1.Role of Perilipin 2 in microvesicular hepatic steatosis induced by CGI-58 specific knockout in mice
Yixin ZHANG ; Jie LI ; Xiaoqin WAN ; Xiaoqing JIANG ; Jianghui CHEN ; Fang DENG ; Mindian LI ; Qian ZHANG ; Xinyu BAO ; Zhihui ZHANG
Journal of Army Medical University 2024;46(15):1701-1712
Objective To explore whether hepatocyte Perilipin-2(Plin2)is involved in the development of fatty liver related to comparative gene identification-58(CGI-58)deficiency mice and compare the effects of Plin2 and Plin3 on lipid droplet formation and lipid accumulation.Methods Based on CGI-58Flox/Flox mice as animal model,the adeno-associated viruses targeting mouse liver,CGI-58 knockout and Plini2 knockdown were achieved by co-expression Cre protein and micro-RNA targeting Plin2(Mi-KD).Then CGI-58 deficiency mice were used as control(NC)to detect the differences in metabolic phenotype and liver pathology.AML-12 mouse hepatocytes were used as cellular model and interfered with siRNA to achieve Plin2/Plin3 knockdown in AML-12 cells.Lipid droplet formation and lipid accumulation were compared with Bodipy staining and enzyme colorimetry in basal condition or lipid-overloaded condition(OA inducement)after Plin2/Plin3 knockdown.Results Plin2 knockdown(Mi-KD)reduced PLIN2 protein level by>99%in mouse livers.Mi-KD decreased hepatomegaly(P=0.019 5)and liver injury(P=0.000 4),while reduced the histological NAS score(P=0.000 2)and hepatic triglyceride content(P=0.016 6)in the CGI-58 deficiency female mice.Mi-KD prevented microvesicular hepatic steatosis in the CGI-58 deficient female mice.Plin3 knockdown significantly reduced the triglyceride content in basal condition of hepatocytes(P=0.001 4),and Plin2 knockdown just showed a decreased trend.Plin2 or Plin3 knockdown significantly reduced the triglyceride content separately in lipid-overloaded hepatocytes(P<0.05).Conclusion Hepatocyte Plin2 is essential in the development of microvesicular hepatic steatosis caused by CGI-58 deficiency.Both Plin2 and Plin3 are involved in lipid droplet formation and lipid accumulation in hepatocytes,and Plin3 shows a stronger effect.
2.Puerarin inhibits inflammation and lipid accumulation in alcoholic liver disease through regulating MMP8.
Ying HU ; Shuxian WANG ; Lan WU ; Kai YANG ; Fan YANG ; Junfa YANG ; Shuang HU ; Yan YAO ; Xun XIA ; Yixin LIU ; Li PENG ; Jihong WAN ; Chuanpu SHEN ; Tao XU
Chinese Journal of Natural Medicines (English Ed.) 2023;21(9):670-681
Alcoholic liver disease (ALD) is a growing global health concern, and its early pathogenesis includes steatosis and steatohepatitis. Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD. Evidence shows that puerarin (Pue), an isoflavone isolated from Pueraria lobata, exerts cardio-protective, neuroprotective, anti-inflammatory, antioxidant activities. However, the therapeutic potential of Pue on ALD remains unknown. In the study, both the NIAAA model and ethanol (EtOH)-induced AML-12 cell were used to explore the protective effect of Pue on alcoholic liver injury in vivo and in vitro and related mechanism. The results showed that Pue (100 mg·kg-1) attenuated EtOH-induced liver injury and inhibited the levels of SREBP-1c, TNF-α, IL-6 and IL-1β, compared with silymarin (Sil, 100 mg·kg-1). In vitro results were consistent within vivo results. Mechanistically, Pue might suppress liver lipid accumulation and inflammation by regulating MMP8. In conclusion, Pue might be a promising clinical candidate for ALD treatment.
