Design and development of 6-hydrazinonicotinyl-fatty acid-mimetic 99mTc-complex as a potential myocardial imaging agent

Abstract The goal of this work is to identify new fatty acid-mimetic 99mTc-complexes to be used as myocardial imaging agents that allow studying heart abnormalities in high-risk patients. In this sense, we designed a fatty acid-mimetic substructure including an amide moiety that, among other properties, could improve myocardial residence time. A diamide with a chain length of 15 atoms and porting a 6-hydrazinonicotinyl (HYNIC) chelator, and an analog with a short carbon-chain, were prepared with convergent organic synthetic procedures and radiolabeled with 99mTc using tricine as the sole coligand. The in vivo proofs of concept were performed using healthy mice. The new 99mTc-complexes were obtained with adequate radiochemical purity. The lipophilicities were in agreement with the length of the chains. While both 99mTc-complexes showed uptake in the myocardial muscle, the designed radiopharmaceutical with the longest chain length had preferential target-uptake and target-retention compared to other complexes described in the bibliography. Further studies, involving imaging assays, synthetic modifications, and assay of new coligands for 99mTc-HYNIC complexes, are currently ongoing.

Qualitative and Quantitative Analysis of Five Indoles or Indazole Amide Synthetic Cannabinoids in Suspected E-Cigarette Oil by GC-MS / 法医学杂志

OBJECTIVES@#To establish the GC-MS qualitative and quantitative analysis methods for the synthetic cannabinoids, its main matrix and additives in suspicious electronic cigarette (e-cigarette) oil samples.@*METHODS@#The e-cigarette oil samples were analyzed by GC-MS after diluted with methanol. Synthetic cannabinoids, its main matrix and additives in e-cigarette oil samples were qualitatively analyzed by the characteristic fragment ions and retention time. The synthetic cannabinoids were quantitatively analyzed by using the selective ion monitoring mode.@*RESULTS@#The linear range of each compound in GC-MS quantitative method was 0.025-1 mg/mL, the matrix recovery rate was 94%-103%, the intra-day precision relative standard deviations (RSD) was less than 2.5%, and inter-day precision RSD was less than 4.0%. Five indoles or indazole amide synthetic cannabinoids were detected in 25 e-cigarette samples. The main matrixes of e-cigarette samples were propylene glycol and glycerol. Additives such as N,2,3-trimethyl-2-isopropyl butanamide (WS-23), glycerol triacetate and nicotine were detected in some samples. The content range of synthetic cannabinoids in 25 e-cigarette samples was 0.05%-2.74%.@*CONCLUSIONS@#The GC-MS method for synthesizing cannabinoid, matrix and additive in e-cigarette oil samples has good selectivity, high resolution, low detection limit, and can be used for simultaneous qualitative and quantitative analysis of multiple components; The explored fragment ion fragmentation mechanism of the electron bombardment ion source of indole or indoxamide compounds helps to identify such substances or other compounds with similar structures in cases.

Design, synthesis and biological activity of DB02 amino acid derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitors / 药学学报

To improve the stability of amino acid ester derivatives of DB02, a series of 24 amide derivatives of DB02 amino acids as non-nucleoside HIV-1 reverse transcriptase inhibitor were designed and synthesized based on bioisosterism by replacing amino acid ester scaffold with more stable amide bond. The anti-HIV-1 activity of these compounds was evaluated by MTT assay and counting the number of syncytia. Most of the target compounds showed a potential anti-HIV-1 activity, among which compounds 2d, 2i, 2l, 2s, and 2w had better antiviral effect than lead compound DB02, with a therapeutic index > 1 000.00. Finally, the structure-activity relationship of these compounds was discussed, which provided new ideas for the further development of DB02 derivatives.

