Objective To establish a specific HPLC method and a standard fingerprint for quality control ofZiziphi Spinosae Folium.Methods The samples were separated on a Kinetex C18 column (100 mm × 2.1 mm,2.6 μm) by gradient elution at the flow rate of 300 μL/min using acetonitrile and 0.1％ aqueous formic acid as the mobile phase.The column temperature was 30℃.The detection wavelength was 225 nm and the sample size was 10 μL.The fingerprint evaluation software (2012 edition) for Chinese materia medica (CMM) was used to evaluate the similarity of the 12 batches of samples.Results There were 13 characteristic peaks identified in the characteristic spectra ofZiziphi Spinosae Folium samples.Peak 6 was Rutin.The similarities of 13 batches ofZiziphi Spinosae Folium samples were proved to behigher than 0.850.Conclusion The method is available with a good reproducibility and accuraty which can control the quality standards effectively.

Objective To determinate whether the first post-operative day serum parathyroid hormone (PTH) is more effective than serum calcium in predicting hypocalcemia after total thyroidectomy.Methods According to PTH level on the first post-operative day,104 patients after total thyroidectomy were divided into different groups.Patient's serum calcium was measured,the number of patients who developed hypocalcemia and the time for calcium supplement were recored.Results Serum PTH was more accurate in predicting hypocalcemia than serum calcium.There were 26 patients whose PTH value was ＜ 5 pg/ml,among whom 7 patients had transient hypocalcemia and symptoms,while 5 of them developed hypocalcemia for long time and needed long-term calcium supplement.The positive predictive value of group PTH value ＜ 5 pg/ml was 28％,and the accurate rate was 46％,higher than other groups.Besides,the positive predictive value and the accurate rate of PTH value ＜ 5 pg/ml was higher than serum calcium.Conclusion Serum PTH is more effective in determining hypocalcemia after total thyroidectomy than serum calcium,and PTH value ＜ 5 pg/ml on the first post-operative day is a reliable marker in predicting hypocalcemia after total thyroidectomy.

OBJECTIVETo identify the risk factors of early post-TIPS hepatic encephalopathy (HE) and the long-time survival of patients with or without early post-TIPS HE.

METHODSConsecutive cirrhotic patients who underwent TIPS for variceal rebleeding or refractory ascites in our center from January 2003 to December 2008 were included in this study. More than 60 clinical characteristics were enrolled in univariate analysis and logistic regression analysis to define the risk factors of HE in 3 months after TIPS procedure (early post-TIPS HE). The long-time survival of patients with or without early post-TIPS HE was compared by Cox regression with several covariates.

RESULTSAccording to our inclusion criteria, 190 patients were included. The median follow-up was 30.5 months. Lower serum concentration of fibrinogen and higher Child-Pugh score were the independent risk factors for suffering early post-TIPS HE. Patients without early post-TIPS HE after TIPS showed better prognosis than those with early post-TIPS HE after TIPS (P = 0.044).

CONCLUSIONPatients with lower serum fibrinogen and higher Child-Pugh score before TIPS might be more probably attacked by early post-TIPS HE which indicated worse long-term survival.

Adult ; Female ; Fibrinogen ; analysis ; Follow-Up Studies ; Hepatic Encephalopathy ; diagnosis ; etiology ; Humans ; Male ; Middle Aged ; Portasystemic Shunt, Transjugular Intrahepatic ; adverse effects ; Prognosis ; Risk Factors

Background/Aims: Direct‐acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population. Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan. Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10). Conclusions HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.

A derivatizaton method combined with gas chromatography-mass spectrometry(GC-MS)was established for detection of isobutyl chloroformate(IBCF)residue in active pharmaceutical ingredient of agatroban.The extraction and derivatization reagents,derivatization time,qualitative and quantitative ions were selected and optimized,respectively.The possible mechanism of derivatization and characteristic fragment ions fragmentation were speculated.The agatroban samples were dissolved and extracted by methanol,and the residual IBCF was derived with methanol to generate methyl isobutyl carbonate(MIBCB).After 24 h static derivatization at room temperature,IBCF was completely transformed into MIBCB,which could be used to indirectly detect IBCF accurately.The results showed that the linearity of this method was good in the range of 25-500 ng/mL(R2=0.9999).The limit of detection(LOD,S/N=3)was 0.75 μg/g,and the limit of quantification(LOQ,S/N=10)was 2.50 μg/g.Good recoveries(95.2%-97.8%)and relative standard deviations(RSDs)less than 3.1%(n=6)were obtained from agatroban samples at three spiked levels of IBCF(2.50,25.00,50.00 μg/g),which showed good accuracy of this method.Good precision of detection results was obtained by different laboratory technicians at different times,the mean value of spiked sample solution(25.00 μg/g)was 24.28 μg/g,and the RSD was 2.1%(n=12).The durability was good,minor changes of detection conditions had little effect on the results.Under the original condition and conditions with initial column temperature±5℃,heating rate±2℃/min,column flow rate±0.1 mL/min,the IBCF content of spiked sample solution(25.00 μg/g)was detected,the mean value of detection results was 24.16 μg/g,and the RSD was 2.2%(n=7).Eight batches of agatroban samples from two manufacturers were detected using the established method,and the results showed that no IBCF residue was detected in any of these samples.The agatroban samples could be dissolved by methanol,and then the IBCF residue could be simultaneously extracted and derived with methanol as well.This detection method had the advantages of simple operation,high sensitivity,low matrix effect and accurate quantification,which provided a new effective method for detection of IBCF residue in agatroban.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy-lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.

【Objective】 Corin, a transmembrane serine protease that can cleave atrial natriuretic peptide precursor (pro-ANP) into atrial natriuretic peptide with smaller bioactive molecules, participates in the pathophysiological process of hypertension and cardiac hypertrophy. The purpose of this study was to explore the relationship of Corin gene variation with blood pressure responses to sodium and potassium dietary interventions. 【Methods】 In 2004, we recruited 514 participants from 124 families in 7 villages of Baoji, Shaanxi Province, China. All the subjects received a 3-day normal diet, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Fifteen single nucleotide polymorphisms (SNPs) of Corin gene were selected for final analysis. 【Results】 SNPs rs12509275 were significantly associated with diastolic blood pressure (DBP) response to low-salt diet, while rs3749584 was associated with pulse pressure (PP) response to low-salt diet.SNP rs3749584 and rs10517195 were significantly associated with PP response to high-salt diet. In addition,rs17654278 were significantly associated with systolic blood pressure (SBP) response to high-salt and potassium supplementation, rs2271037 was significantly correlated with DBP responses to high-salt and potassium supplementation, and rs4695253, rs12509275, rs2351783, rs36090894 were significantly associated with PP response to high-salt and potassium supplementation. 【Conclusion】 Corin gene polymorphisms were associated with blood pressure response to sodium and potassium, suggesting that Corin gene may be involved in pathophysiological process of salt sensitivity and potassium sensitivity.