Objective To explore the diagnosis of tuberous sclerosis (TSC) combined with Langerhans cell histiocytosis (LCH) and secondary hemophagocytic lymphohistocytosis (HLH).Methods One case diagnosed of TSC combined wiht LCH and secondary with HLH in infancy was retrospectively analyzed.Results One year and 4-month-old Uyghur boy when he was 4-month-old,there was onset of infantile spasm.Gene detection was performed when he was one year old and showed the absence of the exon 3 to 10 ofTSC2 gene.The diagnosis of TSC was confirmed.Meanwhile,the boy also suffered with skin rash all around,fever,hepatosplenomegaly,and bone defect.The diagnosis of LCH was confirmed by skin biopsy.In addition,the boy was complicated HLH.Conclusions It is rarely seen that TSC combined with LCH,and secondary HLH in one case.The clinical features were complex and need to be differetiate.

Objective To explore the clinical feature and therapeutic strategy for children with thrombotic microangiopathy (TMA). Methods The clinical manifestation, auxiliary examination and treatment of 24 cases of children with TMA was analyzed retrospectively. Hemolysis urine toxin syndrome (HUS)occurred in 22 cases, and thrombotic thrombocytopenic purpura (TTP) occurred 2 cases. Results Sixteen cases was onset from May to July,and 8 cases was onset from September to November. Typical HUS (D+HUS) was 8 cases, and atypical HUS (D-HUS) was 14 cases. In 22 HUS children, 18 cases were given hemodialysis or peritoneal dialysis treatment. The illness were significantly improved, and the platelet count and renal function fully recovered normal. But 1 case appeared neurological symptoms such as headache, facial paralysis on one side, gastrointestinal bleeding, and fever, after getting better. Eventually the patient died of disseminated intravascular coagulation. Two cases of TTP were given plasma exchange , anti-infection, large dose of methylprednisolone and anti- platelet aggregation treatment . After treatment, the level of hemoglobin and blood platelets returned normal and consciousness was recuperated. Conclusions HUS and TTP are similar in pathogenesis and clinical manifestation,and it is necessary to be differentiated. Early diagnosis and proper treatment is the key to save the life of children with TMA. As soon as the diagnosis is clear, hemodialysis or peritoneal dialysis treatment should be given to HUS, and plasma exchange to TTP,to quickly control the condition and improve the clinical symptoms.

Objective To explore the effects of ethyl-3,4 dihydroxybenzoate(EDHB), a prolyl hydroxylase inhibitor, pretreatment on the tubular epithelial cells apoptosis induced by albumin and hypoxia. Methods To investigate the effects of albumin and hypoxia on cells, rat tubular epithelial cells(NRK-52E)were incubated for 24 h in:(1)normoxia(5%CO2);(2)hypoxia(1% O2);(3)albumin(30 g/L)under normoxia;(4)albumin(30 g/L)under hypoxia. To investigate the effects of EDHB pretreatment on cells apoptosis, NRK-52E were incubated in hypoxia for 24 h in:(1)normoxia;(2)hypoxia;(3)hypoxia+albumin(30 g/L);(4)hypoxia+EDHB(500 μmol/L);(5)EDHB pretreatment(albumin 30 min after EDHB). Apoptosis was measured by flow cytometry(AnnexinV-FITC-PI). bcl-2, bax and vascular epithelial growth factor(VEGF)mRNA expression were detected by RT-PCR. VEGF protein expression was detected by Western blotting. Results NRK-52E apoptosis was not significantly different between hypoxia and norraoxia groups(P>0.05), but increased significantly in albumin(30 g/L)under hypoxia group compared with albumin(30 g/L)under normoxia group(37.36%?.95% vs 25.59%?.32%, P< 0.05). There was an increase in bax mRNA expression and a decrease in bcl-2 mRNA expression in albumin(30 g/L)under hypoxia group compared with albumin(30 g/L)under normoxia group(P< 0.05). EDHB pretreatment improved these impairments of albumin(30 g/L)under hypoxia on NRK-52E(P< 0.05). VEGF expression elevated in hypoxia compared with normoxia(P<0.05), decreased in albumin(30 g/L)under hypoxia groups compared with that without albumin groups(P<0.05).EDHB pretreatment significantly improved VEGF expression compared with albumin(30 g/L)under hypoxia group(P <0.05). Conclusion NRK-52E cells apoptosis induced by albumin is accelerated by hypoxia, however partially improved by EDHB pretreatment, probably through the up-regulation of VEGF expression.

