Objective:To explore the effect of feeding via the transpyloric route on the gastrointestinal function in very low birth weight (VLBW) infants and find the best early enteral nutrition protocol.Methods:Sixty VLBW infants were randomly devided into transpyloric feeding group(TP group) (n =30) and intragastric feeding group(IG group) (n =30).The frequency of apnoea,weight gain,the time of birth weight regain,feed intolerance,time of reaching full enteral feeding,the incidence of extrauterus-growth retardation (EUGR),motilin,gastrin,the length of hospital stay,necrotizing enterocolitis and duodenal perforation were observed in two groups.Results:The intolerance and time of reaching full enteral feeding were reduced significantly during transpyloric feeding compared with intragastric feeding (P ＜ 0.05).The number of episodes of apnoea was decreased significantly during transpyloric feeding compared with intragastric feeding (P ＜ 0.01).Conclusion:Transpyloric feeding can be used in VLBW infants.

OBJECTIVESince glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common hereditary hemolytic erythrocyte enzyme deficiency, most cases have single nucleotide mutations in the coding region, and current test methods for gene mutation have some missed detections, this study aimed to investigate the feasibility of RT-PCR sequencing in the detection of gene mutation in G6PD deficiency.

METHODSAccording to the G6PD/6GPD ratio, 195 children with anemia of unknown cause or who underwent physical examination between August 2013 and July 2014 were classified into G6PD-deficiency group with 130 children (G6PD/6GPD ratio <1.00) and control group with 65 children (G6PD/6GPD ratio≥1.00). The primer design and PCR amplification conditions were optimized, and RT-PCR sequencing was used to analyze the complete coding sequence and verify the genomic DNA sequence in the two groups.

RESULTSIn the G6PD-deficiency group, the detection rate of gene mutation was 100% and 13 missense mutations were detected, including one new mutation. In the control group, no missense mutation was detected in 28 boys; 13 heterozygous missense mutations, 1 homozygous same-sense mutation (C1191T) which had not been reported in China and abroad, and 14 single nucleotide polymorphisms of C1311T were detected in 37 girls. The control group showed a high rate of missed detection of G6PD deficiency (carriers) in the specimens from girls (35%, 13/37).

CONCLUSIONSRT-PCR sequencing has a high detection rate of G6PD gene mutation and a certain value in clinical diagnosis of G6PD deficiency.

Adolescent ; Child ; Child, Preschool ; Female ; Glucosephosphate Dehydrogenase ; genetics ; Glucosephosphate Dehydrogenase Deficiency ; diagnosis ; genetics ; Humans ; Infant ; Male ; Mutation ; Reverse Transcriptase Polymerase Chain Reaction ; methods ; Sequence Analysis, DNA

Objective To investigate the epidemiological characteristics of incipient neonatal hyperbilirubinemia. Methods The clinical data of admitted neonates with hyperbilirubinemia were retrospectively analyzed from June 2012 to May 2013. Results Two hundred and eight-four neonates with hyperbilirubinemia were enrolled and the ratio of male:female was 1.51:1. For the causes of hyperbilirubinemia, the incidences of ABO hemolytic and sepsis were higher in term infants than those in preterm infants, and the incidences of pneumonia, necrotizing enterocolitis and intracranial hemorrhage were higher in preterm infants than those in term infants (P<0.05). Compared with the preterm infants, the term infants had jaundice appearance and peak at earlier time, shorter duration of jaundice, faster decline rate of jaundice, higher levels of albumin and indirect bilirubin at the peak of jaundice (P<0.01). In the term infants, the time of jaundice appearance and peak were earlier in hemolytic group than those in non-hemolytic group (P<0.05). In preterm infants, the peak of transcutaneous bilirubin was higher in hemolytic group than that in non-hemolytic group (P<0.05). Six cases with bilirubin encephalopathy had abnormalities cranial MRI imaging, and the MRI was not entirely consistent with the peak level of bilirubin. Conclusions There are clinical differences between hemolytic and non-hemolytic hyperbilirubinemia in both term and preterm infants.

