Combination therapy for thick submacular hemorrhage / 中华眼底病杂志

Objective:To observe the efficacy and safety of vitrectomy combined with submacular injection of tissue-type plasminogen activator (t-PA), gas filling and anti-VEGF drugs (multiple therapy) for thick submacular hemorrhage.Methods:A retrospective case study. From January 2014 to June 2018, 24 patients (24 eyes) with thick submacular hemorrhage who received multiple therapy at the Department of Ophthalmology of Peking University Third Hospital were included in the study. Among them, there were 15 males and 9 females with the average age of 69.05±8.86 years. The average submacular bleeding time was 17.15±10.30 days, the average bleeding area was 13.85±8.63 DD. Seventeen eyes showed hemorrhagic RPE detachment. The international standard visual acuity chart was used to BCVA examination, which was converted to logMAR visual acuity in statistics. The frequency domain OCT was used to measure the height of the foveal elevation. The average logMAR BCVA of the affected eye was 1.37±0.38. The average height of the macular fovea was 824.94±294.38 μm. All eyes underwent 23G or 25G vitrectomy. During the operation, 0.1-0.5 ml t-PA (10 μg/0.1 ml) was injected under the macula. The vitreous cavity was filled with 15% C 3F 8 after gas-liquid exchange in 13 eyes, and 11 eyes were filled with sterilized air. Eleven eyes were injected with anti-VEGF drugs at the end of the operation, and anti-VEGF drugs were given PRN treatment according to the activity of the lesion. The average follow-up time after treatment was 27.90±22.21 months. The absorption of bleeding under the macula, the improvement of vision, the occurrence of rebleeding and treatment-related complications were observed and recorded. The Wilcoxon rank sum test was performed to compare the BCVA and the height of foveal elevation before and after treatment. Results:One month after the treatment, the blood in the fovea of all affected eyes was cleared. At the last follow-up, the logMAR BCVA and macular foveal elevation were 0.82±0.28 and 253.88±71.75 μm, respectively. Compared with those before treatment, the difference was statistically significant ( Z=-3.727, -3.234; P<0.001, <0.001). The average intravitreal injection of anti-VEGF drugs was 1.08 times. During the operation, a tiny hole was formed in the center of the macula when t-PA was injected under the retina. Two eyes showed mild vitreous hemorrhage early after the operation. During the follow-up period, bleeding recurred in 2 eyes. Conclusions:Vitrectomy combined with submacular injection of t-PA, gas filling, and anti-VEGF drugs is an optimal combination for the treatment of thick submacular hemorrhage. It can effectively remove submacular hemorrhage, improve vision, reduce foveal elevation with good safety.

Effect of Memantine on blocking abnormal glutamate signal transmission in immature white matter induced by ischemia in vitro and in vivo / 中华实用儿科临床杂志

