Evaluation of screening performance of first-trimester competing-risks prediction model for small-for-gestational age in Asian population.

OBJECTIVE: To examine the external validity of the Fetal Medicine Foundation (FMF) competing-risks model for the prediction of small-for-gestational age (SGA) at 11-14 weeks' gestation in an Asian population. METHODS: This was a secondary analysis of a multicenter prospective cohort study in 10 120 women with a singleton pregnancy undergoing routine assessment at 11-14 weeks' gestation. We applied the FMF competing-risks model for the first-trimester prediction of SGA, combining maternal characteristics and medical history with measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF) concentration. We calculated risks for different cut-offs of birth-weight percentile (< 10th , < 5th or < 3rd percentile) and gestational age at delivery (< 37 weeks (preterm SGA) or SGA at any gestational age). Predictive performance was examined in terms of discrimination and calibration. RESULTS: The predictive performance of the competing-risks model for SGA was similar to that reported in the original FMF study. Specifically, the combination of maternal factors with MAP, UtA-PI and PlGF yielded the best performance for the prediction of preterm SGA with birth weight < 10th percentile (SGA < 10th ) and preterm SGA with birth weight < 5th percentile (SGA < 5th ), with areas under the receiver-operating-characteristics curve (AUCs) of 0.765 (95% CI, 0.720-0.809) and 0.789 (95% CI, 0.736-0.841), respectively. Combining maternal factors with MAP and PlGF yielded the best model for predicting preterm SGA with birth weight < 3rd percentile (SGA < 3rd ) (AUC, 0.797 (95% CI, 0.744-0.850)). After excluding cases with pre-eclampsia, the combination of maternal factors with MAP, UtA-PI and PlGF yielded the best performance for the prediction of preterm SGA < 10th and preterm SGA < 5th , with AUCs of 0.743 (95% CI, 0.691-0.795) and 0.762 (95% CI, 0.700-0.824), respectively. However, the best model for predicting preterm SGA < 3rd without pre-eclampsia was the combination of maternal factors and PlGF (AUC, 0.786 (95% CI, 0.723-0.849)). The FMF competing-risks model including maternal factors, MAP, UtA-PI and PlGF achieved detection rates of 42.2%, 47.3% and 48.1%, at a fixed false-positive rate of 10%, for the prediction of preterm SGA < 10th , preterm SGA < 5th and preterm SGA < 3rd , respectively. The calibration of the model was satisfactory. CONCLUSION: The screening performance of the FMF first-trimester competing-risks model for SGA in a large, independent cohort of Asian women is comparable with that reported in the original FMF study in a mixed European population. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

First-trimester pre-eclampsia biomarker profiles in Asian population: multicenter cohort study.

OBJECTIVES: To (i) evaluate the applicability of the European-derived biomarker multiples of the median (MoM) formulae for risk assessment of preterm pre-eclampsia (PE) in seven Asian populations, spanning the east, southeast and south regions of the continent, (ii) perform quality-assurance (QA) assessment of the biomarker measurements and (iii) establish criteria for prospective ongoing QA assessment of biomarker measurements. METHODS: This was a prospective, non-intervention, multicenter study in 4023 singleton pregnancies, at 11 to 13 + 6 weeks' gestation, in 11 recruiting centers in China, Hong Kong, India, Japan, Singapore, Taiwan and Thailand. Women were screened for preterm PE between December 2016 and June 2018 and gave written informed consent to participate in the study. Maternal and pregnancy characteristics were recorded and mean arterial pressure (MAP), mean uterine artery pulsatility index (UtA-PI) and maternal serum placental growth factor (PlGF) were measured in accordance with The Fetal Medicine Foundation (FMF) standardized measurement protocols. MAP, UtA-PI and PlGF were transformed into MoMs using the published FMF formulae, derived from a largely Caucasian population in Europe, which adjust for gestational age and covariates that affect directly the biomarker levels. Variations in biomarker MoM values and their dispersion (SD) and cumulative sum tests over time were evaluated in order to identify systematic deviations in biomarker measurements from the expected distributions. RESULTS: In the total screened population, the median (95% CI) MoM values of MAP, UtA-PI and PlGF were 0.961 (0.956-0.965), 1.018 (0.996-1.030) and 0.891 (0.861-0.909), respectively. Women in this largely Asian cohort had approximately 4% and 11% lower MAP and PlGF MoM levels, respectively, compared with those expected from normal median formulae, based on a largely Caucasian population, whilst UtA-PI MoM values were similar. UtA-PI and PlGF MoMs were beyond the 0.4 to 2.5 MoM range (truncation limits) in 16 (0.4%) and 256 (6.4%) pregnancies, respectively. QA assessment tools indicated that women in all centers had consistently lower MAP MoM values than expected, but were within 10% of the expected value. UtA-PI MoM values were within 10% of the expected value at all sites except one. Most PlGF MoM values were systematically 10% lower than the expected value, except for those derived from a South Asian population, which were 37% higher. CONCLUSIONS: Owing to the anthropometric differences in Asian compared with Caucasian women, significant differences in biomarker MoM values for PE screening, particularly MAP and PlGF MoMs, were noted in Asian populations compared with the expected values based on European-derived formulae. If reliable and consistent patient-specific risks for preterm PE are to be reported, adjustment for additional factors or development of Asian-specific formulae for the calculation of biomarker MoMs is required. We have also demonstrated the importance and need for regular quality assessment of biomarker values. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Intravenous ketamine infusion for a patient with treatment-resistant major depression: a 10-month follow-up.

