[P.F. von Siebold and his destiny with Chinese materia medica (Ben Cao)].

P. F. von Siebold (1796-1866) was a physician at the Dutch Business Centre (Shang Wu Hui Guan) located at Nagasaki, Japan, in the Edo period. He collected a great amount of botanical and mineral specimens, books, and living wares when he stayed in Japan. He brought these materials to Europe and kept some of them at the Japan Museum Siebold Huis in Leiden in Netherlands. This collection showed the role of Siebold in connecting scientific and cultural exchanges between East and West and provided references in the research of the transmission of traditional Chinese medicine worldwide in the 19th century.

The efficacy and safety of different doses of calcitriol combined with neutral phosphate in X-linked hypophosphatemia: a prospective study.

The present study was the first prospective cohort evaluated the efficacy and safety of different doses of calcitriol in XLH children. The results suggested that a dose of 40 ng/kg/day calcitriol, compared with 20 ng/kg/day, was more effective in relieving the rickets, with similar safety outcomes. Further investigations were expected to set more dose groups. INTRODUCTION: Dose recommended for calcitriol in X-linked hypophosphatemia (XLH) varies in different studies. Therefore, we aimed to compare the efficacy as well as the safety of 20 ng/kg/d and 40 ng/kg/d calcitriol in Chinese XLH pediatrics population. METHODS: A 2-year, randomized, open-label, prospective study recruited 68 XLH children, which were randomized to receive either 40 ng/kg/day or 20 ng/kg/day calcitriol. Efficacy endpoints were the total Thacher ricket severity score (RSS) change from baseline to month 12 and 24, the difference in serum TALP level, fasting serum phosphate level, body height Z-score, and frequency of dental abscess. Safety assessments were done using renal ultrasound nephrocalcinosis grades (0-4), fasting serum and 24 h urine calcium level, and the occurrence of hyperparathyroidism. RESULTS: The decrease in the total RSS from baseline was more significant in the high-dose group at 12 (difference 0.87, p = 0.049) and 24 month (difference 1.23, p = 0.011). The serum TALP level was significantly lower in the high-dose group at 6 months. Pi level, height Z-score change, frequency of dental abscess and ratio of de novo nephrocalcinosis were comparable. A lower incidence of secondary hyperparathyroidism was seen in the high-dose group (p < 0.0001). CONCLUSION: For the first time in this prospective cohort, 40 ng/kg/d calcitriol was shown to be the more effective therapy in XLH children than the 20 ng/kg/d. Moreover, 40 ng/kg/d calcitriol was not associated with increasing adverse events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT 03,820,518.

[Efficacy and safety of Kangbingdu granules in the treatment of influenza: a randomized, double-blind, double-dummy, positive-drug parallel control multicenter clinical trial].

Objective: To observe the efficacy and safety of Kangbingdu granules (KBD) in the treatment of influenza. Methods: A multicenter, randomized, double-blind, double-dummy, and positive-drug parallel control trial was conducted in 27 Grade ⅢA hospitals in China and the subjects were randomly assigned to the KBD test group or the oseltamivir phosphate capsule control group at a ratio of 1∶1. 200 subjects were planned to be enrolled in each group. The experimental group was given KBD (18g each time, 3 times a day) and oseltamivir phosphate simulator orally, while the control group was given oseltamivir phosphate capsule (75 mg each time, twice a day) and KBD simulator orally for 5 days. The primary efficacy indicators included the remission time of major clinical symptoms and the time of complete defervescence. The secondary efficacy indicators included dosage of acetaminophen, the change of traditional Chinese medicine (TCM) syndrome score and the remission time of other important clinical symptoms. The efficacy of KBD in the test group and Oseltamivir phosphate control group were compared. Adverse events or adverse reactions were observed at the same time to evaluate the safety of KBD Granules. Results: A total of 393 subjects from 27 Grade ⅢA hospitals in China were enrolled. The experimental group included 195 subjects and 191 subjects (97.95%) completed the trial, While the control group included 198 subjects and 195 subjects (98.48%) completed the trial. There was no significant difference in the shedding rate and rejection rate between the two groups (P>0.05). In the Full Analysis Set (FAS), the mean age of the experimental group was (34.9±14.4) years old, with 83 males (42.78%). The mean age of the control group was (33.3±13.5) years old, with 78 males (39.59%). There were no statistically significant differences between the two groups in demographic data, physical examination, viral pathogen detection, total score of TCM syndromes and scores of each symptom at baseline (P>0.05). In the FAS, the remission time M (Q1, Q3) of major clinical symptoms was 3.0 (3.0, 4.0) days in the experimental group and 3.0 (3.0, 4.0) days in the control group, and the difference was not statistically significant (P>0.05). The time M (Q1, Q3) of complete defervescence was 34.0 (20.3, 49.0) hours in the experimental group and 36.5 (19.6, 48.8) hours in the control group, and the difference was not statistically significant (P>0.05). KBD granules had the same effect as Oseltamivir phosphate capsule (P>0.05) in terms of acetaminophen dosage, TCM syndrome effect and disappearance rate of most important clinical symptoms. Meanwhile, the disappearance rate of dizziness and chest distress on day 3 in the KBD granules group was better than that of oseltamivir phosphate capsule (P<0.05). Conclusion: KBD granules have the same efficacy as Oseltamivir Phosphate capsule in the treatment of influenza and the drug safety is good.

