Diagnostic value of gamma-glutamyltransferase/aspartate aminotransferase ratio, protein induced by vitamin K absence or antagonist II, and alpha-fetoprotein in hepatitis B virus-related hepatocellular carcinoma

BACKGROUND Researchers have investigated the diagnostic value of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and obtained abundant clinical diagnostic data. However, PIVKA-II and AFP have unsatisfactory specificity and sensitivity in the diagnosis of early-stage HBV-related HCC. Gamma-glutamyltransferase (γ-GT) and aspartate aminotransferase (AST) are common biomarkers for evaluating liver function, and we hypothesized that the γ-GT/AST ratio in combination with PIVKA-II and AFP would improve the diagnosis of early-stage HBV-related HCC. AIM To evaluate the diagnostic value of γ-GT/AST ratio alone or in combination with PIVKA-II and AFP in HBV-related HCC. METHODS Serum levels of γ-GT, AST, PIVKA-II, and AFP were detected and analysed in 176 patients with HBV-related HCC and in 359 patients with chronic hepatitis B. According to tumour size and serum level of HBV DNA, HBV-related HCC patients were divided into the following categories: Early-stage HCC patients, HCC patients, HBV DNA positive (HBV DNA+) HCC patients, and HBV DNA negative (HBV DNA-) HCC patients. Receiver-operating characteristic (ROC) curves were used to analyse and compare the diagnostic value of the single and combined detection of various biomarkers in different types of HBV-related HCC. RESULTS Tumour size was positively correlated with serum levels of PIVKA-II and AFP in HCC patients (r = 0.529, aP < 0.001 and r = 0.270, bP < 0.001, respectively), but there was no correlation between tumour size and the γ-GT/AST ratio (r = 0.073, P = 0.336). The areas under the receiver-operating characteristic curves (AUROCs) of the γ-GT/AST ratio in early-stage HCC patients, HBV DNA+ HCC patients and HBV DNA- HCC patients were not significantly different from that in the total HCC patients (0.754, 0.802, and 0.705 vs 0.779, respectively;P > 0.05). When PIVKA-II was combined with the γ-GT/AST ratio in the diagnosis of earlystage HCC, HCC, and HBV DNA+ HCC, the AUROCs of PIVKA-II increased, with values of 0.857 vs 0.835, 0.925 vs 0.913, and 0.958 vs 0.954, respectively. When AFP was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, HBV DNA+ HCC, and HBV DNA- HCC, the AUROCs of AFP increased, with values of 0.757 vs 0.621, 0.837 vs 0.744, 0.868 vs 0.757, and 0.840 vs 0.828, respectively. CONCLUSION The γ-GT/AST ratio may be better than PIVKA-II and AFP in the diagnosis of early-stage HBV-related HCC, and its combination with PIVKA-II and AFP can improve the diagnostic value for HBV-related HCC.

Vitamin K and hepatocellular carcinoma: The basic and clinic

Vitamin K(VK), which was originally identified as a cofactor involved in the production of functional coagulation factors in the liver, has been shown to be involved in various aspects of physiological and pathological events, including bone metabolism, cardiovascular diseases and tumor biology. The mechanisms and roles of VK are gradually becoming clear. Several novel enzymes involved in the VK cycle were identified and have been shown to be linked to tumorigenesis. The VKs have been shown to suppress liver cancer cell growth through multiple signaling pathways via the transcription factors and protein kinases. A VK2 analog was applied to the chemoprevention of hepatocellular carcinoma(HCC) recurrence after curative therapy and was shown to have beneficial effects, both in the suppression of HCC recurrence and in patient survival. Although a large scale randomized control study failed to demonstrate the suppression of HCC recurrence, a meta-analysis suggested a beneficial effect on the long-term survival of HCC patients. However, the beneficial effects of VK administration alone were not sufficient to prevent or treat HCC in clinical settings. Thus its combination with other anti-cancer reagents and the development of more potent novel VK derivatives are the focus of ongoing research which seeks to achieve satisfactory therapeutic effects against HCC.

