Objective To investigate the expression and clinical significance of 12 plasma cytokines in patients with pancreatic cancer.Methods The study included 120 patients with pancreatic cancer diagnosed and treated at Qingdao University Affiliated Hospital and 68 healthy controls from March 2023 to June 2024.The levels of 12 plasma cytokines,including interleukin(IL)-1 β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12P,IL-17,interferon(IFN)-α,IFN-γ,and tumor necrosis factor(TNF)-α,were detected using mul-tiplex bead-based flow immunoassay.The levels of tumor markers carcinoembryonic antigen(CEA),carbohydrate antigen 19-9(CA19-9)and carbohydrate antigen 72-4(CA 72-4)in the serum of pancreatic cancer patients were detected by electrochemilumines-cence,while carbohydrate antigen 242(CA242)were detected by chemiluminescence methods.The correlation between the expression levels of differentially expressed cytokines and those of tumor markers was analyzed using Spearman's rank correlation.Results The plasma levels of 9 cytokines(IL-1 β,IL-4,IL-5,IL-6,IL-8,IL-10,IL-17,IFN-α,and IFN-γ)in the patients with pancreatic canc-er were significantly higher than those in controls(all P＜0.05).The levels of IL-1 β,IL-6,IL-8,IL-10,and IL-17 in the advanced pancreatic cancer group were significantly higher than those in the early-stage group(P＜0.05).The plasma IL-6 level in the poorly dif-ferentiated pancreatic cancer group was significantly higher than that in the well-differentiated group(P＜0.05).The serum levels of CEA,CA19-9,CA242,and CA72-4 in the advanced pancreatic cancer group were significantly higher than those in the early-stage group(P＜0.05).The serum CEA level in the poorly differentiated pancreatic cancer group was significantly higher than that in the moderately differentiated pancreatic cancer group(P＜0.05).After four cycles of chemotherapy,IL-8 levels in the disease control group were significantly reduced compared to pre-treatment levels(P＜0.05),while IL-6,IL-8,and IL-10 levels in the disease progression group were significantly elevated compared to pre-treatment levels(all P＜0.05).In the patients with pancreatic cancer,plasma IL-6 levels were positively correlated with serum CEA levels(rs=0.238,P＜0.01)and serum CA19-9 levels(rs=0.186,P＜0.05).The plasma IL-10 levels were positively correlated with serum CA72-4(rs=0.220,P＜0.05)levels in the patients.Conclusion Nine cyto-kines in plasma,such as IL-6,etc.may be involved in the formation of the inflammatory microenvironment of pancreatic cancer,as well as in the proliferation and differentiation of tumor cells.The determination of their plasma levels should be helpful for the assessing disease conditions and therapeutic effects.

Objective To investigate the expression and clinical significance of 12 plasma cytokines in patients with pancreatic cancer.Methods The study included 120 patients with pancreatic cancer diagnosed and treated at Qingdao University Affiliated Hospital and 68 healthy controls from March 2023 to June 2024.The levels of 12 plasma cytokines,including interleukin(IL)-1 β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12P,IL-17,interferon(IFN)-α,IFN-γ,and tumor necrosis factor(TNF)-α,were detected using mul-tiplex bead-based flow immunoassay.The levels of tumor markers carcinoembryonic antigen(CEA),carbohydrate antigen 19-9(CA19-9)and carbohydrate antigen 72-4(CA 72-4)in the serum of pancreatic cancer patients were detected by electrochemilumines-cence,while carbohydrate antigen 242(CA242)were detected by chemiluminescence methods.The correlation between the expression levels of differentially expressed cytokines and those of tumor markers was analyzed using Spearman's rank correlation.Results The plasma levels of 9 cytokines(IL-1 β,IL-4,IL-5,IL-6,IL-8,IL-10,IL-17,IFN-α,and IFN-γ)in the patients with pancreatic canc-er were significantly higher than those in controls(all P＜0.05).The levels of IL-1 β,IL-6,IL-8,IL-10,and IL-17 in the advanced pancreatic cancer group were significantly higher than those in the early-stage group(P＜0.05).The plasma IL-6 level in the poorly dif-ferentiated pancreatic cancer group was significantly higher than that in the well-differentiated group(P＜0.05).The serum levels of CEA,CA19-9,CA242,and CA72-4 in the advanced pancreatic cancer group were significantly higher than those in the early-stage group(P＜0.05).The serum CEA level in the poorly differentiated pancreatic cancer group was significantly higher than that in the moderately differentiated pancreatic cancer group(P＜0.05).After four cycles of chemotherapy,IL-8 levels in the disease control group were significantly reduced compared to pre-treatment levels(P＜0.05),while IL-6,IL-8,and IL-10 levels in the disease progression group were significantly elevated compared to pre-treatment levels(all P＜0.05).In the patients with pancreatic cancer,plasma IL-6 levels were positively correlated with serum CEA levels(rs=0.238,P＜0.01)and serum CA19-9 levels(rs=0.186,P＜0.05).The plasma IL-10 levels were positively correlated with serum CA72-4(rs=0.220,P＜0.05)levels in the patients.Conclusion Nine cyto-kines in plasma,such as IL-6,etc.may be involved in the formation of the inflammatory microenvironment of pancreatic cancer,as well as in the proliferation and differentiation of tumor cells.The determination of their plasma levels should be helpful for the assessing disease conditions and therapeutic effects.

