[Effects of different doses of glucocorticoids on minimally invasive procedures in pain patients with type 2 diabetes].

Objective: To investigate the effects of different doses of glucocorticoids on minimally invasive procedures in patients with type 2 diabetes mellitus (T2DM), and optimize the clinical pathways of minimally invasive procedures. Methods: The clinical data of 284 patients with T2DM who received minially invasive procedures from the Department of Pain Medicine, West China Hospital, Sichuan University from May 2017 to May 2020 were retrospectively reviewed. The patients were divided into two groups according to the main diagnostic types: spine-related group (n=148) and herpes zoster group (n=136). According to the cumulative dose of glucocorticoids (GCs) per unit body surface area during the hospitalization, patients were further divided into three subgroups: low-dose group (GCs<3.5 mg/m2), medium-dose group (3.5 mg/m2 ≤GCs<7 mg/m2), and high-dose group (GCs≥7 mg/m2). The clinical characteristics of the patients in different subgroups of the two diseases groups were compared. The effects of the glucocorticoids on the pain intensity, blood glucose, length of hospital stay (LOS) and total hospitalization cost were compared among the 3 subgroups of the two diseases groups. Results: There were no significant differences in the age, gender, height, weight, visual analog scale (VAS) and fasting blood glucose before procedures between the two groups (all P>0.05). The VAS score of the low-dose group from the spine-related group was 4.5±1.6, which was higher than that of the medium-dose group (3.5±1.3) (P=0.004). VAS score was 4.3±1.3 in the medium-dose group and 4.4±1.6 in the high-dose group from the herpes zoster group, which were higher than that in the low-dose group (3.5±0.9) (P=0.006). In terms of blood glucose, the impact on the fasting blood glucose before and after the procedures in the low-dose group from the spine-related group was less than that in the medium dose group (P=0.013). In the herpes zoster group, the blood glucose of the low-dose group was (11±5) mmol/L, which had less influence on the blood glucose fluctuation during the hospitalization than that in the high-dose group [(15±5) mmol/L] (P<0.05). The LOS and hospitalization cost in the low-dose group from the spine-related group were (9±4) d and (10 583±4 851) yuan, respectively, which were less than those in the medium-dose group [(11±3) d and (15 202±7 418) yuan] and high-dose group [(13±6) d and (18 100±4 138) yuan] (all P<0.05); however, there was no significant difference among different subgroups in the herpes zoster group (all P>0.05). Conclusion: When used in the patients with T2DM undergoing minimally invasive procedures for spine-related diseases, low-dose glucocorticoids can obtain more clinical benefit than high dose, and high dose can lead to raised blood glucose, prolong the LOS, and increase the hospitalization cost.

[Hepatotoxicity associated with tumor immune checkpoint inhibitors].

Although tumor immune checkpoint inhibitors therapy brings survival benefits to cancer patients, it also faces many challenges, such as the occurrence of immune-mediated hepatotoxicity. Therefore, an in-depth understanding of the conditions, possible mechanisms, and risk factors that cause liver injury during the treatment of tumor immune checkpoint inhibitors will facilitate better clinical management.

H3K27me3 may be associated with Oct4 and Sox2 in mouse preimplantation embryos.

As a core member of polycomb repressive complex 2, the transcription and enzyme activity of enhancer of zeste homolog 2 (Ezh2) is directly involved in the trimethylation of lysine 27 on histone H3. In this study, the fluorescence intensity of H3K27me3 in mouse in vivo morulae and blastocysts was compared by indirect immunofluorescence staining. We found that demethylation of H3K27me3 occurred during the blastocyst stage. Real-time polymerase chain reaction was performed to investigate Ezh2 expression in oocytes and in preimplantation embryos. Ezh2 expression peaked during the zygote stage and gradually decreased from the 2-cell stage, exhibiting an inverse pattern when compared with Oct4 and Sox2 mRNA in mouse preimplantation embryos. To understand the role of development-related genes on the transcription of mouse Ezh2, a promoter assay was performed in NIH/3T3 cells. Ezh2 expression was markedly suppressed by Oct4 and Sox2 alone in a dose-dependent manner, while Ezh2 promoter activity in co-transfection with Nanog, Klf-4, and c-Myc groups showed no significant change as compared with the control. Our data suggest that the demethylation of H3K27me3 is caused by the degressive expression and activity of Ezh2 in blastocysts, leading to increased expression of developmentally important transcription factors. We also observed negative effects of Oct4 and Sox2 on the transcription of Ezh2 and identified Oct4 and Sox2 as novel negative regulators of Ezh2 at the post-translation level in a mouse preimplantation embryo.