Protein induced by vitamin K absence or antagonist Ⅱ-producing gastric cancer

Protein induced by vitamin K absence or antagonist Ⅱ(PIVKA-Ⅱ) is a putative specific marker of hepatocellular carcinoma(HCC),but it may also be produced by asmall number of gastric cancers.To date,16 cases of PIVKA-Ⅱ-producing gastric cancer have been reported,2 of which were reported by us and all of which were identified in Japan.There are no symptoms specific to PIVKA-Ⅱ-producing gastric cancer,and the representative clinical symptoms are general fatigue,appetite loss,and upper abdominal pain.Serum alpha-feto-protein(AFP)levels are also increased in almost allcases.Liver metastasis is observed in approximately 80% of cases and portal vein tumor thrombus is ob-served in approximately 20% of cases.Differential diagnosis between metastatic liver tumor and HCC is often difficult.Grossly,almost all cases appear as advanced gastric cancer.Histologically,a hepatoid pattern is observed in many cases,in addition to a moderately to poorly differentiated adenocarcinoma component.The production of PIVKA-Ⅱ and AFP is usually confirmed using immunohistochemical staining.Treatment and prognosis largely depends on the existence of liver meta-stasis,and the prognosis of patients with liver metas-tasis is very poor.PIVKA-Ⅱ may be produced during the hepatocellular metaplasia of the tumor cells.

Assessment of Oral Anticoagulation with Vitamin K Antagonists in Patients Living in a Low-Income Country of West Africa

Introduction: Despite the rise of direct oral anticoagulants (DOACs), vitamin K antagonists (VKA) remain the most widely used oral anticoagulants in developing countries. The aim of this study was to estimate the prevalence of good anticoagulation in patients treated with VKA in Lomé and describe associated factors. Methods: This was a cross-sectional study conducted from November 2019 to October 2020 in the cardiology departments of two University teaching hospitals in Lomé (CHU Sylvanus Olympio and CHU Campus), involving patients on VKA for ≥3 months, with a target international normalized ratio (INR) of 2.5 and a therapeutic margin between 2 and 3. The quality of anticoagulation was assessed by the time in therapeutic range (TTR) which was assessed by the Rosendaal method. Good anticoagulation was defined by a TTR > 70%. Results: A total of 344 patients were included (mean age = 58 ± 13.8 years, women = 56.1%). Indications for VKA treatment were represented by venous thromboembolic disease (43.3%), supraventricular arrhythmia (28.2%), severe left ventricular systolic dysfunction (19.8%) and pulmonary hypertension (8.7%). The average TTR was 47.6 ± 20.8%. The rate of good anticoagulation was 17.7%. Factors associated with good anticoagulation were the use of fluindione vs acenocoumarol (OR = 11.17;95% CI: 3.2 - 39.6;p = 0.0002), concomitant low-dose aspirin (OR 4.44;95% CI: 1.4 - 13.9;p = 0.01) and INR monitoring exclusively by the patient himself (OR = 4.92;95% CI: 1.5 - 16.3;p = 0.008). The rate of thromboembolic and hemorrhagic complications was each 2.6% and was not correlated with the quality of anticoagulation. Quality of anticoagulation by VKAs was poor in our practice. Factors associated with good anticoagulation were the use of fluindione vs acenocoumarol, concomitant low-dose aspirin and monitoring of INR exclusively by the patient himself. Conclusion: The quality of oral anticoagulation by VKAs could be improved in our practice by the creation of anticoagulation clinics for better therapeutic education of patients and efficient management of VKA dose, and the use of prescription assistance software.

Hepatocellular Carcinoma: Known and Emerging Risk Factors

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer with a high mortality rate. While chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections represent the leading risk factors worldwide, the spreading of metabolic disorders, such as diabetes, obesity and non-alcoholic fatty liver disease (NAFLD) justifies the increasing attention on their oncogenic mechanisms. This review discusses about the main pathogenic mechanisms implicated in occurrence of HCC in presence of viral and metabolic diseases. Additionally, it points to the importance of clinical surveillance for those patients considered at risk of HCC and highlights the strategical role of serum markers, such as alfa-fetoprotein (αFP) and Protein Induced by Vitamin K Absence or Antagonist II (PIVKA-II), which, in association to a strictly instrumental follow-up, contribute to the early detection of hepatic nodules with a better prognosis for affected patients.

