1.Clinical values of SAA and hs-CRP in the diagnosis of postoperative infection in patients with ovarian tumor
Guoqiang FU ; Jiayun XIA ; Guangyong WANG
Chinese Journal of Primary Medicine and Pharmacy 2017;24(7):1069-1072
Objective To investigate the clinical values of serum amyloid A (SAA) and hypersensitivity C reactive protein(hs-CRP) in the diagnosis of postoperative infection in patients with ovarian tumor.Methods Clinical data of 679 patients with ovarian tumor were retrospectively analyzed.According to the development of postoperative infection or not,all patients were assigned into infection group(n =45) or non-infection group(n =634).The primary outcomes indicators were SAA,hs-CRP,C reactive protein(CRP) and white blood cell.Results Compared with the non-infection group,the infection group got a significantly higher levels of SAA [(104.73 ± 34.74) mg/L vs.(6.12 ±0.74) mg/L,t =25.546,P =0.000] and hs-CRP [(142.35 ± 43.84) mg/L vs.(18.45 ± 5.39) mg/L,t =24.595,P =0.000] and white blood cell [(11.48 ± 3.59) × 109/L vs.(7.49 ± 2.83) × 109/L,t =6.305,P =0.000] and CRP [(32.58 ± 10.48) mg/L vs.(16.34 ± 8.47) mg/L,t =8.496,P =0.000].The area under the Receiver Operating Characteristic of SAA,hs-CRP,white blood cell and CRP were 0.879 (95% confidence interval:0.825 ~ 0.920,P =0.000),0.858(95% confidence interval:0.792 ~0.925,P =0.000),0.737(95% confidence interval:0.658 ~0.817,P =0.000) and 0.767 (95 % confidence interval:0.713 ~ 0.822,P =0.000).Z tests showed that the areas under the curve of SAA and hs-CRP in the diagnosis of postoperative infection in patients with ovarian tumor were higher than white blood cells and CRP(all P < 0.05).Conclusion SAA and hs-CRP have better diagnostic values in the postoperative infection of ovarian tumor,and it is worth to be popularized.
2.Cortistatin expression in renal tissue of humans and IgA nephropathy patients
Xiaoyuan NING ; Xia CHEN ; Xiaojing JIAO ; Xueguang ZHANG ; Jiayun XU
Military Medical Sciences 2017;41(2):106-110
Objective To explore the condition of cortistatin (CST)expression in human renal tissue and the changes in the level of CST in IgA nephropathy (IgAN)of different degrees.Methods Ten tumor adjacent normal renal tissue samples were collected.The mRNA and protein expressions of CST in human renal tissue were detected by reverse transcription-polymerase chain reaction (RT-PCR)and Western blotting,respectively.Immunohistochemisty (IHC)was performed to locate the expression of CST in renal tissue.According to the grading system of Lee et al,IgAN was divided into three groups:grade Ⅰ -Ⅱ (group A),grade Ⅲ -Ⅳ (group B),and grade Ⅴ (group C),and ten renal biopsy tissue samples were collected for each group.IHC was performed to detect the change in the level of CST in normal and IgAN renal tissue of different degrees.The effect of clinical indices on the level of CST in IgAN renal tissue was assessed by multiple linear regression analysis.Results RT-PCR and Western blotting showed that CST was expressed in renal tissue and IHC showed that CST was expressed on renal tubular epithelial cells.In IgAN,the higher the pathological grade was, the higher the expression of CST in renal tubules was.Multiple linear regression analysis showed that the pathological grade was associated with the expression of CST in renal tissue (r =0.875,P <0.01).Conclusion CST may participate in the inflammatory reaction of IgAN pathological injury and exert anti-inflammation effects.
