Strategies for exogenous RNA delivery in RNAi-mediated pest management / 生物工程学报

Plant diseases and insect pests threaten the safety of crop production greatly. Traditional methods for pest management are challenged by the problems such as environmental pollution, off-target effects, and resistance of pathogens and insects. New biotechnology-based strategies for pest control are expected to be developed. RNA interference (RNAi) is an endogenous process of gene regulation, which has been widely used to study the gene functions in various organisms. In recent years, RNAi-based pest management has received increasing attention. The effective delivery of the exogenous interference RNA into the targets is a key step in RNAi-mediated plant diseases and pest control. Considerable advances were made on the mechanism of RNAi, and various RNA delivery systems were developed for efficient pest control. Here we review the latest advances on mechanisms and influencing factors of RNA delivery, summarize the strategies of exogenous RNA delivery in RNAi-mediated pest control, and highlight the advantages of nanoparticle complexes in dsRNA delivery.

Progress of cancer-associated fibroblasts in breast cancer / 肿瘤研究与临床

Tumor tissue is a complex of tumor cells, stromal cells, and extracellular matrix, and they constitute a disordered and aggressive microenvironment, which plays an indispensable role in the occurrence and development of tumors. In breast cancer, cancer-associated fibroblasts (CAF) not only promote the occurrence, proliferation, invasion, metastasis, and drug resistance of tumor, but also participate in events including angiogenesis, lymph angiogenesis, extracellular matrix remodeling, and reconstruction of the microenvironment, which are known to induce cancer. Therefore, a new strategy for tumor therapy is provided by targeting CAF. This article reviews the research progress of CAF in breast cancer.

Tyrosine hydroxylase deficiency: a case of autosomal recessive dopa-responsive dystonia / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the clinical characteristics of the patient with tyrosine hydroxylase deficiency, and investigate it's molecular mechanism.</p><p><b>METHOD</b>The clinical characteristics of a patient with tyrosine hydroxylase deficiency were summarized and analyzed, his and his family's peripheral blood specimens were collected after informed consent was signed. All exons and the intron-exon boundaries of guanosine triphosphate hydroxylase I gene, tyrosine hydroxylase gene and sepiapterin reductase gene were examined by DNA-PCR, bi-directional sequencing.</p><p><b>RESULT</b>The patient was a 3-year-old boy, presented with unexplained dystonia for 3 years, without significant impairment of intelligence. Physical examination showed limb muscle strength grade V, rigidity of extremities, hypertonicity, brisk deep tendon reflexes in limbs, without obvious abnormalities in auxiliary examination, such as brain MRI, hepatic biochemical panel, creatine kinase, and ceruloplasmin. He dramatically responded to small doses of levodopa in the follow-up for half a year. A homozygous missense change in exon 5 of TH gene, c.605G > A (p.R202H), which was a known pathogenic mutation, was found in the patient. His parents were heterozygous for the R202H mutation.</p><p><b>CONCLUSION</b>The age of onset in tyrosine hydroxylase deficiency patients is usually within the first year of life. Unexplained dystonia and hypokinesia were the main clinical features of tyrosine hydroxylase deficiency. The dopa-responsive effects for some patients are so obvious that we should strengthen awareness of the disease. TH gene c.605G > A (p.R202H) may be a common type of causative mutations for the mild form at home and abroad.</p>

Gene mutations and prenatal diagnosis in families with maple syrup urine disease / 中华围产医学杂志