Objective To explore the protective effect of rosiglitazone on insulin resistance( IR)induced by high glucose in vascular endothelial cells and its possible mechanism. Methods Human umbilical vein endothelial cells( HUVECs) was divided into 3 groups:the normal control group cultivated in DEME medium with 5. 5 mmol·L-1 glucose;the high glucose group( HG)cultivated in DEME medium with 33 mmol · L-1 glucose for 24 h after the IR model was set up;the rosiglitazone group cultivated in DEME medium with 33 mmol·L-1 glucose and 10 μmol·L-1 of rosiglitazone for 24 h after the IR model was set up. The cell viability,nitric oxide(NO),endothelin-1(ET-1),mitochondrial membrane potential,reactive oxygen species ( ROS),p-IKK and IkBa protein levels were detected. Results Compared with the normal control,the cell viability,the level of NO and the mitochondrial membrane potential were decreased,levels of ET-1 and ROS increased,p-IKK expression was up-regulated,and IκBα expression was down-regulated in HG group(all P〈0. 01). Rosiglitazone reversed these changes in a time-dependent manner(P〈0. 05). Conclusion Rosiglitazone has the protective effect on insulin resistance induced by high glucose in vascular endothelial cells via inhibiting ROS/IKK signaling pathway.

Objective To investigate the effects of dexamethasone on expressions of epithelial neutrophil activating protein-78 (ENA-78) and transforming growth factor- beta 1 (TGF-β1) in neutrophil of asthma rats.Methods Thirty male SD rats were randomly divided into three groups on average, including asthma group, control group and dexamethasone treated group. In this experiment, the rat model of asthma were established by sentization and challenge with ovalbumin. Blood neutrophil were isolated and purified. The expression of ENA-78 was detected by flow cytometry. The expression of TGF-β1 was detected by immunohistochemical method in blood neutrophil and bronchial wall. Results Expression of ENA-78 in blood neutrophil in dexamethasone treated group(71.82 ±8. 87 mean fluorescence intensity)was lower than that in asthma group, but higher than that in control group(all P ＜0. 01). And expressions of TGF-β1 protein in dexamethasone treated group(0. 173 ± 0. 014,0. 202 ± 0. 019 optical density, respectively) was lower than that in asthma group(all P ＜0. 01) ,but higher than that in control group(all P ＜0. 01). There were significant positive correlation between ENA-78 expression at blood neutrophil and numbers of total inflammation cells in bronchoalveolar lavage fluid (n = 29, γ = 0. 762, P ＜ 0. 01). Conclusion The beneficial effect of glucocorticoid(dexamethasone) on airway inflammation in asthma rats could be at least in part due to their direct inhibitory effect on ENA-78 and TGF-β1 protein generation by neutrophil.

