Pharmacokinetics and pharmacodynamics of antibiotics in septic children treated with extracorporeal membrane oxygenation / 中华儿科杂志

Objective: To investigate the characteristics of pharmacokinetic (PK) and pharmacodynamic (PD) parameters of antibacterial agents in children with sepsis treated by extracorporeal membrane oxygenation (ECMO). Methods: In this prospective cohort study, 20 children with sepsis (confirmed or suspected) who were treated with ECMO and antimicrobial in the Department of Critical Medicine of Hunan Children's Hospital from March 2021 to December 2022 were enrolled as the ECMO group. Through therapeutic drug monitoring (TDM), the PK-PD parameters of antibacterial agents were analyzed. Twenty five children with sepsis in the same department who were treated with vancomycin but no ECMO at the same time were enrolled as the control group. The individual PK parameters of vancomycin were calculated by Bayesian feedback method. The PK parameters in the two groups were compared, and the correlation between trough concentration and area under the curve (AUC) was analyzed. Wilcoxon rank sum test was used for inter group comparison. Results: Twenty patients in the ECMO group, included 6 males and 14 females, with an onset age of 47 (9, 76) months. In the ECMO group, 12 children (60%) were treated with vancomycin, and the trough concentration was less than 10 mg/L in 7 cases, 10-20 mg/L in 3 cases, and >20 mg/L in 2 cases; AUC/minimum inhibitory concentration (MIC) (MIC=1 mg/L)<400 was in 1 case, 400-600 in 3 cases, and >600 in 8 cases. Among the 11 children (55%) who were treated with β-lactam antibiotics, there were 10 cases with drug concentration at 50% dosing interval (CT50)>4 MIC and 9 cases with trough concentration>MIC, both CT50 and trough concentration of cefoperazone reached the target. Among the 25 cases of control group, 16 were males and 9 females, with an onset age of 12 (8, 32) months. There was a positive correlation between vancomycin trough concentration and AUC (r2=0.36, P<0.001). The half-life of vancomycin and the 24-hour AUC (AUC0-24 h) in the ECMO group were higher than those in the control group (5.3 (3.6, 6.8) vs. 1.9 (1.5, 2.9) h, and 685 (505, 1 227) vs. 261 (210, 355) mg·h/L, Z=2.99, 3.50, respectively; both P<0.05), and the elimination rate constant and clearance rate was lower than those in the control group (0.1 (0.1, 0.2) vs. 0.4 (0.2, 0.5), 0.7 (0.5, 1.3) vs. 2.0 (1.1, 2.8) L/h, Z=2.99, 2.11, respectively; both P<0.05). Conclusion: The PK-PD parameters in septic children treated by ECMO varied with a longer half-life, higher AUC0-24 h, lower elimination rate constant and clearance rate.

Polymerase chain reaction-based assays facilitate the breeding and study of mouse models of Klinefelter syndrome / 亚洲男科学杂志(英文版)

Klinefelter syndrome (KS) is one of the most frequent genetic abnormalities and the leading genetic cause of nonobstructive azoospermia. The breeding and study of KS mouse models are essential to advancing our knowledge of the underlying pathological mechanism. Karyotyping and fluorescence in situ hybridization are reliable methods for identifying chromosomal contents. However, technical issues associated with these methods can decrease the efficiency of breeding KS mouse models and limit studies that require rapid identification of target mice. To overcome these limitations, we developed three polymerase chain reaction-based assays to measure specific genetic information, including presence or absence of the sex determining region of chromosome Y (Sry), copy number of amelogenin, X-linked (Amelx), and inactive X specific transcripts (Xist) levels. Through a combined analysis of the assay results, we can infer the karyotype of target mice. We confirmed the utility of our assays with the successful generation of KS mouse models. Our assays are rapid, inexpensive, high capacity, easy to perform, and only require small sample amounts. Therefore, they facilitate the breeding and study of KS mouse models and help advance our knowledge of the pathological mechanism underlying KS.

