Detection of Various Traditional Chinese Medicinal Metabolites as Angiotensin-Converting Enzyme Inhibitors: Molecular Docking, Activity Testing, and Surface Plasmon Resonance Approaches.

Angiotensin-converting enzyme 1 (ACE1) is a peptide involved in fluid and blood pressure management. It regulates blood pressure by converting angiotensin I to angiotensin II, which has vasoconstrictive effects. Previous studies have shown that certain compounds of natural origin can inhibit the activity of angiotensin-converting enzymes and exert blood pressure-regulating effects. Surface Plasmon Resonance (SPR) biosensor technology is the industry standard method for observing biomolecule interactions. In our study, we used molecular simulation methods to investigate the docking energies of various herbal metabolites with ACE1 proteins, tested the real-time binding affinities between various herbal metabolites and sACE1 by SPR, and analyzed the relationship between real-time binding affinity and docking energy. In addition, to further explore the connection between inhibitor activity and real-time binding affinity, several herbal metabolites' in vitro inhibitory activities were tested using an ACE1 activity test kit. The molecular docking simulation technique's results and the real-time affinity tested by the SPR technique were found to be negatively correlated, and the virtual docking technique still has some drawbacks as a tool for forecasting proteins' affinities to the metabolites of Chinese herbal metabolites. There may be a positive correlation between the enzyme inhibitory activity and the real-time affinity detected by the SPR technique, and the results from the SPR technique may provide convincing evidence to prove the interaction between herbal metabolites and ACE1 target proteins.

Melatonin Restores Autophagic Flux by Activating the Sirt3/TFEB Signaling Pathway to Attenuate Doxorubicin-Induced Cardiomyopathy.

Doxorubicin (DOX) chemotherapy in cancer patients increases the risk of the occurrence of cardiac dysfunction and even results in congestive heart failure. Despite the great progress of pathology in DOX-induced cardiomyopathy, the underlying molecular mechanisms remain elusive. Here, we investigate the protective effects and the underlying mechanisms of melatonin in DOX-induced cardiomyopathy. Our results clearly show that oral administration of melatonin prevented the deterioration of cardiac function caused by DOX treatment, which was evaluated by left ventricular ejection fraction and fractional shortening as well as cardiac fibrosis. The ejection fraction and fractional shortening in the DOX group were 49.48% and 25.5%, respectively, while melatonin treatment increased the ejection fraction and fractional shortening to 60.33 and 31.39 in wild-type mice. Cardiac fibrosis in the DOX group was 3.97%, while melatonin reduced cardiac fibrosis to 1.95% in wild-type mice. Sirt3 is a mitochondrial deacetylase and shows protective effects in diverse cardiovascular diseases. Therefore, to test whether Sirt3 is a key factor in protection, Sirt3 knockout mice were used, and it was found that the protective effects of melatonin in DOX-induced cardiomyopathy were partly abolished. Further analysis revealed that Sirt3 and its downstream molecule TFEB were downregulated in response to DOX treatment, while melatonin administration was able to significantly enhance the expressions of Sirt3 and TFEB. Our in vitro study demonstrated that melatonin enhanced lysosomal function by increasing the Sirt3-mediated increase at the TFEB level, and the accumulation of autolysosomes induced by DOX treatment was attenuated. Thus, autophagic flux disrupted by DOX treatment was restored by melatonin supplementation. In summary, our results demonstrate that melatonin protects the heart against DOX injury by the restoration of autophagic flux via the activation of the Sirt3/TFEB signaling pathway.

Biosynthesis of 6- and 7-Mono-Demethylated Nobiletins by a Newly Isolated Strain of Yeast.

Demethylated nobiletins (DMNs), which are generally recognized as the metabolites of orally administered nobiletin, are widely investigated. However, studies related to 8-demethylated-nobiletin, 7-demethylated-nobiletin (7DMN), and 6-demethylated-nobiletin (6DMN) are limited due to the lack of a synthesis method. In this study, a strain of microbe able to metabolize nobiletin was isolated from aged orange peel. Internal transcribed spacers (ITS) rRNA sequencing analysis showed it belonged to the yeast family, Filobasidium magnum specie. High-performance liquid chromatography (HPLC), HPLC-MS, and 13C NMR results proved that the metabolites were 7DMN and 6DMN. Growth curves of the isolated yeast were studied at different temperatures, media pH, NaCl, and glucose concentrations. Meanwhile, factors that influence the demethylation efficiencies were also investigated. This study lays the groundwork for the investigation of the biological functions of these two compounds and opens a new window for further research of the metabolic fate of nobiletin in the human body.