[Looking for the roots of Wa Na Qi].

Wa Na Qi(), is a traditional-curing male impotence medicinal. We have made several conclusions through a field investigation to Antarctica, material medica literature research, and current market investigation. Throughout history, Wa Na Qi (also known ashaigou shen) was a word of vague connotation which was not the meaning of a specific product. However, the most common meaning of Wa Na Qi was the penises of several different species of seals. The name Wa Na Qi was adapted from a foreign word, and it is believed to sound like walrus, which has also been credited as a source for Wa Na Qi. In Chinese, Wa Na was a reference to the roundness of the walrus but eventually became a general description of heaviness. Later, it became a name for fur seals. The Song Dynasty Materia Medica Bencao Tujing(, Illustration of Materia Medica) and the Ming Dynasty Materia Medica Bencao Pinhui Jingyao(, Collected Essentials of Species of Materia Medica) both had animal illustrations resembling fur seals. The illustrations in the Compendium of Materia Medica, or Bencao Gangmu, Jinling edition also had characteristics of a fur seal. However, in the Buyi Leigong Paozhi Bianlan(, Lei Gong's Guide to Drug Preparation with Addenda) and later materia medica works, the animal illustrations became distorted and almost myth-like. After a field investigation in Antarctica, we learned that historically, name Wa Na Qi probably originated from seals, such as fur seals. This information matches the current medicines available on the market.

[Investigation of Compendium of Materia Medica in Japan].

Published in the Ming Dynasty around 1593 to 1596, the Jinling Edition of the Compendium of Materia Medica is considered the earliest engraved version. This edition has considerable literary and academic value. Only a handful of copies remain as they had to survive more than 400 years of human conflict and environmental damage such as mold and mildew. Throughout history, many ancient books, including herbal materia medica, have been exported to overseas, following the expansion of trade and cultural exchange. In Japan, many of these books are still well preserved. The author conducted a field investigation to Tohoku University in Sendai, Tokyo's Oriental Library, the Cabinet Library of the National Archives, and the National Diet Library to study four very well-preserved Jinling Editions of the Compendium of Materia Medica to fully understand the development of traditional medicine in Japan.

Effects of exercise on sex hormones and expression of relevant genes in the hypothalamus in obese mice.

This study aimed to investigate the effect of different exercise loads on sex hormones and expressions of relevant genes in hypothalamus in obese mice. Sixty weaning male C57BL/6 mice were used as subjects. Among them, 15 mice were randomly classified into the normal diet group (CON group), and the remaining 45 mice into high-fat diet group (MOB group). The obesity was successfully achieved by high-fat diet 10 weeks later. Then the rats were randomly divided into three groups based on weight, namely, obesity control group (OBC group), obesity with moderate-intensity exercise group (MOBC group), and obesity with high-intensity exercise group (HOBC group), with 15 mice in each group. Mice in the MOBC group and HOBC group were offered 8 weeks of swimming training, and the exercise time increased incrementally until 2 h and 4 h per day. After the training was over, ELISA method was used to determine the serum levels of Adiponectin (Adipo), luteotropic hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T). Real-time PCR was implemented to detect the transcriptional levels of genes of Adipo and other relevant proteins in the hypothalamus. The result showed that compared with the CON group, there was a significant reduction in the serum levels of Adipo, LH, FSH and T in the OBC group (P<0.05). As compared with the OBC group, the serum levels of Adipo, LH, FSH and T increased significantly in the OBC group (P<0.05). There was a significant increase in the transcriptional levels of Adipo, Adipo receptor 1 (Adipo R1), and AMP-activated protein kinase (AMPK) in the OBC group (P<0.05) compared to in the CON group; meanwhile, the transcriptional levels of kisspeptin (Kiss) and gonadotropin-releasing hormone (GnRH) decreased significantly (P<0.05). In conclusion, long-term moderate-intensity exercise could improve the negative effect of obesity on sex development. Long-term high-intensity exercises could not improve the inhibitory effect of obesity on sex development.