Food safety risk monitoring ability of institutions for disease control and prevention in a province / 上海预防医学

Objective:To determine the current situation of food safety risk monitoring ability of centers for disease control and prevention （CDCs） in a province， and provide reference for strengthening the construction of food safety monitoring ability in the future. Methods:A self-administered questionnaire survey was conducted among 14 CDCs who are responsible for food safety risk monitoring in the province in 2018. Results:The ratio of food inspection staff with senior， middle， and primary professional titles was 1∶1∶1. The educational background of food inspection staff at the provincial and municipal levels was mainly bachelor degree or above， while that of county level directly under the administration of the province was mainly college degree. The age composition of the staff at the provincial level tended to be elder； however， there were more staff with less working experience at the county level. The qualification proportion of laboratory area was 50%. The distribution proportion of food inspection equipment in the CDC at all levels was 83.3%， 79.5% and 36.3%， respectively. In total， 14 CDCs completed the monitoring task as required. They were all accredited with laboratory qualifications； however， one CDC did not conduct re-evaluation after the certification of food inspection qualification expired. Each CDC ensured the accuracy and reliability of monitoring data through the supervision in food testing. Conclusion:The food safety risk monitoring ability of the CDCs in the province is continuously improved， which can meet the needs of routine monitoring. However， the composition of professional titles of food inspection staff is not very reasonable. There is still a gap between the equipment configuration and the national requirements. The ability of food inspection needs to be improved， in which quality management and laboratory qualification should be further strengthened.

Digital screw path analog measurement of C4-6 posterior fixation parameters in adolescents aged 12-14 years and its clinical significance / 中国组织工程研究

BACKGROUND: For recent decades, there has been a younger tendency in age of occurrence of the cervical spondylosis, and posterior fusion is the main method for cervical degeneration and injury, but no relevant fixation parameters are available in clinical practice for adolescents. OBJECTIVE: To measure the anatomical parameters of C4-6posterior fixation in the adolescents aged 12-14 years after three-dimensional reconstruction. METHODS: Twenty-one adolescents aged 12-14 years, who underwent cervical examination at the Affiliated Hospital of Inner Mongolia Medical University and Department of Orthopedics of the Second Hospital of Ulanqab between January 2014 and December 2016 were randomly selected, and the CT data of the C4-6were collected, and then imported into Mimics16.01 software for three-dimensional reconstruction. We measured the anteroposterior and transverse diameters and the heights of the vertebral body, anteroposterior and transverse diameters of the transverse foramina, angles of the left and right pedicle axes to sagittal and horizontal axes, and left and right pedicle axis lengths. RESULTS AND CONCLUSION: (1) Both anteroposterior and transverse diameters of the transverse foramina were increased with vertebral level incveasing. Both angles of pedicle axis to sagittal and horizontal axes, and pedicle axis lengths were increased with vertebral level. The anteroposterior diameter of the vertebral body at C4-6was in the range of 6.0-8.0 mm, the transversal diameter was in 25.0°-30.0°, the angle between the posterior screw and the horizontal axis was 29.0°-35.0°; in the sagittal plane, the angle to the sagittal axis was no more than 5°; and the pedicle screw path length was in 6-7 mm. (2) These results show the anatomical parameters of C4-6posterior fixation in the adolescents aged 12-14 years are successfully obtained by three-dimensional reconstruction.

The Association of GSDMB and ORMDL3 Gene Polymorphisms With Asthma: A Meta-Analysis

PURPOSE: ORM1-like 3 (ORMDL3) belongs to a highly conserved protein family which is anchored as transmembrane protein in the endoplasmic reticulum. Gasdermin B (GSDMB) is adjacent to ORMDL3 on chromosome 17q21.2 and belongs to the gasdermin-domain containing the protein family (GSDM family). Recent reports suggest that GSDMB and ORMDL3 are associated with asthma in several populations. However, genetic association studies that examined the association of GSDMB and ORMDL3 gene variants with asthma showed conflicting results. To assess whether combined evidence shows the association between GSDMB/ORMDL3 polymorphism and asthma. METHODS: A bibliographic search from MEDLINE identified 13 original articles using the search keywords 'GSDMB', 'ORMDL3', and 'asthma'. An updated literature-based meta-analysis involving 6,691 subjects with asthma, 9,281 control individuals, and 1,360 families were conducted. Meta-odds ratios (ORs) and 95% confidence intervals (CIs) based on the fixed effects model or the random effects model depended on Cochran's Q-statistic and I2 values. Data from case-control and TDT studies were analyzed in an allelic model using the Catmap software. RESULTS: We selected and identified 3 SNPs of ORMDL3 associated with asthma (rs8076131: OR=1.10; 95% CI, 1.02-1.20; P=0.012. rs12603332: OR=1.15; 95% CI, 1.05-1.25; P=0.002. rs3744246: OR=1.10; 95% CI, 1.02-1.17; P=0.008) and 1 SNP of GSDMB associated with asthma (rs7216389: OR=1.37; 95% CI, 1.27-1.47; P<0.01). Publication bias was estimated using modified Egger's linear regression test proposed by Harbordetal and revealed no evidence of biases. Furthermore, cumulative meta-analysis in chronological order showed the inclination toward significant association for rs7216389 and rs12603332 with continually adding studies, and the inclination toward null-significant association for rs3744246 and rs8076131. CONCLUSIONS: Moderate evidence exists for associations of the ORMDL3 rs8076131, rs12603332, and rs3744246 and GSDMB rs7216389 variants with asthma. Large sample size and representative population-based studies and TDT studies with homogeneous asthmatic patients and well-matched controls are warranted to confirm this finding.

