Observed index is a very important element in a research design, because it is a specific reflection of the effects of research factors on the research subjects and is indispensable in any research. Generally, there are two types of observed indexes: the indexes that reflect natural attributes, habits or states of the research subjects and the indexes that reflect the effects of different drugs or treatments on research subjects. This article mainly introduces the definition, characteristics, selection and observation of research indexes and the major and minor indexes.

AIM:To point the susceptible gene in Avellino corneal dystrophy family with autosomal dominant inheritance.
●METHODS: Genomic DNA was extracted from the peripheral blood samples of all individuals of the pedigree. Several microsatellite makers were selected for gene scan in the hot regions of mutation. Linkage analysis was carried out using a Linkage software package. The haplotype data were processed using Cyrillic software to define the region of the disease gene.
●RESULTS: ln our pedigree, significant evidence of linkage was obtained at marker D5S396 and D5S393 [LOD score (Z)=3. 01, recombination fraction (θ)=0. 00]. The haplotype analysis of our pedigree was located between the microsatellite markers D5S808 and D5S638.
●CONCLUSION:The pathogenic gene of the Avellino corneal dystrophy pedigree is traced to a 11. 2 cM region in the chromosome 5q.

Lipoproteins are biological lipids carriers. The natural and reconstituted lipoprotein based drug delivery systems have been extensively developed in recent years. This article reviews the development of natural and reconstituted low-density lipoprotein and high-density lipoprotein based vehicles in the antitumor area.
Animals ; Antineoplastic Agents ; administration & dosage ; chemistry ; Apolipoproteins B ; administration & dosage ; chemistry ; Drug Carriers ; administration & dosage ; chemistry ; Humans ; Lipoproteins ; administration & dosage ; chemistry ; Lipoproteins, HDL ; administration & dosage ; chemistry ; Lipoproteins, LDL ; administration & dosage ; chemistry ; Nanoparticles ; Neoplasms ; drug therapy ; Peptides ; administration & dosage ; chemistry ; Pharmaceutical Vehicles ; chemistry

OBJECTIVE To map a comprehensive metabolic pathway of herbacetin in rats, specifically, to elucidate the biotransformation of herbacetin in vivo and to simultaneously monitor the pharmacokinetic process of both parent drug and its major metabolites. METHODS liquid chromatography/ion trap mass spectrometry (LC/MSn) and ultra-liquid chromatography coupled with mass spectrometry (UPLC/MS) were combined in the current study for qualitative and quantitative determinations of herbacetin and its metabolites in bile, urine and feces after both oral and intravenous administration of herbacetin to rats. Enzyme kinetic studies on the intestinal and hepatic metabolism of herbacetin were further conducted to elucidate metabolic profiles of herbacetin in rat tissues and organs. Additionally, plasma concentration profiles of herbacetin and its metabolites in rats were obtained to characterize the overall pharmacokinetic behavior of herbacetin. RESULTS It was found that herbacetin was excreted primarily from rat urine in the form of glucuronide-conjugations. Subsequent in vitro enzyme kinetic studies and in vivo pharmacokinetic investigations suggested an extensive hepatic metabolism of herbacetin and the high exposure of herbacetin- glucuronides in systemic circulation. The clearance, half- life and bioavailability of herbacetin in rats were determined as (16.4±1.92)mL·kg-1·min-1, (11.9±2.7)min, and 1.32%, respectively. On basis of these findings, a comprehensive metabolic pathway of herbacetin in rats was composed. In addition, a physiology based pharmacokinetic (PBPK) model was successfully developed with the aid of the GastroPlus to simulate the pharmacokinetic process of herbacetin in rats. Application of the PBPK modeling can provide a useful starting point to understand and extrapolate pharmacokinetic parameters among different species, populations, and disease states. CONCLUSION After oral administration, herbacetin was subjected to colonic degradation and extensive first pass metabolism, with glucuronidation as its dominating in vivo metabolic pathway.

