Micro-RNA Clusters Integrate Evolutionary Constraints on Expression and Target Affinities: The miR-6/5/4/286/3/309 Cluster in Drosophila.

A striking feature of micro-RNAs is that they are often clustered in the genomes of animals. The functional and evolutionary consequences of this clustering remain obscure. Here, we investigated a micro-RNA cluster miR-6/5/4/286/3/309 that is conserved across drosophilid lineages. Small RNA sequencing revealed expression of this micro-RNA cluster in Drosophila melanogaster leg discs, and conditional overexpression of the whole cluster resulted in leg appendage shortening. Transgenic overexpression lines expressing different combinations of micro-RNA cluster members were also constructed. Expression of individual micro-RNAs from the cluster resulted in a normal wild-type phenotype, but either the expression of several ancient micro-RNAs together (miR-5/4/286/3/309) or more recently evolved clustered micro-RNAs (miR-6-1/2/3) can recapitulate the phenotypes generated by the whole-cluster overexpression. Screening of transgenic fly lines revealed downregulation of leg-patterning gene cassettes in generation of the leg-shortening phenotype. Furthermore, cell transfection with different combinations of micro-RNA cluster members revealed a suite of downstream genes targeted by all cluster members, as well as complements of targets that are unique for distinct micro-RNAs. Considered together, the micro-RNA targets and the evolutionary ages of each micro-RNA in the cluster demonstrate the importance of micro-RNA clustering, where new members can reinforce and modify the selection forces on both the cluster regulation and the gene regulatory network of existing micro-RNAs. Key words: micro-RNA, cluster, evolution.

Electroacupuncture of both single- and multi-acupoints promotes recovery of gastrointestinal function in laparoscopic cholecystectomy patients / 针刺研究

OBJECTIVE: To compare the therapeutic effect of electroacupuncture (EA) of single-acupoint Zusanli (ST36) and multi-acupoints Zusanli (ST36), Shangjuxu (ST37) and Neiguan (PC6) in promoting the recovery of gastrointestinal movement in laparoscopic cholecystectomy (LC) patients undergoing general anesthesia. METHODS: A total of 70 LC patients (American Society of Anesthesiologists [ASA] grade I and II) were recruited and randomly divided into control (n＝23), single ST36 (n＝23) and ST36＋ST37＋PC6 (n＝24) groups. The patients in the control group only received routine basic treatments (postoperative fasting and water deprivation, intravenous drip of biotics, water-electrolyte and acid-base balancing, oxygen uptake, etc). EA (10 Hz, 5 mA, 30 min every time) was applied to the abovementioned single-acupoint or multi-acupoints groups before, and 4, 22, 34 and 46 h after the operation. The time-points of postoperative borborygmus recovery, first anal exhaust and defecation, post-operative abdominal distension (mild, moderate and severe), nausea and vomiting (grade Ⅰ， Ⅱ， Ⅲ and Ⅳ) at 6, 24 and 48 h after surgery were recorded and analyzed. RESULTS: Compared to the control group, the time of borborygmus recovery, first anal exhaust and defecation were markedly earlier in both single ST36 and ST36＋ST37＋PC6 groups (P0.05). CONCLUSION: EA of both single ST36 and ST36＋ST37＋PC6 can promote gastrointestinal function recovery in LC patients, without remarkable difference between them.

Pathological evaluation of immune system in drug safety study / 药物评价研究

The immune system is a complex system involving multiple organs,and it is vulnerable to age,gender,environment and other factors.For a variation normal physiological range,it is a great challenge to evaluate drug-induced immunotoxicity in preclinical safety study.Histomorphologic assessment of the immune system is a recognized cornerstone in the identification of immunotoxicity at present.In this paper,the principles of pathological evaluation for immune system,and pathological evaluation for important immune organs including thymus,spleen,lymph nodes are discussed briefly,so that it is intended to assist toxicity pathologists in the accurate and consistent characterization of intended and unintended drug-induced alterations of the immune system.

