1.Effect of Ginkgo biloba extract on improving hepatic insulin resistance induced by arsenic exposure based on network pharmacology
Zhida HU ; Shiqing XU ; Ruru MENG ; Yanfeng JIA ; Qiyao ZHANG ; Bohao BIAN ; Shurui WANG ; Yang LIU ; Li WANG ; Yanrong GAO
Journal of Environmental and Occupational Medicine 2024;41(7):751-759
Background Arsenic exposure is a common and important environmental and occupational hazardous factor in China, and arsenic-induced insulin resistance (IR) has attracted widespread attention as a negative health outcome to the population. Objective To explore part of the mechanism of hepatic IR induced by arsenic exposure based on the peroxisome proliferators-activated receptors γ (PPARγ)/ glucose transporter 4 (GLUT4) pathway, and to investigate potential effects of Ginkgo biloba extract (GBE) on hepatic IR induced by arsenic exposure and associated mechanism of action. Methods The target of drug action was predicted by network pharmacology and verified by in vivo and in vitro experiments. In vivo experiments: 48 SPF C57BL/6J male mice were divided into 4 groups, including control group, 50 mg·L−1 NaAsO2 model group (NaAsO2), 50 mg·L−1 NaAsO2+10 mg·kg−1 GBE intervene group (NaAsO2+GBE), and 10 mg·kg−1 GBE group (GBE), 12 mice in each group. The animals were given free access to purified water containing 50 mg·L−1 NaAsO2, or given intraperitoneal injection of normal saline containing 10 mg·kg−1 GBE once per week. After 6 months of exposure, blood glucose detection, intraperitoneal glucose tolerance test (IPGTT), and insulin tolerance test (ITT) were performed. Serum and liver tissues were collected after the mice were neutralized, liver histopathological sections were obtained, serum insulin levels, liver tissue glycogen content, glucose content were detected by enzyme linked immunosorbent assay (ELISA), and the expression of PPARγ and GLUT4 proteins was detected by Western blot (WB). In vitro experiments: HepG2 cells were divided into 4 groups, including control group, 8 μmol·L−1 NaAsO2 group (NaAsO2), 8 μmol·L−1 NaAsO2 + 200 mg·L−1 GBE intervene group (NaAsO2+GBE), and 200 mg·L−1 GBE group (GBE). The levels of glycogen and glucose were detected by ELISA, and the expression of PPARγ and GLUT4 proteins was detected by WB. Results A strong binding effect between GBE and PPARγ was revealed by network pharmacology. In in vivo experiments, the NaAsO2 group exhibited an elevated blood glucose compared to the control group, and the NaAsO2+GBE group showed a decreased blood glucose compared to the NaAsO2 group (P<0.01). The histopathological sections indicated severe liver structural damage in the arsenic exposure groups (NaAsO2 group and NaAsO2+GBE group), with varying staining intensity, partial liver cell necrosis, and diffuse red blood cell appearance. Both results of in vitro and in vivo experiments showed a decrease in glycogen synthesis and glucose uptake in the NaAsO2 groups compared to the control groups, which was alleviated in the NaAsO2+GBE group (P<0.01). The results of WB revealed inhibited PPARγ expression and reduced GLUT4 levels on the cell membrane, and all these changes were alleviated in the NaAsO2+GBE group (P<0.01). Conclusion This study findings suggest that GBE antagonizes arsenic exposure-induced hepatic IR by regulating the PPARγ/GLUT4 pathway, indicating that GBE has a protective effect on arsenic exposure-induced hepatic IR, and PPARγ may be a potential therapeutic target for arsenic exposure-induced hepatic IR.
