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BACKGROUND:In recent years,the treatment method of injecting bone cement into the intervertebral space has been introduced from abroad for the treatment of lumbar recurrent pain caused by lumbar disc degeneration and intervertebral space narrowing;however,some patients had vertebral fractures after treatment;the fracture may occur because the bone cement injected into the intervertebral space has a poor elastic modulus. OBJECTIVE:To analyze the effect of bone cement with different elastic moduli injected into the intervertebral space on the maximum stress of upper and lower vertebrae using a three-dimensional finite element model. METHODS:A volunteer with normal spine was recruited to obtain CT data.The finite element model of L2-L5 lumbar spine was established using Mimics,Geomagic,SolidWorks,and Ansys.Subsequently,a L3-L4 intervertebral space injection model with different doses(1 mL and 4 mL)of bone cement was established.Four different elastic moduli(1 000,2 000,4 000,and 8 000 MPa)were assigned to bone cement at each dose.Pressure and bending moment were applied on the surface of the L2 vertebral body to analyze the stress on the lower surface of the L3 vertebral body and the upper surface of the L4 vertebral body. RESULTS AND CONCLUSION:(1)In the case of the same amount of bone cement injection,as the elastic modulus of bone cement increased,the stress on the lower surface of L3 vertebral body and the upper surface of L4 vertebral body increased.Among them,the bone cement with an elastic modulus of 1 000 MPa had the least effect on the lower surface of L3 vertebral body and the upper surface of L4 vertebral body.Bone cement with elastic modulus of 8 000 MPa had the greatest effect on the lower surface of L3 vertebral body and the upper surface of L4 vertebral body.Bone cement with different elastic moduli had little effect on the motion range of the whole lumbar spine.(2)The results indicate that injecting bone cement with lower elastic modulus while meeting treatment requirements can reduce the risk of postoperative fractures.
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Objective To explore the clinical effect of neurointervention assisted alteplase thrombolysis in the treatment of acute ischemic stroke(AIS).Methods A total of 104 AIS patients admitted to Beijing Shunyi Hospital from June 2022 to June 2023 were selected as the research subjects,and they were divided into observation group and control group according to the treatment method,with 52 cases in each group.The patients in the control group were treated with alteplase thrombolysis,and the patients in the observation group were treated with neurointervention assisted alteplase thrombolysis.The therapeutic effect of patients in the two groups was evaluated according to the National Institutes of Health stroke scale(NIHSS)score at two weeks after treatment.Before treatment and 3,7 days after treatment,the serum nerve growth factor(NGF),neuron specific enolase(NSE),central nervous system specific protein S100β levels of patients in the two groups were detected by enzyme-linked immunosorbent assay;the peak systolic velocities of common carotid artery,basilar artery and vertebral artery of patients in the two groups were detected by ultrasound transcranial Doppler blood analyzer;the degree of neurological damage of patients in the two groups was evaluated by NIHSS scores.The occurrence of drug-related adverse reactions during treatment of patients in the two groups were recorded;the comprehensive living ability of patients in the two groups was evaluated by improved Rankin score at three months after treatment.Results The total effective rates of patients in the control group and the observation group were 80.77%(42/52)and 96.15%(50/52),respectively;the total effective rate of patients in the observation group was significantly higher than that in the control group(x2=6.029,P<0.05).There was no significant difference in the serum NGF,NSE,S100β levels of patients between the two groups before treatment(P>0.05).Compared with before treatment,the serum NGF level of patients in the two groups increased,and the serum NSE,S100β levels decreased at 3,7 days after treatment(P<0.05).At 3,7 days after treatment,the serum NGF level of patients in the observation group was significantly higher than that in the control group,and the serum NSE,S100β levels were significantly lower than those in the control group(P<0.05).There was no significant difference in the peak systolic velocities of common carotid artery,basilar artery and vertebral artery of patients between the two groups before treatment(P>0.05).The peak systolic velocities of common carotid artery,basilar arteryand vertebral artery of patients at 3,7 days after treatment were significantly lower than those before treatment in the two groups(P<0.05).After 3,7 days after treatment,the peak systolic velocities of common artery,basilar artery,and vertebral artery of patients in the observation group were significantly lower than those in the control group(P<0.05).There was no significant difference in NIHSS score of patients between the two groups before treatment(P>0.05).The NIHSS score of patients at 3,7 days after treatment was significantly lower than that before treatment in the two groups(P<0.05).At 3,7 days after treatment,the NIHSS score of patients in the observation group was significantly lower than that in the control group(P<0.05).The total incidence of adverse reactions of patients during treatment in the control group and observation group was 7.69%(4/52)and 9.62%(5/52),respectively;there was no significant difference in the total incidence of adverse reactions during treatment of patients between the two groups(x2=0.000,P>0.05).At 3 months after treatment,the comprehensive living ability of patients in the observation group was better than that in the control group(P<0.05).Conclusion Neurointer-vention assisted with alteplase thrombolysis in the treatment of AIS patients can significantly improve the treatment efficacy and the expression of neurolin,reduce the degree of neurological impairment and improve comprehensive living ability,and has a certain degree of safety.