Suppression effect and safety of acupuncture on colonic spasm during colonoscopy: a randomized controlled trial.

Background: Intestinal spasm and peristalsis during colonoscopy are common but undesirable phenomena, which can easily lead to a missed diagnosis of colorectal polyps and other diseases, and antispasmodic drugs can have adverse side effects. Previous studies find that acupuncture can regulate abnormal gastrointestinal motility. But evidence quality is low and limited at present, and high-quality studies are required. So this study sought to explore the efficacy and safety of acupuncture in inhibiting colonic spasm during endoscopy. Methods: In this prospective, single-blinded, randomized controlled trial, 54 patients experiencing intestinal spasms during colonoscopy were randomly assigned to receive either acupuncture of the bilateral Hegu (LI 4) and Neiguan (PC 6) points (n=27) or sham acupuncture (n=27). The sham points were located 1 cm above the proximal end of the true points and had no known function. The primary outcome was the latency time to colonic spasm suppression, and the secondary outcomes were the duration of colonic spasm suppression, the proportion of patients with rebound spasms within 5 minutes, and adverse events related to acupuncture-related side effects. Results: A total of 54 patients were eligible, and 27 in each group. There was no significant difference in the background characteristics of the patients in the 2 groups. The latency time to spasm suppression of the treatment group was significantly shorter than that of the sham control group (acupuncture: 32.00 s vs. sham: 82.00 s; P<0.001). However, the duration of colonic spasm suppression was similar (acupuncture: 300 s vs. sham: 268 s; P=0.142). No rebound spasms were observed in the treatment group but rebound spasms were observed in 3 patients in the sham control group (acupuncture: 0% vs. sham: 11.1%; P=0.236). No adverse events were observed in either group. Conclusions: Acupuncture of the bilateral Hegu (LI 4) and Neiguan (PC 6) points can shorten the latency time to spasm suppression, and may be used to suppress colonic spasm during colonoscopy. Trial registration: Chinese Clinical Trial Registry ChiCTR2000037796.

Thermal-triggered packing of lipophilic NIR dye IR780 in hepatitis B core at critical ionic strength and cargo-host ratio for improved stability and enhanced cancer phototherapy.

Virus-like particles (VLPs) holding internal cavity with diameter from tens up to one hundred nanometers are attractive platform for drug delivery. Nevertheless, the packing of drugs in the nanocage mainly relies on complicated disassembly-reassembly process. In this study, hepatitis B core protein (HBc) VLPs which can withstand temperature up to 90 °C was employed as carrier to load a lipophilic near infrared dye IR780. It was found that an attaching-dis-atching-diffusing process was involved for the entering of IR780 in the cavity of HBc. The first two steps were associated with the electrostatic interactions between oppositely charged HBc and IR780, which was critically manipulated by ionic strength and HBc/IR780 mass ratio at which they were mixed; while the diffusion of IR780 across the shell of HBc showed a temperature-dependent manner that can be triggered by thermal induced pore-opening of the HBc capsid. At optimized condition, about 1055 IR780 molecules were encapsulated in each HBc by simply mixing them for 10 min at 60 °C. Compared with free IR780, the HBc-IR780 particles showed significantly improved aqueous and photostability, as well as enhanced photothermal and photodynamic performance for cancer therapy. This study provides a novel drug loading strategy and nanomemedicine for cancer phototherapies.

[Advances in the experimental mechanism of acupuncture in the treatment of Alzheimer's disease based on Wnt/ß-catenin pathway].

Alzheimer's disease is a neurodegenerative disease closely related to age, which is characterized by cognitive and memory impairment. Extensive studies have confirmed that Wnt/ß-catenin signal pathway is involved in the occurrence and development of Alzheimer's disease. With the characteristics of holistic concept and syndrome differentiation, acupuncture is widely used in clinic. Acupuncture plays a role in the treatment of Alzheimer's disease through the regulation of each target and the whole of the pathway. The author reviewed and combed the research on acupuncture treatment of Alzheimer's disease in recent years, and reviewed the regulatory effects of acupuncture on the important components of Wnt/ß-catenin signal pathway (Wnt protein, ß-catenin, glycogen synthase kinase-3ß) and whole, ATP-binding cassette subfamily B member 1 (ABCB1), low density lipoprotein receptor associated protein-1 (LRP-1)．.