Analysis of clinical efficacy and safety of excimer laser technology in the treatment of bullous keratopathy / 国际眼科杂志(Guoji Yanke Zazhi)

To investigate the clinical efficacy and safety of phototherapeutic keratectomy ( PTK ) in the treatment of bullous keratopathy ( BK) .METHODS: A retrospective analysis of 60 cases ( 60 eyes) of BK patients from Department of Ophthalmology in our hospital October 2011 to July 2014 was undergone. Clinical data of all patients with treatment of PTK were analyzed. Best corrected visual acuity ( BCVA ) , corneal curvature, corneal astigmatism, corneal thickness and corneal endothelial cell density ( ECD ) , postoperative complications before and after surgery were compared. RESULTS: BCVA, corneal curvature, corneal astigmatism of patients before surgery were 0. 05 ± 0. 01 and 37. 02±5. 38, 1. 08±0. 67D, which were significantly less than those of postoperative ( respectively 0. 45 ± 0. 13 and 46. 27 ± 7. 02, 1. 92 ± 0. 73D ), the differences were statistically significant (all P<0. 05). Corneal thickness of patients was 492. 33 ± 18. 27μm before surgery, which was higher than that after surgery 377.27±22.49μm (P<0.05). The difference of visual acuity before and after surgery was statistically significant in this group (P<0. 05). During the follow-up period of 6mo, no recurrence of the original corneal lesions, only 2 cases of postoperative slight haze, it was completely dissipated after given the hormone eye drops.CONCLUSlON: Excimer laser technology has high safety in the treatment of bullous keratopathy, it should be promoted in clinical practice.

Changes of CD34(+) and CD71(+)CD45(-) cell levels in bone marrow of MDS and AA patients / 中国实验血液学杂志

This study was aimed to investigate the changes of CD34(+) and CD71(+)CD45(-) cell levels in MDS and AA patients. A total of 25 cases MDS and 43 cases of AA (18 cases SAA and 25 cases of NSAA) from January 2010 to October 2013 in the Department of Hematology, affiliated hospital of Hebei United University were enrolled in this study. The complete blood count, bone marrow smears, bone marrow biopsy, karyotype analysis and bone marrow blood cell immune genotyping (mainly the proportion of CD34(+) cells, CD71(+)CD45(-) cells in nucleated cells) were carried out for all patients; the changes of CD34(+) and CD71(+)CD45(-) cell levels in patients with MDS and AA (SAA NSAA) were compared; the differences of white blood cell count, platelet count and hemoglobin concentration in patients with count of CD71(+)CD45(-) ≥ 15% or <15% were analyzed. The results showed that the count of CD34(+) in MDS group was higher than that in AA (NSAA and SAA) group (P < 0.05). The count of CD71(+)CD45(-) cells in MDS group was higher than that in SAA (P < 0.05), there was no significant difference between NSAA group and MDS group. In MDS group with CD71(+)CD45(-) ≥ 15%, the platelet count was significantly higher than that in NSAA group (P < 0.05); and there was no statistical difference for leukocyte, platelet count and hemoglobin level between MDS and NSAA group with CD71(+)CD45(-) <15% (P > 0.05). It is concluded that the count of CD34(+) cells in MDS patients is significantly higher than that in AA and SAA patients. The count of CD71(+)CD45(-) cells in MDS group is significantly higher than that of SAA group. The platelet count in MDS patients with CD71(+)CD45(-) cells ≥ 15% is significantly higher than that of the NSAA group.