Remission of Abdominal Colic During Enteroscopy by Injecting Vitamin K_3 into Zusanli Acupoint

In 1970s,sedatives or spasmolytics needed to beadministered 30 minutes prior to performingenteroscopy to relieve abdominal colic during theexamination.Owing to the improvement in operatingskills,such drugs are no more used today.However,anumber of patients still suffer from abdominal coliccaused by irritated colon in the process ofenteroscopy.For severe cases,the operator has nochoice but to suspend the examination.To find a

GA_3对烤烟品种新K326上部烟叶农艺性状及烟碱含量的影响

研究了植物生长调节剂赤霉酸(GA3)水溶液叶面喷施对烤烟品种新K326上部烟叶长度、宽度及厚度的影响,并探讨了外源GA3喷施浓度与上部烟叶烟碱含量及糖碱比值间的关系、GA3喷施浓度与烟叶等级结构和产值间的关系.主要结果是:(1)外源GA3浓度与上部烟叶的长度、宽度及糖碱比值均呈正相关,前二者达显著水平,后者达极显著水平;而与上部烟叶的厚度及总烟碱含量分别呈显著与极显著负相关.(2)GA3的最佳喷施质量分数为25×10-6.该处理的上部烟叶中倒数第四叶位B2L等级初烤烟的厚度、总烟碱含量与糖碱比值分别为90.6μm,2.97%与8.3,与对照相比其厚度与总烟碱含量显著下降、糖碱比值显著上升,烟叶的可用性明显提高,且质量分数为25×10-6喷施处理后上部烟叶的上中等烟百分率与产值都较高.(3)GA3喷施上部烟叶可使中部烟叶的总烟碱含量稍有下降、糖碱比值稍有上升,但对中部烟叶的厚度、中下部烟叶的上中等烟百分率与产值影响不大.

Dietary Vitamin K Restriction and Effectiveness of Vitamin K Antagonists Prescribed at the CNHU-HKM University Cardiology Clinic/BENIN

Introduction: Their efficacy in preventing thrombotic and embolic events has been proven in numerous studies, but their narrow therapeutic index requires particular vigilance, especially in terms of biology. In addition, treatment-related hemorrhagic complications are not uncommon. This study explores the influence of dietary vitamin K restriction on the efficacy of antivitamin K treatment at the University Cardiology Clinic of CNHU-HKM. Methods: Cross-sectional and descriptive study that took place from 25 April to 29 August 2019. Patients’ dietary behaviors and successive INR values were collected. Information on dietary intake was obtained by 2 non-consecutive 24-hour recalls. The effectiveness of VKA treatment was assessed by the “Time in Therapeutic Range” (TTR) of the INR. VKA treatment was considered effective for a TTR greater than 65%. Results: At the end of this study, 40 patients were surveyed. The mean age of the participants was 58.05 years ± 13.32 years, with a sex ratio of 1.35. Complete arrhythmia due to atrial fibrillation was the main indication for VKA treatment (37.50%) and fluindione was the most commonly prescribed drug (77.50%). The duration of treatment was less than or equal to 2 years in 47.5% of the subjects surveyed. Before starting treatment, 85% of patients received advice on restricting vitamin K-rich foods, and 45% of patients reported “food burnout” after a period of compliance with the restriction. The majority of respondents (97.50%) complied with the restriction on vitamin K-rich foods. All respondents had high energy intakes and a poor distribution of macronutrients, with a predominance of carbohydrates and proteins. 2.5% of respondents were on effective anti-vitamin K therapy with a TTR of over 65%. Conclusion: Restriction of vitamin K-rich foods is not conducive to effective treatment with vitamin K antagonists.