Intracranial Aneurysm and Arteriovenous Malformation: Relationship of Expression of VEGF and Clinical Features / 现代生物医学进展

Objective:To investigate the relationship of expression of vascular endothelial growth factor (VEGF) and clinical features in patients with intracranial aneurysm and arteriovenous malformation (AVM).Methods:A total of 64 patients with AVM and intracranial aneurysm,who were treated in First Hospital of Shijiazhuang from February 2011 to November 2015,were chosen as research subjects,AVM were 32 cases and intracranial aneurysm were 32 cases.The samples were sectioned for VEGF immunohistochemical staining;the location and intensity of staining were recorded;the positive indexes were computed.The VEGF expression of different age and Hunt&Hess classification in patients with intracranial aneurysms were analysed;the VEGF expression of different diameters,ages,Spetzler classification in patients with AVM were analysed.Results:There were no statistical differences in the VEGF expression of different ages in patients with intracranial aneurysms (P＞0.05);the VEGF expression of different Hunt&Hess classification in patients with intracranial aneurysms was statistical difference (P＜0.05).The positive rate of VEGF in the artery of AVM was lower than that in the vein,the difference was statistically significant (P＜0.05).There were no statistical differences in the VEGF expression of the different Spetzler classification,different diameters and different ages in patients with AVM (P＞0.05).Conclusion:The expression of VEGF in the vein and the artery of patients with AVM is different,the expression of VEGF is not correlated with the age of intracranial aneurysm and the size and age of AVM.VEGF cannot be used as a predictor in the patients with intracranial aneurysms and AVM.

Examination and assessment of target organ toxicity in toxicologic pathology of preclinical safety evaluation of drugs / 药物评价研究

Examination and assessment of target organ toxicity in toxicologic pathology of preclinical safety evaluation of drugs should combine the results of the gross pathology,histopathology and clinical pathology examination data in a well-considered,stepwise approach.In addition,the nomenclature and diagnostic criteria recommended by INHAND should be used to avoid subjective and inappropriate diagnosis.In this paper,we briefly introduced the basic principles for the examination of organ toxicity in toxicology studies,gross pathology,histopathology,diagnostic approach,procedures,and considerations,international harmonization of diagnostic term and criteria,clinical pathology parameters analysis,results of a well-concerted combination of anatomical and clinical pathology data so as to provide some reference for the examination and assessment of target organ toxicity in toxicologic pathology in the field ofpreclinical safety evaluation of drugs in China.

Major factors influencing quality of neuropathology evaluation of drug toxicology / 药物评价研究

Neurotoxicity is one common adverse effect caused by many drugs or compounds.In the early phase of new drug development,it is necessary to screen for neurotoxicants.Neurotoxicity studies in nonhuman primates (NHP) are used to evaluate the neurotoxicity of small-molecule drugs or vaccines that may affect the nervous system across the blood-brain barrier during preclinical safety assessment.Toxicologic pathological evaluation or neuropathological examination is the "gold standard" for the evaluation of drug neurotoxicity in preclinical drug safety studies.In this paper,the majory factors influencing the quality of neuropathology evaluation in toxicology,including the general strategy of neuropathology evaluation,the optimal timing of evaluation,the specific blood-brain barrier in the nervous system,the method of sampling in the histopathology of nerve tissue,and the interference of artificial artifacts in diagnosis of neuropathology,were detailly analyzed in order to provide a reference for setting guidelines of neurotoxicity risk assessment in China and pathologists and toxicologists engaged in nonclinical neurotoxicity studies.