Research progress of pharmacological action and mechanism of piperine / 中国药房

Piperine is a kind of amide alkaloids presenting in Piper nigrum L.，which has the pharmacological action such as protecting cardiovascular system ，regulating glucose and lipid metabolism ，anti-tumor，improving nervous system diseases ， anti-inflammation and so on. This paper summarized the pharmacological action and mechanisms of piperine in recent years and found that piperine ，as the main active ingredient of P. nigrum ，could protect the cardiovascular system by reducing inflammation and oxidative stress ；improve mitochondrial function through anti-inflammatory and antioxidant effects ，thereby regulate glucose and lipid metabolism ；play an anti-tumor role by mediating the signaling pathways of Wnt/β-catenin，NF-κB/Nrf-2/KeAP-1/HO-1， PI3K/Akt，TGF-β1/Smad2/ERK1/2；improve neurological diseases by inhibiting autophagy ，relieving inflammation ，improving antioxidant，inhibiting neuronal apoptosis and regulating the expression of related proteins in neurons ；play an anti-inflammatory effect by inhibiting the activity of NF-κB and other signaling pathways and reducing the expression of inflammation-related proteins. However，the mechanism of action of piperine is not perfect ，and most of the studies have been confined to the pharmacological level or a certain signaling pathway and a certain target ，without being able to elucidate the interconnection between the relevant signaling pathway and the specific target from a holistic perspective. In the follow-up ，the specific targets of piperine can be identified and clinical trials can be carried out to provide support for the clinical application of piperine.

Application of amide proton transfer-weighted MRI for grading of brainstem glioma in children / 中华全科医师杂志

Objective:To evaluate the application of amide proton transfer weighted (APTw) magnetic resonance imaging(MRI) for grading of brainstem glioma (BSG) in children.Methods:Twenty-five children (16 males and 9 females) aged 0.7-12.4(5.6±3.3)years were diagnosed as BSG by surgery or biopsy in Beijing Children′s Hospital from December 2019 to March 2022, including 13 cases of low-grade BSG and 12 cases of high-grade BSG. APTw imaging and conventional MRI were performed on a 3.0 T MRI scanner. The differences in gender distribution, age, conventional MRI appearance, APTw signal intensity and apparent diffusion coefficient (ADC) between children with high and low grade BSG were analyzed. Receiver operating characteristic (ROC) curve was used to analyze the efficacy of APTw signal intensity in the differential diagnosis of high and low grade BSG, and Youden index was calculated to obtain the optimal diagnostic threshold. Pearson′s correlation coefficient analysis was used to evaluate the correlation between APTw signal intensity and Ki-67 expression.Results:There was no significant difference in age and gender distribution between high-grade and low-grade BSG patients. The maximum diameter of high-grade BSG was significantly larger than that of low-grade BSG [(4.7±0.9) vs. (3.1±1.7)cm; t=-2.94, P=0.007]; the maximum signal intensity of APTw (APTw max) in high-grade BSG was significantly higher than that in low-grade BSG [(4.9±0.6)% vs. (3.0±1.2)%; t=-5.14, P<0.001]; the average signal intensity of APTw (APTw mean) in high-grade BSG was significantly higher than that in low-grade BSG[(3.6±0.4%) vs. (2.7±1.1)%; t=-2.66, P=0.014].The area under the curve(AUC)of APTw max in distinguishing high-and low-grade BSG was 0.897; with 4.07% as the optimal diagnostic threshold of APTw max, the sensitivity for the diagnosis of high-grade BSG was 0.917 and specificity was 0.846. The AUC of APTw mean in distinguishing high-and low-grade BSG was 0.769; with 2.85% as the optimal diagnostic threshold of APTw mean, the sensitivity for the diagnosis of high-grade BSG was 0.917 and specificity was 0.692. There was a positive correlation between the value of APTw max and Ki-67 expression( r=0.453, P=0.023). Conclusion:APTw imaging is helpful to distinguish high-grade and low-grade BSG in children. APTw max value can be used to effectively evaluate the proliferative activity of BSG in children.

