Objective To investigate the expression of marrow-derived thyroid stimulating hormone β (TSHβ) splice variant in thyroid of mouse with autoimmune thyroiditis induced by thyroglobulin(Tg) immunization,and to analyze whether TSHβ splice variant participated in the pathological process of autoimmune thyroiditis.Methods Using random number table,forty-eight mice(24 females and 24 males) of 7 to 8 weeks old with body mass 20 to 25 g were randomly divided into 4 groups(12 females and 12 males in each group) based on body weight and gender.The control group:fed with deionized water; the Tg-treated group(TG):fed with deionized water,and immunized subcutaneously with 0.1 mg Tg at 8 weeks old,boost immunized twice at 11 and 15 weeks old,respectively; the high iodine-treated group (HI):fed with deionized water containing 0.05％ sodium iodide (NaI); the Tg combined with HI group (TG + HI):fed with deionized water containing 0.05％ NaI,and immunized the same way as the TG group did.Peripheral blood was collected after 8 weeks treatment,which was used for determination of total tetraiodothyronine (TT4),free tetraiothyronine (FT4),total triiodothyronine (TT3) and free triiodothyronine (FT3) with chemiluminescence immunoassay (CIA); thyroid glands were collected to examine the expression of TSHβ splice variant with SYBR Green fluorescent quantitative real-time PCR,and frozen sections were HE stained for observation of histopathological changes of thyroid cells under light microscopy.Results Under naked eyes,the thyroid gland enlarged significantly,and looked dark red in HI and TG + HI groups.Under an optical microscope,thyroid follicular epithelial cells presented cuboidal,with abundant cytoplasm,presented abundant glial in follicular cavity,without lymphocyte infiltration in the control group; in TG group,the thyroid follicular epithelial cells presented cuboidal,with some single scattered lymphocytes; in HI group,colloid volume expansion appeared in thyroid follicles,thyroid follicular epithelial cells presented low cuboidal or flat,with few single scattered lymphocytes; in TG + HI group,most colloid accumulative large follicles presented in thyroid,thyroid follicular epithelial cells presented flat,some destructive thyroid follicular structure and infiltrating lymphocytes appeared.The differences of FT3,TT4,FT4 and TSHβ splice variant between groups were statistically significant(F =4.00,12.54,31.92,214.29,all P ＜ 0.05).Compared to the control group,the serum TT3(nmol/L:0.92 ± 0.07 vs.1.30 ± 0.33,t =-2.24),TT4(nmol/L:1.30 ± 0.33 vs.95.60 ± 14.10,t =-3.02),FT4(pmoL/L:54.07 ± 3.67 vs.154.80 ± 0.01,t =-54.87) and the thyroids' TSHβ(× 10-3:4.11±0.32 vs.8.38 ± 0.22,t =-19.11) were higher in TG group(all P ＜ 0.05) ; the serum TT4(nmol/L:67.75 ± 11.91 vs.45.50± 3.85,t =3.55,P ＜ 0.05) was lower in HI group; the serum FT4(pmol/L:54.07 ± 3.67 vs.139.46 ± 30.00,t =-5.65) and the thyroids' TSHβ splice variant (× 10-3:4.11 ± 0.32 vs.5.33 ± 1.47,t =-5.95) were higher in TG + HI group (all P ＜ 0.05).Conclusions High iodine has aggravated thyroiditis of BALB/c mice induced by Tg immunization; the level of thyroid TSHβ in mice with autoimmune thyroiditis is higher; all of these results indicated that TSHβ is involved in the pathogenesis of autoimmune thyroiditis.