3.Hepatotoxic mechanism of diclofenac sodium on broiler chicken revealed by iTRAQ-based proteomics analysis
Chuanxi SUN ; Tianyi ZHU ; Yuwei ZHU ; Bing LI ; Jiaming ZHANG ; Yixin LIU ; Changning JUAN ; Shifa YANG ; Zengcheng ZHAO ; Renzhong WAN ; Shuqian LIN ; Bin YIN
Journal of Veterinary Science 2022;23(4):e56-
Background:
At the therapeutic doses, diclofenac sodium (DFS) has few toxic side effects on mammals. On the other hand, DFS exhibits potent toxicity against birds and the mechanisms remain ambiguous.
Objectives:
This paper was designed to probe the toxicity of DFS exposure on the hepatic proteome of broiler chickens.
Methods:
Twenty 30-day-old broiler chickens were randomized evenly into two groups (n = 10).DFS was administered orally at 10 mg/kg body weight in group A, while the chickens in group B were perfused with saline as a control. Histopathological observations, serum biochemical examinations, and quantitative real-time polymerase chain reaction were performed to assess the liver injury induced by DFS. Proteomics analysis of the liver samples was conducted using isobaric tags for relative and absolute quantification (iTRAQ) technology.
Results:
Ultimately, 201 differentially expressed proteins (DEPs) were obtained, of which 47 were up regulated, and 154 were down regulated. The Gene Ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to screen target DEPs associated with DFS hepatotoxicity. The regulatory relationships between DEPs and signaling pathways were embodied via a protein-protein interaction network. The results showed that the DEPs enriched in multiple pathways, which might be related to the hepatotoxicity of DFS, were “protein processing in endoplasmic reticulum,” “retinol metabolism,” and “glycine, serine, and threonine metabolism.”
Conclusions
The hepatotoxicity of DFS on broiler chickens might be achieved by inducing the apoptosis of hepatocytes and affecting the metabolism of retinol and purine. The present study could provide molecular insights into the hepatotoxicity of DFS on broiler chickens.
4.Risk factors and predictive biomarkers of immune checkpoint inhibitor-associated pneumonia in non-small cell lung cancer
Hui WANG ; Rong XIA ; Qingwen WEI ; Yixin WAN
Journal of International Oncology 2021;48(5):296-301
The use of immune checkpoint inhibitors (ICIs) has changed the clinical outcome of non-small cell lung cancer (NSCLC), with the widespread application of ICIs, immune-related adverse events (irAEs) have also appeared. Immune checkpoint inhibitor pneumonitis (CIP) is a serious adverse event of ICIs treatment that needs attention. Therefore, early identification of high-risk groups of CIPs and early intervention can reduce the occurrence of permanent drug withdrawal and severe CIPs, thereby improving patients′ prognosis.
5.Prevention and treatment of cross infection of novel coronavirus pneumonia in thoracic surgery ward
WANG Qi ; KUANG Wan ; PING Wei ; GAO Yi ; HAO Zhipeng ; CAI Yixin ; LI Yangkai ; ZHANG Ni ; FU Xiangning
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2020;27(04):371-375
Objective By summarizing the clinical characteristics of perioperative patients with cross infection of novel coronavirus in thoracic surgery ward, to guide the prevention and treatment of nosocomial infection during the anti-epidemic period. Methods The clinical data of 451 patients with chest diseases in the Department of Thoracic Surgery of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 1st to 24th, 2020 were analyzed and followed up. There were 245 surgical patients and 206 non-surgical patients. Results In the department, 7 patients (7/451, 1.55%) were infected with the novel coronavirus and all of them were surgical patients, whose preoperative imaging data did not reveal the imaging changes of novel coronavirus. There were 5 males and 2 females, aged 56 to 68 years. The patients with old age, smoking, surgery, coronary heart disease, chronic liver disease and tumor history were more susceptible to infection. From the spatial distribution of patient beds, it was found that the distance among infected patients was greater than 1 m, and no cross infection was found in the other patients of the same ward. During follow-up, two family members of noninfected patients were found to be infected one week after discharge. However, there was no overlap of spatiotemporal distribution between the family members and the infected patients during the hospitalization period. Conclusion The novel coronavirus pneumonia rate in the department of thoracic surgery is low, which may be opportunistic infection. At the same time, a good control and prevention of epidemic disease can reduce the occurrence of cross infection in the department of thoracic surgery.
