Humans ; Occupational Diseases ; epidemiology ; prevention & control ; Risk Assessment

Fanconi anaemia (FA) is an autosomal recessive inherited disorder caused by defects in hematopoietic stem cells. The clinical manifestations of FA are diverse and complicated. FA cells display high hypersensitivity to agents which produce interstrand DNA cross-links such as mitomycin C (MMC) or diepoxybutane (DEB). At least eight complementation groups with defects in eight genes (FANCA, FANCB, FANCC, FANCD(1), FANCD(2), FANCE, FANCF and FANCG) have been identified by gene analysis. Six genes (corresponding to subtypes A, C, D(2), E, F and G) have been coloned, and the encoded FA proteins interact in a common cellular pathway - "FA Pathway", through which modulate DNA repair. The progress of research on FA molecular mechanism provides gene therapy of FA with theory basis. FA cells transduced with the use of retrovirus carring the normal FA gene cDNA manifestate phenotypic correction of hypersensitivity to DNA cross-linking agents, such as MMC. In this review the clinical manifestations and gene composition of FA, and the functions of encoded FA proteins were summarized. The hematopoietic stem cell transplantation and gene therapy for FA patients were discussed.
Cell Cycle Proteins ; DNA-Binding Proteins ; Fanconi Anemia ; genetics ; metabolism ; therapy ; Fanconi Anemia Complementation Group C Protein ; Fanconi Anemia Complementation Group D2 Protein ; Fanconi Anemia Complementation Group Proteins ; Genetic Therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Mutation ; Nuclear Proteins ; genetics ; Proteins ; analysis ; genetics

The hydroxycamptothecin (HCPT) PEGylated liposomes (HCPT-LP) were modified with RGD cyclopeptide formed the tumor-targeting liposomes (HCPT-RGD-LP). HCPT-LP and HCPT-RGD-LP were injected intravenously with single dose of 5 mg x kg(-1) to rats. The drug concentration in plasma was determined and the pharmacokinetic behaviour was compared. The HCPT distribution in heart, liver, spleen, lung, kidney and plasma of mice was investigated following intravenous administration of HCPT-LP and HCPT injection. The nude mice implanted human hepatoma HepG2 cells were studied by in vivo imaging. The fluorescent probe was DiR and the nude mice were injected with DiR PEGylated liposomes (DiR-LP) and DiR-LP modified with RGD cyclopeptide (DiR-RGD-LP). The results showed that there was no significant difference (P > 0.05) of main pharmacokinetic parameters t1/2beta, CL, V(c), AUC(0-48 h), AUC(0-inifinity), MRT(0-48 h), MRT(0-infinity) between HCPT-RGD-LP and HCPT-LP. HCPT-LP had a remarkably better long-circulating effect than HCPT injection in mice and the concentration of HCPT was highest in liver. The DiR accumulation in tumors of DiR-RGD-LP was higher than that of DiR-LP by the visualized fluorescence of in vivo imaging. It indicated that such PEGylated liposomes modified with RGD cyclopeptide could improve the tumor targeting efficacy.
Animals ; Area Under Curve ; Camptothecin ; administration & dosage ; analogs & derivatives ; chemistry ; pharmacokinetics ; Diagnostic Imaging ; Drug Delivery Systems ; Female ; Fluorescent Dyes ; Hep G2 Cells ; Humans ; Liposomes ; administration & dosage ; chemistry ; pharmacokinetics ; Liver Neoplasms ; diagnosis ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Oligopeptides ; administration & dosage ; chemistry ; pharmacokinetics ; Polyethylene Glycols ; administration & dosage ; chemistry ; pharmacokinetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spectroscopy, Near-Infrared ; Tissue Distribution

BACKGROUNDDense congenital cataracts often cause severe visual impairment. The results of long-term follow-up of dense bilateral congenital cataract in China have not been well documented. The purpose of this study was to evaluate the long-term visual function in children who underwent cataract extraction for dense bilateral congenital cataract in southern part of China.

