OBJECTIVETo observe the images of early lesions of condylar cartilage of osteoarthritic rats in synchrotron radiation diffraction enhanced imaging (DEI).

METHODSThe animal model of temporomandibular joint osteoarthrosis was established in rat following the method of partial resection of the joint disc. The changes of osteoarthritic condylar cartilage in different pathological stages were observed by DEI and compared with those in situ histopathological sections.

RESULTSWith DEI, straight and orbicular lines were detected in condylar cartilage 45 to 60 days after discs resection. The lines were confirmed by histopathology to be collagen degradation and tiny fissure formation inside the cartilage.

CONCLUSIONSDEI is capable of imaging the early stages of pathological changes of excised condylar cartilage such as collagen degradation and tiny fissure formation, and this technique is of potential value to clinical application.

Animals ; Cartilage, Articular ; diagnostic imaging ; pathology ; Male ; Mandibular Condyle ; diagnostic imaging ; pathology ; Radiography ; Rats ; Rats, Wistar ; Temporomandibular Joint Disorders ; diagnostic imaging ; pathology ; X-Ray Diffraction ; methods

OBJECTIVETo investigate the changes in peripheral blood bone marrow stem cells and tumor necrosis factor-alpha gene expression in the ischemic myocardium in rabbit models of hibernating myocardium.

METHODSTwenty-four male Japanese white rabbits were randomized into 4 groups, including a sham-operated group and 3 model groups with hibernating myocardium induced by partial ligation of the left anterior descending coronary artery. The percentage of CD34-positive cells in the peripheral blood was evaluated by flow cytometry, and TNF-alpha mRNA expression in the ischemic myocardium was determined by real-time RT-PCR in the 3 model groups (at 3, 7, or 28 days after the operation) and in the sham-operated group.

RESULTSIn rabbits with partial ligation of the left anterior descending coronary artery, the percentage of CD34-positive cells in the peripheral blood and myocardial TNF-alpha mRNA expression were significantly increased at 3 and 7 days after the operation in comparison with those in the sham-operated group and those at 28 days postoperatively (P<0.01). No significant differences were found in the percentage of CD34 positive cells or myocardial TNF-alpha mRNA expression between the sham-operated group and the rabbits 28 days after the coronary artery ligation (P>0.05).

CONCLUSIONBone marrow stem cell can be mobilized into the peripheral blood in rabbit hibernating myocardium model possibly by increasing TNF-alpha gene expression in the ischemic myocardium.

Animals ; Antigens, CD34 ; metabolism ; Bone Marrow Cells ; cytology ; Coronary Vessels ; surgery ; Disease Models, Animal ; Gene Expression Regulation ; Hematopoietic Stem Cell Mobilization ; Hibernation ; Ligation ; Male ; Myocardial Ischemia ; metabolism ; physiopathology ; surgery ; therapy ; RNA, Messenger ; genetics ; metabolism ; Rabbits ; Tumor Necrosis Factor-alpha ; genetics

OBJECTIVETo investigate the prognosis evaluation and treatment strategy of chronic severe hepatitis (CSH) patients using a model of end-stage liver disease (MELD).

METHODSThe MELD scores of 135 CSH patients on the day of their admittance to our hospital and the DeltaMELD scores after two-weeks of medical treatment were retrospectively analyzed. They were also compared with the scores of the three-month mortality rate of the patients.

RESULTSThe mean MELD score calculated on the first day of the patients who died after their admission to the hospital was 37.00+/-6.50, while that of the living group was 25.80+/-5.20. The difference was highly significant (chi(2)=72.00, P < 0.01). MELD score after two-weeks medical treatment of the patients who died was 1.57+/-0.89, while that of the living group was -0.99+/-0.73; the difference was also highly significant (chi(2)=56.35, P < 0.01). The area under the ROC curve of MELD score (c-statistic) was 0.90, while the c-statistic for DeltaMELD score was 0.76. On the first day of their admission, when the MELD score was < 25, the three-month mortality rate was 2%; when it was 25 or= 35, the three-month mortality rate was 81%; the differences between these groups were all highly significant (P less than 0.01). When MELD scores were above zero, the three-month mortality was 51%, and when DeltaMELD scores were less than or equal to zero, the three-month mortality rate was 13%. All the differences were highly significant (P < 0.01).

