1.Dynamic observation of asthma model induced by allergen in mice from acute inflammation to chronic remodeling
Fangqi ZHANG ; Xinpeng HAN ; Fang ZHANG ; Xuemin YANG ; Dong XIANG ; Zhikui LI
Chinese Journal of Pathophysiology 2017;33(2):380-384
AIM:To dynamically observe and compare the relative changes of the indexes from the process of acute inflammation to chronic remodeling in asthmatic mice induced by ovalbumin ( OVA) .METHODS:Female BALB/c mice (n=60) were randomly divided into normal control group and asthma group .The mice in asthma group were sensi-tized and challenged by OVA , while the mice in normal group received equal volume of normal saline ( NS) .The challenge was performed for 3 consecutive days from the 21th day to observe the response of acute inflammation , and then the mice in different groups were challenged once per week for 5 weeks.Detailed comparisons of the dynamic changes of cell infiltra-tion, cytokine expression and airway remodeling were conducted .RESULTS:Compared with NS group , the mice in OVA group showed a predominantly eosinophilic infiltration into the airway lumen , increased production of Th 2-type cytokines , secretion of epithelial mucus and deposition of subepithelial collagen .In OVA challenge groups , the levels of inflammatory cells and inflammatory factors were remarkably higher in 24 d group, whereas the most obvious changes of goblet cell hyper-plasia and airway remodeling were observed in 52 d group.CONCLUSION:Acute asthma model is sufficiently induced by 3 consecutive days of OVA challenge protocol , which is accompanied with high levels of inflammatory cells and inflammato-ry factors.The OVA challenge protocol once per week for 5 weeks could induce a chronic asthma model with obvious airway remodeling .
2.Prognostic value and sensitivity to chemotherapy of microsatellite instability in advanced colorectal cancer
Yuchen WU ; Changsheng ZHANG ; Fei LIANG ; Dan HUANG ; Ji ZHU ; Ye XU ; Fangqi LIU
China Oncology 2015;(7):522-528
Background and purpose:Microsatellite instability (MSI) status is commonly applied to predict the prognosis and chemosensitivity in stage Ⅱ and stage Ⅲ colorectal cancer patients. However, researches of its function on metastasis colorectal cancer are limited. This study investigated its value on prognosis and chemosensitivity in metastatic colorectal cancer (CRC) patients.Methods:We retrospectively investigated tumor tissues from metastasis CRC patients who were treated with oxaliplatin and 5-FU-based therapy regimens (FOLFOX and XELOX). Immunostaining of proteins of the mismatch repair genehMLH1,hMSH2,hMSH6 andhPMS2 was performed. Prognostic value and chemosensitivity in patients with MSI status were also determined.Results:Clinical features from 113 patients were analyzed. No cor-relation of overall survival (OS) and chemosensitivity with MSI status was found. We further investigated 79 patients with synchronous metastasis and palliatively tumor resection. Median progression free survival (PFS) from 22 MSI patients was significant longer than that in 57 MSS patients (19.9 monthsvs 7 months,P=0.005). No significant difference was seen in OS comparison (P=0.07). MSI status was also an independent prognostic factors of PFS by Cox multivariate analysis (MSS/MSI,HR=2.079,P=0.043). Moreover, in this group, MSI patients had improved disease control rate (59.1%vs 31.6%, P=0.025) in chemosensitivity analysis than MSS patients.Conclusion:A better PFS in MSI patients with synchronous metastasis and palliative tumor resection was found after treated with oxaliplatin and 5-FU-based therapy and a better chemosensitivity in MSI patients was also found.
3.RBRVS-based performance appraisal: application at a hospital
Jie CHEN ; Bo PANG ; Xiaoren ZHANG ; Fangqi YANG
Chinese Journal of Hospital Administration 2018;34(9):765-769
With the resource based relative value scale (RBRVS) application at a hospital cited as an example, the paper covered its use in performance appraisal for optimal performance-based distribution as follows. In view of hospital specifics, such appraisal indexes as the quantity, quality, technical difficulty and cost control are quantified as key indicators, to form its own RBRVS scores and weights. In combination of the case mixed index as well, such factors as specific appraisal, quality of care and research/teaching work are taken into account for the purpose of rational and optimal pay for performance.