Objective This paper is intended for establishing quality standard of Ershiwuwei Shanhu pill. Methods The TLC was used to indentify Pyrethrum tatsienense, Sesami nigrum semen, Aquilariae lignum resinatum, Caryophmlli flos, Acori calami rhizoma, Chebulae fructus, Aucklandiae radix and Glycyrrhizae radix et rhizome. For hydroxysafflor yellow A, the HPLC system consisted of WondaSil-C18 (250 mm×4.6 mm, 5μm), methanol-acetonitrile- 0.7% phosphoric acid (26:2:72) as mobile phase, flow rate of 1.0 ml/min, detection wavelength at 403 nm. For liquiritin, the HPLC system consisted of WondaSil-C18 (250 mm×4.6 mm, 5μm), acetonitrile (A)-0.05% phosphoric acid (B) as mobile phase, flow rate of 1.0 ml/min, detection wavelength at 237 nm. And for crocin-I, the HPLC system consisted of WondaSil-C18 (250 mm×4.6 mm, 5μm), methanol-water (49:51) as mobile phase, flow rate of 1.0 ml/min, detection wavelength at 440 nm. Results The methods of TLC were simple with strong specificity and good reproducibility. The results of HPLC showed that calibration curve was linear in the ranges of 0.046 7-0.233 8μg for hydroxysafflor yellow A, and 0.510 6-1.531 8μg for liquiritin and 0.048 1-0.340 5μg for crocin-I. The average recovery rate was 102.01%, 99.50%and 99.32%, respectively. Conclusion The new method is more appropriate for the quality control of Ershiwuwei Shanhu pill.

Objective To investigate the expression and prognostic value of Ikaros6 in adult T-cell acute lymphoblastic leukemia(T-ALL) patients.Methods The RNA was extracted from mononuclear cells of bone marrow in 74 adult T-ALL patients.The expression of Ikaros6 was examined by reverse transcription-PCR,and the results were confirmed by sequencing.Clinical features and prognosis were analyzed based on clinical data.Results In 74 T-ALL patients,the incidence rate of Ikaros6 was 21.6 ％ (16/74).Extramedullary infiltrations were occurred often (x2 =4.084,P =0.043),had higher WBC (103.15 × 109/L vs 15.60×109/L,t =0.214,P =0.831),more severe anemia (75.95 g/L vs 107.00 g/L,t =1.504,P =0.142) and lower platelet count (26.0×109/L vs 67.0×109/L,t =1.421,P =0.164) in patients with Ikaros6 positive.Meanwhile Ikaros6-positive patients had inferior survival and were increased risk of relapse as compared with the Ikaros6-negative patients.Conclusions The incidence of Ikaros6 is high in adult T-ALL patients.Ikaros6-positive patients are more likely to have extramedullary infiltration and higher WBC,meanwhile they had inferior survival and increased risk of relapse.Thus Ikaros6 may be served as a valuable factor for risk stratification and prognosis evaluation in adult T-ALL patients.

Objective To describe the status of prevalence,awareness,treatment,and control of hypertension among the residents in severe historical endemic areas of Keshan Disease in Heilongjiang Province,and to provide scientific evidence for prevention and control of hypertension.Methods In December 2015,Yongjin,Yongli groups of Yongjin Village,and Fengnian,Fengtian,Fengfu groups of Fengnian Village in Fanrong Township,Fuyu County,Qiqihaer City,Heilongjiang Province were selected via the cross-sectional method.The residents aged 18 years or older were surveyed as respondents by cluster sampling.Demography,risk factors,hypertension related information were collected through questionnaire survey.Blood pressure,height and weight were measured through physical examination.Blood pressure measurement was conducted with Omron HEM-1020 electronic sphygmomanometer,the diagnostic criteria was Chinese Guidelines for Prevention and Treatment of Hypertension (revised in 2010).Results Totally 683 residents were surveyed,the valid participants were 669,the prevalence of hypertension was 49.2％ (329/669),the standardized prevalence was 37.9％,the prevalence of men [58.0％ (164/283)] was higher than that of women [42.7％ (165/386),x2 =15.103,P ＜ 0.01],the prevalence increased with increasing age (total,men,women:x2tendency =9.044,4.560,7.789,all P ＜ 0.01).The awareness of hypertensive patients was 60.8％ (200/329),the standardized awareness was 41.2％,the awareness of men [54.3％ (89/164)] was lower than that of women [67.3％ (111/165),x2 =5.836,P ＜ 0.05],the awareness of hypertensive patients increased with increasing age (total,men,women:x2tendency =3.638,2.686,2.419,all P ＜ 0.05).The treatment of hypertensive patients was 51.1％ (168/329),the treatment of men [43.9％ (72/164)] was lower than that of women [58.2％ (96/165),x2=6.711,P ＜ 0.05],the treatment of hypertensive patients increased with increasing age (total,men,women:x2tendency =4.422,2.704,3.633,all P ＜ 0.01).The control rate of hypertensive patients was 5.5％ (18/329),the control rate among the treatment was 10.7％ (18/168).Conclusions The standardized prevalence of hypertension among the residents of the severe historical endemic areas of Keshan disease in Heilongjiang Province is higher than the national average (25.2％),the standardized awareness is lower than the national average (46.5％),the treatment and the control are low.We should pay more attention to the hypertension in the severe historical endemic areas of Keshan disease.