Age-related changes in biomechanical properties of rabbit corneas / 医用生物力学

Objective To study the age-related changes in biomechanical properties of rabbit cornea by using the data from uniaxial extension testing on rabbit cornea strips. Methods To obtain the experiment data, the uniaxial extension test on rabbit cornea strips of both 3-month old and 7 to 8 month-old were performed. The exponential function model and power function model were used to fit the strain-stress curves, and two kinds of viscoelastic mechanical models were used to analyze the stress relaxation curves. Results The mechanical behavior of the rabbit cornea strip presented a nonlinear and viscoelastic property. Within the range of error permitting, the age was not an important factor to affect the stress-strain, as no significant difference was found in nonlinear stress-strain curve of rabbit cornea strips between different ages. The cornea strips of 7 to 8 month-old rabbit had a slightly bigger elastic modulus and a faster stress relaxation than those of 3 month-old one. Different stretching rates had no obvious influence on the nonlinear stress-strain of 3-month old rabbit cornea strips, but the cornea strips at high stretching rate could have a faster stress relaxation. Conclusions The tangent modulus of rabbit cornea increases slightly with age, but its relaxation properties would change greatly with age.

Organotypic slice culture of neonatal rat cortex and induced neural stem cell differentiation / 南方医科大学学报

<p><b>OBJECTIVE</b>To establish a method for organotypic slice culture of neonatal rat cortex in a modified condition and investigate the effect of spatial signals on neural stem cell (NSC) differentiation.</p><p><b>METHODS</b>The brain slices (200 µm in thickness) of neonatal SD rats (3 to 5 days old) were prepared and cultured in modified serum-free DMEM/F12 medium at 37 degrees celsius; with 95% O(2) and 5% CO(2). The organotypic slice cultures were observed regularly. NSCs isolated from the cortex of rat embryos (14-15 embryonic days) were cultured in serum-free DMEM/F12 supplemented with B27 and N2, and the passage 3 NSCs were labeled by CM-DiI before transplanted onto the organotypic slices cultured for 2 weeks. The survival of transplanted NSCs was assessed, and the cell differentiation was identified by immunofluorescence staining.</p><p><b>RESULTS</b>The organotypic slice cultures were well maintained for at least 4 weeks in the modified medium. The thickness of the organotypic slices reduced from 200 µm to 130 µm after 2-week culture in vitro due to the migration of the cells on the edge of the slices. CM-DiI-labeled NSCs survived well and differentiated into GFAP(+) glia and β-tubullin III(+) neurons.</p><p><b>CONCLUSION</b>Neonatal rat organotypic brain slice can be successfully cultured in a modified condition to serve as a model for studying NSC differentiation induced by spatial signals.</p>

Association of the C1155547T polymorphism in WNK4 gene with essential hypertension in Xinjiang Kazakhs / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate whether the WNK lysine deficient protein kinase 4 (WNK4) gene C1155547T polymorphism is associated with essential hypertension (EH) in Xinjiang Kazakhs and to assess the effect of the interaction between this polymorphism and environment factors on EH.</p><p><b>METHODS</b>The study covered 556 hypertension patients and 341 normotensive controls. The C1155547T was determined by Taqman probe real-time PCR method. Some biochemical index such as glucose, triglyceride and total cholesterol were also measured. All of these results were analyzed with Logistic regression analysis. Additive model was applied to assess the effect of interaction between the WNK4 gene C1155547T polymorphism and environment factors on hypertension.</p><p><b>RESULTS</b>The C1155547T polymorphism was consistent with Hardy-Weinberg equilibrium in both the case and control groups. There was significant difference in the genotype frequencies (P=0.003). The T allele frequency was significantly higher in the patient group (P=0.002). Logistic regression analysis revealed that the age, body mass index (BMI), total cholesterol as well as the CT+TT genotype frequency conferred increased risks for EH. Positive interaction between the C1155547T polymorphism and gender, BMI, glucose was observed. The ORs were 3.85 (95%CI:1.23-12.04), 5.91 (95%CI:1.99-17.57) and 8.77 (95%CI:1.04-73.93), respectively.</p><p><b>CONCLUSION</b>The result suggested that the exon 7 C1155547T polymorphism in WNK4 gene might be associated with EH in Xinjiang Kazakhs, the T allele might be the risk factor of essential hypertension. There were interactive effects between the WNK4 gene C1155547T polymorphism and gender, BMI and glucose.</p>

