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Chen-Yu Han, Xiao-Mei Ye, Jia-Ping Lu, Hai-Ying Jin, Ping Wang, Wei-Wei Xu, Min Zhang Department of Endocrinology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, 201700, People’s Republic of ChinaCorrespondence: Min Zhang, Department of Endocrinology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, No. 1158 of Gongyuan Road, Qingpu District, Shanghai, 201700, People’s Republic of China, Tel +86 18116016187, Fax +86 021-69719190, Email zhangmin1497mm@outlook.comObjective: Benaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA) that has been approved in the treatment of type 2 diabetes mellitus (T2DM). It is known to lead to significant weight loss, and it is hypothesized that changes in gut microbiota may play a significant role in such weight loss. However, it is unclear how gut microbiota and metabolites change as a result of benaglutide treatment.Methods: Healthy participants and patients with T2DM were included in this study. They received differentiated treatments, and stool specimens were collected separately. These stool specimens were subjected to 16S ribosomal RNA amplicon and metagenomic sequencing to create fecal metabolomic profiles. The diversity of gut microbiota and metabolic products in the stools of each participant was analyzed.Results: The data showed that Faecalibacterium prausnitzii was abundant in the gut microbiota of the control group, which was entirely made up of healthy individuals; however, it showed a statistically significant decrease in patients with T2DM treated with metformin alone, while no significant decrease was observed in patients treated with metformin combined with benaglutide. A metagenomic analysis revealed that benaglutide could improve the fecal microbiota diversity in patients with T2DM. Furthermore, there was a statistically significant correlation between the changes in the metabolites of patients with T2DM and the changes in their gut microbiota (including F. prausnitzii) after treatment with metformin and benaglutide.Conclusion: These findings suggest that the weight-reducing effect of benaglutide is attributed to its ability to normalize the gut microbiota of patients with T2DM, particularly by increasing the abundance of F. prausnitzii.Keywords: benaglutide, gut microbiota, metabolites, type 2 diabetes mellitus, T2DM

Chen-Yu Han, Xiao-Mei Ye, Jia-Ping Lu, Hai-Ying Jin, Wei-Wei Xu, Ping Wang, Min Zhang Department of Endocrinology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, 201700, People’s Republic of ChinaCorrespondence: Min Zhang, Department of Endocrinology, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, No. 1158 of Gongyuan Road, Qingpu District, Shanghai, 201700, People’s Republic of China, Tel +86 18116016187, Fax +86 021-69719190, Email zhangmin1497mm@outlook.comBackground: Exogenous insulin antibody syndrome (EIAS) is an immunological disorder caused by circulating insulin antibodies (IAs), featuring hypersensitivity to exogenous insulin and insulin resistance. With the wide use of recombinant human insulin and insulin analogs, there has been a significant proliferation of EIAS.Case Report: We describe two cases of diabetes mellitus (DM) with hyperinsulinemia and high serum levels of IAs. They had never been exposed to methimazole, glutathione, lipoic acid, and other sulfhydryl drugs, but they all received insulin treatment. The patient in case 1 had recurrent hypoglycemia before hospitalization. A prolonged oral glucose tolerance test (OGTT) showed hypoglycemia with inappropriately high insulin levels. The patient in case 2 was hospitalized for diabetic ketosis. An OGTT indicated hyperglycemia with hyperinsulinemia and low levels of C-peptide. IAs induced by exogenous insulin in the two patients with DM were positive at high titers, prompting a diagnosis of another condition—EIAS.Conclusion: We discussed the differences between these two cases of EIAS in clinical manifestations and treatment and summarized all patients of EIAS treated in our department to date.Keywords: diabetes mellitus, exogenous insulin, hyperinsulinemia, insulin antibodies, IAs

Chad Yixian Han,1 Yogesh Sharma,2,3 Alison Yaxley,1 Claire Baldwin,1 Richard Woodman,2 Michelle Miller1 1Caring Futures Institute, College of Nursing and Health Sciences, Flinders University, Adelaide, SA, Australia; 2College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia; 3Department of General Medicine, Flinders Medical Centre, Adelaide, SA, AustraliaCorrespondence: Chad Yixian Han, Caring Futures Institute, College of Nursing and Health Sciences, Flinders University, Sturt Road, Bedford Park, SA5042; GPO Box 2100, Adelaide, SA, 5001, Australia, Tel +61 8201 3911, Email chad.han@flinders.edu.auPurpose: Pre-frailty and frailty in older adults are associated with poor health outcomes and increase health-care costs, and further worsening during hospitalization. This study aimed to examine the effect of an individualized hospital to home, exercise-nutrition self-managed intervention for pre-frail and frail hospitalized older adults.Patients and Methods: Older adults admitted to an acute medical unit of a tertiary hospital in South Australia who were pre-frail or frail were recruited from September 2020 to June 2021, randomized to either control or intervention group and followed up at 3 and 6 months. The outcome variables were program adherence, frailty status by the Edmonton Frail Scale (EFS) score, lower extremity physical function, handgrip strength, nutritional status, cognition, mood, health-related quality of life, risk of functional decline, unplanned readmissions.Results: Participants were 79.2 ± 6.6 years old, 63% female, mostly frail (67%), with EFS of 8.6± 1.9. Adherence to the inpatient and home visits/telehealth intervention were high (91± 13% and 92± 21%, respectively). Intention-to-treat analysis using linear regression models showed that participants in the intervention group had significantly greater reduction in EFS at 3 (− 3.0; 95% CI: − 4.8 to − 3.0) and 6 months (− 2.5; 95% CI: − 3.8 to − 1.0, P< 0.001 for both) compared to the control group; particularly the functional performance component. There were also improvements in overall Short Physical Performance Battery score at 3 (4.0; 95% CI: 1.3 to 6.6) and 6 months (3.9; 95% CI: 1.0 to 6.9, P< 0.05 for both), mini-mental state examination (2.6; 95% 0.3– 4.8, P=0.029) at 3 months and handgrip strength (3.7; 95% CI: 0.2– 7.1, P=0.039) and Geriatric Depression Scale, at 6 months (− 2.2; 95% CI: − 4.1 to − 0.30, P=0.026) in the intervention group as compared to control.Conclusion: This study provided evidence of acceptability to a patient self-managed exercise-nutrition program that may benefit and alleviate pre-frailty and frailty in hospitalised older adults.Keywords: frailty, self-management, exercise, nutrition therapy

