Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Parkinson's disease (PD) is a progressive neurodegenerative disease with a high clinical heterogeneity. According to its motor symptoms, PD patients are divided into predominant tremor-dominant, postural instability and gait difficulty-dominant/akinetic-rigid and mixed subtypes. Different subtypes show different prognostic characteristics and different sensitivities to drugs. Therefore, the early classification of PD is of great significance for the treatment and prognosis of the disease. This paper reviews the clinical classification methods of different subtypes of PD, summarizes the latest biochemical markers and imaging features, and analyzed the differences in incidence, prognosis and pathological mechanism. The current clinical treatment drugs and methods have been preliminarily targeted for treatment based on PD classification, and there are many animal models of PD subtypes have been studied, providing new methods and strategies for mechanism research and preclinical pharmacodynamics evaluation of PD subtypes.

OBJECTIVE: To explore the possible long-term health effects of the defoamer used in seawater desalination by sub-chronic toxicity testing. METHODS: Blood analysis, internal organ assessment, and histopathological examination were carried out in rats exposed to low, medium, and high (0.5, 1.0, and 2.0 g/kg BW, respectively) doses of defoamer for 90 days through oral administration. RESULTS: The high dose group showed decreased blood alanine aminotransferase and aspartate aminotransferase (P < 0.05). All doses resulted in a significant increase in albumin and decrease in globulin (P < 0.05). The direct bilirubin and indirect bilirubin were decreased in the medium and high dose groups (P < 0.05). All dose groups showed significant induction of alkaline phosphatase (P < 0.05). Pathological examination revealed a case of liver mononuclear cell infiltration in the medium dose group and three cases of liver congestion, steatosis of hepatic cells around the central vein, and punctate necrosis with multiple focal mononuclear cell infiltration in male rats administered the high dose. The No Observed Adverse Effect Level was 0.5 g/kg BW in rats, with albumin and total bilirubin as health effect indices. CONCLUSION Long-term defoamer exposure may cause liver injury but has no significant impact on renal function in rats. The effect on blood cells in female rats was more prominent than that in male rats.
Administration, Oral ; Animals ; Antifoaming Agents ; toxicity ; Blood Chemical Analysis ; Body Weight ; drug effects ; Eating ; drug effects ; Female ; Male ; Rats, Wistar ; Toxicity Tests, Subchronic

BACKGROUND: C-telopeptide and N-telopeptide cross-linked collagen type Ⅰ (CTx and NTx, respectively) are specific biochemical bone markers that can reflect bone formation and resorption. OBJECTIVE: To analyze the association of CTx with disuse osteoporosis. METHODS: Male Sprague-Dawley rats, weighing 180-220 g, were randomly divided into control and disuse osteoporosis groups. Right hind limbs of the rats in the disuse osteoporosis group were immobilitzed for 4 weeks by ankle-tail fixation to establish the rat model of disuse osteoporosis. Peritoneal venous blood was collected before and after modeling, and the femur was then removed to measure the serum CTx level and bone mineral density of the bilateral femurs. RESULTS AND CONCLUSION: The serum CTx level did not differ significantly between groups before modeling (P > 0.05). At 4 weeks after modeling, the serum CTx level in the disuse osteoporosis group was significantly higher than that in the control group and at baseline (P <0.01). The serum CTx level showed no significant change in the control group before and after modeling (P > 0.05). The increment of serum CTx in the disuse osteoporosis group exhibited a negative correlation with the bone mineral density of the bilateral femurs (r=0.426, P < 0.01). The bone mineral density of the right femur in the disuse osteoporosis group was significantly lower than that of the left one in the disuse osteoporosis group and the right one in the control group (P < 0.01), and there was no significant difference in the bone mineral density between left and right femurs in the control group (P > 0.05). These results imply that the model of disuse osteoporosis by ankle-tail fixation is established successfully. Disuse osteoporosis can promote the production of CTx further reducing bone mineral density; CTx is positively correlated with the degree of bone loss, so it can be used for therapeutic assessment and diagnosis of osteoporosis.

