Biological Clocks ; Genetic Therapy ; Heart Diseases ; therapy ; Humans ; Stem Cell Transplantation

Background Congenital cataract is an important cause of blindness and amblyopia in children,and about 50％ of congenital cataract is hereditary.Objective The aim of this study was to determine the diseasecausing gene of one Hui congenital cataract pedigree by using exon combined target region capture sequencing chip of eye diseases.Methods This study was approved by Ethic Committee of Ningxia People's Hospital and followed Declaration of Helsinki.One Hui congenital cataract pedigree was recruited in Ningxia Eye Hospital in 2011.All the disease history of the members in this family were collected and recorded,and the eye examinations were performed.The peripheral blood specimens were collected from family members and 300 healthy individuals for the extraction of DNA.Exon combined target region capture sequencing chip of eye diseases was used to screen the candidate diseasecausing mutations,then PCR and direct sequencing were used to confirm the disease-causing mutations.Results This H ui family included 61 members of 6 generations,and 18 patients were diagnosed in serial 5 passages,conforming to autosomal dominant inheritance pattern.Among 18 cataract patients,7 individuals were associated with nystagmus and strabismus,and 4 patients had high myopia.Eight candidate pathogenetic mutations were detected by exon combined target region capture sequencing chip of eye diseases and bioinformatics method,with 5 mutations in noncoding regions and 3 in coding regions.The mutation P24T of CYRGD gene was confirmed as pathogenic mutation of this pedigree by using PCR and direct sequencing methods.These mutations co-segregated with affected members of the family,and the mutations were not found in the unaffected family members and 300 unrelated controls.Conclusions P24T of CYRGD gene mutation is confirmed as pathogenic mutation of this pedigree.Exon combined target region capture sequencing chip provides a new approach to detect disease-causing mutations of congenital cataract with diversity clinical phenotypes.

Background Mycophenolate mofetil (MMF) has been used to prevent transplant rejection for many years and has been shown to have protective effects against renal failure.The objective was to investigate the effect of MMF on monocyte Toll-like receptor 4 (TLR4) signaling in the early stages of renal ischemia/reperfusion injury (IRI) of mice.Methods Sixty BALB/C mice were randomly divided into two groups:an IRI group,in which renal IRI was induced by clamping the renal pedicles for 45 minutes,and an MMF group,in which MMF was given (40 mg·kg-1·d-1,intraperitoneally) from 2 days before renal IRI.The plasma creatinine level and renal tissue damage of each group mice were observed 6,12,24,and 48 hours after reperfusion.The concentration of plasma high-mobility group box 1 (HMGB-1) (TLR4 ligand),interleukin 6 (IL-6),monocyte chemoattractant protein-1 (MCP-1),and tumor necrosis factor α (TNF-α) and the expression of TLR-4 on monocytes were determined.Results The plasma creatinine concentration in the MMF group was lower compared to the IRI group (after reperfusion of 6,12,24,or 48 hours,P ＜0.05).Pathological analysis showed that the renal damage was slighter,TLR-4 expression was reduced (after reperfusion of 6,12,24,or 48 hours,P ＜0.05),and the concentration of cytokines in the plasma was lower (P ＜0.05) in the MMF group.No differences in the concentrations of HMGB-1 were observed (P ＞0.05).Conclusion Monocyte TLR4 signaling is important in the early stage of kidney IRI,but MMF can inhibit it and improve renal function.