Adequate antiplatelet regimen in patients on chronic anti-vitamin K treatment undergoing percutaneous coronary intervention

AIM: To investigate the impact of dual antiplatelet therapy (DAT) in patients on antivitamin K (AVK) regimen requiring percutaneous coronary intervention (PCI).METHODS: Between February 2006 and February 2008, 138 consecutive patients under chronic AVK treatment were enrolled in this registry. Of them, 122 received bare metal stent implantation and 16 received drug elutingstent implantation. The duration of DAT, on top of AVK treatment, was decided at the discretion of the clinician. Adequate duration of DAT was def ined according to type of stent implanted and to its clinical indication. RESULTS: The baseline clinical characteristics of patients reflect their high risk, with high incidence of comorbid conditions (Charlson score ≥ 3 in 89% of the patients). At a mean follow-up of 17 ± 11 mo, 22.9% of patients developed a major adverse cardiac event (MACE): 12.6% died from cardiovascular disease and almost 6% had an acute myocardial infarction. Major hemorrhagic events were observed in 7.4%. Adequate DAT was obtained in only 44% of patients. In the multivariate analysis, no adequate DAT and Charlson score were the only independent predictors of MACE (both P = 0.02). CONCLUSION: Patients on chronic AVK therapy represent a high risk population and suffer from a high MACE rate after PCI. An adequate DAT regimen and absence of comorbid conditions are strongly associated with better clinical outcomes.

Effect of Vitamin K1 on Cell Growth Inhibition and Apoptosis on the U937 Cell Line

This experiment was conducted in order to verify the role of Vitamin K1 as a cell growth inhibitor on the U937 cell line. This experiment was performed in two parts—one with a lesser concentration of Vitamin K1, and the other with a range of concentrations from low-to-high. Through the remaining number of U937 cells, as well as cell areas, it was concluded that the presence of Vitamin K1 reduces the number of cancer cells. It was also concluded that as Vitamin K1 concentration increases, so does the frequency and effects of apoptosis.

Clinical Study of Vitamin K_3 Acupoint Injection In Treating Pelvic Pain

Pelvic pain is one of the most common symptoms in gynecologic outpatients. Primary dysmenorrhea, acute or chronic pelvic inflammatory disease, endometriosis, post-operational pelvic adhesion, blood stagnation of pelvic vein, etc. , are mentioned as the often encountered causes of pelvic pain. It has been reported in the recent ten or more years that intramuscular injection of vitamin K3 (Vit K3) could relieve pain induced by smooth muscle spasm. In order to evaluate the effect of Vit K3 administered by acupoint injection in relieving pelvic pain, 180 patients were treated and observed from April 1997 to April 1999 in our hospital, and good therapeutic effect was obtained. It was reported as follows.

Prohibitins, novel vitamin K2 target factors in osteoblast

Vitamin K2 (VK2, menaquinone) is a drug for osteoporosis. VK2 acts as a cofactor for γ-glutamyl carboxylase, which catalyzes the carboxylation of specific glutamic acid residues (γ-carboxylation) of substrate proteins. Here we demonstrate that VK2 also regulate osteoblastgenic marker gene expression. Using VK2-immobilzed nanobeads new target proteins were purified and identified from osteoblastic cell line. They are prohibitin 1 and 2 (PHB1 & 2), respectively. To confirm the PHBs function on VK2-dependent transcription, PHB1 & 2 were knock-down and osteocalcin gene 2 transcriptions were analyzed, indicating that PHBs regulate VK2-dependent transcription. Taken together PHBs are VK2 target proteins for osteoblastgenic transcription.

Biochemical changes in phenols,flavonoids,tannins,vitamin E,β-carotene and antioxidant activity during soaking of three white sorghum varieties

