Objective To investigate the clinical efficacy of Liraglutide(Lir) combined with short-term insulin intensive therapy in newly diagnosed overweight/obese patients with type 2 diabetes mellitus (T2DM). Methods A total of 144 newly diagnosed overweight/obese patients with T2DM admitted to the Endocrinology Department of Anqing Municipal Hospital from November 2022 to October 2023 were enrolled and randomly divided into intensive treatment(Int) group and Lir group with 72 cases in each group. The intensive Int group received oral Metformin tablets combined with subcutaneous injections of insulin before meals and insulin glargine before bedtime. The Lir group received subcutaneous injections of Liraglutide in addition to the Int group. The changes in blood pressure (BP),weight,BMI,WC,WHR,blood glucose(BG),blood lipids,SUA,HOMA-IR,HOMA-β,BG target time,insulin dosage and injection frequency,number of cases of meal-time insulin discontinuation and incidence of hypoglycemia before and after 1,4,and 12 weeks of treatment were evaluated and compared between the two groups. Results After 4 and 12 weeks of treatment,the BP,weight,BMI,WC and WHR were significantly lower than before treatment in the Lir group (P<0.05). 2 hPG at 1,4 and 12 weeks after treatment was significantly lower in Lir group than in Int group (P<0.05),and HbA1c after 12 weeks of treatment were significantly lower in Lir group than in Int group[(6.49±0.41)％ vs (8.31±0.75)％,P<0.05]. After 4 and 12 weeks of treatment,HDL-C,1 hC-P and HOMA-β were significantly higher in Lir group than in Int group,while TC,TG,LDL-C,SUA and HOMA-IR was significantly lower in Lir group than in Int group (P<0.05). The time for BG to reach the standard was significantly shorter in Lir group than in Int group[(4.23±1.55) vs (6.23±1.78) d,P<0.05].After treatment for 4 and 12 weeks,the basal insulin dosage decreased significantly. After treatment for 1,4,and 12 weeks,the insulin dosage during meals,the number of subcutaneous insulin injections,and the incidence of hypoglycemia were significantly reduced in Lir group than in Int group(P<0.05).The number of patients with discontinued insulin during meals has significantly increased (P<0.05). Conclusions In newly diagnosed overweight/obese patients with T2DM,the combination of Lir and insulin intensive therapy is beneficial in controlling BP,weight,BMI,WC,WHR,BG and SUA,promoting the improvement of pancreatic β cell function,shortening the time for BG to reach the standard,reducing insulin dosage and injection frequency,and lowering the risk of hypoglycemia.

Objective To investigate the clinical efficacy of Liraglutide(Lir) combined with short-term insulin intensive therapy in newly diagnosed overweight/obese patients with type 2 diabetes mellitus (T2DM). Methods A total of 144 newly diagnosed overweight/obese patients with T2DM admitted to the Endocrinology Department of Anqing Municipal Hospital from November 2022 to October 2023 were enrolled and randomly divided into intensive treatment(Int) group and Lir group with 72 cases in each group. The intensive Int group received oral Metformin tablets combined with subcutaneous injections of insulin before meals and insulin glargine before bedtime. The Lir group received subcutaneous injections of Liraglutide in addition to the Int group. The changes in blood pressure (BP),weight,BMI,WC,WHR,blood glucose(BG),blood lipids,SUA,HOMA-IR,HOMA-β,BG target time,insulin dosage and injection frequency,number of cases of meal-time insulin discontinuation and incidence of hypoglycemia before and after 1,4,and 12 weeks of treatment were evaluated and compared between the two groups. Results After 4 and 12 weeks of treatment,the BP,weight,BMI,WC and WHR were significantly lower than before treatment in the Lir group (P<0.05). 2 hPG at 1,4 and 12 weeks after treatment was significantly lower in Lir group than in Int group (P<0.05),and HbA1c after 12 weeks of treatment were significantly lower in Lir group than in Int group[(6.49±0.41)％ vs (8.31±0.75)％,P<0.05]. After 4 and 12 weeks of treatment,HDL-C,1 hC-P and HOMA-β were significantly higher in Lir group than in Int group,while TC,TG,LDL-C,SUA and HOMA-IR was significantly lower in Lir group than in Int group (P<0.05). The time for BG to reach the standard was significantly shorter in Lir group than in Int group[(4.23±1.55) vs (6.23±1.78) d,P<0.05].After treatment for 4 and 12 weeks,the basal insulin dosage decreased significantly. After treatment for 1,4,and 12 weeks,the insulin dosage during meals,the number of subcutaneous insulin injections,and the incidence of hypoglycemia were significantly reduced in Lir group than in Int group(P<0.05).The number of patients with discontinued insulin during meals has significantly increased (P<0.05). Conclusions In newly diagnosed overweight/obese patients with T2DM,the combination of Lir and insulin intensive therapy is beneficial in controlling BP,weight,BMI,WC,WHR,BG and SUA,promoting the improvement of pancreatic β cell function,shortening the time for BG to reach the standard,reducing insulin dosage and injection frequency,and lowering the risk of hypoglycemia.