Objective Maple syrup urine disease (MSUD) is a rare metabolic disorder caused by deficiency of the activity of branched-chain 2-keto acid dehydrogenase complex.The complex contains E1α,E1β and E2 subunits which are encoded by BCKDHA,BCKDHB or DBT genes respectively.Mutation in any gene will cause MSUD.The aim of this study was to analyze the gene mutations of four cases with MSUD and carry out prenatal diagnosis for these four families for MSUD.Methods From 2005 to 2010,four neonates (two males and two females) were diagnosed as MSUD at 2,5,10and 26 days of life.The coding regions of BCKDHA gene and BCKDHB gene in the above four cases were amplified by polymerase chain reaction and analyzed by direct DNA sequencing.During the second pregnancy of the same mother,the amniotic fluid was drawn out at 16-20 weeks for gene mutation analysis after the amniocytes were cultured.Results Mutation analysis revealed six mutations in four patients,including four novel mutations (c.308T＞C,c.562G＞T,c.1279C＞G and c.1280-1291de112) and two previously reported mutations.Five mutations (c.308T＞C,c.562G ＞T,c.868G＞A,c.1279C＞G and c.1280-1291de112) were detected on BCKDHA gene in three patients.While one mutation (c.853C＞T) was found on BCKDHB gene in one patient.Only one mutation was found in the amniocytes of each patient's mother at their second pregnancies suggesting a MSUD heterozygous fetus.Conclusions Analysis of BCKDHA and BCKDHB allowed preliminary understand of gene mutations in the four MSUD families,and made prenatal diagnosis possible,which helped in consultation in the second pregnancy.

Effect of Tongbihuoluo Tang on the cerebral infarction / 中国基层医药

Objective To observe the effect of Tongbihuoluo Tang on the cerebral infarction.Methods 148cases in recovery of cerebral infarction were randomly divided into control and treated groups(each n =74),the control group was treated with conventional western medicine,while the treated group was treated with Tongbihuoluo Tang based on the conventional treatment,the course was 28d,then the clinical efficacy of the two groups was compared.Results After treatment the neurological deficit score was significantly improved compared with before treatment,the treated group was better than the control group.The efficacy of the treated group was significantly better than the control group,the total effective rate was 94.6％,which was significantly higher than 75.5％ in control group,the difference between the two groups was significant(P ＜0.05).Conclusion Tongbihuoluo Tang may be helpful to the patients on the basis of western medicine,and it was worthy to be used in clinical practice.

Clinical and gene mutation analysis in patients with methylmalonic acidemia and homocystelnemia / 中华内分泌代谢杂志

ld have an improved outcome after reasonable treatments. The gene mutation detection suggests that 609G>A (W203X) may be the hot spot mutation of MMACHC gene in Chinese patients.

Analysis of the MUT gene mutations in patients with methylmalonic acidemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the MUT gene mutations in patients with methylmalonic acidemia (MMA), and analyze the genotype-phenotype correlation in patients with methylmalonyl-CoA mutase deficiency.</p><p><b>METHODS</b>The diagnosis of the disease mainly depends on the measurement of C3 (acylcarnitine), C3/C0 (free carnitine) and C3/C2 (acetylcarnitine) in the blood by tandem mass spectrometry, the detection of methylmalonic acid in the urine by gas-chromatography mass spectrometry, the determination of total homocysteine in the serum, and the loading test of vitamin B(12). The entire coding region of the MUT gene was screened by PCR combined with direct DNA sequencing in 21 isolated MMA patients. Novel mutations were identified by restriction fragment length polymorphism (RFLP) and sequence analysis in 100 controls.</p><p><b>RESULTS</b>Seventeen MUT gene mutations were detected in 14 of the 21 patients, among them 8 mutations were novel, and R108H, D244LfsX39 and G544X were more frequent, with the frequencies of 9.5%, 7.1% and 9.5%, respectively. Most mutations were missense mutations (64.7%), and majority of them were in exons 2 and 3 (55.6%). Ten out of the 14 patients with MUT gene mutations had early-onset disease, while one case had late-onset disease, and the remaining 3 cases were detected by newborn screening. In addition, 11 of these 14 patients did not respond to vitamin B(12).</p><p><b>CONCLUSION</b>This study revealed partial MUT gene mutation spectrum in Chinese patients with isolated MMA. The patients carrying MUT mutations often had early-onset disease, and most of them were VitB(12)- non-responsive.</p>

Expression of Fas, FasL system and C-erbB-2 in breast cancer and its clinical significance / 肿瘤研究与临床

