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.

Basal insulin is essential for blood glucose management. However, its clinical application in China faces multiple challenges such as delayed initiation, low initial dosage, and inadequate dose adjustments. The BEYOND series of studies were conducted to provide an evidence-based basis for optimizing basal insulin use in China. Moreover, basal insulin is advancing towards weekly preparation. Phase Ⅲ clinical trials have demonstrated that weekly basal insulin is both effective and safe, and its reduced injection frequency may help address the challenges associated with basal insulin use in China.

Objective:To explore the association of different obesity measurement indexes on serum C-reactive protein (CRP) in Chinese adult women.Methods:The data were obtained from baseline and follow-up surveys of the urban Breast Cancer Screening Program in Shuangliu District, Chengdu. A total of 441 adult women were included in the study. A questionnaire survey, physical examination, and laboratory testing were conducted on the subjects. Multivariate logistic regression model, two-level mixed effects logistic regression model, and restricted cubic spline method were used to investigate the linear and nonlinear correlation between different obesity measurement indexes and serum CRP in adult women.Results:For every 1 unit increase in BMI, waist circumference (WC), and adiposity, the risk of elevated serum CRP or exacerbation of chronic low-grade inflammation in adult women increased by 16.5%, 5.0%, and 11.1% ( P<0.05), respectively. Both BMI and adiposity were nonlinear correlated with serum CRP. Using BMI=24.0 kg/m 2 as the reference point, serum CRP level increased with the increase of BMI when BMI >24.0 kg/m 2. Using adiposity=30% as the reference point, serum CRP level increased with the increase of adiposity when adiposity >30%. Conclusions:Overall, obesity reflected by BMI had the strongest association with serum CRP in adult women, followed by body fat content reflected by adiposity, and central obesity reflected by WC had the weakest association with CRP. Adult women with BMI >24.0 kg/m 2 or adiposity >30% are at high risk for obesity-related inflammatory manifestations.

Objective:To evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pseudomyxoma peritonei (PMP).Methods:In this descriptive case series study, we retrospective analyzed the records of PMP patients treated with CRS and HIPEC between January 2013 and June 2023 at Affiliated Cancer Hospital and Institute of Guangzhou Medical University. The inclusion criteria were as follows: (1) Aged 18 to 75 years and nonpregnant women. (2) Histologically confirmed diagnosis of pseudomyxoma peritonei. (3) Karnofsky Performance Scale (KPS)>70. (4) The functions of major organs such as the heart, liver, lungs, and kidneys can tolerate major surgery for long periods of time. (5) No evidence of extra-abdominal metastasis. Patients with extensive intra-abdominal adhesions or severe infectious diseases were excluded. The main outcomes were overall survival (OS) and postoperative major complications. The postoperative major complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). We used the peritoneal cancer index (PCI) score to quantitatively assess the peritoneal metastases and the completeness of cytoreduction (CCR) score at the end of surgery (CCR-0 and CCR-1 considered to be complete CRS).Results:A total of the 186 PMP patients with a median age of 56 (interquartile range extremes (IQRE), 48-64) years were included, 65 (34.9%) males and 121 (65.1%) females. The median peritoneal cancer index (PCI) score was 28 (20-34). Appendiceal origin accounted for 91.4%. Histological types were low grade in 99 patients (53.2%), high grade in 57 patients (30.6%), and 55 patients (29.6%) received complete cytoreduction (CCR-0/1). The median operative duration was 300 (211-430) minutes for all patients. Treatment-related 30-day mortality was 2.7%; 90-day mortality 4.3%; reoperation 1.6%; and severe morbidity 43.0%. Within the entire series, anemia(27.4%), electrolyte disturbance(11.6%), and hypoalbuminemia(7.5%) were the most frequent major complications (grade 3-4). The incidences of gastrointestinal anastomotic leakage, abdominal bleeding, and abdominal infection were 2.2%, 2.2%, and 4.3%, respectively. After a median follow-up of 38.1 (95%CI:31.2-45.1) months, the 5-year OS was 50.3% (95%CI: 40.7%-59.9%) with a median survival time of 66.1 (95%CI: 43.1-89.1) months. The survival analysis showed that patients with pathological low grade, low PCI, and low CCR score had better survival with statistically significant differences (all P<0.05). Further stratified into complete and incomplete CRS subgroups, the 5-year OS of the CCR-0 and CCR-1 subgroups was 88.9% (95%CI: 68.3%-100.0%) and 77.6% (95%CI: 62.7%-92.5%), respectively; and 42.0% (95%CI: 29.5%-54.5%) in the CCR-2/3 subgroup. Conclusions:CRS and HIPEC may result in a long-term survival benefit for PMP patients with acceptable perioperative morbidity and mortality. This strategy, when complete CRS is possible, could significantly prolong survival for strictly selected patients at experienced centers.