METHODSMedical records of children who underwent surgery of dense bilateral congenital cataract between January 1992 and December 2000 at Zhongshan Ophthalmic Center of Sun Yat-sen University were retroactively reviewed. In 38 children available for current follow-up, best corrected visual acuity (BCVA) and stereoscopic vision, as well as nystagmus, strabismus, and other complications, were evaluated. The mean follow-up period was 107.6 months (range 60 to 167 months).

RESULTSThe mean age of cataract extraction and secondary intraocular lens implantation were 5.6 months (range 3 to 12 months) and 4.2 years (range 2.4 to 15 years), respectively. The mean BCVA was 0.25 in the better eye and 0.16 in the fellow eye. Stereoscopic vision was absent in all patients, and 3 children had simultaneous perception. Nystagmus was detected in all cases and strabismus in 35 cases. A high correlation was found between timing of cataract extraction and final BCVA of the better eye (r = -0.55, P = 0.00). A statistically significant difference was found in BCVA between post- and pre-treatment of amblyopia (t = 5.65, P = 0.00).

CONCLUSIONSLong-term visual function in children with dense bilateral congenital cataract was poor when cataract surgery was performed at age of 3 months or later. Earlier cataract surgery with adequate optical rehabilitation contributed to better visual outcome.

Adolescent ; Cataract ; congenital ; Cataract Extraction ; Child ; Child, Preschool ; Follow-Up Studies ; Humans ; Infant ; Retrospective Studies ; Visual Acuity

The study was purposed to investigate the effects and mechanism of bone marrow-derived mesenchymal stem cells (MSCs) on graft-versus-host desease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The model of GVHD in rat had been established by allo-HSCT with donor derived T cells. The occurence of GVHD in recipients was observed in condition with or without donor derived MSC co-transplantation. Effects of MSCs on GVHD were analyzed by model rat survival rate and pathology. Proportions of CD4+CD25+ regulatory T cells were determined by using label spleen lymphocytes and thymocytes with double fluorescent-labeled antibodies and flow cytometry. The results showed that MSCs inhibited the lethal GVHD after HSC co-transplantation and increased the survival rate. The ratio of CD4/CD8 deceased in GVHD group in different levels, as compared with that in the experimental group. The proportion of CD4+CD25+ regulatory T cells of spleen lymphocytes was 31.55 +/- 7.58% and 20.90 +/- 1.90% in experimental and GVHD groups, respectively. Similarly, the proportion of CD4+CD25+ regulatory T cells of thymocytes was 93.20 +/- 2.69% and 57.17 +/- 6.79% in experimental and the GVHD groups, respectively. Meanwhile the proportion of CD4+CD25+ regulatory T cells was higher in experimental group than that in GVHD group. It is concluded that MSCs may prevent the lethal GVHD after allo-HSC co-transplantation and raise the survival rate of model rats by acting on the CD4+CD25+ regulatory T cells in vivo.
Animals ; Bone Marrow Cells ; cytology ; Bone Marrow Transplantation ; adverse effects ; CD4-Positive T-Lymphocytes ; immunology ; CD8-Positive T-Lymphocytes ; immunology ; Graft vs Host Disease ; immunology ; Interleukin-2 Receptor alpha Subunit ; immunology ; Mesenchymal Stromal Cells ; immunology ; physiology ; Rats ; Rats, Inbred F344 ; Rats, Wistar ; T-Lymphocytes, Regulatory ; immunology

OBJECTIVETo explore the effect of Bcl-xl on tumor necrosis factor-alpha (TNFalpha)-induced apoptosis signal pathway and apoptosis.

