Objective To investigate the relationship between serum 25-(OH) D3 and autoimmune thyroid diseases (AITD).Methods Serum levels of 25-(OH) D3, thyroid antibodies (thyroid stimulating hormone receptor antibody (TRAb), TGAb (thyroid globulin antibody), thyroid peroxidase antibody (TPOAb) and thyroid function of 32 cases patients with Graves' diseases (GD), 17 cases patients without remission of GD,10 cases patients with remission of GD,35 cases patients with Hashimoto's thyroiditis (HT),and 58 cases healthy subjects were measured,and the relationships between serum 25-(OH) D3 and the above clinical index were analyzed.Results The serum level of 25-(OH) D3 in patients with GD or HT were obviously lower than that in healthy subjects((50.75±17.60) μg/L, (36.40±21.65) μg/L, (43.05±19.53) μg/L,P＜0.05).No significant difference of the serum level of 25-(OH) D3 was found between patients refractory of GD and those with GD in remission((32.43±17.50) μg/L, (31.88±14.48) μg/L,P=0.866).However,compared with the normal control group,both diseased groups showed significantly decrease (P＜0.05).No correlation was found between serum 25-(OH) D3 and TRAb, FT3, Fr4 as well as TSH in GD group.No correlation was found between serum 25-(OH) D3 and TGAb, TPOAb (P＞ 0.05).Conclusion Serum vitamin D levels are decreased in patients with AITD, which has been speculated as a potential therapeutic method for AITD, though further investigations are needed to establish the precise role of 25-(OH) D3 in AITD.

Objective:To evaluate the effectiveness and safety of 3.5% lidocaine hydrochloride ophthalmic gel for eye surface anesthesia.Methods:A multicenter, randomized, double-blind, placebo controlled clinical trial was conducted in 10 hospitals in China from August 2018 to April 2019 under the approval of an Ethics Committee of Beijing Hospital (No.2018BJYYEC-014-02). A total of 220 fellow eyes of 220 subjects who received ocular surgery in one eye were actually enrolled according to a same included criteria in different institutes.The 220 eyes were randomly divided into control group and trail group.Two drops of lidocaine hydrochloride gel were dropped at about 5 mm away from corneal limbus at 6 o'clock direction of experimental eye of the trail group, and the blank gel was used in the eyes of the control group in the same way.The pain sensation was assessed with a 0.3 mm toothless micro forceps on conjunctiva within a specified time, and ''pain'' or ''no pain'' was answered by the subjects.The primary effective indexes, namely the number of eyes and percentage of ''no pain'' within 5 minutes following dropping, as well as the secondary indexes including the onset time point of the drug and the duration of anesthesia were recorded and evaluated.Safety evaluation took ocular and system adverse events into account.Results:Within 5 minutes after dropping, ''no pain'' occurred in 104 eyes (94.55%) and 29 eyes (26.36%) in the trail group and control group, respectively, showing a significant difference between the two groups ( χ2=106.948, P<0.001). And there was a significant difference in anesthesia onset time between the trail group and control group (40.0 seconds vs. 300.0 seconds) ( Z=-15.17, P<0.001). The duration of anesthesia was 860.5 (577.5, 1 180.0) seconds in the trail group and 676.0 (280.0, 1 401.0) seconds in the control group, with no statistically significant difference between the two groups ( Z=0.898, P>0.05). The incidence of adverse events in the trail group and control group were 5.45% (6/110) and 4.55% (5/110), respectively, without statistical significance between them ( P=1.000). Conclusions:The 3.5% lidocaine hydrochloride is a safe, effective, easy to use and high-quality surface anesthesia drug for eye surgery.

