1.The characteristic analysis of lipid metabolism and intestinal flora in platinum-resistant ovarian cancer at stage Ⅲ-Ⅳ based on the theory of"tumour toxicity"in traditional Chinese medicine
Haili JIANG ; Yingquan YE ; Die HU ; Rui SHENG ; Chaozheng GAO ; Shuqi ZHAN ; Mei ZHANG ; Ting WANG
Acta Universitatis Medicinalis Anhui 2024;59(10):1863-1870
Objective To compare the differences in lipid metabolism between platinum-resistant and platinum-sensitive ovarian cancer patients at stage Ⅲ-Ⅳ,to analyze the differential intestinal flora using 16S rRNA sequen-cing,and to explore the associations among intestinal flora,lipid metabolism characteristics and platinum resistance in ovarian cancer.Methods Patients diagnosed with ovarian cancer at stage Ⅲ-Ⅳ through surgical pathology were selected,including a platinum-resistant group(11 cases)and a platinum-sensitive group(11 cases).The differences in lipid metabolism between the two groups were compared.The differences in gut microbiota between the two groups were investigated using fecal 16S rRNA sequencing.The association among gut microbiota,lipid metabolism characteristics,and platinum resistance in ovarian cancer was analyzed.Results Significant differ-ences were observed in lipid metabolism-related indicators[total cholesterol(TC),high-density lipoprotein choles-terol(HDL-C),non-high-density lipoprotein cholesterol(n-HDL),low-density lipoprotein cholesterol(LDL-C),apolipoprotein(B)]between the two groups,with higher levels in the platinum-resistant group.The Shannon in-dex(P=0.008 3)and Simpson index(P=0.008 2)both showed higher diversity of gut microbiota in platinum-resistant ovarian cancer patients compared to the platinum-sensitive group.However,based on OTUs species clus-tering and relative abundance statistics,certain bacterial abundances differed significantly between the groups.Spe-cies such as Parabacteroides,Akkermansia,Blautia,Lachnoclostridium,Fusicatenibacter,and Megamonas had sig-nificantly higher abundances in the platinum-sensitive ovarian cancer group,and Akkermansia(a lipid metabolism-related bacterial group)was the most prevalent.Conclusion The platinum-resistant group of ovarian cancer ex-hibits significantly higher levels of lipid metabolism and gut microbiota diversity compared to the platinum-sensitive group.This suggests that the increase in lipid metabolism levels and fecal microbiota diversity may be associated with the development of platinum resistance.However,certain microbial taxa are reduced in abundance in the plat-inum-resistant group,such as the distinct Akkermansia genus(a lipid metabolism-related microbial community),which may serve as one of the factors inducing platinum-resistance in ovarian cancer.
2.Expression levels of serum high-mobility group box 1,soluble CD163,and prostaglandin E2 in patients with hepatitis B virus-related chronic-on-acute liver failure and their value in predicting prognosis
Chenlu HAN ; Haijun LIANG ; Daokun YANG ; Haiyan CHANG ; Shuai WEI ; Xingwei WANG ; Haili GAO
Journal of Clinical Hepatology 2024;40(6):1130-1135
Objective To investigate the expression levels of serum high-mobility group box 1(HMGB1),soluble CD163(sCD163),and prostaglandin E2(PGE2)in patients with hepatitis B virus-related chronic-on-acute liver failure(HBV-ACLF),and to evaluate the value of the three indicators used alone or in combination in predicting prognosis.Methods A total of 76 patients with HBV-ACLF who were hospitalized in Department of Infectious Diseases,The First Affiliated Hospital of Xinxiang Medical University,from July 1,2022 to September 30,2023 were enrolled,and according to the 28-day prognosis,they were divided into survival group with 48 patients and death group with 28 patients.General data were collected,Model for End-Stage Liver Disease(MELD)score was calculated,and ELISA was used to measure the serum levels of HMGB1,sCD163,and PGE2.