Objective : To investigate the effect of miR-141-3p on LPS induced A549 cell injury by targeting high mobility group protein 1 (HMGB1) ． Methods : A549 cells derived from type Ⅱ alveolar epithelial cells were taken as the study object，miR-141-3p mimics，mimics NC，HMGB1 gene overexpression plasmid (pcDNA3. 1-HMGB1) and empty Vector were transfected into A549 cells respectively or co-transfected，then 10 μg / ml LPS was used for 24 h．Cell proliferation activity was detected by cell counting kit-8 ( CCK-8) ．The activity of lactate dehydrogenase ( LDH) in the supernatant of cell culture was detected by colorimetry．The apoptosis level of each group was detec- ted by flow cytometry．The levels of interleukin (IL) -1 β , IL-6 and tumor necrosis factor α (TNF-α) were detected by enzyme-linked immunosorbent assay (Elisa) ．Dual luciferase reporter gene assay verified the targeted regulatory relationship between miR-141-3p and HMGB1 . Results : After treatment with LPS ，the proliferative activity of A549 cells and the expression level of miR-141-3p decreased ( P ＜0. 05 ) ，the apoptosis rate increased ( P < 0. 05) ，the levels of IL-1 β , IL-6，TNF-α and the activity of LDH in supernatant increased (P＜0. 05) ．Overex- pression of miR-141-3p increased the proliferation activity of A549 cells treated with LPS (P ＜0. 05 ) ，and de- creased the apoptosis rate and the levels of IL-1 β , IL-6，TNF-α in cells and LDH activity in supernatant (P < 0. 05) ．However，overexpression of HMGB1 gene could reverse the ameliorative effect of miR-141-3p on LPS-in- duced A549 cell injury．Dual luciferase reporter gene experiment confirmed that HMGB1 was the downstream target gene of miR-141-3p． Conclusion miR-141-3p can inhibit LPS-induced apoptosis，reduce the expression level of inflammatory factors，and improve the damage of A549 cells，which may be related to the targeted regulation of HMGB1 expression.

Objective:To discuss the effect of inhibiting microRNA(miR)-193a-5p expression on pulmonary fibrosis in the rats with acute respiratory distress syndrome(ARDS),and to clarify the related mechanism.Methods:A total of 60 male SD rats were divided into sham operation group,model group,miR-193a-5p antagonist group(Antagomir group),and negative control group(Antagomir-NC group),and there were 15 rats in each group.The ARDS animal model was induced by administering 10 mg·kg-1 lipopolysaccharide(LPS)via tracheal instillation,while the rats in sham operation group received an equal volume of saline.After successful modeling,the rats in Antagomir group and Antagomir-NC group were treated with miR-193a-5p Antagomir or Antagomir-NC via tail vein injection.The arterial partial pressure of oxygen(PaO2)and oxygenation index(OI)of the rats in various groups were measured;HE staining and Masson staining were used to observe the pathology and collagen fiber deposition in lung tissue of the rats;kit was used to detect the level of hydroxyproline(Hyp)in lung tissue of the rats in various groups;enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of inflammatory factors tumor necrosis factor α(TNF-α),interleukin(IL)-1β,and IL-6 in bronchoalveolar lavage fluid(BALF)of the rats in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of miR-193a-5p in lung tissue of the rats in various groups;Western blotting method was used to detect the expression levels of β-catenin,Snail family transcriptional repressor 1(Snail1),and α-smooth muscle actin(α-SMA)proteins in lung tissue of the rats in various groups.Results:Compared with sham operation group,the PaO2 and OI of the rats in model group were significantly decreased(P<0.05);compared with model group,the PaO2 and OI of the rats in Antagomir group were significantly increased(P<0.05).The HE staining results showed that the lung tissue structure of the rats in sham operation group was normal,and there were no obvious inflammatory changes;compared with sham operation group,mild abnormalities in lung tissue structure,alveolar atrophy,and collapse were observed in the rats in model group and Antagomir-NC group,with a large number of lymphocytes and a small number of neutrophils infiltrating in the alveolar cavities,and widened alveolar spaces;compared with model group,the rats in Antagomir group showed a significant reduction in lymphocytes and neutrophil infiltration in the alveolar cavities and there were no obvious hyperplasia.The Masson staining results showed no obvious blue collagen fiber deposition in lung tissue of the rats in sham operation group;compared with sham operation group,significant blue collagen fiber deposition was observed in lung tissue of the rats in model group and Antagomir-NC group,with severe damage of the alveolar structure,indicating obvious pulmonary fibrosis;compared with model group,the deposition of blue-stained collagen fibers in lung tissue of the rats in Antagomir group was significantly reduced.Compared with sham operation group,the level of Hyp in lung tissue of the rats in model group was significantly increased(P<0.05);compared with model group,the level of Hyp of the rats in Antagomir group was significantly decreased(P<0.05).The ELISA results showed that compared with sham operation group,the levels of TNF-α,IL-1β,and IL-6 in BALF of the rats in model group were significantly increased(P<0.05);compared with model group,the levels of TNF-α,IL-1β,and IL-6 of the rats in Antagomir group were significantly decreased(P<0.05).The RT-qPCR results showed that compared with sham operation group,the expression level of miR-193a-5p in lung tissue of the rats in model group was significantly increased(P<0.05);compared with model group,the expression level of miR-193a-5p of the rats in Antagomir group was significantly decreased(P<0.05).The Western blotting results showed that compared with sham operation group,the expression levels of β-catenin,Snail1,and α-SMA proteins in lung tissue of the rats in model group were significantly increased(P<0.05);compared with model group,the expression levels of β-catenin,Snail1,and α-SMA proteins in lung tissue of the rats in Antagomir group were significantly decreased(P<0.05).Conclusion:Inhibition of miR-193a-5p expression can improve the lung function and alleviate the pulmonary fibrosis in the ARDS rats by reducing the inflammatory responses and downregulating the expressions of β-catenin,Snail1,and α-SMA proteins.