Objective: To observe the dynamics of antibody response in great gerbils infected with Yersinia pestis in experiment. Method: A total of 211 great gerbils were captured in the southern margin of plague natural focus of Junggar Basin of the Xinjiang Uygur Autonomous Region in 2011. Among them, there were 167 great gerbils without infection of Y. pestis and 44 great gerbils infected by Y.pestis. Y.pestis No. 2504 was employed for this experimental strain, which was strong toxic strain with negativity in the reduction experiment of nitrate. 35 great gerbils without the infection of Y. pestis were divided randomly and averagely into 7 groups including 6 experimental groups and 1 control group. Great gerbils in the 1st to 6th experimental groups were exposed first with 1 × 10⁶-1 × 10¹¹ CFU/ml of bacterial fluid with 10 times of gradient dilution; groin areas of great gerbils in the control group were injected subcutaneously with physiological saline; and the amount of infection was all 1 ml. 17 great gerbils infected with Y. pestis and the first detection of F1-antibody titer in 1∶256-1∶4 096 were grouped according to F1-antibody titer: group 1∶4 096 (n=4), group 1∶2 048 (n=4), group 1∶1 024 (n=3), group 1∶512 (n=3) and group 1∶256 (n=3); and blood in caudal regions was collected in asepsis for the detection of F1-antibody, with a total of 5 times. 9 great gerbils which were selected from the remaining great gerbils infected with Y. pestis and detected F1-antibody negative 2 times were exposed 1×10⁶ CFU/ml of bacterial fluid for the second infection, with the amount of infection being 1 ml. Blood in caudal regions of great gerbils after the first and second infection were collected for the detection of plague F1-antibody on the 3rd, 5th, 7th, 15th, 30th, 60th, 90th and 120th day after infection. Declined regression models for great gerbils' antibodies were established with unary linear regression equation; declined change diagrams for the antibodies were drawn to observe the declined F1-antibody after great gerbils were exposed to Y. pestis. Results: In great gerbils with the first infection of Y. pestis, antibodies were detected in the 1 × 10⁶-1 × 10⁸ CFU/ml of group on the 30th, 15th and 15th day, respectively; the positive rates of antibody were 1/4, 3/4 and 4/5, respectively; the group 1×10⁷ and 1× 10⁸ CFU/ml reached to the highest antibody titer with 1∶256 on the 120th day; antibodies were revealed in the group 1×10⁹, 1×10¹⁰ and 1×10¹¹ CFU/ml from the 5th to 7th day when the seroconversion of all antibodies was observed; group 1×10¹¹ CFU/ml reached to the highest antibody titer on the 120th day with 1∶4 096. In the great gerbils with the second exposure to Y.pestis, positive antibodies were detected on the 3rd day with the positive rate being 2/9; and the highest antibody titer with 1∶2 048 was noted on the 90th day. Unary linear regression equation of declined F1 antibody of great gerbils was y=0.045x- 0.321 (F=115.40, P< 0.001), and the shortest duration for F1-antibody titer declining from 1∶4 096 to 0 was 140 d and the longest duration 200 d. Conclusion Great gerbils infected with the high concentration of Y. pestis fluid show shorter duration in producing F1-antibody, the antibody positive rate is also higher, and the highest antibody titer can reach 1∶4 096. The great gerbils could hold the plague F1 antibodies for a long time which was about 140 to 200 days from the highest titer.

Objective: To understand the histopathological and ultrastructural pathology changes of great gerbils in the Junggar Basin to Yersinia pestis infection. Methods: Forty captured great gerbils from the Junggar Basin that tested negative for anti-F1 antibodies were infected. The Y. pestis strain 2504, isolated from a live great gerbil in the natural plague foci of the Junggar Basin in 2005 with a median lethal dose (LD₅₀) of <10 CFU/ml, was used in this study. Forty great gerbils were divided into seven infection groups and were subcutaneously infected with 7.4×10⁵, 7.4×10⁶, 7.4×10⁷, 7.4×10⁸, 7.4×10⁹, 7.4×10¹⁰, or 3.0×10¹¹ CFU/ml of 2504. One milliliter of physiological saline was injected in the noninfected group as a control. We collected the liver, spleen, heart, and lung from all animals for histopathologic and ultrastructural pathology examination. Results: Great gerbils in the 7.4×10⁸-3.0×10¹¹ CFU/ml groups did not survive and exhibited pathological changes and altered ultrastructural pathology. The liver tissue of infected great gerbils showed spotty necrosis and fatty degeneration, intranuclear canaliculi with increased hepatocytes, and uneven distribution of organelles. Additionally, reactive proliferation of lymphoid tissue in the spleen, blood sinusoid lacunae with neutrophil infiltration, and phagocytosed bacteria in phagocyte cells were observed. Myocardial fiber hypertrophy and interstitial indistinction, nuclear matrices decreased in cardiac myocytes, and loose arrangement of myogenic fibers in myocardial cells were also observed. Angiectasia, capillary congestion, and tissue necrosis were found in the lung. No significant difference in histopathological and ultrastructural pathology in the parenchymal organ was observed between the 7.4×10⁵-7.4×10⁷ CFU/ml groups and the 7.4×10⁸-3.0×10¹¹ CFU/ml groups, and no specific death caused by Y. pestis infection was apparent in the 7.4×10⁵-7.4×10⁷ CFU/ml groups. Conclusion Y. pestis infection altered tissue and ultrastructural pathology in the parenchyma apparatus of great gerbils. In particular, the liver and spleen appeared to be the primary site of Y. pestis infection in great gerbils.

