BackgroundSmad4,a key intracellular mediator in transforming growth factor-β (TGF-β)signaling,plays a critical role in the normal development of many tissues/organs.However,its functional role in the development of lacrimal gland has rarely been reported.ObjectiveThe aim of this study was to investigate the role that Smad4 may play in the development of lacrimal glands using Smad4 conditional knockout (CKO) mice( C57BL/6 mouse line),MethodsSmad4 in lacrimal glands,as well as in the lens,cornea and ectoderm of the eyelids,was conditionally inactivated by the Pax6 promoter-driven Cre transgenic mice and Smad4 conditional gene mice,LacZ reporter was used to visualize the developing lacrimal gland by X-gal staining,and standard histological approaches were used to reveal morphological changes.Six or more mice or embryos in each group were used for comparisons at the same stage.ResultsLacZ staining showed that E15.0,Smad4 CKO mice could still develop primary lacrimal bud,but much shorter than the wild-type ones.At E16.5,the primary lacrimal bud in wild-type mice began branching,but no branching was found in Smad4 CKO mice except that the primary lacimal bud became blunt at the tip.At E18.0,although Smad4 CKO mice develop some acini,the branching and size and number of acini were obviously less than ones in Smad4 wild-type mice.Based on histological findings,lacrimal glands in Smad4 CKO mice developed slowly,and the size was considerably smaller,and the numbers of lobes as well as the numbers of acini were much fewer than those of Smad4 wild-type mice lacrimal glands at various stages.Pigment and adipose tissue were also observed within the lacrimal glands starting from P7 in Smad4 CKO mice and increased with age growing.Lacrimal glands in mutant adult mice were eventually replaced by adipose tissue and accumulation of pigments.Conclusions These results support the notion that Smad4 is essential for the normal development and maintenance of the mouse LG and may be involved in the metabolism of pigment and adipose tissue in LG.

Objective To investigate the correlation between chronic insomniacs' sleep quality and age,gender,education level,anxiety,depression and sympathetic skin response (SSR) in chronic insomniacs.Methods General information of 197 outpatients with chronic insomnia was recorded,including age,gender and education,etc.They were tested by Pittsburgh's Sleep Quality Index (PSQI),Hamilton's Anxiety Scale (14 item version) (HAMA14),Hamilton's Depression Scale (24 item version)(HAMD24) and Sympathetic Skin Response (SSR).Distribution properties of different age,gender and education groups were studied.Chronic insomniacs were divided into mild insomnia group (7 ≤ PSQI ＜ 14)and moderate-severe insomnia group (PSQI ≥ 14).Dependency relation analysis and stepwise linear regression analysis were conducted among indices of PSQI scores,HAMA14 scores and total score,HAMD24 scores and total score,SSR positive incidence.Results Among 197 chronic insomniacs (male,50 cases,25.4％;female,147 cases,74.6％),insomniacs aged over 40 accounted for 77.2％.Female patients were older than male patients with statistical significance,of whom those aged 40-60 years accounted for the highest proportion of 37.1％.Female patients with less education (junior high school and below)accounted for the highest proportion of 50.3％ (73/197),whose education level was generally lower than male patients.Among 197 chronic insomniacs,104 cases (52.8％,99/197) had mild insomnia and 93cases (47.2％) had moderate-severe insomnia.Total score of HAMA14 of patients with moderate-severe insomnia was significantly higher than that of patients with mild insomnia (16.47 ± 5.40 vs 12.51 ± 4.53;t =5.552,P＜0.01).There was statistically significanct difference in subitem HAMA14 scores of anxiety somatization factor (4.31 ± 2.26 vs 5.90-3.10,t =5.600,P ＜ 0.01) and spiritualized anxiety factor (10.5 ± 72.97 vs 8.20 ± 3.00,t =4.157,P ＜ 0.01) between mild and moderate-severe groups with insomnia.Total score of HAMD24 of patients with moderate-severe insomnia was significantly higher than that of patients with mild insomnia (18.04 ± 5.91 vs 13.41 ± 5.05;t=3.931,P＜ 0.01).There was statistically significanct difference in scores of most HAMD24 subitems including anxiety/somatization (3.56 ± 1.51 vs 2.94 ± 1.28;t =3.110,P =0.002),cognitive dysfunction (2.91 ± 1.68 vs 2.17 ± 1.57;t=3.191,P=0.002),retardation (2.331 ±1.31 vs 1.72 ±1.22;t=3.939,P=0.01),dyssomnia (4.51 ± 1.54 vs 3.01 ± 1.80;t =6.228,P ＜0.01) and hopelessness factor (2.29 ± 1.46 vs 1.66 ± 1.07,t =3.459,P =0.001;except body weight and diurnal variation factor) between groups with different degrees of insomnia.SSR abnormal incidences of moderate-severe insomniacs were significantly higher than that of mild insomniacs.The proportion of poorly differentiated waveform and not elicited waveform in SSR abnormal groups had statistically significant difference.The Pearson correlation analysis showed that PSQI scores in chronic insomnia patients and HAMA14,HAMD24 score as well as abnormal rate of SSR were positively correlated (r =0.439,0.465,0.249,all P ＜ 0.01).Conclusions Chronic insomnia was commonly seen in middle-aged women with education level of junor high school and below.The degree of sleep quality and anxiety,depression as well as the abnormal rate of SSR was positively correlated in patients with chronic insomnia.