The active copper-containing carbon nanodots were prepared by hydrothermal method, and then characterized by fluorescence spectroscopy and UV-visible absorption spectroscopy.Subsequently, a highly sensitive and selective electrochemical biosensor was fabricated on the basis of this synthesized carbon nanodots with electro-deposition technique.The electrode behavior was investigated by cyclic voltammetry, electrochemical impedance spectroscopy, and differential pulse voltammetry.Furthermore, the catalysis mechanism was studied.The experimental results indicated that the biosensor exhibited a strong electrocatalytic activity toward the oxidation of uric acid (UA).What′s more, the interference from ascorbic acid and dopamine was eliminated effectively.Under the optimum conditions, there were linear relationships between the anodic peak current and the concentration of UA (1.00-300.0 μmol/L), and the limit detection was 0.30 μmol/L (S/N=3).The prepared biosensor had advantages such as easy fabrication, strong anti-interference ability, high sensitivity, and wide detection range, and could be used for real sample detection.

AIM:To establish a mouse model of immuno-inflammation in central nervous system (CNS) associated with cognitive dysfunction.METHODS:C57BL/6J male mice were divided into 3 groups.Lipopolysaccharide (LPS) was intraperitoneally injected into the mice to induce cognitive impairment.Morris water maze test, passive avoidance test and pole test were used to observe the behavioral changes of mice.The histomorphology was analyzed by the method of immunofluorescence.The detailed molecular mechanism was determined by Western blot.RESULTS:Compared with saline group, LPS induced mouse sickness behavior and memory loss.Microglia activation and neuronal loss in the hippocampus were observed.The expression of neuroinflammatory proteins COX-2 and iNOS in the brain of LPS-induced mice was increased.CONCLUSION:Intraperitoneal injection of LPS induces cognitive dysfunction in mice.

AIM:To investigate the protective effect of lycopene on primary mouse cerebrocortical neurons ex -posed to tert-butyl hydroperoxide ( t-BHP) and its mechanisms of in vitro.METHODS:Primary cerebrocortical neurons of newborn C57 mice were extracted and divided into normal group , t-BHP group, lycopene +t-BHP group and lycopene group.The neuronal damage was induced by t-BHP exposure for 24 h, and the cell viability was examined by MTT assay . ROS content was measured by flow cytometry , and the protein levels of Bax , Bcl-2, caspase-3, cleaved caspase-3 and cyto-chrome C were examined by Western blot .RESULTS:The primary mouse cortical neurons expressed MAP-2 protein.Ly-copene at concentration of 4μmol/L reversed the decrease in cell viability .Flow cytometry revealed that lycopene treatment attenuated ROS content under the condition of t-BHP exposure.In addition, the protein level of Bcl-2 was increased, and the expression of Bax , cleaved caspase-3 and cytochrome-C was suppressed in lycopene +t-BHP group.CONCLUSION:The protective effect of lycopene on cortical neurons with t-BHP-induced injury may be involved in the mechanism of neuro-nal antioxidative response by down-regulating caspase-3 and Bax/Bcl-2 through the mitochondrial apoptotic pathway .