Objective To explore the relationship between dysfunctional attitudes and social adaptability in patients with gestational diabetes mellitus in order to provide the basis for improving their social adaptability .Methods Two hundred and thirty-nine patients with gestational diabetes mellitus from May 2011 to May 2013 were chosen , and were surveyed by the questionnaire on dysfunctional attitudes and the social adaptability scale.Results The score of dysfunctional attitudes was (4.50 ±0.50), and the score of social adaptability was ( 2.25 ±0.36 ), and the dysfunctional attitudes was significantly correlated with social adaptability (P<0.05).The three dimensions of dysfunctional attitudes including perfect attitude , mandatory, seeking praise could predict 28.7%variation of social adaptability .Conclusions The dysfunctional attitudes in patients with gestational diabetes mellitus are at the medium level , and the social adaptability is at the low level . The three dimensions of dysfunctional attitudes can effectively predict the patients 'social adaptability , and the nurses should control the dysfunctional attitudes of patients so as to improve their social adaptability .

Objective To observe the effect of Delta-like ligand 4 (Dll-4) on the pathological structure of retina in early diabetic rats (DM) and its relationship with vascular endothelial growth receptor-2 (VEGFR-2).Methods A total of 70 male Sprague-Dawley rats were randomly divided into normal group and DM group,with 10 and 60 rats in each group,respectively.The rats of DM group was induced by intraperitoneal injection of streptozotocin to established DM model.The rats with blood glucose recovery and death were excluded,and the final 60 rats were included in the statistics.Rats in the normal group were injected with an equal volume of citric acid-sodium citrate buffer.Rats in the DM group were divided into DM 1 month (DM lm) group,DM 2 months (DM 2m) group,DM 3 months (DM 3m) group and DM 3m + Anti group,DM 3m + phosphate buffer solution (PBS) group by random number table method,and 10 rats in each group.In the DM 3m+Anti group,4 μl ofantiDll-4 polyclonal antibody was injected into the vitreous cavity,and the antibody concentration was 0.25 mg/ml.The DM 3m+PBS group was intravitreally injected with an equal volume of PBS.Five days after the injection,the rats were sacrificed.Rats in the DM 3m group and the normal group were not treated,and were sacrificed 3 months after the model was established.The structure and microvascular changes of the retina were observed by hematoxylin-eosin staining,and the total thickness of the retina was measured.The expression of Dll-4 and VEGFR-2 in the retina was detected by immunohistochemistry and fluorescence quantitative polymerase chain reaction (PCR).One-way analysis of variance was used to compare the expression of Dll-4 and VEGFR-2 in the retina of each group.The least significant difference t test was used to compare the two groups.Results Light microscopy showed that the retinal ganglion cells layer in the DM 3m group were obviously edematous,the inner and outer nuclear layers were thinner,the number of cells was reduced,the arrangement was disordered,the edema of outer plexiform layer was obvious,and the microvessels were abnormally dilated.In the DM 3m+Anti group,the edema of outer plexiform layer was lessened than that of the DM 3m group,and the other layers were not significantly different from the DM 3m group.Compared with the normal group,the total retinal thickness of the DM 3m group,the DM 3m+Anti group and the DM 3m+PBS group increased (t=5.596,3.290,4.286;P=0.000,0.008,0.002).Immunohistochemical staining showed that a small amount of Dl14 was positively expressed in the retinal ganglion cell layer of the normal group;a small amount of VEGFR-2 was positively expressed in the ganglion cell layer and the inner and outer nuclear layers.The positive expression of Dll-4 and VEGFR-2 in retinal vascular endothelial cells of DM 3m group increased significantly.The expression of Dll-4 was significantly decreased in the retinal layers and vascular endothelial cells ofDM 3m+Anti group,while the expression of VEGFR-2 was significantly increased.There was no significant difference between the positive expression of Dll4 and VEGFR-2 in the DM 3m+PBS group and the DM 3m group.The results of real-time PCR showed that the relative expression of Dll-4 and VEGFR-2 mRNA in the DM 3m group was significantly higher than that in the normal group (t=6.705,20.871;P＜0.05).Compared with DM 3m group,the relative expression of Dll-4 mRNA in DM 3m+Anti group decreased,and the relative expression of VEGFR-2 mRNA increased (t=2.681,3.639;P＜0.05).The relative expressions of Dll-4 and VEGFR-2 mRNA in the DM 3m+PBS group and DM 3m group were not statistically significant (t=0.513,0.657;P＜0.05).Conclusions The expression of Dll-4 in retinal vascular endothelial cells is gradually increased during the early retinopathy of DM rats.The expression of Dll-4 is inhibited,the expression of VEGFR-2 is up-regulated,and the plexus edema is alleviated.

