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Ommaya reservoir implantation is generally used in the treatment of hydrocephalus and intraventricular drug administration. Ommaya reservoir implantation in the subarachnoid space of the spinal cord for the intrathecal drug administration has not been carried out in China, and only several reports can be retrieved from PubMed. About 60%-90% of untreated patients with spinal muscular atrophy type 2 (SMA2) who survive to adulthood often have complex scoliosis and joint deformities. Nusinersen is an effective drug for the treatment of SMA2. And the route of administration is intrathecal injection, which is difficult for patients with severe scoliosis. This article summarizes the process of Ommaya reservoir implantation and postoperative drug administration in a patient with complex scoliosis type SMA2, which provides a new method for clinical treatment of this disease.
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Myelodysplastic syndrome (MDS) is characterized by dysplastic and ineffective hematopoiesis that can result from aberrant expansion and activation of myeloid-derived suppressor cells (MDSC) within the bone marrow microenvironment. The proliferation and activation of MDSC lead to the dysfunction and depletion of natural killer cells and CD8 + T cells, and the recruitment of inflammatory cells and factors leads to the further accumulation of genetic abnormalities in MDS patients, leading to the progression of MDS. The accumulation of inflammatory cytokines in the tumor environment induces the expression of programmed death receptor 1 (PD-1) in hematopoietic stem cells and hematopoietic progenitor cells and the overexpression of programmed death receptor ligand 1 (PD-L1) in MDSC, and the interaction of PD-1/PD-L1 leads to the apoptosis of MDS hematopoietic progenitor cells and ineffective hematopoiesis. The experiments and clinical studies targeting MDSC have confirmed that correcting or reversing the bone marrow microenvironment of immune disorders in MDS is a therapeutic strategy to restore effective hematopoietic function.
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OBJECTIVE： To investigate the research status，hotspots and frontiers of the artificial intelligence （AI） technology applicated in pharmaceutical field， and to provide ideas for the development of related research in China. METHODS： Using bibliometric method， relevant journals and proceeding papers from 1998 to 2017 were searched from Web of Science database （“Article” and “Proceeding Paper” as retrieval words）. Using analysis and retrieval results of ISI Web of Knowledge and its function of creating citation report， CiteSpace 5.2.R1 software was employed to draw knowledge map； quantitative statistics and qualitative analysis was conducted to summarized the research volume， co-citation， main research countries/areas， main research institutions， main researchers， research hotspots and research frontiers in this field. RESULTS： A total of 3 674 related literatures were retrieved， and the number of global published literatures in this field increased rapidly from 1998 to 2017； the dominant nations included America， China， Britain and Germany because of their large number of publications，but China showd an obvious lack of international cooperation and excellent core teams. From the researcher’s point of view， the research in this field was in a state of “partially concentrated and overall dispersed” and lacked team cooperation. The research hotspots contained important core of AI technology （machine learning algorithms） and its application in pharmaceutical field （drug discovery and design）， the classification of disease or adverse drug reaction， the establishment and optimization of pharmaceutical mode， drugs screening or pharmacodynamics prediction， the estbalishment of pharmaceutical database， etc. The recent research frontiers included “molecular docking” “machine learning” “Meta analysis” “precision medicine” “targeted therapy”， etc. CONCLUSIONS： AI applicated in pharmaceutical field is a hot research field with strong timeliness， and its application in the development of pharmaceutical industry is the general trend. However， there is still a gap between the current research level in this field in China and the international frontier research. In order to adapt to the international trend of the combination of AI technology and pharmacy， pharmacists in China should strengthen their cooperation with researchers in AI fields while doing well the basic work of experimental research and clinical trials，etc.
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Aromatic antiepileptic drugs such as carbamazepine are the first-line treatment for epilepsy. The adverse reactions have greatly limited their clinical application. The occurrence rate of severe skin adverse reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) is low,but they are often fatal.Human leukocyte antigen (HLA) gene polymorphisms are reported to be related with skin adverse reactions caused by aromatic antiepileptic drugs,but the exact mechanism is unclear.This article will perform a review about the correlation between skin adverse reactions caused by aromatic antiepileptic drugs and HLA gene polymorphisms published in recent years,in order to provide theoretical basis for further study of HLA susceptibility genes in Chinese Han population,and provide a reference for achieving individualized treatment of epilepsy.