2.Risk factors and prognosis of respiratory failure in patients after cardiac surgery
Qiansheng WU ; Kaili HU ; Ling XU ; Zhao CHEN ; Yanrong ZHOU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2024;31(3):272-276
Objective To observe the incidence and prognosis of respiratory failure in patients after cardiac surgery,and the risk factors were analyzed.Methods A total of 559 patients who underwent cardiac surgery were enrolled in Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology from July 2020 to November 2023.Clinical data were extracted through the hospital information system(HIS).This included general data such as gender,age,body mass index(BMI),smoking history,alcohol history,comorbidities,and basic disease data like occurrence of respiratory tract infection in the past 1 month before surgery,preoperative use of antimicrobial drugs,ejection fraction,operation time,cardiopulmonary bypass time,intraoperative blood transfusion,nasogastric tube indwelling,nosocomial infection,secondary thoracotomy,preoperative white blood cell count(WBC),length of intensive care unit(ICU)stay,secondary intubation and tracheostomy,discharge diagnosis,and outcome.The patients were divided into two groups according to whether or not they had expiratory failure.The difference of the above data between the two groups was compared.Multivariate Logistic regression was used to analyze the risk factors of respiratory failure in patients after cardiac surgery,the prediction model was constructed based on the above risk factors,and the receiver operator characteristic curve(ROC curve)was drawn to analyze the predictive value of the prediction model for patients with respiratory failure.Results The incidence of respiratory failure in patients after cardiac surgery was 7.51%(42 cases).Multivariate Logistic regression analysis showed that intraoperative blood transfusion>2000 mL,nasogastric tube,and nosocomial infection were risk factors for respiratory failure in patients after cardiac surgery[odds ratio(OR)and 95%confidence interval(95%CI)were 4.136(1.794-9.535),3.162(1.454-6.878)and 3.488(1.262-9.638),all P<0.05].The ROC curve analysis showed that the prediction model had a certain predictive value for the occurrence of respiratory failure in patients after cardiac surgery[area under the curve(AUC)=0.738,95%CI was 0.658-0.818,P<0.001].The length of ICU stay of patients in the group with respiratory failure was significantly longer than that in the group without respiratory failure(hours:8.16±7.62 vs.4.52±3.95),the secondary intubation rate[80.95%(34/42)vs.0(0/517)]and the tracheostomy rate[88.10%(37/42)vs.0(0/517)]were significantly higher than those in the non-respiratory failure group,and the recovery/improvement rate was significantly lower than that in the non-respiratory failure group[59.52%(25/42)vs.90.13%(466/517)],the differences were statistically significant(all P<0.05).Conclusions Patients with intraoperative blood transfusion>2000 mL,nasogastric tube inserted,and nosocomial infection are the high-risk groups for respiratory failure after cardiac surgery.Medical staff should strengthen the identification of high-risk groups and actively take intervention measures to improve the prognosis of patients.
3.Comparative Study of Two Common In Vitro Models for the Pancreatic Islet with MIN6
Xinxin CHAO ; Furong ZHAO ; Jiawei HU ; Yanrong YU ; Renjian XIE ; Jianing ZHONG ; Miao HUANG ; Tai ZENG ; Hui YANG ; Dan LUO ; Weijie PENG
Tissue Engineering and Regenerative Medicine 2023;20(1):127-141
BACKGROUND:
Islet transplantation is currently considered the most promising method for treating insulin-dependent diabetes. The two most-studied artificial islets are alginate-encapsulated b cells or b cell spheroids. As three-dimensional (3D) models, both artificial islets have better insulin secretory functions and transplantation efficiencies than cells in twodimensional (2D) monolayer culture. However, the effects of these two methods have not been compared yet. Therefore, in this study, cells from the mouse islet b cell line Min6 were constructed as scaffold-free spheroids or alginate-encapsulated dispersed cells.
METHODS:
MIN6 cell spheroids were prepared by using Agarose-base microwell arrays. The insulin secretion level was determined by mouse insulin ELISA kit, and the gene and protein expression status of the MIN6 were performed by Quantitative polymerase chain reaction and immunoblot, respectively.
RESULTS:
Both 3D cultures effectively promoted the proliferation and glucose-stimulated insulin release (GSIS) of MIN6 cells compared to 2D adherent cells. Furthermore, 1% alginate-encapsulated MIN6 cells demonstrated more significant effects than the spheroids. In general, three pancreatic genes were expressed at higher levels in response to the 3D culture than to the 2D culture, and pancreatic/duodenal homeobox-1 (PDX1) expression was higher in the cells encapsulated in 1% alginate than that in the spheroids. A western blot analysis showed that 1% alginate-encapsulated MIN6 cells activated the phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (AKT)/forkhead transcription factor FKHR (FoxO1) pathway more than the spheroids, 0.5% alginate-, or 2% alginate-encapsulated cells did. The 3D MIN6 culture, therefore, showed improved effects compared to the 2D culture, and the 1% alginate-encapsulated MIN6 cells exhibited better effects than the spheroids. The upregulation of PDX1 expression through the activation of the PI3K/AKT/FoxO1 pathway may mediate the improved cell proliferation and GSIS in 1% alginate-encapsulated MIN6 cells.