Effects of STI571 combined with As₂O₃ on proliferation, apoptosis and caspase 3, Bcl-xL expression of K562 cells / 中国实验血液学杂志

This study was aimed to explore the effects of STI571 alone or with As₂O₃ on proliferation, apoptosis and caspase 3, bcl-xL mRNA expression of K562 cells, and the molecular mechanism of As₂O₃ enhancing the anti-leukemia effect of STI571 so as to provide the scientific basis for clinical treatment of chronic myeloid leukemia. The effect of drugs on proliferation of K562 cells was assayed by MTT method, the apoptosis rate of K562 cells was detected by flow cytometry with Annexin V/PI double staining, the caspase 3, bcl-xL mRNA expressions of K562 cells were determined by real time quantitative PCR. The results showed that STI571 alone or with As₂O₃ both could inhibit the proliferation of K562 cells. OD value in test groups reduced along with prolonging of action times, the OD values between different time points were significantly different (p < 0.05), furthermore the OD values at 72 hours in test groups were lowest, while as compared with control group, OD values at same time points in test groups all gradually decreased, among which decrease of OD value in test 5 group was most significant. The flow cytometric detection indicated that along with time prolonging, the apoptotic rate in control group not obviously changed, but the apoptotic rate in test groups gradually increased, the difference between time points was significant (p < 0.05), moreover apoptotic rate increased most obviously at 72 hours, while as compared with control group, apoptotic rate at same time points in test groups was gradually enhanced (p < 0.05), among which the apoptotic rate in test 5 group was highest. The real time qPCR assay revealed that as compared with control group, the bcl-xL mRNA expression in test groups reduced with decrease of 2-ΔΔCT value, furthermore the decrease of expression level in test 3 group was higher than that in test 2 group (p < 0.05), while the caspase 3 mRNA expression in test groups was enhanced with increase of 2-ΔΔCT value, moreover the increase of expression level in test 3 group was higher than that in test 2 group (p < 0.05). It is concluded that the STI571 can inhibit the proliferation of K562 cells, accelerate the apoptosis of K562 cells. The STI571 combined with As₂O₃ can enhance these two effects, increase the expression of caspase-3 mRNA and decrease the expression of bcl-xL mRNA. Therefore, the effect of STI571 combined with As₂O₃ on expression of caspase 3 and bcl-xL mRNA may be one of molecular mechanisms underlying their synergic antileukemia efficacy.

OATP 1B1 T521C/A388G is an important polymorphism gene related to neonatal hyperbilirubinemia / 中华儿科杂志

