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Drug adulteration and contamination are serious threats to human health therefore,their accurate monitoring is very important.Allopurinol(Alp)and theophylline(Thp)are commonly used drugs for the treatment of gout and bronchitis,while their isomers hypoxanthine(Hyt)and theobromine(Thm)have no effect and affect the efficacy of the drug.In this work,the drug isomers of Alp/Hyt and Thp/Thm are simply mixed with α-,β-,y-cyclodextrin(CD)and metal ions and separated using trapped ion mobility spectrometry-mass spectrometry(TIMS-MS).TIMS-MS results showed that Alp/Hyt and Thp/Thm iso-mers could interact with CD and metal ions and form corresponding binary or ternary complexes to achieve their TIMS separation.Different metal ions and CDs showed different separation effect for the isomers,among which Alp and Hyt could be successfully distinguished from the complexes of[Alp/Hyt+y-CD+Cu-H]+with separation resolution(Rp-p)of 1.51;whereas Thp and Thm could be baseline separated by[Thp/Thm+y-CD+Ca-H]+with Rp-p of 1.96.Besides,chemical calculations revealed that the complexes were in the inclusion forms,and microscopic interactions were somewhat different,making their mobility separation.Moreover,relative and absolute quantification was investigated with an internal standard to determine the precise isomers content,and good linearity(R2＞0.99)was ob-tained.Finally,the method was applied for the adulteration detection where different drugs and urine were analyzed.In addition,due to the advantages of fast speed,simple operation,high sensitivity,and no chromatographic separation required,the proposed method provides an effective strategy for the drug adulteration detection of isomers.
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Reperfusion therapy, including intravenous thrombolysis and endovascular therapy, is an effective treatment for acute ischemic stroke. As a common complication after reperfusion therapy, hemorrhagic transformation is closely associated with the poor outcomes of patients. Early evaluation of clinical features, imaging and blood biomarkers can predict the risk of hemorrhagic transformation, so as to better guide the reperfusion treatment in patients with acute ischemic stroke.
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Objective:To investigate the efficacy and safety of rivaroxaban combined with antiplatelet in ischemic stroke patients with non-valvular atrial fibrillation and moderate or severe intracranial artery stenosis.Methods:The consecutive ischemic stroke patients with non-valvular atrial fibrillation and moderate or severe intracranial artery stenosis admitted to Yantai Yuhuangding Hospital of Qingdao University from August 2019 to March 2022 were retrospectively included. According to the secondary prevention drugs, the patients were divided into rivaroxaban and rivaroxaban combined with antiplatelet treatment group. The basic characteristics of the two groups were compared. The primary outcome was the recurrence rate of stroke at 3 months, and the secondary outcome included the incidence of any bleeding event at 3 months, the all-cause mortality rate, the improvement rate of neurological function, and the good outcome rate. The good outcome was defined as the modified Rankin Scale ≤2 points at 3 months.Results:A total of 108 patients aged 70.72±8.08 years old were included in the study. There were 56 patients (51.9%) in the rivaroxaban group and 52 (48.1%) in the combined treatment group. In terms of primary outcome, the recurrence rate of stroke in the combined treatment group was significantly lower than that in the rivaroxaban group at 3 months (7.69% vs. 21.43%; P<0.05). In terms of secondary outcomes, the incidence of bleeding events in the combined treatment group at 3 months was significantly higher than that in the rivaroxaban group (26.92% vs. 7.14%; P<0.05), with one death event in each group. The rate of good outcome in the combined treatment group was significantly higher than that in the rivaroxaban group (75.00% vs. 51.79%; P=0.013). Multivariate logistic regression analysis showed that high National Institutes of Health Stroke Scale (NIHSS) score at admission was an independent risk factor for poor outcome (odds ratio 1.370, 95% confidence interval 1.057-1.776; P=0.018), while the rivaroxaban combined antiplatelet treatment was an independent protective factor for stroke recurrence (odds ratio 0.203, 95% confidence interval 0.054-0.758; P=0.018). Conclusion:After ischemic stroke in patients with non-valvular atrial fibrillation complicated with moderate and severe stenosis of intracranial artery, rivaroxaban combined with antiplatelet treatment can reduce the recurrence rate of stroke and improve the clinical outcome, but it may increase the risk of bleeding.