CONCLUSION
This study may contribute to the construction of in vitro culture systems for pancreatic islets to meet clinical requirements.
4.Application of family empowerment model in postoperative delirium management of patients with Stanford type A aortic dissection
Jun ZHAO ; Shan ZHANG ; Hongxia ZHAO ; Xiaohong HU ; Yanrong QIN ; Ying WU
Chinese Journal of Modern Nursing 2023;29(21):2886-2891
Objective:To analyze the application effect of family empowerment model on postoperative delirium management in Stanford type A aortic dissection patients.Methods:Using the convenient sampling method, a total of 316 patients with Stanford type A aortic dissection who underwent surgery in Beijing Anzhen Hospital from February to December 2019 were selected as the research objects. The research objects were divided into the observation group ( n=204) and the control group ( n=112) based on whether they have received postoperative delirium management based on family empowerment mode. The Richmond Agitation and Sedation Scale (RASS) and Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) were used to evaluate postoperative delirium in patients. The incidence of delirium, length of ICU stay, the total length of hospital stay and incidence of ICU acquired infection were compared between the two groups. The duration of delirium was recorded and compared between the two groups. Results:The incidence of delirium in the control group was 16.96% (19/112), and the duration of delirium was 3 (3, 4) d. The incidence of delirium in the observation group was 9.31% (19/204), and the duration of delirium was 3 (2, 3) d. The differences between the two groups were statistically significant ( P<0.05). The length of ICU stay in the observation group was (3.38±1.12) d, while that in the control group was (3.74±1.44) d. There was statistically significant difference in the length of ICU stay between the two groups ( P< 0.05). There was no statistically significant difference in the total hospital stay and incidence of ICU acquired infection between the two groups ( P>0.05) . Conclusions:Family empowerment based postoperative delirium management can reduce the incidence and duration of postoperative delirium in Stanford type A aortic dissection patients. Family empowerment mode can reduce the length of ICU hospitalization for patients without increasing the incidence of ICU acquired infections.
5.Qualitative screening of 52 illegally adulterated weight-losing compounds in foods by ultra high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry
Jian SUN ; Yanrong ZHU ; Qing HU ; Hong YU ; Jingxian ZHANG ; Xianxian LIU ; Shen JI
Shanghai Journal of Preventive Medicine 2022;34(6):519-525
ObjectiveAn analytical method was developed for the qualitative screening of 52 illegally adulterated weight-losing compounds in foods by ultra high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. MethodsThe samples were extracted by methanol. Waters CORTECS T3 column (100 mm×2.1 mm, 2.7 μm) was used with acetonitrile -0.1% formic acid aqueous solution as mobile phases by gradient elution. The compounds were detected by electrospray ionization mass spectrometry and Q-TOF-MS detector in positive and negative ion mode. A standard spectrum library was established by reference standards, and the qualitative analysis was finished by the comparison of the retention time, parent ion and fragment ion accurate molecular mass of each compound in the sample and the library. ResultsThe method was specific without interference of blank matrix, and repeatable in sextuplicate. The detection limits of 52 compounds in 5 matrix were 1‒100 mg‧kg-1. The method was successfully applied to the analysis of actual samples,and 16 compounds were checked out in 246 samples. ConclusionThe method is accurate, specific and sensitive, which can be used to combat the illegal adulteration behavior effectively.
6.Natural compounds modulate the autophagy with potential implication of stroke.
Anil AHSAN ; Mengru LIU ; Yanrong ZHENG ; Wenping YAN ; Lin PAN ; Yue LI ; Shijia MA ; Xingxian ZHANG ; Ming CAO ; Zhanxun WU ; Weiwei HU ; Zhong CHEN ; Xiangnan ZHANG
Acta Pharmaceutica Sinica B 2021;11(7):1708-1720
Stroke is considered a leading cause of mortality and neurological disability, which puts a huge burden on individuals and the community. To date, effective therapy for stroke has been limited by its complex pathological mechanisms. Autophagy refers to an intracellular degrading process with the involvement of lysosomes. Autophagy plays a critical role in maintaining the homeostasis and survival of cells by eliminating damaged or non-essential cellular constituents. Increasing evidence support that autophagy protects neuronal cells from ischemic injury. However, under certain circumstances, autophagy activation induces cell death and aggravates ischemic brain injury. Diverse naturally derived compounds have been found to modulate autophagy and exert neuroprotection against stroke. In the present work, we have reviewed recent advances in naturally derived compounds that regulate autophagy and discussed their potential application in stroke treatment.