Hypothyroidism is a common adverse reaction in clinical multi-target tyrosine kinase inhibitor (TKI) and may be used as a predictor of efficacy of TKI drugs.Studies show that hypothyroidism is significantly associated with good prognosis in patients with renal cell carcinoma treated with multi-target TKI,which may be related to inhibition of vascular endothelial growth factor receptor pathway,potential off-target effects and inhibition of cell proliferation.Whereas in the patients with hepatocellular carcinoma who received multi-target TKI therapy,hypothyroidism is an indicator of poor prognosis,which is related to the T3/TR pathway regulating liver cancer growth and invasion.The predictive function and mechanism of thyroid hormone levels in different tumor patients receiving multi-target TKI drugs are different,and further research is still needed.

Objective:To investigate the immunoregulatory effects of Glycyrrhiza uralensis ethanol extract(GUEE) on the maturation of dendritic cells (DCs) and the adjuvant effect of GUEE on OVA in na?ve BALB/c mice and an ovalbumin (OVA)-induced asthma mouse model. Methods:GUEE was prepared, and the effects of different concentrations of GUEE on the maturation of DCs and the secreted cytokines as well as the effects of GUEE on bacterial lipopolysaccharide (LPS)-induced DC maturation were examined in vitro. The effect of GUEE on the morphology of mouse bone marrow derived DCs was observed using microscopy. Molecular expression levels on the surface of DCs were detected using flow cytometry. The levels of interleukin-1β (IL-1β), IL-6, IL-12, and tumor necrosis factor-α (TNF-α) in the supernatant of DCs cultures were measured by enzyme-linked immunosorbent assay (ELISA). The maturation status of DCs was detected by flow cytometry by injecting different concentrations of GUEE into the paws of mice and isolating the draining lymph nodes 24 h later. The naive BALB/c mice were co-immunized with OVA, and the changes in regulatory T cells (Treg) were detected by flow cytometry. An OVA-protein-induced mouse asthma model was established to investigate whether GUEE as a tolerogenic adjuvant has an antigen-specific therapeutic effect on asthmatic mice. Pulmonary pathological changes were analyzed by hematoxylin-eosin staining (HE) and PAS staining. OVA-specific antibodies in serum and the frequencies of Tregs, CD4 + IFN-γ + and CD4 + IL-4 + T cells in the spleen were detected by ELISA and flow cytometry, respectively. Results:GUEE suppressed DCs maturation induced by LPS both in vitro and in vivo (all P<0.05), and reduced proinflammatory cytokine production, including IL-1β, IL-6, IL-12 and TNF-α in the absence or presence of LPS (all P<0.05). Moreover, co-immunization with OVA and GUEE increased the amount of Tregs in na?ve BALB/c mice ( P<0.05). In OVA-induced asthmatic mice, OVA and GUEE co-immunization and GUEE alone treatment substantially ameliorated the inflammation of lung tissues, decreased the levels of IgG 1 and the amount of CD4 + IL-4 + T cells, and increased the amount of Tregs (all P<0.05). Conclusions:GUEE alone or as the tolerogenic adjuvant can ameliorate allergic diseases through inhibition of DC maturation and type 2 helper T cell responses and induction of Tregs.

Objective: Progressive supranuclear palsy (PSP) involves a variety of visual symptoms that are thought to be partially caused by structural abnormalities of the retina. However, the relationship between retinal structural changes, disease severity, and intracranial alterations remains unknown. We investigated distinct retinal thinning patterns and their relationship with clinical severity and intracranial alterations in a PSP cohort. Methods: We enrolled 19 patients with PSP (38 eyes) and 20 age-matched healthy controls (40 eyes). All of the participants underwent peripapillary and macular optical coherence tomography. Brain 11C-2β-carbomethoxy-3β-(4-fluorophenyl) tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography imaging were also performed in patients with PSP. We investigated the association between retinal thickness changes and clinical features, striatal dopamine transporter availability, and cerebral glucose metabolism. Results: The peripapillary retinal nerve fiber layer (pRNFL) and macula were significantly thinner in patients with PSP than in controls. The thickness of the superior sector of the pRNFL demonstrated a significant negative relationship with the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III and Hoehn and Yahr staging scale scores. A significant negative correlation was found between outer inferior macular thickness and disease duration. Outer temporal macular thickness was positively correlated with Montreal Cognitive Assessment scores. In PSP, lower outer temporal macular thickness was also positively correlated with decreased dopamine transporter binding in the caudate. Conclusion The pRNFL and macular thinning may be candidate markers for monitoring disease severity. Additionally, macular thinning may be an in vivo indicator of nigrostriatal dopaminergic cell degeneration in PSP patients.