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Objective To evaluate the uncertainty for the determination of salicylic acid in human plasma by ultra performance liquid chromatography(UPLC).Methods All sources of uncertainty in the whole process of salicylic acid determination were analyzed,then the combined and expanded uncertainty were evaluated.Results The expanded uncertainty at concentrations of the lowest limit of quantitation(0.23 μg·mL-1) and a high level(39.43 μg·mL-1) of salicylic acid(P=95%,k=2) was 0.014 and 7.34 μg·mL-1,respectively.Conclusion The uncertainty of salicylic acid determination in human plasma by UPLC was mainly caused by recovery,repeatability and sample preparation at the lowest limit of quantitation and high qulity control concentration.
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Objective To explore the correlation of metabolic disorder of newly diagnosed type 2 metabolism(T2DM) and nonalcoholic fatty liver disease (NAFLD).Methods A total of 117 patients with newly diagnosed T2DM in Beijing Ditan Hospital Affiliated to Capital Medical University from June 2014 to June 2015 were enrolled.Patients were divided into two groups:T2DM with NAFLD of 57 cases and T2DM without NAFLD of 60 cases.Body mass index (BMI),waist circumference (WC),liver and kidney function,serum lipid,glycosylated hemoglobin A1c (HbA1c),fasting glucose,fasting insulin and C-peptide (FCP) were detected.The insulin resistance and β-cell function were assessed by homeostasis model assessment insulin resistance (HOMA-IR) and HOMA-β.Results The incidence of NAFLD in T2DM patients was 51％ (that was,60 cases of T2DM patients with NAFLD),compared with 2TDM group,the metabolic index of T2DM without NAFLD was significantly increased (blood triglyceride (TG):(2.58 + 1.8) mmol/1 vs.(1.22 + 0.4) mmol/l,fasting blood glucose:(11.5+6.1) mmol/l vs.(9.2+4.3) mmol/l,serum uric acid:(465.3+65) umol/l vs.(325.3+72) umoL/l;P =0.03,0.03,0.02);HOMA-IR was more serious ((4.9 ± 2.8) vs.(3.8 ± 2.7);P =0.03);insulin β-cell function was compensatory more obvious ((49.2 ± 27) vs.(29.5 ± 18);P =0.02);prevalence rate of obesity,hypertension and diabetic ketoacidosis (DKD),diabetic retinopathy (DR),diabetic peripheral neuropathy(DPN) were significantly increased(P＜0.05).Logistic regression analysis showed that,smoking(OR=1.405,95％CI:1.262-1.567),male(OR=1.037,95％CI:1.015-1.063),BMI(OR=1.113,95％CI:1.278-2.531),WC (OR =1.624,95％ CI:1.162-1.761) and TG (OR =1.823,95％ CI:1.2822.563) were risk factors of NAFLD (P ＜ 0.05).Conclusion T2DM patients with NAFLD have severer insulin resistance than those without NAFLD.The β-cell function of those patients is compensatory increased.NAFLD prevalence rate significantly increase in patients with obesity,especially in male diabetic patients who smoking.
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Objective To analyze literature distribution and research of clinical molecular diagnosis in recent years using bib-liometric method.Methods The “clinicalmolecular diagnosis”as the topic,the papers related to clinical molecular diagnosis were searched from the database of “Web of Sciences”(from 1986 to 2015.8.31).The resulting papers were analyzed using bibliometric method concerning the paper numbers,countries/districts,institutes,journal distribution,etc.Summary of the times cited and citing papers were also investigated.Results A total of 6 279 papers were obtained from the database,and the annual number of publications and citations increased all the time.United States and West European countries (France, Italy,Germany,England,Spain,etc.)issued the largest number of papers.The mean number of citation and h-index were 16.6 times and 118,respectively.The papers about the usage of clinical molecular diagnosis on disease diagnosis,treatment and prognosis had the most citations.Conclusion Clinical molecular diagnostics technology is in the development stage.It plays a larger role in the diagnosis and treatment of disease.The application of this technology may improve our services lev-el significantly.