WHAT IS KNOWN AND OBJECTIVE: Ketamine in a subanaesthetic dose has been shown to produce rapid antidepressant effects. Here, we describe a long-term follow-up case of a Korean patient with severe major depression who received repeated ketamine intravenous therapy (KIT). CASE DESCRIPTION: A 49-year-old woman with a 6-year history of treatment-resistant major depression was given KIT once every 1 or 2 weeks over 10 months, for a total of 36 treatments. Her mood stabilized, and she showed a nearly 50% reduction in the severity of her depressive symptom. WHAT IS NEW AND CONCLUSION: Long-term repeated KIT may be an option for alleviating treatment-resistant and relapsing major depression. Further research and large clinical trials are needed on the optimum KIT protocol, including dose, dosing interval, total number of treatments and when to stop.

Prolonged inspiratory time produces better gas exchange in patients undergoing laparoscopic surgery: A randomised trial.

BACKGROUND: Laparoscopic surgery performed with a patient in the Trendelenburg position is known to have adverse effects on pulmonary gas exchange and respiratory mechanics. We supposed that prolonged inspiratory time can improve gas exchange at lower airway pressure. METHODS: One hundred patients undergoing gynaecologic laparoscopic surgery were randomly assigned to one of four groups: conventional inspiratory-to-expiratory (I : E) ratio (Group 1 : 2), I : E ratio of 1 : 1 (Group 1 : 1), 2 : 1 (Group 2 : 1), or 1 : 2 with external positive end-expiratory pressure (PEEP) of 5 cmH2 O (Group 1 : 2 PEEP). Tidal volume was set to 6 ml/kg, and I : E ratio was adjusted at the onset of pneumoperitoneum. Arterial blood gas analysis with measurements of partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2 /FiO2 ), and physiologic dead space-to-tidal volume ratio (VD /VT ) was performed 15 min after anaesthetic induction (T1), and 30 (T2) and 60 min (T3) after onset of CO2 insufflation. RESULTS: PaO2 /FiO2 at T3 in Groups 1 : 1, 2 : 1, and 1 : 2 PEEP were higher than Group 1 : 2. The partial pressure of arterial carbon dioxide at T3 in Group 2 : 1 was lower than the other groups. The VD /VT at T2 and T3 were lower in Groups 1 : 1 and 2 : 1 than Groups 1 : 2 and 1 : 2 PEEP. Peak or plateau airway pressure was higher in Group 1 : 2 PEEP than the other groups. CONCLUSIONS: A prolonged inspiratory time demonstrated a beneficial effect on oxygenation. Furthermore, it showed better CO2 elimination without elevating the peak or plateau airway pressure compared with applying external PEEP. In terms of gas exchange and respiratory mechanics, a prolonged inspiratory time appears to be superior to applying external PEEP in patients undergoing laparoscopic surgery in the Trendelenburg position.

The influence of patient position on withdrawal force of thoracic epidural catheters.