Objective To develop psychosocial skills training module for schizophrenic outpatients.Methods Structured psychosocial skills training program, which were made according to community rehabilitation plan for schizophrenia, featured convenience and well operability. Subjects were 96 of 204 schizorenic outpatients in remission who were randomly assigned to receive psychosocial skills training combined medicine(observation group) or medicine only(control group) and followed up by 24 months. The changes during treatment were evaluated by positive and negative syndrome scale(PANSS), Social Disability Screening Schedule(SDSS) and patients' cognition function were also evaluated longitudinally. Results Relapse rate of control group (37%) is higer than observation group (17.7%, P＜0.01). After Last Observation Carried Forward(LOCF), control group showed higer scores than observation group on positive syndrome (8.34±2.04 vs 7.66±0.97), negative syndrome(9.15±1.97 vs 813±1.15), total score (37.64±5.58 vs 34.79±3.64) and Social disability (2.81±1.90 vs 2.07±1.47) (P＜0.01); observation group also showed a significant progress on cognition function(P＜0.05). Conclusion This trial demonstrated the efficacy of the easy-operating structured psychosocial skill training grogram in preventing relapse and improving social adoptive function for schizophrenia.

ObjectiveTo evaluate the efficacy of comprehensive rehabilitation therapy on hand function after nerve and tendon repair in wrist.Methods22 patients after nerve and tendons repaired in wrist accepted comprehensive rehabilitation treatment such as ultrasound therapy,electrical nerve stimulating and function training in the whole course.1,3,6 and 12 months after treatment,re-assessment of the involved hand were performed with digital movement,sensation function and Carroll upper extremities function test(UEFT).ResultsThe excellent rate of hand function recovery in all measures were 95% 12 months after treatment.ConclusionComprehensive rehabilitation therapy is effective significantly in the improvement of hand function after nerve and tendon repaired in wrist.

To develop a parent-metabolite pharmacokinetic model for risperidone (RIP) and its major active metabolite (9-hydroxyrisperidone) and investigate their pharmacokinetics characteristics in healthy male volunteers, twenty-two healthy volunteers were orally given a single dose of 2 mg RIP. Plasma samples were collected in the period of 96 hours and concentrations of RIP and 9-hydroxyrisperidone were measured by a validated HPLC/MS method. CYP2D6 phenotypes were identified by the T1/2 of RIP and 9-hydroxyrisperidone according to the literature. Model structure identifiability analysis was performed by the similarity transformation approach to investigate whether the unknown parameters of the proposed model could be estimated from the designed experiment. Pharmacokinetics parameters were estimated using weighted least squares method, and the final pharmacokinetics model were tested and evaluated by Monte Carlo simulation. Eighteen volunteers were phenotyped as extensive metabolizers (EM) and four volunteers were identified as intermediate metabolizers (IM). The final model included central and peripheral compartment for both parent (RIP) and metabolite (9-hydroxyrisperidone) respectively. Model structure identifiability analysis indicated that the proposed model was local identifiable. However, if the ratio of RIP converted to 9-hydroxyrisperidone was assumed to be 32% in EM, and 22% in IM, the model could be globally identifiable. The predicted time-concentration curve and AUC(0-t), C(max), T(max) of RIP and 9-hydroxyrisperidone estimated by the established model were in agreement with the observations and noncompartment analysis. Rate constant of RIP conversion to 9-hydroxyrisperidone was (0.12 +/- 0.08) h(-1) and (0.014 +/- 0.007) h(-1) for EM and IM, respectively. Elimination rate constants of RIP were (0.25 +/- 0.18) and (0.05 +/- 0.23) h(-1) for EM and IM, respectively. Model validation result showed that all parameters derived from the concentration data fitted well with the theoretical value, with mean prediction error of most PK parameter within +/- 15%. The established model well defined the disposition of RIP and 9-hydroxyrisperidone simultaneously and showed large inter-individual pharmacokinetics variation in different CYP2D6 phenotype. The model also provide a useful approach to characterize pharmacokinetics of other parent-metabolite drugs.
Adult ; Cytochrome P-450 CYP2D6 ; physiology ; Humans ; Isoxazoles ; pharmacokinetics ; Male ; Models, Biological ; Monte Carlo Method ; Paliperidone Palmitate ; Pyrimidines ; pharmacokinetics ; Risperidone ; pharmacokinetics

