Drug adulteration analysis based on complexation with cyclodextrin and metal ions using ion mobility spectrometry / 药物分析学报

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.

Clinical outcomes of redo median sternotomy on proximal aortic repair / 中华胸心血管外科杂志

Objective:To summarize the clinical outcomes and experience of redo median sternotomy on proximal aortic repair. Investigate the relationship between first operation and reoperation, reoperation indications, cardiopulmonary bypass strategy, intraoperative technical details, early and mid-term postoperative results.Methods:There were 28 patients underwent 29 times of redo median sternotomy on proximal aorta from April 2017 to December 2019. There were 23 males (79.3%) with an average age of (45.1±12.7) years (26-79 years), 15 Marfan syndrome (15/29, 51.7%) and 3 Behcet's disease (3/29, 10.3%). The primary operation included aortic valve or mitral valve replacement, Bentall procedure, ascending aortic replacement, simultaneous abdominal aortic replacement, Sun's procedure and coronary artery bypass grafting. The indications for reoperation were: aortic root aneurysm or coronary artery aneurysm, anastomotic leakage, perivalvular leakage due to inflammatory aortic disease, acute or chronic type A aortic dissection and aortic root abscess, aortic arch aneurysm. The surgical methods were Bentall, Cabrol, wheat, aortic valve sparing root replacement with replantation, anastomotic leakage repair, CABG, total arch replacement + stent elephant trunk implantation (Sun's procedure), ascending aorta to abdominal aorta bypass, abdominal aortic replacement.Results:One patient (3.4%) died in hospital because of severe postoperative pulmonary complications, consolidation of both lungs, ARDS and hypoxia. Postoperative low cardiac output was occurred in 2 cases (6.9%), 1 case was cured by ECMO, and 1 case died half a year after operation during follow up period. Re-exploration for postoperative hemorrhage was occurred in three cases (10.3%). Renal failure requires dialysis was 3 cases (10.3%), and transient paresis was 1 cases (3.4%), respectively. All of them were recovered before discharge. During the follow-up period, one patient died of multiple organ failure due to low cardiac output, and one patient underwent total thoracoabdominal aortic replacement. One patient underwent Cabrol for aneurysm of the coronary artery after Bentall procedure. One year later, type A dissection occurred again and Sun's procedure was performed through a median sternotomy.Conclusion:Reoperation of proximal aorta after cardiac and aortic surgery is safe and effective, with good short-term and medium-term results. Comprehensive preoperative evaluation, successful sternotomy, establishment of cardiopulmonary bypass and effective organ protection are the key to successful operation. Patients with aortic diseases, especially Marfan syndrome, are more likely to undergo reoperation. Close follow-up and timely reoperation are necessary to avoid aortic rupture. Sun's procedure is suitable for redo complex arch operation.

LIN28 coordinately promotes nucleolar/ribosomal functions and represses the 2C-like transcriptional program in pluripotent stem cells

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.

Application of aortic valve sparing root replacement with reimplantation technique / 中华胸心血管外科杂志

Objective:To summarize our clinical experience in the treatment of aortic root aneurysm by aortic valve sparing root replacement.Methods:From May 2017 to October 2019, a total of 20 patients with aortic root aneurysm underwent aortic valve sparing root replacement by reimplantation method. There were 17 males and 3 females, with an average age of(35.6±15.8) years(12-63 years). There were 11 cases of Marfan syndrome, 5 cases of bicuspid aortic valve, and 1 case of redo operation. The preoperative diameter of ascending aorta was(40.6±9.7)mm, the diameter of aortic sinus was(52.2±9.2)mm, and the diameter of aortic valve ring was(27.1±3.6)mm. There were 10 cases of no or mild regurgitation, 5 cases of moderate regurgitation and 5 cases of severe regurgitation. In the whole group of patients, the root replacement of aortic valve was retained by reimplantation, and the artificial graft were selected as: 26, 28 and 30mm straight vessels, 1, 3 and 6 cases, respectively, 26 and 28mm artificial graft with valsalva sinus, 4 and 6 cases, respectively. During the operation, aortic valve cusp repair was performed in 6 cases, such as plication of the free margin( 4 cases), decalcification(1 case) and raphe release(1 case).Results:None of the patients died in hospital or underwent rethoracotomy for hemostasis. During the operation, the duration of CPB time was(171.0±25.6) minutes and the duration of cross-clamp time was(134.0±23.2) minutes. There were 12 cases of aortic valve regurgitation and 8 cases of mild regurgitation. The mean follow-up was(15.1±9.8) months(4-33 months). During the follow-up period, there were 2 cases with moderate aortic regurgitation no need reoperation, while the rest of the patients had no or mild regurgitation. There are no patients undergoing reoperation. During the follow-up, 1 patient suffered coronary artery embolism in left circumflex artery and recovered after medicine treatment.Conclusion:Reimplantation with aortic valve sparing root replacement is safe and effective in the treatment of aortic root aneurysm, and the early and mid-term follow-up results are satisfactory, which can avoid anticoagulation-related complications and is suitable for young patients.