We investigated the forces required to remove thoracic epidural catheters to determine the effect of patient position on removal. Eighty-four patients undergoing open thoracotomy and thoracic patient-controlled epidural analgesia were enrolled. Catheterisation was performed under fluoroscopic guidance before surgery, and the patients were allocated to one of three position groups for removal: prone; sitting; and lateral. On the third postoperative day, the peak tension during withdrawal in the assigned position was measured. No differences in mean (SD) forces were found between groups: prone 1.61 (0.39) N, supine 1.62 (0.61) N and lateral 1.36 (0.56) N (p = 0.140). The withdrawal forces required to remove thoracic epidural catheters were not affected by the position. Thus, the position for removal can be determined by patient's choice and clinical judgement.

Comparison of desaturation and resaturation response times between transmission and reflectance pulse oximeters.

BACKGROUND: In general, there is a response time between actual arterial hypoxemia and its detection by pulse oximeters. We compared the desaturation and resaturation response times between two types of pulse oximeters, transmission and reflectance pulse oximeters, to find out which oximeter has a more rapid response time. METHODS: Thirty-three ASA 1 or 2 patients were enrolled in this study. A transmission pulse oximeter was placed on the index finger and a reflectance pulse oximeter was placed on the forehead and monitored simultaneously. After the induction of general anesthesia without pre-oxygenation, we waited until the oxygen saturation value of any of two pulse oximeters declined to 90%, and then mask ventilation was started with 100% oxygen. Oxygen saturation was recorded at an interval of 2 s during this time. RESULTS: The desaturation response time of SpO(2) to 95% after apnea was 82.0 s (interquartile range: 67.0-98.5 s) vs. 94.0 s (interquartile range: 84.0-106.5 s) (P<0.001) and SpO(2) to 90% was 94.0 s (interquartile range: 75.5-109.5 s) vs. 100.0 s (interquartile range: 84.5-114.5 s) (P<0.001) in the reflectance and transmission oximeters, respectively. The resaturation response time from mask ventilation to 100% SpO(2) was 23.2+/-5.6 vs. 28.9+/-7.6 s (P<0.001) in the reflectance and transmission oximeters, respectively. CONCLUSION: In clinical situations in which rapid changes in oxygen saturation are expected, we recommend the forehead reflectance pulse oximeter because it responds more quickly in detecting oxygen desaturation and resaturation compared with the transmission pulse oximeter.

Risk of intravascular injection in transforaminal epidural injections.

Transforaminal epidural injection is an effective method for treating spinal pain but can cause devastating complications that result from accidental vascular uptake of the injectate or a direct vascular injury. We prospectively evaluated the patient factors that might be associated with intravascular uptake during transforaminal epidural injections. A total of 2145 injections were performed on 1088 patients under contrast-enhanced real-time fluoroscopic guidance. The collected data included the patient's age, sex, body mass index, diagnosis, injection level, side of injection, history of spinal surgery at the targeted level, and the number of injections at the targeted site. The overall incidence of intravascular injection was 10.5% (224/2145). The highest incidence was at the cervical level (28/136; 20.6%), followed by the sacral level (111/673; 16.5%), the thoracic level (23/280; 8.2%) and the lumbar level (64/1056; 6.1%). The difference was significant for the cervical and sacral level compared with the lumbar and thoracic levels (p < 0.001). Intravascular injection was not associated with the other patient characteristics studied.

Comparison between high and low molecular weight hyaluronates in knee osteoarthritis patients: open-label, randomized, multicentre clinical trial.

Efficacy and safety of high and low molecular weight hyaluronates in knee osteoarthritis patients were compared in a randomized, open-label trial. Patients in the high molecular weight hyaluronate group were treated once weekly for 3 weeks and in the low molecular weight group once weekly for 5 weeks. We evaluated weight-bearing pain, degree of flexion, swelling and knee tenderness; frequency and amount of rescue medication; patient and investigator global assessment of pain, and safety over 12 weeks after final injection of study medication. Significant improvements in pain and WOMAC-Likert scores were observed in both groups, but not between groups. Knee joint pain improvement was noted in both groups by patients and investigators during follow-up. Close correlation was observed between patient- and investigator-reported data. There was no significant difference in side-effects between the groups. In conclusion, the efficacy and safety of high and low molecular weight hyaluronate are similar.

The sensing of plant signal molecules by Agrobacterium: genetic evidence for direct recognition of phenolic inducers by the VirA protein.

