Myocardial infarction (MI) is one of the leading causes of death in the world. With the improvement of clinical therapy, the mortality of acute MI has been significantly reduced. However, as for the long-term impact of MI on cardiac remodeling and cardiac function, there is no effective prevention and treatment measures. Erythropoietin (EPO), a glycoprotein cytokine essential to hematopoiesis, has anti-apoptotic and pro-angiogenetic effects. Studies have shown that EPO plays a protective role in cardiomyocytes in cardiovascular diseases, such as cardiac ischemia injury and heart failure. EPO has been demonstrated to protect ischemic myocardium and improve MI repair by promoting the activation of cardiac progenitor cells (CPCs). This study aimed to investigate whether EPO can promote MI repair by enhancing the activity of stem cell antigen 1 positive stem cells (Sca-1⁺ SCs). Darbepoetin alpha (a long-acting EPO analog, EPO_anlg) was injected into the border zone of MI in adult mice. Infarct size, cardiac remodeling and performance, cardiomyocyte apoptosis and microvessel density were measured. Lin^- Sca-1⁺ SCs were isolated from neonatal and adult mouse hearts by magnetic sorting technology, and were used to identify the colony forming ability and the effect of EPO, respectively. The results showed that, compared to MI alone, EPO_anlg reduced the infarct percentage, cardiomyocyte apoptosis ratio and left ventricular (LV) chamber dilatation, improved cardiac performance, and increased the numbers of coronary microvessels in vivo. In vitro, EPO increased the proliferation, migration and clone formation of Lin^- Sca-1⁺ SCs likely via the EPO receptor and downstream STAT-5/p38 MAPK signaling pathways. These results suggest that EPO participates in the repair process of MI by activating Sca-1⁺ SCs.
Animals ; Mice ; Ventricular Remodeling ; Erythropoietin ; Myocardial Infarction ; Heart ; Stem Cells

OBJECTIVE: To investigate the effects of mTOR inhibitors everolimus (EVE) and gemcitabine (GEM) on the proliferation, apoptosis and cell cycle of diffuse large B-cell lymphoma (DLBCL) cell line U2932, and further explore the molecular mechanisms, so as to provide new ideas and experimental basis for the clinical treatment of DLBCL. METHODS: The effect of EVE and GEM on the proliferation of U2932 cells was detected by CCK-8 assay, the IC₅₀ of the two drugs was calculated, and the combination index (CI=) of the two drugs was calculated by CompuSyn software. The effect of EVE and GEM on apoptosis of U2932 cells was detected by flow cytometry with AnnexinV-FITC/PI staining. Flow cytometry with propidium iodide (PI) staining was used to detect the effect of EVE and GEM on the cell cycle of U2932 cells. Western blot assay was used to detect the effects of EVE and GEM on the channel proteins p-mTOR and p-4EBP1, the anti-apoptotic proteins MCL-1 and Survivin, and the cell cycle protein Cyclin D1. RESULTS: Both EVE and GEM could significantly inhitbit the proliferation of U2932 cells in a time- and dose-dependent manner (r=0.465, 0.848; 0.555, 0.796). According to the calculation of CompuSyn software, EVE combined with GEM inhibited the proliferation of U2932 cells at 24, 48 and 72 h with CI=<1, which had a synergistic effect. After treated U2932 cells with 10 nmol/L EVE, 250 nmol/L GEM alone and in combination for 48 h, both EVE and GEM induced apoptosis, and the difference was statistically significant compared with the control group (P<0.05). The apoptosis rate was significantly enhanced after EVE in combination with GEM compared with single-agent (P<0.05). Both EVE and GEM alone and in combination significantly increased the proportion of cells in G₁ phase compared with the control group (P<0.05). The proportion of cells in G₁ phase was significantly increased when the two drugs were combined (P<0.05). The expression of p-mTOR and effector protein p-4EBP1 was significantly downregulated in the EVE combined with GEM group, the expression of anti-apoptotic proteins MCL-1, Survivin and cell cycle protein cyclin D1 was downregulated too (P<0.05). CONCLUSION EVE combined with GEM can synergistically inhibit the proliferation of U2932 cells, and the mechanism may be that they can synergistically induce apoptosis by downregulating the expression of MCL-1 and Survivin proteins and block the cell cycle progression by downregulating the expression of Cyclin D1.
Humans ; Gemcitabine ; Everolimus/pharmacology* ; Survivin/pharmacology* ; Cyclin D1/pharmacology* ; Myeloid Cell Leukemia Sequence 1 Protein ; Cell Line, Tumor ; Cell Proliferation ; TOR Serine-Threonine Kinases ; Apoptosis ; Apoptosis Regulatory Proteins ; Cell Cycle Proteins ; Lymphoma, Large B-Cell, Diffuse