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ObjectiveTo analyze the development status and quality of clinical practice guidelines for the treatment of dominant diseases with Chinese patent medicines (CPMs). MethodsDatabases were searched from Jan. 2019 to Dec.2023 to collect the published clinical practice guidelines of CPMs for the treatment of dominant diseases. The information about the title, the participants, clinical problems, outcomes, evidence grade, recommendations, and recommendation strength in the included clinical practice guidelines were collected, for which the development status was analyzed, and the quality was evaluated with the Scientific, Transparent and Applicable Rankings (STAR) tool for clinical practice guidelines. ResultsTotally, 34 guidelines were included, involving 273 kinds of CPMs. One to ten (with the medium five) clinical problems were proposed from 29 clinical practice guidelines respectively. All the guidelines divided the evidence into four grades according to Grade of Recommendation Assessment, Deve-lopement an Evaluation. And 28 guidelines had five levels of recommendation strength. A total of 344 recommendations were extracted, including 86 strong-recommendations, 191 weak-recommendations (including 36 weak recommendations only based on expert consensus) and 67 recommendations with unclear recommendation strength. All guidelines had high scores in the three areas of “clinical questions (94.20%)”, “evidence (91.45%)” and “recommendations (89.06%)”, while the scores in the three areas of “registry (22.06%)”, “protocol (19.00%)” and “accessibility (31.51%)” were low. The STAR recommended stars of 8 guidelines were 5.0~4.0 stars, while that of 18 guidelines were 3.5~2.5 stars, and 8 guidelines were 2.0~1.0 stars. The three guidelines with the highest recommended stars were depressive disorder, community-acquired pneumonia, and influenza in adult. ConclusionThere is a certain gap in the quality of the published clinical practice guidelines of CPMs, and the quality of the guidelines could be further improved in registry, protocols, funds, and accessibility.
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Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.
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OBJECTIVE To expl ore the clinical significance of folic acid metabolic gene detection in methotrexate (MTX) treatment of acute myeloid leukemia (AML). METHODS Therapeutic drug monitoring (TDM)pharmacists participated in the treatment process of an AML patient who had neurotoxic side effects such as dizziness ,headache,and vomiting after intrathecal injection of MTX. According to the results of the test of the folic acid metabolic gene MTHFR C677T(rs1801133)(mutant homozygous)and the results of MTX blood concentration monitoring (<0.05 μmol/L),combined with clinical manifestations ,it was recommended to stop MTX ,give intravenous drip of calcium folinate for rescue ,and consider using azacytidine for follow-up treatment. RESULTS The doctor took the advice of TDM pharmacist ,and the above symptoms were significantly relieved after the patient rescued for 2 times and successfully discharged from the hospital. CONCLUSIONS For AML patients who meet the indications and receive intrathecal injection of MTX ,drug metabolism genetics testing and MTX drug concentration monitoring can be performed before medication ,which helps doctors and pharmacists evaluate the feasibility of drug treatment options and reduce medical risks.