Objective To compare the differences in the use of effects of improved and traditional abdominal positioning locator card in the empty nest elderly diabetic patients with insulin pen injection. Methods 100 discharged cases of empty nest elderly diabetic patients with insulin treated were enrolled. They were divided into two groups by random digital table method, 50 cases in traditional positioning card injection group and 50 cases in improved positioning card injection group. Usage rate of two sets of locator cart, adverse reactions in local skin injection and blood glucose control were observed for 12 months. Results After 12 months, 44 cases occupied 88%in improved positioning card injection group were not about using positioning card while 30 cases occupied 60%in traditional positioning card injection group. The difference was statistical significance (P<0.05). After 12 months, only 3 cases in improved positioning card injection group appeared local injection site reactions which was significantly lower than 31 cases in the traditional positioning card injection group, and the difference was statistically significant (P<0.05);12 months later, fasting blood glucose (FBG), 2 hour postprandial blood glucose (2 h PBG), glycosylated hemoglobin (HbA 1c) of improved positioning card injection group and traditional positioning card injection group [(7.0 ±1.5) mmol/L and(7.8±1.9)mmol/L,(10.7±2.1)mmol/L and(12.3±2.2)mmol/L,(7.1±1.3)% and(7.7±1.5)%] were all decreased significantly than before. The difference was statistically significant (P<0.05). FBG,2 h PBG, HbA1c of improved positioning card injection group were decreased more significantly than that in traditional positioning card injection group and the difference was statistically significant (P<0.05). The standard rate of HbA1c [64% (32/50)] in improved positioning card injection group was higher than that in traditional positioning card injection group [42%(21/50)]. The difference was statistically significant (P<0.05). Conclusions The modified abdominal injection locator card can improve patients′positioning card usage rate, optimize insulin injection technique, reduce the occurrence of adverse reactions in local skin injection and improve the control of blood glucose.

Objective To establish the CTRP4 transgenic mouse model and investigate the function of the novel adipocytokine CTRP4.Methods CTRP4 overexpressing vector in pCAGGS was firstly constructed and then microinjected into zygote to establish the founder transgenic mice .F1 heterozygotes were generated by founder mice mating with wildtype mice, and the CTRP4 transgenic homozygotes were generated by F 1 littermates.The genotype was confirmed by PCR and test cross method .The expression level of CTRP 4 in transgenic mice was detected by western blot .Result The human CTRP4 transgenic homozygote mice line was established , and the expression level of CTRP 4 was confirmed raletively high in detected tissues including heart , liver, brain and kidney . Conclusion The human CTRP4 transgenic mice was successfully established .

Objective To research whether the inhibitory oligonucleotides could improve the immune status of the BXSB mice. The purpose was to provide a valuable direction for treating systemic lupus erythematosus. Methods 3-month-old BXSB lupus mice were divided into three groups (including inhibitory oligonucleotides group, saline group and blank control group). The 24 hours urine proteins were determined before treatment. After treatment,the urine protein, anti-dsDNA, peripheral blood lymphocytes apoptosis and immune complex in renal glomeruli were measured. Results Before treatment,the urine proteins had no statistical differences among the three groups ( P > 0.05 ).After treatment,the urine protein, anti-dsDNA levels in inhibitory oligonucleotides group were significantly lower than that of control group(P < 0.01 ). Apoptosis of peripheral blood lymphocytes in inhibitory oligonucleotides group was significantly higher than that of control group( P < 0.05 ) ,immune complex in renal glomeruli in inhibitory oligonucleotides group was significantly lower than that of the other groups ( P < 0.05 ). Compared with saline group, inhibitory oligonucleotides had prolonged life period of BXSB mice ( P < 0.01 ). Conclusion The inhibitory oligonucleotides could improve immune status of BXSB, and could put off the disease progression.