Objective To assess inter-observer variations(IOV)in the delineation of target volumes and organs-at-risk(OAR)for intensity-modulated radiotherapy(IMRT)of nasopharyngeal carcinoma(NPC)among physicians from different levels of cancer centers,thereby providing a reference for quality control in multi-center clinical trials.Methods Twelve patients with NPC of different TMN stages were randomly selected.Three physicians from the same municipal cancer center manually delineated the target volume(GTVnx)and OAR for each patient.The manually modified and confirmed target volume(GTVnx)and OAR delineation structures by radiotherapy experts from the regional cancer center were used as the standard delineation.The absolute volume difference ratio(△V_diff),maximum/minimum volume ratio(MMR),coefficient of variation(CV),and Dice similarity coefficient(DSC)were used to compare the differences in organ delineation among physicians from different levels of cancer centers and among the 3 physicians from the same municipal cancer center.Furthermore,the IOV of GTVnx and OAR among physicians from different levels cancer centers were compared across different TMN stages.Results Significant differences in the delineation of GTVnx were observed among physicians from different levels of cancer centers.Among the 3 physicians,the maximum values of △V_diff,MMR,and CV were 97.23%±83.45%,2.19±0.75,and 0.31±0.14,respectively,with an average DSC of less than 0.7.Additionally,there were considerable differences in the delineation of small-volume OAR such as the left and right optic nerves,chiasm,and pituitary,with average MMR>2.8,CV>0.37,and DSC<0.51.However,relatively smaller differences were observed in the delineation of large-volume OAR such as the brainstem,spinal cord,left and right eyeballs,and left and right mandible,with average△V_diff<42%,MMR<1.55,and DSC>0.7.Compared with the differences among physicians from different levels cancer centers,the differences among the 3 physicians from the municipal cancer center were slightly reduced.Furthermore,there were also differences in the delineation of target volumes for NPC among physicians from different levels cancer centers,depending on the staging of the disease.Compared with the delineation of target volumes for earlier stage patients(stages I or II),the differences among physicians in the delineation of target volumes for advanced stage patients(stages III or IV)were smaller,with average △V_diff and DSC of 98.31%±67.36%vs 69.38%±72.61%(P<0.05)and 0.55±0.08 vs 0.72±0.12(P<0.05),respectively.Conclusion There are differences in the delineation of GTVnx and OAR in radiation therapy for NPC among physicians from different levels of cancer centers,especially in the delineation of target volume(GTVnx)and small-volume OAR for early-stage patients.To ensure the accuracy of multicenter clinical trials,it is recommended to provide unified training to physicians from different levels of cancer centers and review their delineation results to reduce the effect of differences on treatment outcomes.