Objective:To investigate the impact of China's Mental Health Law on the work of psychological counseling in colleges and universities, and to explore ways to improve the law. Methods: Totally 12 heads of college and university counseling centers in Beijing were conducted with semi-structured interviews. The average age of the interviewees was (40 ±7) years old, with master or doctor degrees in psychology or related disciplines. The method of content analysis was used to analyze the interviewees' understanding of the " Mental Health Law". Results: All of the 12 interviewees had gained some understanding of the "Mental Health Law", and accordingly amended the regulation of their counseling centers. Also, interviewees suggested the positive and negative impacts brought by the law, such as enhancing practitioners' legislative sense, clarifying their responsibilities and boundaries as college and university counseling, as well as difficulties to distinguish psychotherapy and psychological counseling, ambiguity in the legality of working with students who were diagnosed with mental disorders. Moreover, interviewees threw out suggestions on improving the law from the aspect of industry standard, supervision department and vocational qualification. Conclusion: The execution of "Mental Health Law" improves practitioners' legislative sense, clarifies their responsibility. Nevertheless, it does not clearly distinguish psychotherapy from psychological counseling, and be lack of regulation on the psychological counseling industry.

Immune checkpoint inhibitors (ICIs) targeting CTLA-4 and PD-1 /PD-L1 are increasingly used to treat several types of cancer.Although several agents have been approved,only 10％ to 30％ of patients have benefited from them.Some studies have shown that intestinal micro-ecology can affect the outcome of ICIs through immune regulation in cancer patients.This literature review s summarized the regulation and predictive functions of intestinal micro-ecology on ICIs treatment,and introduced possible mechanisms of intestinal micro-ecology that affacted the efficacy of immunotherapy.In addition,some approaches for detecting gut microbiome were also summarized.Gut microbiota highlighted in this review may serve as novel biomarkers to predict clinical outcomes in cancer patients.

Objective To understand the pathway of iodine intaking among Tibetan, and provide basic data for prevention and control of iodine deficiency disorders (IDD). Methods Through the method of random sampling, the boarding and day student aged 8 - 10 and women of childbearing age were conducted dietary survey to understand the condition of food intaking via the 24 h review method in 2015. Samples of urine, drinking water, dried beef, milk, Qula and fried noodles were collected and tested iodine level. Results Due to taking iodized salt three times a day with meals, the median of urinary iodine among 492 investigated boarding students was 179.2 μg/L;differently, the median of urinary iodine among 298 day students in this investigation was 79.6 μg/L who taking iodized salt only at lunch at school;and in the study, the median of urinary iodine among 158 women of childbearing age who took iodine-free salt daily was 33.7 μg/L. The iodine contents in 51 drinking water samples, 66 dried beef samples, 48 milk samples, 20 Qula samples and 37 fried noodle samples were quantified respectively, and the average iodine contents of each food were 0.8 μg/L in drinking water, 59.1 μg/kg in dried beef, 61.5 μg/kg in milk, 226.4 μg/kg in Qula and 17.0 μg/kg in fried noodles. The acceptable daily intake (ADI) of iodine of the boarding and day students aged from 8 to 10 and women of child bearing age were 234.0, 126.4 and 76.7 μg/d, respectively, among which the ADI of iodine with iodized salt were 208.0, 78.0 and 0.0 μg/d. Conclusion Consuming iodized salt is a main method to get iodine among Tibetans in Nangqian County, so that it is significant to carried out this measure for a long time for free to let them have iodized salt every day instead of iodine-free one.