Expression and clinical significance of soluble intercellular adhesion molecule 1, soluble P-selectin and coagulation function in patients with infective endocarditis / 中国综合临床

Objective:To investigate the expression and significance of T helper cell 17 (Th17), soluble intercellular adhesion molecule-1 (sICAM-1) and coagulation function in patients with infectious endocarditis(IE).Methods:From December 2016 to December 2018, IE patients in Beijing Anzhen Hospital Affiliated to Capital Medical University who met the inclusion criteria were selected for cardiac surgery to analyze prospectively, 38 IE patients were selected as the observation group, and 30 healthy people were selected as the control group.The concentrations of serum Th17 related factors (IL-1β, IL-6, IL-17 and IL-21), sICAM-1 and coagulation index(P selectin(sP-SLT)) were measured by enzyme-linked immunosorbent assay(ELISA) and the difference between the two groups were statistically analyzed.Results:The concentrations of serum IL-1β, IL-6, IL-17 and IL-21((29.88±6.49), (14.89±3.31), (21.89±3.01), (563.26±67.36) ng/L) in the observation group were significantly higher than those in the control group((16.56±4.11), (7.52±2.34), (12.91±1.01), (423.38±56.49) ng/L)(all P<0.05). The level of serum sICAM-1 and sP-SLT ((1 247.57(581.39, 1 794.66) μg/L, (60.29±6.61) mg/L)in the observation group were significantly higher than those in the control group((837.28(405.68, 954.47) μg/L, (27.37±5.56) mg/L), and the difference was statistically significant( Z=12.37, t=22.30, all P<0.05). The level of serum IL-1β, IL-6, IL-17 and IL-21 in patients with postoperative infective endocarditis((16.19±4.07), (7.73±2.40), (13.83±0.94), (425.33±52.12) ng/L) were significantly lower than those before operation((29.88±6.49), (14.89±2.31), (21.89±3.01), (563.26±67.36) ng/L), and the differences were statistically significant(t values were 11.02, 13.25, 15.76, 9.98, all P<0.05). The levels of sICAM-1 and sP-SLT1 in patients with postoperative infective endocarditis((901.46(472.15, 1276.58) μg/L, (30.70±5.31) mg/L) were significantly lower than those before operation((1 057.26±463.06) μg/L, (60.29±6.61) mg/L)and the differences were statistically significant( Z=11.16, t=21.51, P<0.05). Conclusion:Th17 related factors, sICAM-1 and sP-SLT were highly expressed in IE patients, and the concentrations of these factors decreased after operation, suggesting that the above factors may be used as related factors for the diagnosis and prognosis of IE patients.