4.Survey of RBRVS-based performance appraisal methods at 12 public hospitals
Jie CHEN ; Xiaoren ZHANG ; Bo PANG ; Fangqi YANG ; Hui ZHAO
Chinese Journal of Hospital Administration 2018;34(9):770-773
Objective To learn the initial application of RBRVS related performance appraisal at public hospitals in China. Methods 12 tertiary public hospitals which took the lead to introduce RBRVS models, via third-party cooperation, in medical stuff performance assessment over one year were surveyed. The study summarized their design emphases of RBRVS performance appraisal, covering such aspects as appraisal level, accounting method, conceptual design, points setup and items charged as cost. Descriptive statistics was used to analyze the data so acquired. Results As shown in the performance appraisal level, most hospitals were found with defects in refining levels, as eight hospitals only appraise down to the department level, three to diagnostic group level, and only one hospital to individuals. Of these hospitals, over eight hospitals used RBRVS to elevate the efficiency and inventiveness of employees, while half of these hospitals reported the method can improve service, reduce cost and enhance quality of care. Conclusions Public hospitals enjoy advantages via third-party cooperation RVRBS method in RVRBS-related reforms. Introduction of this method calls for localization design based specifics and management goals of public hospitals.
5.Role and mechanism of XPOT inhibition by atractylenolide I in gastric cancer cells
Yi ZHANG ; Fangqi MA ; Siyuan WEI ; Xuejun LI
The Journal of Practical Medicine 2024;40(14):1928-1934
Objective This study aimed to investigate the role and mechanism of atractylenolide Ⅰ in inhibiting XPOT proliferation and invasion in gastric cancer cells.Methods This study included exploration of XPOT expression in gastric cancer tissues,analysis of gene expression data from GC patients in TCGA and GEO databases,as well as various cellular assays to detect the ability of cancer cells to proliferate,migrate,and invade.Protein expression levels of XPOT,SKP2,CyclinA,and P27 mRNA were also detected by qPCR and Western Blot.Results Analysis confirmed that XPOT was highly expressed in gastric cancer tissues,indicating a poor prognosis.In vitro studies revealed that AT-1 inhibits the proliferation and invasion ability of GC cells;XPOT down-regulation also inhibits these abilities.Furthermore,AT-1 down-regulates the expression of XPOT which then regulates SKP2,P27,and CyclinA-ultimately inhibiting the proliferation and invasion of gastric cancer cells through the regulation of the XPOT pathway.Conclusion The overexpression of XPOT in gastric cancer tissues can indicate a poor prognosis.Atractylenolide Ⅰ down-regulates the XPOT-regulated ubiquitination-proteasome pathway to inhibit proliferation and invasion of gastric cancer cells.
6. Analysis of risk factors for postsurgical gastroparesis syndrome (PGS) after operation for gastric cancer
Delian LIU ; Xuewei ZHANG ; Fangqi LYU
Chinese Journal of Oncology 2017;39(2):150-153
Objective:
To investigate the risk factors for postsurgical gastroparesis syndrome (PGS) after surgery for stomach cancer.
Methods:
A total of 684 patients with gastric cancer who underwent surgery for stomach cancer from Jan. 1, 2010 to Dec. 31, 2014 in Tai′an Tumor Prevention and Treatment Hospital, including 475 males and 209 females, with an average age of 59.9 years were identified and included in this study. There were 206 cases of gastric cardia and gastric fundus cancers and 478 cases of gastric antrum cancer. 206 cases underwent proximal radical subtotal gastrectomy and D2 lymph node dissection, 478 distal radical subtotal gastrectomy, 206 residual esophagogastric anastomosis, 311 Billroth-Ⅰ anastomosis, 99 Billroth-Ⅱ anastomosis, and 68 Billroth-Ⅱ plus Roux-en-y anastomosis. The incidence and risk factors of PGS were analyzed.