Objective To investigate the effect and mechanism of miR-141-3p on pulmonary fibrosis in rats with acute respiratory distress syndrome(ARDS).Methods Rats were divided into the control group,the model group,the agomir negative control group and the miR-141-3p agomir group according to random number table,with 10 rats in each group.In addition to the control group,the ARDS rat model was established by lipopolysaccharide(LPS)infusion.Rat alveolar typeⅡepithelial cells RLE-6TN cells were divided into the NC group,the LPS group,the miR-NC group,the miR-141-3p mimics group,the miR-141-3p mimics+pcDNA group and the miR-141-3p mimics+NRF2 and Kelch-like ring associated protein 1(Keap1)group.LPS cell model was established in all groups except the NC group.The mRNA expression levels of miR-141-3p and Keap1 in lung tissue and cells were detected by qPCR.Western blot assay was used to analyze lung tissue and cell epithelial cadherin(E-cadherin),neural cadherin(N-cadherin),microtubule associated protein light chain 3B(LC3B),autophagy associated gene Beclin-1,α-smooth muscle actin(α-SMA),type I collagen(Col-Ⅰ),Keap1 and nuclear factors E2 related factor 2(NRF2)and heme oxygenase 1(HO-1).HE staining and Masson staining were used to observe pathological changes of lung tissue and to estimate the area of lung tissue injury and pulmonary fibrosis.Hydroxyproline(Hyp)in lung tissue was detected by the kit.Levels of inflammatory factor interleukin-1β,tumor necrosis factor(TNF-α)and oxidative stress index malondialdehyde(MDA)and superoxide dismutase(SOD)were detected by ELISA.Dual luciferase reporting experiment was used to verify the targeting relationship between miR-141-3p and Keap1.Results The expression of miR-141-3p was down-regulated and the expression of Keap1 was up-regulated in lung tissue and cells(P＜0.05).Overexpression of miR-141-3p can reduce the degree of pathological damage and fibrosis of lung tissue in rats,Hyp content,and up-regulate expression levels of SOD,E-cadherin,LC3B,Beclin-1,NRF2 and HO-1 in lung tissue and cells,and down-regulate the expression levels of IL-1β,TNF-α,MDA,N-cadherin,α-SMA,Col-I and Keap1(P＜0.05).Overexpression of Keap1 was able to reverse the improvement effect of overexpression of miR-141-3p on alveolar epithelial cell damage in ARDS rats(P＜0.05).Double Luciferase reporter gene experiment confirmed that miR-141-3p and Keap1 may have a targeted regulatory relationship.Conclusion Overexpression of miR-141-3p may activate the Keap1-NRF2/ARE signaling pathway,activate autophagy,inhibit inflammatory response,oxidative stress,and EMT progression,and improve pulmonary fibrosis in ARDS rats.

