芪苈强心胶囊配合保元汤加减治疗慢性心力衰竭临床研究

目的:观察芪苈强心胶囊配合保元汤加减用于慢性心力衰竭的治疗效果。方法:选取收治的慢性心力衰竭患者104例作为研究对象,运用随机数字表法将其分为观察组(52例)和对照组(52例),两组患者均接受常规治疗,对照组采用保元汤治疗,观察组同时应用芪苈强心胶囊联合保元汤治疗。观察患者治疗前及治疗后6个月的6 min步行试验的步行距离(6MWD)及纽约心脏病学会心功能分级(NYHA)、血清学指标N末端B型利尿钠肽原(NT-proBNP)、半乳糖凝集素3(Galectin-3)及白介素6(IL-6)、超敏C反应蛋白(hs-CRP)、肿瘤坏死因子α(TNF-α)、心脏指数(CI)、左室射血分数(LVEF)、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、左室重量指数(LVMI)和室壁运动指数(WMI)、左室间隔厚度(IVST)变化情况。结果:治疗前后,两组患者比较心功能指标、Galectin-3、炎性因子指标、心室重构指标差异有统计学意义(P<0.05); 观察组与对照组患者相比,6 min步行距离、CI、LVEF、升高更为显著(P<0.05); 观察组患者NYHA分级、NT-proBNP、Galectin-3、IL-6、hs-CRP、TNF-α、LVEDD、LVESD、LVMI、WMI、IVST降低更为显著(P<0.05)。结论:芪苈强心胶囊辅助保元汤加减能够有效改善慢性心力衰竭患者心脏功能,有利于患者体内炎性因子及Galectin-3水平降低,抑制心室重构进展,患者心脏舒缩功能改善效果更佳。     

The Comprehensive Analysis of Efficacy and Safety of CalliSpheres^® Drug-Eluting Beads Transarterial Chemoembolization in 367 Liver Cancer Patients: A Multiple-Center,Cohort Study

This study aimed to investigate the efficacy, safety, and prognostic factors of drug-eluting beads transarterial chemoembolization (DEB-TACE) in treating Chinese patients with liver cancer. A total of 367 liver cancer patients from 24 medical centers were consecutively enrolled in this multiple-center, prospective cohort study, including 275 hepatocellular carcinoma (HCC) cases, 37 intrahepatic cholangiocarcinoma (ICC) cases, and 55 secondary liver cancer cases. All the patients received CalliSpheres^® DEB-TACE treatment. Treatment response, overall survival (OS), change of liver function, and adverse events (AEs) were assessed. DEB-TACE treatment achieved 19.9% complete response (CR) and 79.6% objective response rate (ORR), with mean OS of 384 days [95% confidence interval (CI): 375–393 days]. CR and ORR were both higher in HCC patients compared with primary ICC patients and secondary liver cancer patients, while no difference was discovered in OS. Portal vein invasion was an independent risk factor for CR, while portal vein invasion, previous conventional TACE (cTACE) treatment, and abnormal blood creatinine (BCr) were independent risk factors for ORR. In addition, largest nodule size 5.0 cm, abnormal albumin (ALB), and abnormal total bilirubin (TBIL) independently correlated with unfavorable OS. Most liver function indexes were recovered to baseline levels at 1–3 months after DEB-TACE. Common AEs were pain, fever, vomiting, and nausea; most of them were at mild grade. CalliSpheres^® DEB-TACE is efficient and well tolerated in Chinese liver cancer patients. Portal vein invasion, previous cTACE treatment, largest nodule size, abnormal BCr, ALB, and TBIL correlate with worse prognosis independently.     