OBJECTIVE To investigate the effect of hypoxia on the pharmacokinetic process of salidrosidein rats and to explore its underlying mechanisms. METHODS The Caco-2 cell monolayerwas exposed to 1% oxygen (O2) concentration for 24 h to build the hypoxiccell model. The transportation mode of salidroside was investigated with the aid of this hypoxia model by detecting the apparent permeability coefficient(Papp). Healthy Sprague Dawley (SD) rats were exposed to 9% O2 for 72 h for the construction of hypoxic rat model. Liver sample was subsequently collected from the hypoxic rats with an aim to identify enzymes responsible for salidroside metabolism. The expression levels of sali?droside-transporting and salidroside-metabolizing enzymes, including Sodium-dependent glucose cotrans?porters (SGLT1), β-glucosidase (GBA3)and sulfotransferase (SULT2A1), were thereafter detected by RT-PCR and Western blot. The metabolic activity of GBA3 and SULT2A1 was monitored by rat liver microsome incubation.In addition, the renal function of rats under hypoxia was assessed by detecting concentrations of blood urea nitrogen and creatinine. RESULTS The AUC and t1/2 values of salidroside in hypoxic rats were more than doubled, while the in vivo clearance was significantly reduced. Mechanistic study demonstrated that the PappA- B/PappB- A eualsto 10.3, indicating the potential active transport of salidrosile. The expression of SGLT1 and GBA3 was significantly decreased, which indicated a reduced metabolism of salidroside under hypoxia. Moreover, rat under hypoxia was found to suffer from renal dysfunction, with an abnormal value of blood urea nitrogen. CONCLUSION Due to the reduced metabolism and the abnormal renal function under hypoxia, the systemic exposure of salidroside in rats was signifi?cantly enhanced.

For microbial production of lycopene, the lycopene synthetic genes from Pantoea agglomerans were integrated into Saccharomyces cerevisiae strain BY4742, to obtain strain ZD-L-000 for production of 0.17 mg · L(-1) lycopene. Improving supplies of isoprenoid precursors was then investigated for increasing lycopene production. Four key genes were chosen to be overexpressed, inclu- ding truncated 3-hydroxy-3-methylglutaryl-CoA reductase gene (tHMG1), which is the major rate-limiting enzyme in the mevalonate (MVA) pathway, a mutated global regulatory factor gene (upc2.1), a fusion gene of FPP synthase (ERG20) and endogenous GGPP synthase (BTS1), which is a key enzyme in the diterpenoid synthetic pathway, and GGPP synthase gene (SaGGPS) from Sulfolobus acidocaldarius. Over-expression of upc2.1 could not improve lycopene production, while over-expression of tHMGI , BTS1-ERG20 and SaGGPS genes led to 2-, 16. 9- and20. 5-fold increase of lycopene production, respectively. In addition, three effective genes, tHMG1, BTS1-ERG20 and SaGGPS, were integrated into rDNA sites of ZD-L-000, resulting in strain ZD-L-201 for production of 13.23 mg · L(-1) lycopene, which was 77-fold higher than that of the parent strain. Finally, two-phase extractive fermentation was performed. The titer of lycopene increased 10-fold to 135.21 mg · L(-1). The engineered yeast strains obtained in this work provided the basis for fermentative production of lycopene.
Bacterial Proteins ; genetics ; metabolism ; Biosynthetic Pathways ; Carotenoids ; biosynthesis ; Genes, Synthetic ; Genetic Engineering ; Pantoea ; enzymology ; genetics ; Saccharomyces cerevisiae ; genetics ; metabolism

