1.Secreted Frizzled-Related Protein 5 Mediates Wnt5a Expression in Microcystin-Leucine-Arginine-Induced Liver Lipid Metabolism Disorder in Mice
Yang MEIYAN ; Yu FURONG ; Ji QIANQIAN ; Zhang HUIYING ; Zhang JIAXIANG ; Chen DAOJUN
Biomedical and Environmental Sciences 2024;37(8):850-864
Objective Microcystin-leucine-arginine(MC-LR)exposure induces lipid metabolism disorders in the liver.Secreted frizzled-related protein 5(SFRP5)is a natural antagonist of winglesstype MMTV integration site family,member 5A(Wnt5a)and an anti-inflammatory adipocytokine.In this study,we aimed to investigate whether MC-LR can induce lipid metabolism disorders in hepatocytes and whether SFRP5,which has anti-inflammatory effects,can alleviate the effects of hepatic lipid metabolism by inhibiting the Wnt5a/Jun N-terminal kinase(JNK)pathway. Methods We exposed mice to MC-LR in vivo to induce liver lipid metabolism disorders.Subsequently,mouse hepatocytes that overexpressed SFRP5 or did not express SFRP5 were exposed to MC-LR,and the effects of SFRP5 overexpression on inflammation and Wnt5a/JNK activation by MC-LR were observed. Results MC-LR exposure induced liver lipid metabolism disorders in mice and significantly decreased SFRP5 mRNA and protein levels in a concentration-dependent manner.SFRP5 overexpression in AML12 cells suppressed MC-LR-induced inflammation.Overexpression of SFRP5 also inhibited Wnt5a and phosphorylation of JNK. Conclusion MC-LR can induce lipid metabolism disorders in mice,and SFRP5 can attenuate lipid metabolism disorders in the mouse liver by inhibiting Wnt5a/JNK signaling.
2.Analysis of surgical situations and prognosis of pancreaticoduodenectomy in Jiangsu province (a report of 2 886 cases)
Zipeng LU ; Xin GAO ; Hao CHENG ; Ning WANG ; Kai ZHANG ; Jie YIN ; Lingdi YIN ; Youting LIN ; Xinrui ZHU ; Dongzhi WANG ; Hongqin MA ; Tongtai LIU ; Yongzi XU ; Daojun ZHU ; Yabin YU ; Yang YANG ; Fei LIU ; Chao PAN ; Jincao TANG ; Minjie HU ; Zhiyuan HUA ; Fuming XUAN ; Leizhou XIA ; Dong QIAN ; Yong WANG ; Susu WANG ; Wentao GAO ; Yudong QIU ; Dongming ZHU ; Yi MIAO ; Kuirong JIANG
Chinese Journal of Digestive Surgery 2024;23(5):685-693
Objective:To investigate the surgical situations and perioperative outcome of pancreaticoduodenectomy in Jiangsu Province and the influencing factors for postoperative 90-day mortality.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 886 patients who underwent pancreaticoduodenectomy in 21 large tertiary hospitals of Jiangsu Quality Control Center for Pancreatic Diseases, including The First Affiliated Hospital of Nanjing Medical University, from March 2021 to December 2022 were collected. There were 1 732 males and 1 154 females, aged 65(57,71)years. Under the framework of the Jiangsu Provincial Pancreatic Disease Quality Control Project, the Jiangsu Quality Control Center for Pancreatic Diseases adopted a multi-center registration research method to establish a provincial electronic database for pancrea-ticoduodenectomy. Observation indicators: (1) clinical characteristics; (2) intraoperative and post-operative conditions; (3) influencing factors for 90-day mortality after pancreaticoduodenectomy. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(IQR), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or constituent ratio, and comparison between groups was conducted using the chi-square test, continuity correction chi-square test and Fisher exact probability. Maximal Youden index method was used to determine the cutoff value of continuous variables. Univariate analysis was performed using the corresponding statistical methods based on data types. Multivariate analysis was performed using the Logistic multiple regression model. Results:(1) Clinical characteristics. Of the 2 886 patients who underwent pancreaticoduodenectomy, there were 1 175 and 1 711 cases in 2021 and 2022, respectively. Of the 21 hospitals, 8 hospitals had an average annual surgical volume of <36 cases for pancreaticoduodenectomy, 10 hospitals had an average annual surgical volume of 36-119 cases, and 3 hospitals had an average annual surgical volume of ≥120 cases. There were 2 584 cases performed pancreaticoduodenectomy in thirteen hospitals with an average annual surgical volume of ≥36 cases, accounting for 89.536%(2 584/2 886)of the total cases. There were 1 357 cases performed pancrea-ticoduodenectomy in three hospitals with an average annual surgical volume of ≥120 cases, accounting for 47.020%(1 