METHODSA dominant negative mutant of ikB (pmi kappaB) and Green Fluorescent Protein (GFP) expression plasmid pEGFP-C1, pmi kappab and pEGFP-C1 and Bcl-xl expression construct pBcl-xl/HA, were co-transfected into HeLa cells. Expression plasmid pBcl-xl/HA was introduced into p65-/-MEF cells in which nuclear factor-kappaB (NF-kappaB)/p65 was deficient, to establish cell line p65-/-Bcl-xl expressing Bcl-xl by selection with puromycin. These cells were treated with TNFalpha at a concentration of 10 ng/ml, and apoptotic cell death was examined microscopically with trypan blue staining. The proteins were abstracted from treated cells, and caspase 8 activation and cleavage of poly (ADP-ribose) polymerase (PARP) were examined by western blot using a specific antibody that recognized cleaved caspase 8 and cleaved PARP, respectively.

RESULTSHeLa cells transfected with pmi kappaB, TNFalpha showed significant cell death as they became rounded, shrank, and detached. However in HeLa cells co-transfected with pBcl-xl and pmi kappaB, no cell death was observed after treatment with TNFalpha. In p65-/- MEF cells; cell death was observed at 4 hours after treatment with TNFalpha, and cell death reached 90% at 12 hours after the treatment. However, in p65-/-Bcl-xl/HA cells expressing Bcl-xl, no cell death was seen even when treated with TNFa for 24 hours. Meanwhile, in pmikB/HeLa cells transfected with pmi kappaB, TNFalpha induced caspase 8 activation and PARP cleavage, but in the HeLa cells co-transfected with pBcl-xl and pmi kappaB, no activated caspase 8 and cleaved PARP were observed after treatment with TNFalpha.

CONCLUSIONIn the experimental system in which NF-kB was inhibited, Bcl-xl blocked TNFalpha-induced apoptosis signal pathway and apoptosis. These results bring to light that further studies of the pathogenesis and therapy of TNFa-related diseases are needed.

Apoptosis ; drug effects ; Caspase 8 ; metabolism ; HeLa Cells ; Humans ; NF-kappa B ; metabolism ; Tumor Necrosis Factor-alpha ; pharmacology ; bcl-X Protein ; pharmacology

OBJECTIVETo investigate the screening methods for identifying the populations susceptible and resistant to noise-induced hearing loss (NIHL) and to provide a reference for future research.

METHODSWorkers who were exposed to 75 ∼ 120 dB noise in enterprises were included in the study. Field investigation of occupational health was conducted; workers' basic information and data on hearing threshold levels were collected. Paired chi-square test was used to compare each two of three screening methods, which were used at home and abroad to identify noise-susceptible and noise-sensitive populations, in terms of noise exposure level, general information, and noise-induced hearing threshold shift.

RESULTSThere were no significant differences in the noise exposure level, basic information, and left and right ears' hearing threshold levels of noise-susceptible and noise-sensitive populations between each two of the three screening methods (P > 0.05), according to the paired chi-square test. However, high-frequency hearing threshold had statistically significant difference among the three methods. As a whole, methods B and C were superior to method A.

CONCLUSIONThe workers in China are younger than before, with more awareness of self-protection, and individual protection is enhanced in them. Currently, method B is more suitable for screening out the population susceptible to NIHL in China.

Adult ; China ; Disease Susceptibility ; Female ; Hearing Loss, Noise-Induced ; diagnosis ; Humans ; Male ; Mass Screening ; Noise, Occupational ; adverse effects ; Surveys and Questionnaires ; Young Adult

Objective To analyze the prognosis of children with severe mycoplasma pneumonia (MPP) and its correlation with serum SAA, PCT and SF levels, so as to provide a basis for evaluating the prognosis of children with MPP. Methods A total of 273 children with MPP admitted to our hospital from January 2020 to December 2020 were divided into mild MPP children (n=187) and severe MPP children (n=86) according to the severity of their disease. According to the prognosis, children with severe MPP were divided into survival group (n=65) and death group (n=21). Serum SAA, PCT and SF levels were determined. Pearson correlation analysis was used to analyze the correlation between serum SAA, PCT and SF levels and APACHE ⅱ score. ROC curve was used to analyze the predictive value of serum SAA, PCT and SF levels for poor prognosis of children with severe MPP. Results The levels of serum SAA, PCT and SF and APACHE II score in children with severe MPP were significantly higher than those in children with mild MPP (P<0.05). Serum SAA, PCT and SF levels and APACHE II score in death group were significantly higher than those in survival group (P<0.05). Pearson correlation analysis showed that APACHE II score was positively correlated with serum SAA, PCT and SF levels (r =0.474,0.519,0.446,P<0.05). The AUC, sensitivity and specificity of combined ROC curve analysis to predict the prognosis of severe MPP were 0.871, 85.9% and 93.6% respectively, which were higher than those of SAA, PCT and SF alone. Conclusion SAA, PCT and SF are closely related to the prognosis of severe MPP, and can be used as potential markers to predict poor prognosis of severe MPP children.