Surgical treatment of Stanford A intramural hematoma / 中华胸心血管外科杂志

Objective@#To summarize experience and result in surgical treatment of Stanford type A intramural hematoma.@*Methods@#60 patients with Stanford type A intramural hematoma were operated from February 2015 to August 2017. Surgery was indicated in complicated cases with penetrating ulcer or ulcer-like projection in ascending aorta, maximum aorta diameter≥50 mm, progressive maximum aortic wall thickness≥10 mm, pericardial or pleural effusion, persistent or recurrent pain. Aortic valve regurgitation. In our group, 46 patients recieved ascending aorta replacement+ Sun' s procedure. 6 patients recieved Bentall+ Sun' s procedure. 4 patients recieved asceding aorta+ hemiarch replacement. 2 patients recieved Bentall+ hemiarch replacement. 2 patients recieved asceding aorta replacement.@*Results@#In the whole group, there was 1(1.7%)operative death because of multiple organ failure after operation. Hyoxemiaoccured in 5(8.3%) patients, 2(3.3%) patients occurred new renal failure and required CRRT treatment, cerebrovascular complication occurred in 1 (1.7%)patient, re-sternotomy due to bleeeding occured in 1 (1.7%)patient and paraplegia occured in 1(1.7%) patient after operation. but they recoved quickly after proper treatment. During follow up period, there were 4 cases need reintervention, including TEVAR for type B dissection at 3 months and distal stent-graft new entry at 1 year. Two other reinterventions were performed for endoleak by interventional occlusion. During the follow-up, hematoma absorption rates after treatment 1、3 and 6 months were 68.6%, 84.7% and 94.8%.@*Conclusion@#Given the dynamic evolution of acute type A IMH pre-operative accurate indications and the proper surgical strategy maybe the keys for success.

Surgical treatment of Stanford A intramural hematoma / 中华胸心血管外科杂志

Objective To summarize experience and result in surgical treatment of Stanford type A intramural hematoma.Methods 60 patients with Stanford type A intramural hematoma were operated from February 2015 to August 2017.Surgery was indicated in complicated cases with penetrating ulcer or ulcer-like projection in ascending aorta,maximum aorta diameter≥50 mm,progressive maximum aortic wall thickness≥i0 mm,pericardial or pleural effusion,persistent or recurrent pain.Aortic valve regurgitation.In our group,46 patients recieved ascending aorta replacement + Sun's procedure.6 patients recieved Bentall + Sun's procedure.4 patients recieved asceding aorta + hemiarch replacement.2 patients recieved Bentall + hemiarch replacement.2 patients recieved asceding aorta replacement.Results In the whole group,there was 1 (1.7％) operative death because of multiple organ failure after operation.Hyoxemiaoccured in 5(8.3％) patients,2(3.3％) patients occurred new renal failure and required CRRT treatment,cerebrovascular complication occurred in 1 (1.7％)patient,re-sternotomy due to bleeeding occured in 1 (1.7％) patient and paraplegia occured in 1 (1.7％) patient after operation.but they recoved quickly after proper treatment.During follow up period,there were 4 cases need reintervention,including TEVAR for type B dissection at 3 months and distal stent-graft new entry at 1 year.Two other reinterventions were performed for endoleak by interventional occlusion.During the follow-up,hematoma absorption rates after treatment 1、3 and 6 months were 68.6％,84.7％ and 94.8％.Conclusion Given the dynamic evolution of acute type A IMH pre-operative accurate indications and the proper surgical strategy maybe the keys for success.

DavidⅠ versus Bentall in aortic root disease / 中华胸心血管外科杂志

Objective To evaluate the safety and efficiency in aortic root disease .Methods From April 2017 to April 2018,46 cases of aortic root disease accepted DavidⅠ[20 cases, 15 males and 5 females, aged(39.6 ±15.8)years, aortic root diameter was(58.3 ±4.4)mm] or Bentall[26 cases, 22 males and 4 females, aged(50.8 ±12.6)years,aortic root diam-eter was(59.5 ±5.0)mm], the data in the peri-operation and heart function in recent period after operation.Results No mortality was observed in the study.Morbidity occurred in both group was comparable.Mean cross-clamp time(129.5 ±28.6) min vs.(94.3 ±35.3)min(P<0.05).Blood transfusion(342.0 ±476.4)ml vs.(330.8 ±651.3)ml(P>0.05).ICU sta-ying time(1.0 ±0.2)day vs.(1.1 ±0.3)day(P>0.05).At the latest visit(10.5 ±6.8)months in David Ⅰ, no obviously regurgitation of aortic valve were observed 0.75 ±0.44 vs 1.0 ±1.3(P>0.05).Conclusion Except for the prolonged cross-clamp time, David Ⅰ is safely and effective in aortic root disease compared with Bentall in peri-operative period .The long term results need further follow-up.