357/2 886) of the total cases. (2) Intraoperative and postoperative conditions. Of the 2 886 patients, the surgical approach was open surgery in 2 397 cases, minimally invasive surgery in 488 cases, and it is unknown in 1 case. The pylorus was preserved in 871 cases, not preserved in 1 952 cases, and it is unknown in 63 cases. Combined organ resection was performed in 305 cases (including vascular resection in 209 cases), not combined organ resection in 2 579 cases, and it is unknown in 2 cases. The operation time of 2 885 patients was 290(115)minutes, the volume of intra-operative blood loss of 2 882 patients was 240(250)mL, and the intraoperative blood transfusion rate of 2 880 patients was 27.153%(782/2 880). Of the 2 886 patients, the invasive treatment rate was 11.342%(327/2 883), the unplanned Intensive Care Unit (ICU) treatment rate was 3.087%(89/2 883), the reoperation rate was 1.590%(45/2 830), the duration of postoperative hospital stay was 17(11)days, the hospitalization mortality rate was 0.798%(23/2 882), and the failure rate of rescue data in 2 083 cases with severe complications was 6.529%(19/291). There were 2 477 patients receiving postoperative 90-day follow-up, with the 90-day mortality of 2.705%(67/2477). The total incidence rate of complication in 2 886 patients was 58.997%(1 423/2 412). The incidence rate of severe complication was 13.970%(291/2 083). The comprehensive complication index was 8.7(22.6) in 2 078 patients. (3) Influencing factors for 90-day mortality after pancreaticoduodenectomy. Results of multivariate analysis showed that age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment were independent risk factors for 90-day mortality after pancreaticoduodenectomy ( odds ratio=2.403, 2.609, 16.141, 95% confidence interval as 1.281-4.510, 1.298-5.244, 7.119-36.596, P<0.05). Average annual surgical volume ≥36 cases in the hospital was an independent protective factor for 90-day mortality after pancreaticoduodenectomy ( odds ratio=0.368, 95% confidence interval as 0.168-0.808, P<0.05). Conclusions:Pancreaticoduodenectomy in Jiangsu Province is highly con-centrated in some hospitals, with a high incidence of postoperative complications, and the risk of postoperative 90-day mortality is significant higher than that of hospitallization mortality. Age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment are independent risk factors for 90-day motality after pancreaticoduodenectomy, and average annual surgical volume ≥36 cases in the hospital is an independent protective factor.
3.Value of generalized equivalent uniform dose optimization in radiotherapy for chest malignant tumors
Feng ZHANG ; Daojun ZHA ; Yu BAO
Chinese Journal of Radiological Health 2023;32(3):349-354
Objective To explore the value of generalized equivalent uniform dose (gEUD) optimization in radiotherapy for chest malignant tumors. Methods Sixty patients with chest malignant tumors who were treated in Center for Tumor Radiotherapy, Chizhou Municipal People’s Hospital, Anhui Province, China from October 2021 to June 2022 were enrolled; each patient underwent tumor localization with a conventional fixed computed tomography scan. The patients were divided into two groups using the same field direction and weight in the Varian Eclipse 15.6 planning system. The first group was planned using the conventional physical dose-volume objective function plus the Upper gEUD objective function, with organs at risks (OARs) optimized with the EUD values suggested by the Varian Eclipse 15.6 planning system. The second group only adopted the conventional physical dose-volume objective function for OARs optimization. The two groups were compared for the radiation doses delivered to the OARs. Results Compared with the conventional physical dose-volume objective function alone, the addition of Upper gEUD objective function resulted in no significant difference in lung V5Gy, but resulted in significant reductions in V20Gy and mean dose in the lungs; some reductions in V30Gy, V40Gy, and mean dose in the heart; and significant reductions in the maximum dose in the spinal cord. Conclusion The gEUD objective optimization can effectively protect the normal tissue in the radiotherapy for chest malignant tumors and thus is recommended in radiotherapy planning.
4.Abrogation of HnRNP L enhances anti-PD-1 therapy efficacy via diminishing PD-L1 and promoting CD8+ T cell-mediated ferroptosis in castration-resistant prostate cancer.
