in non-obese group and 24. 20% (218/901) in obese group,which also showed remarkable difference (P < 0. 01). The rate of T2DM were 2. 53% (26/1027) in nonobese group and 7.44% (67/901) in obese group, which reached significant difference (P < 0. 01).Conclusion Abnormal glucose metabolism was observed more frequently in overweight or obese PCOS women.
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Objective To investigate the in vitro anti-candidal activity of the essential oil of Illicium verum (EOIV) alone and in combination with fluconazole. Methods The minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) of EOIV were determined in 130 clinically isolated Candida strains by NCCLS-M27-A microdilution method, and fluconazole was used as positive control. Meanwhile the checkerboard microdilution method was applied to assay the combined effect of EOIV and fluconazole in 18 candidal strains. Results For the 18 candidal strains the MICs and the MFCs of EOIV were 1 517.16 ?g/mL and 2 248.55 ?g/mL for C. albicans, 1 169.24 ?g/mL and 2 338.49 ?g/mL for C. glabrata, 1 320.03 ?g/mL and 1 741.79 ?g/mL for C. parapsilosis, 1 203.50 ?g/mL and 2 407.01 ?g/mL for C. tropicalis, 1 516.32 ?g/mL and 2 144.40 ?g/mL for C. krusei, and 1 072.64 ?g/mL and 2 144.40 ?g/mL for C. guilliermondii, respectively. Significant synergistic and additive effects were observed after the combination of EOIV with fluconazole, and no antagonism was found. There was no significant difference in the mean fractional inhibitory concentration index (FICI) between the fluconazole-susceptible and the fluconazole-resistant candidal strains (P = 0.671). Conclusion EOIV has antifungal effects on medically important Candida spp.. The combination of EOIV with fluconazole presents a synergistic and additive effects.
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Objective To investigate the changes of collagen types Ⅰ and Ⅲ, the effects of Oleum Curcumae Aromaticae oil injection on injuried rat arteries and collagen types Ⅰ and Ⅲ after balloon angioplasty Methods The left common carotid artery in rats was denuded with a balloon catheter The rats were killed 14 days after injury Cross sections stained with picrosirius red from the injuried segments were processed for distribution, arrangememt, amount, proportion of collagen type Ⅰ and type Ⅲ by polarizing microscope, and those stained with hematoxylin eosin for histological and morphological changes studied by computer assisted picture analysis system Results Fourteen days after balloon injury, collagen type Ⅰ and type Ⅲ of the model group were found mainly in adventitia, much more, thicker, brighter and more disordered than those of the sham operation group Compared with the model group, collagen type Ⅰ and type Ⅲ of the E Zhu You group were found mainly in adventitia, less, thinner, dimmer and more orderly Lumen area, EEL perimeter, IEL perimeter of the model group were decreased and the areas of collagen types Ⅰ and Ⅲ increased more significantly than those of the sham operation group Compared with the model group, maximal intimal thickness, neointima area, the areas of collagen type Ⅰ and Ⅲ of the E Zhu You group were decreased significantly which was not different from those of the sham operation group Lumen area, EEL perimeter and IEL perimeter were increased markedly up to those of the sham operation group The ratio of collagen subtypes Ⅰ/Ⅲ was not significantly different between the two of the three groups Conclusion The accumulation and derangement of collagen types Ⅰ and Ⅲ may be more important in restenosis than the ratio of collagen subtypes Ⅰ/Ⅲ We concluded that Oleum Curcumae Aromaticae oil injection inhibits neointimal formation and vascular remodeling after arterial injury by mechanisms involving collagen types Ⅰ and Ⅲ production and their arrangement