Discrete Superconducting Phases in FeSe-Derived Superconductors.

A general feature of unconventional superconductors is the existence of a superconducting dome in the phase diagram. Here we report a series of discrete superconducting phases in the simplest iron-based superconductor, FeSe thin flakes, by continuously tuning the carrier concentration through the intercalation of Li and Na ions with a solid ionic gating technique. Such discrete superconducting phases are robust against the substitution of 20% S for Se, but they are vulnerable to the substitution of 2% Cu for Fe, highlighting the importance of the iron site being intact. The superconducting phase diagram for FeSe derivatives is given, which is distinct from that of other unconventional superconductors.

[A forgotten and unnoticed Museum of Chinese medicine].

Kam Wah Chung Company, located in the Oregan State in the northwestern United States, was co-created by Dr. Ing Hay and Mr. Lung On. In 1952, when Dr. Ing Hay passed away, his entire clinic building and collections were donated to the government and had been set up as a Museum for later generations to understand the history. The pictures, objects and videos used in the Museum to vividly and objectively compress and reproduce the process and history of early generation of Chinese immigrants crossing the ocean, travelling to northwestern United States and started their new life more than 100 years ago. The precious Chinese medicine materials in the Museum are of great significance to the research and the dissemination of Chinese Medicine culture overseas.

[Neurofeedback therapy in the treatment of tinnitus].

Neurofeedback therapy is a fast-growing field of tinnitus treatment, which is a new type of biofeedback therapy. In the past, the "muscle tone" and "blood flow" were used as feedback signals in biofeedback therapy to treat tinnitus, however there was no long-term follow-up report. Instead, neurofeedback therapy utilizes EEG (electroencephalogram) as the feedback signal, which is also called EEG biofeedback therapy. At present, most treatments of tinnitus only record subjective measures of patients as evaluation indicators, whereas neurofeedback therapy is more convincing for using comprehensive evaluation including changes of brain wave as objective indicators and subjective measures of patients. A significant number of tinnitus patients have varying degree of hearing loss. As neurofeedback therapy takes advantage of EEG as feedback signal that is delivered to the patients through visual information, it has unique advantages of being not affected by the degree of hearing loss compared to the sound masking or other sound treatment. Long-term follow-up results showed that the efficacy of neurofeedback therapy was stable after half a year of short-term treatment. This paper summarizes the progress of the various types of biofeedback therapy in the treatment of tinnitus, and focuses on the neurofeedback therapy for the mechanism, indication, process, efficacy evaluation, defect and prospect of neurofeedback therapy in tinnitus treatment in order to help promote the development of domestic clinical neurofeedback therapy in tinnitus.

[Clinical characteristics and outcome comparison between atrial fibrillation patients underwent catheter ablation under general aesthesia or local anesthesia and sedation].