Objective Through exploring the concordance of objective multi-parameters analysis and perceptual evaluation,to establish an objective multi-parameters evaluation protocol of voice disorder and to make the evaluation of voice objectification and quantification. Methods Voice samples from 271 patients ( 124 female and 147 male)with dysphonia and 69 control subjects with normal voice (37 female and 32 male)were recorded and assessed by a jury composed of 5 experts in phoniatrics from different hospitals.The jury was instructed to classify voice samples according to the G (grade) component of the GRBAS scale on a visual analogue scale secondarily transformed in a 4-point scale ranging from 0 for normal to 3 for severe dysphonia. The voice samples were unified sentences and ordered randomly 3 times,the mean of 3 evaluation scores were the final results.The objective parameters,including fundamental frequency ( F0),jitter,shimmer,fundamental frequency standard deviation (FOSD),normalized noise energy (NNE),harmonic-to-noise ratio (HNR) and maximal phonatory time ( MPT),were measured on a 2-second sustained vowel/a/ including its initial segment,using the software Dr.Speech for Windows.The data were analyzed using SPSS11.0.Results All objective parameters except for F0 had high correlation with G and the variance tendency of these parameters values was coherent with the extent of voice disorder.And there were statistical differences between adjacent voice disorder groups. Male and female objective multi-parameters protocols were established respectively consisting of jitter,shimmer,FOSD, NNE,HNR and MPT using discriminant analysis ( P ＜ 0.05 ). The concordance between perceptual evaluation and objective multiparameters evaluation was 81.6％ in male and 83.2％ in female.The concordance of evaluation of normal voice and severe voice disorder groups were better than that of mild and moderate voice disorder groups.All mis-grading voices were judged in the adjacent voice group.Conclusions The objective parameters of voice are able to reflect the characteristic of its perceptual evaluation and the concordance between perceptual evaluation and objective multi-parameters evaluation is good. The objective multi-parameters evaluation protocol we established could provide an objective and quantitative evaluation method for voice disorders.

Objective: To denvolop HPLC an method for the determination of the content of three saponins in Zhixiao suppositories. Methods: Analysis carriedout was performed on a Kromasil C18 column (4.6 mm×250 mm., 5μm)at 23℃. The mobile phases were methanol and 0.2% phosphoricacid solution in a gradient elution. The flow rate was set at 1.0 mL·min-1 and the ultraviolet detector was operated at 203 nm. Results: The linear ranges of notoginsenoside R1, ginsenoside Rg1 and ginsenoside Rb1 were 0.368～2.76μg,0.676～5.07 μg and 0.812～6.09μg,respectively. The average recoveries of the three saponins were 98.53%, 99.20% and 99.35%, respectively. The RSD (n=5) were 2.11%, 1.88% and 2.38%, respectively. Conclusion: The separation is a good and the results are accurate and reproducible. It can be used for the quality control of Zhixiao suppositories.

Objective To investigate the effect and safety of sildenafil on persistent pulmonary hypertension of the newborn (PPHN). Also compared the effect of sildenafil with tolazoline and milrione. Methods Forty five neonates with PPHN were recruited from January 2005 through October 2008 in NICU, 25 males and 20 females. The median gestational age was (39.3 + 2.4) weeks, the median birthweight was (3 114.0±10.2) g, and the median age were (13.0±0.8) hours. The patients were randomly assigned to receive sildenafil, tolazoline and milrione therapy. The pulmonary artery pressure (PAP) was measured by echocardiography. Results Thirty patients were cured, 6 patients were improved and 9 patients were of no effect. The total effective rate was 80%. There was no statistical difference among sildenafil, tolazoline and milrione. The PAP decreased when the patients were treated with sildenafil, tolazoline and milrione. No side effects happened in all patients treated with the three drugs. Conclusions Sildenafil is an effective and safe drug to reduce PAP of PPHN and it also help to improve cardiac function.

BACKGROUND:Some scholars have found that cervical vertebral body bone trabecula was reduced,became thin,even perforated in old patients with osteoporosis.Whether this change will induce cervical vertebral body deformation,and what relationship to the onset of cervical syndromeOBJECTIVE:To study the relation of cervical spondylotic myelopathy and osteoporosis by measuring and comparing.METHODS:A totaI of 40 subjects with normal lumbar vertebra density and without cervical spondylosis were enrolled as control group,averagely 32 5 years.A total of 30 patients with cervical spondylosis served as cervical spondylosis group,averagely 43.6 years.Totally 46 patients with cervical spondylosis and osteoporosis served as combined with osteoporosis group,averagely 58.6 years.116 subjects underwent radiograph Height and sagittal diameter of the vertebral body ratio of height to sagittal diameter of the vertebral body.and ratio of sagittal diameter of cervical canal/vertebra body were measured.RESULTS AND CONCLUSION:Compared with the control group.vertebral height was decreased.and sagittal diameter became longer(P＜0.05),and the ratio of sagittal diameter of cervical canal/vertebra body became smaller(P＜0.05)in the combined with osteoporosis group.Vertebral body deformation was characterized by decreased vertebral height and prolonged sagittal diameter became flat.Results suggested that osteoporosis induced cervical vertebral deformation,correlation between osteoporosis and cervical spondylosis,which may be a factor for cervical spondylosis development.