The value of three-dimensional amide proton transfer-weighted imaging and its combination with diffusion weighted imaging in diagnosing breast benign and malignant lesions / 中华放射学杂志

Objective:To investigate the diagnostic value of three-dimensional amide proton transfer-weighted imaging (APTWI) and its combination with diffusion weighted imaging (DWI) for differentiating breast benign from malignant lesions.Methods:This was a prospective study. From July to December 2020, 226 patients with breast lesions confirmed by surgery or puncture pathology in the First Affiliated Hospital of Zhengzhou University were collected. All patients underwent MR T 1-weighted imaging, T 2-weighted imaging, DWI, APTWI, and dynamic contrast-enhanced MRI, and the apparent diffusion coefficient (ADC) value and the magnetization transfer ratio asymmetry at an offset of 3.5 ppm [MTRasym(3.5 ppm)] were obtained from DWI and APTWI respectively. Mann-Whitney U test was used for the comparison of DWI and APTWI parameters between breast benign and malignant lesions. Receiver operating characteristic (ROC) curve was used to evaluate the differences of diagnostic efficacy between DWI, APTWI, and their combination. Results:There were 226 patients with 226 breast lesions, including 124 malignant and 102 benign lesions. The ADC values of patients with malignant breast lesions [1.03 (0.93, 1.13)×10 -3 mm 2/s] and MTRasym (3.5 ppm) [1.95% (1.10%, 2.88%)] were lower than those of benign breast lesions [1.38 (1.11, 1.55)×10 -3 mm 2/s, 3.30% (2.20%, 4.20%), respectively], and the differences were statistically significant ( Z=-8.19, -6.51, P<0.05). The area under the ROC curves (AUC) of DWI, APTWI, and its combination in the differential diagnosis of benign and malignant breast lesions were 0.817, 0.752, and 0.868, respectively. The AUC of the combination of DWI and APTWI was higher than that of DWI and APTWI ( Z=4.00, 2.93, P<0.05), and there was no significant difference in the AUC between DWI and APTWI diagnoses ( Z=1.58, P>0.05). Taking 1.25×10 -3 mm 2/s as the optimal cut-off value for ADC values, the sensitivity, specificity, and accuracy in differentiating benign from malignant breast lesions were 94.4% (117/124), 62.7% (64/102), and 80.1% (181/226), respectively; Taking 2.70% as the optimal cut-off value for MTRasym (3.5 ppm), the sensitivity, specificity, and accuracy in differentiating benign from malignant breast lesions were 73.4% (91/124), 64.7% (66/102), and 69.5% (157/226), respectively, and the sensitivity, specificity, and accuracy of DWI combined with APTWI in differentiating benign from malignant breast lesions were 82.3% (102/124), 79.4% (81/102), and 81.0% (183/226), respectively. Conclusion:APTWI can be used for the differential diagnosis of benign and malignant breast lesions, and the combination of APTWI and DWI can obtain the better diagnostic performance than the single method.

The value of MR amide proton transfer weighted imaging technique in predicting the pathological grade of brainstem glioma / 中华放射学杂志

Objective:To evaluate the clinical application value of MR amide proton transfer weighted imaging (APTWI) in predicting the pathological grade of brainstem glioma (BSG).Methods:The data of 41 BSG patients in Beijing Tiantan Hospital, Capital Medical University from August 2019 to June 2020 who underwent both MRI and APTWI 2 weeks before surgery and had pathological grading results were retrospectively analyzed. According to the pathological results, 41 patients were classified into high-grade BSG (20 patients) and low-grade BSG (21 patients). Combined with conventional MR images, the signal intensity (%) of amide proton transfer (APT) in the parenchymal area of the tumor was obtained on APTWI images. χ 2 test or independent sample t-test was used to analyze the differences in gender distribution, age and APT signal intensity between patients with high and low grade BSG. Receiver operating characteristic (ROC) curve was drawn to predict the efficacy of APT signal intensity in the differential diagnosis of high and low grade BSG, and Youden index was calculated to obtain the optimal diagnostic threshold; the predictive ability of APT signal intensity was analyzed in combination with Hosmer-Lemeshow goodness of fit test. Results:There was no significant difference in age [(23±18) years, (20±17) years, t=0.97, P=0.340] and gender distribution (9/11, 9/12 for males/females, χ 2=0.02, P=0.890) between high-grade and low-grade BSG patients. The APT signal intensity of high-grade BSG [(3.9±0.9)%] was significantly higher than that of low-grade BSG [(2.8±0.9)%], and the difference had statistical significance ( t=4.16, P<0.001). The area under the ROC curve of APT signal intensity to distinguish high-grade and low grade BSG was 0.836, and with 2.85% as the optimal diagnostic threshold of APT signal intensity, its sensitivity for the diagnosis of high-grade BSG was 90.0% and specificity was 71.4%. The Hosmer-Lemeshow test showed that APTWI had a good predictive ability for BSG grade (χ 2=13.33, P=0.101). Conclusion:APTWI can be applied in distinguishing high grade BSG from low grade BSG, and has clinical value in predicting glioma grading.

