Objective To investigate the blockade effects of soluble PD-1 (sPD-1) expressed in vivo on B7-H1/PD-1 signal transduction,and inhibitory effect in pulmonary metastasis of melanoma with combi- nation of Hsp70-B16 antigen peptides in mice.Methods The pulmonary metastasis model of melanoma was established in mice.Immunohistochemical staining and flow cytometry were utilized to detect the expres- sion of PD-1 and B7-H1 respectively in pulmonary metastasis loci.Four days after the inoculation of tumor cells,forty murine models of pulmonary metastasis were randomly divided to be immunized with normal sodium (group A),empty vector pcDNA3.1 (group B),PDlA plasmid (group C) respectively via tail vein injection,subcutaneous injection of Hsp70-B16 antigen peptides (group D) or with the combination of intra- venous PDlA plasmid and subcutaneous Hsp70-B 16 antigen peptides (group E).The local infiltration with lymphocytes in pulmonary metastasis loci was observed and a series of immunological parameters were assessed 17 days after the inoculation of tumor cells.Results The melanoma pulmonary metastasis model was successfully established.There were a lot of PD-1 positive cells in these loci,and B7-H1 molecule was massively expressed on the surface of B16 cells in metastasis loci.The pulmonary metastasis was inhibited in the mice of group E,and the inhibition rate was 95%,higher than that in other groups (53%,76%,9% in group C,D,B,respectively).The quantity of CD8~+ T cells in pulmonary metastasis loci,cytotoxicity of spleen lymphocytes to tumor cells,and serum concentration of IL-2 and IFN-?were all significantly elevated in the mice of group E as compared with those of other groups (all P

Abstract: Objective To understand the mental health literacy level of residents in Hainan Province, and to provide evidence for promoting mental health promotion and improving the mental health literacy level of residents. Methods Multi-stage random sampling method was used to investigate The National Mental Health Literacy Questionnaire among 6 895 residents in 12 districts including Changjiang, Chengmai, Dongfang, Ledong, Lingshui, Haikou Longhua District, Haikou Meilan District, Qionghai, Sanya, Tunchang, Wenchang and Wuzhishan. Results　In the survey 6 895 residents in 12 counties, cities, districts of Hainan Province, 365 of them reached the standard of mental health with the standard rate of 5.3%. The mental health knowledge score was (54.00±17.02) with the standard rate of 7.7%; the self-assessment score was (26.11±3.99) with the standard rate of 75.9%; the score of mental health skill was (26.22±7.25) with the standard rate of 44.8%. The mental health literacy level of medical workers was the highest, with the standard rate of 13.5% (112/830), and the mental health literacy level of farmers was the lowest, with the standard rate of 0.8% (13/1 647). The results of unconditional Logistic regression showed that the factors entering the regression model included educational background (OR=2.268), personal monthly income (OR=1.129), gender (OR=1.302), household registration (OR=0.776), and whether they had participated in mental health related courses OR training (OR=0.511). The higher the educational background and personal monthly income, the higher the psychological quality. The mental health of women was higher than that of men, and that of urban was higher than that of rural, and those who had participated in mental health related courses were higher than those who had not. Conclusions The mental health literacy level of Hainan residents is at a low level, and the influencing factors are multifaceted. It is suggested to strengthen the mental health monitoring comprehensively and carry out rich health education service mode for different groups.

OBJECTIVETo explore the possible negative regulatory elements induced by the treatment of experimental murine hepatoma with 4-1BBL, and to investigate the synergistic effects and mechanisms of 4-1BBL and soluble PD-1 (sPD-1) in tumor therapy.

METHODSMice were inoculated intramuscularly (i.m.) with 5 x 10(5) H22 tumor cells in the right hind thigh to establish the experimental hepatoma model. The mice were randomly divided into 5 groups (12 mice in each group) after inoculation. The mice of group A, B, C and D were injected with NS, plasmid pcDNA3.1, plasmid p4-1BBL and plasmid pPD-1A respectively. The mice in group E, the combinatorial treatment group, were injected with plasmid p4-1BBL and pPD-1A together. Then the anti-tumor effects, using the tumor growth rates and mice survival rates and others as parameters, were recorded. Meanwhile, the phenotype of lymphocytes and residual tumor cells in the peri-tumor tissue were analyzed.

RESULTSEither transfection with 4-1BBL gene alone or with sPD-1 alone could inhibit tumor growth to some extent, but a more significant anticancer effect was obtained in the combinatorial treatment group (group E), in which the tumors were completely inhibited in 42% of the mice, compared with 0 in the other groups. In addition, the survival rate of mice in group E was 100%, compared with 30% in group B, 65% in group C and 62% in group D. The FACS analysis results showed that the expression level of B7-H1 and B7-DC on residual tumor cells in group C (injected with p4-1BBL alone) was higher than that on cells in other groups. The amount of CD8+ T cells in the peri-tumor tissue of group E was significantly increased.