Objective To study the expression of anticentromere antibody (ACA)on multiple diseases to help the clinical diag-nosis and treatment.Methods The clinical and laboratory data of 129 cases with positive ACA were retrospectively ana-lyzed.Results ①116 females and 13 males were found among 129 cases with positive ACA,and serology titer of ACA in fe-male patients was higher than male and more compound antibody were shown in female patients,which was significantly dif-ferent compared with males (χ2=6.28,P=0.01;χ2=6.85,P=0.003).②Among 118 cases which had detailed clinical in-formation,there were 65 patients suffered from autoimmune diseases (55.08%)and 53 cases suffered from non-autoimmune diseases (44.92%).Autoimmune disease cases showed more compound and high serology titer,there were significant differ-ence between the two groups (χ2=21.97,P<0.001;χ2=11.44,P=0.001).Conclusion Though ACA was rarely found,it was shown in autoimmune and non-autoimmune diseases and can be not too severe or fetal and even lead to multi-organ fail-ure.So it should be taken seriously.

Objective To determine the effect of deferoxamine administration on autophagy in a rat model of blast-induced brain injury.Methods Thirty-nine male SD rats were allotted to shamoperated group,injury group and deferoxamine group with 13 rats in each,according to the random number table.Feeney's method was applied to establish the model.Deferoxamine group received deferoxamine of 100 mg/kg intraperitoneally.Sham-operated and injury group were injected with saline intraperitoneally.All treatments were started two hours postinjury at 12 hour interval for up to 28 days.Hemoglobin,rectal temperature,blood glucose and mortality were detected at 1,3,7,14 and 28 days.Morris water maze was conducted.Rats were killed later for detecting the brain defect volume and level of Beclin 1 at the site of injury.Results There were no significant differences among the three groups with respect to hemoglobin,rectal temperature and blood glucose (P ＞ 0.05).Mortality in injury versus deferoxamine groups did not differ significantly (P ＞ 0.05).Volume of defected brain in deferoxamine group was (115.35 ± 13.70) mm3,smaller than (209.99 ± 16.70) mm3 in injury group (P ＜ 0.05).In Morris water maze test,the time spent in the searching the platform and latency to reach the platform were improved in deferoxamine group compared to those in injury group [(3.13 ± 0.35) vs (2.13 ± 0.64);(36.15 ± 26.63) s vs (110 ± 47.34) s respectively] (P ＜ 0.05).Both immunohistochemisty and western blot showed dramatically increased level of Beclin 1 after injury,but treatment with deferoxamine significantly reduced the Beclin 1 expression.Conclusion Level of Beclin 1 is significantly upregulated after blast-induced brain injury in rats,resulting in elevated autophagy postinjury,but the treatment with deferoxamine is neuroprotective possible by lessening autophagy damage.

ObjectiveTo observe the subcutaneous and intraperitoneal insulin injection's effect of the level of oxygen free radicals of type 2 diabetes model.MethodsC57BL/6J mice were chosen as normal control group (C group,n=9).KK mice were randomly divided into intraperitoneal injection of insulin group (i.p.group,n=9),the subcutaneous insulin group (s.c.group,n=9) and untreated group (U group,n =9).The i.p.group and the s.c.groups were given certain amount of insulin (insulin injecta and protamine insulin injecta by volume ratio of 2:1 mixture)for one month,maintained the GLU at normal levels (6±1.5) mmol/L.SOD,GSH-PX activity and MDA content of serum,liver,kidney and heart in each group were detected.Results The liver,kidney,heart and serum's SOD and GSH-PX activity significantly reduced and MDA content significantly increased in the U group.Both kinds of delivery methods could increase serum SOD and GSH-PX activity and reduce the content of MDA to the normal control group level,but the intraperitoneal injection had stronger effect.Two kinds of delivery methods could both reduce the MDA content of liver,and had almost the same effect; but the subcutaneous injection group had better effect on increasing the liver's SOD activity,and the intraperitoneal injection had better effect on increasing liver's GSH-PX activity.Intraperitoneal injection had better effect on reducing kidney' s MDA content and increased SOD activity.Two kinds of delivery methods had the same effect on reducing the heart's MDA content.Conclusion The two delivery methods can both make the MDA levels of KK mice in serum,heart,liver and kidney fall to as normal as that of control group,but the two delivery methods have different ways of improving the antioxidant capacity in different organs.Intraperitoneal injection can reduce MDA content in serum and kidney better.