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.The Spearman rank correlation test was used to analyze the correlation of HMGB1,sCD163,and PGE2 with MELD score;the receiver operating characteristic(ROC)curve was used to analyze the value of HMGB1,sCD163,and PGE2 used alone or in combination in predicting the prognosis of HBV-ACLF patients.Results There were significant differences between the two groups in total bilirubin,white blood cell count,the percentage of neutrophils,procalcitonin,serum amyloid A,interleukin-6,serum sodium,and serum creatinine(all P<0.05).Compared with the survival group,the death group had significantly higher serum levels of HMGB1(Z=-2.997,P=0.003)and sCD163(Z=-2.972,P=0.003),a significantly higher MELD score(t=-6.997,P<0.001),and a significantly lower serum level of PGE2(Z=-4.909,P<0.001).The Spearman rank correlation test showed that HMGB1 and sCD163 were positively correlated with MELD score(r=0.431 and 0.319,both P<0.05),while PGE2 was negatively correlated with MELD score(r=-0.412,P<0.05).The ROC curve analysis showed that HMGB1,sCD163,and PGE2 used alone had an area under the ROC curve(AUC)of 0.717,0.716,and 0.856,respectively,while the combination of the three indicators had the highest predictive value,with an AUC of 0.930,a sensitivity of 0.778,and a specificity of 0.920.Conclusion Serum HMGB1,sCD163,and PGE2 used alone or in combination have a good reference value in predicting the prognosis of HBV-ACLF patients,and the combination of the three indicators has the highest predictive value,which holds promise for further observation and research.
3.Methods and Challenges for Identifying and Controlling Confounding Factors in Traditional Chinese Medicine Observational Studies
Guozhen ZHAO ; Ziheng GAO ; Chen ZHAO ; Huizhen LI ; Ning LIANG ; Bin LIU ; Qianzi CHE ; Haili ZHANG ; Yixiang LI ; Feng ZHOU ; He LI ; Bo LI ; Nannan SHI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):120-126
As a supplement to randomized controlled trials, observational studies can provide evidence for the effectiveness of traditional Chinese medicine (TCM) treatment measures. They can also study influencing factors of diseases, etiology, and prognosis. However, there is a confounding effect due to the lack of randomization, which seriously affects the causal inference between the study factors and the outcome, resulting in confounding bias. Therefore, identifying and controlling confounding factors are key issues to be addressed in TCM observational studies. According to the causal network and the characteristics of TCM theory, confounding factors can be categorized into measured and unmeasured confounding factors. In addition, attention must be paid to identifying confounding factors and intermediate variables, as well as the interaction between confounding factors and study factors. For methods of controlling confounding factors, measured confounding factors can be controlled by stratification, multifactor analysis, propensity scores, and disease risk scores. Unmeasured and unknown confounding factors can be corrected using instrumental variable methods, difference-in-difference methods, and correction for underlying event rate ratios. Correcting and controlling confounding factors can ensure a balance between groups, and confounding bias can be reduced. In addition, methods such as sensitivity analysis and determination of interactions make the control of confounding factors more comprehensive. Due to the unique characteristics of TCM, observational studies of TCM face unique challenges in identifying and controlling confounding factors, including the ever-changing TCM treatment measures received by patients, the often-overlooked confounding effects in the four diagnostic information of TCM, and the lack of objective criteria for TCM evidence-based diagnosis. Some scholars have already conducted innovative explorations to address these issues, providing a methodological basis for conducting higher-quality TCM observational studies, so as to obtain more rigorous real-world evidence of TCM and gradually develop quality evaluation criteria for OS that are consistent with the characteristics of TCM.
4.Hollow copper sulfide nanoparticles carrying ISRIB for the sensitized photothermal therapy of breast cancer and brain metastases through inhibiting stress granule formation and reprogramming tumor-associated macrophages.
Fan TONG ; Haili HU ; Yanyan XU ; Yang ZHOU ; Rou XIE ; Ting LEI ; Yufan DU ; Wenqin YANG ; Siqin HE ; Yuan HUANG ; Tao GONG ; Huile GAO
Acta Pharmaceutica Sinica B 2023;13(8):3471-3488
As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.