Determination of five prostaglandin analogs in eyelash enhancing cosmetics by LC-MS/MS / 上海预防医学

Objective To determine bimatoprost， tafluprost ethyl amide， latanoprost， travoprost and tafluprost in eyelash enhancing cosmetics by establishing a LC-MS/MS method. Methods The samples were extracted with a 50% acetonitrile water solution. A salt mixture（4 g NaCl， 1 g MgSO4） was added to the solution to induce phase separation. After centrifugation and filtration， the analysis of five prostaglandin analogs was performed with an Agilent Poroshell 120 PFP-C18 （2.7 μm， 2.1 mm×100 mm） column， using 0.02% formic acid containing 5 mmol·L-1 Acetic acid amine and acetonitrile by gradient elution at a flow rate of 0.5 mL·min-1. The analytes were detected with electrospray ionization source in positive ion mode （ESI+） and multiple reaction monitoring （MRM）， and quantified by external standard curve. Results The results showed that it had a good linearity in the range of locatable ambit of concentration with correlation coefficients （r） larger than 0.999. The detection limit of five prostaglandin analogs （LOD） was 0.000 2‒1.5 μg·g-1. The spiked recoveries were 93.2% to 103.5% with a relative standard deviation （RSD） of 1.2% to 3.4%. Conclusion The method is simple， rapid and highly sensitive. It is suitable for the determination of five prostaglandin analogs in eyelash enhancing cosmetics.

Research Progress on Chemical Constituents and Pharmacological Effects of Piperis Fructus / 中国实验方剂学杂志

Piperis Fructus is the dried nearly ripe or ripe fruit of Piperaceae, which is an important spice material and a traditional Chinese medicine (TCM), it is widely used in the world. It is recorded to possess the efficacy of warming spleen and stomach for dispelling cold, depressing Qi and dissolving phlegm. Piperis Fructus mainly contains amide alkaloids with piperine as the main ingredient and volatile oil dominated by monoterpenoids and sesquiterpenoids, which have a wide range of biological activities, such as anti-cancer, anti-oxidation, anti-inflammatory, etc. By referring to relevant papers at home and abroad, the researches on chemical compositions from different parts and pharmacological effects of Piperis Fructus in recent 5 years were summarized and analyzed. It was found that Piperis Fructus has great potential for drug development as a TCM with homology of medicine and food, which can provide a reference for further research and comprehensive utilization of Piperis Fructus.

Study on synthesis and biological activities of quercetin-3-O-amide derivatives / 中草药