Objective:To investigate the blocking effect of non-competitive N-methyl-D-aspartic acid(NMDA) receptor antagonist Memantine on glutamate abnormal signal transmission in immature white matter induced by ischemia in vitro and in vivo. Methods:The oligodendrocyte (OL) precursor oxygen glucose deprivation (OGD) cell models of 2-day-old newborn rats were prepared and divided into the normal control group, the OGD group and the Memantine group.The extracellular glutamate level of the OL precursor was measured by high performance liquid chromatography, while the concentration of intracellular calcium and the apoptosis rate of OL precursor were detected by flow cytometry.The animal models of ischemic periventricular leukomalacia (PVL) were established and divided into the sham group, the PVL group and the Memantine group.The pathological evaluation of white matter was performed under light microscope.The positive OL expression rate of myelin basic protein(MBP) was detected by immunohistoche-mistry.The myelination of white matter was evaluated under electron microscope.Results:Compared with the normal control group in vitro, the OGD group had a higher extracellular glutamate level of the OL precursor [(24.60±2.42) μmol/L vs.(9.49±1.08) μmol/L, t=9.28, P<0.01], a higher intracellular calcium concentration [(32.9±6.9)% vs.(6.9±3.5)%, t=4.41, P<0.01], a higher apoptosis rate of the OL precursor [(24.77±2.05)% vs.(6.65±1.39)%, t=15.01, P<0.01]. After treatment with Memantine, the extracellular glutamate level [(14.70±1.70) μmol/L, t=5.68, P<0.01], the intracellular calcium concentration [(23.1±2.0)%, t=6.13, P<0.01], and the apoptosis rate of the OL precursor [(11.80±2.06)%, t=5.18, P<0.01] decreased significantly.Compared with the sham group in vivo, the white matter of the PVL group showed mild or severe pathological changes, and the PVL group had a lower MBP-positive OL expression rate in the white matter [(5.94±1.37)% vs.(15.40±3.22)%, t=4.63, P<0.01]less myelin sheaths (4.00±1.00 vs.14.67±2.70, t=6.11, P<0.01) and thinner myelin sheaths [(33.83±3.21) nm vs.(79.67±6.45) nm , t=10.43, P<0.01]. After the treatment with Memantine, the number of myelin sheaths (10.30±1.50, t=6.01, P<0.01), the thickness of myelin sheaths [(57.21±4.05) nm, t=7.47, P<0.01], and the pathological changes in the white matter of newborn rats ( Z=88.479, P<0.01) all improved markedly, and the MBP positive OL expression rate in the cerebral white matter [(11.02±1.35)%, t=4.40, P<0.05] also increased significantly. Conclusions:Ischemia-induced abnormal signal transmission of glutamate in immature white matter is the important pathway leading to ischemic PVL.Memantine can effectively block the abnormal signal transmission and thus may probably provide a new approach for the effective prevention and treatment of PVL in premature infants.

Analysis of clinical manifestation and genetic mutation in a child with X-linked chondrodysplasia punctata 2 / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze clinical manifestations and genetic mutation in a child with severe short stature and other malformations.</p><p><b>METHODS</b>The child has undergone history taking and physical examination. Genome DNA was extracted from peripheral blood samples of the proband and her family members. Candidate genes were captured with Agilent SureSelect and sequenced on an Illumina platform. Suspected mutation was verified by Sanger sequencing.</p><p><b>RESULTS</b>The patient, a six-year-and-10-month old girl, presented with non-symmetrical short stature, dysmorphism, abnormalities of limbs and spine, amblyopia of left eye, and cataract of right eye, in addition with frequent respiratory infection and micturition. Laboratory testing suggested 25-hydroxy vitamin D deficiency (18.9 ng/mL). Spine X-ray showed multiple malformations with centrums. Her mother also featured short stature (138 cm). Her aunt had short stature (130 cm) and limb-length discrepancy. Her little brother was 2.5 years old, and his height was 81 cm (-3.4 SD). Exome sequencing revealed a heterozygous mutation c.184C to T (p.Arg62Trp) in the proband and her mother. The same mutation was not found in her father and brother.</p><p><b>CONCLUSION</b>The patient was diagnosed with X-linked chondrodysplasia punctata 2. Mutation of the EBP gene probably underlied the disease in this family.</p>

Expression of Th17 related cytokines on ocular surface of dry eye and its significance / 中华实验眼科杂志

