Objective To explore the effect of ghrelin on insulin release of mouse pancreatic islet ?-cell line(NIT-1 cells) and its probable mechanism.Methods NIT-1 cells were incubated in high-glucose DMEM with ghrelin.Then,the media was sampled for the assay of insulin by RIA.The(mRNA) expressions of glucose transporter 2(GluT2),pancreatic-duodenal homeobox-1(PDX-1),inwardly rectifying potassium channel with two transmembrane regions(Kir6.2) and sulphonylurea receptor 1(SUR-1) in the cells were detected by using RT-PCR.The cell proliferation was determined by MTT assay.Results(1) 10~(-9)mol/L to 10~(-7)mol/L of ghrelin inhibited dose-dependently the high-glucose challenged insulin release of the NIT-1 cells.(2) The mRNA expression of Kir6.2,but not GluT2,PDX-1and SUR-1,was down-regulated by 10~(-7)mol/L of ghrelin.(3) Ghrelin had no effect on proliferation of the cells.Conclusions Ghrelin inhibits high-glucose induced insulin secretion of the islet ?-cells.This effect may be secondary to the down-regulation for the expression of Kir6.2,(a component) of ATP-sensitive potassium channel.

Objective To investigate the effects of glucagon-like peptide-1(GLP-1)on the expression of apoptosis-related molecules including programmed cell death 5(PDCD-5)gene in pancreatic ? cells induced by proinflammatory cytokines.Methods Mouse islet ?-cell line NIT-1 was incubated for 24 h with cytokine mixture(Mix)in the absence or presence of GLP-1.The apoptotic cells were assayed by flow cytometry after stained with annexin V-FITC and propidium iodide(PI).The expressions of PDCD5,Fas,and caspase 3 were detected using reverse transcription-polymerase chain reaction(RT-PCR)and Western blot.Results The number of both annexin V single positive cells and annexin V/PI double positive cells significantly increased in the cells treated with 30 U/mL interleukin-1?(IL-1?)+ 100 U/mL interferon-?(IFN-?)+ 100 U/mL tumor necrosis factor-?(TNF-?).The expressions of PDCD5,Fas,and caspase 3 at both mRNA and protein levels were upregulated in the cells exposed to the cytokines.The above-mentioned effects of the cytokines were reversed by 10 nmol/L of GLP-1.Conclusion These data show that the proinflammatory cytokines cause pancreatic ? cell apoptosis via activation of PDCD5 signal pathway and that GLP-1 inhibits the upregulation of PDCD5 expression and the subsequent event of apoptosis induced by the cytokines.

Objective To investigate the efficacy and safety of domestic exenatide injection versus imported exenatide injection in type 2 diabetic patients with inadequate glycemic control on monotherapy or combination therapy of metformin and insulin secretagogues. Methods A multicenter, randomized, parallel-controlled, and non-inferiority trial was carried out. A total of 240 subjects were randomized at a 1:1 ratio to add domestic exenatide injection (trial group) or imported exenatide injection (control group) on the background therapies. The primary endpoint of efficacy was HbA1C change from baseline to week 16. The secondary endpoints of efficacy were the proportion of HbA1C<7.0%, and the changes in fasting plasma glucose (FPG), 2 h plasma glucose after standard meal (2hPG), 7-point self monitoring of blood glucose (7P-SMBG), and body weight from baseline to week 16. Results Among subjects of per-protocol sets, adjusted mean HbA1C reduction was -1.07% in the trial group versus -1.06% in the control group after 16 weeks of treatment. The lower boundary of the two-sided 95% confidence intervals of the mean HbA1C reduction difference between the trial and control groups was -0.29%, which was more than -0.35%, suggesting that the predefined statistical criterion for non-inferiority was achieved. The proportions of subjects achieving HbA1C<7.0% at the end of the 16-week treatment were 56.19% and 54.08% in the trial and control groups, respectively (P>0.05). The changes in FPG, 2hPG, 7P-SMBG and body weight from baseline to week 16 were comparable between the two groups (all P>0.05). Moreover, the incidences of hypoglycemia and adverse events were similar between the two groups (both P>0.05). Conclusion In type 2 diabetic patients inadequately controlled by monotherapy or combination therapy of metformin and insulin secretagogues, the efficacy of cotreatment with domestic exenatide injection is not inferior to that of imported product ones, with a similar safety profile.

Objective To evaluate the efficacy and safety of biphasic insulin aspart 30 (BIAsp30)plus metformin in type 2 diabetes subjects switching from basal insulin plus oral antidiabetic drugs (OAD)Methods During 16 weeks, multiple-center, open-label, and single-arm study including 2 weeks of screening period,4 weeks of run-in period,and 16 weeks of treatment period were carried out. Subjects with type 2 diabetes mellitus inadequately controlled on basal insulin therapy with or without oral antidiabetic drugs were switched to twice-daily BIAsp30 plus metformin with dose titration to achieve fasting plasma glucose target. Results Of the 293 Chinese subjects exposed to trial drugs [age: ( 54.0±9.6 ) years, diabetes duration: ( 8.54±5.49 ) years, body mass index: (24.89±3.28)kg/m2, baseline HbA1c: 8.16% ±0.89%], 122 were previously treated with basal insulin analogues and 169 with human basal insulin. At end of the trial ,the mean reduction of HbA1 c was 1.30% ±0.96% (P＜0. 01 ). The proportion of patients achieved HbA1c＜7.0% and HbA1c ≤6.5% was 60.4% and 38.9% respectively. 8-point plasma glucose measurements showed significant improvements at all the time points examined ( all P＜0. 01 ) ,and the average value of all 8 points measured decreased from ( 10.53±2.58 ) mmol/L atbaseline to (7.79± 1.58 ) mmol/L at the end of treatment ( P＜0. 01 ), reduced by 2.76 mmol/L. Postprandial glucose increments were significantly reduced after breakfast ( -1.73 mmol/L,P＜0.01 )and dinner ( -1.28 mmol/L,P＜0.01 ), while no significant reduction was observed after lunch ( -0.09 mmol/L, P = 0. 734 5 ). No severe adverse effect and no major hypoglycemia were reported. The overall hypoglycaemia rate was 2.68 events/subject year. The average weight gain was (0. 76 ±0. 14 )kg (P＜0. 0l ). Conclusion Twice-daily BIAsp30 plus metformin is effective and safe to type 2 diabetic subjects inadequately controlled on basal insulin treatment.BIAsp30 treatment should be considered for type 2 diabetic subjects who have unsatisfactory response to previous basal insulin treatment.