Objective: To compare the outcome of radiofrequency catheter ablation under local anesthesia/sedation (S) or general anesthesia(GA) in atrial fibrillation patients. Methods: Data of 498 patients with atrial fibrillation undergoing radiofrequency catheter ablation in our departmentfrom January 2014 to December 2015 were retrospectively analyzed. Two hundred and twenty patients assigned to the GA group, the other 278 patients to the S group. Patients were followed clinically every 3 months within one year after procedure. Immediate electrocardiogram was performed in patients with palpitation or choking sensation in chest. The end point of the study was recurrence of any atrial tachyarrhythmia lasting >30 seconds in device interrogation, 24-hour Holter monitoring or 12-lead electrocardiogram after a single procedure. After the ablation procedure, a blanking period of 3 months was allowed according to the guidelines. Procedure time, radiofrequency time, fluoroscopy time, the detection of paroxysmal supraventricular tachycardia, the success rate and the complications were compared between the two groups. Results: There was no difference in the baseline characteristics between the two groups, such as age, gender, BMI, complications, LVEF, LAD (all P>0.05). The duration of procedure ((117.8±51.7)minutes vs.(115.4±36.9)minutes, P=0.79), duration of fluoroscopy((12.5±11.2)minutes vs. (10.4±10.2)minutes, P=0.35), duration of radiofrequency((40.1±12.9)minutes vs. (48.6±44.3)minutes, P=0.48) were similar between the two groups (P>0.05). Compared with S group, discovery of the frequency of atrioventricular node reentrant tachycardia (AVNRT) was significantly lower in GA group (0 vs. 3.6%(10/278), P<0.01), but the difference disappeared with repeat electrophysiological examination when patients become conscious from GA(3.2%(7/220) vs. 3.6%(10/278), P=0.311). The difference of atrioventricular reentrant tachycardia (AVRT) was similar between the two groups(0.9%(2/220) vs. 0.7%(2/278), P=0.841). Compared with S group, reflection of vagus nerve was less in GA group (1.4%(3/220) vs. 8.6%(24/278), P=0.026). After following up of (356±92) days, freedom from atrial fibrillation/atrial flutter/atrial tachyarrhythmia was similar between the two groups(77.9%(162/208) vs. 79.9%(215/269), P=0.818). Conclusion: General anesthesia is a promising method to atrial fibrillation ablation, in view of stable patient status and safety for the procedure. There is no difference in complications, recurrence of arrhythmia between the two groups, but detection rate of AVNRT is lower in GA group.

Effects of fish oil-derived fatty acids on suboptimal cardiovascular health: A multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND AND AIMS: Suboptimal health and metabolic disorders are common in the general population. Both are related to cardiovascular disease. Suboptimal cardiovascular health is defined by the presence of both suboptimal health and metabolic disorders. The aim of the study was to investigate the potential benefit of n-3 long-chain polyunsaturated fatty acids (LCPUFA) in participants with suboptimal cardiovascular health. METHODS AND RESULTS: A total of 422 participants with suboptimal cardiovascular health, from two clinics in China, were enrolled from September 2014 to April 2015. All the enrolled participants were randomly assigned to receive 4 g/d of fish oil or placebo for three months. Suboptimal health was defined using an accepted questionnaire. Metabolic disorders were defined as one or more abnormalities in blood pressure, fasting plasma glucose, blood lipids, and body mass index (BMI). After treatment, the mean BMI fell significantly more in the n-3 LCPUFA group than in the placebo group (-0.29 ± 0.06 kg/m2 vs. -0.02 ± 0.06 kg/m2, P = 0.003). Similar results were found in the changes of suboptimal health status and suboptimal cardiovascular health status (P < 0.05 for all). In a multivariate analysis, the n-3 LCPUFA group was 5.44 (1.15, 25.67) times more likely to have optimal cardiovascular health status after treatment. CONCLUSIONS: n-3 LCPUFA intake improved suboptimal cardiovascular health in this placebo-controlled, randomized, double-blind trial. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.govNCT02103517.

Genetic analysis of a hybrid sterility gene that causes both pollen and embryo sac sterility in hybrids between Oryza sativa L. and Oryza longistaminata.