5.Factors influencing changes in total radioactivity in differentiated thyroid cancer patients after 131I treatment
Liuyan GAO ; Wei HE ; Yunbo LI ; Haili TANG ; Menghui YUAN ; Junyan WANG ; Qianrong BAI ; Guangming WEI
Chinese Journal of Radiological Medicine and Protection 2022;42(12):973-979
Objective:To investigate the changes in total radioactivity in patient body with differentiated thyroid carcinoma (DTC) after 131I treatment and the factors influencing its metabolism. Methods:The clinical data from 218 patients after DTC treatment in the Department of Nuclear Medicine, the Second Affiliated Hospital of Air Force Medical University from September 2021 to April 2022 were retrospectively analyzed. Based on administrated 131I dose, 171 patients were divided into low-dose group (≤ 3.7 GBq) and 47 into high-dose group (>3.7 GBq) . A whole body dynamic radiation monitoring system was used to measure the in vivo residual activity of 131I 24, 48 and 72 h after 131I administration and to explore their influencing factors. Results:24, 48 and 72 h after adimination of 131I, the residual activity of 131I in the low-dose group patients was significantly lower than in the high-dose group patients ( t= -7.46, -3.31, -2.01, P<0.05) . The discharge compliance rate at 24 and 48 h in the low-dose group was significantly higher than that in the high-dose group (21.0% vs. 4.3%, 98.2% vs. 89.4%, χ2 = 7.23, 5.91, P<0.05) , and all patients could meet the discharge criteria at 72 h. Univariate analysis showed that the residual 131I activity at 24 and 48 h was dependent on age, body mass index (BMI) , basal metabolism rate (BMR) and thyroid stimulating hormone (TSH) . As have been shown by multiple linear regression analysis, in the low-dose group, the older age, the higher BMR and the higher TSH level at 24 h tended to the higher 131I residual activity in the body. At 48 h, the higher BMI and the higher TSH level lead to the higher 131I residual activity in patient body. Meanwhile, in the high-dose group, the higher age and BMR at 24 h, tended to the higher in vivo131I residual activity. The influencing factors were analyzed in terms that 131I residual activity reaching 400 MBq in patient body at 24 and 36 h. The result showed that at 24 h the lower TSH level leaded to the lower 131I residual activity in patient body. At 36 h, the younger age, the lower TSH level, and the smaller 131I treatment dose tended to the lower in vivo131I residual activity. Conclusions:Age, BMI, BMR and TSH levels are the influencing factors for the change in total activity in patient body after 131I treatment of DTC. Radiation dose assessment based on the above indicators can provide a reference for adjusting the length of hospitalization time.
6.Matrix metalloproteinase regulates natural killer cells function in methicilin-resistant staphylococcus aureus sepsis
Haijun LIANG ; Yanhui CUI ; Yanping WANG ; Xinwei WANG ; Haili GAO ; Baoxin CHEN ; Daokun YANG
Chinese Journal of Emergency Medicine 2020;29(6):835-840
Objective:To investigate the characteristics of natural killer (NK) cell subsets and function in methicillin-resistant staphylococcus aureus (MRSA) sepsis, and to assess the influence of matrix metalloproteinase (MMP) to NK cell function in MRSA sepsis patients.Methods:Twenty-one MRSA sepsis patients who were hospitalized in our department between January 2017 and June 2018 were enrolled. Eleven healthy individuals were served as healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated. NK cell subsets were investigated by flow cytometry. NK cell function was assessed by measuring CD107a, CD69, and CD16 expression in co-culture system between PBMCs and different target cells. MMP mRNA was semi-quantified by real-time PCR in purified NK cells. The influence of NK cell function was assessed by measuring CD107a expression in co-culture system between NK cells with MMP inhibitor stimulation and target cells.Results:There was no significant difference of total NK cell percentage between healthy controls and MRSA sepsis patients ( P>0.05). CD56brightCD16 -NK [(5.36±1.02)% vs (4.30±0.89)%] and CD56 -CD16 +NK [(24.04±2.92)% vs (9.70±1.54)%] percentage was elevated ( P<0.05), while CD56dimCD16 +NK percentage [(71.22±13.03)% vs (87.64±7.05)%, P<0.01] was reduced in MRSA sepsis. NK cells recognized and killed target cells via different receptors upon activation. CD107a [(33.55±3.84)% vs (25.34±6.20)%] and CD69 percentage [(14.96±1.47)% vs(18.80±1.49)%] was decreased ( P<0.0001), while CD16 MFI was increased [(247.1±50.31) vs (189.4±57.54), P<0.01] in MRSA sepsis patients in comparison with healthy controls. MMP-1/2/3/9 mRNA relative levels were elevated in purified NK cells from MRSA sepsis patients ( P<0.01). Inhibition of MMP in NK cells from MRSA sepsis patients promoted CD107a percentage [(33.67±8.03)% vs (25.87±6.23)%, P=0.018]. Conclusions:NK cell subsets imbalance and exhaustion is existed in MRSA sepsis, which might be due to the MMP-induced down-regulation of antibody-dependent cell-mediated cytotoxicity.