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Post-stroke aphasia (PSA) is an acquired language disorder, which can seriously affect daily communication and lead to long-term disability. Previous studies were mostly limited to the changes of brain morphology, and it was difficult to reveal the functional changes of brain tissue after aphasia. Resting-state functional magnetic resonance imaging (rs-fMRI) can observe the functional changes of brain regions and brain networks. This article reviews the literature on the use of rs-fMRI to explore the pathogenesis and recovery mechanism of aphasia and the changes of brain function before and after treatment, in order to provide valuable information on the neural remodeling mechanism of PSA and guide more accurate treatment.
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Chest trauma is one of the most common injuries. Venous thromboembolism (VTE) as a common complication of chest trauma seriously affects the quality of patients′ life and even leads to death. Although there are some consensus and guidelines on the prevention and treatment of VTE at home and abroad, the current literatures lack specificity considering the diagnosis, treatment and prevention of VTE in patients with chest trauma have their own characteristics, especially for those with blunt trauma. Accordingly, China Chest Injury Research Society and editorial board of Chinese Journal of Traumatology organized relevant domestic experts to jointly formulate the Chinese expert consensus on the diagnosis, treatment and prevention of chest trauma venous thromboembolism associated with chest trauma (2022 version). This consensus provides expert recommendations of different levels as academic guidance in terms of the characteristics, clinical manifestations, risk assessment, diagnosis, treatment, and prevention of chest trauma-related VTE, so as to offer a reference for clinical application.
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Asymmetrically prominent veins sign (APVS) displayed by susceptibility-weighted imaging (SWI) can noninvasively reflect the dynamic changes of brain tissue in patients with acute ischemic stroke (AIS). It provides blood flow and metabolic information from the perspective of pathophysiology, which is helpful to evaluate the clinical condition and outcome of patients with AIS. This article reviews the clinical significance of the presence of APVS on SWI in patients with AIS.
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Susceptibility-weighted imaging (SWI) is a high resolution, three-dimensional gradient echo T 2* sequence magnetic resonance technique. It uses the different susceptibilities between tissues to display the susceptibility image, which is extremely sensitive to paramagnetic substance such as deoxyhemoglobin and blood breakdown substances. In the acute stage of ischemic stroke, SWI can effectively evaluate the severity of the disease, guide the treatment plan, and predict the clinical outcome. This article reviews the research progress of SWI in the acute phase of ischemic stroke.
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Vascular recanalization is an important treatment method for acute ischemic stroke. Antiplatelet drugs combined with intravenous thrombolysis and endovascular therapy have become the research hotspots in recent years. Platelet glycoprotein Ⅱb/Ⅲa receptor antagonist is a new class of antiplatelet drugs that work by inhibiting the last common pathway in the platelet aggregation process. Its safety and effectiveness in the treatment of acute coronary syndrome have been proven, but its application in patients with acute ischemic stroke is still in the exploratory stage. This article reviews the application of tirofiban in the treatment of acute ischemic stroke reperfusion.
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[Abstraet] Alteplase intravenous thrombolysis is the most effective drug treatment for acute ischemic stroke at present.Hemorrhagic transformation after thrombolysis,especially symptomatic intracranial hemorrhage (sICH),will seriously affect the outcomes after intravenous thrombolysis,and even threaten the life of patients.Therefore,the prediction and treatment of sICH after intravenous thrombolysis is particularly important.This article reviews the prediction and treatment of sICH after intravenous thrombolysis.
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Objective To investigate the value of PET/CT imaging of cerebral glucose metabolism (CGM)and cerebral blood flow (CBF)in evaluating chronic disorders of consciousness (CDC).Methods A total of 10 CDC patients (5 males,5 females,age (50.9 ±17.2)years)and 10 healthy controls (5 males,5 females,age (52.0±10.3)years)from January 2016 to March 2017 were recruited to perform brain PET/CT of CGMand CBF.The brain PET imaging using 13 N-Ammonia was performed and followed by 18 F-fluorodeoxyglucose (FDG)PET.The mean standardized uptake values (SUVmean )of frontal,parietal, temporal and occipital lobes as well as basal ganglia,thalamus were obtained.The SUVmean of cerebral re-gions/SUVmean of cerebellum ratios (SUVr )were acquired.The SUVr were compared between the patients and controls.The imaging characteristics of CGM and CBF were investigated,and their relationships with clinical scores were further analyzed.Two-sample t test and Pearson correlation analysis were used to analyze the data.Results The radioactive distribution in the brain of healthy controls was symmetrical.SUVr of cer-ebral regions in the affected side of patients were significantly lower than those of the controls both in CGM imaging and CBF imaging (t values:2.90-5.19,all P<0.05).In 10 CDC patients,there were 9 with hypo-metabolism in basal ganglia and thalamus,8 with hypometabolism in frontal and parietal lobes,and 7 with hypometabolism in temporal and occipital lobes.At the same time,there were 7 with parietal hypoperfusion and 6 with hypoperfusion in other cerebral regions in the CDC patients.In the frontal,parietal lobes and basal ganglia,the CGMand CBF were both correlated with the clinical scores (r values:0.473-0.606,all P<0.05).Abnormal metabolism-perfusion patterns were divided into 3 types.Type Ⅰ included 2 patients and their hypometabolism and hypoperfusion were mismatched completely.Type Ⅱ included 3 patients and their hypometabolism and hypoperfusion were matched in frontal,parietal,occipital and temporal lobes,while mismatched in basal ganglia and thalamus.Type Ⅲ included 5 patients and their hypometabolism and hypoperfusion were matched completely.The clinical scores of typeⅠ,Ⅱand Ⅲ were 10.5,8.3 and 5.6, respectively.Conclusion The PET/CT imaging of cerebral blood flow and metabolism is useful in evalua-ting the disorders of consciousness.