CalliSpheres载药微球TACE联合微波消融治疗原发性大肝癌疗效评价

目的探讨CalliSpheres载药微球经导管肝动脉化疗栓塞术(TACE)联合微波消融治疗原发性大肝癌的临床疗效。方法23例直径5~10cm原发性肝癌患者施行了CalliSpheres载药微球TACE联合微波消融治疗。术后1、3、6、9、12个月及以后每3个月采用肝脏增强MRI随访。结果23例患者共行33次CalliSpheres载药微球TACE联合微波消融治疗,无肝脓肿、胆脂瘤等并发症发生。23例患者随访3~22(平均9.2±3.9)个月,术后1、3、6、9、12和15个月客观缓解率分别为86.9%、87%、93.8%、77.0%、63.6%、57.2%,疾病控制率分别为100.0%、95.7%、93.8%、92.3%、81.8%、85.7%。术后3、6、9、12和15个月生存率分别为100%、93.8%、84.6%、81.8%、71.4%。结论CalliSpheres载药微球TACE联合微波消融治疗原发性大肝癌安全可靠,近中期疗效较好。     

Glycopolymer Code: Programming Synthetic Macromolecules for Biological Targeting

Targeting in a cellular level is still one of the major challenges in biomedical treatments. However, new synthetic and analytical techniques now allow the development of precisely prepared macromolecules. Thus, glycopolymer chains are reported to be prepared with controlled length, monomer sequences, as well as chain‐folded structures. A high level of complexity in synthetic macromolecules also allows increased selectivity in targeting, which is a key factor in biomedical applications.     

Mannose-derived FimH antagonists: a promising anti-virulence therapeutic strategy for urinary tract infections and Crohn’s disease

Introduction: Type 1 pili are utilized by Gram-negative bacteria to adhere to host tissue and thus are a key virulence factor in urinary tract infections (UTIs) and Crohn’s disease (CD). This adhesion is mediated through specific binding of the terminal adhesin, FimH, to mannosylated host glycoproteins. FimH is essential for UTI pathogenesis and thus is a promising therapeutic target.

Areas Covered: Herein, we review the structural frameworks of FimH antagonists disclosed in the patent literature. X-ray crystallographic binding studies of D-mannose and early FimH antagonists have uncovered key molecular interactions. Exploiting this knowledge, mannosides with extraordinarily high binding affinities have been designed. Structure-activity relationships (SAR) and structure-property relationship (SPR) studies have resulted in the rapid development of orally bioavailable FimH antagonists with promising therapeutic potential for UTI and CD.

Expert opinion: It is our opinion that biaryl or ‘two-ring’ mannosides, which represent the largest and most thoroughly tested class of FimH antagonists, also hold the most promise as a novel treatment for UTIs. These antagonists have also been shown to have efficacy in treating CD. Judging from the strong preclinical data, we predict that one or more FimH antagonists will be entering the clinic within the next 1–2 years.     

Phase 0 Study of Vandetanib-Eluting Radiopaque Embolics as a Preoperative Embolization Treatment in Patients with Resectable Liver Malignancies

PurposeTo assess the safety and tolerability of a vandetanib-eluting radiopaque embolic (BTG-002814) for transarterial chemoembolization (TACE) in patients with resectable liver malignancies.Materials and MethodsThe VEROnA clinical trial was a first-in-human, phase 0, single-arm, window-of-opportunity study. Eligible patients were aged ≥18 years and had resectable hepatocellular carcinoma (HCC) (Child-Pugh A) or metastatic colorectal cancer (mCRC). Patients received 1 mL of BTG-002814 transarterially (containing 100 mg of vandetanib) 7–21 days prior to surgery. The primary objectives were to establish the safety and tolerability of BTG-002814 and determine the concentrations of vandetanib and the N-desmethyl vandetanib metabolite in the plasma and resected liver after treatment. Biomarker studies included circulating proangiogenic factors, perfusion computed tomography, and dynamic contrast-enhanced magnetic resonance imaging.ResultsEight patients were enrolled: 2 with HCC and 6 with mCRC. There was 1 grade 3 adverse event (AE) before surgery and 18 after surgery; 6 AEs were deemed to be related to BTG-002814. Surgical resection was not delayed. Vandetanib was present in the plasma of all patients 12 days after treatment, with a mean maximum concentration of 24.3 ng/mL (standard deviation ± 13.94 ng/mL), and in resected liver tissue up to 32 days after treatment (441–404,000 ng/g). The median percentage of tumor necrosis was 92.5% (range, 5%–100%). There were no significant changes in perfusion imaging parameters after TACE.ConclusionsBTG-002814 has an acceptable safety profile in patients before surgery. The presence of vandetanib in the tumor specimens up to 32 days after treatment suggests sustained anticancer activity, while the low vandetanib levels in the plasma suggest minimal release into the systemic circulation. Further evaluation of this TACE combination is warranted in dose-finding and efficacy studies.     