Xumin ZHOU ; Libin ZOU ; Hangyu LIAO ; Junqi LUO ; Taowei YANG ; Jun WU ; Wenbin CHEN ; Kaihui WU ; Shengren CEN ; Daojun LV ; Fangpeng SHU ; Yu YANG ; Chun LI ; Bingkun LI ; Xiangming MAO
Acta Pharmaceutica Sinica B 2022;12(2):692-707
Owing to incurable castration-resistant prostate cancer (CRPC) ultimately developing after treating with androgen deprivation therapy (ADT), it is vital to devise new therapeutic strategies to treat CRPC. Treatments that target programmed cell death protein 1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved for human cancers with clinical benefit. However, many patients, especially prostate cancer, fail to respond to anti-PD-1/PD-L1 treatment, so it is an urgent need to seek a support strategy for improving the traditional PD-1/PD-L1 targeting immunotherapy. In the present study, analyzing the data from our prostate cancer tissue microarray, we found that PD-L1 expression was positively correlated with the expression of heterogeneous nuclear ribonucleoprotein L (HnRNP L). Hence, we further investigated the potential role of HnRNP L on the PD-L1 expression, the sensitivity of cancer cells to T-cell killing and the synergistic effect with anti-PD-1 therapy in CRPC. Indeed, HnRNP L knockdown effectively decreased PD-L1 expression and recovered the sensitivity of cancer cells to T-cell killing in vitro and in vivo, on the contrary, HnRNP L overexpression led to the opposite effect in CRPC cells. In addition, consistent with the previous study, we revealed that ferroptosis played a critical role in T-cell-induced cancer cell death, and HnRNP L promoted the cancer immune escape partly through targeting YY1/PD-L1 axis and inhibiting ferroptosis in CRPC cells. Furthermore, HnRNP L knockdown enhanced antitumor immunity by recruiting infiltrating CD8+ T cells and synergized with anti-PD-1 therapy in CRPC tumors. This study provided biological evidence that HnRNP L knockdown might be a novel therapeutic agent in PD-L1/PD-1 blockade strategy that enhanced anti-tumor immune response in CRPC.
5.Expression of long noncoding RNA in papillary thyroid carcinoma with Hashimoto's thyroiditis
Yu ZHANG ; Jinwang DING ; Dingcun LUO ; You PENG ; Wo ZHANG ; Gang PAN ; Daojun YU
Chinese Journal of Endocrine Surgery 2018;12(1):24-29
Objective To analyze long noncoding RNAs (lncRNAs) expression profiles in papillary thyroid carcinoma (PTC) with Hashimoto's thyroiditis (PTC-HT,group A) and PTC only (PTC,group B).Methods 55 cases of thyroid species were collected.High-throughput microarray lncRNh was used to detect the expression difference of lncRNAs between group A and group B.Real-time quantitative PCR (QRT-PCR) was used to verify.Results 1031 lncRNAs and 1338 mRNAs were detected abnormally expressed in tissue samples of group A compared to B.GO and Pathway analysis of mRNAs suggested some biological processes changed obviously,such as immune system and immune reaction.QRT-PCR showed that the expression of uc002stn.1,ENST00000452578 and uc002sti.1 in group A and group B was significantly different.Conclusion IncRNAs expression was significantly different in PTC with or without HT,which may play important roles in the pathogenesis of PTC with HT.
6.Surgical and micro-invasive treatment of pancreatic duct stones: an analysis of 42 patients
Liyuan WANG ; Daojun GONG ; Shian YU ; Xuemin LI ; Xiaokang WU ; Longtang XU ; Genjun MAO ; Rongjin WU ; Bin YANG ; Chi GUO ; Jiamin ZHANG ; Zhangdong ZHENG
Chinese Journal of Hepatobiliary Surgery 2018;24(2):122-123
Pancreatic duct stone is a sequel of chronic pancreatitis and may be found in the main ducts,side branches or parenchyma.These stones obstruct the pancreatic ducts and produce ductal hypertension,which leads to pain,the cardinal feature of CP.Surgical operation has been the preferred treatment of pancreatic duct stones in many domestic and external pancreatic medical centers.Lithotomy by longitudinal pancreatic duct incision and Roux-en-Y anastomosis of pancreatic duct to jejunum is the main and effective surgical procedure,while micro-surgery was also rational for the treatment of pancreatic duct stones.However,further studies with a larger sample size and longer follow-up duration are needed to improve the surgical technique and verify our initial results.
7.Relationship between serum free fatty acids level and insulin resistance in patients with type 2 diabetes mellitus
Miao YU ; Li ZHANG ; Bing QIN ; Daojun HU
Journal of Clinical Medicine in Practice 2018;22(7):120-122
Objective To investigate the relationship between serum free fatty acids (FFA) and insulin resistance (IR) in patients with type 2 diabetes mellitus (T2DM).Methods Totally 106 T2DM patients were selected as observation group,and 106 healthy people were selected as control group.Body mass index (BMI),FPG,FFA,HbAlc,TG,TC and HOMA-IR were compared between two groups.According to the blood glucose level,the T2DM patients were divided into good control group (n =56) and bad control group (n =50),and the FFA and HOMA-IR were compared two groups.Correlation between serum FFA and HOMA-IR in patients with T2DM was analyzed.Results In the observation group,BMI,FPG,FFA,HbA1 C,TC,TG and HOMA-IR were significantly higher than the control group (P < 0.05).FFA and HOMA-IR in bad control group were significantly higher than the good control group (P < 0.05).Correlation analysis showed that serum FFA was positively correlated with HOMA-IR level in T2DM patients (r =0.621,P < 0.05).Conclusion Serum free fatty acids level is closely related to insulin resistance in patients with T2DM,which can reflect the blood glucose control level.
