3-氯丙二醇和2、3-氧丙醇合并长期、间歇给药对恒河猴及大鼠毒性作用的观察

本文介绍了3-氯丙二醇和2,3-氧丙醇合并长期间歇用药对猴及大鼠的毒性观察,结果表明,以日剂量5mg/kg 3-氯丙二醇和75mg/kg 2,3-氧丙醇合并应用,可导至大鼠可逆性不育;对猴及大鼠的内脏器官、骨髓细胞增生度及微核数量、末梢血液细胞计数、分类,以及猴的染色体常规检查未见明显影响。表明合并用药有用药量小,给药时间短、起效快、毒性低等优点。     

SYNCRIP controls miR-137 and striatal learning in animal models of methamphetamine abstinence

Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome. Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA–target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine (MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR, LC–MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.     

Effects of traditional herbal medicine, Hwaotang, on atherosclerosis using the spontaneous familial hypercholesterolemia model, Kurosawa and Kusanagi-hypercholesterolemic rabbits and the venous thrombosis rats

Hwaotang (HOT), a traditional Korean medicinal formulation, is a dried decoctum of a mixture of seven herbal medicines, consisting of Angelica gigantis Radix, Rehmanniae Radix, Paeoniae Radix, Ciniamomi Cortex, Cnidii Rhizoma, Persicae Semen and Carthami Flos. In the present study, the inhibitory effects and anti thrombic properties of HOT on the progression of atherosclerotic lesions were studied using the spontaneous familial hypercholesterolemia (FH) model, Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits and rats. Changes in blood chemistry, pathology and low-density lipoprotein (LDL) oxidation were measured in a control and HOT group. In the control group, the area of atheromatous plaques of the aorta progressed between week 12 (36.65%) and week 14 (46.22%). This progression of atherosclerotic lesions did not occur in the HOT-treated group after 12 (24.24%) and 14 (23.34%) weeks. Antioxidative effects on LDL were seen in the HOT in weeks 12 and 14. HOT improved the hypercholesterolemia in the KHC rabbits. On the other hand, HOT and five of the seven herbs, except Cnidii Rhizoma and Carthami Flos, inhibited the endotoxin-induced hepatic venous thrombosis in high cholesterol diet-treated rats. However, Ciniamomi Cortex showed a very weak inhibitory effect on the endotoxin-induced hepatic venous thrombosis. The extract also inhibited the endotoxin-induced decrease in blood platelets and fibrinogen, and endotoxin-induced increase in fibrin degradation products (FDP) on disseminated intravascular coagulation in normal rats. In conclusion, these results suggest that HOT has inhibitory effects on the development of atheromatous plaque formation in spontaneous FH rabbits. It is also suggested that the antioxidative effects of HOT on LDL led to the beneficial effects observed in this study. The protection by HOT and its herbs on the artificially induced ischemic infarction might be related to their inhibitory effects on disseminated intravascular coagulation, platelet coagulation and thrombotic action.     

Role of adjuvant chemoradiotherapy and chemotherapy in patients with resected gallbladder carcinoma: a multi-institutional analysis (KROG 19-04)

Objective:The effectiveness of adjuvant treatments for resected gallbladder carcinoma (GBC) has remained unclear due to lack of randomized controlled trials; thus, the aim of present study was to evaluate the role of adjuvant treatments, including chemoradiotherapy (CRT) and/or chemotherapy (CTx), in patients with resected GBC.Methods:A total of 733 GBC patients who received curative-intent surgical resection were identified in a multi-institutional database. Of 733 patients, 372 (50.8%) did not receive adjuvant treatment, whereas 215 (29.3%) and 146 (19.9%) received adjuvant CTx and CRT, respectively. The locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS), and overall survival (OS) of the adjuvant treatment groups were compared according to tumor stage (stage II vs. stage III–IV).Results:In stage II disease (n = 381), the 5-year LRFS, RFS, and OS were not significantly different among the no-adjuvant therapy, CTx, and CRT groups, and positive resection margin, presence of perineural invasion, and Nx classification were consistently associated with worse LRFS, RFS, and OS in the multivariate analysis (P < 0.05). For stage III–IV (n = 352), the CRT group had significantly higher 5-year LRFS, RFS, and OS than the no-adjuvant therapy and CTx groups (67.8%, 45.2%, and 56.9%; 37.9%, 28.8%, and 35.4%; and 45.0%, 30.0%, and 45.7%, respectively) (P < 0.05).Conclusions:CRT has value as adjuvant treatment for resected GBC with stage III–IV disease. Further study is needed for stage II disease with high-risk features.     