[Inhibitory effect of samarium-153-labeled ethylenediaminetetramethylene phosphonate (EDTMP) on bone invasion and osteolysis in Walker 256 carcinoma bearing rats].

OBJECTIVE: To investigate the inhibitory effect of samarium-153 EDTMP on bone invasion and osteolysis in Walker 256 carcinoma bearing rats. METHODS: Invasion and resorption of tibia by Walker 256 carcinoma in rats were evaluated by X-ray and histological examination. RESULTS: Intravenous administration of 153Sm-EDTMP at a dose of 74 or 148 MBq/kg, the rat numbers with tibia invasion and bone resorption were reduced by fifty percent. 153Sm-EDTMP at a dose of 37 MBq/kg still exhibited inhibitory effect on bone invasion and osteolysis as compared with the control group. However, there was no indication of change in the weight of primary tumor even at the highest dose utilized. CONCLUSION: Samarium-153 EDTMP can inhibit bone invasion and osteolysis by Walker 256 carcinoma in rats, but it has no effect on the growth of the transplanted tumor. Therefore, that the effect of 153Sm-EDTMP is due to a reduction in tumor growth leading to decreased bone invasion and osteolysis can be reasonably ruled out.

[Study on pharmacokinetics of human granulocyte-macrophage colony stimulating factor (hGM-CSF) in rats using a sensitive immunoassay (ELISA)].

A sensitive and reliable sandwich enzyme linked immunosorbent assay (ELISA) has been developed for determination of concentration of recombinant human granulocyte-macrophage colony-stimulating factor (hGM-CSF). The assay is quantitative between 0.39-12.5 ng.ml-1 for bacterially synthesized hGM-CSF in rat serum and urine. The method was shown to be highly specific and did not significantly alter the determination when adding some potential interfering substances. After single sc injection of hGM-CSF 50, 100 or 200 micrograms.kg-1, a high hGM-CSF level was detected about 15 min in rat serum, the highest level of hGM-CSF was two apparent phases with half-lives T1/20 of 0.72, 0.70, 0.80 h and T1/28 of 8.77, 8.87 and 5.58 h. A detectable urinary excretion occured after sc injection of hGM-CSF 200 micrograms.kg-1, but the total urinary excretion of unchanged hGM-CSF was very low.

[Studies on the synthesis and bioactivity of some new shikimic acid derivatives].

Ten new shikimic acid derivatives, some of which are analogs of dioxolamycin were synthesized from methyl shikimate because the bioactivity of shikimic acid derivatives has received considerably less attention to date. Compounds 4-10, 12, 16 were subjected to antimicrobial test in vitro, and showed no activity (MIC greater than 25 micrograms/ml). Compounds 4-10, 12, 13, and 16 were subjected to cytostatic activity test against cultured L 1210 Leukemia cells in vitro. Compounds 4, 6, 13 and 16 showed cytostatic activity like dioxolamycin.

[Studies on the chemical components of Viscum coloratum. VI. Chirality of the acyl group of viscumneoside IV].

In order to determine the absolute configuration of the chiral center of viscumneoside IV, which was isolated from Viscum coloratum (Kom) Nakai, (R, S)-mevalonolactone was synthesized as shown in scheme 1. Then treatment with (S) (-)-1-phenylethylamine in THF gave two diasteromeric amides, which were transformed into the monoacetates and separated by HPLC. The first eluted peak (tR10.07 min.) had the (R)-configuration and the second one the (S)-configuration (tR11.20 min). Viscumneoside IV was treated with borane and hydrolyzed to give mevalonolactone which was treated with (S)-(-)-1-phenylethylamine in THF as mentioned above. The monoacetates of the resulting amides were subjected to HPLC. By comparison with the reference peaks, the absolute configuration at the acyl moiety of viscumneoside IV was shown to have the (R)-configuration.