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Objective:To explore the influencing factors for postoperative delirium in General Ward of Neurosurgery and evaluate the influence of serum acetylcholinesterase level in it.Methods:A retrospective study was performed. Two hundred and ninety-eight patients accepted surgery and diverted into General Ward of Neurosurgery in our hospital from January 2021 to July 2021 were chosen in our study. The 4AT delirium scoring tool was used to evaluate whether the patients had delirium, and these patients were, then, divided into non-delirium group and delirium group. The preoperative general data, history of deseases and laboratory results (serum acetylcholinesterase level) were collected. Univariate analysis and multivariate Logistic regression analysis were used to determine the independent factors affecting the occurrence of postoperative delirium, especially the relation between preoperative serum acetylcholinesterase level and postoperative delirium. Receiver operating characteristics (ROC) curve was drawn to evaluate the predictive value of serum acetylcholinesterase in postoperative delirium.Results:The incidence of postoperative delirium in 298 patients in General Ward of Neurosurgery was 24%, including 225 patients into the non-delirium group and 73 patients into the delirium group. There were significant differences between the two groups in the proportions of patients having resuscitation in anesthesia ICU, using postoperative analgesic pump and having alcoholism history, surgical duration, intraoperative bleeding, proportion of patients accepting skull base surgery, proportion of patients remaining awake 2 h after surgery, and incidence of bilateral frontal lobe pneumatosis after surgery ( P<0.05). Preoperative serum acetylcholinesterase level in delirium group ([2.35±0.49] U/mL) was significantly lower than that in non-delirium group ([2.78±0.48] U/mL, P<0.05). Preoperative serum acetylcholinesterase level ( OR=0.116, 95%CI: 0.034-0.394, P=0.001), postoperative resuscitation in anesthesia ICU ( OR=0.043, 95%CI: 0.002-0.878, P=0.041), keeping awake 2 h after surgery ( OR=7.641, 95%CI: 1.675-34.858, P=0.009), surgical duration ( OR=1.887, 95%CI: 1.192-2.987, P=0.007), intraoperative bleeding ( OR=1.010, 95%CI: 1.006-1.014, P<0.001), and skull base surgery ( OR=6.700, 95%CI: 1.907-23.547, P=0.003) were all independent influencing factors for postoperative delirium in patients in General Ward of Neurosurgery. The area under ROC curve for serum AchE level to predict the occurrence of postoperative delirium was 0.735(95%CI: 0.679-0.800, P<0.001); when the cut-off value was 2.67 U/mL, the sensitivity and specificity were 64% and 75%. Conclusions:Skull base surgery, keeping awake 2 h after surgery, long surgical duration and large amount of intraoperative bleeding can promote the occurrence of postoperative delirium; admission to anesthesia ICU after surgery can reduce the occurrence of delirium. When the preoperative serum AchE level is less than 2.67 U/mL, the possibility of postoperative delirium should be warned.
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Chemotherapy outcomes for the treatment of glioma remains unsatisfactory due to the inefficient drug transport across the blood-brain barrier (BBB) and insufficient drug accumulation in the tumor region. Although many approaches, including various nanosystems, have been developed to promote the distribution of chemotherapeutics in the brain tumor, the delivery efficiency and the possible damage to the normal brain function still greatly restrict the clinical application of the nanocarriers. Therefore, it is urgent and necessary to discover more safe and effective BBB penetration and glioma-targeting strategies. In the present study, menthol, one of the strongest BBB penetration enhancers screened from traditional Chinese medicine, was conjugated to casein, a natural food protein with brain targeting capability. Then the conjugate self-assembled into the nanoparticles to load anti-cancer drugs. The nanoparticles were characterized to have appropriate size, spheroid shape and high loading drug capacity. Tumor spheroid penetration experiments demonstrated that penetration ability of menthol-modified casein nanoparticles (M-CA-NP) into the tumor were much deeper than that of unmodified nanoparticles. imaging further verified that M-CA-NPs exhibited higher brain tumor distribution than unmodified nanoparticles. The median survival time of glioma-bearing mice treated with HCPT-M-CA-NPs was significantly prolonged than those treated with free HCPT or HCPT-CA-NPs. HE staining of the organs indicated the safety of the nanoparticles. Therefore, the study combined the advantages of traditional Chinese medicine strategy with modern delivery technology for brain targeting, and provide a safe and effective approach for glioma therapy.