Objective: To design and synthesize quercetin amide derivatives and study the antitumor activity of these compounds in vitro. Methods: The cheap rutin was used as the raw material, the benzyl group was selectively protected, the Williamson was converted into ether, and then the target product was obtained by the hydrogenation debenzylation of Pd/C catalyst. The antioxidant activity of the target compound was investigated by the DPPH method. The inhibitory effects of the target compounds on the proliferation of human esophageal squamous cell carcinoma cell EC109, human esophageal squamous cell carcinoma cell EC9706, human gastric cancer cell SGC7901, and mouse melanoma cells B16-F10 were investigated by MTT method. Results: The structures of the 15 quercetin amide derivatives were confirmed by 1H-NMR, 13C-NMR, and ESI-MS. The antioxidant results showed that the SC50 of most target compounds was smaller than or equivalent to quercetin, which suggests that 3-OH is not an essential group for the antioxidant activity of quercetin. The results of anti-tumor experiments showed that after the structural modification of quercetin by chemical methods, its anti-tumor activity was significantly enhanced in vitro. Among them, the inhibitory effect of compound 7-6 on EC109 (IC50 = 10.25 μmol/L) is significantly better than that of the parent drugs quercetin (IC50 = 31.884 μmol/L) and 5-FU (IC50 = 41.738 μmol/L). Potential new antitumor candidate compounds. Conclusion: The 15 quercetin-3-O-amide derivatives are all new compounds. Among them, compounds 7-6 have good antitumor activity and deserve further study.

Effect and Mechanism of Amide Alkaloids of Lycii Cortex on Improving Lipid Metabolism in HepG2 Cells / 中国药学杂志

OBJECTIVE: To investigate the effect of two amide alkaloid derivatives (LCAA and LCAB) from Lycii Cortex on lipid metabolism in HepG2 cells and explore their possible mechanisms. METHODS: The lipid accumulation model of HepG2 cells induced by sodium oleate was established. The cells were pretreated with different concentrations of LCAA and LCAB, and the lipid accumulation was observed by oil red O staining. The content of TC in HepG2 cells was measured by oxidizing enzyme method, and the content of TG in HepG2 cells was measured by GPO-PAP method. The expression of lipid metabolism related proteins, such as SIRT1, FOXO1, AMPK and phospho-AMPK (p-AMPK), was detected by Western blot. The mRNA expression of AMPK, SIRT1, ACC2, COXII and COXIII were detected by RT-qPCR. RESULTS: Both LCAA and LCAB could significantly decrease the lipid accumulation in HepG2 cells induced by sodium oleate (200 μmol•L-1) (P<0.01) and the TC and TG levels (P<0.05 or P<0.01). At the same time, the sodium oleate-induced high expression of p-AMPK protein, the low expression of SIRT1, FOXO1 (P<0.01), and the low expression of AMPK, SIRT1, ACC2, COXII and COXIII mRNA (P<0 05 or P<0 01) were all improved by LCAA and LCAB. CONCLUSION: Both LCAA and LCAB can significantly improve lipid metabolism in HepG2 cells, and regulate lipid metabolism by regulating lipid metabolism-related proteins p-AMPK, SIRT1, FOXO1 and mitochondrial oxidation-related factors COXII and COXIII.

Two new phenylpropanoid amide glycosides from whole plants of Corydalis racemosa / 中国中药杂志

Two new phenylpropanoid amide glycosides and ten analogues were isolated from the CH_2Cl_2 layer of 95% ethanol extract of the whole plants of Corydalis racemosa by using various chromatographic techniques, including silica gel, Sephadex LH-20, ODS column chromatographies, and semi-preparative HPLC. Their structures were identified on the basis of physicochemical properties, MS, NMR, and IR spectroscopic data as N-cis-sinapoyltyramine-4'-O-β-glucoside(1), N-cis-sinapoyl-3-methoxytyramine-4'-O-β-glucoside(2), N-cis-sinapoyltyramine(3), N-cis-feruloyltyramine(4), N-trans-cinnamoyltyramine(5), N-trans-feruloylphenethylamine(6), N-trans-p-methoxycinnamoyl-3-hydoxyoctopamine(7), N-cis-feruloyl-3-methoxytyramine(8), N-trans-feruloyltyramine(9), N-trans-feruloyl-3-methoxytyramine(10), N-trans-sinapoyltyramine(11), and N-trans-p-coumaroyltyramine(12). Compounds 1 and 2 are new compounds. Compounds 3-7 are obtained from the plants of Papaveraceae for the first time, and compounds 8-12 are firstly isolated from C. racemosa.