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Objective To investigate the kinesin family member 17 (KIF17) expression and cellular localization in the hippocampus and temporal lobe cortex in the rat lithium-pilocarpine model of epilepsy,and discuss its function in the epilepsy pathogenesis.Methods The animal model was established by lithiumpilocarpine induction in rats.Totally 49 adult healthy male Wistar rats were randomly divided into control group (n =7) and experimental group (n =42).The experimental group included 6 subgroups (n =7)according to sacrifice time (24 h,72 h,7 d,14 d,1 month and 2 months).The expression and localization of KIF17 were examined by western blot and double-label immunofluorescence,respectively.Results In rat hippocampus,the expression of KIF17 protein increased after the onset of seizure (the ration of KIF17/β-actin were:24 h 0.516 ± 0.196,72 h 0.742 ± 0.313),reached its peak in 7 days (0.888 +0.319)and then slowed down (14 d 0.770 ± 0.271,1 month 0.742 ± 0.261,2 months 0.714 ± 0.271),all of which were significantly higher than that in the control group (0.495 ± 0.203).And all the differences had statistical significance (t =7.051,4.974,7.419,8.795,8.264,6.676,all P ＜ 0.05).In rat cortex of temporal lobe,the expression of KIF17 protein increased after the onset of seizure and reached its peak in 30 d.The optical density ration in the experimental groups were higher than that in the control group.Doublelabel immunofluorescence disclosed that the KIF17 localized in the neurons,including excitable neurons and inhibitory neurons,but not in the astrocytes which were performed with anti-microtubule-associated protein 2,anti-brain-specific Na-dependent inorganic phosphate cotransporter,anti-glutamate decarboxylase 1 and anti-glial fibrillary acidic protein,respectively.Conclusion KIF17 may play a potential role in the pathogenetic mechanisms of the rat lithium-pilocarpine model of epilepsy.
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Objective To study clinical effects and complications of minimal invasive neurosurgery for pituitary adenoma through superciliaryarch-keyhole approach. Methods 127 cases pituitary adenoma in three hospitals in Shangdong province from May. 2006 to Sept. 2009 confirmed by surgery were analyzed. Patients were treated by different operative approaches, 53 cases using surgery through superciliaryarch-keyhole approach and 74 cases through conventional subfrontal approach. Clinical parameters were compared in patients undergoing surgery through different approaches. Results There were no differences in two groups, in aspects such as resection rate, improvment of endocrine hormone secretion and acuity of vision with campus visualis, electrolyte disturbances, hypothalamus damage (P ＞0.05). Significant differeces reside in average hospitalization days, subcutaneous fluidify, psychiatric symptom and circumscribed cerebral ischemia ( P ＜ 0.05 ). Conclusion Advantages of minimal invasive neurosurgery through superciliary arch approach such as less trauma, better expose,shorter hospitalization days, less subcutaneous fluid accumulation and psychiatric symptoms in terms of this apporach are suitable for removing hypophyseal adenomas that grow on or around sella turcica.
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Epithelial membrane protein 3 (EMP3) is a trans-membrane signaling molecule with important roles in the regulation of apoptosis, differentiation and invasion of cancer cells, but the detailed is largely still unknown. We analyzed the mRNA levels and methylation statuses of EMP3 in 63 primary breast carcinomas and assessed their correlations with clinicopathologic variables. The expression of EMP3 mRNA in primary breast carcinomas was significantly higher than the expression of 20 normal breast tissues (p<10(-7)). EMP3 overexpression in breast carcinomas was significantly related to histological grade III (p=3.9X10(-7)), lymph node metastasis (p= 0.003), and strong Her-2 expression (p=3.3X10(-6)). Hypermethylation frequencies of EMP3 were detected in 36.5% of breast carcinomas by methylation-specific polymerase chain reaction. However, no significant correlations were found between methylation status of EMP3 and mRNA expression levels as well as other clinical parameters. In conclusion, EMP3 may be a novel marker of tumor aggressiveness. Overexpression of EMP3 in primary breast carcinoma is not associated with DNA methylation.
