Objective To explore the pharmacodynamic substances of Simiao Wan for the treatment of hyperuricemia and gout.Methods The pharmacological model of hyperuricemia was established.The chemical components in vivo and in vitro of Simiao Wan were analyzed by UPLC-Q-Exactive-MS.Based on the components absorbed in blood,the"active ingredient-target-pathway"network of Simiao Wan for regulating hyperuricemia and gout was constructed by network pharmacology method.The key ingredients were used for molecular docking with key targets[uricogenase(XDH),uric acid transporter(ABCG2,GLUT9,OAT1,URAT1)and inflammatory targets(PTGS2,TLR2,TLR4)]of hyperuricemia and gout.Finally,experimental verification was conducted according to the results of molecular docking.Our aim is to identify the key pharmacodynamic substances of Simiao Wan for the treatment of hyperuricemia and gout.Results Eighty-nine components of Simiao Wan were identified by UPLC-Q-Exactive-MS analysis,including 74 components absorbed in blood,which were confirmed as candidate ingredients.Network pharmacology was used to constructed"components absorbed in blood-target-pathway"network,and components absorbed in blood were matched with 116 targets of hyperuricemia and 173 targets of gout.It is involved in the regulation of biological processes,such as glucose and lipid metabolism,oxidative stress,inflammatory response,ERK1 and ERK2 cascade,MAPK cascade,PI3K signal transduction.Moreover,Simiao Wan plays a role in regulating the network of hyperuricemia and gout through regulating blood lipids and atherosclerosis,apoptosis,AGE-RAGE,TNF,PI3K-Akt,MAPK,TLRs,JAK-STAT,NF-κB and other signaling pathways.Molecular docking studies showed that berberine,phellodendrine,magnoflorine,jatrorrhizine,palmatine,obacunone,limonin,atractylodin,taxifolin,atractylenolide Ⅲ and β-ecdysterone had good affinity with uric acid synthase,uric acid transporter and inflammatory targets.Western Blot test showed that taxifolin negatively regulates the expression of URAT1.The above-mentioned compounds were the main pharmacodynamic substances of Simiao Wan for the treatment of hyperuricemia and gout.Conclusion This article describes the main pharmacodynamic substances of Simiao Wan in the regulation of hyperuricemia and gout,which can provides a scientific basis for the clinical application,improvement in quality evaluation and standard of Simiao Wan.

Drastic surges in intracellular reactive oxygen species (ROS) induce cell apoptosis, while most chemotherapy drugs lead to the accumulation of ROS. Here, we constructed an organic compound, arsenical N-‍(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide (AAZ2), which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer (GC). Mechanistically, by targeting pyruvate dehydrogenase kinase 1 (PDK1), AAZ2 caused metabolism alteration and the imbalance of redox homeostasis, followed by the inhibition of phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and leading to the activation of B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax)/caspase-9 (Cas9)/Cas3 cascades. Importantly, our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft. Overall, our data suggested that AAZ2 could contribute to metabolic abnormalities, leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.
Humans ; Signal Transduction ; Stomach Neoplasms/drug therapy* ; Reactive Oxygen Species/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2 ; Cell Line, Tumor

Objective To investigate the perioperative risk factors associated with prognoses of patients with acute ischemic stroke accepted mechanical thrombectomy under general anesthesia.Methods The clinical data of 108 patients with acute ischemic stroke,admitted to and accepted mechanical thrombectomy under general anesthesia in our hospital from January l,2016 to October 31,2018,were collected.According to modified Rankin scale (mRS) scores 90 d after surgery,patients were divided into good prognosis group (mRS scores ≤2) and poor prognosis group (mRS scores ≥3).Univariate analysis was used to compare the general data (age,gender,body mass index,and underlying diseases) and perioperative conditions (immediate heart rate,systolic and diastolic blood pressures immediately after admission,operative time,and anesthesia time) between the two groups of patients.Multivariate Logistic regression analysis was used to identify the perioperative risk factors influencing the prognoses of patients with acute ischemic stroke accepted mechanical thrombectomy.Results Among the 108 patients,65 had good prognosis and 43 had poor prognosis.Univariate analysis showed that there was no significant difference in general data between the two groups (P＞0.05),but there were significant differences in heart rate immediately after admission,National Institutes of Health Stroke Scale (NIHSS) scores immediately after admission and 3 d after operation,maximum hemoglobin and blood glucose values from immediately after admission to 3rd d of operation,and thrombolysis in myocardial infarction (TIMI) blood flow classification (P＜0.05).Multivariate Logistic regression analysis showed that heartrate immediately after admission (OR=1.035,95％CI:1.002-1.067,P=0.037) and NIHSS scores 3 d after operation (OR=1.153,95％CI:1.016-1.272,P=0.030) were the perioperative risk factors influencing the prognoses of patients with acute ischemic stroke accepted mechanical thrombectomy.Conclusion For patients with acute ischemic stroke who have rapid heart rate immediately after admission and high NIHSS scores 3 d after mechanical thrombectomy,possibility of poor prognosis should be noticed.