ObjectiveTo investigate the protective effect of paraoxonase 1 (PON1) gene against liver oxidative stress injury in mice due to dichlorvos poisoning.Methods Experiment 1: 12 male Balb/c mice were randomly divided into three groups, with 4 mice in each group: control group, green fluorescent protein lentivirus control group (Lv-GFP group), and recombinant PON1 lentivirus group (Lv-PON1 group). 2×107 TU of Lv-GFP or Lv-PON1 was transfected via tail vein, while normal saline was given to those in control group. Blood was collected on 0, 1, 3, 5, 7, 9 days via fundus venous plexus for the assay of serum PON1 activity. PON1 mRNA and protein expression levels were respectively determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot on the 3rd post-lentivirus transfection day. Experiment 2: according to the random number table method, another 96 male Balb/c mice were divided into four groups of 24 mice in each control group, dichlorvos group, Lv-GFP intervention group, and Lv-PON1 intervention group. Lv-GFP or Lv-PON1 was transfected via tail vein followed by intraperitoneal injection of dichlorvos 9 mg/kg, while those in control group were given normal saline. Six mice in each group were sacrificed respectively at 6, 12, 24, 48 hours, and liver tissue was collected. PON1 mRNA and nuclear factor E2-related factor 2 (Nrf2) mRNA expression levels were determined by RT-PCR, and PON1 protein level was determined by Western Blot. The content of malondialdehyde (MDA) and glutathione (GSH) in the liver tissue were determined by chemical colorimetry. The activity of superoxide dismutase (SOD) and catalase (CAT) were measured by double antibody sandwich enzyme linked immunosorbent assay (ELISA).Results Experiment 1: after Lv-PON1 was transfected to normal mice, PON1 activity in serum gradually increased and maintained a high level on 3rd day, while that of the control group and Lv-GFP group showed a normal low level. On the 3rd post-lentivirus transfection day, PON1 mRNA and PON1 protein expressions in liver were significantly higher than those of control group and Lv-GFP group. Experiment 2: compared with control group, the mice in dichlorvos group showed significant decreases in PON1 mRNA, PON1 protein, Nrf2 mRNA as well as GSH, SOD, CAT levels at 6 hours [PON1 mRNA (gray value):0.237±0.075 vs. 0.674±0.011, PON1 protein (gray value): 0.602±0.086 vs. 0.998±0.124, Nrf2 mRNA (gray value): 0.089±0.012 vs. 0.126±0.010, GSH (mg/g): 3.84±0.33 vs. 5.52±0.40, SOD (μg/g): 0.383±0.040 vs. 0.564±0.052, CAT (ng/g): 7.32±1.28 vs. 12.46±1.54, allP< 0.05], and remarkable increase in MDA content (nmol/g: 7.78±0.41 vs. 2.34±0.25,P< 0.05). With the extension of time, PON1 mRNA, PON1 protein, Nrf2 mRNA and GSH, SOD, CAT levels gradually increased, MDA content gradually decreased, Nrf2 mRNA expression level had risen to the level of control group at 24 hours (0.133±0.019 vs. 0.126±0.009,P> 0.05), and it was higher than that of the control group at 48 hours (0.206±0.028 vs. 0.124±0.010,P< 0.05). Compared with that of the dichlorvos group, Lv-PON1 intervention group showed a significant increase in PON1 mRNA, PON1 protein, Nrf2 mRNA and GSH, SOD, CAT levels [PON1 mRNA (gray value): 0.726±0.021 vs. 0.237±0.075, PON1 protein (gray value): 0.739±0.050 vs. 0.602±0.086, Nrf2 mRNA (gray value): 0.158±0.007 vs. 0.089±0.012, GSH (mg/g): 4.30±0.22 vs. 3.84±0.33, SOD (μg/g): 0.454±0.062 vs. 0.383±0.040, CAT (ng/g): 8.98±1.02 vs. 7.32±1.28, allP< 0.05], and a decrease in MDA content (nmol/g: 6.56±0.44 vs. 7.78±0.41,P< 0.05).Conclusion Regulation of PON1 gene can reduce MDA content, enhance SOD and CAT activities, increase GSH content, and it may also up-regulate Nrf2 mRNA expression to play a protective effect against oxidative stress of liver injury induced by dichlorvos poisoning.