Validation of computerized system in facilities for preclinical safety evaluation of drugs / 药物评价研究

Computerized system has been played an increasingly important role in preclinical safety evaluation of drugs and has been used directly or indirectly for data acquisition,processing,reporting as well as raw data storage.However,the computerized system has not been widely used in facilities for preclinical safety evaluation of drugs or only some functions of modules of computerized system have been used.Based on the current application status of the computerized system in the facilities for preclinical safety evaluation of drugs in China,this paper briefly introduced the following aspects about validation of computerized system,such as GLP regulatory requirements of validation of the computerized system,validation process of the computerized system,maintenance of validation state of the computerized system,safety precautions of performance of the computerized system,as well as electronic records and electronic signatures with the purpose to provide some references for carrying out and speeding up the validation of computerized system and to further improve the efficiency of the computerized system in facilities for preclinical safety evaluation of drugs in China and to be in line with international practice.

Principles of necropsy and gross pathology examination for toxicologic pathology assessment / 药物评价研究

Toxicologic pathology plays an important role in the safety evaluation of drugs.The results of toxicologic pathology can answer the basic problems of pathological lesions such as location,severity grading,nature and prognosis,etc.Necropsy and gross pathology examination are important aspects of toxicologic pathology assessment.Procedures typically include preparation for the necropsy,euthanasia procedures,identification and recording all gross lesions,collection of tissues listed in the study protocol,determination of organ weight,as well as tissue fixation so as to be ready for the subsequent tissue processing and histopathology examination.All the procedures must be done in a consistent manner and in accordance with standard operating procedures (SOPs).The present paper briefly introduced the principles of necropsy and gross pathology examination for toxicologic pathology in order to standardize the procedures and to lay foundation for the improvement of the histopathology examination in the field of preclinical safety evaluation of drugs of China.

Toxicological pathology in preclinical drug safety evaluation / 药物评价研究

Toxicological pathology is a morphological elucidatet ion of tissue damage caused by drug toxicity,including damage type,location,severity grade and prognosis.It provides objective and accurate data to support preclinical drug safety evaluation.Therefore,toxicological pathology plays an important role in drug safety evaluation,and the pathologic data or conclusion often determines the termination or continuation in many drug development projects.In this paper,the characteristic of toxicological pathology,standardized management,the development of new techniques including in situ hybridization,laser scanning cytometry and laser capture microdissection,and related problems in pathology are discussed briefly.

[Anatomical presentation of edentulous sites in the posterior maxillary in cone beam computed tomography].

OBJECTIVE: This study aimed to analyze the bone anatomy of edentulous sites in the posterior maxillary by cone beam computed tomography (CBCT). METHODS: A total of 100 CBCT radiographs from patients with missing maxillary posterior teeth were obtained, resulting in a sample size of 217 edentulous sites. The width and height of edentulous were assessed by three-dimensional reconstruction. In addition, the angle A and morphology of the maxillary sinus walls were evaluated. RESULTS: The mean bone height was 9.53 mm, and the percentage of sites than 10 mm was 62.67% (136/217). The mean bone width was 9.30 mm, and the percentage of sites more than 6 mm was 91.71% (199/217). The bone height decreased from premolar to molar areas, but the opposite trend was observed in bone width. Regarding the morphology of the sinus floor, 64.52% exhibited an oblique configuration. In angle A, the group of less than 30° was 10.14%, 30°-60° was 42.40%, and greater than 60° was 47.47%. CONCLUSION: A high percentage of edentulous sites in the posterior maxillary requires sinus floor elevation to allow the placement of dental implants. Thus, the use of CBCT scans is recommended to evaluate the anatomical structure of the maxillary sinus for reasonable implant planning.