The virulence (vir) genes of Agrobacterium tumefaciens are induced by low-molecular-weight phenolic compounds and monosaccharides through a two-component regulatory system consisting of the VirA and VirG proteins. Although it is clear that the monosaccharides require binding to a periplasmic binding protein before they can interact with the sensor VirA protein, it is not certain whether the phenolic compounds also interact with a binding protein or directly interact with the sensor protein. To shed light on this question, we tested the vir-inducing abilities of several different phenolic compounds using two wild-type strains of A. tumefaciens, KU12 and A6. We found that several compounds such as 4-hydroxyacetophone and p-coumaric acid induced the vir of KU12, but not A6. On the other hand, acetosyringone and several other phenolic compounds induced the vir of A6, but not KU12. By transferring different Ti plasmids into isogenic chromosomal backgrounds, we showed that the phenolic sensing determinant is associated with the Ti plasmid. Subcloning of the Ti plasmid indicated that the virA locus determines which phenolic compounds can function as vir inducers. These results suggest that VirA directly senses the phenolic compounds for vir activation.

Characterization of an unusual sensor gene (virA) of Agrobacterium.

Previous studies have shown that the virulence(vir) genes of Agrobacterium tumefaciens strain KU12 are induced by a unique set of phenolic compounds that are non-functional in most strains of Agrobacterium. Further, strain KU12 is not induced by phenolic compounds that induce the vir genes in other strains. Previous studies have shown that these differences in inducing activity result from differences in the sensor protein for these signal molecules, the VirA protein. To gain some understanding of the basis for these differences in sensing ability, we sequenced the entire virA locus of pTiKU12, including its promoter region and compared this sequence with five different published virA sequences that respond in different ways to inducing compounds. The virA gene of KU12 is composed of an open single reading frame coding for 851 aa. At the aa level, the VirA protein of pTiKU12 is 45, 45, 49, 49 and 64% identical to the VirA proteins from pTiA6, pTi15955, pRiA4, pTiC58 and pTiAg162, respectively. The transcription start sites of pTiKU12 and pTiA6 virA genes differ significantly when mapped by primer extension. Unlike all other vir genes, except the virA gene of pTiAg162, pTiKU12 virA is constitutively expressed, and its synthesis is not induced by phenolic compounds. The lack of induction is accounted for by the fact that the promoter region does not have the conserved VirG-binding dodecadeoxynucleotide sequence (vir-box) that was previously identified in all promoter regions of inducible vir genes.

Molecular characterization of the virulence gene virG of pTiKU 12.

The virulence (vir) genes of Agrobacterium tumefaciens KU12, a Korean strain, were not induced by acetosyringone and the strain showed weak tumor forming ability and broad plant host ranges. We identified complete nucleotide sequence of virG of pTiKU12, an octopine Ti plasmid of this strain. When it was compared with those of other Ti plasmids, pTiKU12 virG contained an open reading frame (ORF) of 726 nucleotides which showed much lower homology (about 77%) than those (above 98%) already known among octopine Ti plasmids and it started with GTG codon instead of TTG found in other Ti plasmids. Only two vir boxes and one promoter region were confirmed in 5'-untranslated region instead of three vir boxes and two promoters which were found in pTiA6 virG. Nevertheless, important amino acids for the functional activity of VirG were so conserved that the virG included in pUCDG could complement a virG mutant Agrobacterium tumefaciens Mx19 in beta-galactosidase activity assays and on plant tumor tests.

The role of inverted repeat (IR) sequence of the virE gene expression in Agrobacterium tumefaciens pTiA6.

Agrobacterium tumefaciens pTiA6 virE promoter has a vir box, an inverted repeat (IR) sequence, a putative -35 region and a consensus -10 region. To study how the IR sequence of the virE promoter plays a role in virE gene expression, various mutants were constructed by base substitution and deletion in the virE promoter region. Substitution of the 3'-end region of the IR sequence, 5'-TCCGTTTCAA-3' to 5'-GCGGCCGCTC-3' displayed 2.6% of the native virE promoter activity. A deletion mutant of 5'-CGTTTCAA-3' on the 3'-end region of the IR sequence expressed 6% of the native virE promoter activity. These mutational analyses demonstrated that the IR sequence of the virE promoter plays a role as a cis-acting element in virE expression.