Objective:To evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pseudomyxoma peritonei (PMP).Methods:In this descriptive case series study, we retrospective analyzed the records of PMP patients treated with CRS and HIPEC between January 2013 and June 2023 at Affiliated Cancer Hospital and Institute of Guangzhou Medical University. The inclusion criteria were as follows: (1) Aged 18 to 75 years and nonpregnant women. (2) Histologically confirmed diagnosis of pseudomyxoma peritonei. (3) Karnofsky Performance Scale (KPS)>70. (4) The functions of major organs such as the heart, liver, lungs, and kidneys can tolerate major surgery for long periods of time. (5) No evidence of extra-abdominal metastasis. Patients with extensive intra-abdominal adhesions or severe infectious diseases were excluded. The main outcomes were overall survival (OS) and postoperative major complications. The postoperative major complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). We used the peritoneal cancer index (PCI) score to quantitatively assess the peritoneal metastases and the completeness of cytoreduction (CCR) score at the end of surgery (CCR-0 and CCR-1 considered to be complete CRS).Results:A total of the 186 PMP patients with a median age of 56 (interquartile range extremes (IQRE), 48-64) years were included, 65 (34.9%) males and 121 (65.1%) females. The median peritoneal cancer index (PCI) score was 28 (20-34). Appendiceal origin accounted for 91.4%. Histological types were low grade in 99 patients (53.2%), high grade in 57 patients (30.6%), and 55 patients (29.6%) received complete cytoreduction (CCR-0/1). The median operative duration was 300 (211-430) minutes for all patients. Treatment-related 30-day mortality was 2.7%; 90-day mortality 4.3%; reoperation 1.6%; and severe morbidity 43.0%. Within the entire series, anemia(27.4%), electrolyte disturbance(11.6%), and hypoalbuminemia(7.5%) were the most frequent major complications (grade 3-4). The incidences of gastrointestinal anastomotic leakage, abdominal bleeding, and abdominal infection were 2.2%, 2.2%, and 4.3%, respectively. After a median follow-up of 38.1 (95%CI:31.2-45.1) months, the 5-year OS was 50.3% (95%CI: 40.7%-59.9%) with a median survival time of 66.1 (95%CI: 43.1-89.1) months. The survival analysis showed that patients with pathological low grade, low PCI, and low CCR score had better survival with statistically significant differences (all P<0.05). Further stratified into complete and incomplete CRS subgroups, the 5-year OS of the CCR-0 and CCR-1 subgroups was 88.9% (95%CI: 68.3%-100.0%) and 77.6% (95%CI: 62.7%-92.5%), respectively; and 42.0% (95%CI: 29.5%-54.5%) in the CCR-2/3 subgroup. Conclusions:CRS and HIPEC may result in a long-term survival benefit for PMP patients with acceptable perioperative morbidity and mortality. This strategy, when complete CRS is possible, could significantly prolong survival for strictly selected patients at experienced centers.