Objective To discuss the correlation between MSCT morphological index of emphysema and pulmonary function test (PFT) indexes. Methods We randomly selected 33 cases with chronic obstructive pulmonary disease (COPD),and conducted CT and PFT in a week. The whole lung was scanned by MSCT at the end of deep aspiration,and the post-processing workstation was used for quantitative determination of a total of 12 morphological indexes,including the density of lung, pulmonary diameter line,lung volume,and etc,then their correlation with lung function index was analyzed.Results FEV1.0%had correlation with upper right lung density ( =0.391, =0.391), lower right lung density ( =0.465, =0.038),the mean lung density ( =0.576,=0.576), and total lung capacity (=0.471, =0.471),upper right lung volume ( =0.413, =0.049) . FEV1.0/FVC had correlation with left lower lung density ( =0.392, =0.024), the mean lung density ( =0.703, = 0.000), total lung transverse diameter ( = 0.521, = 0.521), upper right lung maximum transverse diameter ( =0.627, =0.627), and total lung capacity ( =0.549, =0.549) correlation. FVC had correlation with upper right lung maximum transverse diameter ( = 0.378, = 0.378), characterized by maximum transverse diameter (=0.349, =0.037) . TLC had correlation with mean lung density (=0.523,=0.523), upper right lung maximum transverse diameter ( =0.454, =0.454), and total lung capacity (= 0.001), the right lung volume ( = 0.492, = 0.492) . Conclusion MSCT lung morphology quantitative indicators have good clinical application value in the diagnosis and assessment of emphysema patients.

Objective To explore the influence of coal-arsenic exposure on human T cells proliferation and its mechanism.Methods Blood samples colleoted from individuals which lived in arsenism area of coal-burning type and non-arsenism area in Guizhou Province were divided into exposed group(17),mild(35),moderate(38) and severe arsenism group(19)and control group(35)according to Diagnosis Smndard for Endemic Arsenism (WS/T 211-2001).T cell stimulation index wag determined by methyl thiazolyl tetrazolium(MTT)colorimetric method.The intracellular Ca2+ exponential(IECa2+)in peripheral blood mononuclear cell(PBMC)was analyzed by Fho-3/AM dye and flow cytometry.DNA binding activity of actively T cells nuclear factor(NF-AT)in PBMC was evaluated by electrophoretie mobility shift assay(EMSA).Results Concanavalin A(ConA)stimulation decreased the T cells stimulation indexes in exposed group,mild,moderate and severe arsenism groups(1.315±0.962, 1.611±1.224,1.114±0.545,1.289±0.875)compared with control group(2.322±1.241),all the differences being statistically significant(P＜0.01).After stimulated by anti-CD3 monoclonal antibody(McAb),the T cells stimulation index in exposed group,mild,moderate and severe arsenism group(0.997±0.177,1.103±0.291,1.007±0.221, 0.957±0.205) were lower than that of control group(1.842±0.429,P ＜ 0.01 ). IECa2+ of PBMC after treated by anti-CD3 McAb in mild,moderate and severe arsenism group( 110.130±49.637,92.429±31.191,77.640± 35.372) were lower compared with control group(145.986±59.450,P ＜0.01 ). Moreover,IECa2+ in moderat and severe arsenism group were lower than exposed group(121.337±46.410,P ＜ 0.05). DNA binding activity of PBMC NF-AT in mild,moderate and severe arsenism group(1.354±0.446,1.290±0.291,1.159±0.411 ) were lowered than that of control group(1.722±0.291,P ＜ 0.01) and exposed group(1.611±0.294,P ＜ 0.05). Conclusions The coal-arsenic exposure can reduce the human T cells stimulation indexes,IECa2+ in PBMC and the DNA binding activity of NF-AT. It suggest that arsenic may suppress the proliferation ability of human T cells,which may be partly related to the influence of arsenic on T cell receptor(TCR)/CD3 signal transduetion pathway.