Aged citrus peel (chenpi) extract causes dynamic alteration of colonic microbiota in high-fat diet induced obese mice.

Aged citrus peels (chenpi) have been used as a dietary supplement for gastrointestinal health maintenance in China. Recently, it was reported to exhibit anti-obesity activity. However, the relationship between the modulation effect of chenpi on gut microbiota and obesity prevention is not clearly understood. In this study, mice were fed with a high-fat diet (HFD), HFD supplemented with 0.25%- and 0.5%-chenpi extract, and normal diet, respectively, for 11 weeks. Chenpi extract significantly increased fecal short chain fatty acids by 43% for acetic acid and 86% for propionic acid. In addition, chenpi could decrease the prevalence of Proteobacteria and the ratio of Firmicutes to Bacteroidetes by about 88% and 70%, respectively. Moreover, this study was the first work to demonstrate the dynamics of two beneficial bacteria-Akkermansia spp. and Allobaculum spp. in a dose- and time-dependent manner for chenpi treatment via monitoring the dynamic change of the gut microbiota. Metagenomic analysis of the gut microbiota showed that several pathways, such as a two-component system, a tight junction, Staphylococcus aureus infection and others, were enhanced dynamically. The improved biological process of metabolism especially in benzoate derivatives might refer to the increased metabolic transformation of polymethoxyflavones from chenpi in the colon. Our study indicated that the modulation effect of chenpi on the gut microbiota may be an important pathway for its anti-obesity mechanisms.

[Construction of IL-6/STAT3 reporter gene system for screening and validation of traditional Chinese medicine monomers inhibiting IL-6/STAT3 signaling pathway].

It is important to find monomers of traditional Chinese medicine that can inhibit the activation of IL-6/STAT3 signaling pathway to suppress the growth and deterioration of tumors. A novel expression vector containing STAT3 enhancer sequence and NanoLuc (NLuc) reporter gene sequence was constructed by gene recombination technology, then a cell line expressing NLuc luciferase and regulated by STAT3 was further established. The cell line was used to quantitatively detect the regulatory effects of various traditional Chinese medicine monomers on the IL-6/STAT3 signal pathway. The effects of the traditional Chinese medicine monomers inhibiting the IL-6/STAT3 signal pathway were verified by Western blotting immunoassay and Real-time PCR analysis. By enzyme digestion and DNA sequencing analysis, it showed that the reporter gene expression vector pQCXIP-STAT3-Nluc was constructed successfully. The addition of Interleukin-6 (IL-6), a stimulator of STAT3 transcription factor, to the constructed cell line specifically enhanced the luciferase enzymatic reaction in a dose dependent manner. These results demonstrated that the cell line expressing NLuc luciferase and regulated by STAT3 has been constructed successfully. We used the the cell line screened out dendrobiine and tetrandrine which could significantly inhibit IL-6/STAT3 signal pathway and down-regulated the expression of Bcl-2 and Bcl-x in a dose-dependent manner. In conclusion, we have constructed an efficient reporter gene system to detect the transcriptional activity of STAT3, by which the Chinese medicine monomers inhibiting IL-6/STAT3 signaling pathway were successfully screened out, which has some potential theoretical and practical values.

Identification of bioactive compounds that contribute to the α-glucosidase inhibitory activity of rosemary.

To investigate the bioactive compounds that contribute to the α-glucosidase inhibitory activity of rosemary, phenolics and triterpene acids were characterized and quantified using quadrupole-Orbitrap mass spectrometry and enzyme assay. Two phenolic diterpenes (carnosol and hydroxy p-quinone carnosic acid) and two triterpene acids (betulinic acid and ursolic acid) were identified as potent α-glucosidase inhibitors. Carnosol, a major diterpene in rosemary, showed significant α-glucosidase inhibitory activity with IC50 value of 12 µg mL-1, and its inhibition mode was competitive. The inhibition mechanism of carnosol on α-glucosidase was further investigated by a combination of surface plasmon resonance (SPR) spectroscopy, fluorescence quenching studies and molecular-modeling techniques. The SPR assay suggested that carnosol had a high affinity to α-glucosidase with equilibrium dissociation constant (KD) value of 72.6 M. Fluorescence quenching studies indicated that the binding between carnosol and α-glucosidase was spontaneous and mainly driven by hydrophobic forces. Molecular docking studies revealed that carnosol bound to the active site of α-glucosidase. Furthermore, the oral administration of carnosol at 30 mg kg-1 significantly reduced the postprandial blood glucose levels of normal mice. This is the first report on the α-glucosidase inhibition and hypoglycemic activity of phenolic diterpenes, and these results could facilitate the utilization of rosemary as a dietary supplement for the treatment of diabetes.