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Objective To explore the consistency of time-of-flight (TOF) technology of PET/MRI and PET/CT for max standardized uptake value (SUVmax) of body malignant tumors.Methods A retrospective analysis of TOF-PET/CT and TOF-PET/MR imaging data about twenty patients with body malignant tumors was performed.Patients were divided into two groups (each n=10),including PET/CT first and sequentially PET/MR group and PET/MR first and sequentially PET/CT group.Bland-Altman figure was used to evaluate consistency of SUVmax of malignant lesions between TOF-PET/CT and TOF-PET/MR.Multi-way ANOVA was used to analysis effect of machine type and exam order on SUVmaxof malignant lesions in TOF-PET/CT and TOF-PET/MR.Results SUVmax of malignant lesions in TOF-PET/CT and TOF-PET/MR had good consistency in two groups (PET/CT first and sequentially PET/MR group:Mean difference was 3.06,95％CI was [-7.5,13.6];PET/MR first and sequentially PET/CT group:Mean difference was 3.0,95％CI was [-2.4,8.3]).SUVmax was not influenced by machine type (F=0.005,P=0.95),but exam order (F=46.00,P＜0.001).Conclusion PET/MR and PET/CT with TOF technology have comparative diagnostic value in SUVmaxof body malignant lesions.SUVmax of body malignant lesions increases in delay time,which is not related to machine type,but exam time.
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Objective To investigate the relationship between spatial distribution of default mode network and glucose uptake.Methods Nine healthy subjects were scanned with hybrid PET/MR.Resting state MRI (rs-fMRI) and PET data were obtained.Spatial distribution analysis was performed between default mode network and glucose uptake.The relationship between the functional connectivity of default mode network and the distribution of glucose uptake were further analyzed.Results The similar spatial distribution pattern was found between default mode network and glucose uptake.Correlation between functional connectivity and glucose uptake in the default mode network showed that the best correlation coefficient between the values of functional connectivity and relative glucose uptake (rGU) was achieved in the right posterior cingulate cortex (rs =0.833,P＜0.001).Conclusion Hybrid PET/MR is very important to investigate neural mechanism of default mode network.
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Objective To prepare a novel radiolabeled FR?positive tumor targeting agent 99 Tcm?( HYNIC?NHHN?FA) ( EDDA) and evaluate its biological properties. Methods FA derivative FA?NHHN?HYNIC was synthesized and radiolabeled with 99 Tcm using EDDA as a coligand. The radiochemical purity, octanal/water partition coefficient and in vitro stabilities of the complex were studied after purified by HPLC. In vitro cellular uptakes were performed on FR?positive KB cells ( human oral epidermoid carcinoma cells) . Biodistribution and microSPECT/CT imaging were investigated on normal Kunming mice and nude mice bearing KB tumors, respectively. Results The radiochemical purity of the complex was over 95% after pu?rified by HPLC. It displayed high stability both in saline and in serum. It also exhibited high specific FR binding in FR?positive KB cells in vitro. The binding ratio was (6.76±0.60)%1 h after incubation, and de?creased to (0.24±0.02)% after adding excessive FA. The results of biodistribution showed high kidney up?take in normal mice, and the uptake reached (21.79±9.79) %ID/g 0.5 h after injection. Flank KB tumors were clearly visualized with 99 Tcm?( HYNIC?NHHN?FA ) ( EDDA ) by microSPECT/CT imaging at 2 h postinjection, and the uptake could be inhibited by excessive FA. Conclusions 99 Tcm?( HYNIC?NHHN?FA) ( EDDA) exhibits good pharmacokinetic properties, suggesting its potential as a promising FA targeting agent for tumor imaging.
