Analysis of TUBB4A gene variant in a patient with adolescent-onset hypomyelinating leukodystrophy with atrophy of basal ganglia and cerebellum / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic etiology of a patient with adolescent-onset hypomyelinated leukodystrophy with atrophy of basal ganglia and cerebellum (H-ABC).@*METHODS@#A patient who was diagnosed with H-ABC in March 2018 at the First Affiliated Hospital of Nanjing Medical University was selected as the study subject. Clinical data was collected. Peripheral venous blood samples of the patient and his parents were collected. The patient was subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.@*RESULTS@#The patient, a 31-year-old male, had manifested with developmental retardation, cognitive decline and abnormal gait. WES revealed that he has harbored a heterozygous c.286G>A variant of the TUBB4A gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. Analysis with SIFT online software indicated the amino acid encoded by this variant is highly conserved among various species. This variant has been recorded by the Human Gene Mutation Database (HGMD) with a low population frequency. The 3D structure constructed by PyMOL software showed that the variant has a harmful effect on the structure and function of the protein. According to the guidelines formulated by the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic.@*CONCLUSION@#The c.286G>A (p.Gly96Arg) variant of the TUBB4A gene probably underlay the hypomyelinating leukodystrophy with atrophy of basal ganglia and cerebellum in this patient. Above finding has enriched the spectrum of TUBB4A gene variants and enabled early definitive diagnosis of this disorder.

Effect of white matter hyperintensities location on clinical outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis / 国际脑血管病杂志

Objective:To investigate the effect of white matter hyperintensities (WMHs) location on the clinical outcomes in patients with anterior circulation acute ischemic stroke (AIS) after intravenous thrombolysis.Methods:Patients with anterior circulation AIS treated with alteplase intravenous thrombolysis in Xuzhou Central Hospital from February 2015 to February 2020 were enrolled retrospectively. The severity of periventricular WMHs (PWMHs) and deep WMHs (DWMHs) was assessed by Fazekas scale. According to the score of the modified Rankin Scale at 90 d after onset, the patients were divided into good outcome group (0-2) and poor outcome group (3-6). The demographic and clinical data were compared between the two groups. Multivariate logistic regression analysis was used to investigate the effect of WMHs location on the clinical outcome in AIS patients treated with intravenous thrombolysis. Results:A total of 408 patients with anterior circulation AIS were enrolled in the study, including 272 males (66.7%) and 136 females (33.3%). Their age was 64.1±12.1 years (range, 40-92years). The baseline median National Institutes of Health Stroke Scale (NIHSS) score was 6 (interquartile range, 4-16). Three hundred and fourteen patients (77.0%) were in the good outcome group and 94 (23.0%) were in the poor outcome group. There were significant differences in age, atrial fibrillation, diabetes mellitus, baseline NIHSS score, blood glucose level before thrombolysis, etiological classification of stroke, PWMHs, DWMHs, hemorrhagic transformation, early neurological deterioration and stroke recurrence between the two groups (all P<0.05). Multivariate logistic regression analysis showed that moderate to severe PWMHs were significantly and independently associated with the poor outcomes in patients with anterior circulation AIS treated with intravenous thrombolysis at 90 d after onset (odds ratio 2.357, 95% confidence interval 1.086-5.115; P=0.030). Other independent related factors included age, baseline NIHSS score, etiological classification of stroke (large artery atherosclerosis and cardiogenic embolism), early neurological deterioration, hemorrhagic transformation, and stroke recurrence. Conclusion:Moderate to severe PWMHs is an independent risk factor for poor outcomes at 90 d after onset in patients with anterior circulation AIS treated with intravenous thrombolysis.

Transcript levels of the Treponema pallidum protein Tp0751 in skin lesions of a rabbit model of early syphilis / 中华皮肤科杂志