Oryza longistaminata originates from African wild rice and contains valuable traits conferring tolerance to biotic and abiotic stress. However, interspecific crosses between O. longistaminata and Oryza sativa cultivars are hindered by reproductive barriers. To dissect the mechanism of interspecific hybrid sterility, we developed a near-isogenic line (NIL) using indica variety RD23 as the recipient parent and O. longistaminata as the donor parent. Both pollen and embryo sac semi-sterility were observed in F1 hybrids between RD23 and NIL. Cytological analysis demonstrated that pollen abortion in F1 hybrids occurred at the early bi-nucleate stage due to a failure of the first mitosis in microspores. Partial embryo sacs in the F1 hybrids were defective during the functional megaspore formation stage. Most notably, nearly half of the male or female gametes were aborted in heterozygotes S40iS40l, regardless of their genotypes. Thus, S40 was indicated as a one-locus sporophytic sterility gene controlling both male and female fertility in hybrids between RD23 and O. longistaminata. A population of 16 802 plants derived from the hybrid RD23/NIL-S40 was developed to fine-map S40. Finally, the S40 locus was delimited to an 80-kb region on the short arm of chromosome 1 in terms with reference sequences of cv. 93-11. Eight open reading frames (ORFs) were localized in this region. On the basis of gene expression and genomic sequence analysis, ORF5 and ORF8 were identified as candidate genes for the S40 locus. These results are helpful in cloning the S40 gene and marker-assisted transferring of the corresponding neutral allele in rice breeding programs.

[Correlation of liver stiffness measured by FibroTouch and FibroScan with Ishak fibrosis score in patients with chronic hepatitis B].

Objective: To investigate the correlation of liver stiffness measured by FibroTouch (FT) and FibroScan (FS) with Ishak fibrosis score in patients with chronic hepatitis B. Methods: A total of 313 patients with chronic hepatitis B who visited Department of Liver Cirrhosis in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from November 2014 to May 2016 were enrolled. All the patients underwent liver biopsy, and FT and FS were used to determine liver stiffness measurement (LSM). Serum biochemical parameters were measured, and the aspartate aminotransferase-to-platelet ratio index (APRI) in a multi-parameter model of liver fibrosis and fibrosis-4 (FIB-4) index were calculated. The consistency between the results of four noninvasive examinations and Ishak fibrosis score was compared. The t-test was used for comparison of LSM determined by FT and FS. Pearson correlation analysis was used investigate the correlation between LSM determined by FT and FS; Spearman correlation analysis was used to investigate the correlation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and Knodell score with LSM determined by FT and FS; the correlation between LSM determined by FT and FS and fibrosis stage was analyzed by partial correlation analysis adjusted by Knodell score for liver inflammatory activity; Spearman correlation analysis was used for APRI, FIB-4, and fibrosis stage. Based on the Ishak fibrosis score, the receiver operating characteristic (ROC) curve was used to analyze the values of four noninvasive methods in the diagnosis of liver fibrosis. Results: There was no significant difference in LSM measured by FT and FS in all patients (15.75±9.42 kPa vs 15.42±10.52 kPa, P > 0.05) and Pearson correlation analysis indicated a significant positive correlation between them (r = 0.858, P < 0.01); serum ALT and AST levels and liver inflammatory activity were correlated with LSM determined by FT and FS. There was a significant positive correlation between LSM determined by FT and FS and fibrosis stage (r = 0.501 and 0.526, both P < 0.001), and APRI and FIB-4 were also positively correlated with fibrosis stage (r = 0.236 and 0.218, both P < 0.001). Based on the Ishak fibrosis score, in the diagnosis of fibrosis stages F3, F4, F5, and F6, the areas under the ROC curve were 0.915/0.856/0.839/0.816 for FT, 0.933/0.883/0.849/0.856 for FS, 0.618/0.630/0.608/0.638 for APRI, and 0.614/0.624/0.595/0.649 for FIB-4, and FT and FS had a significantly larger areas under the ROC curve than APRI and FIB-4. Conclusion: LSM determined by FT or FS has a good correlation with the Ishak fibrosis score, so FT and FS have a significantly better diagnostic performance for liver fibrosis than APRI and FIB-4.

Effectiveness of adjunctive interventions for accelerating orthodontic tooth movement: a systematic review of systematic reviews.