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@#Objective To evaluate the cerebrovascular reserve (CVR) with 13N-ammonia PET/CT and methazolamide in patients with cerebral ischemic disease. Methods From January, 2014 to December, 2015, basal and stress PET/CT were performed in ten healthy persons and 53 patients with unilateral internal carotid artery or middle cerebral artery stenosis. Radioactive counts were measured on mirror regions of bilateral frontal lobe, parietal lobe, temporal lobe, occipital lobe, basal ganglia and thalamus to calculate the blood flow change rate. Results For the healthy persons, the radioactive distribution of bilateral frontal lobe, parietal lobe, temporal lobe, occipital lobe, basal ganglia and thalamus were roughly symmetrical on both basal and stress PET/CT. The radioactive counts were more in basal ganglia and thalamus than in cortex, and the least in white matter. The radioactive counts were more on stress PET/CT than basal PET/CT, and there was no significant difference between both sides (t=1.552, P=0.132). For the patients, the blood flow perfusion decreased in 39 patients with 126 regions on basal PET/CT, and 49 patients with 183 regions on stress PET/CT. Within the 39 patients who found decreased blood flow perfusion regions, 16 patients were found new regions on stress PET/CT, and 29 regions of 13 patients improved in blood flow perfusion on stress PET/ CT. The blood flow change rate was significantly different between basal and stress PET/CT (t=2.466, P<0.05). Conclusion 13N-ammonia PET/CT cerebral blood flow perfusion imaging combined with methazolamide stress test can evaluate the cerebrovascular reserve in patients with unilateral internal carotid artery or middle cerebral artery stenosis, and is valuable for clinical assessment and early intervention for patients with cerebral ischemic disease.
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Objective To explore the growth and developmental parameters and behavioral characteristics of rhesus monkeys during the first year of birth and to establish the background data.Methods A total of 18 (♂=11,♀=7 ) infant rhesus monkeys born from individually caged mothers and with known genetic background and postnatal days were monitored monthly for body weight, body height, head circumference, chest circumference, forelimb length, hind limb length, crown-rump length, tail length and anal-genital distance from postnatal day ( PND) 1 to 360, while hematology, blood chemistry and lymphocyte subsets were examined on PND 28, 175 and 360, and finger maze test was carried out on PND 208.Results The body weight showed linear growth with no significant difference between genders (P>0.05). Except for the anal-genital distance of male infants was significantly greater than that of female infants ( P0.05).Compared with that at PND28, TP and BUN were significantly increased (P0.05) at PND 175 and 360.Compared with that at PND28, CD4 +and CD4 +/CD8 +were significantly decreased ( P<0.01) while CD8+significantly increased ( P<0.01) at PND175 and 360.The number of sessions to solve task 2 in learning test was significantly greater than other tasks with females significantly less than males ( P<0.05) .The females had higher correct rate than males in the 2-day random memory test (P<0.05).Conclusions Body weight and morphological parameters show a linear growth.The PND.The RBC, HGB, LYMPH, TP, BUN, ALP, CD4 +, CD8 +and CD4 +/CD8+in hematology, blood chemistry and lymphocyte subsets show relevant changes to the growth and development of organs and systems in infants, which should be highly concerned in drug evaluation.The finger maze test indicates that female infants have better reversal learning and long-term memory than male infants.Background data and behavioral characteristics of infant rhesus monkeys during the first 12 months of birth are established in this study, which provide useful reference and support the evaluation of developmental and reproductive toxicity of drugs in rhesus monkeys.
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BACKGROUND: With good biocompatibility, osteoconduction and biodegradability, calcium phosphate ceramics is considered as a substitute of autologous bone; furthermore, it also has the potentiel of osteoinduction after structure optimization. OBJECTIVE: To review the physicochemical properties of calcium phosphate ceramic and its osteoinduction. METHODS: A computer-based search of databases such as PubMed, Springer, ResearchGate and Baidu Academic was performed for articles relevant to calcium phosphate ceramics published from January 2000 to October 2015. And the keywords were “calcium phosphate, osteoinduction, tissue engineering, scaffolds” in English. RESULTS AND CONCLUSION: To date, there are four ideal kinds of calcium phosphate materials including hydroxyapatite, tricalcium phosphate, amorphous calcium phosphate and hydroxyapatite/tricalcium phosphate biphasic ceramic material. Hydroxyapatite has better strength and cel adsorption capacity, but has poor biodegradation. Tricalcium phosphate has good abilities of osteogenesis and degradation, but its degradation rate is hard to match the new bone formation,and its strength is also relatively poor. Amorphous calcium phosphate has neither strength nor solubility. In contrast, biphasic calcium phosphate ceramics has moderate degradation rate between hydroxyapatite and tricalcium phosphate, and therefore, it either can be replaced by autologous bone after degradation or exhibits proper strength. While how to further improve the physical properties and promote osteogenesis stil need much deeper research.