[Progress of gene editing technologies and prospect in traditional Chinese medicine].

Gene editing is a kind of technologies that makes precise modification to the genome. It can be used to knock out/in and replace the specific DNA fragment, and make accurate gene editing on the genome level. The essence of the technique is the DNA sequence change with use of non homologous end link repair and homologous recombination repair, combined with specific DNA target recognition and endonuclease.This technology has wide range of development prospects and high application value in terms of scientific research, agriculture, medical treatment and other fields. In the field of gene therapy, gene editing technology has achieved cross-time success in cancers such as leukemia, genetic disorders such as hemophilia, thalassemia, multiple muscle nutritional disorders and retrovirus associated infectious diseases such as AIDS and other diseases. The preparation work for new experimental methods and animal models combined with gene editing technology is under rapid development and improvement. Laboratories around the world have also applied gene editing technique in prevention of malaria, organ transplantation, biological pharmaceuticals, agricultural breeding improvement, resurrection of extinct species, and other research areas. This paper summarizes the application and development status of gene editing technique in the above fields, and also preliminarily explores the potential application prospect of the technology in the field of traditional Chinese medicine, and discusses the present controversy and thoughts.

Targeted cancer imaging and photothermal therapy via monosaccharide-imprinted gold nanorods.

Plasmonic nanomaterials have been widely used for photothermal therapy (PTT) of cancer, but their recognition specificity remains challenging. We prepared monosaccharide-imprinted gold nanorods (AuNRs) for targeted cancer PTT, using sialic acid (SA) as a representative monosaccharide. The SA-imprinted AuNRs exhibited good specificity, enabling the killing of cancer cells without damaging healthy cells.

Coumarins with α-glucosidase and α-amylase inhibitory activities from the flower of Edgeworthia gardneri.

The flower of Edgeworthia gardneri is consumed in beverages in Tibet and has potential health benefits for diabetes. As a part of our continuous studies on dietary supplements for diabetes, two monomers, five dimers and one trimer of coumarins were isolated from the flowers of E. gardneri. One dimer was a new compound (1) and its structure was determined by spectroscopic methods, including multiple NMR techniques and mass spectrometry. The inhibitory activities of all coumarins against α-amylase and α-glucosidase were evaluated. Compound 4 displayed potent inhibitory effect on both α-amylase and α-glucosidase, with an IC50 of 90 and 86µg/mL, respectively. The IC50 of compound 3 against α-glucosidase was 18.7µg/mL, and its inhibition mode was noncompetitive. Based on the fluorescence analysis, the binding constant and the number of binding sites of compound 3 were calculated as 2.05×10(5) and 1.24, respectively. Furthermore, the interaction between compound 3 and α-glucosidase was a spontaneous process that was driven mainly by hydrophobic force. This study could facilitate the utilization of E gardneri as functional food ingredient.

α-Glucosidase Inhibition and Antihyperglycemic Activity of Phenolics from the Flowers of Edgeworthia gardneri.

The flowers of Edgeworthia gardneri are consumed as an herbal tea in Tibet with potential health benefits. To complement the current knowledge regarding the chemical composition and antihyperglycemic activity of the flower of E. gardneri, two new phenolics, gardnerol A and B (1 and 2), along with 19 known phenolics were isolated from the flower of E. gardneri. All isolates were evaluated for their inhibitory activity against α-glucosidase. Compound 5, identified as the major constituent of the flower of E. gardneri, showed a significant α-glucosidase inhibitory activity and acted as a competitive inhibitor. The oral administration of compound 5 at a dose of 300 mg/kg significantly reduced the postprandial blood glucose levels of normal and streptozotocin (STZ)-induced diabetic mice. Furthermore, compound 5 significantly decreased the fasting blood glucose levels in STZ-induced diabetic mice.

Very long-chain acyl-coenzyme A dehydrogenase deficiency in Chinese patients: eight case reports, including one case of prenatal diagnosis.