7.Short-term treatment efficacy of NK cells for ovarian cancer ascites
HU Jianhua ; ZHANG Yan ; JIANG Longwei ; GAO Yanrong ; SHI Ruifang ; ZHAO Hua ; YAO Lu ; JIA Shaochang
Chinese Journal of Cancer Biotherapy 2020;27(10):1152-1155
[Abstract] Objective: To investigate the short-term clinical efficacy and safety of intraperitoneal perfusion of natural killer (NK) cells
in the treatment of ovarian cancer with ascites. Methods: The clinical data of 15 ovarian cancer patients with ascites effusion, who
received NK cell perfusion in the Qinhuai Medical District of the General Hospital of Eastern Theater Command from November 2016
to January 2019, were analyzed. The peripheral blood was collected to isolate the peripheral blood mononuclear cells, and to further
obtain the NK cells after culture. NK cell suspension was intraperitoneally perfused into the abdominal cavity (no less than 2×109 cells/
time). The volume of peritoneal effusion, the level of serum tumor marker CA-125, the level of serum cytokines IL-2, INF-γ and TNF-α
as well as the changes in peripheral blood lymphocyte subsets were detected before and after the treatment; Moreover, the clinical
efficacy and adverse reactions were observed. Results: The effective rate of intraperitoneal perfusion of NK cells was 66.7%, and there
were no obvious treatment-related adverse reactions. Compared with before treatment, the serum tumor marker CA-125 level
significantly decreased after treatment (P<0.05), and the levels of IL-15, IFN-γ and TNF-α increased significantly (P<0.05 or P<0.01),
while there was no significant changes in peripheral blood lymphocyte subsets (all P>0.05). Conclusion: Intraperitoneal infusion of NK
cells in the treatment of ovarian cancer associated peritoneal effusion has a good short-term clinical efficacy with little adverse
reactions, which is a promising method for the treatment of cancerous peritoneal effusion.
8.Efficacy observation of nano-particle albumin bound paclitaxel combined with cisplatin for treatment of advanced and relapsed cervical cancer
Jianxun WEI ; Yanrong LI ; Gaiqin HU ; Nan WANG
Cancer Research and Clinic 2020;32(5):331-334
Objective:To investigate the efficacy and safety of nano-particle albumin bound paclitaxel in the treatment of patients with advanced and relapsed cervical cancer.Methods:A retrospective cohort study was conducted. Among the cervical cancer patients who were diagnosed and treated in Affiliated Hospital of Yan'an University from January 2013 to January 2018, 52 advanced and relapsed cases were selected as the research objects. The chemotherapy protocol of nano-particle albumin bound paclitaxel and cisplatin was used, and the efficacy and toxicity of chemotherapy were analyzed.Results:The total objective remission rate of 52 patients with advanced or relapsed cervical cancer was 67.3% (35/52), the disease control rate was 88.5% (46/52), and the progression-free survival time was (11.7±3.6) months. The objective remission rate in patients who had received radiotherapy and with a time interval of > 12 months since their last chemotherapy was higher than that in patients who had not received radiotherapy and with a time interval of ≤ 12 months since their last chemotherapy [76.9% (30/39) vs. 46.2% (6/13), χ2 = 4.333, P = 0.037; 78.9% (15/19) vs. 43.8% (7/16), χ2 = 4.609, P = 0.032]. Late stage, relapse, whether received radiotherapy, whether received chemotherapy and the time from the previous chemotherapy had no effect on the disease control rate (all P > 0.05). The progression-free survival time in patients who underwent radiotherapy and with a time interval of > 12 months since their last chemotherapy was longer than that in patients who had not received radiotherapy and with a time interval of ≤12 months since their last chemotherapy [(13.0±4.4) months vs.(8.7±2.9) months, t = 3.029, P = 0.004; (12.8±3.1) months vs. (9.6±4.0) months, t = 2.665, P = 0.012]. The highest incidence rates of adverse reactions were myelosuppression (82.7%, 43/52) and gastrointestinal reaction (65.4%, 34/52), and the most common grade Ⅲ-Ⅳ adverse reaction was myelosuppression (20 cases). Conclusion:The efficacy and safety of nano-particle albumin bound paclitaxel combined with cisplatin in the treatment of advanced and relapsed cervical cancer are reliable.