3.Exploration and Practice of Question-and-answer Practice Teaching in Pharmacy Department of Hospital
Yanling WU ; Yuanwen WU ; Wei HU ; Xiaoming PAN ; Lulu XIA ; Jiayun LU
China Pharmacy 2015;(30):4309-4310,4311
OBJECTIVE:To explore the feasibility of question-and-answer practice teaching in the pharmacy department of our hospital. METHODS:The practice teaching of pharmacy department was taken as a pilot,and the question-and-answer practice teaching was used in emergency and outpatient pharmacies,inpatient pharmacy,PIVAS,drug warehouse,clinical pharmaceutics room,preparation room and drug testing laboratory. The effects of the practice teaching on internships,teachers,pharmacy depart-ments and patients were excavated. RESULTS & CONCLUSIONS:Satisfaction of teachers,pharmacy,patients and clinics for the question-and-answer practice teaching was 100%,and satisfaction of internships was 94.5%. The question-and-answer practice teaching has improved their professional knowledge and competence,resolved difficulty of patients about drug counseling and helped the improvement of overall business level in department.
4.An automatic VMAT planning method for primary liver cancer radiotherapy based on predicting the feasibility DVH
Fei HAN ; Wenlong XIA ; Pan MA ; Wenting REN ; Jiayun CHEN ; Kuo MEN ; Bo CHEN ; Jianrong DAI
Chinese Journal of Radiation Oncology 2021;30(8):797-802
Objective:To establish an automatic planning method using volumetric-modulated arc therapy (VMAT) for primary liver cancer (PLC) radiotherapy based on predicting the feasibility dose-volume histogram (DVH) and evaluate its performance.Methods:Ten patients with PLC were randomly chosen in this retrospective study. Pinnacle Auto-Planning was used to design the VMAT automatic plan, and the feasibility DVH curve was obtained through the PlanIQ dose prediction, and the initial optimization objectives of the automatic plan were set according to the displayed feasible objectives interval. The plans were accessed according to dosimetric parameters of the planning target volume and organs at risk as well as the monitor units. All patients′ automatic plans were compared with clinically accepted manual plans by using the paired t-test. Results:There was no significant difference of the planning target volume D 2%, D 98%, D mean or homogeneity index between the automatic and manual plans ((58.55±2.81) Gy vs.(57.98±4.17) Gy, (47.15±1.58) Gy vs.(47.82±1.38) Gy, (53.14±0.95) Gy vs.(53.44±1.67) Gy and 1.15±0.05 vs. 1.14±0.07, all P>0.05). The planning target volume conformity index of the manual plan was slightly higher than that of the automatic plan (0.77±0.08 vs. 0.69±0.06, P<0.05). The mean doses of normal liver, V 30Gy, V 20Gy, V 10Gy, V 5Gy and V< 5Gy of the automatic plan were significantly better than those of the manual plan ((26.68±11.13)% vs.(28.00±10.95)%, (29.96±11.50)% vs.(31.89±11.51)%, (34.88±11.51)% vs.(38.66±11.67)%, (45.38±12.40)% vs.(50.74±13.56)%, and (628.52±191.80) cm 3vs.(563.15±188.39) cm 3, all P<0.05). The mean doses of the small intestine, the duodenum, and the heart, as well as lung V 10 of the automatic plan were significantly less than those of the manual plan ((1.83±2.17) Gy vs.(2.37±2.81) Gy, (9.15±9.36) Gy vs.(11.18±10.49) Gy, and (5.44±3.10) Gy vs.(6.25±3.26) Gy, as well as (12.70±7.08)% vs.(14.47±8.11)%, all P<0.05). Monitor units did not significantly differ between two plans ((710.67±163.72) MU vs.(707.53±155.89) MU, P>0.05). Conclusions:The automatic planning method using VMAT for PLC radiotherapy based on predicting the feasibility DVH enhances the quality for PLC plans, especially in terms of normal liver sparing. Besides, it also has advantages for the protection of the intestine, whole lung and heart.