Objective To investigate the activation of T lymphocytes in human peripheral blood and the signaling molecules in protein kinase C/nuclear factor KB(PKC/NF-κB) pathway expressivity or activity changes in human peripheral blood mononuclear cells(PBMCs) exposed to coal-arsenic,to explore the role of PKC/NF-κB signal pathway in activation of T cells in human exposed to coal-arsenic. Methods Blood samples were collected from individuals who lived in arsenism area of coal-burning in Guizhou province, and were divided into asymptomatically exposed group (12),mild arsenism group (33),moderate arsenism group (34) and severe arscnism group (15) according to Diagnosis Standard for Endemic Arsenism (WS/T 211-2001). The individuals who lived in non-arsenism area were control group(27). The ratio of activated T ceils was analyzed by flow cytometry. DNA binding activity of NF-κB in PBMCs was evaluated by electrophoretic mobility shift assay(EMSA). The expression of PKCθ and phospho-PKCθ(pPKCθ) in PBMCs were detected with western blotting analysis. Results The ratio of activating T cells in asymptomatically exposed group[(21.76±15.31)%],mild arsenism group[(18.41±11.36)%],moderate arsenism group[(17.78±11.93)%]and severe arsenism group[(18.79±13.38)%]were all higher than that of control group[(3.19±2.12)%],the difference among all groups being statistically significant(F = 7.893,P < 0.05). DNA binding activity of PBMCs NF-κB in asymptomatically exposed group,mild arsenism group,moderate arsenism group and severe arsenism group(1.49±0.24,1.58±0.30,1.57±0.34,1.51±0.16) were higher than that of the control group(1.30±0.17),the difference being statistically sign/ficant(P < 0.05 or < 0.01). The expression of PBMCs pPKCθ in mild arsenism group,moderate arsenism group and severe arsenism group(0.64± 0.14,0.64±0.27,0.62±0.12) were all lower than that of the control group(0.93±0.20),the difference being statistically significant(P < 0.05). There were significant negative correlations between the expression of pPKCθ and the activity of NF-κB(r =-0.565,P < 0.01). There were significant positive correlations between the activity of NF-κB and the ratio of activating T cells(r = 0.546,P < 0.01). Conclusion Coal-arsenic enhances the DNA binding activity of NF-κB,reduces the expression of PBMCs pPKCθ in human PBMCs and up-regulates the activity of T cells. It suggests that the PKC/NF-κB signal might be one of transduction pathway via activating of T cells by coal-arsenic.

Adolescent ; Antimetabolites, Antineoplastic ; administration & dosage ; Child ; Child, Preschool ; Female ; Humans ; Infusions, Intravenous ; Leucovorin ; administration & dosage ; Lymphoma, Non-Hodgkin ; drug therapy ; Male ; Methotrexate ; administration & dosage ; adverse effects ; blood ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy

Objective To investigate the clinical significance of serum transforming growth factor-β( TGF-β),tumor necrosis factor-α( TNF-α) and interferon-γ( IFN-γ) levels in patients with pre-eclampsia. Methods Thirty-two cases of maternal pre-eclampsia( 22 cases were mild pre-eclampsia,10 cases were severe pre-eclampsia),30 cases of gestational hypertension and 30 cases of normal mothers were selected as our subjects. Serum TGF-β,TNF-α IFN-γ levels were detected. Adverse pregnancy outcomes in patients were collected and analyzed. Results Serum TGF-β,TNF-α,IFN-γlevels in patients with severe pre-eclampsia were (90. 4 ± 23. 4)μg/L,(84. 5 ± 13. 6)μg/L and(146. 5 ± 13. 4)μg/L respectively,significantly higher than that in normal mothers((11. 3 ± 3. 7)μg/L,(5. 6 ± 1. 2)μg/L and(82. 5 ± 19. 4)μg/L),the gestational hypertension group(( 35. 3 ± 8. 4 )μg/L,( 10. 4 ± 2. 9 )μg/L and( 96. 4 ± 15. 8 )μg/L ),and mild pre-eclampsia group((76. 5 ± 15. 4)μg/L,(26. 5 ± 3. 2)μg/L and(120. 4 ± 20. 5)μg/L),and the difference were significant(F=11. 363,15. 982,7. 431;P﹤0. 001). Serum TGF-β,TNF-α and IFN-γ levels in mild pre-eclampsia were significantly higher than those in normal mothers and gestational hypertension patients( P﹤0. 05). Incidence of preterm delivery in patients with high TGF-β,TNF-α,IFN-γ expression was significantly higher than patients with low expression(7 cases vs. 2 cases;χ2 =4. 037,P=0. 044). Incidence of in patients with high FGR,TGF-β,TNF-α expression was significantly higher than patients with low expression( 6 cases vs. 1 case;χ2 =4. 969,P =0. 025 ). Conclusion Detection of maternal serum cytokines can evaluate the severity of pre-eclampsia to a certain extent and predicted adverse pregnancy outcomes.

Objective To investigate methods for prenatal diagnosis of spinocerebellar ataxia type 3 (SCA3).Methods Cordocentesis were performed in the pregnant SCA3 female proband of pedigree during the 20th gestational week.Polymerase chain reaction (PCR) and short tandem repeat (STR) analysis based on CEQS000 sequencer were applied to analyze the CAG repeat of SCA3 gene.Results The proband had 31/75 CAG repeat alleles of SCA3 gene; her spouse had 14/27 CAG repeat alleles; the fetuse had 14/31 CAG repeat alleles (14 repeat from the father,and 31 repeat from the mother),which is in conformity with Medelian inheritance.The fetuse inherited the normal CAG repeat allele from the mother.The above results of the fetuse were verified after its birth.Conclusion Detecting CAG repeat dynamic mutation of SCA3 gene based on umbilical cord blood and STR analysis could be a rapid and reliable method for prenatal diagnosis of SCA3.

This paper summarizes the key points of safety management for 15 patients with severe pulmonary arterial hypertension treated by aerosolized iloprost. All patients achieved significant improvements and none of them suffered any severe side effect. Complete safety management during the therapeutic procedure improved the patients' treatment confidence and compliance,and thereafter strengthened the efficacy of treatment.

OBJECTIVE: To explore the role of hydrogen sulfide (H2S) in acute liver injury induced by crushing hind limbs of rats. METHODS: The rats were randomly divided into the following groups: control, crushing, H2S donor sodium hydrosulfide (NaHS) + crushing, H2S inhibitor propargylglycine (PAG) + crushing group. The acute liver injury model was established by 'crushing the hind limbs of rats with standard weight. Rats were sacrificed at 30 min and 120 min after the crush. The activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured by colorimetric method, and the content of H2S in plasma and the contents of malondialdehyde (MDA), protein carbonyl, glutathione (GSH) in the liver and the activity of H2S generating enzyme (cystathionine y-lyase, CSE) were determined by chemical method. The expression of CSE mRNA in liver was detected by RT-PCR. RESULTS: For crush injury group, the levels of AST and ALT in serum, MDA and protein carbonyl in liver increased. The levels of GSH, CSE, CSE mRNA in liver and H2S in serum decreased. The administration of NaHS before limbs crush could attenuate the changes of liver injury, but the pre-treatment with PAG could exacerbate the changes. CONCLUSION The decrease of H2S production could involve in mediating the acute liver injury induced by traumatic stress in rats.
Alanine Transaminase/blood* ; Alkynes/pharmacology* ; Animals ; Aspartate Aminotransferases/blood* ; Cystathionine gamma-Lyase/metabolism* ; Glutathione/metabolism* ; Glycine/pharmacology* ; Hydrogen Sulfide/pharmacology* ; Liver/injuries* ; Malondialdehyde/metabolism* ; Protein Carbonylation ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sulfides/pharmacology*