Objective:To investigate the changes in total phenols,flavonoids,tannins,vitamin E, β-carotene and antioxidant activity during soaking of three white sorghum varieties.Methods: The changes in total phenols,total ilavonoids,tannins,phenolic acids compounds,flavonoid components,vitamin E,P-carotene and antioxidant activity during soaking of sorghum grains were determined.Results:Total phenols,total flavonoids,tannins,vitamin E,P-carotene and antioxidant activity in raw sorghum were ranged from 109.21 to 116.70,45.91 to 54.69,1.39 to 21.79 mg/100 g,1.74 to 5.25,0.54 to 1.19 mg/kg and 21.72%to 27.69%and 25.29%to 31.97%,respectively. The above measured compounds were significantly decreased after soaking.p-Hydroxybenzoic acid,vanillic acid,syringic acid and cinnamic acid represent the major phenolic acids in Dorado variety.While ferulic acid,p-coumaric acid,gallic acid and caffeic acid represent the major phenolic acids in Shandaweel-6.On the other hand,protocatechuic acid represents the major phenolic acids in Giza-15.Regarding flavonoids components,Dorado was the highest variety in kampferol and naringenin while Shandaweel-6 was the highest variety in luteolin, apigenin,hypersoid,quercelin and christen.Finally,Giza-15 was the highest variety in catechin. Phenolic acids,flavonoid compounds and antioxidant activities were decreased after soaking. Conclusions:Sorghum varieties have moderate quantities from total phenols,total flavonoids, tannins,phenolic acids compounds,flavonoid components,vitamin E,P-carotene and antioxidant activity which decreased after soaking.

Synthesis of Vitamin K_(2(10))

The Diels-Alder adduct, which is prepared from a phase transfer catalyzed reaction of menadione witb cyclopentadiene, was alkylated with geranyl chloride on sodium amide as a deproteined reagent to form the corresponding alkylation product, from which vitamin K2(10) is obtained by a retro-DielsAlder reaction.

纯化ETEC K88菌毛特异性卵黄抗体的加工贮藏及体外抗粘附性研究

分离、纯化产肠毒素大肠杆菌(ETEC) K88ac菌毛蛋白,将其免疫产蛋鸡,经喷雾干燥制备抗ETEC菌毛抗原特异性卵黄抗体粉。间接ELISA法检测卵黄抗体效价,试验结果表明,喷雾干燥(140℃进气,65℃出气)对卵黄抗体活性无影响,加工前后抗体滴度均为1∶1280;卵黄抗体粉在90℃干热条件下处理5min后抗体效价下降50%,而90℃湿热条件下处理5min抗体效价无明显变化,但处理15min后下降75%;经过1h的干热或湿热处理,抗体均基本失活;4℃和常温下放置半年对卵黄抗体粉活性无影响;体外抑制粘附试验表明,抗K88卵黄抗体能抑制K88对肠上皮细胞的粘附。

The risk of bleeding of triple therapy with vitamin K-antagonists,aspirin and clopidogrel after coronary stent implantation:Facts and questions

Background Triple therapy(TT)with vitamin K-antagonists(VKA),aspirin and clopidogrel is the recommended antithrombotic treatment following percutaneous coronary intervention with stent implantation(PCI-S)in patients with an indication for oral anticoagulation.TT is associated with an increased risk of bleeding,but available evidence is flawed by important limitations,including the limited size and the retrospective design of most of the studies,as well as the rare reporting of the incidence of in-hospital bleeding and the treatment which was actually ongoing at the time of bleeding.Since the perceived high bleeding risk of TT may deny patients effective strategies,the determination of the true safety profile of TT is of paramount importance.Methods All the 27 published studies where the incidence of bleeding at various time points during follow-up has been reported separately for patients on TT were reviewed,and the weakness of the data was analyzed.Results The absolute incidence of major bleeding upon discharge at in-hospital,≤1 month,6 months,12 months and≥12 months was:3.3%±1.9%,5.1%±6.7%,8.0%±5.2%,9.0%±8.0,and 6.2%±7.8%,respectively,and not substantially different from that observed in previous studies with prolonged dual antiplatelet treatment with aspirin and clopidogrel.Conclusions While waiting for the ongoing,large-scale,registries and clinical trials to clarify the few facts and to answer the many questions regarding the risk of bleeding of TT,this treatment should not be denied to patients with an indication for VKA undergoing PCI-S provided that the proper measures and cautions are implemented.