9.CT characteristic of ectopic pheochromocytoma
Mingzhe HU ; Yanrong ZHANG ; Da LIN ; Qiande QIU
Chinese Journal of Postgraduates of Medicine 2018;41(12):1102-1105
Objective To investigate the CT characteristics of ectopic pheochromocytoma and improve the diagnostic accuracy. Methods The CT imaging of 27 cases with surgery and pathology proved ectopic pheochromocytoma were retrospectively analyzed, and the tumor site, size, shape, density, cystic change, calcification, boundary and strengthening characteristics of these tumors were observed. Results Tumor located in mesentery in 6 cases and in the left side of abdominal aorta in 6 cases. Tumor located in duodenal ampulla, inferior vena cava, hepatic hilum, left renal portal, right adrenal gland and bladder in 2 cases for each spot. Tumor located in right jugular foramen, left carotid body and right lower lung in 1 case for each spot. The maximum diameter of the tumor was 2.8-19.0 (6.3 ± 2.4) cm. CT plain scan showed low density in 9 cases, isodensity in 10 cases, and high density in 8 cases. CT value was 20-58 (35.0 ± 11.6) HU. Enhanced CT scan showed that the CT value was 40-96 (74.0 ± 16.4) HU, 37- 90 (63.0 ± 14.2) HU in venous phase and 35-67(55.0 ± 12.6) HU in delayed phase. In arterial phase, 15 cases showed marked enhancement in parenchyma, 5 cases showed moderate enhancement, and 7 cases showed mild enhancement. In venous phase, the degree of enhancement decreased significantly in 5 cases, slightly in 15 cases, and continued in 7 cases. In delayed phase, the degree of enhancement decreased in 20 cases and continued in 7 cases. Conclusions The CT findings of ectopic pheochromocytoma have certain characteristics, CT examination is helpful to locate and characterize ectopic pheochromocytoma and to clarify the relationship between tumor and surrounding tissue structure.
10.Multi-slice CT imaging features of pancreatic neuroendocrine carcinoma
Yanrong ZHANG ; Mingzhe HU ; Zhihan YAN
Chinese Journal of Postgraduates of Medicine 2018;41(6):543-547
Objective To investigate the multi-slice CT (MSCT) imaging features of pancreatic neuroendocrine carcinoma (PNEC). Methods A retrospective analysis of the MSCT and pathological findings of 10 PNEC patients confirmed by surgery and pathology was performed. Results Among the 10 patients, the tumor locating at pancreatic head was in 1 case, at pancreatic body was in 1 case, and at pancreatic tail was in 8 cases. The maximum diameter was 1.8-8.5 (4.7 ± 3.6) cm. The boundary between mass and normal pancreas was unclear, among which there was a circle-like shape in 4 cases, and irregular shape in 6 cases. The plain scan showed that there were cystic changes in the mass, including cystic lesion locating in the center of the lesion in 7 cases, and that locatingd in the periphery of the lesion in 3 cases. The plain CT value was (36.0 ± 8.3) HU. The enhancement scan showed that the circumference was mainly ring enhancement, the arterial phase CT values was (78.0 ± 6.7) HU, the portal venous phase CT values was (83.0 ± 8.2) HU, and the balanced phase CT values was (69.0 ± 9.1) HU. Under the microscope, found that the tumor were made up of small cells and large cells, the tumor tissue was invasive. The atypia of tumor cells was obvious, diffuse and distribution was diffuse, with necrosis. The nuclear division was more common. The immunohistochemical result showed that synaptophysin (Syn) positive was in 10 cases, neuron-specific enolase (NSE) positive was in 7 cases, chromogranin A (CgA) positive was in 7 cases, and CD56 positive was in 6 cases; the percentage of Ki-67 expression positive cell < 3% was in 3 cases, 3%-20% was in 4 cases, and >20% was in 3 cases. Conclusions The MSCT imaging findings of PNEC has certain characteristics, and multi-period dynamic contrast-enhanced scan is helpful for the diagnosis of pancreatic neuroendocrine carcinoma.

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