Progress in Clinical Research of Amide Proton Transfer Imaging / 中国医疗器械杂志

As a new type of magnetic resonance imaging method, amide proton transfer (APT) imaging can detect the chemical exchange characteristics of free proprotein, peptide amide proton and water proton by water signal changes, reflecting the changes of protein and pH in tissues. In recent years, clinical research on brain tumors, multiple sclerosis, hepatic encephalopathy and cervical cancer have been carried out. It is a radiation-free and non-invasive new magnetic resonance molecular imaging technology. This study briefly reviews the principle of APT technology and its clinical application, and prospects its application prospects in children's abdominal tumors.

Efficacy of transversus abdominis plane block with different doses of dexmedetomidine mixed with ropivacaine in pediatric patients undergoing laparoscopic surgery with general anesthesia / 中华麻醉学杂志

Objective@#To evaluate the efficacy of transversus abdominis plane block (TAPB) with different doses of dexmedetomidine mixed with ropivacaine in the pediatric patients undergoing laparoscopic surgery with general anesthesia.@*Methods@#Eighty patients of both sexes, aged 3-6 yr, weighing 10-30 kg, scheduled for elective single-channel laparoscopic appendectomy, were divided into 4 groups (n=20 each) using a random number table method: 0.5 μg/kg dexmedetomidine plus ropivacaine group (group DR1), 1.0 μg/kg dexmedetomidine plus ropivacaine group (group DR2), 1.5 μg/kg dexmedetomidine plus ropivacaine group (group DR3), and ropivacaine group (R group). Bilateral TAPB was performed under ultrasound guidance after the end of anesthesia induction.In group TR, 0.25% ropivacaine 0.5 ml/kg was injected, the 0.5 ml/kg mixture of 0.5, 1.0 and 1.5 μg/kg dexmedetomidine and ropivacaine at a final concentration of 0.25% was injected in DR1, DR2 and DR3 groups.Anesthesia was maintained by intravenously infusing remifentanil and inhaling sevoflurane.Cisatracurium was intermittently injected to maintain muscle relaxation.Ibuprofen was taken orally to maintain postoperative FLACC score <4.The intraoperative consumption of remifentanil, tracheal extubation time, duration of anesthetic recovery room stay, requirement for ibuprofen, and occurrence of opioids- and TAPB-related complications were recorded.@*Results@#There was no significant difference in the intraoperative consumption of remifentanil or tracheal extubation time between four groups (P>0.05). Compared with group R, the requirement for ibuprofen was significantly decreased in DR2 and DR3 groups, the duration of anesthetic recovery room stay was significantly prolonged in group DR3 (P<0.05), and no significant change was found in the requirement for ibuprofen in group DR1 or in the duration of anesthetic recovery room stay in DR1 and DR2 groups (P>0.05). Compared with group DR1, the duration of anesthetic recovery room stay was significantly prolonged, and the requirement for ibuprofen was decreased in group DR3, and the requirement for ibuprofen was significantly decreased (P<0.05), and no significant change was found in the duration of anesthetic recovery room stay in group DR2 (P>0.05). Compared with group DR2, the duration of anesthetic recovery room stay was significantly prolonged (P<0.05), and no significant change was found in the other parameters in group DR3 (P>0.05). No patients developed opioids- or TAPB-related complications.@*Conclusion@#TAPB with 1.0 μg/kg dexmedetomidine mixed with ropivacaine provides good efficacy for the pediatric patients undergoing laparoscopic surgery with general anesthesia.