Objective To trace changes in the transcript level of the Treponema pallidum(Tp)protein Tp0751 in skin lesions of a rabbit model of early syphilis. Methods Three New Zealand white rabbits were intracutaneously injected with 0.1 ml of Tp (Nichols Seattle strains)suspensions (107 treponemes/ml)at 10 sites on the shaved back to establish a model of early syphilis. All the rabbits received a single injection with the total amount of treponemes being 107. Then, skin changes at injection sites were observed, and the size of skin rashes was recorded on a daily basis. Skin specimens sized 0.4 cm × 0.4 cm were excised from an injection site and a non-injection site(negative control)separately every 3 days for the detection of Tp0751 and Tp0574 mRNAs. The whole experiment lasted 30 days, and a total of 11 skin biopsies were carried out. Fluorescence-based quantitative PCR was performed to measure the mRNA expressions of Tp0751 and Tp0574 continuously and dynamically during the development of chancre. Results After intracutaneous injection of Tp suspensions, red papules occurred on the back of rabbits on day 6, and reached maximum size on day 19 with the formation of ulcer and chancre. On day 25, disseminated secondary syphilides gradually appeared all over the body surface of the rabbits. The mRNA expression levels of Tp0574 and Tp0751 increased at the early stage, peaked onday 15 (compared with the other time points, all P < 0.05), thereafter rapidly declined, but rose slightly on day 27. The standardized expression level of Tp0751 mRNA increased gradually after day 15, and peaked on day 24 (compared with the other time points, all P < 0.05). Conclusion The transcript level of Tp0751 was high in rabbits at the late stage of Tp clearance when generalized disseminated secondary syphilides had not appeared, suggesting that Tp0751 may be involved in the systemic spread of Tp.

Comparison of CT enterography(CTE)and capsule endoscopy(CE)for small bowel diseases / 中华消化内镜杂志

Objective To compare the role of CTE and CE on the diagnosis of small bowel diseases and evaluate their advantages in patients with different indications.Methods Patients underwent both CTE and CE(interval time <2 weeks)at our institution in recent 3 years were enrolled.The positive detection rates,lesion properties and characteristics of CTE and CE were compared.The diagnostic accuracy of combined method was also analyzed.Results A total of 47 patients were enrolled and the indications included suspected or established Crohn′s disease (28 cases),unexplained abdominal pain (14 cases), obscure gastrointestinal bleeding(3 cases),insufficient small bowel obstruction(1 case)and protein losing enteropathy(1 case).Diagnostic yield of CTE and CE for whole small bowel disorders showed no significant difference(CE 83.0% VS CTE 78.7%,P =0.791).For suspected or established CD,CE had a higher diagnostic accuracy than CTE (78.6% VS 35.7%,P =0.002 ),especially in detecting lesions in the jejunum(CE 50.0% VS CTE 7.1%,P =0.002).The diagnostic accuracy reached 100.0% when two meth-ods were combined.For unexplained abdominal pain,no significant difference was found in the diagnostic ac-curacy of CE and CTE(CTE 42.8% VS CE 50.0%,P =1.000).Diagnostic accuracy of combining CTE and CE was 85.7%.Conclusion CTE and CE are both valuable in detecting small bowel lesions.For pa-tients with suspected or established CD,CE is better than CTE.For patients with unexplained abdominal pain,a combination of CTE and CE may be a better strategy than use CTE or CE alone.

Experimental research on the characteristics of pancreatic cells regeneration in an animal model for isolated pancreatic trauma / 重庆医学

Objective To study the relationships between tissue damage and the ability of the pancreatic cells to regenerate ,and analyze the alteration of the pancreatic cells regeneration .Methods Sixty rats were divided into two groups :impact group(the pan‐creas was injured by a BIM‐Ⅲ biotical impact machine ,40 rats) and control group(sham operated ,20 rats) .All rats were sacrificed at 6 h ,24 h ,72 h ,7 d after operation .The level of AMS ,LPS in the serum were detected by spectrophotometry ,pancreatic cells re‐generation were examined and analyzed by TUNEL staining and flow cytomertry ,and the Bcl‐2 and Bax expression were measured by Western blot .Results In the impact groups ,LPS was activated later than AMS ,and lasted persistently .The results from TUNEL stain ,flow cytometry and Western blot indicated that pancreatic trauma induces cell death and the compensatory prolifera‐tion of pancreatic cells .The characteristics of pancreatic cells regeneration in the animal model of isolated pancreatic trauma indicate that the proper remedial time is in the first 24h after the pancreatic trauma .Conclusion Detecting AMS and LPS at the same time can help us to determine the exocrine function of pancrease .

Study on systematic dynamics of tactical reserve of medicine supplies / 第二军医大学学报

Objective: To study the properties and behavior of dynamics in the tactical reserve models of medicine supplies. Methods: A tactical reserve model of medicine supplies was established with methods of systematic dynamics, and the behaviors of the system was simulated by computer program when parameters changed. Results:The quantity of initial reserve did not obviously effect the average inventory and amount of goods in short. However, objective reserve, rate of supply and rate of deliver evidently affected average inventory and amount of goods in short. Conclusion: The system efficiency is not influenced if the rate of supply is guaranteed.