Mannose binding lectin 2 promotor-221 X/Y gene polymorphism in Egyptian systemic lupus erythematosus patients

Aim of the workThe present study was undertaken to determine whether mannose binding lectin-2 (MBL2) promotor-221X/Y gene polymorphism had a possible association with systemic lupus erythematosus (SLE) in Mansoura city.Patients and methodsWe analyzed functional polymorphisms in the promoter of MBL2 gene in 106 Egyptian SLE patients and 99 healthy controls by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). SLE disease activity was evaluated using SLE Disease Activity Index (SLEDAI) and organ damage was evaluated using SLE International Collaborating Clinic Damage Index (SLICC/DI).ResultsThe patients were 95 females and 11 males with a mean age of 34.4 ± 10.2 years and disease duration of 4 ± 3.03 years. Genotype frequencies of MBL2 were significantly different between patients and controls. The YY genotype was significantly associated with SLE in 77 (72.6%) patients compared to the control in 59 (59.6%) (p = 0.048). The XY genotype was in 29 (27.4%) patients and in 40 (40.4%) control. An association was found between the XY genotype and alopecia (p = 0.048), central nervous system involvement (p = 0.03), vasculitis (p = 0.004) and anti-phospholipid syndrome (p = 0.001) while the YY genotype was associated with discoid rash, low serum complement level (C3; p = 0.014 and C4; p = 0.008) and with the presence of anticardiolipin antibodies (p = 0.032). MBL genotype did not show any correlation with SLEDAI or SLICC/DI.ConclusionOur results indicate that MBL2 promotor-221X/Y polymorphism is a possible key-player for SLE development as well as the occurrence of some clinical and laboratory features. Further longitudinal studies including other single nucleoproteins are needed to clarify the role of MBL2.     

Mannose-binding lectin 2 rs11003123 polymor-phism is associated with the development of hepatocellular carcinoma in patients with hepa-titis B-related cirrhosis in the Chinese population

BACKGROUND: Mannose-binding lectin 2 (MBL2) plays a key role in the host immune response, but whether it is associ-ated with hepatocellular carcinoma (HCC) is not clear. The present study aimed to identify the association between MBL2 gene polymorphisms and HCC in patients with hepatitis B virus (HBV)-related cirrhosis in the Chinese population.
METHODS: A single-nucleotide polymorphism of MBL2, rs11003123, was genotyped and analyzed in a case-control study of HBV-related cirrhotic patients with HCC (n=77) and without HCC (n=40).
RESULTS: We found that Child-Pugh proifles, model for end-stage liver disease score, and the incidence of encephalopathy were all higher in the non-HCC group (P<0.05). A signiifcant association between allele mutants and HCC occurrence was demonstrated by allele comparison (A vs G) (OR=0.34; 95%CI: 0.15-0.76;P=0.006). Heterozygous comparison (GA vs GG) revealed that the individuals with GA mutants had a reduced risk of HCC occurrence compared with those with GG wild type (adjusted OR=0.28; 95% CI: 0.10-0.80;P=0.004). In a dominant model (GA+AA vs GG), a decreased risk of HCC occurrence was observed in individuals with variant geno-types (GA and AA) compared with those with the wild type (adjusted OR=0.30; 95% CI: 0.11-0.85;P=0.004). However, no statistically signiifcant associations were observed between rs11003123 and prognosis of patients with HCC after liver transplantation in both recurrence-free survival and overall survival (P=0.449 andP=0.384, respectively).
CONCLUSION: MBL2 rs11003123 polymorphism may be a marker for the risk of HCC occurrence in patients with HBV-related cirrhosis in the Chinese population.