Effect of Mangiferin on mRNA Expressions of Hepatic PRPS, PRPPAT and Cerebral HGPRT in Hyperuricemic Mice Induced by Potassium Oxonate / 中国实验方剂学杂志

Objective:To investigate the effect of mangiferin on the mRNA expression of phosphoribosylpyrohoosphate synthetase (PRPS), phosphate ribose pyrophosphate amide transferase (PRPPAT) in liver and hypoxanthine-guanine phosphate transfer enzyme (HGPRT) in brain of hyperuricemic mice induced by potassium oxonate. Method:Hyperuricemic mice were induced through intraperitoneal injection with uricase inhibitor potassium oxonate. The serum uric acid level was determined by the phosphotungstic acid method. The mRNA expression levels of PRPS and PRPPAT in liver as well as HGPRT in brain of hyperuricemic mice were measured by reverse transcriptase polymerase chain reaction (RT-PCR). Result:An intraperitoneal injection with potassium oxonate caused a marked increase in serum uric acid level, compared with normal control group (P-1 was able to significantly reduce serum uric acid levels, compared with hyperuricemic control group (PPConclusion:The hyporuricemic effect of mangiferin might not be related with PRPS, PRPPAT and HGPRT in therapeutic dose.

A new amide compound from Onchidium verruculatum / 中草药

Objective: To study the chemical composition of the marine characteristic resource, Onchidium verruculatum from Hainan Island. Methods: Compound was separated and purified by silica gel and semi-preparative HPLC, detected by TLC, and identified by NMR and MS data. Compound 1 was evaluated for cytotoxic activity against four kinds of human tumor cell lines HepG-2, BEL-7042, A549, and MCF-7. Results: A new amide compound, N-(2-hydroxy-4-methoxy-5-methylphenyl)formamide (1), was isolated from mucus and muscle tissue of O. verruculatum. The results showed that compound 1 has moderate toxic activity against A549 and BEL-7402 cell lines, with IC50 value of 11.5 μg/mL and 19.4 μg/mL. Conclusion: Compound 1 is a new amide compound named onchumamide with moderate toxic activity on human tumor cells.

Amide proton transfer weighted imaging evaluation on isocitrate dehydrogenase mutation status in patients with high-grade gliomas / 中国医学影像技术

Objective: To observe the value of amide proton transfer weighted (APTw) imaging in predicting isocitrate dehydrogenase (IDH) wild type and IDH mutant of high-grade gliomas. Methods: Twenty-five patients with pathologically confirmed high-grade gliomas were enrolled. All patients underwent preoperative MR scanning, including routine sequences, T1WI enhancement and APTw scanning. According to the pathology, the patients were divided into IDH wild type group and IDH mutant group. ROIs were placed on FLAIR images of all tumor layers to select the solid components of the tumor, and APT values of each layer were obtained to get the mean value. Differences of APT values were analyzed between groups using independent sample t test, and ROC curve analysis was performed to evaluate the diagnostic efficacy of APT values in assessing the gene status of IDH. Results: Among 25 patients of high-grade gliomas, 9 cases were IDH mutant and 16 cases were IDH wild type. APT value of IDH wild type group ([3.21±0.82]%) was significantly higher than that of IDH mutant group ([2.23±0.72]%; t=2.89, P<0.05), and the AUC was 0.84 (P<0.05). The sensitivity and specificity of IDH wild type diagnosis was 93.8% and 66.7%, respectively. Conclusion: APTw imaging can be used to predict gene status of IDH in high-grade gliomas.

Efficacy of transversus abdominis plane block with different doses of dexmedetomidine mixed with ropivacaine in pediatric patients undergoing laparoscopic surgery with general anesthesia / 中华麻醉学杂志