8.Relationship between serum free fatty acids level and insulin resistance in patients with type 2 diabetes mellitus
Miao YU ; Li ZHANG ; Bing QIN ; Daojun HU
Journal of Clinical Medicine in Practice 2018;22(7):120-122
Objective To investigate the relationship between serum free fatty acids (FFA) and insulin resistance (IR) in patients with type 2 diabetes mellitus (T2DM).Methods Totally 106 T2DM patients were selected as observation group,and 106 healthy people were selected as control group.Body mass index (BMI),FPG,FFA,HbAlc,TG,TC and HOMA-IR were compared between two groups.According to the blood glucose level,the T2DM patients were divided into good control group (n =56) and bad control group (n =50),and the FFA and HOMA-IR were compared two groups.Correlation between serum FFA and HOMA-IR in patients with T2DM was analyzed.Results In the observation group,BMI,FPG,FFA,HbA1 C,TC,TG and HOMA-IR were significantly higher than the control group (P < 0.05).FFA and HOMA-IR in bad control group were significantly higher than the good control group (P < 0.05).Correlation analysis showed that serum FFA was positively correlated with HOMA-IR level in T2DM patients (r =0.621,P < 0.05).Conclusion Serum free fatty acids level is closely related to insulin resistance in patients with T2DM,which can reflect the blood glucose control level.
9.Comprehensive Evaluation of the Diagnostic Value of the Combined Detection of IMA,NLR,hs-CRP and CK-MB for Acute Myocardial Infarction Based on ROC Curve and Logistic Regression Analysis
Daojun HU ; Miao YU ; Honglei ZHANG ; Yi TANG ; Li ZHANG
Journal of Modern Laboratory Medicine 2016;31(5):76-80
Objective To assess the diagnostic value of IMA,NLR,hs-CRP and CK-MB individually and the combined detec-tion for early acute myocardial infarction using ROC curve and Logistic regression.Methods To detect levels of IMA,NLR, hs-CRP,CK-MB and cTnI in serum or whole blood of AMI patients that had chest pain within 3 hours or between 3 and 6 hours,compared with 60 healthy people from Physical Examination Center.Applied Logistic regression,plotted ROC curve and calculated the area under ROC curve (AUC)to assess the diagnostic value of each index.Results The serum IMA,hs-CRP,CK-MB and cTnI or whole blood NLR levels of AMI patients with 3 hours were remarkably higher than normal con-trol,showing significant statistical difference (P<0.01)(AMI group:mean values of IMA,NLR,hs-CRP,CK-MB and cTnI were 96.04 U/L,3.77,13.39 mg/L,43.26 U/L and 0.063 ng/ml;normal control group:mean values of IMA,NLR,hs-CRP,CK-MB and cTnI were 78.10 U/L,2.02,3.12 mg/L,19.37 U/L and 0.040 ng/ml.The serum IMA,NLR,hs-CRP, CK-MB and cTnI levels of AMI patients in the group between 3~6 hours were higher than in the group within 3 hours (P<0.05).The AUC of combined detection of IMA,NLR,hs-CRP and CK-MB for early AMI was 0.98,higher than solo de-tection of IMA,NLR,hs-CRP and CK-MB,which were 0.89,0.83,0.79 and 0.85 respectively.Meanwhile,the AUC of com-bined detection for four markers also surpassed that of cTnI alone that was recognized as a classic serological marker to diag-nose AMI (AUC=0.78).Conclusion The combined detection of IMA,NLR,hs-CRP and CK-MB is superior to a single in-dex detection,which can significantly improve diagnostic efficiency for early AMI.
10.Advances of long non-coding RNA in thyroid tumor
Yu ZHANG ; Jinwang DING ; You PENG ; Xiaocheng XU ; Dingcun LUO ; Daojun YU ; Qiaofeng TU
Chinese Journal of Endocrine Surgery 2016;10(4):336-339
Long non-coding RNA(lncRNA) is non-protein coding transcripts longer than 200 nucleotides,which plays an important role in the development of the metabolic process.Thyroid cancer is the most common cancer of the endocrine system,and as reported,lncRNA is related to the occurrence and development of thyroid tumors.Therefore,this paper reports the latest domestic and foreign research progress about lncRNA in thyroid tumor,in order to provide new ideas for molecular diagnosis and treatment of thyroid cancer.

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