OBJECTIVES: To explore the genetic variation sites of caveolin （CAV） and their correlation with sudden unexplained death （SUD）. METHODS: The blood samples were collected from SUD group （71 cases）, coronary artery disease （CAD） group （62 cases） and control group （60 cases）, respectively. The genome DNA were extracted and sequencing was performed directly by amplifying gene coding region and exon-intron splicing region of CAV1 and CAV3 using PCR. The type of heritable variation of CVA was confirmed and statistical analysis was performed. RESULTS: A total of 4 variation sites that maybe significative were identified in SUD group, and two were newfound which were CAV1： c.45C>T （T15T） and CAV1：c.512G>A （R171H）, and two were SNP loci which were CAV1：c.246C>T （rs35242077） and CAV3：c.99C>T （rs1008642） and had significant difference （P<0.05） in allele and genotype frequencies between SUD and control groups. Forementioned variation sites were not found in CAD group. CONCLUSIONS The variants of CAV1 and CAV3 may be correlated with a part of SUD group.
Caveolins/genetics* ; Coronary Artery Disease ; Death, Sudden/etiology* ; Exons ; Genotype ; Humans ; Male ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide

During the process of growth, harvesting, transportation, processing and storage, Chinese herbal medicines (CHMs) can be easily contaminated by fungi and their metabolites like mycotoxins, which not only express negative effects on the quality and safety of CHMs and their processed products, but also pose great threats to human health. Now, some chemical synthetic fungicides have been frequently used to control the growth of fungi and accumulation of mycotoxins in the preservation of CHMs. However, the concentration and type of chemical fungicides allowed for postharvest application are restricted due to the disadvantages of their high residual toxicity, long degradation period and pollution to the environment and so on. Therefore, it is critical to research and develop some highly effective, safe and non-toxic, natural, environment-friendly fungistatic agents from plants to prevent CHMs from being contaminated by fungi and mycotoxins. The paper reviews mycotoxins and their harmfulness, the effective compounds of fungistatic plants as well as the antifungal mechanism to provide scientific evidences for developing novel and effective fungistatic agents plants. Then, the application prospect of fungistatic agents from plants in the preservation of CHMs was discussed.
Animals ; Fungi ; drug effects ; metabolism ; Fungicides, Industrial ; pharmacology ; Humans ; Mycotoxins ; metabolism ; toxicity ; Plant Diseases ; microbiology ; prevention & control ; Plant Extracts ; pharmacology ; Plants, Medicinal ; chemistry ; microbiology ; Preservation, Biological ; methods

OBJECTIVETo study the immunoregulatory effect of hepatitis B virus (HBV) e antigen (HBeAg) on peripheral blood monocytes (PBMCs).

METHODSPBMCs were isolated from patients with chronic hepatitis B (CHB; both HBeAg- and HBeAg+) and healthy controls, and cultured with recombinant HBeAg. The HBeAg-induced changes in expression of PD-1/PD-L1 were measured by flow cytometry of the cells and in secreted cytokines were measured by enzyme-linked immunosorbent assay of the supernatants. Comparisons between two groups were made by the independent-samples t-test; the relationship between PD-1/B7-H1 level and HBV DNA copy number was evaluated by Spearman's correlation analysis.

RESULTSExposure to HBeAg led to a significant decrease in CD3+CD4+ T lymphocyte-specific expression of IFNa for both the CHB patients' and healthy controls' samples (t = 2.382 and -4.190 respectively, P less than 0.01). For the HBeAg- CHB patients' and healthy controls' samples, the HBeAg exposure led to increased levels of secreted cytokines IL-6, IL-10 and TNFa (t = 2.504, 3.583 and 4.324, P less than 0.01 and t = 3.542, 6.246 and 5.273, P less than 0.01 respectively) and of CD14+ PBMC-specific expression of PD-L1 (t = 4.815 and 3.454, P less than 0.05 respectively). Compared to the HBeAg-negative CHB patients' and healthy controls' samples, the HBeAg+ CHB patients' samples had significantly lower CD3+CD4+ T cell-specific expression of IFNa (t = -3.177 and -4.541, P less than 0.01 respectively), but significantly higher levels of secreted IL-4 (t = 3.382 and 4.393, P less than 0.01 respectively), of CD3+ T cells-specific expression of PD-1/PD-L1 (t = 4.755, 2.942 and 4.518, 4.595, P less than 0.01 respectively), and of CD14+ T cells-specific expression of PD-L1 (t = 5.092 and 5.473, P less than 0.01 respectively). The CD3+ T cells-specific expression of PD-L1 was significantly higher in the samples from HBeAg- CHB patients than from the healthy controls (t = 3.214, P less than 0.01).

CONCLUSIONHBeAg was able to down-regulate the production of Th1-type cytokines (IFNgamma), and up-regulate the secretion of Th2-type cytokines (IL-6, IL-10) and the expression of PD-1/PD-L1on monocytes. These changes are conducive to the formation of immune tolerance to HBV. Therefore, HBeAg may play an important role in immune tolerance to chronic HBV infection.