Objective: Alport syndrome was an inherited kidney disease caused by the mutation of COL4A3, COL4A4, or COL4A5. Whole-exome sequencing was used to detect the mutations on these genes for the molecular diagnosis of Alport syndrome. Methods: A 6-year-old girl found accidentally with microscopic hematuria at the age of 4. The clinical data and blood sample of the family including proband, parents, brothers, and sisters were collected. Whole exome sequencing was conducted using their genomic DNAs. Results: A novel heterozygous frameshift mutation c.1826delC (p.Pro609Glnfs*44) was found in the exon 25 of the COL4A4 (NM_000092) in the proband, the father, and the sister, showing an autosomal dominant inheritance pattern of Alport syndrome. This mutation of COL4A4 was confirmed by mutation analysis, and the mutation of c.1826delC was verified by Sanger sequencing. No mutations on COL4A3 and COL4A5 were detected in this family. And the mother and brother are normal wide-type. Conclusions This novel mutation is a valuable addition to the current genetic profile of Alport syndrome, and provide us a better understanding of the disease. Whole-exome sequencing is a power tool to identify the novel mutations of inherited disease and contribute to the molecular diagnosis of disease.

OBJECTIVETo investigate the molecular mechanism of TFE (total flavone of epimedium) in the treatment of osteoporosis, and then provide experimental evidence for modernization and further development of TFE as an traditional Chinese medicine.

METHODSSixty healthy female SD rats with aged 4 months were randomly divided into three groups (including control group in which rats received sham surgery, OVX group in which ovariectomized rats didn't give any medicine after the removal of ovaries and TFE group in which ovariectomized rats administrated TFE), 20 rats in each group. Compared bone mineral density (BMD) between before operation and at 4th week after operation in order to verify the establishment of osteoporotic model (criteria: BMD decreased more than 20% at 4th week after operation). The rats in TEF group were administrated total flavone of epimedium(concentration 30 mg/ml, 10 ml/kg, qd) orally for 4 weeks. After this, killed rats to harvest the lower part of the femur and detected BMD again. Applying the reverse transcriptase-polymerase chain reaction technique (RT-PCR) to detect expression of OPG, OPGL mRNA in bone tissue.

RESULTS(1) At 4th week after ovariectomy, the mean BMD of lumbar vertebra in TFE group fell to (0.084 +/- 0.020) g/cm2. Administrated with TFE for 4 weeks,the BMD increased to (0.112 +/- 0.009) g/cm2. There was significant improvement compare with the OVX group (P < 0.05). (2) Compared between OVX group and TFE group, The OPG mRNA expression of TFE group obviously enhanced. There was significant difference in statistics (P < 0.05). However,the promotion for OPGL mRNA expression were detected between OVX group and TFE group,there was no significant difference in statistics (P > 0.05).

CONCLUSIONThis study showed that TFE could inhibit differentiation and maturation of osteoclast through enhancing OPG mRNA expression, accordingly,to treat osteoporosis.

Animals ; Bone Density ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Epimedium ; chemistry ; Female ; Flavones ; Flavonoids ; pharmacology ; Gene Expression Regulation ; drug effects ; Osteoblasts ; drug effects ; metabolism ; physiology ; Osteoprotegerin ; genetics ; Ovariectomy ; RANK Ligand ; genetics ; RNA, Messenger ; genetics ; metabolism ; Rats