Objective To evaluate the efficacy of transversus abdominis plane block (TAPB) with different doses of dexmedetomidine mixed with ropivacaine in the pediatric patients undergoing laparoscopic surgery with general anesthesia.Methods Eighty patients of both sexes,aged 3-6 yr,weighing 10-30kg,scheduled for elective single-channel laparoscopic appendectomy,were divided into 4 groups (n =20each) using a random number table method:0.5 μg/kg dexmedetomidine plus ropivacaine group (group DR1),1.0 μg/kg dexmedetomidine plus ropivacaine group (group DR2),1.5 μg/kg dexmedetomidine plus ropivacaine group (group DR3),and ropivacaine group (R group).Bilateral TAPB was performed under ultrasound guidance after the end of anesthesia induction.In group TR,0.25％ ropivacaine 0.5 ml/kg was injected,the 0.5 ml/kg mixture of 0.5,1.0 and 1.5 μg/kg dexmedetomidine and ropivacaine at a final concentration of 0.25％ was injected in DR1,DR2 and DR3 groups.Anesthesia was maintained by intravenously infusing remifentanil and inhaling sevoflurane.Cisatracurium was intermittently injected to maintain muscle relaxation.Ibuprofen was taken orally to maintain postoperative FLACC score ＜4.The intraoperative consumption of remifentanil,tracheal extubation time,duration of anesthetic recovery room stay,requirement for ibuprofen,and occurrence of opioids-and TAPB-related complications were recorded.Results There was no significant difference in the intraoperative consumption of remifentanil or tracheal extubation time between four groups (P＞0.05).Compared with group R,the requirement for ibuprofen was significantly decreased in DR2 and DR3 groups,the duration of anesthetic recovery room stay was significantly prolonged in group DR3 (P＜0.05),and no significant change was found in the requirement for ibuprofen in group DR1 or in the duration of anesthetic recovery room stay in DR1 and DR2 groups (P＞0.05).Compared with group DR1,the duration of anesthetic recovery room stay was significantly prolonged,and the requirement for ibuprofen was decreased in group DR3,and the requirement for ibuprofen was significantly decreased (P＜0.05),and no significant change was found in the duration of anesthetic recovery room stay in group DR2 (P＞0.05).Compared with group DR2,the duration of anesthetic recovery room stay was significantly prolonged (P＜0.05),and no significant change was found in the other parameters in group DR3 (P＞ 0.05).No patients developed opioids-or TAPB-related complications.Conclusion TAPB with 1.0 μg/kg dexmedetomidine mixed with ropivacaine provides good efficacy for the pediatric patients undergoing laparoscopic surgery with general anesthesia.

Synthesis and lipid-regulating evaluation of caffeic acid amide derivatives / 中草药

Objective To evaluate the anti-lipid metabolic disorder activities of these compounds in vitro, the natural caffeic acid amide derivatives were designed and synthesized. Methods Using caffeic acid as start material, BOP as a condensing agent, and the target compounds were sequentially prepared with fourteen amines, and then the lipid-regulating effect was evaluated using HepG2 cells. Results Fourteen caffeic acid amide compounds CA1-CA14 were synthesized. The structures of the target compounds were identified by spectrum. Pharmacological results showed that fourteen derivatives have potency of lipid-regulating in different levels. In particular, compound CA6 showed significant lipid-regulating effects compared to the lead compounds caffeic acid and Simvastatin. Conclusion Compound CA6, CA7, and CA11 had not been reported in any literatures before. Among them, the novel compounds CA6 and CA11 have showed potential of lipid-regulating activities, and deserved further research.

Synthesis and Antitumor Activity Evaluation of C-3 (Rhodanine Unsaturated Ketone) Amides as Ofloxacin Derivatives / 中国药学杂志

OBJECTIVE: To explore an efficient strategy for converting the antibacterial activity of fluoroquinolones to antitumor activity. METHODS: An amide group as an isostere modified by rhodanine unsaturated ketone moiety corresponding to the C-3 carboxylic acid group resulted in 12 new title C-3 (5-arylidene-2-thioxo-1, 3-thiozolidin-2, 4 -dione-3-yl) amides (6a - 6l) from ofloxacin 1. Their structures were characterized by elemental analysis and spectral data, and the in vitro antitumor activity of the title compounds against three tested cell lines was evaluated by MTT assay. RESULTS: Twelve new title compounds were synthesized from ofloxacin and exhibited significantly higher potency than the parent compound ofloxacin. CONCLUSION: Using a rhodanine unsaturated ketone hybrided amide group as the C-3 bioisostere is favorable to improve antitumor activity.