OBJECTIVE: Very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD) is a rare mitochondrial fatty acid ß-oxidation disorder. We aimed to explore the clinical, biochemical, and genetic findings, treatments and outcomes in eight Chinese VLCADD patients. METHODS: Eight patients from six unrelated Chinese families with symptomatic VLCADD were diagnosed in the past 4 years. The clinical features and ACADVL gene mutations were analyzed. RESULTS: One patient underwent newborn screening and has been treated timely, she hardly had any symptoms. The remaining seven patients were found because of edema, diarrhea, coma, liver damage and psychomotor retardation. Seven patients had fatty liver. Five had myopathy. All patients had elevated blood tetradecanoylcarnitine. Nine heterozygous mutations of the ACADVL gene were found. Three (c.1102C > T, c.1795G > A and IVS10, +6T > A) were novel. Seven patients completely recovered after treatment. One patient died before diagnosis due to cardiomyopathy. His mother underwent amniocentesis for prenatal diagnosis. The fetus had the same gene mutation of the proband and markedly elevated tetradecanoylcarnitine in amniotic fluid. The boy has been treated after birth and he is healthy now. CONCLUSIONS: Dietary treatment usually leads to good outcomes to VLCADD patients. Amniocytes ACADVL mutations and amniotic fluid tetradecanoylcarnitine analysis are useful for the prenatal diagnosis.

Structural investigation and biological activity of sesquiterpene lactones from the traditional Chinese herb Inula racemosa.

Five new sesquiterpene lactones, racemosalactones A-E (1-5), along with 19 known sesquiterpene latones (6-24), were isolated from the roots of Inula racemosa. Their structures were elucidated by extensive spectroscopic analysis, and the absolute configuration of 2 was deduced from X-ray diffraction analysis. Compounds 1, 6, 8, 10, 12, 14, and 17 exhibited antiproliferative activities with IC50 values ranging from 0.38 to 4.19 µg/mL against human non-small-cell lung cancer A549, hepatocellular carcinoma HepG2, and human fibrosarcoma HT1080 cells. Compounds 6 and 8 exhibited antiproliferative activities against endothelial cells with IC50 values of 2.4 and 2.5 µg/mL, respectively. Furthermore, compounds 6 and 8 both inhibited endothelial cell tube formation at 1.0 µg/mL. A method for the rapid and straightforward preparative-scale isolation of compound 6 from alantolides is described.

[Study on compatibility of traditional Chinese medicine active constituents with antioxidant activity].

OBJECTIVE: To find a research method suitable to multi-component multi-index composition-activity relationship of traditional Chinese medicines (TCMs) with the antioxidant activity of four compatible active constituents of TCMs as the subject. METHOD: LARS-based regression algorithm and comprehensive weight coefficient method were adopted to study in vitro clearance of DPPH and polyaromatic hydrocarbon with different doses of four compatible active constituents--total flavonoids of Glycyrrhizae Radix et Rhizoma (TFG), Ginkgo Folium extract (GBE), total flavonoids of Epimedii Folium (TFE) and astragaloside (AST) according to the comprehensive efficacy assessment procedures, that is test design, efficacy test and mathematical modeling (model verification). RESULT: LARS and comprehensive weight coefficient method was adopted to assess the optimal comprehensive efficacy of clearing DPPH and polyaromatic hydrocarbon. The results showed that the optimal dose combination of compatible constituents is TFG-GBE-TFE-AST 1: 0.2545: 0.007 6:0.011 5. CONCLUSION: The above compatibility of TCMs constituents can effectively clear polyaromatic hydrocarbon and DPPH with a good antioxidation. The uniform design adopted in this experiment, in combination of synthetic weight method, is suitable to the data analysis of "non-linear and small-sample" biotic experiment and the study on screening and assessment of compatibility of TCMs constituents.

Comparison of the effects of carbamyl-beta-methylcholine chloride administered by intravenous, intramuscular and intra-acupuncture point injections.

OBJECTIVE: To compare the effects of carbamyl-beta-methylcholine chloride (CMCC) administered by intra-acupuncture point injection (IAI), intramuscular injection (IMI), and intravenous injection (IVI), and to analyze the mechanisms. METHODS: In the IAI group, CMCC was injected into the Zusanli acupoint (ST 36) immediately after 30-min stimulation by electro-acupuncture (EA) at the acupoints, and into the femoral vein and skeletal muscle in IVI and IMI groups, respectively. Intra-gastric pressure was detected. The plasma concentration of CMCC was measured at various times. RESULTS: The gastric effect of CMCC in the IVI group was enhanced and attenuated more rapidly than in the other groups. In the IAI group, this effect was significantly stronger than that in the IMI group at 2 min and 15 min, but not significantly different between the two groups at 5 min and 30 min. Plasma concentration of CMCC in the IAI group was similar to that in the IVI group at 2 min, but higher than that in the IMI group. The concentration in the IAI group was higher than that in the IV group and similar to that in the IMI group at 5, 15 and 30 min, indicating rapid increase and slower reduction of the plasma concentration of the drug in the IAI group. There was a positive correlation between the plasma concentration of CMCC and intragastric pressure in all groups. CONCLUSION: The effect of IAI with CMCC was stronger than that of IMI and longer-lasting than that of IVI, which correlated with the blood concentration of CMCC.

