1.Preparation and detection of controlled release insulin ultra-porous hydrogel
Denghui HU ; Xiuli WANG ; Leilei REN
Journal of Pharmaceutical Practice 2021;39(1):44-48
Objective To prepare an ultra-porous hydrogel capable of controlled release and investigate the drug loading, releasing, administration route and efficacy with insulin as a model drug. Methods The polymer interpenetrating network method was used to prepare ultra-porous hydrogels (SPH-IPN). Insulin was selected as a model drug to study the drug loading and efficacy. Fourier transform infrared spectroscopy and nuclear magnetic resonance carbon spectroscopy were used to investigate the structure of the gel. The swelling ratio and porosity were measured to evaluate the gel performance. Results The drug loading capacity of insulin ultra-porous hydrogel was 3.19%. The insulin-loaded freeze-dried gel exhibited good hypoglycemic effect on diabetic rats in 1−24 hours from the experimental results on rats with subcutaneous implantation. Conclusion The subcutaneously embedded lyophilized insulin ultra-porous hydrogel provided good controlled release efficacy. It maintained stable blood glucose levels within 24 hours.
2.Correlation between body mass index and clinicopathological characteristics of papillary thyroid carcinoma
Zhixin YANG ; Chang DENG ; Daixing HU ; Denghui WANG ; Jiang ZHU ; Xinliang SU
Chinese Journal of Endocrine Surgery 2021;15(5):494-498
Objective:To analyze the relationship between body mass index (BMI) and clinicopathological characteristics of papillary thyroid carcinoma (PTC) .Methods:The clinicopathological data of 1025 PTC patients who underwent surgery therapy in Department of Endocrine and Breast surgery of the First Affiliated Hospital of Chongqing Medical University from Jan. 2016 to Dec. 2017 were retrospectively analyzed. BMI was calculated according to height and weight, and patients were divided into normal weight group (BMI<24 kg/m 2) and overweight and obese group (BMI≥24 kg/m 2) . The differences in clinicopathological characteristics of PTC patients in different BMI groups were compared, and the correlation between BMI and clinicopathological characteristics of PTC patients was studied. In addition, 342 PTC patients who underwent BRAF V600E and TERT gene tests were compared with different BMI groups to explore the relationship between BMI and BRAF V600E and TERT gene mutations. Results:In this research, there were 591 (57.66%) patients in the normal weight group and 434 (42.34%) patients in the overweight and obese group. Univariate analysis showed that BMI was associated with gender, age and Hashimoto’s thyroiditis. There were more male gender ( P<0.001) , and age≥55 years ( P<0.001) in overweight and obese groups, and less with Hashimoto’s thyroiditis ( P=0.045) in overweight and obese groups. There was no correlation between BMI and the clinicopathological features of PTC, such as bilaterality, multiformity, tumor size, etc. Otherwise, BMI was a weak protective factor for numbers of lymph node metastasis>5 of PTC ( OR=0.947, CI95%=0.9900-0.997, P=0.037) , and it was not correlated with extra thyroidal extension. There were no significant correlation between BMI and the clinicopathological characteristics of PTC patients of different genders, such as tumor size, bilaterality, extra thyroidal extension, lymph node metastasis, etc. A significant relationship was found between BMI and BRAF V600E mutation in PTC patients ( P=0.044) , while it was not correlated between BMI and TERT mutation ( P=0.516) . Conclusions:Our study suggests that BMI is associated with age, gender, hashimoto’s thyroiditis and BRAF V600E mutation in PTC patients, while there was no significant correlation with the aggressiveness in PTC. More radical treatment for PTC patients who were overweight or obese is not recommended.