6.The clinical value of endobronchial ultrasound elastography in the diagnosis of medias-tinal and hilar lymph nodes
Li ZHANG ; Hong WANG ; Yixin WAN
Chinese Journal of Clinical Oncology 2019;46(9):463-467
Objective: Four ultrasound elastography parameters were used to compare the color distribution of mediastinal and hilar lymph nodes (LNs) in endobronchial ultrasound real-time elastography (EBUS-RTE), and the clinical value in differentiating benign from malignant mediastinal and hilar lymph nodes were explored. Methods: We selected patients who received EBUS-TBNA in the Second Hospital of Lanzhou University from January 2016 to December 2018 and simultaneously conducted EBUS-RTE. Elastography of lymph nodes were analyzed by elastography image type, elasticity score, strain ratio (SR), and blue color proportion (BCP), respectively. A re-ceiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of the four ultrasound elastography pa-rameters. The area under the curve (AUC) and the critical value of the best diagnosis were calculated, and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the four parameters were compared. Results: A total of 80 pa-tients were enrolled, including 152 lymph nodes with 102 malignant lymph nodes and 50 benign ones. Elastography image type, elas-ticity score, SR, and BCP had statistical significance in the differential diagnosis of benign and malignant lymph nodes (P<0.01). The ac-curacy of BCP in the diagnosis of benign and malignant lymph nodes was the highest (88.3%), and the sensitivity, specificity, positive predictive value, and negative predictive value were 90.0%, 94.1%, 85.4%, and 88.6%, respectively. The optimal definition value of BCP was 85.7%; all the 65 LNs with a BCP≥85.7% were diagnosed as malignant. Conclusions: Elastography image type, elasticity score, SR, and BCP of ultrasound elastography are important in the differential diagnosis of mediastinal and hilar lymph nodes, and BCP showed the highest diagnostic valuation.
7. The relationship between smoking and hyperuricemia in Chinese residents
Henggui CHEN ; Liting SHENG ; Zhenzhen WAN ; Xinchen WANG ; Yuhui LIN ; Yixin WANG ; Xiongfei PAN ; An PAN
Chinese Journal of Preventive Medicine 2018;52(5):524-529
Objective:
To explore the relationship between smoking and hyperuricemia in Chinese residents.
Methods:
Based on data from the China Health and Nutrition Survey (CHNS), residents with blood samples provided in the 2009 round (including information of socio-demographic factors, lifestyle behaviors, medical history, and laboratory examinations etc.) were selected as the participants in the current analysis. Unconditional logistic regression models were utilized to compute the
8.Surgical treatment and prognostic analysis for 57 patients with gastrointestinal lymphoma.
Jianhong PENG ; Binyi XIAO ; Yixin ZHAO ; Cong LI ; Rongxin ZHANG ; Gong CHEN ; Liren LI ; Zhenhai LU ; Peirong DING ; Desen WAN ; Zhizhong PAN ; Xiaojun WU ;
Chinese Journal of Gastrointestinal Surgery 2017;20(9):1040-1044
OBJECTIVETo explore clinicopathologic characteristics, surgical features and prognostic factors in patients with primary gastrointestinal lymphoma(PGIL) in order to provide evidence for optimizing surgical treatment.
METHODSClinicopathological data of 57 PGIL patients undergoing abdominal surgery in Sun Yat-sen University Cancer Center between October 1990 and January 2015 were retrospectively collected. The survival rates were compared among patients with different clinicopathologic characteristics by Kaplan-Meier method, while Cox regression model was employed to analyze the prognostic factors.