Cutaneous allergic reaction to subcutaneous vitamin K_(1):A case report and review of literature

BACKGROUND Vitamin K1(phytomenadione)is a fat-soluble naturally occurring vitamin that is widely used to treat certain coagulation disorders.Adverse cutaneous reactions to vitamin K1 can occur;however,owing to its low incidence and considerable variability in presentation and morphology,its diagnosis can be easily overlooked.Managing these reactions may be challenging for patients and clinicians.Therefore,reviewing the adverse cutaneous reactions to vitamin K1 is important.CASE SUMMARY Here we report the case of a 50-year-old woman with no pre-existing hepatic disease who developed a cutaneous allergic reaction to subcutaneous vitamin K1 that presented as localized eczematous plaques at the vitamin K1 injection site.The eruption developed within 5 d of the injection and persisted for 32 mo despite treatment with topical and intralesional steroids.Eczema was diagnosed based on the results of the pathological examination,immunohistochemical staining,and a skin biopsy.The patient was advised to take herbal medicines orally twice daily.After treatment and follow-up,the patient’s eczematous urticarial plaques improved and her condition stabilized.CONCLUSION Here we present the first case of a cutaneous allergic reaction to subcutaneous vitamin K1 that was successfully treated with Chinese medicine.

Real-world comparison of non-vitamin K antagonist oral anticoagulants and warfarin in Asian octogenarian patients with atrial fibrillation

BackgroundThe 功效和非维生素 K 对手的安全口头的抗凝剂(NOAC ) 和在亚洲八十至八十九岁的 atrial 的 warfarin 纤维性颤动(AF ) 病人没在一个真实世界的背景被建立。我们试图 &#x02265 在 293 个连续病人全部的朝鲜八十至八十九岁的 patients.MethodsA 评估 NOAC 和 warfarin 的功效和安全；有非瓣膜的 AF 的 80 年拿了任何一个 NOAC (148 个盒子， 50.5%) 或 warfarin (145 个盒子， 49.5%) 回顾地被考察。功效结果是击或全身的栓塞合成。安全结果是主要 bleeding.ResultsThe 后续持续时间是 375 耐心年(172 与 NOAC 耐心年并且 203 与 warfarin 耐心年) 。NOAC 上的病人稍微更老(P = 0.006 ) 并且有的稍微更高的有流血分数(P = 0.034 ) 。两抗凝剂的功效高(1.16% 为 NOAC 对 2.98% 为 warfarin 每 100 耐心年， P = 0.46 ) 。安全结果在 NOAC 和 warfarin 组相对高(8.96% 对 12.46% ， P = 0.29 ) 。功效和安全结果趋于比在普通剂量 NOAC 或 warfarin 在低剂量 NOAC 非显著地减少(0.85% 对 1.84% 对 2.98% 在功效结果， P = 0.69；并且 6.97% 对 13.29% 对 12.46% 在安全结果， P = 0.34 ).ConclusionsNOACs 在亚洲八十至八十九岁的 AF 病人为击或全身的栓塞的预防是高度有效的。然而，主要流血在两个抗凝剂组高过分地发生了。进一步的学习在八十至八十九岁的人口在最佳的抗凝剂政体上被要求。

Excess vitamin intake:An unrecognized risk factor for obesity

Over the past few decades,food fortification and infant formula supplementation with high levels of vitamins have led to a sharp increase in vitamin intake among infants,children and adults.This is followed by a sharp increase in the prevalence of obesity and related diseases,with significant disparities among countries and different groups within a country.It has long been known that B vitamins at doses below their toxicity threshold strongly promote body fat gain.Studies have demonstrated that formulas,which have very high levels of vitamins,significantly promote infant weight gain,especially fat mass gain,a known risk factor for children developing obesity.Furthermore,ecological studies have shown that increased B vitamin consumption is strongly correlated with the prevalence of obesity and diabetes.We therefore hypothesize that excess vitamins may play a causal role in the increased prevalence of obesity.This review will discuss:(1)the causes of increased vitamin intake;(2)the non-monotonic effect of excess vitamin intake on weight and fat gain;and(3)the role of vitamin fortification in obesity disparities among countries and different groups within a country.