<p><b>OBJECTIVE</b>Multiple genetic and environmental factors contribute to the onset of many human diseases, such as neonatal hyperbilirubinemia. OATP 1B1 is an important polymorphism gene which transmembrane transports unconjugated bilirubin(UCB). Genetic polymorphisms that affect the functionality of the protein may potentially lead to altered transport characteristics. The T521C/A388G polymorphism of this gene has been reported to considerably reduce the transporting property of drugs like pravastatin, and may be involved in the membrane translocation of bilirubin. Some studies have shown that OATP 1B1 mediates bilirubin uptake from blood into the liver, and the OATP 1B1 polymorphism is a likely mechanism explaining the differences of bilirubin level in peripheral blood. The aim of this study was to evaluate the relationship between OATP 1B1 polymorphisms and neonatal hyperbilirubinemia.</p><p><b>METHODS</b>A total of 220 newborn infants with hyperbilirubinemia were recruited from Hunan Children Hospital from November 2008 to December 2009 according to the diagnostic criteria. Age and sex matched control subjects comprised of 200 unrelated, hyperbilirubinemia-free newborns. Biochemical and clinical data were collected from the case history. One ml venous blood samples in EDTA vials were taken from each subject and DNA was isolated from peripheral leukocytes by standard methods, preserved in 4°C. 1 - 2 ml venous blood samples were also taken for detecting the serum total bilirubin and direct bilirubin level by chemical oxidation method. OATP 1B1 T521C/A388G polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Allele and genotype frequencies were compared between patients and control. The gene polymorphism and risk of disease were also analyzed. Serum total bilirubin, conjugated bilirubin and unconjugated bilirubin levels were compared between different OATP 1B1 T521C/A388G genotypes.</p><p><b>RESULTS</b>Allele frequencies in patients and control population were in Hardy-Weinberg equilibrium (P > 0.05). Allele and genotype frequencies of the OATP 1B1 T521C polymorphism in patients were significantly different from the controls. The OATP 1B1 521C allele frequency was only 8.2% in patients, while reached 14.0% in the control group which was very close to the frequency of common Chinese people. However, the proportion of wild type genotypes was significantly higher than those of the controls, reached 84.1%. The 521 C allele and genotypes carrying 521 C allele illustrated low risk for neonatal hyperbilirubinemia (OR = 0.530, 95%CI = 0.328 - 0.857; OR = 0.541, 95%CI = 0.344 - 0.851). However, the frequencies of alleles and genotypes of SLCO1B1 A388G did not differ significantly from those of the controls, and this polymorphism did not influence susceptibility to such disease. Among the three OATP 1B1 A388G genotypes, the level of total serum bilirubin (TSB), direct bilirubin (DB) and unconjugated bilirubin (UCB) were significantly different. Values of TSB, DB and UCB were the highest in wild type subjects, lower in heterozygotes, and the lowest in mutant homozygotes. TSB and UCB in patients with wild type genotypes reached 602.5 µmol/L and 585.0 µmol/L respectively, nearly twice the average value of homozygous patients. While the TSB and UCB in homozygotes were below the average value of all patients, only 351.7 µmol/L and 338.8 µmol/L respectively.</p><p><b>CONCLUSIONS</b>Our findings indicated that OATP 1B1 A388G polymorphism has a notable influence on the serum bilirubin level in neonatal hyperbilirubinemia patients. The OATP 1B1 521T allele may be a potential risk factor of such disease. OATP 1B1 T521C/A388G was an important polymorphism gene which related with neonatal hyperbilirubinemia. Future study should involve other polymorphisms of OATP 1B1, more candidate genes and environmental risk factors. It is also necessary to investigate their association with the severity and prognosis of this disease in order to elucidate the genetic pathogenesis of neonatal hyperbilirubinemia as a complex disease. This study should be repeated in a larger population and different ethnic groups.</p>

Change of early serum TNF-alpha and IL-6 levels in acute cerebral infarction and its significances / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the change of early serum TNF-alpha and IL-6 levels in acute cerebral infarction and its significances.</p><p><b>METHODS</b>Serum TNF-alpha and IL-6 levels in 30 health subjects and 35 patients with acute cerebral infarction (ACI) within 6 hours of onset were measured by enzyme linked immunosorbent assay (ELISA); neurological deficits scores (NDS) in all cases were determined, and Spearman test was used for correlation.</p><p><b>RESULTS</b>The serum levels of TNF-alpha and IL-6 in ACI group were markedly higher than those in health subjects and there was a positive correlation of TNF-alpha and IL-6 levels with 6 h NDS (rs=0.89 and 0.93, P<0.001) and with NDS progression (rs=0.90 and 0.91, P<0.001). Early serum TNF-alpha and IL-6 levels in progressive cerebral infarction (PCI) group were evidently higher than those in stable cerebral infarction (SCI)[(49.56+/-12.12) pg/L compared with (24.30+/-7.4) ng/L and (39.76+/-7.88) ng/L compared with (20.78+/-6.28) ng/L, respectively, P<0.01)].</p><p><b>CONCLUSION</b>The early serum levels of TNF-alpha and IL-6 in ACI markedly increase and are closely correlated with disease severity; which may be of value in PCI risk evaluation.</p>