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OBJECTIVE: To evaluate the effects of clinical pharmacist-led ischemic stroke management, and to provide reference for chronic disease management. METHODS: Totally 184 patients with ischemic stroke who were hospitalized in neurology department of the First Hospital of Hebei Medical University from May to August 2018 were included prospectively, and then divided into control group (92 cases) and intervention group (92 cases) by random number method. Control group did not receive clinical pharmacist intervention. In the intervention group, clinical pharmacists were the leader in the pharmaceutical care during the hospitalization, the medication education at discharge, and pharmacy follow-up after discharge. The rate of medication compliance (antiplatelet drugs, antihypertensive drugs, hypoglycemic drugs and lipid-lowering drugs) and the rate of secondary prevention and control indicators of ischemic stroke, such as blood pressure, blood glucose [glycated hemoglobin (HbA1c)] and blood lipid [low-density lipoprotein cholesterol (LDL-C)] were investigated between 2 groups at 6 months after discharge. The incidence of adverse drug reaction and the rate of rehospitalization were compared between 2 groups at 6 months after discharge. RESULTS: The number of patients in the intervention group and the control group was 84 and 82, respectively. At 6 months after discharge, the compliance rate of antiplatelet drugs in the intervention group was 96.43%, which was higher than 95.13% of control group, but the difference was not statistically significant. The good compliance rates of antihypertensive drugs, hypoglycemic drugs and lipid-lowering drugs in the intervention group were 92.86%, 91.67% and 77.38%, which were higher than 78.57%, 69.70% and 60.98% of control group, with statistical significance (P<0.05). The qualified rate of index of blood pressure was 89.29% in intervention group, which was higher than 76.79% of control group, but the difference was not statistically significant. The qualified rates of HbA1c and LDL-C in the intervention group were 80.56% and 66.67%, which were higher than 57.58% and 48.785 of control group, with statistical significance (P<0.05). The incidence of total adverse drug reactions in the intervention group was 15.48%, which was lower than 20.73% of control group, but the difference was not statistically significant. The total rehospitalization rate in the intervention group was 7.14%, which was lower than 17.86% of control group, the difference was statistically significant (P<0.05). CONCLUSIONS: The management of ischemic stroke patients with clinical pharmacists as the leading factor can improve the patient’s medication compliance, improve the qualified rate of secondary prevention and control indicators of ischemic stroke, and reduce the rate of rehospitalization.
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Objective To investigate the curative effect of laparoscopic retrograde time full cholecystectomy in the treatment of chronic calculous cholecystitis.Methods From February 2016 to December 2017,100 patients with chronic calculous cholecystitis in the Second People's Hospital of Yuyao were selected as the study objects.All patients were randomly divided into observation group and control group according to digital table method,with 50 cases in each group.The control group were treated by laparoscopic retrograde cholecystectomy all treatment.The observation group were treated by laparoscopic retrograde time full cholecystectomy treatment,the clinical therapeutic effect of the two groups of patients were comparatively analyzed.Results The clinical effective rate of the observation group was 94.00%,which was better than that of the control group (72.00%) (x2 =15.235,P < 0.05).The blood loss [(71.23 ± 18.74) mL],operation time [(46.23 ± 11.88) min],exhaust time [(19.83 ± 6.58) h],the bed movement time[(27.19 ± 5.47) h] and length of hospital stay[(5.23 ± 0.86) d] of the observation group were significantly better than those of the control group [(54.89 ± 11.52) mL,(77.35 ± 12.43) min,(27.85 ± 8.72) h,(35.68 ± 9.56) h,(7.96 ± 1.47) d] (t =12.534,22.563,12.534,22.563,6.113,all P < 0.05).Conclusion The laparoscopic retrograde time full cholecystectomy in the treatment of chronic calculous cholecystitis has better curative effects,which is worth popularizing in clinical use.