Role of -35 sequence and its cooperativity with vir-box for the expression of virE gene.

To elucidate the role of the -35 sequence and its cooperativity with vir box in the expression of the virE gene, various mutants were constructed by either site-directed mutation or deletional mutation of the virE promoter. The expression level of pHBAV, a mutant where its putative -35 sequences (CCGAGT) have been substituted with the consensus -35 sequences of the Escherichia coli promoter (TTGACA), was increased by 386%. pECHV, containing the conserved -35 sequence but lacking the vir box and the 5'-half of the imperfect dyad symmetry region (DSR) showed an increase of 286% in its promoter activity. pESHV, containing the conserved -35 sequence but lacking the complete 5'-upstream region from the mid-region of imperfect DSR, exhibited 244% of the native virE promoter activity. pHBCA, containing the conserved -35 sequence but destroying the vir box, was constructed by substitution of A, C, T at the positions -62, -63, and -65 on the vir-box to T, A, C, respectively. These mutations increased promoter activities by 319%. On the other hand, when the vir box was mutated from imperfect DSR to almost perfect DSR with T to A and G to T substitutions at -60 and -61 positions of the virE promoter containing the conserved -35 sequence (pHBNA), a higher activity of 671% was observed. These results demonstrate that when the putative -35 sequence of virE promoter is replaced with the consensus -35 sequence, the virE gene can be expressed independently without the binding of VirG protein to the vir-box and/or the induction of acetosyringone. Moreover, the presence of an almost perfect dyad symmetry of the vir-box can increase the expression of virE synergistically with the consensus -35 sequence.

The effects of intermittent inflow occlusion and hepatic steatosis on postoperative liver functions in living liver donors undergoing right hepatectomy.

BACKGROUND: Intermittent inflow occlusion (IIO) is a safe, effective method to reduce blood loss during liver resection and preserve function even among patients with underlying diseases such as steatosis and cirrhosis. Therefore, we evaluated the impact of IIO on postoperative liver function tests (LFT) and on morbidity among living liver donors undergoing a right hepatectomy, including donors with mild degrees (5%-30%) of macrovesicular steatosis (MaS). METHODS: We retrospectively reviewed the medical records of 186 living liver donors from August 2008 to September 2010. Donors were divided into two groups according to group IIO (n=81) versus Controls (no IIO, n=105). Within each group, donors were subdivided to evaluate Peak values of LFTs and complications into according the degree of MaS: group I_5 (n=36); IIO+<5% MaS, group I_30 (n=45); IIO+5%-30% MaS, group C_5 (n=55); Control+<5% MaS, and group C_30 (n=50); Control+5%-30% MaS. RESULTS: Peak aspartate aminotransferase (AST) and alanine aminotransferase (ALT) among IIO were significantly higher than Non-IIO. These values in groups I_5 and I_30 were significantly higher than groups C_5 and C_30, respectively (all, P<.01). The overall postoperative complications were comparable between groups IIO and Non-IIO, but significantly higher among group I_30 than groups I_5 (P=0.024) and C_30 (P=.012). CONCLUSIONS: Application of IIO in donors with mild macrosteatosis undergoing right hepatectomy showed significantly higher postoperative peak liver functions tests and number of overall complications than those without IIO.

Impact of hepatic macrovesicular and microvesicular steatosis on the postoperative liver functions after right hepatectomy in living donors.

PURPOSE: The aim of this study was to evaluate the impact of macrovesicular (MaS) and microvesicular steatosis (MiS) on postoperative liver function in living donors undergoing right hepatectomy. METHODS: We retrospectively reviewed the medical records of 450 living liver donors who underwent right hepatectomy between 2000 and 2009. First, we divided the donors into two groups according to the degree of MaS regardless of MiS: group MaS_5 (n=250), donors with <5% MaS and group MaS_30 (n=200), donors with 5% to 30% MaS. Second, we stratified donors according to the degree of MiS regardless of Mas: group MiS_5 (n=163), donors with <5% MiS, group MiS_30 (n=287), and 5%-30% MiS. We evaluated the peak values of total bilirubin (TB), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) until the thirtieth postoperative day (POD). Next, we assessed the relation between MaS or MiS and postoperative peak liver function tests using regression analysis. RESULTS: Peak values of postoperative AST (227±77 vs 203±67, respectively) and ALT (232±85 vs. 198±72, respectively) were significantly higher in the group MaS_30 than MaS_5. Similarly, the peak values of AST (225±80 vs 194±50, respectively) and ALT (228±85 vs 186±60, respectively) were significantly higher in the group MiS_30 than the group MiS_5. Regression models showed a significant modifying influence of MiS (P<0.001) on postoperative peak ALT levels in addition to MaS (P<.036), suggesting have comparable influences of both MiS and MaS on hepatic injury. CONCLUSION: Our results suggested that a mild degree of either MaS or MiS was associated with higher postoperative peak AST and ALT values. A regression analysis showed both MaS and MiS to display similar impacts on postoperative liver functions after living donor right hepatectomy.