BACKGROUND: In recent years, nano-carriers have been regarded as the most promising technologies for breakthrough the bottleneck of gene transfer. Polyamidoamine dendrimer (PAMAM) is a kind of new nanometer material. PAMAM can transfer target gene to the cell with high efficiency and lower toxic both in vivo and in vitro.OBJECTIVE: To evaluate the antitumour effects of survivin antisense oligonucleotide (Survivin-asODN) carried by PAMAM on colorectal cancer transplanted subcutaneously in nude mice.DESIGN, TIME AND SETTING: An in vivo experiment regarding tumor gene therapy was performed from February to August in 2008 at the Laboratory of Bionanometer Engineering, Research Institute of Micro/nanometer Science & Technology of Shanghai Jiao Tong University and Central Laboratory of Zhujiang Hospital of Southern Medical University.MATERIALS: Human colorectal cancer cells SW620 were from Shanghai Cell Institute of Chinese Academy of Sciences.PAMAM dendrimer was offered by the Bionanometer Engineering Laboratory, Research Institute of Micro/nanometer Science & Technology, Shanghai Jiao Tong University. Lipofectamine ~(TM)2000 was purchased from Invitrogen, USA. Survivin-asODN was synthesized by Shanghai Bioengineering Company.METHODS: The PAMAM and cation liposome were respectively mixed with Survivin-asODN to generate the transfection complex carrying antisense gene. The shape of the complex was observed by transmission electron microscope, the particle size was determined by laser particle size analysator and the zeta potential was measured by an analytical tool. The encapsulating efficiency and release progress in vitro were determined by ultraviolet spectrophotometer in centrifuging method. Human colorectal cancer cells SW620 at logarithmic phase were inoculated into the abdominal region of 18 Blab/C nude mice subcutaneously to produce transplanted tumor models in colorectal cancer nude mice, which were randomly divided into 3 groups: liposome, PAMAM and blank control groups. They were injected respectively with Hposome-survivin-asODN complex,PAMAM-survivin-as ODN transfection complex and seroculture liquid. The volumes of tumor were surveyed in the 2 groups.Western blotting method was used to determine the survivin gene expression in the transplanted tumor tissue.MAIN OUTCOME MEASURES: Particle size, zeta potential, gene loading level, encapsulation efficiency, release rate of cationic liposome-survivin-asODN complex and PAMAM-survivin-asODN complex, as well as survivin expression rate and apoptosis rate after transfection, inhibition rate of the transplanted tumor growth, Survivin protein expression and activity in the transplanted tumor cells.RESULTS: The particle size of PAMAM-survivin-asODN complex was smaller (P < 0.01), but the zeta potential was greater (P < 0.05), compared with liposome-survivin-asODN. There was no significant difference between PAMAM and liposome groups in terms of gene loading rate and transfection efficiency. DNA release lasted for 14 days for PAMAM, but only 5 days for liposome.After colorectal cancer cell transfection, survivin protein expression was lower, but apoptosis rate was higher, in the PAMAM-survivin-asODN complex than in the liposome-survivin-asODN complex (P < 0.05).CONCLUSION: PAMAM facilitates delivery of Survivin-asODN into transplanted colorectal cancer cells SW620. As a result,survivin protein expression was decreased, and apoptosis rate was increased in vivo which inhibited transplanied tumour growth.

Objective:To investigate the effect of blocking BRCAA1 gene expression with siRNA on the proliferation of tumor cell line MCF-7 and Rb gene expression.Methods:RNAi was employed to specifically knock down BRCAA1 expression.MCF-7 cells were transfected with complexes constructed with lipids and chemically synthesized Pre-designed anti-BRCAA1 siRNAs.The total RNA was isolated and reversely transcribed after 48 h.The expressions of BRCAA1 and Rb mRNA were determined by Real-Time PCR.Results:Compared with negative control,transfected MCF-7 cells had a 42.3% decrease in expression of BRCAA1 mRNA and an 11.1% increase in Rb mRNA expression.The inhibitory rate of MCF-7 cells proliferation was(81.6?6.1)%.Conclusion:There may be some antagonistic effect between BRCAA1 gene and Rb gene in proliferation of tumor cells,which provides a potential target for anti-tumor gene therapy.