OBJECTIVE: To analyze the clinical characteristics of hemophagocytic syndrome (HLH) children with different EB virus (EBV) DNA loads, and to explore the relationship between differential indicators and prognosis. METHODS: Clinical data of 73 children with HLH treated in our hospital from January 2015 to April 2022 were collected. According to EBV DNA loads, the children were divided into negative group (≤5×10² copies/ml), low load group (>5×10²-<5×10⁵ copies/ml) and high load group (≥5×10⁵copies/ml）. The clinical symptoms and laboratory indexes of the three groups were compared, and the ROC curve was used to determine the best cut-off value of the different indexes. Cox regression model was used to analyze the independent risk factors affecting the prognosis of children, and to analyze the survival of children in each group. RESULTS: The proportion of female children, the swelling rate of liver and spleen lymph nodes and the involvement rate of blood, liver, circulation and central nervous system in the high load group were higher than those in the negative group. The incidence of disseminated intravascular coagulation(DIC) and central nervous system(CNS) involvement in the high load group were higher than those in the low load group. The liver swelling rate and circulatory system involvement rate in the low load group were higher than those in the negative group(P<0.05). PLT counts in the high load group were significantly lower than those in the negative group, and the levels of GGT, TBIL, CK-MB, LDH, TG, SF, and organ involvement were significantly higher than those in the negative group. The levels of CK, LDH, SF and the number of organ involvement in the high load group were significantly higher than those in the low load group. The levels of GGT and TBIL in low load group were significantly higher than those in negative group. In terms of treatment, the proportion of blood purification therapy in the high and low load group was significantly higher than that in the negative group(P<0.01). ROC curve analysis showed that the best cut-off values of PLT, LDH, TG and SF were 49.5, 1139, 3.12 and 1812, respectively. The appellate laboratory indicators were dichotomized according to the cut-off value, and the differential clinical symptoms were included in the Cox regression model. Univariate analysis showed that LDH>1139 U/L, SF>1812 μg/L, dysfunction of central nervous system, number of organ damage, DIC and no blood purification therapy were the risk factors affecting the prognosis of children (P<0.05); Multivariate analysis shows that PLT≤49.5×10⁹/L and dysfunction of central nervous system were risk factors affecting the prognosis of children (P<0.05). Survival analysis showed that there was no significant difference in the survival rate among the three groups. CONCLUSION The incidence of adverse prognostic factors in children with HLH in the EBV-DNA high load group is higher, and there is no significant difference in the survival rate of the three groups after blood purification therapy. Therefore, early identification and application of blood purification therapy is of great significance for children with HLH in the high load group.
Humans ; Child ; Female ; Lymphohistiocytosis, Hemophagocytic ; Retrospective Studies ; Risk Factors ; DNA ; Prognosis

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.

Heavy metals and other harmful elements in traditional Chinese medicines inflict serious damage on public health. Therefore, risk assessment of Chinese raw materials has gained increasing attention. To date, few reports have been published on the health risk assessment of heavy metals and harmful elements in Chinese patent medicines. To gain a comprehensive understanding of heavy metals and other harmful elements in Chinese patent medicines and to establish proper limits, residual Pb, Cd, As, Hg, Cu and Cr in 15 054 samples of 295 drugs was analyzed with regard to distribution and variation between elements and dosage forms. In addition, in accord with procedures including hazard identification, hazard characterization, exposure assessment and risk characterization, basic procedures and specific parameters for risk assessment of heavy metals and harmful elements in Chinese patent medicines were clarified based on the health risk assessment of 14 787 samples and 276 drugs. A method and equation for establishing residual limits is proposed. The results show that content and target hazard quotients (THQs) of the investigated elements in all samples showed a skewed distribution approaching 0. Content of Pb, As, Cu, Hg, Cd or Cr in the samples exceeded 100 mg·kg^-1 and the content of Pb, As, or Cu in individual samples exceeded 1 000 mg·kg^-1. THQs of 586 samples and four drugs were above 1. We believe that the health risk of Hg, Pb and As in Chinese patent medicines with dosage forms of pill, capsule, tablet and powder, especially those in raw powder preparations, warrant concern.