CONCLUSION4-1BBl can induce an up-regulation of negative regulatory elements and at the same time it can enhance the anti-tumor response. The combinatorial treatment with 4-1BBL and sPD-1 can produce a positive synergistic anti-tumor effect on our murine experimental hepatoma.

4-1BB Ligand ; therapeutic use ; Animals ; Antigens, Surface ; therapeutic use ; Apoptosis Regulatory Proteins ; therapeutic use ; Genetic Therapy ; Liver Neoplasms ; metabolism ; therapy ; Liver Neoplasms, Experimental ; metabolism ; therapy ; Mice ; Mice, Inbred BALB C ; Programmed Cell Death 1 Receptor

Objective To investigate the glucose metabolic pattern of brain functional loop in patients with refractory obsessive compulsive disorder (OCD) using 18 F-FDG PET.Methods Eight patients with refractory OCD and 8 age- and gender-matched healthy volunteers underwent 18F-FDG PET brain imaging.SPM software was used for image post-processing and quantitative analysis.Correlation analysis between 18F-FDG uptake and Yale-Brown obsessive compulsive scale(Y-BOCS) score was performed.Results Compared with the controls,the glucose metabolism of bilateral frontal cortices ( including the rectal gyrus,orbital gyrus and cingulate gyrus),left thalamus,right temporal lobe and bilateral cerebellum in refractory OCD patients increased significantly ( Zmax =3.45 - 5.80,all P ＜ 0.001 ).Bilateral motor cortices and bilateral parietal lobes (BA7),however,showed decreased glucose metabolism (Zmax =3.44 - 4.46,all P ＜0.001 ).Y-BOCS score was positively correlated with the glucose metabolism of the bilateral anterior cingulate cortex (Zmax =3.77,3.48 and 2.97,all P ＜ 0.01 ).Conclusions There is a characteristic metabolic pattern of increased glucose utilization in the fronto-striato-thalamic loop and decreased glucose utilization in bilateral motor cortices and parietal lobes in patients with OCD.The glucose metabolism in the anterior cingulate cortex might serve as a quantitative parameter for the assessment of the severity of OCD.

OBJECTIVETo evaluate the effect of JAK/STAT signaling pathway activation on the transdifferentiation and secretion of transforming growth factor-beta1 (TGF-beta1) induced by high glucose in renal proximal tubular epithelial cells.

METHODSHuman kidney cells (HKC) were cultured and then divided into four groups: low glucose (LG) group, high glucose (HG) group, high mannitol (LG + M) group, and HG + AG490 group. Immunoprecipitation and Western blot analysis were used to determine the expression of tryosine phosphorylated Janus kinase 2 ( p-JAK2). The protein expressions of STAT1, STAT3, p-STAT1, and p-STAT3 and the expressions of alpha-SMA and E-Cadherin were observed by Western blot. The contents of TGF-B1, fibronectin and type I collagen in the supernatants of the cultured HKC were detected by enzyme-linked immunosorbent assay (ELISA). The expression of TGF-beta1 mRNA was measured by reverse transcription and polymerase chain reaction (RT-PCR).

RESULTSCompared with LG group, the expressions of JAK2, p-STAT1, p-STAT3, and TGF-beta1, mRNA were significantly increased in HG group from 6 to 72 hours. Meanwhile, the contents of TGF-beta1 and collagen I in the supernatants and the expression of alpha-SMA increased and the expression of E-Cadherin decreased. The expressions of JAK2, p-STAT1, p-STAT3, and TGF-beta mRNA as well as the levels of TGF-beta1 and collagen I in the supernatant s in HG + AG490 group were significantly lower than in the HG group. The expressions of alpha-SMA and E-Cadherin were also decreased in HG + AG490 group.

CONCLUSIONActivation of JAK/STAT signaling pathway may be involved in the high glucose-induced transdifferentiation and overproduction of TGF-beta1, and ECM proteins in HKCs.