Yong-Guang Wei, Cheng-Kun Yang, Zhong-Liu Wei, Xi-Wen Liao, Yong-Fei He, Xin Zhou, Hua-Sheng Huang, Chen-Lu Lan, Chuang-Ye Han, Tao Peng Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaCorrespondence: Tao PengDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuang Yong Road 6, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaTel +86-771-5356528Fax +86-771-5350031Email pengtaogmu@163.comBackground: The protein high-mobility group AT-hook 1 (HMGA1) has been demonstrated that modulated cellular proliferation, invasion, and apoptosis with a poor prognosis in miscellaneous carcinomas. However, the mechanism of circumstantial carcinogenesis and association with the immune microenvironment of HMGA1 in hepatocellular carcinoma (HCC) had not been extensively explored.Methods: The gene expression, clinicopathological correlation, and prognosis analysis were performed in the data obtained from TCGA. The results were further validated by ICGC and GEO database and external validation cohort from Guangxi. The HMGA1 protein expression was further examined in the HPA database. Biological function analyses were conducted by GSEA, STRING database, and Coexpedia online tool. Using TIMER and CIBERSORT method, the relationship between immune infiltrate and HMGA1 was investigated.Results: In HCC, HMGA1 had much higher transcriptional and proteomic expression than in corresponding paraneoplastic tissue. Patients with high HMGA1 expression had a poor prognosis and unpromising clinicopathological features. High HMGA1 expression was closely related to the cell cycle, tumorigenesis, substance metabolism, and immune processes by regulating complex signaling pathways. Notably, HMGA1 may be associated with TP53 mutational carcinogenesis. Moreover, increased HMGA1 expression may lead to an increase in immune infiltration and a decrease in tumor purity in HCC. CIBERSORT analysis elucidated that the amount of B cell naive, B cell memory, T cells gamma delta, macrophages M2, and mast cell resting decreased when HMGA1 expression was high, whereas T cells follicular helper, macrophages M0, and Dendritic cells resting increased.Conclusion: In conclusions, HMGA1 is a potent prognostic biomarker and a sign of immune infiltration in HCC, which may be a potential immunotherapy target for HCC.Keywords: hepatocellular carcinoma, HMGA1, prognostic signature, bioinformatics, immune filtration

Cui-yan Han,1,2 Li-ling Yue,2 Ling-yu Tai,1 Li Zhou,2 Xue-yan Li,2 Gui-hua Xing,2 Xing-gang Yang,1 Ming-shuang Sun,1 Wei-san Pan1 1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 2Qiqihar Medical University, Qiqihar, People’s Republic of China Abstract: The epidermal growth factor receptor (EGFR) serves an important function in the proliferation of tumors in humans and is an effective target for the treatment of cancer. In this paper, we studied the targeting characteristics of small peptides (AEYLR, EYINQ, and PDYQQD) that were derived from three major autophosphorylation sites of the EGFR C-terminus domain in vitro. These small peptides were labeled with fluorescein isothiocyanate (FITC) and used the peptide LARLLT as a positive control, which bound to putative EGFR selected from a virtual peptide library by computer-aided design, and the independent peptide RALEL as a negative control. Analyses with flow cytometry and an internalization assay using NCI-H1299 and K562 with high EGFR and no EGFR expression, respectively, indicated that FITC-AEYLR had high EGFR targeting activity. Biotin-AEYLR that was specifically bound to human EGFR proteins demonstrated a high affinity for human non-small-cell lung tumors. We found that AEYLR peptide-conjugated, nanostructured lipid carriers enhanced specific cellular uptake in vitro during a process that was apparently mediated by tumor cells with high-expression EGFR. Analysis of the MTT assay indicated that the AEYLR peptide did not significantly stimulate or inhibit the growth activity of the cells. These findings suggest that, when mediated by EGFR, AEYLR may be a potentially safe and efficient delivery ligand for targeted chemotherapy, radiotherapy, and gene therapy. Keywords: EGFR, small peptide, tumor targeting, lung cancer, NLC