5.18beta-glycyrrhetinic acid induces ROS-mediated apoptosis to ameliorate hepatic fibrosis by targeting PRDX1/2 in activated HSCs
Zhang QIAN ; Luo PIAO ; Zheng LIUHAI ; Chen JIAYUN ; Zhang JUNZHE ; Tang HUAN ; Liu DANDAN ; He XUELING ; Shi QIAOLI ; Gu LIWEI ; Li JIAHAO ; Guo QIUYAN ; Yang CHUANBIN ; Wong Kwan YIN ; Xia FEI ; Wang JIGANG
Journal of Pharmaceutical Analysis 2022;12(4):570-582
Hepatic stellate cells(HSCs)are essential drivers of fibrogenesis.Inducing activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18β-GA)is a natural com-pound that exists widely in herbal medicines,such as Glycyrrhiza uralensis Fisch,which is used for treating multiple liver diseases,especially in Asia.In the present study,we demonstrated that 18β-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18β-GA inhibited the expression of α-smooth muscle actin and collagen type Ⅰ alpha-1.Using a chemoproteomic approach derived from activity-based protein profiling,together with cellular thermal shift assay and surface plasmon reso-nance,we found that 18β-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18β-GA induced the elevation of reactive oxygen species(ROS),resulting in the apoptosis of activated HSCs.PRDX1 knockdown also led to ROS-mediated apoptosis in activated HSCs.Collectively,our findings revealed the target proteins and molecular mechanisms of 18β-GA in ameliorating hepatic fibrosis,highlighting the future development of 18β-GA as a novel therapeutic drug for hepatic fibrosis.
6.A highly efficient protein corona-based proteomic analysis strategy for the discovery of pharmacodynamic biomarkers
Yuqing MENG ; Jiayun CHEN ; Yanqing LIU ; Yongping ZHU ; Yin-Kwan WONG ; Haining LYU ; Qiaoli SHI ; Fei XIA ; Liwei GU ; Xinwei ZHANG ; Peng GAO ; Huan TANG ; Qiuyan GUO ; Chong QIU ; Chengchao XU ; Xiao HE ; Junzhe ZHANG ; Jigang WANG
Journal of Pharmaceutical Analysis 2022;12(6):879-888
The composition of serum is extremely complex,which complicates the discovery of new pharmaco-dynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich low-abundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and devel-oped a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56%using PC-based proteomic analysis,which was twice the number of proteins iden-tified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.
7.Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice
Qiuyan GUO ; Jiangpeng WU ; Qixin WANG ; Yuwen HUANG ; Lin CHEN ; Jie GONG ; Maobo DU ; Guangqing CHENG ; Tianming LU ; Minghong ZHAO ; Yuan ZHAO ; Chong QIU ; Fei XIA ; Junzhe ZHANG ; Jiayun CHEN ; Feng QIU ; Jigang WANG
Journal of Pharmaceutical Analysis 2023;13(8):908-925
Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated he-patic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and ther-apeutic targets for liver protection.
8.Celastrol induces ferroptosis in activated HSCs to ameliorate hepatic fibrosis via targeting peroxiredoxins and HO-1.
Piao LUO ; Dandan LIU ; Qian ZHANG ; Fan YANG ; Yin-Kwan WONG ; Fei XIA ; Junzhe ZHANG ; Jiayun CHEN ; Ya TIAN ; Chuanbin YANG ; Lingyun DAI ; Han-Ming SHEN ; Jigang WANG
Acta Pharmaceutica Sinica B 2022;12(5):2300-2314
Ferroptosis is a form of regulated cell death, characterized by excessive membrane lipid peroxidation in an iron- and ROS-dependent manner. Celastrol, a natural bioactive triterpenoid extracted from Tripterygium wilfordii, shows effective anti-fibrotic and anti-inflammatory activities in multiple hepatic diseases. However, the exact molecular mechanisms of action and the direct protein targets of celastrol in the treatment of liver fibrosis remain largely elusive. Here, we discover that celastrol exerts anti-fibrotic effects via promoting the production of reactive oxygen species (ROS) and inducing ferroptosis in activated hepatic stellate cells (HSCs). By using activity-based protein profiling (ABPP) in combination with bio-orthogonal click chemistry reaction and cellular thermal shift assay (CETSA), we show that celastrol directly binds to peroxiredoxins (PRDXs), including PRDX1, PRDX2, PRDX4 and PRDX6, through the active cysteine sites, and inhibits their anti-oxidant activities. Celastrol also targets to heme oxygenase 1 (HO-1) and upregulates its expression in activated-HSCs. Knockdown of PRDX1, PRDX2, PRDX4, PRDX6 or HO-1 in HSCs, to varying extent, elevated cellular ROS levels and induced ferroptosis. Taken together, our findings reveal the direct protein targets and molecular mechanisms via which celastrol ameliorates hepatic fibrosis, thus supporting the further development of celastrol as a promising therapeutic agent for liver fibrosis.