In China, the survival rate of liver cancer remains low while the mortality rate is high. Effectively reducing the burden of liver cancer is still a major challenge in the field of public health and chronic disease prevention in the Chinese population. Optimizing screening strategies for liver cancer remains a profound approach to secondary prevention worthy of continuous explora-tion. This guideline was commissioned by the Bureau of Disease Control and Prevention of the National Health Commission. The National Cancer Center of China initiated the guideline develop-ment and convened a multidisciplinary expert panel and working group. Following the World Health Organization Handbook for Guideline Development, this guideline integrated the most up-to-date evidence of liver cancer screening, China′s national conditions, and existing practical experience in liver cancer screening. Evidence-based recommendations on the target population, screening technologies, surveillance strategies, and other key points across the process of liver cancer screening and surveillance management were provided. This guideline would help to standardize the practice of liver cancer screening in China.

In China, the survival rate of liver cancer remains low while the mortality rate is high. Effectively reducing the burden of liver cancer is still a major challenge in the field of public health and chronic disease prevention in the Chinese population. Optimizing screening strategies for liver cancer remains a profound approach to secondary prevention worthy of continuous exploration. To address this pressing issue, the Bureau of Disease Control and Prevention of the National Health Commission commissioned this guideline. The National Cancer Center of China initiated the guideline development and convened a multidisciplinary expert panel and working groups. Following the World Health Organization Handbook for Guideline Development, this guideline integrated the most up-to-date evidence of liver cancer screening, China's national conditions, and existing practical experience in liver cancer screening. Evidence-based recommendations on the target population, screening technologies, surveillance strategies, and other key points across the process of liver cancer screening and surveillance management were provided. This guideline would help standardize the practice of liver cancer screening in China.

In China, the survival rate of liver cancer remains low while the mortality rate is high. Effectively reducing the burden of liver cancer is still a major challenge in the field of public health and chronic disease prevention in the Chinese population. Optimizing screening strategies for liver cancer remains a profound approach to secondary prevention worthy of continuous exploration. To address this pressing issue, the Bureau of Disease Control and Prevention of the National Health Commission commissioned this guideline. The National Cancer Center of China initiated the guideline development and convened a multidisciplinary expert panel and working groups. Following the World Health Organization Handbook for Guideline Development, this guideline integrated the most up-to-date evidence of liver cancer screening, China′s national conditions, and existing practical experience in liver cancer screening. Evidence-based recommendations on the target population, screening technologies, surveillance strategies, and other key points across the process of liver cancer screening and surveillance management were provided. This guideline would help standardize the practice of liver cancer screening in China.

In China, the survival rate of liver cancer remains low while the mortality rate is high. Effectively reducing the burden of liver cancer is still a major challenge in the field of public health and chronic disease prevention in the Chinese population. Optimizing screening strategies for liver cancer remains a profound approach to secondary prevention worthy of continuous exploration. To address this pressing issue, the Bureau of Disease Control and Prevention of the National Health Commission commissioned this guideline. The National Cancer Center of China initiated the guideline development and convened a multidisciplinary expert panel and working groups. Following the World Health Organization Handbook for Guideline Development, this guideline integrated the most up-to-date evidence of liver cancer screening, China′s national conditions, and existing practical experience in liver cancer screening. Evidence-based recommendations on the target population, screening technologies, surveillance strategies, and other key points across the process of liver cancer screening and surveillance management were provided. This guideline would help standardize the practice of liver cancer screening in China.