Cell Line ; Cell Transdifferentiation ; Epithelial Cells ; cytology ; metabolism ; Glucose ; metabolism ; pharmacology ; Humans ; Janus Kinases ; physiology ; Kidney Tubules, Proximal ; cytology ; metabolism ; STAT Transcription Factors ; physiology ; Signal Transduction ; Transforming Growth Factor beta1 ; biosynthesis ; secretion ; Urothelium ; cytology ; metabolism

BACKGROUNDThe synovial fluid concentrations of adiponectin are significantly higher in patients with rheumatoid arthritis (RA) than in patients with osteoarthritis (OA). Accumulating evidence suggests that adiponectin may be an inducer of inflammation in arthritis, but the mechanism remains unclear. The objectives of this study were to compare the expression levels of adiponectin receptors in rheumatoid arthritis synovial fibroblasts (RASF) and osteoarthritis synovial fibroblasts (OASF), evaluate the roles of adiponectin receptors in adiponectin-induced prostaglandin E(2) (PGE(2)) production, and then investigate the effects of a nonsteroidal anti-inflammatory drug (NSAID) and a cyclooxygenase (COX)-2-selective inhibitor on adiponectin-induced PGE(2) release.

METHODSThe expressions of adiponectin receptor 1 (AdipoR1) and AdipoR2 mRNA and protein in synovial fibroblasts from seven patients with RA and eight patients with OA undergoing total knee replacement were evaluated by real-time polymerase chain reaction, immunofluorescence microscopy and Western blotting analysis. Adiponectin-induced PGE(2) production was detected by enzyme-linked immunosorbent assay. RNA interference against the AdipoR1 and AdipoR2 genes was performed to investigate the effects of the adiponectin receptors on adiponectin-induced PGE(2) production in both RASF and OASF.

RESULTSAdipoR1 and AdipoR2 mRNA and protein were expressed by both RASF and OASF. Compared with OASF, RASF exhibited higher levels of AdipoR1, but there was no significant difference for AdipoR2. Adiponectin induced the production of PGE(2) by the synovial fibroblasts in a concentration-dependent manner, and this was more obvious in RASF. RNA interference showed that the difference may be mediated by the diverse distribution of AdipoR1. The adiponectin-induced PGE(2) production was efficiently relieved by the NSAID and COX-2-selective inhibitor.

CONCLUSIONThe present findings suggest that AdipoR1 may mediate the difference in adiponectin-induced PGE(2) production in RASF and OASF.

Adiponectin ; pharmacology ; Arthritis, Rheumatoid ; metabolism ; Blotting, Western ; Cells, Cultured ; Dinoprostone ; metabolism ; Female ; Fibroblasts ; drug effects ; metabolism ; Humans ; Immunoassay ; Male ; Microscopy, Fluorescence ; Middle Aged ; Osteoarthritis ; metabolism ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Receptors, Adiponectin ; genetics ; metabolism ; Synovial Membrane ; cytology

OBJECTIVETo investigate the role of Pediatric Critical Illness Score (PCIS) in evaluating the prognosis and severity of severe hand-foot-mouth disease (HFMD).

METHODSThis study included 424 children with severe HFMD, consisting of 390 survivors and 34 deceased patients. Related physiological parameters and clinical data were collected for calculating PCIS scores. The area under receiver operating characteristic curve (AUC) was employed to assess the performance of PCIS in evaluating the complications and outcomes.

RESULTSThe median of PCIS scores for survivors was higher than that for deceased patients (P<0.01). Of the 424 children with severe HFMD, only 26 (6.1%) had critical illness according to the severity assessment using PCIS. The AUC (95%CI) of PCIS was 0.74 (0.66, 0.82) in predicting pulmonary edema, 0.82 (0.74, 0.90) in predicting pulmonary hemorrhage, and 0.83 (0.75, 0.92) in predicting death.

CONCLUSIONSPCIS can predict the complications and prognosis in children with severe HFMD. However, the existing scoring system of PCIS cannot fully assess the severity of HFMD.

Child, Preschool ; Critical Illness ; Female ; Hand, Foot and Mouth Disease ; diagnosis ; Humans ; Infant ; Male ; Prognosis

Objective To evaluate the outcome of mometasone furoate nasal spray (MFNS) used for 3 months on non-allergic rhinitis (NAR). Methods In this multicenter study, NAR patients were enrolled from eight hospitals and received MFNS 200 microgram once daily for 3 months. The patients were followed-up for three times (at baseline, month 1 and month 3) to record the symptom scores and nasal endoscopic appearances. At the same time, the adverse events frequency was recorded and analyzed.Results A total of 188 NAR cases were enrolled in the study. The total nasal symptom score assessment descended significantly at month 1 (1.70 ± 0. 75) and month 3 (0. 95 ± 0. 79) visits versus at baseline (2. 67 ± 0. 68, Z value were from - 11. 603 to - 10. 491, all P < 0. 01). The individual symptoms,including nasal stuffiness, nasal discharge, nasal stuffiness-related dizziness or headache, hyposmia, sleep quality, daily life activity, work or study efficiency, mental status, and whole body fatigue, also showed less scores at month 1 and month 3 visits versus at baseline (Z value were from - 11. 313 to - 6. 802, all P <0. 01). At the same time, nasal mucosal appearances assessed by endoscopy had lower scores at month 1 (1.40±0. 62) and month 3 (0. 75 ± 0. 71) visits versus at baseline (2. 27 ± 0. 73, Z value were from - 11. 484 to - 10. 002, all P <0. 01). Additionally, adverse events were only observed in 5. 3% cases with light rhinorrhagia and nasal dryness. No other side effect was found. Conclusions A 3-months administration of intranasal mometasone can effectively and safely improve NAR patients' clinical symptom and nasal mucosal appearances.