Background Corneal epithelial abrasion results in corneal ulcer and stroma cloudy evenb irreversible visual impairment.Previous drugs for corneal epithelial injury can only alleviate the inflammatory irritation.So it is very important to seek a drug which regulate the growth of corneal epithelium.Objective This study was to investigate the effects of recombinant human BIGH3 protein eye drops on corneal epithelial abrasion.Methods Fifty right eyes of 50 clean adult New Zealand white rabbits were collected.Two rabbits were sacrificed right away following establishment of corneal epithelial abrasion models (0 hour group).The other 48 rabbits were randomly divided into recombinant human epidermal growth factor (EGF) derivative group (positive control group),normal saline solution group (negative control group),0.25％ or 0.5％ recombinant human BIGH3 protein eye drops group.Corneal abrasion models were created with alcohol corrosion method with a defect area of 7 mm2.The corresponding eye drops were used separately in 4 groups for four times per day after operation.Experimental eyes were examined by the slit lamp microscope,and fluorescein vital staining were performed 12,24,36,48,72 hours after operation.Planimetry was performed and the corneal photographs were analyzed with computer software.The rabbits were sacrificed 12,24,36,48 and 72 hours after operation,respectively,and the histopathological examination of corneal tissue was carried out.Results No obvious irritation response was seen after administered of eye drops in the recombinant human EGF derivative group,normal saline solution group,0.25％ and 0.5％ recombinant human BIGH3 protein eye drops groups.Histopathological examination revealed a full-thickness defect of corneal epithelium after modeling.The defect area was gradually smaller with time lapse,and corneal epithelium migrated from periphery toward the center zone.Corneal epithelial cells increased with time lapse.Compared with normal saline solution group,the defect area of corneal epithelium lessened 12,24,36,48 hours after operation in the 0.25％,0.5％ recombinant human BIGH3 protein eye drops groups and recombinant human EGF derivative group (all at P =0.000),but at 12and 24,36 hours after operation,no significant differences were found between the recombinant human EGF derivative group and normal saline solution group (P =0.321,0.057,0.126).The defect area was smaller in the 0.5％recombinant human BIGH3 protein eye drops group than that of the recombinant human EGF derivative group at various time points (P=0.042,0.039,0.025,0.008).However,significant smaller defect area was exhibited only at 12 hours and 24 hours after operation in the 0.25％ recombinant human BIGH3 protein eye drops group (P=0.047,0.042).No significant differences were seen in corneal defect area at various time points between 0.25％ and 0.5％recombinant human BIGH3 protein eye drops groups (P =0.358,0.259,0.108,0.062).In addition,the corneal defect area was (0.51 ±0.42)mm2 72 hours after operation in the normal saline group;while that in the recombinant human EGF derivative group and recombinant human BIGH3 protein eye drops groups was disappeared.The repairing curves in the recombinant human BIGH3 protein eye drops groups were superior to those of the recombinant human EGF derivative group and normal saline solution group.Conclusions 0.25％ and 0.5％ recombinant human BIGH3 protein eye drops have facilitation effect on the growth of corneal epithelial cells and the healing of corneal injury.

OBJECTIVETo explore diseases in the neonatal period among hospitalized preterm infants.

METHODSThe clinical data of 961 preterm infants who were hospitalized in three hospitals in Changsha in 2008 were retrospectively reviewed.

RESULTSThe most common neonatal disease was respiratory system diseases (73.8%), followed by infectious diseases (39.4%) and nervous system diseases (38.3%). With the increase of gestational age and birth weight, the incidence of circulatory system diseases showed no statistically significant differences (all P>0.05), while the incidences of other diseases, such as respiratory system diseases, neonatal infections, nervous system diseases, and the desirable outcome of the preterm infants became significantly different (all P<0.05). Increased birth weight and gestational age were the protective factors while neonatal asphyxia, hyperbilirubinemia and neonatal scleredema were the risk factors for the outcome of preterm infants.

CONCLUSIONSThe common neonatal diseases for preterm infants are respiratory system diseases, neonatal infections, and nervous system diseases. The incidence of the common diseases is reduced with the increasing gestational age and birth weight. Interventions should be carefully planned based on the protective factors (increased birth weight and gestational age) and risk factors (neonatal asphyxia, hyperbilirubinemia and scleredema) of the outcomes of these diseases.