BACKGROUND: Thyroid cancer stem cells are essential to the recurrence and metastasis of thyroid carcinoma. Leukemia inhibitory factor receptor (LIFR) shows a downward trend in a variety of malignant tumors, and its overexpression can inhibit the recurrence and metastasis of malignant tumors. OBJECTIVE:To explore the effect of LIFR on the stemness maintenance and lung metastasis of thyroid cancer stem cells in vivo. METHODS: Primary thyroid cancer cells TCLM were isolated from the lung metastases of a metastatic thyroid cancer patient. Serum-free suspension culture was used to form tumor cell balls. Flow cytometry was used to screen CD133+phenotype of metastatic thyroid cancer stem cell subpopulation TCLM-S. The overexpressed recombinant lentiviral plasmid containing LIFR and its negative control containing the empty plasmid were infected into thyroid cancer stem cells TCLM-S at the ratio of virus/cell number=20, and screened with 2.0 mg/L puromycin to construct TCLM-SLIFRand TCLM-Scontrolstem cells which stably expressed LIFR and its control. Real-time quantitative PCR (qRT-PCR) was used to detect the expression of LIFR in TCLM-SLIFRand TCLM-Scontrolstem cells. Flow cytometry was used to detect the percentage of CD133+phenotype cell subsets, western blot assay was used to detect the expression of tumor stemness related factors SOX2, Oct4, Nanog and tumor invasion and metastasis related proteins E-cadherin, matrix metalloproteinase (MMP)-2, MMP-7 in TCLM-SLIFRand TCLM-Scontrol stem cells. TCLM-SLIFRand TCLM-Scontrolstem cells were respectively injected into BALB/c nude mice by tail vein, and the lung metastasis model of thyroid cancer stem cells was constructed. The effect of LIFR overexpression on lung metastasis was observed. RESULTS AND CONCLUSION: Compared with TCLM-Scontrolcells, the expression of LIFR in TCLM-SLIFRcells was significantly increased, the proportion of CD133+phenotype stem cell subsets was significantly decreased, the expression of SOX2, Oct4 and Nanog were significantly decreased, the expression of E-cadherin was significantly increased, and the expression of MMP-2 and MMP-7 was significantly decreased. Moreover, the number of lung metastasis in nude mice given TCLM-SLIFRcells was significantly decreased as compared with those given TCLM-Scontrol cells.To conclude,LIFR overexpression can decrease the stemness and ability of lung metastasis in vivo.

Objective To evaluate the effect of air temperature on non-accidental mortality (A00-R99) and years of life lost in Wuxi city. Methods Data on daily non-accidental mortality and meteorology index were collected from 2012 to 2017. Distributed lag non-linear model (DLNM) was used to assess the effect of temperature on non-accidental death and YLL and the cumulative effects between cold and hot temperature on non-accidental mortality and years of life lost with different lag days. Results A V-shaped relationship was noticed between temperature and mortality. Cold effects were delayed by 3 days and persisted for 14 days. Hot effects appeared acute and reached the peak at the same day. Low temperature had stronger gross effect than high temperature had. There were differences of temperature effects between different age and gender groups. Conclusions Low and high temperature were associated with elevated mortality risk. Cold effect had lagged effect and persisted for long time, however, hot effects appeared acute and the impact of low temperature was greater.

AIMTo develop a pharmacokinetic model for the enterohepatic circulation of mycophenolic acid (MPA).

METHODSTwenty healthy volunteers were orally given a single dose of 500 mg mycophenolate mofetil. Plasma samples were collected during 48 hours and MPA concentration was measured by HPLC method. Pharmacokinetic (PK) model was established based on physiological and biopharmaceutical consideration and PK parameters were obtained using nonlinear mixed effect model.

RESULTSThe proposed model included an intestinal compartment and gall bladder compartment in addition to the central compartment. The predicted time-concentration curve and AUC0-t, Cmax, Tmax estimated by the established model were in agreement with the observations.

CONCLUSIONThe established model was well defined for the MPA disposition and could afford a useful approach for the further clinical investigation.

Adult ; Area Under Curve ; Enterohepatic Circulation ; physiology ; Glucuronides ; pharmacokinetics ; Humans ; Immunosuppressive Agents ; pharmacokinetics ; Male ; Models, Biological ; Mycophenolic Acid ; administration & dosage ; analogs & derivatives ; blood ; pharmacokinetics