Splicing abnormalities caused by a novel mutation in the PHKA2 gene in children with glycogen storage disease type IX / 中华肝脏病杂志

Objective: Glycogen storage disease type IX (GSD-IX) is a rare primary glucose metabolism abnormality caused by phosphorylase kinase deficiency and a series of pathogenic gene mutations. The clinical characteristics, gene analysis, and functional verification of a mutation in a child with hepatomegaly are summarized here to clarify the pathogenic cause of the disease. Methods: The clinical data of a child with GSD-IX was collected. Peripheral blood from the child and his parents was collected for genomic DNA extraction. The patient's gene diagnosis was performed by second-generation sequencing. The suspected mutations were verified by Sanger sequencing and bioinformatics analysis. The suspected splicing mutations were verified in vivo by RT-PCR and first-generation sequencing. Results: Hepatomegaly, transaminitis, and hypertriglyceridemia were present in children. Liver biopsy pathological examination results indicated glycogen storage disease. Gene sequencing revealed that the child had a c.285 + 2_285 + 5delTAGG hemizygous mutation in the PHKA2 gene. Sanger sequencing verification showed that the mother of the child was heterozygous and the father of the child was of the wild type. Software such as HSF3.1 and ESEfinder predicted that the gene mutation affected splicing. RT-PCR of peripheral blood from children and his mother confirmed that the mutation had caused the skipping of exon 3 during the constitutive splicing of the PHKA2 gene. Conclusion: The hemizygous mutation in the PHKA2 gene (c.285 + 2_285 + 5delTAGG) is the pathogenic cause of the patient's disease. The detection of the novel mutation site enriches the mutation spectrum of the PHKA2 gene and serves as a basis for the family's genetic counseling.

Formation and Development of Environmental Forensics System in China / 法医学杂志

With the growing attention on ecological environment problems and gradual realization of ecological environment value, environmental damage has jumped from administrative penalty to a new stage, judicial penalty, and environmental damage appraisal has provided a legal weapon to safeguard ecological security. As a new forensic category of China with high comprehensiveness and technical difficulty, environmental damage appraisal involves diversified and complex subjects, fields and appraisal objects, and is still in an early stage in terms of theory and practice. This study aims to provide an important reference for the improvement of the Chinese environmental damage appraisal system of environmental damage by summarizing advanced international experience in areas such as laws and regulations, working mechanism and technical system, and putting forward targeted countermeasures and suggestions based on the problems existing in the development and practice of environmental damage appraisal in China.

Structure elucidation of degradation products of Z-ligustilide by UPLC-QTOF-MS and NMR spectroscopy / 药学学报

Z-Ligustilide, a major phthalide isolated from a widely used traditional Chinese medicine Ligusticum chuanxiong, possesses various pharmacological activities including neuroprotective, anti-inflammatory, antiproliferative and vasorelaxing effects. However, it is unstable and inclined to degrade in natural conditions, which limits its study and application greatly. In this study, degradation behavior of Z-ligustilide and its degradation products stored at room temperature under direct sunlight were investigated and structure elucidated by HPLC-UV, UPLC-QTOF-MS and NMR. Z-ligustilide degradation and total five degradation products were generated and detected. Two degradation products were unequivocally identified as senkyunolide I and senkyunolide H by comparison with reference compounds. Another two degradation products were further isolated by semi-preparative HPLC and structure elucidated as (E)-6, 7-trans-dihydroxyligustilide and (Z)-6, 7-epoxyligustilide by 1H and 13C NMR, respectively. The degradation pathways of Z-ligustilide were finally proposed. Oxidation, hydrolysis and isomerization are the major degradation reactions.

Study on the nutrition status and clinical evaluation in patients with GOLD Ⅱ and GOLD Ⅲ or chronic obstructive pulmonary disease / 中国医师进修杂志

Objective To investigate nutrition status and dyspnea in the patients with chronic obstructive pulmonary disease (COPD) between GOLD Ⅱ and GoLD Ⅲ, and test the evaluative validity of disease status by GOLD classification of COPD. Methods Thirty patients with clinically stable COPD were recruited, including 15 patients of GOLD Ⅱ of COPD and 15 patients of GOLD Ⅲ of COPD. Body mass index (BMI), triceps skin-fold thickness (TSF), serum albumin (Alb), and partial pressure of oxygen in arterial blood (PaO2) were measured in each patient. Dyspnea was assessed by the Borg Scale (BS). Exercise stress test was taken by incremental exercise test. Results BMI was significantly lower in the patients of GOLD Ⅲ than that in the patients of GOLD Ⅱ[(19±5 ) kg/m2 vs (23±3) kg/m2,p < 0.05]. TSF was significantly reduced in the patients of GOLD Ⅲ than that in the patients of GOLD Ⅱ[ (8±3) mm vs(13±5) mm, P < 0.01]. Alia in the patients of GOLD Ⅲ was significantly decreased than that in the patients of GOLD Ⅱ [(32±7) g/L vs (36±6) g/L, P <0.05]. The difference of PaO2 between the patients of GOLD Ⅲ and the patients of GOLD Ⅱ was significant [(72±9) nun Hg (1 mm Hg = 0.133 kPa ) vs (78±8) nun Hg, P < 0.01], and the significant difference of BS was found between the patients of GOLD Ⅲ and the patients of GOLD Ⅱ( 5.0±2.0) grades vs (3.0±1.0) grades, P <0.05 ]. In addition, 12 patients in the patients of GOLD Ⅱ took the exercise stress test and 8 patients were found anaerobic threshold (AT), 5 patients in the patients of GOLD Ⅲ took the exercise stress teat and no AT was found. Conclusions The parameters of BMI, TSF, Alb and PaO2 are significantly reduced in the patients of GOLD Ⅲ than those in the patients of GOLD Ⅱ. In the patients of GOLD Ⅲ, BS is higher than that in the patients of GOLD Ⅱ and AT is difficult to obtain, suggesting more severe in degree of impairment. GOLD classification of COPD reflects the disease stares and prognosis in the patients with COPD, as a valuable parameter in clinical practice.

Risk Factors of Fungal Ventilator-associated Pneumonia / 中华医院感染学杂志

OBJECTIVE To investigate the risk factors of fungal ventilator associated pneumonia(FVAP) and the characteristic of pathogenic fungi.METHODS Thirty seven VAP patients were divided into FVAP group and nonfungal ventilator associated pneumonia(NFVAP) group.Risk factors were compared between the two groups and the characteristic of pathogenic fungi was analyzed.RESULTS Compared to the NFVAP group,the FVAP group showed a significant higher rate in systemic usage of glucocorticosteriod and combined application of antibiotics.The cases of FVAP appeared frequently over the period since 7th to 14th days after intubation.Twelve strains of fungi were isolated from the sputum of patients in FVAP group.Ten strains(83.3%) of the isolates belonged to Candida species included(C.albicans 6 strains(50.0%),C.tropicalis 2 strains(16.7%),C.krusei 1 strain(8.3%),and C.parapsilosis 1 strain(8.3%),and 2 strains(16.7%) of the isolates belonged to Aspergillus.CONCLUSIONS The rate of tracheal intubation should be decreased and the time of mechanical ventilation should be shortened to avoid FVAP.Identifying the strains of fungi and their sensitivity are useful to direct the treatment.