OBJECTIVE:To optimize the formulation of Methotrexate thermosensitive hydrogels,and to study the in vitro re-lease property of it. METHODS:Taking PLGA-PEG-PLGA as matrix and mannitol as viscosity modifiers,Methotrexate thermosen-sitive hydrogels were prepared. Using the absolute value of the deviation of gelation temperature between 35 ℃,its formulation was optimized by orthogonal test using the concentrations of PLGA-PEG-PLGA,methotrexate and mannitol as factors. The dialysis bag method was used to investigate accumulative release rate of Methotrexate thermosensitive hydrogels and methotrexate solution within 336 h in vitro. RESULTS:The optimal formulation was as PLGA-PEG-PLGA of 20%,methotrexate of 0.10% and mannitol of 0.10%;gelation temperature were 35.1,35.0,35.0℃. The average drug-loading rate was more than 90%. 12 d accumulative re-lease rate was more than 90%(r=3). Methotrexate solution has been substantially completely relased within 240 h. CONCLU-SIONS:Methotrexate thermosensitive hydrogels with sustained-release are prepared successfully,and the preparation technology is simple and practical.

Objective To prepare triamcinolone acetonide acetate(TAA)thermosensitive hydrogel for intra-articular injection,and to investigate its release in vitro. Methods TAA suspending thermosensitive hydrogel was prepared by using poly lactic-co-glycolic acid(PLGA)-polyethylene glycol(PEG)-PLGA as gel matrices,xanthan gum as suspending agent and NaCl as flocculant. It was evaluated preliminarily by determining its contents and its in vitro release. Results The best compositions for preparation of TAA suspending thermosensitive hydrogel were 25% PLGA-PEG-PLGA,0.05% xanthan gum, 0.9% NaCl and 4 mg·mL-1 TAA.The gelation temperature was 35.3 ℃ .The average recovery was(98.98±0.31)%. By the method of membraneless dissolution,the accumulative drug release was up to 83. 31% at 16 days. The drug release followed Ritger-Peppas methematical model. Conclusion The TAA thermosensitive hydrogel with obviously sustained release is expected to become a new drug delivery system for intra-articular injection.

Objective:To investigate the radiosensitizing effect of three flavonoids on ovarian cancer SKOV3 cells under hypoxia. Methods:The SKOV3 cells were divided into normoxic group and hypoxic group. The hypoxic SKOV3 cellular model in vitro was es-tablished and tested by measuring the expression profile of HIF-1αprotein in SKOV3 cells. Colony-forming assay was used to detect the radiosensitivity of normoxic and hypoxic SKOV3 cells. The cytotoxicity and radiosensitizing effects of flavonoids were evaluated on the basis of cell death and MTT assay. Results:The Western blot results showed that the gray intensity ratio of HIF-1α/β-Actin in hypoxia group was significantly higher than that in normoxia group (1. 068>0. 117). Radiosensitivity of hypoxic SKOV3 cells in hypoxia group was significantly lower than that in normoxia group. The survival rate of SKOV3 cells was decreased with the increase of concentration. When the concentration was increased, D0 and Dqin chrysin group and quercetin group were significantly decreased (P<0. 01), and SER was increased (P<0. 05). SER showed no significant difference in breviscapine group (P>0. 05). The overall radiobiological parameters of hypoxia group were higher than those of normoxia group. Conclusion: Hypoxia can induce the expression of HIF-1α in SKOV3 cells, which results in the decrease of radiosensitivity. Chrysin and quercetin can enhance the radiosensitivity of SKOV3 cells, and the enhancement is significant under hypoxia, while breviscapine is without such effect. The radiosensitizing effect may be achieved by the level decrease of HIF-1α in SKOV3 cells and inhibition of DNA damage repair.

Objective:To investigate the levels of serum pyrolysis-related factors cysteine protease-1 (caspase-1) and interleukin-18 (IL-18) in patients with gestational diabetes mellitus (GDM) and their relationship with insulin resistance (IR) .Methods:A total of 102 GDM patients admitted to Kaifeng Traditional Chinese Medicine Hospital from Apr. 2019 to Mar. 2021 were selected as the GDM group, and 102 healthy pregnant women undergoing obstetric examination in the same period were included as the normal group. The age, gestational week, fasting insulin (FINS) , pre-pregnancy body mass index (BMI) , triglycerides (TG) , fasting blood glucose (FBG) , total cholesterol (TC) , and homeostatic model insulin resistance index (HOMA-IR) and other materials were compared between the GDM group and the normal group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum caspase-1 and IL-18; Pearson method was used to analyze the correlation between serum caspase-1 and IL-18 levels and HOMA-IR in GDM patients; Logistic regression method was used to analyze the influencing factors of GDM.Results:The levels of TG [ (2.94±0.99) mmol/L vs (2.09±0.70) mmol/L], FBG [ (5.87±1.94) mmol/L vs (4.90±1.67) mmol/L], TC [ (5.72±1.92) mmol/L vs (5.03±1.68) mmol/L], FINS [ (11.45±3.87) mIU/L vs (6.92±2.34) mIU/L], HOMA-IR [ (3.05±0.78) vs (1.51±0.40) ] and levels serum caspase-1 [ (86.27±28.78) pg/mL vs (40.98±13.54) pg/mL] and IL-18 [ (44.26±14.56) pg/L vs (30.45±10.12) pg/L] in the GDM group were higher than those in the normal group (t=7.080, 3.827, 2.731, 10.116, 17.743, 14.381, 7.866, P<0.05) ; the levels of serum caspase-1 and IL-18 in GDM patients were positively correlated with HOMA-IR ( r=0.518, 0.555, P<0.05) ; FBG, TG, FINS, HOMA-IR, caspase-1, IL-18 were risk factors affecting the occurrence of GDM (95% CI=1.578-3.826, 1.454-3.311, 1.477-3.405, 1.678-4.265, 1.406-3.141, 1.511-3.551, P<0.05) . Conclusions:The levels of serum caspase-1 and IL-18 in patients with GDM are relatively high, which are significantly related to IR. Caspase-1 and IL-18 may be potential targets for the treatment of GDM.

Objective:To evaluate the influence of a moisturizer containing oat kernel oil for xeroderma and water content of the stratum corneum in children.Methods:From September to December 2022, 30 children with xeroderma were treated in the Dermatology Department of Tongzhou Maternal and Child Health Hospital of Beijing; 13 were males and 17 were females, and the age was 7.33±2.63 years. This was a single-center self-controlled trial. All children applied the moisturizer on the dry skin of the bilateral limbs two time per day for 14 days, and were followed up at 7 days and 14 days. Efficacy was evaluated according to the water content of the stratum corneum, visual scale, xerosis severity scale (XSS), Specified Symptom Sum Score (SRRC), Visual Analog Scale (VAS) and so on. and side-reactions were recorded.Results:After application of the moisturizer, the median of water content in the stratum corneum was 49.00 (33.83, 87.25), 48.84 (32.58, 100.34) at 7 d and 14 d respectively, showing significant increases compared with that at baseline (median 26.51 (16.00, 47.75) ( Z=-3.075, Z=-2.911, P<0.01). The visual scale, XSS, SRRC and VAS showed that compared with the baseline at 7 d, 14 d, the skin dryness and pruritus scores improved significantly ( Z=-4.424, -4.150, -3.943, -4.400; Z=-4.744, -4.409, -4.260, -4.409, P<0.01). Conclusions:The application of this moisturizer containing oat kernel oil could effectively improve skin dryness and the water content of the stratum corneum without serious adverse reactions.