Results:
All of the 684 patients were successfully operated.Among them, 48 (7.0%)encountered PGS. The univariate analysis showed that age, smoking index, alcohol consumption index,
7.Method for constructing a mouse model of bile stasis caused by partial bile duct ligation
Haiye TU ; Fangqi BAO ; Lizong ZHANG ; Chen JIANG ; Sisi WEN ; Ziyu ZHAO ; Mingsun FANG ; Minli CHEN
Acta Laboratorium Animalis Scientia Sinica 2024;32(5):620-629
Objective To observe the effects of different ligation sites and fasting method on a C57BL/6J mouse model of partial bile duct ligation(pBDL)-induced cholestasis,to establish a pBDL modeling method with a high modeling rate,typical symptoms,and good stability.Methods C57BL/6J mice were subjected to selective ligation of the left hepatic bile duct(L-pBDL)and left-to-median bile duct junction ligation(ML-pBDL)for modeling,and the effects of different pBDL ligation method on serum alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase(ALP),total bilirubin,total bile acid,and liver histopathology were observed.The effects of different fasting method on symptoms and liver injury in the ML-pBDL model were also observed after fasting for 12 and 16 h before surgery,and for 4 h after surgery.Results(1)The incidence of jaundice in the ML-pBDL group was 52.94%and the survival rate within 3 weeks after surgery was 64.71%,while the incidence of jaundice in the L-pBDL group was 11.76%and the survival rate within 3 weeks after surgery was 82.35%.Compared with those in the sham surgery group,serum liver function indicators were significantly increased in the L-pBDL and ML-pBDL groups(P<0.01),and ALP activity was significantly higher in the ML-pBDL group than in the L-pBDL group(P<0.05).Compared with mice in the L-pBDL group,mice in the ML-pBDL group had more severe liver fibrosis at 3 weeks post-surgery(P<0.01).(2)In addition,the incidence of jaundice in the 16 h fasting group was 93.33%and the survival rate within 3 weeks after surgery was 73.77%,while the incidence of jaundice in the 12 h fasting group was 42.86%and the survival rate within 3 weeks after surgery was 71.42%.Compared with those in the normal group,ALP activity,alanine aminotransferase/aspartate aminotransferase ratio,total bile acid level,and proportion of collagen fiber area were all significantly increased in the 16 h and 12 h fasting groups(P<0.05).Although the observed indicators were higher in the 16 h fasting group compared with those in the 12 h fasting group,the difference was not significant(P>0.05).Mice in the 12 h and 16 h fasting groups both showed significant bile duct hyperplasia and liver fibrosis(P<0.01),with more severe liver fibrosis in the 16 h fasting group(P<0.01).Conclusions Both L-pBDL and ML-pBDL ligation method can be used to establish a mouse model of cholestasis;however,symptoms in the L-pBDL model only exhibit transient damage characteristics,while the liver lesions in the ML-pBDL model are typical and stable.Prolonging the preoperative fasting time can improve the modeling rate and stability of the ML-pBDL model and produce more-typical pathological symptoms.
8.Long non-coding RNA AW112010 improves insulin resistance in adipocytes of aging mice through the miR-204/POU2F2 axis
Rui WANG ; Shuwen WANG ; Yifan ZHANG ; Yaqi HU ; Qi YUAN ; Yuan WEN ; Xiaoling CHEN ; Ting LU ; Ying ZHENG ; Zhiyong LIN ; Mengzhen XUE ; Yaqi WANG ; Fangqi XIA ; Leiqi ZHU ; Chengfu YUAN
Chinese Journal of Endocrinology and Metabolism 2024;40(1):44-52
Objective:To investigate whether long non-coding RNA(lncRNA) AW112010 can improve insulin resistance in aging adipocytes through the miR-204/POU2F2 signaling pathway.Methods:In vivo experiment: C57BL/6 mice were divided into young control group(4 months old) and aging model group(18 months old) based on body weight. The expression levels of AW112010, miR-204-5p, POU2F2, aging related indicators(p16, p21), and insulin signaling pathway genes [insulin receptor(INSR), insulin receptor substrate 1(IRS1), phosphatidylinositol kinase(PI3K), protein kinase B(AKT)] in epididymal adipose tissue were detected using real-time fluorescence quantitative PCR(RT-qPCR) and Western blotting. In vitro experiment: Using adriamycin(ADR) to induce 3T3-L1 aging adipocyte model, β-gal staining was used to observe cellular senescence, and miR-204 inhibitor and miR-204 mimic small interfering RNA were successfully constructed and transfected into 3T3-L1 adipocytes. Results:RT-qPCR and Western blot results showed that compared with the young group, the expression of AW112010 in the adipose tissue of aging mice was increased, while the expression of miR-204-5p was decreased. The expressions of POU2F2, p16, and p21 in the adipose tissue of aging mice were increased, while the expressions of INSR, IRS1, PI3K, GLUT4 mRNA and protein were decreased. The β-gal stainging results showed that the number of 3T3-L1 senescent adipocytes induced by ADR was significantly increased, and the expression levels of AW112010, POU2F2, p16, and p21 in ADR-induced senescent adipocytes were increased compared with the control group, while the expression levels of miR-204-5p, INSR, IRS1, PI3K, GLUT4 were decreased, and remaining glucose in the culture medium was increased. Compared with control, overexpression of miR-204 resulted in decreased expressions of aging indicators p16, p21, and target gene POU2F2 while the expressions of INSR and GLUT4 were increased.Conclusion:Upregulation of lncRNA AW112010 in adipocytes of aging mice may induce insulin resistance by targeting miR-204-5p/POU2F2/IRS1.