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BACKGROUND:The phenomenon of osteoinduction by biomaterials has been proven in animal experiments. OBJECTIVE:To investigate whether the ability of a biomaterial to initiate bone formation in ectopic implantation sites improves the performance of osteoinductive biomaterial as a scaffold for tissue-engineered bone. METHODS:We compared ectopic bone formation by combining autologous adipose-derived stromal cells with an osteoinductive and a nonosteoinductive biphasic calcium phosphate ceramic to create a tissue engineering construction in the muscle of dogs. Al implants were implanted in the back muscle of 10 adult dogs for 8 weeks and 12 weeks, including osteoinductive biphasic calcium phosphate ceramic+adipose-derived stromal cells (osteoinductive complex group), osteoinductive biphasic calcium phosphate ceramic (osteoinductive broup), nonosteoinductive biphasic calcium phosphate ceramic+adipose-derived stromal cells (nonosteoinductive complex group), and nonosteoinductive biphasic calcium phosphate ceramic (nonosteoinductive group). Micro-CT analysis and histomorphometry were performed to evaluate and quantify ectopic bone formation. RESULTS AND CONCLUSION:Ectopic bone formation was visible in the osteoinductive complex group and osteoinductive group, and the former group was superior to the latter one in quality of new bone (P<0.05). However, there was no ectopic bone formation in the other two groups. Micro-CT results were consistent with the histomorphological detection. These findings indicate that osteoinductive biphasic calcium phosphate ceramic, as a kind of bone tissue engineering scaffold material, has a better osteogenic capacity, while adipose-derived mesenchymal stem cells serve as seed cells to promote the ectopic bone formation.
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<p><b>OBJECTIVE</b>To explore the effects of recombinant human growth hormone (rhGH) on the serum levels of cytokines in severely burned patients.</p><p><b>METHODS</b>Thirty-six burn patients were enrolled in the study and were randomly divided into 3 groups according to the rhGH dosage used, i.e. small (0.3 IU.kg(-1).d(-1), A), large (0.6 IU.kg(-1).d(-1), B) dose groups and control group (C, with normal saline). The rhGH was administered beginning from 3 postburn days (PBDs) and lasted for 20 days. The dynamic changes in the serum levels of TNFalpha, IL-6, IL-8 and LPS at different time points were observed.</p><p><b>RESULTS</b>When compared with those in C group, the serum levels of TNFalpha, IL-6 in A, B groups were decreased, especially in B group with earlier decrease and bigger range (P < 0.01). Simultaneously, the serum LPS level was decreased accordingly with evident positive correlation with the change in those cytokines (r = 0.9723, P < 0.01). But there was no obvious difference in serum IL-8 level among A, B and C groups (P > 0.05).</p><p><b>CONCLUSION</b>rhGH might decrease the production of postburn inflammatory mediators, especially in higher dose in dose-dependent manner for some degree. The clinical application of rhGH might be a supplementary measure in preventing and ameliorating postburn SIRS and MODS in severely burned patients.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Burns , Blood , Drug Therapy , Cytokines , Blood , Dose-Response Relationship, Drug , Human Growth Hormone , Pharmacology , Therapeutic Uses , Interleukin-6 , Blood , Interleukin-8 , Blood , Lipopolysaccharides , Blood , Multiple Organ Failure , Mortality , Recombinant Proteins , Pharmacology , Therapeutic Uses , Survival Rate , Time Factors , Tumor Necrosis Factor-alpha , MetabolismABSTRACT
Objective In order to explore pathogenesis about inflammation injury of the hematoma peripheral zone after cerebral hemorrhage. Methods 48 adult male wistar rats are randomly divided into intracerebral hemorrhage (ICH) groupand control group. After 3 h, 24 h,72 h and 7 d of ICH, intercellular adhesion molecule-1 (ICAM-1)was detected by immunohistochemical SABC staining in rats brain slice. Positive cells expression of the ICAM-1 were measured by color image analysis system。Brain edema were assayed by dry-wet weight method. Results The expression of ICAM-1 increased at 3 h ( P 0.05) compared to contral group. Conclusions The overexpression of ICAM-1 may play important role in the perihematoma edema formation and ischemic injury.