Objective : To research the feasibility and preliminary clinical effect of an implant-supported fixed bridge based on interactions with the posterior interocclusal space deficiency. Methods: Four patients with multiple implant-supported fixed-bridge restorations for interocclusal space deficiency in posterior teeth were included in this study. The 8 total implant sites had an average interocclusal space size of 3.3 mm. Two abutments with an undercut area were performed, the fixed bridge was placed by rotating it without a common path of insertion, and the abutment screw was then tightened. In the production process, the interaction retention concept and methods were fully communicated to the technician. The abutments and bridges on the implants were placed, and the clinical effect was observed. Results: The prosthesis was fixed well and presented appropriate functioning. At the 3-month and 18-month follow-up examination, the prosthesis and abutments were not loose, and the abutments did not release or break. No swelling or tenderness was observed in the margin of the implants. Conclusion The interaction retention is a good method of resolving the problem of interocclusal space deficiencies in the posterior teeth.

Objective To discuss the application value of modified Hodge test(MHT) for screening carbapenemase-producing Enterobacteriaceae.Methods The 24 Enterobacteriaceae reduced susceptibility to carbapenems were detected by MHT.At the same time,polymerase chain reaction(PCR) was used to detect carbapenemase genes of KPC,NDM,IMP,SIM and VIM.PCR products were sequenced and the results were compared with the sequences of Gen Bank database.Comprehensive analysis the application value of MHT and PCR to detect carbapenemase.Results Among these 24 strains,13 stains appeared to produce carbapenemase by MHT,5 positive strains were found to carry carbapenemase genes by PCR.By comparing with the sequences of Gen Bank database 1 strain were confirmed to KPC-2 and 4 strains were confirmed to IMP-4.We found that 4 strains of Enterobacteriaceae,detected carbapenemase by MHT and PCR at the same time.9 strains of MHT were positive,but we couldn′t detect the carbapenemase genes.1 strain of MHT was negative,but carbapenemase gene was found in the strain.Conclusion The value of MHT to screen carbapenemase-producing Enterobacteriaceae is necessary to further study.

Objective To observe the histological effect of acellular dermal matrix(ADM)on insufficiency in guide keratinized tissue regeneration. Methods 6 cases of single anterior tooth implantation in the hospital in 2016 were included in the study. 3 cases were treated with immediate tooth extraction and implantation. Bone substitution materials were grafted in the space between the tooth extraction socket and the implants. The keratin-ized tissue dehiscence was covered by double layers of acellular dermal matrix membrane(Heal-All?,ZH-BIO, China),which was fixed to the adjacent soft tissue by suturing. Another 3 cases were routinely treated with delayed implantation of single anterior tooth. All the cases were subject to harvesting of the cover soft tissues of implants with a punch 4 months later. The new grown soft tissues were histologically observed. Results All cases were sur-vived. The new grown keratinized tissues were observed. Conclusion Acellular dermal matrix can guide the aug-mentation of keratinized tissues.

Objective : To evaluate the clinical outcomes of custom all-ceramic crown fabricated in zirconia based on CT data in maxillary anterior implant tooth. Methods: 15 patients with single anterior tooth missing were applied to this treatment. Crown remodeling according to the opposite tooth, fabrication of the all-ceramic crown was finished based on the data capture via CT scan. The observation period extended 2-7 years on average. Results: The survival and success rates were 100%. Soft tissue was stabile in follow up photos. All of the patients were satisfied with the restorations. Conclusion The custom all-ceramic crown based on CT data showed good interface friendship with both of the hard and soft tissues and the aesthetics result is predictable.

OBJECTIVETo investigate the factors which may influence the imatinib plasma concentration in Chinese patients with gastrointestinal stromal tumor(GIST), and to illuminate the significance of monitoring imatinib plasma concentration in adjuvant therapy for patients with GIST.

METHODSA cross-sectional study with 60 GIST patients who accepted the imatinib therapy after surgery was conducted. They were respectively administrated in 10 domestic hospitals from December 2014 to April 2016, including The First Affiliated Hospital of Nanjing Medical University(n=28), The Affiliated Hospital of Nantong University(n=9), The Affiliated Hospital of Xuzhou Medical College(n=6), Nanjing Drum Tower Hospital(n=5), The Second Affiliated Hospital of Nanjing Medical University (n=2), Jingling Hospital (n=2), The Second People's Hospital of Lianyungang(n=2), Shandong Provincial Hospital(n=2), Jiangsu Province Tumor Hospital(n=2), and The First Affiliated Hospital of Zhejiang University(n=2). Some specific time points for collecting blood sample before and after taking imatinib were determined, then liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used for monitoring imatinib plasma concentration in patients with GIST. Linear regression analysis was used for the correlation analysis of imatinib plasma concentration with dosage, clinicopathologic feature and side effect.