Objective:To explore the clinical features of poly ADP-ribose polymerase (PARP) inhibitor-related anemia in advanced and relapsed epithelial ovarian cancer (EOC).Methods:Patients diagnosed with advanced or relapsed EOC and treated with PARP inhibitor at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2015 to October 2020 were accrued. The data included PARP inhibitors, treatment details, and lab tests before treatment and during treatment were collected and the clinical characteristics of PARP inhibitor-related anemia were analyzed.Results:(1) A total of 98 patients with a median age of 56.5 years old (30-82 years old) were enrolled in this study. All patients were treated with PARP inhibitor (65 cases of olaparib, 17 cases of niraparib, and 16 cases of fluzoparib). The median treatment duration was 37.5 weeks (4-119 weeks). (2) The anemia rate was 40% (39/98), including 5% (5/98) of grade Ⅰ, 14% (14/98) of grade Ⅱ, 11% (11/98) of grade Ⅲ, and 9% (9/98) of grade Ⅳ. Fourteen patients with pre-treatment grade Ⅰ anemia had a higher rate of anemia events than the 80 patients without pre-treatment anemia, 7/14 vs 35% (28/80; χ2=4.281, P=0.039). (3) The median anemia occurrence time was 7.0 weeks (1-52 weeks), including 41% (16/39) of anemia cases occurred in 1-4 weeks, 26% (10/39) occurred in 5-8 weeks, 13% (5/39) occurred in 9-12 weeks, 3% (1/39) occurred in 13-16 weeks, 10% (4/39) occurred in 17-20 weeks, 8% (3/39) occurred ≥21 weeks. At the time of the lowest hemoglobulin tested, the median value of mean corpuscular volume (MCV) was 106 fl,which was higher than the up limit of normal range (100 fl), 74% (29/39) of anemia patients had an elevated MCV level; the median value of mean corpuscular hemoglobin (MCH) was 36 pg, 54% (21/39) of anemia patients had an elevated MCH level; the median value of mean corpuscular hemoglobin concentration (MCHC) was 320 g/L, 69% (27/39) of anemia patients had a higher MCHC level; 92% (36/39) of anemia patients had a normal level of serum iron; 79% (31/39) of anemia patients had a normal level of transferrin. 74% (29/39) of the anemia patients were macrocytic orthochromatic anemia. (4) Among the 39 patients with anemia, 20 patients (51%, 20/39) withhold the treatment of PARP inhibitor due to grade Ⅲ or Ⅳ anemia, including 10 patients (50%, 10/20) who resumed the PARP inhibitor treatment by suppling iron, folate, and vitamin B 12. The median stopping time of PARP inhibitor was 5.5 weeks (2-10 weeks), while the other 10 patients terminated the PARP inhibitor treatment for not recovering from severe anemia. Conclusions:One of the common adverse effects of PARP inhibitors is anemia, which mostly happened in the first 3 months of treatment. In the treatment of EOC, PARP inhibitor-related anemia mainly manifest as macrocytic orthochromatic anemia, and most patients with normal serum iron and transferrin.