Birth Weight ; Female ; Gestational Age ; Humans ; Incidence ; Infant, Newborn ; Infant, Premature, Diseases ; epidemiology ; Logistic Models ; Male ; Risk Factors

Objective To observe the influence of traditional Chinese Medicine (TCM) Five-element music combined with language induction on the psychological status and quality of life among maintenance hemodialysis patients. Methods A total of 66 maintenance hemodialysis patients were divided into the Five-element music group (n=34) and the routine care group (n=32) according to date of hemodialysis. The routine group accepted routine care. The music group accepted the intervention of traditional Chinese Medicine Five-element music combined with language induction on the basis of routine care. Four weeks later, the changes of Hospital Anxiety Depression Scale (HAD), the MOS item Short From Health Survey (SF- 36) were observed to assess the effect before and after the intervention. Results HAD comparison in the group: After 4-week intervention, in Five-element music group, the depression and anxiety score of HAD and HAD total score were 3, 5, 9 (meadian score), which had improved significantly than before, which were 4, 7, 12 (meadian score), the difference was significant (Z=-2.645,-2.927,-3.220, P<0.01) . After 4 weeks, in the routine group the depression and anxiety score of HAD and HAD total score showed no significant change than before (P>0.05). SF-36 comparison in groups: After 4-week intervention, in Five-element music group, the physical, physiological function,overall health, energy status, social function, emotional function, mental health factors of SF-36 scored 63, 88, 74, 41, 75, 75, 100, 80 (meadian score), which had improved significantly compared with before, which were 45, 0, 68, 40, 58, 75, 17, 72 (meadian score), the difference was significant (Z=-3.895--2.027, P<0.01 or 0.05), body pain and mental health factors had no significant difference (t=-1.785,-1.576, P>0.05). After 4 weeks, the routine group′s each factor score had no significant difference compared with before (P > 0.05). Conclusions TCM Five-element music has a certain effect on improving the psychological status and the quality of life of the patients in maintenance hemodialysis.

Objective To understand the carrying condition of the mutation gene of neonatal deafness in Huzhou City and explore the significance of the combination screening of hearing and deafness genes. Methods 2258 newborns who were born in Huzhou maternal and child health care hospital were screened for hearing and deafness and were followed up to the age of 3. Two kinds of complementarity and relativity of screening were analyzed. Early hearing screening was used by transient evoked otoacoustic emission (TEOAE) screening, hearing rescreening was used by TEOAE and autoauditory brainstem response (AABR) . Collected the neonatal umbilical cord blood and detected GJB2, SLC26A4, GJB3, mitochondrial 12SrRNA 4 genes 20 deafness mutations. Results Early hearing screening failed in 550 cases, with a failure rate of 24.36％. Detected in 118 cases of deafness gene carriers, total carrying rate was 5.23％. GJB2, SLC26A4, GJB3 and mitochondrial 12SrRNA gene mutation rate were 3.10％, 1.46％, 0.58％ and 0.09％ respectively. Initial failure rate of mother and child hearing screening was 16.30 ％ (300/1840) . The rate of gene transfer for deafness mutation was 5.65 ％ (104/1840) . Initial failure rate of NICU hearing screening was 59.81 ％ (250/418) . The rate of gene transfer for deafness mutation was 3.35％ (14/418) . The failure rate of initial hearing screening of NICU newborns was higher than that of mother and child (P<0.01) . There was no statistically significant difference in carrying rate between the two groups (P>0.05) . There was no statistical correlation between initial hearing screening andwhether or not to carry deaf mutation gene (P>0.05) . 52 infants were missed in this study. 12 patients were diagnosed with hearing impairment, and the hearing impairment rate was 0.54％. Among them, 9 cases were normal and 3 cases were abnormal. Conclusion Newborns hearing screening by whether or not had nothing to do with deafness gene.Hearing screening with deafness gene screening at the same time can reduce the delay in diagnosis of deafness and drug deafness can also be prevented early.