The effects of B7H4 on human bone marrow mesenchymal stem cell inhibiting proliferation of PHA activated T cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of B7H4 on human bone marrow mesenchymal stem cells (HBMSC) mediating immune suppression.</p><p><b>METHODS</b>The expression of the negative immunoregulatory factor B7H4 on HBMSC were analyzed by RT-PCR and flow cytometry (FCM), respectively. The blocking experiment was used to detect the effects of B7H4 on HBMSC mediating suppression on PHA induced T cell activation, proliferation and cell cycle. HBMSC inhibiting T cell proliferation was examined by transwell cell culture system.</p><p><b>RESULTS</b>B7H4 was highly expressed on HBMSC. Blocking the B7H4 expression by B7H4mAb significantly attenuated the inhibitory effects of HBMSC on T cell proliferation. Compared with that of the unblocking group, T cell stimulator index (SI) of the B7H4 blocked group was significantly increased (53 +/- 5 vs 15 +/- 8, P < 0.01) and the inhibitory effects of HBMSC on T cell cycle were weakened significantly through down-regulating the cell number in G(0)/G(1) phase \[(85.6 +/- 9.9)% vs (95.8 +/- 9.9)%\] and up-regulating those in S phase\[(5.8 +/- 3.2)% vs (2.3 +/- 2.2)%, P < 0.05\]. The suppressive effects of HBMSC on T cell proliferation were significantly weakened after separating HBMSC from T cells by transwell cell culture system. Compared with the cell to cell contact group, T cell SI was significantly increased (27 +/- 17 vs 15 +/- 3, P < 0.01).</p><p><b>CONCLUSION</b>HBMSC highly express B7H4, which plays an important role in the suppressive effects of HBMSC on T cell proliferation.</p>

Research on the relation between ACE gene I/D polymorphisms and sensitivity to endurance training of Han nationality male / 中国应用生理学杂志

<p><b>AIM</b>In order to seek the marks of the genes, the relation between the influence of endurance training on aerobic ability and ACE Gene I/D Polymorphisms were studied.</p><p><b>METHODS</b>102 army recruits of Han nationality from North China for an 18 week en durance training of 5000m distance. Their VO2(max), VT and the left ventricular structure and function were measured before and after the training. We also tested their ACE Gene I/D Polymorphisms with PCR-AFLP method.</p><p><b>RESULTS</b>The compliance of VO2(max), VT and left ventricular structure and function had improved after the training; the deltaVO2(max) of ID and II type was obviously higher than that of DD type (P < 0.05); there was obviously diference of deltaVO2(VT) in different ACE genotype (P < 0.05), the deltaVO2(VT) of type II was obviously higher than that of DD type (P < 0.05).</p><p><b>CONCLUSION</b>I allele has obviously hereditary advantage on the sensitivity to aerobic training in VO2(max) and VT, and type II has relation on the sensitivity to aerobic training in VT; there is no relation between I/D polymorphism and the sensitivity to aerobic training on the structure and function of left ventricle.</p>

Effect of genetic polymorphism on the activity of drug transporters and its clinical significance / 中南大学学报(医学版)

Drug transport is an important source of inter-individual variations in drug responses and is also a common site where drug-drug interactions happen. In recent years, more and more novel identified transporters have been added into the transporter super family, and this trend will continue in the future. Among the transporter members of this family, ATP-dependent efflux transporter P-glycoprotein (MDR1) and organic anion transporters (OATP) are the most important proteins involved in drug transport. MDR1 is the most well known transporter. Widely distributed in tissues such as the gastrointestinal tract, liver, kidney and so on, MDR1 plays an important role in drug absorption, distribution and excretion. Its functional genetic polymorphisms have significantly changed the pharmacokinetics of its substrate drugs, which has important clinical implications. OATP expressed in multiple tissues, and it mediated the drug excretion through the bile acid and kidney. Some genetic polymorphism of OATP genes is the cause of some abnormal drug responses.

389A/G polymorphism of the human beta1-adrenergic receptor in patients with acute myocardial infarction / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the relation between the 389A/G polymorphism in the human beta 1-adrenergic receptor and acute myocardial infarction (AMI).</p><p><b>METHODS</b>Polymerase chain reaction amplification and restriction fragment length polymorphism analysis were used to detect the genotypes of 150 patients with AMI and 150 age- and sex- matched control subjects, and relative clinical data were obtained. A case-control study and multiple Logistic regression analysis were performed to assess the association between 389A/G polymorphism and AMI.</p><p><b>RESULTS</b>The distributions of the genotypes and allele frequencies were significantly different between two groups (P< 0.01). The prevalence of the A allele was significantly higher in patients with AMI than in control subjects. In the multivariate regression analysis, the 389A/G polymorphism (OR: 2.88, 95%CI: 1.70-4.88, P< 0.01), smoking(OR: 2.72, 95%CI: 1.52-4.88, P< 0.01), hyperlipidemia (OR: 2.85, 95%CI: 1.68-4.86, P< 0.01), diabetes mellitus(OR: 2.38, 95%CI: 1.27-4.47, P< 0.01) and hypertension (OR: 2.00, 95%CI: 1.62-3.45, P< 0.05) were independent risk factors of AMI.</p><p><b>CONCLUSION</b>The 389A/G polymorphism in the human beta 1-adrenergic receptor is associated with AMI and is an independent risk factor of AMI.</p>