Objective: To investigate the incidence and risk factors of peripartum mood disorder (PPMD) in order to improve clinical prevention and intervention of this condition. Methods: This was a prospective cohort study recruiting first-trimester pregnant women (<13 gestational weeks) from Beijing Daxing Maternal and Child Care Hospital from October 1, 2016 to December 31, 2017. Zung Self-rating Anxiety Scale (SAS) and Zung Self-rating Depression Scale (SDS) were used to evaluate the anxiety and depression status in the second and third trimesters, respectively. Their life styles, social and environmental factors exposure during pregnancy were also collected. Statistical analysis was conducted using Chi-square test, student's t test, Mann-Whitney U test and multivariate logistic regression. Results: (1) A total of 478 subjects were enrolled in early pregnancy and 460 (96.2%) and 431 (90.2%) of them completed SAS and SDS assessment in the second and third trimesters, respectively, and 413 (86.4%) of the subjects finished both assessments on two occasions. (2) The prevalence of anxiety and depression was 7.1% (30/425) and 13.9% (59/425) in the second trimester, and 11.2% (44/392) and 21.5% (84/390) in the third. The incidence of anxiety and depression in the third trimester was 7.7% (26/336) and 9.6% (30/313). (3) Cross-sectional data analysis showed that prolonged television watching was a risk factor of anxiety in the second (OR=1.216, 95%CI: 1.055-1.402) and third (OR=1.166, 95%CI: 1.044-1.303) trimester, while exercise was a protect factor (OR=0.238, 95%CI: 0.105-0.541; OR=0.432, 95%CI: 0.212-0.879). Pregnant women with longer sleeping time had lower risks of depression in the second trimester (OR=0.725, 95%CI: 0.554-0.950); those who did exercise had lower risks of depression in the third trimester (OR=0.450, 95%CI: 0.252-0.803). (4) Longitudinal-data analysis revealed that longer television watching time in the second trimester was a risk factor for anxiety (OR=1.264, 95%CI: 1.117-1.432) and depression (OR=1.119, 95%CI: 1.005-1.246) in the third trimester. Conclusions The prevalence of anxiety and depression in the third trimester is higher than that in the second trimester. The incidence of depression is higher than that of anxiety in the third trimester. Prolonged television viewing time in the second trimester is a risk factor for both anxiety and depression in the third trimester.

OBJECTIVE: To analyze the X-ray characteristics in youth neck type of cervical spondylosis with upper crossed syndrome(UCS). METHODS: The patients who had a neck type of cervical spondylosis with or without UCS were selected from January to October 2017, 20 cases in each group, and 10 normal volunteers were chosen in the study. X-ray examination of lateral and hyperextension-hyperflexion of cervical spine were performed to observe cervical spine angle, angular displacement and adjacent vertebral body slip. RESULTS: The cervical spine angle was (-0.40±9.64)° in the UCS group, significantly less than (14.35±9.01)° in the normal group and (12.34±5.65)° in the non-UCS group(<0.05). The change of angular displacement of the upper cervical vertebra in anterior flexion and posterior extension was (8.18±4.81)° in UCS group, which was also significantly less than (12.14±3.48)° in the normal group and (12.34±5.65)° in the non-UCS group(<0.05). The slippage of the vertebral posterior margin of the lower cervical spine in the anterior flexion was 15.41±2.21 in the UCS group, which was significantly greater than 13.26±2.42 in normal group(<0.05), and was not obviously different from 15.64±2.07 in non-UCS group(>0.05). CONCLUSIONS In young patients who has a neck type of cervical spondylosis with UCS, the cervical curvature prone to straighten or reverse, the upper cervical flexion and extension are limited, while the lower cervical is in a flexion.
Adolescent ; Cervical Vertebrae ; Humans ; Neck ; Radiography ; Spondylosis ; X-Rays