Anatomical analysis of computed tomography images for determining the optimal oblique fluoroscope angle for percutaneous coeliac plexus block.

This retrospective study used abdominal computed tomography (CT) scan images to determine the optimal safe oblique angle for fluoroscopy in fluoroscope-assisted coeliac plexus block (CPB). Abdominal CT scans from 131 patients were included in the study: 42 patients with cancer of the pancreas head, 45 with cancer of the pancreas body and tail and 44 with chronic pancreatitis. The oblique angle and entry distance from the midline were measured at the T12 and L1 levels, and the safe angle range that avoided puncture of the organs was also measured. The optimal angle varied between the T12 and L1 levels, and between the right and left sides at the T12 level. There was no difference in the oblique angle between the patient groups. The optimal oblique angle for fluoroscopy was determined to be 17° for right T12, 18° for left T12, and 19° for both left and right L1.

Isolation of two protein factors from maize involved in poly U-dependent polyphenylalanine synthesis by maize ribosomes.

Two protein factors, isolated from S-100 of maize shoots, were found to be required not only for a "Mg(2+) shift" for poly U-dependent polymerization of phenylalanine, but also for polyphenylalanine synthesis. They seem to be crude preparations of EF-1 and EF-2. The poly U-directed amino acid incorporation by washed ribosomes was completely dependent upon these factors.

[A cell-free system of protein synthesis from maize seedlings]. / Ein in vitro Proteinsynthesesystem aus Maiskeimlingen.

An amino acid incorporating system has been prepared from maize seedlings, and it has been characterized with the aid of poly-U and a "mRNA enriched fraction" from the same plant material.The rate of protein synthesis decreases proportionally with the incubation period. It seems to be related to the degradation of polysomes. The optimal Mg(2+) concentration is 20 mM for the poly-U dependent protein synthesis and 10 mM for the synthesis with endogenous polysomes. The poly-U directed polyphenylalanine synthesis is increased 12-fold by addition of exogenous sRNA. Under optimal conditions poly-U causes a 40-fold increase of the phenylalanine incorporation.A "mRNA enriched fraction" was prepared from maize seedlings using proteinase K for deproteination of polysomes. The resulting RNA was further fractionated by successive precipitation with LiCl, NaCl and ethanol and characterized by polyacrylamide gel electrophoresis. The addition of 57 µg of the mRNA-enriched sample increases the incorporation of amino acid into polypeptides by a factor of approximately 2 at a Mg(2+) concentration of 5 mM, and by a factor of 1.5 at 15 mM Mg(2+). The addition of 72 µg rRNA does not stimulate the incorporation at low Mg(2+) concentration, while at 15 mM Mg(2+) a 1.3-fold increase is observed.

Decursin: a cytotoxic agent and protein kinase C activator from the root of Angelica gigas.

A cytotoxic compound was purified from the root of Angelica gigas Nakai by silica gel chromatography and preparative HPLC. As a result of the structure analysis by mass, IR, 1H-NMR, and 13C-NMR spectrometry, the effective compound was identified as decursin, a pyranocoumarin characterized originally from Angelica decursiva Fr. et Sav. In vitro cytotoxicity testing showed that decursin displayed toxic activity against various human cancer cell lines, for which the ED50 of decursin was about 5-16 micrograms/ml. On the other hand, decursin displayed relatively low cytotoxicity against normal fibroblasts. Decursin also activated protein kinase C (PKC) in vitro, which indicates that the cytotoxic activity of decursin may be related to the protein kinase C activation.