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Adult , Female , Humans , Middle Aged , Breast Neoplasms/genetics , Carcinoma/genetics , DNA Methylation , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Lymphatic Metastasis , Membrane Glycoproteins/genetics , Neoplasm Staging , RNA, Messenger/metabolism , Receptor, ErbB-2/genetics , Severity of Illness IndexABSTRACT
<p><b>OBJECTIVE</b>To study the feasibility of digalactosyl diglyceride (DGDG) , which was used as a new type of emulsifier to prepare submicro-emulsion of bay oil.</p><p><b>METHOD</b>Bay oil was employed as the model drug, emulsifer in oil method was used to prepare foremilk. Through single factor investigation and central composite design-response surface methodology (CCD-RSM) , we optimized the preparation technology and formula respectively. The stability of sub-microemulsion was studied.</p><p><b>RESULT</b>The optima technology was following: emulsifer in oil method was used to prepare foremilk, temp was 60 degrees C, the micro emulsion was prepared by two-step high pressure homogen method with that the pressure was 80 Pa, 10 times, micropore film was used to sterilize, filling and sealing at the preservation of nitrogen. The best formula was following: soybean oil was 1.1%, DGDG was 1.6%, and sodium oleate was 0. 16%. The particle size of three batch submicro-emulsions were from 168.0 to 169.3 nm; Zeta potential were from-25.53 to 24.90 mV, pH value were from 8.48 to 8.52. The deviation between measured value and predictive value was 1.8%. It was stable in high temperature and illumination.</p><p><b>CONCLUSION</b>DGDG can be used as the emulsifier of bay oil sub-microemulsion.</p>
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Drug Stability , Emulsifying Agents , Chemistry , Emulsions , Chemistry , Galactolipids , Chemistry , Plant Oils , Chemistry , TemperatureABSTRACT
Background and purpose:Curcumin is the major effective component of curcuma,curcumin has been noted to be able to selectively inhibit proliferation and induce apoptosis in tumor cells. Interferon-?(IFN-?) is one of the most important cytokines used in clinical treatment nowadays. This study was made to investigate the inhibitory effect of interferon-?(IFN-?)and curcumin on Raji cells (B-NHL) and discuss their mechanism.Methods:The variations of morphology of Raji cells were observed in culture medium after being treated by IFN-?(500,100,2000U/L) combined with various concentrations of curcumin (6.25,12.5,25?mol/L), cells were incubated with the compounds for variable times.The inhibitory ratio was measured by MTT assay, apoptosis was quantitated by flow cytometry(FCM) and the expressions of caspase6, caspase8 and caspase9 in Raji cells were detected by Western blot.Results:both IFN-? and curcumin could significantly induce apoptosis and inhibit the proliferation of Raji cells, synergistic effects were found if cells were treated by the combination of IFN-? and curcumin. The overexpressions of caspase6, caspase8 and caspase9 in Raji cells could be observed in a time-and dose-dependent manner.Conclusions:The combination of IFN-? and curcumin could synergistically inhibit proliferation and induce apoptosis, and its potential mechanism is probably associated with upregulating the expressions of caspase6, caspase8 and caspase9 in B-NHL Raji cell.
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In order to examine the strong anticancer action and low toxicity of Trichostatin A (TSA), the effect of TSA was examined on the growth inhibition, acetylation of histone H3 and apoptosis in HL-60 cells by employing MTT, immunocytochemical techniques, and Annexin-V-FITC/ PI assay. Our results showed that TSA could inhibit proliferation of HL- 60 cells in a time- and dose-dependent manner, and the IC50 at the 36th h was 100 ng/ml. The apoptosis-inducing effect of TSA on HL-60 cells was also time- and dose-dependent. But it didn't demonstrate apparent apoptosis induction in NPBMNCs within specific dose and time range. Both of the acetylation of histone H3 in HL-60 cells and NPBMNCs increased significantly (P0.05). It is concluded that TSA can inhibit growth and induce apoptosis of HL-60 cells in a time- and dose-dependent manner, and is able to selectively induce apoptosis in HL-60 cells but does not respond in NPBMNCs under the same conditions. The difference of TSA between HL-60 cells and NPBMNCs can't be explained by the regulation of histone acetylation.
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Acetylation , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , HL-60 Cells , Histone Deacetylases/antagonists & inhibitors , Histone Deacetylases/chemistry , Hydroxamic Acids/pharmacologyABSTRACT
In order to examine the strong anticancer action and low toxicity of Trichostatin A (TSA), the effect of TSA was examined on the growth inhibition, acetylation of histone H3 and apoptosis in HL-60 cells by employing MTT, immunocytochemical techniques, and Annexin-V-FITC/ PI assay. Our results showed that TSA could inhibit proliferation of HL- 60 cells in a time- and dose-dependent manner, and the IC50 at the 36th h was 100 ng/ml. The apoptosis-inducing effect of TSA on HL-60 cells was also time- and dose-dependent. But it didn't demonstrate apparent apoptosis induction in NPBMNCs within specific dose and time range. Both of the acetylation of histone H3 in HL-60 cells and NPBMNCs increased significantly (P<0.05) after treated with 100 ng/ml TSA for 4 h. However, there was no significant differences between the two groups (P>0.05). It is concluded that TSA can inhibit growth and induce apoptosis of HL-60 cells in a time- and dose-dependent manner, and is able to selectively induce apoptosis in HL-60 cells but does not respond in NPBMNCs under the same conditions. The difference of TSA between HL-60 cells and NPBMNCs can't be explained by the regulation of histone acetylation.