Objective To explore the correlations of expression of Fas, FasL and C-erbB-2, its clinical significance and the correlation prognosis. Methods To protect the expression of mFas, mFasL and C-erbB-2 by immunohistochemistry SP method. To protect the sFas content by ELISA method. Results The expression of Fas showed lowest levels in breast carcinoma, showed lower levels in fibro-adenoma of breast and breast atypical hyperplasia, and showed highest levels in normal controls. The expression of FasL showed adversely, sFas showed highest levels in breast carcinoma, then in breast atypical hyperplasia, and showed lowest levels in normal control group. Fas and C-erbB-2 obviously presented negative correlation. Conclusion The expression of mFas showed inhibition in breast carcinoma, adversely the expression of mFasL showed enhancement, hint abnormality expression of mFas, mFasL may relevant tomammary glands cancer of occurrence and development. It can be used for estimating prognosis, but need a further research.

Screening for tetrahydrobiopterin deficiency among hyperphenylalaninemia patients in Southern China / 中华医学杂志(英文版)

<p><b>OBJECTIVES</b>To assess the incidence of tetrahydrobiopterin (BH4) deficiency among patients with hyperphenylalaninemia (HPA) in southern Chinese and evaluate clinical outcome and gene mutations in tetrahydrobiopterin deficient patients.</p><p><b>METHODS</b>Urinary neopterin (N) and biopterin (B) was analyzed in 87 patients with hyperphenylalaninemia by high-performance liquid chromatography. Further combined loading tests with phenylalanine (Phe) (100 mg/kg) and tetrahydrobiopterin (BH4) (7.5 mg/kg) were performed in suspected patients with abnormal urinary pterin profiles. Gene mutation analysis was performed for patients with BH4 deficiency and their parents. BH4 deficient patients were treated with BH4 and neurotransmitter precursors after diagnosis. Blood phenylalanine levels, clinical symptoms and mental development were followed up.</p><p><b>RESULTS</b>Eleven patients were diagnosed as having BH4 deficiency caused by 6-pyruvoyl tetrahydropterin synthase (PTPS) deficiency. The incidence of tetrahydrobiopterin (BH4) deficiency among patients with hyperphenylalaninemia (HPA) in southern Chinese was 10%. Combined loading tests with phenylalanine and oral BH4 were done in 4 of 11 patients and their phenylalanine levels were decreased to normal 4 - 6h after BH4 administration. Four different mutations (P87S, N52S, D96N and G144R) in the PTPS gene were detected in 5 families. Five PTPS-deficient patients were treated with synthetic BH4, neurotransmitter precursors (L-dopa plus carbidopa, and 5-hydroxytryptophan). They had satisfactory physical and mental development after treatment. One patient with partial PTPS deficiency had normal growth and mental development without treatment.</p><p><b>CONCLUSIONS</b>Our results emphasize that screening for BH4 deficiency should be carried out in all patients with hyperphenylalaninemia in order to minimize the misdiagnosis. Patients with BH4 deficiency should be treated early with BH4 and a combination of neurotransmitter precursors.</p>

Urinary pterin analysis in screening of tetrahydrobiopterin def iciency / 中华检验医学杂志

Objective To screen out the tetrahydrobiopterin def iciency in patients with hyperphenylalaninemia by urinary pterin analysis. Methods Analysis of urinary neopterin (N) and biopterin (B) was done in 96 patients with hyperphenylalaninemia by high performance liquid chromatography. Combined BH4 loading test was performed for patients with abnormal urinary pterin profiles. Results Eleven patients were diagnosed as ha ving BH4 deficiency caused by 6 pyruvoyl tetrahydrobiopterin synthase deficiency. They had a much high N/B ratio(N/B:197?250) and a very low B percentage (1.0?0.8)%. Blood phenylalanine levels were decreased from (720 1 200) ?mol/L to (120 240) ?mol/L after taking BH4 tablets in 4 of 11 patients. Conclusion The incidence of BH4 deficiency among hyperphenylalaninemia is about 12%. Analysis of urinary pterin is feasible and effective in screening of BH4 deficiency.