Background The pathogenesis of dry eye has not been clearly established.There are more and more evidences to suggest that it is associated with ocular surface inflammation mediated by immunity.But how T helper cell 17 (Th17) plays its role in dry eye remains unclear.Objective The aim of this study was to investigate the expressions of Th17 related cytokines in ocular surface with dry eye.Methods A prospective cohortl study was designed.This protocol was approved by Ethic Commission of Peking University Third Hospital,and written informed consent was obtained from each subject prior to entering this cohort.Twenty female patients with Sjigren syndrome (SS group),20 patients with non-SS dry eyes and 20 normal volunteers were recruited in Peking University Third Hospital during 2011-2012 duration and all the subjects were menopausal female with the age 50 years old or more.The ocular surface disease index (OSDI)questionnaire designed by Schiffman was performed firstly,and then tear breakup time (BUT),corneal fluorescein staining and Schirmer Ⅰ test (S Ⅰ t) were carried out in the subjects.Expression of Th17 related cytokines mRNA were measured using PCR-Array.The correlation between IL-17A and ocular surface parameters was analyzed.Results The OSDI scores of the SS dry eye group,non-SS dry eye group and normal control group were 50.00 (33.50,66.50),45.00 (35.50,55.00) and 3.00 (0.00,5.00),the S Ⅰ t values were 2.50 (1.00,4.00),5.00 (2.00,5.00) and 15.50 (10.00,18.50),the BUT were 2.00 (1.00,4.00),4.00 (3.00,5.00) and 10.00 (10.00,12.00),the corneal fluorescein staining score were 8.50 (6.00,12.00),5.50 (4.00,7.00)and 0.00 (0.00,0.00),respectively,and significant differences were seen among the SS group,non-SS dry eye group and normal control group (x2=34.11,28.13,93.66,92.25,all at P＜0.01).The relative expression values of IL-17A mRNA,IL-6 mRNA,IL-8 mRNA,IL-22 mRNA and IL-23 mRNA in the ocular surface were 1.98±0.16,11.64±1.32,6.67±1.12,1.88±0.18 and 1.78±0.17 in the SS group patients,and 1.45±0.17,1.32±0.14,1.12 ±0.13,1.23 ±0.15 and 1.23 ±0.13 in the non-SS dry eye group patients,respectively,with significant differences between the two groups (all at P＜0.01).IL-17A level on the ocular surface was significantly negative correlated with BUT (r =-0.56,P＜0.01) and positive correlation with corneal fluorescein staining scores (r=0.44,P=0.01).Conclusions Expressions of Th17 related cytokines in the ocular surface increased in patients with dry eye,especially in those with SS.IL-17A level in ocular surface is associated with BUT and corneal fluorescein staining scores,suggesting that immune is involved in the pathogenesis and devlopment of dry eye.

Effect of application of uridine diphosphate-glucose on self-repairment potentiality of immature cerebral white matter invivo / 临床儿科杂志

Objectives To explore the effect of application of uridine diphosphate-glucose (UDP-glucose) on self-repairment potentiality of immature white matter (WM) in vivo. Methods Five-day-old rats were randomly divided into sham, periventricular leukomalacia (PVL) and UDP-glucose groups. The PVL model was constructed in the PVL and UDP groups, and UDP-glucose (2000mg/kg) was induced by an intraperitoneal injection at once to the rats of UDP group. PVL in-duced proliferation and differentiation of WM-glial progenitor cells invivo were detected by using the three-label lfuorescent immunoanalysis, the apopotosis in WM cell was observed by TUNEL test, and the pathology of WM and myelination were evaluated by light and electron microscopy at day 7 and day 21 after PVL model construction. Results The numbers of new WM-progenitors (NG2+), oligodendrocytes (OLs) progenitor marker (O4+), OL precursors, cyclic nucleotide phosphodiesterase (CNPase+), immature OLs and myelin basic protein (MBP+), and mature OLs in the UDP-glucose group are signiifcantly grea-ter than those in the PVL group at each time interval after induction of PVL (P<0.05). The numbers of the apoptotic cells in UDP-glucose group are less than those in the PVL groups. Under light and electron microscopy, the white matter pathological changes and myelination were found to be better than those in the PVL group (P<0.05). Conclusion The application of UDP-glucose can induce the WM-progenitors to activate, proliferate and differentiate into immature and mature OLs. UDP-glucose can also signiifcantly reduce the apoptotic rate of the WM-new glia cells;improve the white matter pathological changes and the myelin formation.