Objective:To investigate the therapeutic efficacy and potential mechanisms of integrin α vβ 3-targeted radionuclide therapy (TRT) in combination with anti-programmed cell death protein ligand 1 (PD-L1) immunotherapy. Methods:Integrin α vβ 3-targeted molecule Arg-Gly-Asp (RGD) was conjugated with Evans blue (EB) and then labeled with 177Lu to obtain 177Lu-EB-RGD. The radioactivity and radiochemical purity were determined. MicroSPECT imaging, biodistribution, and in vivo therapeutic efficacy were subsequently performed in MC38 murine colon cancer models. Volume of tumor and body mass of mice were observed to assess the therapeutic efficacy and safety ( n=9 in each group). Flow cytometry was used to evaluate therapy response of saline-treated (control, group A), 18.5 MBq 177Lu-EB-RGD-treated (group B), 10 mg/kg PD-L1 antibody-treated (group C), TRT combined with immunotherapy-treated (group D, 18.5 MBq 177Lu-EB-RGD and 10 mg/kg PD-L1 antibody) mice and alterations in tumor microenvironment (PD-L1 + immune cells, CD8 + T cells and regulatory T cells). Independent-sample t test and repeated measures analysis of variance were used for data analysis. Results:The radioactivity of 177Lu-EB-RGD was (55.85±14.00) GBq/μmol. SPECT imaging clearly visualized the MC38 tumors in mice models with high uptake and long retention time, the tumor/muscle ratio reached 14.87±0.88 at 24 h postinjection, while less uptake and retention in normal tissues. Tumor uptake of 177Lu-EB-RGD was significantly higher than that of 177Lu-RGD 4 h post-injection ((12.00±1.60) vs (3.69±0.37) %ID/g; t=8.63, P<0.01). The efficacy results between each treatment group was significantly different ( F=7.32, P=0.03) at day 6 post-treatment. The combination therapy showed the most outstanding anti-tumor efficacy with 7/9 mice showed complete response. Flow cytometry results showed that TRT up-regulated the PD-L1 expression significantly, namely, PD-L1 + immune cells in group B and group A were significantly different (CD45 + /PD-L1: 2.34% vs 0.95%, CD11b + /PD-L1: 2.41% vs 0.66%; t values: 11.17 and 8.70, both P<0.01); immunotherapy and combination therapy dramatically stimulated the infiltration of CD8 + T cells (2.07% vs 0.26%, 2.71% vs 0.26%; t values: 4.10 and 6.03, both P<0.05). Conclusion:TRT in combination with immunotherapy synergistically enhance anti-tumor efficacy, which is expected to play a role in the treatment of patients with advanced tumor where TRT can be applied.

ObjectiveTo investigate the effect of porcine large intestine-processed Dahuang （Radix et Rhizoma Rhei） on defecation in constipation model mice and the possible mechanism. MethodsFifty Kunming mice were randomized to blank group （n=10） and model group （n=40）. Loperamide suspension at the dose of 8 mg/（kg·d） was given by gavage for four consecutive days to establish a model of constipation. The 24 successfully modeled mice were randomly divided into model group， processed Dahuang group， lactulose group， raw Dahuang group， with six mice in each group. Moreover， six randomly selected mice were chosen as control group. Since the fifth day， 8 mg/（kg·d） of loperamide suspension by gavage was given to the model group， processed Dahuang group， raw Dahuang group， and lactulose group； two hours later， the processed and raw Dahuang groups were administered with 0.6 g/（kg·d） of processed and raw Dahuang suspension， respectively， while the lactulose group was given 0.6 g/（kg·d） of latulose suspension， and the blank group and the model group were given 0.2 ml/10 g of distilled water by gavage， all for four days. The general condition， body weight after the last gavage， number of fecal particles within six hours， fecal wet weight， fecal water content ratio， intestinal propulsion rate and colonic histology changes by HE staining of each group were detected. ResultsThe body weight of the mice in the raw Dahuang group was significantly lighter than that in the other groups （P＜0.05 or P＜0.01）. The number of fecal particles， fecal wet weight and intestinal propulsion rate of mice significantly decreased in the model group than in the blank group （P＜0.05 or P＜0.01）. Compared to those in the model group， the number of fecal particles and fecal wet weight in the processed Dahuang group， lactulose group and raw Dahuang group significantly increased， and the fecal water content ratio in the raw Dahuang group increased as well （P＜0.05 or P＜0.01）. Compared to those in the processed Dahuang group， the number of fecal particles and fecal wet weight in the raw Dahuang group decreased， while the fecal water content ratio increased （P＜0.05 or P＜0.01）， and the fecal water content ratio in the lactulose group increased significantly （P＜0.05）. The intestinal propulsion rate in the processed Dahuang group was higher than that in the model group， lactulose group and raw Dahuang group （P＜0.05 or P＜0.01）. Histopathological analysis showed that the colonic crypts and goblet cells in the blank group were normal and clear， and the colonic muscular layer was thicker. The colonic crypts of the mice in the model group were damaged， with reduced goblet cells to varying degrees and changed colonic muscularis. In the lactulose group and raw Dahuang group， part of the crypts were broken， and the goblet cells were damaged to varying degrees， while in the processed Dahuang group， still the colonic tissue structure of the mice was relatively clear， and the colonic crypts and goblet cells were relatively normal， with thickened muscular layer of the colon. ConclusionPorcine large intestine-processed Dahuang could improve defecation in constipation model mice， and reduce the drastic purgation function of raw Dahuang， for which the mechanism may be related to the protection of colon histopathological damage.