ObjectiveTo investigate the effectiveness and safety of insulin glargine in the treatment of patients with type 2 diabetes mellitus (T2DM),and verify the new remedy called one central and three steps for T2DM.MethodsUsed multicenter,random,open and self-control study.Two hundred and three cases with T2DM treated with insulin glargine were divided into four groups according to different therapy:30 cases with one needle method,106 cases with one needle and one pill method,48 cases with one long-acting and several short-acting method,and 19 cases with one long-acting,one pill and several short-acting method.The changes of blood glucose,glycosylated hemoglobin (HbA1c),weight and so on before and after treatment were observed.ResultsThe levels of fasting plasma glucose(FPG),2 h postprandial plasma glucose (2hPPG) and HbA1c decreased significantly after treatment than those before treatment[(5.78 ±0.76)mmol/L,(8.37 ±:1.37) mmol/L,(6.81 ±0.38)％ vs. (11.73 ±4.49) mmol/L,(16.73 ±4.96) mmol/L,(9.43 ± 2.31 )％,P ＜ 0.01 ].The weight and body mass index had no obvious changes before and after treatment( P ＞ 0.05 ).There was significant difference in the level of FPG,2hPPG and HbA1c before and after treatment in four groups respectively(P＜0.01 ).There was only 1 case who occurred hypoglycemia during the treatment.ConclusionThe therapy,one central and three steps,is not only effective and safe,but also convenient and cheap for T2DM.

Objective:To clarify the anti-inflammatory effects and anti-endoplasmic reticulum stress effects of resolvin D2 (RvD2) in viral myocarditis mice and to explore its possible mechanism.Methods:Fifty male BALB/c mice were collected and assigned corresponding numbers. Then 40 male BALB/c mice were selected randomly with 10 mice in each group. They were set as normal control group, RvD2 control group, viral myocarditis group and RvD2 treatment group. Afterwards, mice in the RvD2 control group received continuous intraperitoneal injection of RvD2 for 7 days, while mice in the viral myocarditis group received intraperitoneal injection of Coxsackievirus B3 virus (CVB3) in the purpose of constructing an animal model of viral myocarditis. Then, mice in the RvD2 treatment group were given continuous intraperitoneal injection of RvD2 for 7 days. After these 7 days, the mice of each group were sacrificed and their cardiac tissue and serum samples were taken. The expression levels of serum inflammatory factors including IL-1β and TNF-α were detected by ELISA in each group of mice, and HE staining were used to detect the inflammatory cell infiltration in myocardial tissue of each group. Meanwhile, the expression levels of inflammation-related proteins IL-1β, TNF-α as well as endoplasmic reticulum stress-related proteins like GRP78 and Chop in the myocardial tissue in each group of mice were detected by Western blot experiment. The remaining 10 BALB/c mice were treated with intraperitoneal injection of RvD2 as well as GPR18 protein inhibitors after constructing the animal model of viral myocarditis mentioned above. In the end, the expression levels of GPR18 protein, inflammation-related proteins including IL-1β and TNF-α as well as endoplasmic reticulum stress-related proteins like GRP78 and Chop in the myocardial tissue of each group were detected by Western blot experiments.Results:Compared with the normal control group, the expression levels of inflammatory factors IL-1β and TNF-α in the serum of mice with viral myocarditis were significantly increased, and the degree of infiltration of inflammatory cells in myocardial tissue was also significantly increased. Besides, the expression levels of the inflammation-related proteins IL-1β, TNF-α as well as endoplasmic reticulum stress-related proteins including GRP78 and Chop increased largely. While compared with the viral myocarditis group, the expression levels of serum inflammatory factors IL-1β and TNF-α in the mice of the RvD2 treatment group were significantly reduced and the degree of infiltration of inflammatory cells in the cardiac tissue was significantly reduced. Also, the expression levels of inflammation-related proteins IL-1β and TNF-α as well as endoplasmic reticulum stress-related proteins GRP78 and Chop were significantly reduced. After intraperitoneal injection of RvD2 and GPR18 inhibitor, in the mice treated with viral myocarditis, the expression levels of IL-1β, TNF-α and endoplasmic reticulum stress-related proteins like GRP78 and Chop in myocardial tissue of these mice significantly increased when it came to compare with the RvD2 treatment group, while the expression levels of GPR18 protein were significantly reduced.Conclusions:RvD2 can inhibit the inflammatory response and endoplasmic reticulum stress injury in mice with viral myocarditis by binding to the membrane protein receptor GPR18, thus exerting a protective effect on heart.