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In this paper, we prepared a dual functional system based on dextrin-coated silver nanoparticles which were further attached with iron oxide nanoparticles and cell penetrating peptide (Tat), producing Tat-modified Ag-FeO nanocomposites (Tat-FeAgNPs). To load drugs, an -SH containing linker, 3-mercaptopropanohydrazide, was designed and synthesized. It enabled the silver carriers to load and release doxorubicin (Dox) in a pH-sensitive pattern. The delivery efficiency of this system was assessed using MCF-7 cells, and using null BalB/c mice bearing MCF-7 xenograft tumors. Our results demonstrated that both Tat and externally applied magnetic field could promote cellular uptake and consequently the cytotoxicity of doxorubicin-loaded nanoparticles, with the IC of Tat-FeAgNP-Dox to be 0.63 µmol/L. The delivery efficiency of Tat-FeAgNP carrying Cy5 to the mouse tumor was analyzed using the optical imaging tests, in which Tat-FeAgNP-Cy5 yielded the most efficient accumulation in the tumor (6.7±2.4% ID of Tat-FeAgNPs). Anti-tumor assessment also demonstrated that Tat-FeAgNP-Dox displayed the most significant tumor-inhibiting effects and reduced the specific growth rate of tumor by 29.6% ( = 0.009), which could be attributed to its superior performance in tumor drug delivery in comparison with the control nanovehicles.
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RNAi technology has aroused wide public interest due to its high efficiency and specificity to treat multiple types of diseases. However, the effective delivery of siRNA remains a challenge due to its large molecular weight and strong anionic charge. Considering their remarkable functions and features that are often desired in drug delivery carriers, biomimetic systems for siRNA delivery become an effective and promising strategy. Based on this, covalent attachment of synthetic cell penetrating peptides (CPP) to siRNA has become of great interest. We developed a monomeric covalent conjugate of low molecular weight protamine (LMWP, a well-established CPP) and siRNA a cytosol-cleavable disulfide linkage using PEG as a crosslinker. Results showed that the conjugates didn't generate coagulation, and exhibited much better RNAi potency and intracellular delivery compared with the conventional charge-complexed CPP/siRNA aggregates. Three different synthetic and purification methods were compared in order to optimize synthesis efficiency and product yield. The methodology using hetero-bifunctional NHS-PEG-OPSS as a crosslinker to synthesize LMWP-siRNA simplified the synthesis and purification process and produced the highest yield. These results pave the way towards siRNA biomimetic delivery and future clinical translation.
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Exploiting cells as vehicles combined with nanoparticles combined with therapy has attracted increasing attention in the world recently. Red blood cells, leukocytes and stem cells have been used for tumor immunotherapy, tissue regeneration and inflammatory disorders, and it is known that neutrophils can accumulate in brain lesions in many brain diseases including depression. -Acetyl Pro-Gly-Pro (PGP) peptide shows high specific binding affinity to neutrophils through the CXCR2 receptor. In this study, PGP was used to modify baicalein-loaded solid lipid nanoparticles (PGP-SLNs) to facilitate binding to neutrophils . Brain-targeted delivery to the basolateral amygdala (BLA) was demonstrated by enhanced concentration of baicalein in the BLA. An enhanced anti-depressant effect was observed and The mechanism involved inhibition of apoptosis and a decrease in lactate dehydrogenase release. Behavioral evaluation carried out with rats demonstrated that anti-depression outcomes were achieved. The results indicate that PGP-SLNs decrease immobility time, increase swimming time and climbing time and attenuate locomotion in olfactory-bulbectomized (OB) rats. In conclusion, PGP modification is a strategy for targeting the brain with a cell-nanoparticle delivery system for depression therapy.
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Taking inspiration from nature, the biomimetic concept has been integrated into drug delivery systems in cancer therapy. Disguised with cell membranes, the nanoparticles can acquire various functions of natural cells. The cell membrane-coating technology has pushed the limits of common nano-systems (fast elimination in circulation) to more effectively navigate within the body. Moreover, because of the various functional molecules on the surface, cell membrane-based nanoparticles (CMBNPs) are capable of interacting with the complex biological microenvironment of the tumor. Various sources of cell membranes have been explored to camouflage CMBNPs and different tumor-targeting strategies have been developed to enhance the anti-tumor drug delivery therapy. In this review article we highlight the most recent advances in CMBNP-based cancer targeting systems and address the challenges and opportunities in this field.