Objective:Our study was aimed to analyze the therapeutic effect of early sequential enteral nutrition on postoperative rehabilitation in patients with gastric cancer.Methods:Patients with gastric cancer receiving surgery at our hospital from 2016 to 2017 included and the clinical information was prospective collected and analyzed.Patients were randomly divided into two groups using random number table.Patients in group A were sequentially given amino acid type,short peptide type and then whole protein type,while those in group B received whole protein formulation only.The recovery of gastrointestinal function,postoperative systemic inflammatory response,six-minutes walking test,and enteral nutrition-related complications were compared between the two groups.Results:A total of 71 patients were included in this study (Group A 36 cases,Group B 35 cases).There was no significant difference in terms of the restart anal exhaust between the two groups (P ＞ 0.05).Patients in group A had a significantly shorter postoperative hospitalization (t =4.070;P ＜ 0.01) and the earlier restoration of oral intake than that of Group B (t =3.400;P =0.001).One week after surgery,the levels of CRP (t =2.547;P =0.013) and IL-6 (t =3.172;P =0.002) were significant lower in group A when compared with group B.In addition,patients in group A had a significant higher six minutes walk steps than those in Group B [(416.1 + 36.7) m vs (358.9 ± 32.7) m;t =6.927,P ＜ 0.01].However,no significant difference in enteral nutrition-related complications was found between the two groups (P ＞ 0.05).Conclusion:In patients with gastric cancer,early sequential enteral nutrition can effectively accelerate the postoperative rehabilitation.

Objective To explore the protective effect of astragaloside Ⅳ on the oxidative stress injury of human glomerular mesangial cells under high glucose conditions and the mechanism.Methods The glomerular mesangial cells were dividedinto model group,control group and experimental-L/M/H groups.Model group was treated with 25 mmol · L-1 glucose,experimental-L/M/H groups were given 25,50,100 μmol · L-1 astragaloside Ⅳ on the basis of model group,control group was treated with equivalent normal saline.Each group was cultured for 48 h after inervention.The cells proliferation were detected by methyl thiazolyl tetrazolium (MTF),the reactive oxygen species (ROS) level and fluorescence intensity were detected by fluorescent probe method,the cells Akt/NF-κB signaling pathways related proteins were detected by Western blot.Results The proliferation inhibition rates of glomerular mesangial cells in experimental-L/M/H groups were (6.79 ± 0.12) ％,(17.05 ± 0.15) ％,(28.31 ± 0.23) ％,and increased with the increasing of astragaloside Ⅳ concentration(P ＜0.01).The ROS relative expressions of glomerular mesangial cells in control group,model group and experimental-L/M/H groups were 0.02 ± 0.01,0.07 ± 0.01,0.06 ± 0.02,0.04 ± 0.03,0.02 ± 0.02;the phospho-protein binases (p-Akt) protein relative expression were 0.25 ± 0.03,0.57 ± 0.02,0.46 ± 0.02,0.31 ± 0.04,0.27 ± 0.03;p-IκBαprotein relative expression were 0.44 ± 0.03,0.16 ±0.01,0.21 ±0.02,0.26 ±0.02,0.33 ±0.02.Compared with control group,the ROS relative expression,fluorescence intensity and p-Akt protein relative expression of model group increased significandy (P ＜ 0.01),the p-IκBα protein relative expression decreased significantly (P ＜0.01).Compared with model group,the ROS relative expression,fluorescence intensity and p-Akt protein relative expression of experimental groups decreased significantly with the increasing of astragaloside Ⅳ concentration (P ＜ 0.01);while the p-IκBα relative expression increased with the increasing of astragaloside Ⅳ concentration (P ＜ 0.01).Conclusion Astragaloside Ⅳ can adjust the ROS expression level of glomerular mesangial cells under high glucose conditions effectively,and inhibit the oxidative stress reaction,the action mechanism maybe related to the down-regulation of p-Akt protein and the up-regulation of p-IκBα protein of Akt/NF-κB signaling pathways,which has significant dose-dependent manner.