This study was aimed to summarise published systematic reviews (SRs) that assess the effects of adjunctive interventions on the acceleration of orthodontic tooth movement (OTM). Electronic and manual searches were performed up to August 2016. Systematic reviews investigating the impact of adjunctive techniques on the promotion of OTM were included. The methodological quality of the included reviews was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) scale. The quality of evidence for each intervention was assessed using GRADE. The Jadad decision algorithm was used to select a study to provide body evidence from discordant reviews on the same intervention. A total of 11 SRs were included in this study. AMSTAR scores ranged from 4 to 10 of 11. The quality of evidence ranged from very low to low. The short-term (1-3 months) effects of low-level laser therapy (LLLT, 5 and 8 J cm-2 ) and corticotomy were supported by low-quality evidence. The evidence regarding the efficacy of photobiomodulation, pulsed electromagnetic field, interseptal bone reduction, two vibrational devices (Tooth Masseuse and Orthoaccel) and electrical current was of very low quality. Relaxin injections and extracorporeal shock waves were reported to have no impact on OTM according to low- and very low-quality evidence, respectively. Based on currently available information, we conclude that low-quality evidence indicates that LLLT (5 and 8 J cm-2 ) and corticotomy are effective to promote OTM in the short term. Future high-quality trials are required to determine the optimal protocols, as well as the long-term effects of LLLT and corticotomy, before warranting recommendations for orthodontics clinics.

Systems Pharmacology-Based Discovery of Natural Products for Precision Oncology Through Targeting Cancer Mutated Genes.

Massive cancer genomics data have facilitated the rapid revolution of a novel oncology drug discovery paradigm through targeting clinically relevant driver genes or mutations for the development of precision oncology. Natural products with polypharmacological profiles have been demonstrated as promising agents for the development of novel cancer therapies. In this study, we developed an integrated systems pharmacology framework that facilitated identifying potential natural products that target mutated genes across 15 cancer types or subtypes in the realm of precision medicine. High performance was achieved for our systems pharmacology framework. In case studies, we computationally identified novel anticancer indications for several US Food and Drug Administration-approved or clinically investigational natural products (e.g., resveratrol, quercetin, genistein, and fisetin) through targeting significantly mutated genes in multiple cancer types. In summary, this study provides a powerful tool for the development of molecularly targeted cancer therapies through targeting the clinically actionable alterations by exploiting the systems pharmacology of natural products.

Characterization of Causal Agents of a Novel Disease Inducing Brown-Black Spots on Tender Tea Leaves in China.

A novel disease characterized by small brown-black spots (1 to 2 mm in diameter) on tender tea leaves (Camellia sinensis) has been observed in many regions of Hubei Province, China, which severely affects the yield and quality of tea. Tea leaf samples with typical symptoms were collected from three major tea-cultivation regions of Hubei, and were subjected to pathogen isolation for etiological analysis. As a result, 34 Pestalotiopsis isolates were obtained from 20 samples, and they were identified as Pestalotiopsis theae (14 isolates), P. camelliae (12), and P. clavispora (8), determined by morphologies and phylogenetic analysis based on internal transcribed spacer, and partial ß-tubulin and translation elongation factor 1-alpha genes. Pathogenicity tests on detached tea leaves showed that no matter what mycelial discs or conidium suspensions were used, inoculation of the Pestalotiopsis fungi could result in small brown-black spots (1 to 2 mm in diameter) on wounded leaves, similar to those observed in the field in the sizes and colors. It also revealed that only P. theae had pathogenicity on unwounded tea leaves, and P. theae and P. clavispora showed significantly higher virulence than P. camelliae. Inoculation test with conidium suspension on intact tea leaves in the field further confirmed that P. theae as the pathogen of brown-black spots. Reisolation of the pathogens from diseased leaves confirmed that the symptom was caused by the inoculation of Pestalotiopsis fungi. The P. theae isolates responsible for brown-black spots were also compared with those for tea gray blight disease in growth rate, pathogenicity, and molecular characteristics in parallel. To our knowledge, this is the first report that the Pestalotiopsis fungi cause brown-black spot disease on tender tea leaves. The results provide important implications for the prevention and management of this economically important disease.

[Clinical, biochemical and gene mutation characteristics of short chain acyl-coenzyme A dehydrogenase deficiency by neonatal screening].