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Humans , Acetylation , Antineoplastic Agents , Pharmacology , Apoptosis , HL-60 Cells , Histone Deacetylase Inhibitors , Histone Deacetylases , Chemistry , Hydroxamic Acids , PharmacologyABSTRACT
0.05),but the expression of P300 decreased at intermedieate and high concentration(12.5,25,50 ?mol?L~(-1),P
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Objective To explore the classification of intracranial arachroid cysts(IAC) in CT cisternography(CTC) and its clinicalapplication.Methods 22 cases of IAC diagnosed by plain CT underwent CTC exminaton. IACs were classified into noncommnicatingintracranial arachnoid cyst (NCIAC) and commnicating intracranial arachnoid cyst (CIAC) by wheather or not filled with contrast media in cysts on CTC. NCIAC cases were selected and treated with neuroendoscopic fenestration.Results 15 cases of NCIAC were found by CTC examination. All the NCIAC patients had definite neurologic findings. Postoperatively, all the patients were improved or cured. Follow-upplain CT scan of 9 NCIAC cases showed the cysts were decreased markedly in size, most of the space around the cysts were replaced bynormal cerebral tissue.Conclusion (1)CTC is simple ,safe and specific for making a final diagnosis of IAC. IACs can be classified into CIAC and NCIAC by CTC findings.(2)Neurosurgical indication for IAC is NCIAC patients with symptoms.
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Aim To investigate the effect of Trichostatin A(T SA)on histone deacetylase (HDAC1) and P21 WAF1/CIP1,cyclin dependent ki nase inhibitor,in NB4 cells for exploring the underlying mechanism of TSA in an ti-leukemia.Methods The total proteins and P21 WAF1/CIP1 mRN A were extracted from acute promyelocytic leukemia NB4 cells treated with or wit hout TSA of different concentrations at different time points,Western blot anal ysis was performed to determine the level of HDAC1 and P21 WAF1/CIP1 protei n,respectively,and RT-PCR was performed to detect the level of P21 WAF1/CI P1 mRNA.Results (1)The level of HDAC1 was obviously inhibited by TSA,and had decreased at 4 hours at IC 50 and lasted for 48 h. The inhibi tion of HDAC1 was significant at the TSA concentration of 37.5 nmol?L -1 , but there was no difference between 75~300 nmol?L -1.(2)The levels of P21 WAF1/CIP1 mRNA and protein were up-regulated by TSA in dose-and ti me-dependent manner,and mRNA increased in 8 h,but the P21 WAF1/CIP1 prot ein was detected at 12 hours and lasted for 48 hours.Conclusion TSA could inhibit the level of HDAC1 and enhance the expression of P21 WAF1/CIP1 protein and mRNA,and the results suggest that inhibiting HDAC1 and increasin g P21 WAF1/CIP1 may be one of the possible mechanisms of anti-leukemia by TSA.
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AIM:To study the anti-tumor effect and mechanism of fusion vaccine on DCs and C6 glioma cells.METHODS: PEG was used to fuse DCs with C6 glioma cells.Immunofluorescence with GFAP-FITC was used to identify the DC/C6 fusion cells.Rat brain glioma models were made by stereotactic technique.After 5 days of inoculation of C6,107 fusion cells were injected through tail vein in group A.The same number of DCs and the same volume of PBS were used in group B and group C.The survival time of rats in these three groups was analyzed by Log-rank survival analysis.Tumor samples were checked by HE staining and immunohistochemical staining with CD8Mcab.RESULTS: Positive result of GFAP-FITC immunofluorescence was observed in DC/C6 fusion cells.The Log-rank survival analysis showed that statistically significant difference in group A was observed compared to that in group B and group C(P
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0.05).The ratio of TH~+ cells in the experimental group(7.38?0.84)% was higher than that in the control group(0.53?0.17)%,and there was significant statistical difference between the two group(P