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Objective To evaluate the diagnosis value of the percentage of Tie 2-expressing monocytes(TEMs)in CD14+CD16+monocytes of peripheral blood from hepatocellular carcinoma(HCC) patients with negative AFP and tumor size≤3 cm.Methods Flow Cytometry(FCM)was used to determine the percentage of TEMs in CD14+CD16+monocytes of peripheral blood from patients with HCC(n=82), liver cirrhosis(n=29), chronic hepatitis B(n=28), and healthy controls(n=31).Abbott i2000 microparticle chemiluminescence immunoassay analyzer was used to determine the plasma alpha -fetoprotein (AFP)levels.The difference among multi groups was analyzed by the Kruskal-Wallis H test.Two independent groups were analyzed by the Mann-Whitney U test.The chi-square test was used in the rate comparison.The correlation between TEMs and AFP was analyzed by Spearman rank correlation analysis. Morever, the areas under the receiver operating characteristic curves(ROC-AUC), sensitivity and specificity of TEMs or AFP in differentiating HCC, HCC with AFP negative or tumor size≤3 cm were analyzed.Results The percentage of TEMs in CD14 +CD16 +monocytes of peripheral blood from HCC or HCC with negative AFP or HCC with tumor size≤3 cm was significantly higher than that in patients with liver cirrhosis,chronic hepatitis B and healthy controls(P<0.05).ROC-AUC of TEMs and AFP in the diagnosis of HCC were 0.701(95% CI 0.626-0.768)and 0.712(95% CI 0.638-0.779) respectively.When the cut-off values of TEMs and AFP were 4.95%and 20 μg/L,the sensitivities of TEMs and AFP were 71.95%and 45.12%,and the specificities of TEMs and AFP were 70.45%and 85.23%. The sensitivity of TEMs in the diagnosis of HCC was significantly higher than that of AFP(χ2=12.16,P=0.000).The specificity of AFP was significantly higher than that of TEMs(χ2=5.57,P=0.018).There was a highest sensitivity(89.02%)in TEMs/AFP method,and there was a highest specificity(93.18%) in TEMs+AFP method in the diagnosis of HCC.There was no significant difference between the ROC-AUC for the TEMs and the AFP in the diagnosis of 26 patients with tumor size≤3 cm HCC(0.776 vs 0.645,Z=1.805,P=0.071),TEMs/AFP had the highest sensitivity(84.62%),while TEMs+AFP had the highest specificity(93.18%)in the diagnosis of tumor size≤3cm HCC.The ROC-AUC for the TEMs in the diagnosis of 45 patients with AFP negative HCC was 0.739(95%CI 0.648-0.829).The sensitivity and specificity of TEMs were 80.0% and 70.45% respectively.There was no correlation between the level of plasma AFP and the percentage of TEMs(r=-0.169, P=0.129)determined by Spearmans rank correlation coefficient.Conclusions TEMs is valuable in the diagnosis of HCC with negative AFP and tumor size≤3cm,and the two tests of TEMs and AFP can complement each other in the diagnosis of patients with HCC.
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Objective To investigate the protective effects of N-acetyl-L-tryptophan (L-NAT) on intestinal damage after rat hepatic ischemia reperfusion.Methods Twenty-four healthy adult rats were divided into the sham operation group (Sham),ischemia reperfusion group (IR),ischemia reperfusion and N-acetyl-L-tryptophan group(IR+L-NAT).The hepatic ischemia reperfusion model was established by occluding the afferent vessels of the left and middle lobes.The morphological structures of the small intestine were observed by hematoxylin-eosin (HE) staining.The expressions of active caspase-3,Bax and Bcl-2 were detected by immunohistochemistry staining.Results (1) In the IR group,the structure of intestinal villis was destroyed,the intestinal mucosa showed congestion and exfoliation,the epithelial cells had degeneration and necrosis,and infiltration of inflammatory cells appeared;which could be alleviated by L-NAT.(2)The immunohistochemistry showed that compared with the Sham group,the expression of active caspase-3,Bcl-2 and Bax in the IR group was increased,after L-NAT intervention,the Bax and caspase-3 expression was decreased,while the Bcl-2 expression was further increased.Conclusion L-NAT could inhibit the apoptosis of small intestinal epithelial cells caused by liver ischemic reperfusion and attenuates intestinal epithelial damage.