7.Expression and clinical significance of LKB1 and PTEN in hepatocellular carcinoma
Xingang ZHOU ; Jiamin CHEN ; Haili GAO ; Man LI ; Kun YANG ; Zhiyuan MA ; Peng WANG
Chinese Journal of General Surgery 2018;33(5):420-424
Objective To investigate the expression of liver kinase B1 (LKB1) and phosphatase and tensin homology deleted on chromosome ten (PTEN) in hepatocellular carcinoma (HCC) and their relationship with pathological characteristics and prognosis of HCC.Methods hnmunohistochemistry was used to detect expression of LKB1 and PTEN in 115 HCC cases.The relationship between clinicopathologic factors and the expressions was analyzed.Results The positive expression rate of LKB1 and PTEN was 10.4% (12/115) and 28.7% (33/115) respectively.The coexpression ratio of LKB1 and PTEN was 5.2% (6/115).LKB1 and PTEN double deletion rate was 66.1%,with the latter most often found in those ≥ 50 years of age group (x2 =7.968,P =0.001),middle low differentiation HCC group (x2 =11.297,P =0.025) and vascular tumor thrombus group (x2 =6.797,P =0.011).The 5 year survival rates of LKB1 and PTEN protein coexpression and double deletion patients were 100% and 36.5% (x2 =10.969,P =0.004),respectively.Multivariate COX regression analysis showed that vascular tumor thrombus,PTEN deletion and LKB1/PTEN double deletion were independent risk factors for the prognosis of HCC.Condusions Double deletion of LKB1/PTEN protein is one of the independent factors that affect the survival time of HCC patients.
8.Co-expression and transcriptional regulation network analysis of PD-L1 in lung squamous cell carcinoma
Feiyue FENG ; Bin QIU ; Chunxiao LI ; Haili QIAN ; Shugeng GAO
Medical Journal of Chinese People's Liberation Army 2017;42(5):361-365
Objective To construct a programmed cell death ligand 1(PD-L1) co-expression network in lung squamous cell carcinoma,screen potential PD-L1 co-expression biomarkers,and try to find the genes and pathways participating in PD-L1-regulated tumor immune response.Methods The lung squamous cell carcinoma dataset extracted from TCGA was used to screen the co-expression genes of PD-L 1 at the whole-genome transcriptional level by Venny analysis,and the target genes were screened by multiple types of cluster and molecular network analysis to construct a PD-L1 co-expression network.Results A total of 126 genes moderately co-expressed with PD-L1 were retrieved,most of them are plasma membrane targeting genes participating in immune response.Three transcription factors (IRF2/NFKB1/IRF1) were involved in more than 30% the regulation of the PD-L1 genes transcription.By screening the core molecules of co-expression of PD-L1 gene set and analyzing the connectivity of network node,6 network nodes genes with the highest connectivity were retrieved as follows:IFNG,JAK2,STAT1,CTLA4,CD80 and CCR5.Analysis of the relations of the different expression levels of these genes to the survival situation of patients with lung cancer revealed that CCR5 was a significant prognostic marker.Analysis of the PD-L1 expression and CCR5 gene spectrum data showed the Pearson correlation coefficient is 0.47(P<0.05);GO-BP cluster analysis showed that the function of CCR5 mainly focused on immune regulation,T cell regulation and signal transduction,in accordance with the PD-L1 function of network regulation.Conclusions The main nodes of PD-L1 co-expressing gene set are immune-related molecules,among which IFNG/CCR5/NFKB1 play the most significant regulatory effects in the gene network.This finding lays a foundation for the research and immunotherapy for lung squamous cell carcinoma.