MicroRNA-150 inhibits osteosarcoma cell proliferation by targeting RUNX2 gene / 中南大学学报(医学版)

To investigate the microRNA (miR)-150 expression level in human osteosarcoma cell lines (Saos-2, MG-63) and its function in cell proliferation, and to explore the potential molecular mechanisms. 
 Methods: MiR-150 expression levels in human osteosarcoma cell lines (Saos-2, MG-63) and normal osteoblast cell line (NHOst) were detected by relative quantitative real-time PCR (qRT-PCR). MiR-150 was overexpressed in Saos-2 and MG-63 cells by lentivirus infection. Cell proliferation rates were monitored by MTS assay. RUNX2 and β-actin protein levels were examined by Western blot. Inhibitory effect of miR-150 on binding RUNX2 3'-UTR was detected by Dual-Luciferase assay.
 Results: MiR-150 expression level is lower in human osteosarcoma cell lines (Saos-2, MG-63) compared to the normal osteoblast cell line (NHOst) (0.23±0.02 and 0.32±0.03 vs 1.00±0.02), which showed statistical significance (P<0.01). After lentivirus infection, miR-150 level increased in Saos-2 (P<0.01) and MG-63 cells (P<0.01). Overexpression of miR-150 decreased cell proliferation and RUNX2 protein level in Saos-2 and MG-63 cells. The binding of miR-150 to RUNX2 3'-UTR decreased luciferase activity by 69% in Saos-2 cells (P<0.05) and 59% in MG-63 cells (P<0.05). Administration of exogenous RUNX2 recovered the cell proliferation in miR-150 overexpressed Saos-2 and MG-63 cell lines (P<0.01).
 Conclusion: MiR-150 inhibites proliferation in human osteosarcoma cell lines through binding to RUNX2 3'-UTR, resulting in the reducion of RUNX2 protein level.

Advances in personalized diagnosis and treatment of treatable genetic diseases of pediatric neurology in precision medicine period / 中华实用儿科临床杂志

The development of precision medicine in 21st century has accelerated a new area of medicine,bringing a precise project of diagnosis and treatment.The new techniques for genetic diseases including next generation sequencing and copy number variation detection technology have facilitated the diagnosis and treatment of genetic and rare diseases in children's neural system,providing a new directed therapies especially for creatine deficiency syndromes,pyridoxine dependent epilepsy,glucose transporter type 1 deficiency syndrome,malignant migrating partial seizures in infancy,GRIN2A-related early-onset epileptic encephalopathy,KCNQ2-related epilepsies.With the new area of precision medicine arrival,an epoch-making revolution for the diagnosis and treatment of genetic and rare diseases in children's neural system is coming towards us.

Relationship of CYP2 C19 Gene Polymorphisms and Clopidogrel Resistance in the Patients with PCI in Chi-nese Han Population / 中国药师

Objective:To investigate the relationship of CYP2C19 gene polymorphisms and clopidogrel resistance in the patients with coronary atherosclerotic heart disease ( CAHD) accepted percutaneous coronary intervention ( PCI) in Chinese Han population from north Sichuan. Methods:The patients with CAHD undergoing PCI were recruited. The fluorescence in situ hybridization ( FISH) technology was used to detect the CYP2C19 gene polymorphisms in all the patients. According to the different genotypes, the patients were divided into different groups. The platelet maximum aggregation rate ( MAP) induced by ADP was detected before and after the administration of clopidogrel. Results:The 110 patients were divided into three groups:52(47. 3%) patients were divided into the fast metabolism group, 42(38. 1%) patients were in the moderate metabolism group and 16(14. 6%) patients were in the slow metab-olism group. Before the administration, there was no significant difference in the basic values of the platelet aggregation rate among the groups with various metabolism type (P=0. 873). In 24 hours after the administration of 300mg clopidogrel, there was notable differ-ence in the platelet aggregation rate (17. 74% ± 5. 87% vs 21. 44% ± 8. 71% vs 27. 05% ± 8. 83%, P=0. 044) and the decrease de-gree (20. 08% ± 5. 94% vs 18. 87% ± 4. 72% vs 11. 54% ± 2. 94%, P=0. 01) among the three groups. The moderate metabolism group and slow metabolism group had higher MAP with lower decrease degree than the fast metabolism group. Totally 21 patients (19. 1%)were with CR, and among them, 2 patients (3. 8%) were in the fast metabolism group,12 patients (28. 6%) in the moder-ate metabolism group and 7 ones (43. 8%) in the slow metabolism group, and the difference of CR distribution among the three groups was significant (P<0. 001). The moderate metabolism group and slow metabolism group were more likely to have clopidogrel resist-ance, especially the slow metabolism group. Conclusion: There is a certain relationship of CYP2C19 gene polymorphisms and clopi-dogrel resistance in the patients with CAHD accepted PCI in Chinese Han population from north Sichuan, and those with slow metabo-lism genotype are more likely to have clopidogrel resistance with reduced efficacy.