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Objective To investigate the protective effects of N-acetyl-L-tryptophan (L-NAT) on intestinal damage after rat hepatic ischemia reperfusion.Methods Twenty-four healthy adult rats were divided into the sham operation group (Sham),ischemia reperfusion group (IR),ischemia reperfusion and N-acetyl-L-tryptophan group(IR+L-NAT).The hepatic ischemia reperfusion model was established by occluding the afferent vessels of the left and middle lobes.The morphological structures of the small intestine were observed by hematoxylin-eosin (HE) staining.The expressions of active caspase-3,Bax and Bcl-2 were detected by immunohistochemistry staining.Results (1) In the IR group,the structure of intestinal villis was destroyed,the intestinal mucosa showed congestion and exfoliation,the epithelial cells had degeneration and necrosis,and infiltration of inflammatory cells appeared;which could be alleviated by L-NAT.(2)The immunohistochemistry showed that compared with the Sham group,the expression of active caspase-3,Bcl-2 and Bax in the IR group was increased,after L-NAT intervention,the Bax and caspase-3 expression was decreased,while the Bcl-2 expression was further increased.Conclusion L-NAT could inhibit the apoptosis of small intestinal epithelial cells caused by liver ischemic reperfusion and attenuates intestinal epithelial damage.
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Objective To analyze the specific peptide of cystatin C (CysC) and its characteristics by bioinformatics technology,and verify the predicted results by mass spectrometry.Methods Online software was applied to analyze the physicochemical properties and homology of CysC peptides hydrolyzed by trypsin and predict the associated parameters of ionized fragmentation of specific peptide by mass spectrometry.Precursor ion scan and product ion scan were conducted on the samples of synthetic specific peptide.The recombinant human CysC and serum samples were analyzed by mass spectrometry after trypsin digestion.The results of analysis were compared with the outcomes predicted by bioinformatics.Results T3 (ALDFAVGEYNK) was considered as the specific peptide of CysC by software analysis.When selecting[M + 2H] 2 + for product ion scan,almost all the y and b ions of fragmentation were observed using tandem mass spectrometry (MS/MS),showing consistency with Skyline predictions.Moreover,both the peptides from the human recombinant CysC and serum sample following the trypsin digestion were eluted at the same time with the isotope-labeled T3 * under the fixed conditions.Conclusion Bioinformatics technology could be available for picking out the specific peptides of target protein quickly and efficiently and predicting the ionized fragmentation precisely by mass spectrometry scanning.
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Pancreatic cancer is one of the most aggres sive malignant tumors with dismal prognosis.The 2017 annualmeeting of the American Society of Clinical Oncology (ASCO)brings together thousands of oncology professionals from around the world to discuss state-of-the-art treatment modalities,new therapies,and ongoing controversies in the field.In this paper,authors selected and reviewed pancreatic cancer research from 2017 annual meeting of the ASCO,especially the latest research progress in genetic diagnosis,chemotherapy,immunotherapy,targeted therapy and neoadjuvant treatments.