Objective:To investigate the effects of cerium oxide nanoenzyme-gelatin methacrylate anhydride (GelMA) hydrogel (hereinafter referred to as composite hydrogel) in the repair of infected full-thickness skin defect wounds in mice.Methods:This study was an experimental study. Cerium oxide nanoenzyme with a particle size of (116±9) nm was prepared by hydrothermal method, and GelMA hydrogel with porous network structure and good gelling performance was also prepared. The 25 μg/mL cerium oxide nanoenzyme which could significantly promote the proliferation of human skin fibroblasts and had high superoxide dismutase activity was screened out. It was added to GelMA hydrogel to prepare composite hydrogel. The percentage of cerium oxide nanoenzyme released from the composite hydrogel was calculated after immersing it in phosphate buffer solution (PBS) for 3 and 7 d. The red blood cell suspension of mice was divided into PBS group, Triton X-100 group, cerium oxide nanoenzyme group, GelMA hydrogel group, and composite hydrogel group, which were treated with corresponding solution. The hemolysis of red blood cells was detected by microplate reader after 1 h of treatment. The bacterial concentrations of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli were determined after being cultured with PBS, cerium oxide nanoenzyme, GelMA hydrogel, and composite hydrogel for 2 h. The sample size in all above experiments was 3. Twenty-four 8-week-old male BALB/c mice were taken, and a full-thickness skin defect wound was prepared in the symmetrical position on the back and infected with MRSA. The mice were divided into control group without any drug intervention, and cerium oxide nanoenzyme group, GelMA hydrogel group, and composite hydrogel group applied with corresponding solution, with 6 mice in each group. The wound healing was observed on 3, 7, and 14 d after injury, and the remaining wound areas on 3 and 7 d after injury were measured (the sample size was 5). The concentration of MRSA in the wound exudation of mice on 3 d after injury was measured (the sample size was 3), and the blood flow perfusion in the wound of mice on 5 d after injury was observed using a laser speckle flow imaging system (the sample size was 6). On 14 d after injury, the wound tissue of mice was collected for hematoxylin-eosin staining to observe the newly formed epithelium and for Masson staining to observe the collagen situation (the sample size was both 3). Results:After immersion for 3 and 7 d, the release percentages of cerium oxide nanoenzyme in the composite hydrogel were about 39% and 75%, respectively. After 1 h of treatment, compared with that in Triton X-100 group, the hemolysis of red blood cells in PBS group, GelMA hydrogel group, cerium oxide nanoenzyme group, and composite hydrogel group was significantly decreased ( P<0.05). Compared with that cultured with PBS, the concentrations of MRSA and Escherichia coli cultured with cerium oxide nanoenzyme, GelMA hydrogel, and composite hydrogel for 2 h were significantly decreased ( P<0.05). The wounds of mice in the four groups were gradually healed from 3 to 14 d after injury, and the wounds of mice in composite hydrogel group were all healed on 14 d after injury. On 3 and 7 d after injury, the remaining wound areas of mice in composite hydrogel group were (29±3) and (13±5) mm 2, respectively, which were significantly smaller than (56±12) and (46±10) mm 2 in control group and (51±7) and (38±8) mm 2 in cerium oxide nanoenzyme group (with P values all <0.05), but was similar to (41±5) and (24±9) mm 2 in GelMA hydrogel group (with P values both >0.05). On 3 d after injury, the concentration of MRSA on the wound of mice in composite hydrogel group was significantly lower than that in control group, cerium oxide nanoenzyme group, and GelMA hydrogel group, respectively (with P values all <0.05). On 5 d after injury, the volume of blood perfusion in the wound of mice in composite hydrogel group was significantly higher than that in control group, cerium oxide nanoenzyme group, and GelMA hydrogel group, respectively ( P<0.05). On 14 d after injury, the wound of mice in composite hydrogel group basically completed epithelization, and the epithelization was significantly better than that in the other three groups. Compared with that in the other three groups, the content of collagen in the wound of mice in composite hydrogel group was significantly increased, and the arrangement was also more orderly. Conclusions:The composite hydrogel has good biocompatibility and antibacterial effect in vivo and in vitro. It can continuously sustained release cerium oxide nanoenzyme, improve wound blood perfusion in the early stage, and promote wound re-epithelialization and collagen synthesis, therefore promoting the healing of infected full-thickness skin defect wounds in mice.