9.Contrastive analysis of artifacts produced by metal dental crowns in 3.0 T magnetic resonance imaging with six sequences.
Lan GAO ; Yunmin LIAN ; Pu WANG ; Haili HUAI
West China Journal of Stomatology 2016;34(3):277-280
OBJECTIVEThis study aimed to observe and evaluate six 3.0 T sequences of metallic artifacts produced by metal dental crowns.
METHODSDental crowns fabricated with four different materials (Co-Gr, Ni-Gr, Ti alloy and pure Ti) were evaluated. A mature crossbreed dog was used as the experimental animal, and crowns were fabricated for its upper right second premolar. Each crown was examined through head MRI (3.0 T) with six sequences, namely, T₁ weighted-imaging of spin echo (T₁W/SE), T₂ weighted-imaging of inversion recovery (T₂W/IR), T₂ star gradient echo (T₂*/GRE), T2 weighted-imaging of fast spin echo (T₂W/FSE), T₁ weighted-imaging of fluid attenuate inversion recovery (T₂W/FLAIR), and T₂ weighted-imaging of propeller (T₂W/PROP). The largest area and layers of artifacts were assessed and compared.
RESULTSThe artifact in the T₂*/GRE sequence was significantly wider than those in the other sequences (P < 0.01), whose artifact extent was not significantly different (P > 0.05).
CONCLUSIONT₂*/GRE exhibit the strongest influence on the artifact, whereas the five other sequences contribute equally to artifact generation.
Alloys ; Animals ; Artifacts ; Crowns ; Dogs ; Magnetic Resonance Imaging ; Titanium
10.Effects of complications simulated experience education in elderly patients with type 2 diabetes mellitus
Haili SHAN ; Ni′na WANG ; Na ZHAO ; Weiwei MA ; Yanhong GAO
Chinese Journal of Modern Nursing 2016;22(19):2665-2668
Objective To explore the influence of diabetic complications simulated experience education on blood glucose control and self-behavior management in elderly patients with type 2 diabetes mellitus.Methods A total of 150 elderly patients with type 2 diabetes mellitus were selected according to the diabetic diagnostic criteria by WHO from November 2015 to April 2016.They were randomly divided into intervention group (75 cases, diabetic complications simulated experience education , one-to-one education mode) and control group (75 cases, conventional education for diabetic complications , one-to-one education mode).The differences in fasting blood glucose , 2 hours′postprandial glucose, glycosylated hemoglobin (HbA1c), and self-management behavior were compared before and one month after intervention .Results There were no difference in general situation , every glucose index , the score of diabetes management self efficacy ( Chinese version Diabetes Management Self-Efficacy Scale, C-DMSES), and the score of self-management behavior (Summary of Diabetes Self-Care Activities, SDSCA) between two groups before intervention (P>0.05).After intervention, fasting blood glucose, 2 hours′postprandial glucose, and HbA1c were (6.51 ±1.93) mmol/L,(11.08 ± 5.02)mmol/L,(7.52 ±3.01)% in intervention group, which were lower than (7.31 ±1.80) mmol/L, (12.81 ±5.46) mmol/L,(8.84 ±2.52)%in control group (P<0.05).The scores of C-DMSES and SDSCA in intervention group were higher than those in control group ( P <0.01 ).Conclusions The diabetic complications simulated experience education is better than conventional health education in blood glucose control and self-behavior management in elderly patients with type 2 diabetes mellitus .


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