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Objective To investigate the effect of measuring value transfer for human serum samples assigned by the reference laboratory network on improving the trueness of seven enzyme activities in clinical laboratories,such as ALT,AST,GGT,LDH,CK,AMY and ALP.Methods Depending on the medical imtitutions at all levels contacted by 5 reference laboratories in North China,South China,East China and Southwest China,the corresponding clinical laboratory measuring value transfer/traceability network was established.The frozen human serum samples with good interehangeability and standard material characteristics,including calibrator,sample 1 and sample 2,were provided by Beijing Aerospace General Hospital,and were assigned by 5 reference labotatories in four regiom.These samples were sent to 48 clinical laboratories.These clinical laboratories measured sample 1 and sample 2 according to their standard operating procedures,and then measured.the two samples again after adjusting their measurement system by using the supplied calibrator.The changes of trueness of detection results in these laboratories were evaluated according to the WS/T 403-2012 standard,and the changes of consistency for ALT and AST before and after measuring value tramfer were investigated.Results The results of AMY,ALP,GGT,CK and LDH calibrator,sample 1 and sample 2 assigned by the established network were 138.7 U/L,278.5 U/L and 68.3 U/L,265.3 U/L,94.5 U/L and 134.4 U/L,195.8 U/L,89.0 U/L and 158.9 U/L,393.7 U/L,260.0 U/L and 645.3 U/L,and 302.0 U/L,250.0 U/L and 452.7 U/L,respectively.The percentages of sample 1 and sample 2 which met the bias requirements of the WS/T 403-2012 standard before measuring value transfer for AMY,ALP and GGT were 65.9% and 61.0%,76.6% and 78.7%,and 66.7% and 70.8%,respectively,while after measuring value transfer,they were 89.2% and 83.8%,86.7% and 80.0%,and 85.4% and 91.7%,respectively.The percentages of sample 2 which met the bias requirements of the WS/T 403-2012 standard before measuring value transfer for CK and LDH were 64.6% and 58.3%,respectively,while after measuring value trander,they were 93.5% and 84.8%,respectively.The coefficients of variation (consistency) of sample 1 and sample 2 for ALT and AST before measuring value tramfer were 12.9% and 11.3%,and 10.2% and 8.9%,respectively,while after measuring value transfer,they were 9.3% and 8.2%,and 5.6% and 5.9%,respectively.Conclusion The calibration of routine measurement systems based on the measuring value transfer for human serum samples assigned by the reference laboratory network may improve the comparability of 7 enzyme actvities measurement results in chnical laboratories at all levels obviously,which deserves to be further spread.
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OBJECTIVE:To establish a method for content determination of schizantherin E,gomisin J,angeloylgomisin H,schisantherin A,schisantherin B,schisanhenol,anwuligan,schizandrin A,schizandrin B and schizandrin C in Wuzhi tablets.METHODS:RP-HPLC method was adopted.The determination was performed on Symmetry C18 column with acetonitrile-0.1% phosphoric acid solution (gradient elution) at the flow rate of 1.0 mL/min.The detection wavelength was set 225 rm,and the column temperature was 30 ℃.The sample size was 10 μL.RESULTS:The linear ranges of schizantherin E,gomisin J,angeloylgomisin H,schisantherin A,schisantherin B,schisanhenol,anwuligan,schizandrin A,schizandrin B and schizandrin C were 2.25-67.5ng(r=0.999 6),2.1-63 ng(r=0.999 8),28-840 ng(r=0.999 9),124.6-3 738 ng(r=0.999 9),22.7-681 ng(r=0.999 9),32.7-981 ng(r=0.999 9),47-1 410 ng(r=0.999 9),208-6 240 ng(r=0.999 9),5.36-160.8 rig(r=0.999 9),4.48-134.4 ng(r=0.999 8).The limits of quantitation were 14.17,13.32,9.33,11.37,14.62,19.88,14.66,12.50,16.40,13.55 rg.The limits of detection were 4.62,4.60,3.08,3.76,4.81,6.74,4.93,4.16,5.86,5.03 ng.RSDs of precision,stability and reproducibility tests were less than 3.0%;the recoveries were 96.36%-100.00%(RSD=1.83%,n=6),95.00%-100.00%(RSD=2.07%,n=6),95.00%-98.00%(RSD=1.22%,n=6),95.37%-98.91% (RSD=1.29%,n=6),95.62 %-103.71% (RSD=2.85%,n=6),97.33%-102.67% (RSD=2.00%,n=6),95.00%-99.33% (RSD=1.75%,n=6),97.24%-104.93% (RSD=2.63%,n=6),95.00%-97.50% (RSD=1.42%,n=6),96.00%-102.00% (RSD=2.45%,n=6),respectively.CONCLUSIONS:The developed method is accurate,sensitive and reproducible,and it can be used for content determination of 10 lignanoids in Wuzhi tablets.