Objective:To explore the value of ultrasound-based radiomics combined with clinical parameters in predicting lymph node metastasis of endometrial cancer.Methods:The clinical data and preoperative ultrasound images of 255 patients with endometrial cancer diagnosed after operation in the First Affiliated Hospital of Guangxi Medical University from January 2017 to February 2021 were analyzed retrospectively. The boundary of the tumor, that is, the region of interest(ROI), was determined manually by ITK-SNAP software, and the features were extracted from it. Through random sampling, the data were divided into training group used to build the model and verification group used to evaluate the reliability of the model at the proportion of 7∶3.In the training group, the spearman correlation coefficient was used as the threshold of 0.95 to remove the features with high correlation. The importance of the features were ranked by the decision tree model, the features of the top 6% importance were selected to establish a logical regression model, and then calculated the Radiomics score of each patient. On the basis of logical regression analysis, a comprehensive prediction model was established, the line diagram was drawn, and the prediction effect was evaluated by the analysis of the area under the subject working curve (AUC), calibration curve and the decision curve.Results:After dimensionality reduction and logical regression analysis, 20 features and 2 clinical parameters (CA125, CA153) were obtained to build the model. The AUC of training group and verification group in radiomics model and comprehensive prediction model were 0.81, 0.78 and 0.89, 0.85, respectively. The decision curve analysis showed that both of them had good clinical utility.Conclusions:The ultrasound-based radiomics model and the comprehensive model combined with relevant clinical parameters are effective in predicting lymph node metastasis of endometrial cancer.

To explore the role of methotrexate (MTX) in regulating the number of regulatory T cells (Treg) and the mRNA expression of transcription factor Foxp3.
 Methods: 1) We analyzed the number of Treg and the mRNA expression of Foxp3 by flow cytometry (FCM) and quantitative real-time PCR (qRT-PCR) respectively in patients with psoriasis vulgaris, patients with psoriasis vulgaris after the 8-week treatment of MTX, and healthy people. 2) BALB/c female mice were smeared with imiquimod (IMQ) cream for 6 days. We recorded the change of the lesion in mice every day. The morphological changes of lesion in mice were evaluated by the psoriasis area and severity index (PASI) and HE staining. 3) The mouse model was randomly divided into a control group and an MTX group. The MTX group was treated with different doses of MTX (38.5 and 77.0 nmol/L) on the third day of this experiment. The morphological changes of lesion in mice were evaluated by PASI and HE staining. We tested the number of Treg and the expression level of Foxp3 mRNA in splenic lymphocytes.
 Results: 1) The number of Treg and the expression level of Foxp3 mRNA were lower in psoriasis vulgaris patients than those in the healthy control group (P<0.05). After 8-week treatment of MTX, the number of Treg was increased (P<0.05) and Foxp3 mRNA level was up-regulated (P<0.01). 2) Typical psoriasis-like skin lesions, such as red scaly skin plaque were found after topical application of IMQ. Both the number of Treg in the splenic lymphocytes of mice and the Foxp3 mRNA level of Treg were reduced by IMQ (P<0.01 and P<0.05). 3) Different doses of MTX for mice showed the ability to improve skin lesion, increase the number of Treg in the spleen of mice and Foxp3 mRNA level in psoriatic dermatitis of mice (P<0.05).
 Conclusion: MTX is able to regulate the number of Treg and Foxp3 mRNA expression in psoriasis.
Adjuvants, Immunologic ; pharmacology ; Aminoquinolines ; pharmacology ; Animals ; Case-Control Studies ; Female ; Forkhead Transcription Factors ; metabolism ; Humans ; Imiquimod ; Immunosuppressive Agents ; administration & dosage ; pharmacology ; Lymphocyte Count ; Methotrexate ; administration & dosage ; pharmacology ; Mice ; Mice, Inbred BALB C ; Psoriasis ; drug therapy ; immunology ; metabolism ; pathology ; RNA, Messenger ; metabolism ; Random Allocation ; Spleen ; cytology ; T-Lymphocytes, Regulatory ; cytology ; drug effects ; metabolism

The blood-brain barrier (BBB) and the poor ability of many drugs to cross that barrier greatly limits the efficacy of chemotherapies for glioblastoma multiforme (GBM). The present study exploits albumin as drug delivery vehicle to promote the chemotherapeutic efficacy of paclitaxel (PTX) by improving the stability and targeting efficiency of PTX/albumin nanoparticles (NPs). Here we characterize PTX-loaded human serum albumin (HSA) NPs stabilized with intramolecular disulfide bonds and modified with substance P (SP) peptide as the targeting ligand. The fabricated SP-HSA-PTX NPs exhibited satisfactory drug-loading content (7.89%) and entrapment efficiency (85.7%) with a spherical structure (about 150 nm) and zeta potential of -12.0 mV. The drug release from SP-HSA-PTX NPs occurred in a redox-responsive manner. Due to the targeting effect of the SP peptide, cellular uptake of SP-HSA-PTX NPs into brain capillary endothelial cells (BCECs) and U87 cells was greatly improved. The low IC, prolonged survival period and the obvious pro-apoptotic effect shown by TUNEL analysis all demonstrated that the fabricated SP-HSA-PTX NPs showed a satisfactory anti-tumor effect and could serve as a novel strategy for GBM treatment.

Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People’s Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories’ results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.