RESULTSPatients who could not tolerate 400 mg imatinib per day(n=3) received 300 mg per day. There was no significant difference in imatinib plasma concentration between patients with 300 mg and those with 400 mg imatinib(n=53)(P=0.527). However, the imatinib plasma concentration in patients with 600 mg imatinib per day (n=4) was significantly higher as compared to those with 400 mg(P=0.000). Linear regression analysis indicated a negative correlation between the imatinib plasma concentration in patients with 400mg imatinib per day for 90 days continuously and body surface area(R=0.074, P=0.035), but no significant correlations of with age, creatinine clearance and serum albumin concentration were observed (all P>0.05). The differences in imatinib plasma concentration were not statistically significant between patients of different gender and those taking proton-pump inhibitor (PPI) or not (both P>0.05). Difference in imatinib plasma concentration between patients with different surgery was significant (P=0.026). Compared to patients who underwent wedge resection, enterectomy and other surgeries, the imatinib plasma concentration of patients with subtotal gastrectomy or total gastrectomy decreased significantly (all P<0.05). After 90 days of taking imatinib continuously, linear regression analysis revealed a negative correlation between imatinib plasma concentration in patients with 400 mg imatinib per day and white blood cell count (R=0.103, P=0.013), and a positive correlation with serum alanine aminotransferase (ALT) concentration (R=0.076, P=0.033).

CONCLUSIONSThe imatinib plasma concentration in patients with larger body surface area, subtotal gastrectomy or total gastrectomy may be lower. For these patients, dosage of imatinib should be considered to increase in order to achieve effective plasma concentration. Excessive imatinib plasma concentration can result in some side effects, such as decrease of white blood cells and liver damage. Therefore, it is significant for receiving optimal clinical therapeutic efficacy to monitor imatinib plasma concentration, adjust imatinib dosage timely and keep imatinib plasma concentration in effective and safe range.

Adult ; Antineoplastic Agents ; administration & dosage ; pharmacokinetics ; Benzamides ; Combined Modality Therapy ; Cross-Sectional Studies ; Female ; Gastrectomy ; Gastrointestinal Stromal Tumors ; drug therapy ; surgery ; Humans ; Imatinib Mesylate ; administration & dosage ; pharmacokinetics ; Male ; Middle Aged ; Piperazines ; Pyrimidines ; Tandem Mass Spectrometry

Objective To investigate the SCCmec types of clinically isolated methicillin‐resistant Staphylococcus epidermidis (M RSE) .Methods Eighty‐four strains of clinically isolated Staphylococcus epidermidis identified by the fully automatic microbio‐logical identification system were collected and performed the MRSE identification by PCR for amplifying esp and mecA genes and SCCmec typing .Its distribution characteristics were analyzed .Results Esp gene was amplified in 84 strains and the detection rate of mecA was 76 .19% (64/84) ,in which the MRSE detection rates in blood ,sputum ,urine and wound secretion were 76 .8% , 68 .8% ,100% and 71 .4% respectively .The multiple PCR amplification displayed that among 64 strains of MRSE ,19 strains were SCCmec simple type ,in which 19 strains were SCCmec type Ⅰ and 3 strains were SCCmec type Ⅲ ;42 strains were SCCmec mixed type ,in which 2 strains were SCCmec mixed type Ⅰ and Ⅱ ,14 strains were SCCmec mixed type Ⅰ and Ⅲ ,12 strains were SCCmec mixed type Ⅰ ,Ⅱ and Ⅲ ,5 strains were SCCmec mixed type Ⅱ and Ⅲ ,a strains were and SCCmec mixed type Ⅲ and Ⅳ .Conclu‐sion The SCCmec type in clinically isolated MRSE shows obvious diversity and its majority is SCCmec mixed type .

Objective To construct mutant strains of methicillin resistant Staphylococcus epidermi-dis (MRSE) with psm-mec gene deletion and to investigate the function of psm-mec gene.Methods The drug sensitivity test and DNA sequence analysis were performed to screen out the tetracycline and chloram -phenicol sensitive clinical strains of MRSE , whose upstream and downstream sequences of psm-mec gene were identical to those of the Staphylococcus epidermidis reference strain RP62A.The recombinant plasmid pBT2-Δpsm-mec was constructed by using the fusion PCR and a temperature sensitive shuttle plasmid .After being identified , the plasmid was transformed into the Staphylococcus aureus RN4220 strain by electropora-tion, and then transformed into the selected clinical isolates of MRSE .The mutant strains of MRSE with psm-mec deletion were screened out and identified after homologous recombination .The differences in biofilm formation between the mutant and wild-type strains were analyzed for further elucidation the relationships be-tween the psm-mec gene and biofilm formation in MRSE strains .Results Three clinical MRSE isolates for the construction of mutant strains with psm-mec gene deletion were screened out and identified by using drug sensitivity test and sequence alignment analysis .The mutants constructed via homogenous recombination were screened out and identified .Compared with the corresponding wild-type strains, the three mutants with psm-mec gene deletion showed significantly decreased ability of biofilm formation , demonstrating that the psm-mec genes strains induced the biofilm formation of MRSE .Conclusion The Δpsm-mec mutant strains were successfully constructed .The psm-mec gene played an important role in the biofilm formation of Staphy-lococcus epidermdis.