Adult ; Case-Control Studies ; Cells, Cultured ; Female ; Hepatitis B e Antigens ; genetics ; immunology ; Hepatitis B, Chronic ; blood ; immunology ; Humans ; Interferon-gamma ; immunology ; Interleukin-10 ; immunology ; Interleukin-6 ; immunology ; Leukocytes, Mononuclear ; immunology ; metabolism ; Male ; Middle Aged ; Recombinant Proteins ; immunology ; Th1 Cells ; immunology ; Th1-Th2 Balance ; Th2 Cells ; immunology

Objective To explore the effect and adverse reactions of immunoadsorption treatment on patients with sever systemic lupus erythematosus (SLE) and discuss related nursing.Methods Seventy-eight severe SLE patients from May 2009 to August 2012 were chosen and randomly divided into the treatment group and the control group.The treatment group was treated with immuno-adsorption combined with hormone and immunosuppressant,while the control group was treated with only hormone immunosuppressant.SLEDAI score and laboratorial indexes were compared between two groups before and after the treatment.Results All indexes were better in the treatment group than in the control group after treatment,with statistically significant difference (P＜0.05).The count of white blood cell and blood sedimentation was respectively(6.4 ±2.3) × 109/L and (20 ± 15) g/L in the treatment group,both higher than (5.1 ± 2.5) x 109/L and (17 ± 2.3) g/L in the control group.Conclusions Strict pre-treatment preparation,proper operation and careful nursing can improve the safety and the tolerability of immunoadsorption treatment.

Objective To investigate the association of post-stroke depression (PSD) with gene polymorphisms of catechol-O-methyl transferase (COMT) Val1 08/158Met and dopamine transporter 40bp variable number of tandem repeats (VNTR) in dopamine metabolism system. Methods Sixty-eight patients with PSD and 91 patients only suffered from stroke, admitted to our hospital from January 2010to June 2010, were chosen; the gene polymorphisms ofCOMT Val108/158Met and DAT 40 bp VNTR were analyzed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results The genotypes of COMT gene amplifications were wild type (G/G),homozygous mutant type (A/A) and heterozygous type (A/G); 7 repeated genotypes (7/7, 9/7, 10/7, 10/9,10/10, 11/10 and 11/11) were noted in the DA T gene amplifications; frequencies of COMT alleles and genotypes were significantly different between the 2 groups (x2=5.703, P=0.017;x2=6.489, P=0.039). The frequencies of COMT alleles and genotypes were significantly different between the 2 female groups (x2=4.610, P=0.032;x2=6.547, P=0.024), but no significant differences were found between the 2 male groups (P＞0.05). The frequencies and heterozygosity of DAT alleles and genotypes showed no obvious differences between the 2 groups (P＞0.05). Conclusion The gene polymorphism of COMT Val108/158Met may be associated with PSD, while that of DAT 40bp VNTR is not.

OBJECTIVETo assess the in-stent lumen visibility and image quality of coronary stents by dual-source computed tomography (DSCT) coronary angiography, and the diagnostic accuracy of DSCT in the detection of coronary in-stent restenosis.

METHODSDSCT was performed at 147 stents in 78 patients at an interval of (21.8?22.2) months after coronary stent implantation. Axial multi-planar reconstruction of the stents and curved-planar reconstruction through the median of the stents were evaluated for stent image quality on a 5-point scale, and the stent lumen diameters were detected. Thirty out of these 78 patients underwent conventional coronary angiography within one month after CT angiography. The patency of 60 stents were independently evaluated by two blinded readers.

RESULTSImage quality was good to excellent on average score (1.6?0.6) . Stent image quality score was correlated with stent diameter, stent location, and heart rate. All stents were assessable in lumen visibility with an average visible lumen diameter percentage of (72.2?12.2) %. Visible lumen diameter percentage was correlated with stent diameter and stent location. For the stents with calcified plaques, the visible lumen diameter percentage at the calcified site was significantly lower than that at the non-calcified site (P<0.001) . Compared with the conventional coronary angiography, 12 out of 14 in-stent stenoses were correctly detected. The sensitivity, specificity, positive predictive value, and negative predictive value for the detection of in-stent stenosis was 85.7%, 95.7%, 85.7%, and 95.7%, respectively. For stents whose diameter >0.275cm, the sensitivity, specificity, positive predictive value, and negative predictive value were all 100%. The agreement between CT findings and coronary angiography results was 93.3%, and it was correlated with stent diameter and heart rate.

CONCLUSIONSUsing a DSCT, coronary stent lumen is partially visible and the image quality is high. Stent diameter and location can influence the stent lumen visibility and image quality. DSCT has a high diagnostic accuracy for the detection of in-stent restenosis and may be a valuable modality for the follow-up of coronary artery stent patency."

Aged ; Coronary Angiography ; methods ; Coronary Restenosis ; diagnostic imaging ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Sensitivity and Specificity ; Stents ; Tomography, X-Ray Computed ; methods ; Vascular Patency