INTRODUCTION: Three doses of SARS-CoV-2 mRNA vaccines have been recommended for cancer patients to reduce the risk of severe disease. Anti-neoplastic treatment, such as chemotherapy, may affect long-term vaccine immunogenicity. METHOD: Patients with solid or haematological cancer were recruited from 2 hospitals between July 2021 and March 2022. Humoral response was evaluated using GenScript cPASS surrogate virus neutralisation assays. Clinical outcomes were obtained from medical records and national mandatory-reporting databases. RESULTS: A total of 273 patients were recruited, with 40 having haematological malignancies and the rest solid tumours. Among the participants, 204 (74.7%) were receiving active cancer therapy, including 98 (35.9%) undergoing systemic chemotherapy and the rest targeted therapy or immunotherapy. All patients were seronegative at baseline. Seroconversion rates after receiving 1, 2 and 3 doses of SARS-CoV-2 mRNA vaccination were 35.2%, 79.4% and 92.4%, respectively. After 3 doses, patients on active treatment for haematological malignancies had lower antibodies (57.3%±46.2) when compared to patients on immunotherapy (94.1%±9.56, P<0.05) and chemotherapy (92.8%±18.1, P<0.05). SARS-CoV-2 infection was reported in 77 (28.2%) patients, of which 18 were severe. No patient receiving a third dose within 90 days of the second dose experienced severe infection. CONCLUSION This study demonstrates the benefit of early administration of the third dose among cancer patients.
Humans ; SARS-CoV-2 ; COVID-19/prevention & control* ; Treatment Outcome ; Neoplasms/drug therapy* ; Hematologic Neoplasms ; Vaccination ; RNA, Messenger ; Antibodies, Viral ; Immunogenicity, Vaccine

OBJECTIVE: To investigate the effect of Cyr61 on imatinib (IM) resistance in chronic myeloid leukemia (CML) and its mechanism. METHODS: Cyr61 level in cell culture supernatant was determined by enzyme-linked immunosorbent assay. The expression of Cyr61 and Bcl-xL were measured by real-time PCR and Western blot. Cell apoptosis was analyzed using an Annexin V-APC Kit. Expression of signal pathways related proteins was determined by Western blot. RESULTS: The level of Cyr61 obviously increased in K562G cells (IM resistance to CML cell line K562). Down-regulating the expression of Cyr61 decreased the resistance of K562G cells to IM and promoted IM induced apoptosis. In CML mouse model, down-regulating the expression of Cyr61 could increase the sensitivity of K562G cells to IM. The mechanism studies showed that Cyr61 mediated IM resistance in CML cells was related to the regulation of ERK1/2 pathways and apoptosis related molecule Bcl-xL by Cyr61. CONCLUSION Cyr61 plays an important role in promoting IM resistance of CML cells. Targeting Cyr61 or its related effectors pathways may be one of the ways to overcome IM resistance of CML cells.
Animals ; Humans ; Mice ; Apoptosis ; Drug Resistance, Neoplasm ; Imatinib Mesylate/pharmacology* ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism* ; Signal Transduction

OBJECTIVE: To investigate the spatial patterns of the prevalence, awareness, treatment, and control rates of dyslipidemia at the provincial level in China. METHODS: A national and provincial representative cross-sectional survey was conducted among 178,558 Chinese adults in 31 provinces in mainland China in 2018-2019, using a multi-stage, stratified, cluster-randomized sampling design. Subjects, as households, were selected, followed by a home visit to collect information. Both descriptive and linear regression procedures were applied in the analyses. RESULTS: The overall prevalence of dyslipidemia was 35.6%, and wide geographic variations of prevalence, treatment, and control rates of dyslipidemia were identified among 178,558 eligible participants with a mean age of 55.1 ± 13.8 years. The highest-lowest difference regarding the provincial level prevalence rates were 19.7% vs. 2.1% for high low-density lipoprotein cholesterol, 16.7% vs. 2.5% for high total cholesterol, 35.9% vs. 5.4% for high triglycerides, and 31.4% vs. 10.5% for low high-density lipoprotein cholesterol. The treatment rate of dyslipidemia was correlated with the socio-demographic index ( P < 0.001), urbanization rate ( P = 0.01), and affordable basic technologies and essential medicines ( P < 0.001). CONCLUSION Prevailing dyslipidemia among the Chinese population and its wide geographic variations in prevalence, treatment, and control suggest that China needs both integrated and localized public health strategies across provinces to improve lipid management.
Humans ; Adult ; Middle Aged ; Aged ; Cross-Sectional Studies ; Prevalence ; East Asian People ; Dyslipidemias/prevention & control* ; China/epidemiology* ; Cholesterol, HDL ; Risk Factors ; Triglycerides