Clinical features and gene mutations analysis in 62 children with early - onset epileptic encephalopathy of un-known causes / 中华实用儿科临床杂志

Objective To study the clinical features and gene mutations of early - onset epileptic encephalo-pathy(EOEE)of unknown causes and to identify pathogenic mutations of EOEE by next generation sequencing. Methods The clinical data of 62 cases diagnosed with unexplained EOEE between June 2013 and June 2015 were ob-tained and analyzed. Specimens were collected from the selected children and their parents. Next generation sequencing was used to detect epilepsy - related genes,and Sanger sequencing was performed to verify the results and confirm the source of the parents,further to identify suspected pathogenic mutations of EOEE. Results Among 62 cases with unex-plained EOEE,37 cases(61% )were diagnosed as non - specific EOEE,17 cases(27% )with West syndrome,6 ca-ses(10% )with Dravet syndrome,1 case(1% )with Ohtahara syndrome,1 case(1% )with early myoclonic epileptic encephalopathy. The pathogenic mutations were not detected among 17 cases with West syndrome and the early myoclonic epileptic encephalopathy. Among 37 cases with non - specific EOEE,suspected pathogenic mutations were detected in 7 cases. Three cases of missense mutations for PCDH19 gene,1 case of frame - shift mutation and 1 case of splice site mutation for CDKL5 gene,1 case of denovo nonsense mutation for KCNQ2 gene,and 1 case of missense muta-tion for GRIN2A gene were detected. Among 6 children with Dravet syndrome,2 cases of frame - shift mutations and 1 case of missense mutation for SCN1A gene were detected,of which 2 cases were of frame - shift mutations,1 case was denovo mutation,1 case of missense mutation for SCN1A gene and 1 case of missense mutation for SCN1A combined with SCN9A gene were detected. One case of denovo nonsense mutation for STXBP1 gene was detected. After treatment, 22 cases with clinical seizures were under control,and 40 cases were out of control. Conclusions The clinical pheno-types for children with unexplained EOEE were varied. SCN1A,SCN9A,STXBP1,PCDH19,CDKL5,KCNQ2 and GRIN2A genes detected in China are in accordance with those reported internationally and some gene sites are denovo mutations which have not been reported. The SCN9A gene may be the new pathogenic mutation for Dravet syndrome. And the KCNQ2 gene nonsense mutation may be the lethal mutation.

Empirical Study on the Application of Drug Utilization Evaluation Model in Special Rectification Activities of Antibacterial Drug / 中国药师

Objective:To investigate the application of drug utilization evaluation( DUE) as a kind of clinical pharmacy work model in the antibacterial drug special rectification. Methods: Following the steps of DUE schedule,retrospective method was conducted to collect the data of the use of vancomycin in one institution and the model of clinical drug use was improved by the evaluation result. Re-sults:The rationality of vancomycin use was improved in the institution. The index of drug use reasons and key disease course indica-tors was improved significantly. The qualification rate of indications and drug indications was increased from 79. 5% to 95. 0%,and the qualification rate of antibacterial drugs classification management was increased from 63. 3% to 92. 7%. The qualification rate of dosing frequency was increased from 72. 5% to 96. 0%. Conclusion:As a program for continual improvement of new clinical pharmacy work mode and medical care quality,the mode plays an important role in the institution and improves the rational use of vancomycin.