9.Advances in Research on Pathological and Molecular Mechanism of Hyperuricemic Nephropathy Based on Animal Models
Fangqi BAO ; Haiye TU ; Mingsun FANG ; Qian ZHANG ; Minli CHEN
Laboratory Animal and Comparative Medicine 2024;44(2):180-191
Uric acid (UA), the final product of human purine metabolism, can cause hyperuricemia (HUA) when excessively accumulated. HUA is closely linked to chronic kidney diseases (CKD) and is considered an independent risk factor. Hyperuricemic nephropathy, a form of CKD induced by HUA, has seen significant advances in understanding through research into the pathogenic roles of uric acid and the development of HUA animal models. Although progress has been made in understanding the pathophysiological mechanisms by which UA induces CKD, much remains to be learned about its pathological molecular mechanisms. New approaches in animal modeling or the selection of model animals may potentially lead to significant breakthroughs in research on hyperuricemia as well as related CKD. This paper reviews the research progress on the molecular mechanisms of hyperuricemic nephropathy, focusing on oxidative stress, inflammation, autophagy, fibrosis, and gut microbiota. Oxidative stress is induced by uric acid intracellularly through xanthine oxidase, NADPH oxidases, and mitochondria, leading to cellular damage. In terms of inflammation, uric acid crystals can activate the NLRP3 inflammasome, triggering an inflammatory cascade. The role of free uric acid as a pro-inflammatory agent, however, remains controversial. Depending on the study conducted, autophagy has been found to either alleviate or exacerbate inflammation induced by uric acid. Fibrosis, particularly through epithelial-mesenchymal transition (EMT), is a major mechanism by which uric acid causes glomerulosclerosis and tubulointerstitial fibrosis. Extensive research has explored various signaling pathways involved in uric acid-induced EMT. Beneficial gut microbiota protect the kidneys by synthesizing short-chain fatty acids, reducing urea’s enterohepatic circulation, and decreasing uric acid production. This paper aims to enhance understanding of the complex relationships between HUA and CKD, serving as a reference for further research and new drug development.
10.Study on protective effect and mechanism of Modified Yupingfeng nasal spray on nasal mucosal injury in AR model rats
Yuan XI ; Xinning HE ; Yuyin LIU ; Na ZHANG ; Ting LIU ; Fangqi LIANG ; Li TIAN
China Pharmacy 2023;34(10):1204-1210
OBJECTIVE To study protective effect and potential mechanism of Modified yupingfeng nasal spray (YPF+) on nasal mucosal injury in allergic rhinitis (AR) model rats. METHODS AR model was induced by ovalbumin (OVA) and randomly divided into model group, YPF+group (50 µg/side,twice a day), positive control group (Mometasone furoate aqueous nasal spray, 50 µg/side,once a day); the blank group was set up, with 10 rats in each group. Administration groups were given relevant medicine, and blank group and model group were given equivalent normal saline for consecutive 4 weeks. Thirty minutes after last medication, the behavioral scores of rats were recorded, and the pathological changes of their nasal mucosa tissue were observed. The level of reactive oxygen species (ROS) in nasal mucosa tissue was detected. The protein and mRNA expressions of nucleotide- binding oligomerization domain-like receptor protein 3 (NLRP3),caspase-1,gasdermin D (GSDMD) were detected; the contents of interleukin-1β (IL-1β) and IL-18 in serum were also determined. RESULTS Compared with blank group, in model group, the nasal mucosa tissue structure was disordered, inflammatory cells infiltrated seriously, and lamina propria vascular dilation was visible; its behavioral score and pathological score, the level of ROS, protein and mRNA expressions of NLRP3, caspase-1 and GSDMD, serum contents of IL-1β and IL-18 in nasal mucosa tissue were increased significantly (P<0.05). Compared with model group, the symptoms of nasal mucosal injury in rats of each drug group were improved to varying degrees, and the above indicators were significantly reduced (P<0.05). CONCLUSIONS YPF+ may improve nasal mucosal injury of rats, relieve AR symptoms such as sneezing, itchy nose, runny nose, the mechanism of which may be associated with reducing the production of ROS in nasal mucosa and downregulating NLRP3/caspase-1/ GSDMD pathway.