BACKGROUNDThe nevus of Ota, is a common benign pigmentary dermatosis, mainly involve innervation area of first and second branch of trigeminal nerve. The classification of nevus of Ota was proposed by Tanino, based on 26 cases of nevus of Ota from 1937 to 1940. Studies about its classification are rarely seen in last 70 years, while it is still practical today.

METHODSBased on the clinical photographs, 1079 consecutive patients with nevus of Ota were verified and reclassified according to the innervation areas of the trigeminal nerve branches.

RESULTSIn these 1079 cases, 866 patients were in line with Tanino's classification (80.26%), and 213 patients were not (19.74%). We put forward a new clinical classification (Peking Union Medical College Hospital classification, PUMCH classification) of nevus of Ota based on the innervation area of the trigeminal nerve branches, composed of 5 types and 14 subtypes. The 5 types were as follows: Type I - pigmentation maculeses involving the innervation area of one of the three trigeminal nerve branches, of which there were 424 cases (39.3%), comprising 6 subtypes; Type II - pigmentation macules involving the innervation area of two branches of the three trigeminal nerve branches, of which there were 221 cases (20.48%), comprising 4 subtypes; Type III - pigmentation macules involving the innervation area of all three trigeminal nerve branches, of which there were 361 cases (33.45%), comprising 2 subtypes; Type IV - bilateral type, in which the pigmentation macules involves the bilateral cheek, of which there were 63 cases (5.84%), comprising 2 subtypes; and Type V - complications occurred in the patient, of which there were 10 cases (0.93%).

CONCLUSIONThe new classification of nevus of Ota is based on the innervation area of the trigeminal nerve branches, and it covers all types of Tanino's classifications; on that basis, some new types and subtypes are brought in and cover almost every clinical condition.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Middle Aged ; Nevus of Ota ; classification ; diagnosis ; Trigeminal Nerve ; pathology ; Young Adult

Uch37 is a de-ubiquitinating enzyme that is activated by Rpn13 and involved in the proteasomal degradation of proteins. The full-length Uch37 was shown to exhibit low iso-peptidase activity and is thought to be auto-inhibited. Structural comparisons revealed that within a homo-dimer of Uch37, each of the catalytic domains was blocking the other's ubiquitin (Ub)-binding site. This blockage likely prevented Ub from entering the active site of Uch37 and might form the basis of auto-inhibition. To understand the mode of auto-inhibition clearly and shed light on the activation mechanism of Uch37 by Rpn13, we investigated the Uch37-Rpn13 complex using a combination of mutagenesis, biochemical, NMR, and small-angle X-ray scattering (SAXS) techniques. Our results also proved that Uch37 oligomerized in solution and had very low activity against the fluorogenic substrate ubiquitin-7-amino-4-methylcoumarin (Ub-AMC) of de-ubiquitinating enzymes. Uch37Δ(Hb,Hc,KEKE), a truncation removal of the C-terminal extension region (residues 256-329) converted oligomeric Uch37 into a monomeric form that exhibited iso-peptidase activity comparable to that of a truncation-containing the Uch37 catalytic domain only. We also demonstrated that Rpn13C (Rpn13 residues 270-407) could disrupt the oligomerization of Uch37 by sequestering Uch37 and forming a Uch37-Rpn13 complex. Uch37 was activated in such a complex, exhibiting 12-fold-higher activity than Uch37 alone. Time-resolved SAXS (TR-SAXS) and FRET experiments supported the proposed mode of auto-inhibition and the activation mechanism of Uch37 by Rpn13. Rpn13 activated Uch37 by forming a 1:1 stoichiometric complex in which the active site of Uch37 was accessible to Ub.
Binding Sites ; Catalytic Domain ; Chromatography, Gel ; Crystallography, X-Ray ; Humans ; Membrane Glycoproteins ; chemistry ; genetics ; metabolism ; Nuclear Magnetic Resonance, Biomolecular ; Protein Binding ; Protein Conformation ; Protein Multimerization ; Scattering, Small Angle ; Ubiquitin Thiolesterase ; chemistry ; genetics ; metabolism ; Ultracentrifugation