The effects of oral steroid duration on stricture prevention after extensive endoscopic submucosal dissection for superficial esophageal cancer

BackgroundEsophageal stricture is a major complication of endoscopic submucosal dissection (ESD) in patients with superficial esophageal cancer (SEC). Oral steroids have been used to prevent esophageal stricture in patients with more than 75% of the esophageal circumference resected. However, there are no established guidelines regarding the optimal duration of steroid use. This retrospective observational study aimed to compare the incidence of esophageal stricture according to the period of prophylactic oral steroid use and to identify the risk factors for esophageal stricture.MethodsEighty-one patients who were prescribed prophylactic steroid after undergoing ESD for SEC with more than 75% of esophageal circumference resected were enrolled. Patients were classified into the four-week steroid group (n=72) or eight-week steroid group (n=9) to compare the incidence of esophageal stricture. In addition, the patients were subdivided into those who developed esophageal stricture (n=24) and those who did not (n=57) to identify the risk factors for esophageal stricture.ResultsTwenty patients (27.8%) in the four-week oral steroid group and four patients (44.4%) in the eight-week oral steroid group developed esophageal stricture (P=0.44). The univariable analysis identified tumor size, longitudinal length of semi-circumferential resection, and proportion of circumferential resection as risk factors of esophageal stricture. The multivariable analysis identified the proportion of circumferential resection as an independent risk factor. After adjusting for the proportion of circumferential resection, the incidence of stricture was marginally higher in the eight-week steroid group [P=0.05; odds ratio (OR): 5.69; 95% confidence interval (CI): 1.01–32.15].ConclusionsEight weeks of oral steroid prophylaxis does not reduce the risk of stricture after extensive ESD more than four weeks of oral steroid prophylaxis. The proportion of circumferential resection is the strongest risk factor for stricture in patients with SEC undergoing ESD.     

Venous Thromboembolism Risk in Asian Patients with Inflammatory Bowel Disease: A Population-Based Nationwide Inception Cohort Study

Background/AimsInflammatory bowel disease (IBD) is associated with the occurrence of venous thromboembolism (VTE). However, to date, there have been few studies on the risk of VTE in Asian IBD patients. We aimed to estimate the incidence of VTE in Asian IBD patients and to determine if IBD is related to increased VTE risk.MethodsWe performed a population-based cohort study between 2004 and 2015 using Korean National Health Insurance data. IBD and VTE were defined by ICD-10 codes. Incidence rates of VTE were calculated among patients with IBD and among age- and sex-matched controls. Hazard ratios were estimated using Cox regression with adjustment for multiple variables. We performed additional analyses stratifying by age, sex, Charlson comorbidity index (CCI) score, and disease type.ResultsAmong the 45,037 patients with IBD (IBD cohort) and 133,019 matched controls (non-IBD cohort) included in our analysis, 411 IBD patients and 641 controls developed VTE. The IBD cohort had a higher incidence rate ratio and risk of VTE than the non-IBD cohort (incidence rate ratio 1.92 and hazard ratio 1.93). Older age, female sex, higher CCI scores, cardiovascular disease, chronic kidney disease, use of steroids, and hospitalization were significant risk factors for VTE in patients with IBD.ConclusionsThe IBD patients in this study were approximately two times more likely to develop VTE than the non-IBD individuals. Our findings support the need for thromboprophylaxis in Asian IBD patients with various factors that further increase the risk of VTE.     

Triple Therapy-Based on Tegoprazan,a New Potassium-Competitive Acid Blocker,for First-Line Treatment of Helicobacter pylori Infection: A Randomized,Double-Blind,Phase III,Clinical Trial

Background/AimsWe examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication.MethodsA randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)-based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases.ResultsIn total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences.ConclusionsTPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT03317223","term_id":"NCT03317223"}}NCT03317223).