Thyroid hormones affect alveolar bone density / 中国组织工程研究

BACKGROUND:Overproduction of thyroid hormones is shown to increase the activities of osteoblasts and osteoclasts, stimulating bone resorption and transformation. Inadequate compensation of increased bone resorption by bone transformation results in an increased loss of bone mass. OBJECTIVE:To investigate the effects of hyperthyroidism on the density of the alveolar bone. METHODS:Twenty-four New Zealand rabbits were equal y randomized into hyperthyroidism group and control group. Rabbits in the hyperthyroidism group or control group were daily injected intraperitoneal y with 50μg/kg levothyrocine diluted in physiological saline solution or equal volume of physiological saline. At 8 weeks after treatment, serum levels of thyroid hormones (FT3 and FT4), alkaline phosphatase, magnesium and calcium, phosphorus were determined;meanwhile, the bone densities of the lumbar vertebra, mandible, bilateral distal femur were determined by dual energy X-ray absorptiometry and the correlation analysis was performed. RESULTS AND CONCLUSION:At 8 weeks after treatment, serum levels of FT3, FT4, alkaline phosphatase calcium, phosphorus, and magnesium in the hyperthyroidism group were significantly increased (P<0.01), while the bone densities of the lumbar vertebra, mandible, bilateral distal femur were significantly decreased (P<0.05), compared with the control group. Bone density of the mandible was positively correlated with the bone density the lumbar vertebra and bilateral distal femur. These findings suggest that the changes in FT3 and FT4 are sufficient for the diagnosis of hyperthyroidism. Hyperthyroidism results in the decreased density of the alveolar bone, indicating the occurrence of osteoporosis.

Anatomical presentation of edentulous sites in the posterior maxillary in cone beam computed tomography / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study aimed to analyze the bone anatomy of edentulous sites in the posterior maxillary by cone beam computed tomography (CBCT).</p><p><b>METHODS</b>A total of 100 CBCT radiographs from patients with missing maxillary posterior teeth were obtained, resulting in a sample size of 217 edentulous sites. The width and height of edentulous were assessed by three-dimensional reconstruction. In addition, the angle A and morphology of the maxillary sinus walls were evaluated.</p><p><b>RESULTS</b>The mean bone height was 9.53 mm, and the percentage of sites than 10 mm was 62.67% (136/217). The mean bone width was 9.30 mm, and the percentage of sites more than 6 mm was 91.71% (199/217). The bone height decreased from premolar to molar areas, but the opposite trend was observed in bone width. Regarding the morphology of the sinus floor, 64.52% exhibited an oblique configuration. In angle A, the group of less than 30° was 10.14%, 30°-60° was 42.40%, and greater than 60° was 47.47%.</p><p><b>CONCLUSION</b>A high percentage of edentulous sites in the posterior maxillary requires sinus floor elevation to allow the placement of dental implants. Thus, the use of CBCT scans is recommended to evaluate the anatomical structure of the maxillary sinus for reasonable implant planning.</p>

Genomic sequence and experimental tractability of a new decapod shrimp model, Neocaridina denticulata.

The speciose Crustacea is the largest subphylum of arthropods on the planet after the Insecta. To date, however, the only publically available sequenced crustacean genome is that of the water flea, Daphnia pulex, a member of the Branchiopoda. While Daphnia is a well-established ecotoxicological model, previous study showed that one-third of genes contained in its genome are lineage-specific and could not be identified in any other metazoan genomes. To better understand the genomic evolution of crustaceans and arthropods, we have sequenced the genome of a novel shrimp model, Neocaridina denticulata, and tested its experimental malleability. A library of 170-bp nominal fragment size was constructed from DNA of a starved single adult and sequenced using the Illumina HiSeq2000 platform. Core eukaryotic genes, the mitochondrial genome, developmental patterning genes (such as Hox) and microRNA processing pathway genes are all present in this animal, suggesting it has not undergone massive genomic loss. Comparison with the published genome of Daphnia pulex has allowed us to reveal 3750 genes that are indeed specific to the lineage containing malacostracans and branchiopods, rather than Daphnia-specific (E-value: 10⁻6). We also show the experimental tractability of N. denticulata, which, together with the genomic resources presented here, make it an ideal model for a wide range of further aquacultural, developmental, ecotoxicological, food safety, genetic, hormonal, physiological and reproductive research, allowing better understanding of the evolution of crustaceans and other arthropods.