mRNA expression of voltage-dependent potassium channels in the brain of rats after middle cerebral artery occlusion / 药学学报

<p><b>AIM</b>To study the mRNA expression changes in the brain of rats after middle cerebral artery occlusion.</p><p><b>METHODS</b>Middle cerebral artery occlusion was used to induce ischemia in rat brain. The mRNA expression of voltage-dependent potassium channel subtypes, including Kv1.4, Kv1.5, Kv2.1 and Kv4.2, were detected in rat hippocampus and cortex by RT-PCR.</p><p><b>RESULTS</b>Middle cerebral artery occlusion induced a significant neurological injury in rats. After ischemia 2 h, the mRNA of Kv1.4, Kv2.1 and Kv4.2 in hippocampus increased by 50%, 67% and 90% , respectively. And the mRNA of Kv1.4 and Kv4.2 maintained at a high level in hippocampus after ischemia 24 h. In cortex, the mRNA level of all the four subtypes were not changed significantly after ischemia 2 h, but the mRNA of Kv2.1 and Kv4.2 increased by 70% and 62% after ischemia 24 h, respectively.</p><p><b>CONCLUSION</b>The mRNA expression levels of voltage-dependent potassium channels were up-regulated in rat hippocampus and cortex after middle cerebral artery occlusion.</p>

Gastrointestinal contrast agents for improving imaging quality of MRCP:comparison between Gd-DTPA and BaSO_4 suspension / 上海第二医科大学学报

Objective To assess and compare the effectiveness of gadolinium diethylenetriamine pentacetic acid(Gd-DTPA) solution and barium sulfate(BaSO4) suspension with different concentrations in improving the imaging quality of magnetic resonance cholangiopancreatography(MRCP). Methods The phantom study was carried out to determine the optimal concentration of Gd-DTPA and BaSO4 suspension used as an oral negative contrast agent in MRCP.The patients were grouped randomly and performed MRCP before and after using oral contrast agents in combination with intravenous injection of contrast agents.A comparison of the influence of BaSO4 suspension and Gd-DTPA with different concentrations on the signal intensity of the fluid in gastrointestinal tract on MRCP images was made.Results The phantom study showed that the dilution ratio 1∶10 of Gd-DTPA solution and 100%(W/V)BaSO4 suspension were the optimal concentrations in decreasing the signal intensity.In all patients the high signal intensity of the gastrointestinal fluid was completely suppressed after oral administration of Gd-DTPA diluted solution(P

Effect of 17beta-estradiol on Kv2.1 current and delayed rectifier potassium current in cultured rat hippocampal neurons / 药学学报

<p><b>AIM</b>To study the effects of 17beta-estradiol on Kv2.1 potassium channel current and delayed rectifier potassium current (IK) in cultured rat hippocampal neurons.</p><p><b>METHODS</b>The effects of 17beta-estradiol on Kv2.1 channel current and IK in cultured rat hippocampal neurons were observed using the whole cell patch clamp techniques.</p><p><b>RESULTS</b>17beta-Estradiol was shown to reduce the amplitude of Kv2.1 current and IK in concentration-dependent manners. The IC50s of 17beta-estradiol blocking Kv2.1 and IK were 2.4 and 4.0 micromol x L(-1), respectively. 17beta-Estradiol (3 micromol x l(-1)) significantly shifted the steady-state activation and inactivation curves of Kv2.1 current to negative potentials. However, it only produced the shift of the steady-state activation curve of IK to the negative potential without effect on the steady-state inactivation of IK.</p><p><b>CONCLUSION</b>17beta-Estradiol inhibits Kv2.1 and IK of hippocampus at similar level. The inhibition of 17beta-estradiol on IK current may be partially via blocking Kv2.1 current.</p>