Crohn’s disease complicated with erythromelalgia:report of 1 case and literature review / 临床儿科杂志

Objectives To explore the clinical features, diagnosis and treatment of Crohn’s disease complicated by erythromelalgia (EM) in a pediatric case. Methods The clinical manifestation, results of laboratory testing and endoscopy, mutational analysis of the SCN9A gene, and the follow-up record were collected and analyzed based on review of literature to a thirteen-year-old girl with Crohn’s disease complicated by erythromelalgia. Results The patient experienced symptoms of anorexia, fatigue, diarrhea, dark red and swelling skin, increased skin temperature and burning pain in her both lower extremities during the course of disease. The endoscopic ifndings included multiple ulcerations and polypoid protrusion lesion in colon, and the pathological examination showed the local abscess formation in colonic mucosa. The mutation in SCN9A gene of the child was excluded by gene analysis. The symptoms were gradually ameliorated after treatment using prednisone and mesalazine combined with dipyridamole and low-molecular-weight heparin calcium. Conclusions Crohn’s disease complicated by erythromelalgia is rare. The pathogenesis may relate to immune factors, thrombocytosis, and hyper-coagulable states, etc. The combination of glucocorticoids, 5-aminosalicylic acid and anticoagulants may lead to a better therapeutic effect.

Genetic polymorphism of 19 STR loci in Xinjiang Barkol Kazakh population / 中南大学学报(医学版)

OBJECTIVE@#To investigate 19 short tandem repeat (STR) loci in Chinese Kazakh population in Barkol County with Goldeneye™20A multiplex amplification system.@*METHODS@#DNA samples were screened from 81 unrelated individuals. The 19 loci were D8S1179, D21S11, CSF1PO, D3S1358, D7S820, TH01, D13S317, D2S1338, D18S51, D16S539, TPOX, vWA, D19S433, D5S818, PentaD, PentaE, D6S1043, D12S391 and FGA. The PCR products were analyzed and genotyped by ABI3130XL sequencer.@*RESULTS@#These loci were highly polymorphic. The combined power of discrimination was 0.999999999 and the combined paternity of exclusion was 0.999998914.@*CONCLUSION@#Goldeneye™20A multiplex amplification system is very useful in forensic case investigation for Barkol Kazakh population.

Incidences of brain injuries in premature infants in seven large cities of China / 临床儿科杂志

Objectives To investigate the incidence of brain injuri in premature infants in ten hospitals of seven large cities in China sponsored by the Subspecialty Group of Neonatology of Pediatric Society, China Medical Association. Methods All premature infants with gestational age less than 37 weeks in ten hospitals were given routine cranial ultrasound within three days of birth, and then repeated every 3-7 days till the discharge from the hospital during January 2005 to August 2006. Results Incidence of intraventricular hemorrhage (IVH) and severe IVH were 10.8% (406/3 768) and 2.4% (92/3 768) with 22.6% (92/406) for grade 1, 54.7% (222/406) for grade 2, 17.2% (70/406) for grade 3 and 5.4% (22/406) for grade 4 in nine hospitals; incidence of periventricular leukomalacia (PVL) and cystic PVL were 2.3% (112/4 933) and 0.3% (16/4 933) with 85.7% (96/112) for grade 1, 12.5% (14/112) for grade 2, and 1.8% (2/112) for grade 3 including all ten hospitals, respectively. Risk factors associated with increased severity of IVH were vaginal delivery (OR = 1.874, 95% CI = 1.172 - 2.997, P < 0.01), perinatal asphyxia (OR = 1.598, 95% CI = 1.077 - 2.372, P < 0.05), mechanical ventilation (OR = 3.988, 95% CI= 2.448 -6.948, P< 0.01), and amniotic fluid contamination (OR = 2.192, 95% CI = 1.054 - 4.544, P< 0.05). Risk factors that might result in the development of cystic PVL were vaginal delivery (OR = 1.400, 95% CI = 1.186 - 1.652, P < 0.001) and mechanical ventilation (OR = 3.000, 95% CI = 1.015 - 8.864, P < 0.05). Conclusions These data reflect basically the prevalence of brain injuriy in premature infants in major cities of China. However, more than 60% of population lives in the rural area, further multicenter investigation including the rural area is expected to be undertaken in future.