Identification of a novel HLA allele B 4446 by sequencing-based typing / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify a novel HLA allele in Chinese population.</p><p><b>METHODS</b>A new HLA-B allele was initially detected by an usual PCR-SSP and PCR-SSOP in routine typing HLA allele. Sequence-based typing (SBT) was used to identify and analysis the difference between the new allele and HLA-B 4409 allele.</p><p><b>RESULTS</b>The HLA-B exon 3 nucleotide sequence of the novel allele was different from all other known alleles. The allele had 3 nucleotides replaced of the closest matching B 4409 allele at nt538(G>C), nt539(A>T) and nt540 (C>G) in exon 3, resulting in an amino acid change from D(GAC) to L(CTG) at codon 180.</p><p><b>CONCLUSION</b>A novel HLA allele was confirmed by the SBT and it was officially designated as HLA-B 4446 by WHO Nomenclature Committee for Factors of the HLA System in September,2005.</p>

Polymorphism distribution of HLA-DRB1 gene locus in Han race population in Liaoning of China / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To elucidate the genotype distribution of HLA-DRB1 polymorphisms in the Han race population in Liaoning of China and to evaluate its value on forensic medicine.</p><p><b>METHODS</b>The blood DNA samples from 13265 unrelated Chinese individuals of Han race population in Liaoning province were investigated and HLA-DRB1 alleles were genotyped with PCR-SSP and PCR-SSOP in low resolution level.</p><p><b>RESULTS</b>Thirteen HLA-A alleles were found, in which HLA-DRB1*15, 09, 12, 07 were the commonest but HLA-DRB1*03(18), HLA-DRB1*14(8) were absent. The population data conformed to the Hardy-Weinberg equilibrium(chi-square was 73.34, df was 78, P> 0.5). The exclusion probability of paternity was 64.7%, the power of discrimination was 97.9% and the heterozygosity was 89.4%.</p><p><b>CONCLUSION</b>The HLA-DRB1 polymorphism of Liaoning Han populations show the special characters and HLA-DRB1 genotyping is useful genetic marker to paternity testing and personal identification.</p>

Implementation of Preventive Maintenance of Ultrasonic Instrument in Field Hospital / 医疗卫生装备

The preventive maintenance of medical instruments is very important in field hospital. Because of effective preventive maintenance,the ultrasonic instrument ran normally and efficiently in field hospital. The method of preventive maintenance are introduced,including quakeproof,power supply,hot & moist resistance,dustproof,antijam,probe maintenance,etc. These maintenance methods can provide reference for diversified military affairs.

Application of Ultrasonic Scalpel in Clinical Surgery / 医疗卫生装备

Ultrasonic scalpels,including incision type and aspiration type,are introduced from aspects of the principles,key technologies and clinical application.Uitrasonic scalpel has the advantages of less bleeding,exact incision,,safety,shortened time of operation and less damage to surrounding tissue.Some technology problems of ultrasonic scalpel are also summarized.It is pointed out that ultrasonic scalpel is the tendency and direction of clinical surgery development,which has extensive application prospects.

Characteristics and Implementation of Maintenance of Medical Instruments in Field Hospital / 医疗卫生装备

Influence on diagnosis equipment in field hospital for earthquake relief are stated such as weather, voltage, noise and interference. It is necessary to maintain diagnosis equipment in field condition.

Safety Operation and Protection of Radio Knife / 医疗卫生装备

The widely application of the radio knife alleviates the patient's pain and improve the medical quality.The radio knife is high frequency power equipment based on the theory that electricity concentrates on the skin.It can directly cut the tissue,homeostasis and cauterize.The safety requirement of this equipment is very strict because unsafe operation will burn the tissue,cause temporal unaware hurt and even endanger the patient's life.If the safety support system is imperfect,disastrous loss or medical conflict will be caused.Users must be cautious in using and familiar with the safety and protection of the radio knife.[Chinese Medical Equipment Journal,2008,29(2):96-98,104]