Objective:To explore the difference of lymphocyte subsets in peripheral blood(PB)between aplastic anemia(AA)and hypoplastic myelodysplastic syndrome(hypo-MDS)patients,meanwhile to compare the clinical parameters obtained from PB and bone marrow(BM).Methods:The lymphocyte subsets in hypo-MDS(n=25)and AA(n=33)patients were investigated by flow cytometry.Meanwhile,the differences in PB cell counts,biochemical indicators,BM cell counts and abnormal chromosomes between the two groups were analyzed.Results:The percentage of CD8+T cells in A A group was significantly higher than that in hypo-MDS group(P=0.001),while the percentage of CD4+T cells and the CD4+/CD8+ratio in AA group were obviously lower than those in hypo-MDS group(P=0.015 and0.001,respectively).Furthermore,the proportion of CD4+andCD8+activated T(TA)cells,and memory Tregs in AA group was distinctly lower than those in hypo-MDS group(P=0.043,0.015 and 0.024,respectively).Nevertheless,the percentage of CD8+naive T(TN)cells in AA patients was remarkably higher(P=0.044).And hypo-MDS patients had declined lymphocyte counts(P=0.025),increased levels of total bilirubin(TBil),lactate dehydrogenase(LDH),vitamin B12 and proportion of BM blasts than AA patients(P=0.019,0.023,0.027 and 0.045,respectively).Conclusion:In this study it was confirmed that the percentages of CD4+and CD8+TA cells,memory Tregs and CD8+TN cells were significantly different between AA and hypo-MDS patients,which provide an essential basis for the identification of these two diseases.

Objective: To assess the association between short-term exposure level of nitrogen dioxide and the hospitalization risk of heart failure. Methods: Based on China-PEACE Retrospective Heart Failure Study, 117 364 hospitalized patients with heart failure were recruited from 92 hospitals in 62 cities throughout China between January 1, 2015 and December 31, 2015. The daily exposure level of nitrogen dioxide, temperature, and humidity in the same cities during the same period were also collected. We applied the generalized additive model and Bayesian hierarchical model to quantify the lagged effect and cumulative effect of short-term (0-3 days) exposure to ambient nitrogen dioxide on the hospitalization risk of heart failure. We further conducted stratified analyses by age, region, and season to identify any difference in the associations between short-term nitrogen dioxide exposure and heart failure among subgroups. Results: The mean age for participants in the analysis was (70.32±12.22) years. The median, minimum and maximum of daily nitrogen dioxide concentration in 62 cities from January 1, 2015 to December 31, 2015 was 26.4 μg/m³, 2.33 μg/m³ and 150.25 μg/m³, respectively. The exposure level of nitrogen dioxide at the same day was associated with the hospitalization risk of heart failure (OR=1.022, 95%CI: 1.012, 1.031). Significant effects were also observed in the moving average concentrations from lag 0-1 to lag 0-3 day (OR=1.020, 95%CI: 1.009, 1.030; OR=1.016, 95%CI: 1.004, 1.028; OR=1.013, 95%CI: 1.001, 1.026). Moreover, all of the associations between short-term exposure to nitrogen dioxide and the risk of heart failure hospitalization were statistically significant, with no significant difference in all subgroups stratified by age, region, and season. Conclusion: A higher level of short-term exposure to nitrogen dioxide could trigger more hospitalizations with heart failure.
Aged ; Aged, 80 and over ; Air Pollutants/analysis* ; Air Pollution/analysis* ; Bayes Theorem ; China/epidemiology* ; Environmental Exposure/analysis* ; Heart Failure/epidemiology* ; Hospitalization ; Humans ; Middle Aged ; Nitrogen Dioxide/analysis* ; Particulate Matter/analysis* ; Retrospective Studies ; Sulfur Dioxide/analysis*

This study aims to acetylate Rehmannia glutinosa polysaccharides by acetic anhydride method, optimize process parameters and evaluate their antioxidant activity. With the degree of substitution(D_s) as a criterion, the effects of reaction time, acetic anhydride-to-polysaccharides ratio and temperature were investigated. Process parameters were optimized by single-factor experiment and response surface methodology. The infrared spectroscopy(IR) and scanning electron microscopy(SEM) proved the successful acetylation and were employed to preliminarily analyze the structural characteristics of acetylated derivatives. The results showed that the D_s was 0.327 under the optimal technological conditions, including m(acetic anhydride):m(R. glutinosa polysaccharides)=2.70, reaction time 3.0 h and temperature 48 ℃. Further, the antioxidant properties of acetylated derivatives were investigated in vitro and acetylation was found effective to improve the antioxidant activity of R. glutinosa polysaccharides. This study provides a reference for the further development and application of R. glutinosa polysaccharides.
Acetylation ; Antioxidants/pharmacology* ; Polysaccharides/pharmacology* ; Rehmannia/chemistry*

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.