3.Protective effect of coenzyme Q10 on renal injury in diquat poisoned rats by inhibiting the expression of IL-17/NF-κB protein
Denghui YANG ; Jin WU ; Jie HU ; Jiangshan ZHAN ; Anjing LU ; Fuping LAI ; Yingmao JIA ; Yuanlan LU
Chinese Journal of Emergency Medicine 2024;33(9):1249-1256
Objective:To explore whether antioxidant coenzyme Q10 (CoQ10) is involved in the regulation of renal injury induced by diquat poisoning (DQ) in rats through anti-oxidative stress and inhibition of interleukin (IL)-17 and nuclear factor kappa-B (NF-κB) signaling pathway, and whether this mechanism is related to alleviating mitochondrial dysfunction.Methods:The expressions of NF-κB inhibitory protein α (IKB-α), phosphorylated nuclear factor κB (P-NF-κB), JNK-related leucine zipper protein (JLP) and neuroprotective protein PTEN-induced putative kinase 1(PINK1) pathway proteins were detected in vivo and in vitro. Biochemical detection of renal injury markers and inflammatory cytokines: serum urea nitrogen (BUN), serum creatinine (Cr), Cystatin C (CysC), renal injury molecule 1, Malondialdehyde, Supemxidedismutase (SOD), neutrophil gelatinase-associated lipocalin (NGAL), etc. Renal pathology HE staining was used to observe the degree of renal injury and pathological score under light microscope. The expression of reactive oxygen species (ROS) was detected by immunofluorescence. CCK-8 experiment was used to observe the level of cell proliferation after administration.Results:In vivo experiment, the indexes of renal function injury (Cr, BUN, CysC, NAGL, KIM-1) in plasma and kidney samples were significantly increased after 72 h of exposure in DQ group, and there were significant histopathological changes and pathological scores increased. In vitro experiment HK-2 cells were exposed to DQ for 48 h, and the cell viability decreased by half. After exposure to DQ, serum SOD decreased, MDA increased, and the immunofluorescence value of ROS in renal tissue increased. Intervention with CoQ10 can alleviate the pathological damage induced by DQ in rats, enhance the vitality of HK-2 cells, alleviate renal injury and reduce the level of oxidative stress. In addition, the expression of pro-inflammatory cytokines (IL-6, TNF-α and IL-17) increased in DQ group in vivo, the expression of P-NF-κBp65 protein in DQ group in vivo and HK-2 cell DQ group in vitro increased significantly, the expression of mitochondrial dysfunction index PINK1 protein increased significantly, and the expression of JLP protein and IκB-α protein decreased significantly. After intervention with CoQ10, the expression of P-NF-κBp65 protein and PINK1 can be decreased, while the expression of IκB-α protein can be increased and the degradation of JLP could be alleviated, and CoQ10 could improve the mitochondrial dysfunction after DQ poisoning.Conclusions:CoQ10 can alleviate the kidney injury induced by DQ poisoning in rats, and its mechanism may be related to the fact that CoQ10 regulates the expression of IL-17 and NF-κB signaling pathway through anti-oxidative stress, and further improves mitochondrial dysfunction.
4.Clinical features and early warning indicators of patients with acute-on-chronic liver failure and bacterial infection
Zhanhu BI ; Linxu WANG ; Haifeng HU ; Hong DU ; Yidi DING ; Xiaofei YANG ; Jiayi ZHAN ; Fei HU ; Denghui YU ; Hongkai XU ; Jianqi LIAN
Journal of Clinical Hepatology 2024;40(4):760-766
ObjectiveTo investigate the clinical features of patients with acute-on-chronic liver failure (ACLF) and bacterial infection and early warning indicators associated with multidrug-resistant infections. MethodsA retrospective analysis was performed for 130 patients with ACLF and bacterial infection who attended The Second Affiliated Hospital of Air Force Medical University from January 1, 2010 to December 31, 2021, and according to the drug susceptibility results, the patients were divided into multidrug-resistant (MDR) bacterial infection group with 80 patients and non-MDR bacterial infection group with 50 patients. General information and laboratory examination results were compared between the two groups to screen for the early warning indicators associated with MDR bacterial infection. The Student’s t-test was used for comparison of normally distributed continuous data with homogeneity of variance between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data or continuous data with heterogeneity of variance between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The binary logistic regression analysis and the receiver operating characteristic (ROC) curve were used to assess the predictive value of early warning indicators. ResultsAmong the 130 patients with ACLF and bacterial infection, sputum (27.7%) was the most common specimen for detection, followed by blood (24.6%), urine (18.5%), and ascites (17.7%). Bacterial infections were dominated by Gram-negative bacteria (58.5%). Of all bacteria, Escherichia coli (18.5%), Klebsiella pneumoniae (14.6%), and Enterococcus faecium (13.8%) were the most common pathogens. Gram-positive bacteria had a high resistance rate to the antibacterial drugs such as erythromycin (72.2%), penicillin (57.4%), ampicillin (55.6%), and ciprofloxacin (53.7%), while Gram-negative bacteria had a high resistance rate to the antibacterial drugs such as ampicillin (73.3%), cefazolin (50.0%), and cefepime (47.4%). The patients with ACLF and bacterial infection had a relatively high rate of MDR bacterial infection (61.5%). Comparison of clinical data between the two groups showed that compared with the patients with non-MDR bacterial infection, the patients with MDR bacterial infection had significantly higher levels of alanine aminotransferase (Z=2.089, P=0.037), aspartate aminotransferase (Z=2.063, P=0.039), white blood cell count (Z=2.207, P=0.027), and monocyte count (Z=4.413, P<0.001). The binary logistic regression analysis showed that monocyte count was an independent risk factor for MDR bacterial infection (odds ratio=7.120, 95% confidence interval [CI]: 2.478 — 20.456,P<0.001) and had an area under the ROC curve of 0.686 (95%CI: 0.597 — 0.776) in predicting ACLF with MDR bacterial infection(P<0.001), with the optimal cut-off value of 0.50×109/L, a sensitivity of 0.725, and a specificity of 0.400. ConclusionACLF combined with bacterial infections is mainly caused by Gram-negative bacteria, with the common pathogens of Escherichia coli and Klebsiella pneumoniae and a relatively high MDR rate in clinical practice. An increase in monocyte count can be used as an early warning indicator to distinguish MDR bacterial infection from non-MDR bacterial infection.