Preparation, cultivation and identification of neural stem cells in fetal rat cerebral cortex: Do they have multiple differentiation potency? / 中国组织工程研究

BACKGROUND: Periventricular leukomalacia is a major syndrome of premature infant brain injury, which has been not prevented and cured yet. Theoretically, neural stem cells which were transplanted into white matter with an absence of oligodendroglial cells might be an ideal method to cure periventricular leukomalacia. OBJECTIVE: To prepare the multi-lineage potential of neural stem cells for the use of intraventricular transplantation. METHODS: Cerebral cortex was obtained from 12-14-day fetal rats and sectioned into 1.0-mm~3 sections. The single cell suspension was separated and purified. The neurospheres were incubated with DMEM/F12 culture medium containing fetal bovine serum to observe primary and passage culture of neural stem cells. The differentiation of neural stem cells was determined using immunohistochemical method. RESULTS AND CONCLUSION: The viability of cultured neural stem cells was (94.3±2.2)%. The neurosphere was formed at day 3 after primary culture. The proliferation of neurosphere slowed down after 10-passage culture, and some cells became old. All neurospheres were positively Nestin-staining, thus they were considered as neural stem cells. A further incubation of 4-passage neurospheres, immunohistochemical method indicated that the neurosphere was positively GFAP, β-tublin, and O4 staining, respectively. This suggested that cultured neural stem cells are able to self-renew, proliferate, and differentiate into neurons, astrocytes and oligodendroglial cells.

The regulatory effect of memantine on expression and synthesis of heat shock protein 70 gene in neonatal rat models with cerebral hypoxic ischemia / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the neuroprotective effect of memantine, a non-competitive antagonist at the N-methyl-D-aspartate receptor, against hypoxic ischemia (HI) by exploring its regulation on the expression and synthesis of heat shock protein 70 (HSP70) gene in neonatal rat models with cerebral HI.</p><p><b>METHODS</b>Memantine was intraperitoneally injected at a dose of 20 mg/kg in neonatal rat models either before (PRE group) or after (POST group) induction of HI. The expression and synthesis of the HSP70 gene and its corresponding product were determined by rapid competitive PCR and immunohistochemistry, respectively.</p><p><b>RESULTS</b>There was an increase in the expression of HSP70 mRNA two hours after induction of HI, which reached its peak at 48 hours, then decreased gradually. The same expression occurred at relatively low levels in the control group. Also, HSP70 synthesis was detected as early as 2h after HI, reached its peak between 48 and 72 hours, then declined over time. After memantine administration, the expression of the gene and its synthesis of the corresponding product decreased significantly during the time intervals 24 - 72 h for the gene and 48 - 72 h for the product compared to the HI group.</p><p><b>CONCLUSION</b>It was shown that HI is very sensitive to the expression of the HSP70 gene and synthesis of its corresponding product, which could be regulated by memantine. The latter may have the ability to reduce brain damage; thus decreased HSP70 mRNA expression could be a marker for HI. It is suggested that memantine can be a promising agent for neuroprotection against HI, although an overall and objective assessment of memantine is required to see if it can be used on neonates clinically later on.</p>

Pathological Research of Cerebral Protection of Memantine in Neonatal Rat Models with Hypoxic-ischemia / 中华围产医学杂志

Objective To investigate the cerebral protection of Memantine in neonatal rats with hypoxic ischemia. Methods Memantine was intraperitoneally injected at a dose of 20 mg/kg in neonatal rats of cerebral hypoxic ischemia (HI). Employing a quantized score system of cerebral pathology for hypoxic ischemia developed, the neuroprotective effect of Memantine was evaluated pathologically. Results There were significantly decreased scores in either PRE group (Memantine was given one hour before HI) or POST group (Memantine was given after HI immediately) comparing to HI group with higher score. Conclusion Memantine can improve cerebral hypoxic ischemic damage significantly, and be potentially valuable for the treatment of neonatal hypoxic ischemic brain damage.