[Intrahepatic cholestasis due to mitochondrial respiratory chain complex I deficiency in a Chinese boy].

Mitochondrial respiratory chain deficiency is a common cause of mitochondrial disease in children. This study aimed to review the clinical, enzymatic and genetic characteristics of a Chinese boy with progressive intrahepatic cholestasis due to mitochondrial respiratory chain complex I deficiency. The boy developed diarrhea from the age of 13 months, followed by progressive body weight loss, jaundice and weakness. His urine organic acids, blood amino acids and acylcarnitines profiles were normal. Mitochondrial respiratory chain complexes I to V activities in peripheral leukocytes were measured using spectrophotometric assay. Complex I activity was reduced. 5821G>A mutation was indentified by gene sequencing on tRNA-cys of mitochondrial gene in the patient and his mother. Vitamin supplements, liver protection, antibiotics and plasma infusion were not effective in the patient. Unfortunately, the boy died at the age of 17 months. Mitochondrial respiratory chain complex I deficiency is the most common mitochondrial respiratory chain disorder. This was the first case of intrahepatic cholestasis due to complex I deficiency confirmed by mitochondrial respiratory chain enzyme activity assay and gene analysis in China. It was concluded that mitochondrial hepatopathy is one of major causes of metabolic hepatopathy. Biochemical assay, mitochondrial respiratory chain complex activities assay and genetic analysis are crucial for the etiological diagnosis of metabolic hepatopathy.

Nutritional and metabolic findings in patients with Prader-Willi syndrome diagnosed in early infancy.

OBJECTIVE: Early treatment (growth hormone and nutritional support) improves development in infants with Prader-Willi syndrome. This study aimed to evaluate the nutritional and metabolic condition of nine patients who were diagnosed and treated in early infancy. METHODS: Nine patients were hospitalized at the age of \xe2\u20ac\xa810 days to 11 months because of severe feeding difficulties, failure to thrive, or developmental delay. The diagnosis of Prader-Willi syndrome was confirmed by fluorescence in situ hybridization or other molecular genetic techniques. Nutritional and metabolic investigations including urinary organic acid analysis, blood amino acid, and acylcarnitine profiles were performed. RESULTS: The diagnosis was made at the mean age of 6.3 months. A deletion of the paternal gene in the 15q11-13 region was detected in all patients. Eight patients had ketosis, seven had malnutrition, five had hyperammonemia, three had liver dysfunction, three had low blood cholesterol level, and two had hypoglycemia. All patients had reduction of serum multiple amino acids and free carnitine. Significant arginine deficiency was found in all patients. Six patients had mildly elevated blood long-chain and very long-chain acylcarnitine. After supplementation with l-arginine, medium-chain fatty acids, l-carnitine, and vitamins, all patients responded with improvement of motor development and nutritional conditions. Four patients were almost caught up on physical and psychomotor development. CONCLUSIONS: Patients with Prader-Willi syndrome are in bad metabolic condition in the early period. Early diagnosis and individual nutritional interventions may improve the nutritional and developmental progress and decrease death rate in infancy.

[Considerations about study on mechanisms of acupuncture underlying efficacy-enhancement and toxicity-attenuation of digitalis drugs for heart failure].

Digitalis glycosides, a group of cardiotonic agents for heart failure, have been used for a long time, but may often trigger arrhythmias as a result of digitalis intoxication. It is of great significance in finding a method to reduce their toxicity and improve clinical curative effects simultaneously in the application of digitalis glycosides. It has been well documented that acupuncture has good therapeutic effects in improving cardiac function and inhibiting arrhythmia induced by myocardial ischemia. Acupuncture combined with chemotherapeutics can reduce the adverse effects of chemotherapeutics. Accordingly, acupuncture combined with digitalis is likely to reduce the side effects of digitalis by regulating intracellular Ca2+, improving the function of Ca(2+)-ATPase in the sarcoplasmic reticulum, increasing calcium sensitivity of cardiac troponin, etc. These considerations may provide a novel clue for treatment of heart failure by joint administration of acupuncture and drugs.