Objective To compare the efficacy of trastuzumab plus pertuzumab (HP) combined with either nab-paclitaxel plus carboplatin or docetaxel plus carboplatin as neoadjuvant therapy for HER2-positive breast cancer in real-world clinical practice. Methods Clinical data of HER2-positive breast cancer patients who received neoadjuvant therapy with either HP combined with nab-paclitaxel plus carboplatin or HP combined with docetaxel plus carboplatin and subsequently underwent surgery were retrospectively collected from 11 tertiary grade-A hospitals in Hebei Province from June 2019 to December 2021. The total pathological complete response (tpCR) rates of the two groups were compared. Results A total of 76 patients were included in the study, with 47 in the nab-paclitaxel group and 29 in the docetaxel group. The tpCR rate was significantly higher in the nab-paclitaxel group than that in the docetaxel group (72.3% vs. 48.3%, χ²=4.463, P=0.035). Subgroup analysis indicated that patients older than 40 years, with cN2-3, cTNM stage Ⅲ, hormone receptor-positive status, and Ki67>30% had significantly higher tpCR rates in the nab-paclitaxel group than those in the docetaxel group (P<0.05). Conclusion In real-world clinical practice, the efficacy of HP combined with nab-paclitaxel plus carboplatin as neoadjuvant therapy for HER2-positive breast cancer is superior to that of HP combined with docetaxel plus carboplatin.

Objective: To explore the changes and clinical significance of serum prolactin and estrogen levels in women with autoimmune thyroid diseases. Methods: From January 2018 to December 2018, 76 newly diagnosed female patients with autoimmune thyroid diseasein outpatient and inpatient clinics of the People's Hospital of Hebei Province were selected as study group, including 40 cases of Graves' disease and 36 cases of hashimoto's thyroiditis.And 60 healthy women with age matched were selected as control group.Serum estrogen, prolactin, thyroid hormone and their antibodies, IL-2, IL-6, IL-10 and other related indicators were determined before and after treatment, and the correlation analysis was performed. Results: The levels of estrogen[(302.85±78.62)ng/L], prolactin [(15.98±4.18)μg/L], IL-2 [(224.45±61.28)ng/L], IL-6 [(211.46±67.25)ng/L] in the study group were all higher than those in the control group [(228.4±71.38)ng/L, (10.35±3.21)μg/L, (120.34±38.27)ng/L, (165.51±50.09)ng/L], and the IL-10 level in the study group was lower than that in the control group [study group: (15.65±4.86)ng/L; control group: (20.12±4.83)ng/L] , there were statistically significant difference between the two groups(t=5.78, 3.11, 8.98, 3.94, all P<0.05). After treatment, the levels of estrogen [(237.11±70.42)ng/L], prolactin[(10.40±3.32)μg/L], IL-2[(122.67±38.99)ng/L], IL-6[(166.24±52.09)ng/L] in the study group were significantly decreased compared with before treatment(t=5.56, 3.76, 9.04, 4.02, all P<0.05), and the IL-10 level [(19.96±4.93)ng/L] was significantly increased (t=3.95, P<0.05). However, there was no statistically significant difference in thyroid antibody between the two groups (P>0.05). Estrogen level was positively correlated with prolactin, IL-2 and IL-6(r=0.327, 0.298, 0.336, all P<0.01), and negatively correlated with IL-10(r=-0.285, P<0.05). Conclusion Elevated levels of estrogen and prolactin can stimulate the production and release of inflammatory cytokines, thus affecting the level of thyroid hormone, which is closely related to the female autoimmune thyroid disease.

ObjectiveTo investigate the effect of transcranial direct current stimulation (tDCS) combined with constraint-induced weight training (CIWT) on Pusher syndrome after stroke. MethodsA total of 60 stroke inpatients with Pusher syndrome in the First Affiliated Hospital of Soochow University from January to December, 2021 were randomly divided into tDCS group, CIWT group and combination group, with 20 cases in each group. The three groups accepted routine rehabilitation training, the tDCS group received anode tDCS, the CIWT group received CIWT of the affected lower limb, and the combination group received CIWT of the affected lower limb and tDCS, for eight weeks. They were assessed with Berg Balance Scale (BBS), Fugl-Meyer Assessment-Lower Extremities (FMA-LE), Burke Lateropulsion Scale (BLS) and Holden Walking Functional Ambulation Category (FAC) before and after treatment. ResultsAfter treatment, the scores of BBS, FMA-LE, BLS and FAC improved (|t| > 1.452, P < 0.05) in all the groups, and improved the most in the combination group (|F| > 1.827, P < 0.05). ConclusiontDCS combined with CIWT of the affected lower extremity can effectively improve the function of stroke patients with Pusher syndrome.