Objective:To explore the serum cyclic polypeptide biomarkers for ovarian cancer diagnosis.Methods:A total of 54 patients with epithelial ovarian cancer confirmed by pathology in Cancer Hospital, Chinese Academy of Medical Sciences from March 2018 to September 2018 were selected as the study subjects, and 40 healthy women with normal examination results in the cancer screening center were selected as the control. All of the samples were randomly divided into training set and validation set at the ratio of 1∶1 with a random number. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with magnetic bead technology was used for detecting peptide profiling in serum samples to screen significantly differently expressed peptides between ovarian cancer group and control group of the training set (score>5). Receiver operating characteristic (ROC) curve analysis was used to screen differential peptide peaks with area under curve (AUC) ≥0.8, sensitivity and specificity>90% in the training set and validation set. Liquid chromatography-mass spectrometry (LC-MS/MS) was further used to determine the composition of differentially expressed peptides.Results:By comparing the peptide profiles of the two groups, 102 differential peptide peaks were initially detected in the mass-to-charge ratio range of 1 000 to 10 000. ROC curve analysis showed that there were 42 differential peptide peaks with AUC ≥0.8 in both training set and validation set, 19 of which were highly expressed in ovarian cancer group, and 23 were lowly expressed. There were 15 different peptide peaks in highly expressed ovarian cancer group with sensitivity and specificity over 90%. The mass-to-charge ratios were 7 744.27, 5 913.41, 5 329.87, 4 634.21, 4 202.02, 3 879.26, 3 273.35, 3 253.79, 3 234.34, 2 950.33, 2 664.51, 2 018.38, 1 893.37, 1 498.69 and 1 287.55. There were 15 different peptide peaks in lowly expressed ovarian cancer group with sensitivity and specificity over 90%, the mass-to-charge ratios were 9 288.46, 7 759.77, 5 925.24, 4 652.77, 4 210.42, 3 887.02, 3 279.90, 3 240.82, 2 962.15, 2 932.70, 2 022.42, 1 897.16, 1 501.69, 1 337.38 and 1 290.13. No protein composition was identified in 15 different peptide peaks in lowly expressed ovarian cancer group. The two protein compositions identified in 15 different peptide peaks in highly expressed ovarian cancer group were recombinant serglycin (SRGN) and fibinogen alpha chain (FGA), the mass-to-charge ratios of which were 1 498.696 and 5 913.417, respectively. The sensitivity and specificity of the two proteins for ovarian cancer diagnosis were 100%, 100% and 90.9%, 100%, respectively.Conclusion:SRGN and FGA are highly expressed in the serum of ovarian cancer patients, which may be potential diagnostic markers for ovarian cancer.

Objective:To explore the serum cyclic polypeptide biomarkers for ovarian cancer diagnosis.Methods:A total of 54 patients with epithelial ovarian cancer confirmed by pathology in Cancer Hospital, Chinese Academy of Medical Sciences from March 2018 to September 2018 were selected as the study subjects, and 40 healthy women with normal examination results in the cancer screening center were selected as the control. All of the samples were randomly divided into training set and validation set at the ratio of 1∶1 with a random number. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with magnetic bead technology was used for detecting peptide profiling in serum samples to screen significantly differently expressed peptides between ovarian cancer group and control group of the training set (score>5). Receiver operating characteristic (ROC) curve analysis was used to screen differential peptide peaks with area under curve (AUC) ≥0.8, sensitivity and specificity>90% in the training set and validation set. Liquid chromatography-mass spectrometry (LC-MS/MS) was further used to determine the composition of differentially expressed peptides.Results:By comparing the peptide profiles of the two groups, 102 differential peptide peaks were initially detected in the mass-to-charge ratio range of 1 000 to 10 000. ROC curve analysis showed that there were 42 differential peptide peaks with AUC ≥0.8 in both training set and validation set, 19 of which were highly expressed in ovarian cancer group, and 23 were lowly expressed. There were 15 different peptide peaks in highly expressed ovarian cancer group with sensitivity and specificity over 90%. The mass-to-charge ratios were 7 744.27, 5 913.41, 5 329.87, 4 634.21, 4 202.02, 3 879.26, 3 273.35, 3 253.79, 3 234.34, 2 950.33, 2 664.51, 2 018.38, 1 893.37, 1 498.69 and 1 287.55. There were 15 different peptide peaks in lowly expressed ovarian cancer group with sensitivity and specificity over 90%, the mass-to-charge ratios were 9 288.46, 7 759.77, 5 925.24, 4 652.77, 4 210.42, 3 887.02, 3 279.90, 3 240.82, 2 962.15, 2 932.70, 2 022.42, 1 897.16, 1 501.69, 1 337.38 and 1 290.13. No protein composition was identified in 15 different peptide peaks in lowly expressed ovarian cancer group. The two protein compositions identified in 15 different peptide peaks in highly expressed ovarian cancer group were recombinant serglycin (SRGN) and fibinogen alpha chain (FGA), the mass-to-charge ratios of which were 1 498.696 and 5 913.417, respectively. The sensitivity and specificity of the two proteins for ovarian cancer diagnosis were 100%, 100% and 90.9%, 100%, respectively.Conclusion:SRGN and FGA are highly expressed in the serum of ovarian cancer patients, which may be potential diagnostic markers for ovarian cancer.