RESULTSAmong 57 patients, 43 were male and 14 were female, with a median age of 48 (range 16 to 80) years. Seventeen (29.8%) cases were classified as Musshoff I( stage, 19 (33.3%) cases as II( stage, 9 (15.8%) cases as III( stage, and 12(21.1%) cases as IIII( stage. Forty-four (77.2%) cases underwent selective operation, 13(22.8%) cases underwent emergent operation due to acute abdomen. Thirty-two(56.1%) cases had radical resection, 18 (31.6%) cases had partial resection and the rest 7(12.3%) cases failed to perform resection. Four (7.0%) cases received simple surgical operation, and 53 (93.0%) cases received comprehensive treatment, including 5(8.8%) cases with preoperative chemotherapy and surgery, 40 (70.2%) cases with surgery and postoperative chemotherapy, and 8 (14.0%) cases with surgery and perioperative chemotherapy. Stage III( and IIII( accounted for 76.9%(10/13) in patients undergoing emergent operation and accounted for 25.0%(11/44) in patients undergoing selective operation, whose difference was statistically significant (χ=9.503, P=0.002). Univariate prognostic analysis showed that T lymphocyte source pathological cell phenotype (P=0.000), clinical Musshoff stage III( and IIII((P=0.001), emergent operation (P=0.000) and incomplete tumor resection(P=0.007) had worse 5-year overall survival. Multivariate Cox regression analysis indicated that tumor pathological cell phenotype (HR=13.75, 95%CI:3.546-53.308, P=0.000) and surgical timing (HR=7.497, 95%CI:1.163-48.313, P=0.034) were independent prognostic risk factors of patients with stage I( and II(.
CONCLUSIONSSurgical operation is an important part of comprehensive treatment for PGIL. T lymphocyte source and ulcerative lymphoma indicates poorer prognosis.
9.A preliminary study on the promotion of angiogenesis by NETs in rheumatoid arthritis
Haimei MENG ; Yachong JIAO ; Yixin LIU ; Chunyou WAN ; Donghong XING ; Jun MA ; Fang ZHENG
Tianjin Medical Journal 2017;45(1):13-16
Objective To investigate the effect of neutrophil extracellular traps (NETs) on inflammation of rheumatoid arthritis (RA), especially angiogenesis. Methods The presence of NETs in synovial tissues of RA and osteoarthritis (OA) was observed by immunofluorescence assay. Neutrophils were isolated from peripheral blood of health volunteers. Neutrophils were cultured in vitro, the formation of NETs was observed. NETs were extracted as a stimulating agent. The effects of NETs on the proliferation of human umbilical vein endothelial cells (HUVECs) and synovial fibroblasts (RAFLS) were evaluated by MTT, and which were classified into two groups: HUVECs group and RAFLS group, with the following treatment: control and NETs (0.28 mg/L). Wound repair assay was employed to evaluate the effect on the cell migration stimulated with NETs. The experiment was divided into three groups:control, VEGF (40μg/L VEGF) and NETs (0.28 mg/L NETs). Results (1) Compared with OA, NETs were found more in the synovial tissue of RA. (2) NETs formation was induced by stimulator in vitro. The concentration of extracted NETs-DNA was 27.8 mg/L. (3) MTT assay showed that compared with the control groups, low concentration of NETs (0.28 mg/L) promoted the proliferation of HUVECs (0.499 ± 0.011 vs. 0.393 ± 0.009, P<0.05) and RAFLS (0.266 ± 0.007 vs. 0.192 ± 0.007, P<0.05). (4) It was showed that a significant wound closure induced by low concentration of NETs (0.28 mg/L) was found compared with control. Conclusion Our present study suggests that NETs are found more in the synovial tissue of RA, and low concentration of NETs can promote angiogenesis in RA.
10.Progress in sleep-disordered breathing in idiopathic pulmonary fibrosis
Ying ZHOU ; Runxu SONG ; Danbei DIWU ; Yixin WAN
Journal of Central South University(Medical Sciences) 2017;42(6):720-724
Idiopathic pulmonary fibrosis (IPF) is one of the most common idiopathic interstitial pneumonia.The main symptoms for IPF are dry cough and exertional shortness of breath,which is worsen gradually with the development of pulmonary fibrosis.Patients with IPF often suffer from sleep disordered breathing (SDB).Sleep architecture for these patients including the sleep efficiency,deep sleep,rapid eye movement sleep and arousal index,are changed,which seriously affects the quality of life.In the absence of effective therapies,optimizing the quality of life may become a major therapeutic target for IPF.The diagnosis and treatment of SDB can significantly improve the quality of life for patients with IPF.

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