Objective: To investigate the incidence, clinical, biochemical and gene mutation characteristics of short chain acyl-coenzyme A dehydrogenase deficiency (SCADD). Method: From January, 2009 to October, 2015, a retrospective analysis of the urine organic acids and acyl-coenzyme A dehydrogenase (ACADS) gene mutation characteristics of patients diagnosed as SCADD by newborn screening using tandem mass spectrometry in Department of Genetics and Metabolism (Newborn screening Center of Zhejiang Province), Children's Hospital, Zhejiang University School of Medicine. Dietary guidance, life management and supplementation of L-carnitine were conducted, and growth and intelligence development were observed during follow-up among the SCADD patients. Result: A total of 1 430 024 neonates, seventeen cases were diagnosed with SCADD with an incidence of 1/84 117. All patients had no clinical symptoms, and intelligence and physical development were normal. Blood butylacyl-carnitine (C4) levels and the ratios increased, C4 0.713.14 µmol/L(reference value 0.03-0.48 µmol/L), C4/C2 0.07-0.23(reference value 0.01-0.04), C4/C3 0.65-2.04(reference value 0.05-0.39). Thirteen with increased urinary ethyl malonic acid (9.30-90.99 mg/g creatinine (reference value 0-6.20 mg/g creatinine )), one patient was accompanied by increased methyl succinic acid (12.33 mg/g creatinine(reference value 0-6.40 mg/g creatinine)), one subject with increased acetylglycine (3.52 mg/g creatinine(reference value 0-0.70 mg/g creatinine)). A total of 13 known mutations were detected in the ACADS gene, 1 homozygous mutation (c.1031A>G), the others are compound heterozygous mutations. One frameshift mutation (c.508_509delGC) and 12 missense mutations were detected. Common mutation were c. 1031A>G(35.3%), c. 164C>T(20.6%) and c. 991G>A(11.8%). SCADD in newborn screening program had no clinical symptoms and normal growth development after 8-42 months follow-up. Conclusion: Cases with SCADD had no clinical symptoms with an incidence of 1/84117. The c. 164C>T and c. 1031A>G may be the common mutations.

Identification of an orally available compound with potent and broad FLT3 inhibition activity.

FLT3 internal tandem duplication (FLT3-ITD) is an activating mutation found in 20-30% of patients with acute myeloid leukemia (AML), which makes FLT3 an attractive target for the treatment of AML. Although FLT3-mutant patients respond to current FLT3 inhibitors, relapse usually happens because of the acquisition of resistant secondary mutations at the FLT3 catalytic domain, which is mainly on D835. In the search for compounds with broad FLT3 inhibition activities, we screened a kinase inhibitor library by using our unique FLT3 substrate and identified JAK3 inhibitor VI (designated JI6 hereafter) as a novel FLT3 inhibitor, which selectively targets FLT3 D835 mutants as well as FLT3-ITD. JI6 effectively inhibited FLT3-ITD-containing MV4-11 cells and HCD-57 cells transformed with FLT3-ITD and D835 mutants. Furthermore, administration of JI6 effectively targeted FLT3 signaling in vivo and suppressed the myeloproliferative phenotypes in FLT3-ITD knock-in mice, and significantly prolonged the survival of immunodeficient mice implanted with the transformed HCD-57 cells. Therefore, JI6 is a promising candidate for the development of next-generation anti-AML drugs.

Effects of atorvastatin combined with trimetazidine on myocardial injury and inflammatory mediator in unstable angina patients during perioperative of percutaneous coronary intervention.

OBJECTIVE: To investigate the effects of atorvastatin combined with trimetazidine on periprocedural myocardial injury and serum inflammatory mediators in unstable angina pectoris (UAP) patients following percutaneous coronary intervention (PCI) treatment. PATIENTS AND METHODS: 90 patients with UAP treated with conventional medications and PCI were recruited and were randomly divided into the control group and the experimental group. The control group had 42 patients were treated with atorvastatin alone, while the experimental group had 48 cases treated with atorvastatin combined with trimetazidine. All the patients were checked the preoperative 24h and postoperative 24h PCI concentrations of cardiac troponin I (cTnI), hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), serum interferon-γ (IFN-γ) and interlukin-10 (IL-10). RESULTS: At the pre-PCI stage, every serum factors was no significant difference. 24 hours after the PCI intervention, the occurence of abnormal cTnI level in the experimental group was remarkable reduced than the control group. In the experimental group, the serum levels of TNF-α and IFN-γ significantly decreased (p < 0.05); while IL-10 was increased. In the control group, all the mediators were increased significantly except the hs-CRP (p < 0.05). CONCLUSIONS: No unexpected symptom was found in patients with large dose atorvastatin combined with large dose trimetazidine. The administration of conventional medications together with the atorvastatin plus trimetazidine were able to reduce the prevalence of postoperative myocardial injury.