CONCLUSIONA high MELD score and a high Delta MELD score herald high three-month mortality rates in patients with CSH. MELD is quite usable in assessing the prognosis in patients suffering CSH. The choice of treatment for the CSH patients could be made by integrating the MELD score calculated on the first day of being admitted to a hospital and the Delta MELD score after their medical treatment.

Adolescent ; Adult ; Aged ; Female ; Hepatitis, Chronic ; mortality ; therapy ; Humans ; Liver Failure ; mortality ; therapy ; Male ; Middle Aged ; Models, Statistical ; Prognosis ; Survival Rate ; Young Adult

OBJECTIVETo evaluate the clinical characteristics and risk factors of clonal evolution after immunosuppressive therapy (IST) in children with severe/very severe aplastic anemia (SAA/VSAA).

METHODSThe clinical data of 231 children with newly-diagnosed SAA/VSAA who received IST were retrospectively studied. The incidence and risk factors of clonal evolution after IST were analyzed.

RESULTSThe 5-year overall survival rate of the 231 patients was 82.7%. Except for 18 cases of early deaths, 213 patients were evaluated for IST efficacy. Among the 231 patients, cytogenetic abnormalities for at least two chromosome metaphase were detectable in 14 (7.4%) patients, and PNH clones were detectable in either peripheral red blood cells or neutrophils for 95 patients. Among the 213 patients evaluated for IST efficacy, 15 patients experienced clonal evolution after IST. Five patients had PNH and trisomy 8 which were defined as favorable progressions, and ten patients experienced monosomy 7 and MDS/AML as unfavorable progressions. The 5-year accumulative incidence of favorable and unfavorable progression were (2.2±2.2)% and (4.8±3.3)%, respectively. Until the last follow-up, 100% (5/5) of patients with favorable progressions and 50% (5/10) of patients with unfavorable progressions survived. WBC>3.5×10/L, CD3T cell percentage>80%, dosage of antithymocyte globulin >3.0 mg/(kg·d) and no response to IST were related to unfavorable progressions by univariate analysis. Cox multivariate analysis revealed that an increased CD3T cell percentage (>80%) and no response to IST were independent risk factors for unfavorable progressions.

CONCLUSIONSThe children with SAA/VSAA who have an increased CD3T cell percentage at diagnosis or have no response to IST are in high risks of unfavorable progressions.

Adolescent ; Anemia, Aplastic ; drug therapy ; genetics ; immunology ; mortality ; Child ; Child, Preschool ; Chromosome Aberrations ; Clonal Evolution ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Infant ; Male ; Proportional Hazards Models ; Retrospective Studies

OBJECTIVETo investigate the value of multiparameter flow cytometry (MFC) and flow cytometric scoring system (FCSS) in the diagnosis and prognostic evaluation of childhood myelodysplastic syndrome (MDS).

METHODSA retrospective analysis was performed for the clinical data of 42 children who were diagnosed with MDS. MFC was performed to investigate the phenotype and proportion of each lineage of bone marrow cells. The correlations of FCSS score with MDS type, International Prognostic Scoring System (IPSS) score, and revised IPSS (IPSS-R) score were analyzed.

RESULTSOf all the 42 children, 20 (48%) had an increase in abnormal marrow blasts, 19 (45%) had a lymphoid/myeloid ratio of >1, 14 (33%) had abnormal cross-lineage expression of lymphoid antigens in myeloid cells, 8 (19%) had abnormal CD13/CD16 differentiation antigens, 5 (12%) had abnormal expression of CD56, 3 (7%) had reduced or increased side scatter of granulocytes, 3 (7%) had reduced expression of CD36 in nucleated red blood cells, 2 (5%) had reduced expression of CD71 in nucleated red blood cells, 1 (2%) had absent expression of CD33 in myeloid cells, 1 (2%) had reduced or absent expression of CD11b in granulocytes, and 1 (2%) had absent expression of CD56 and CD14 in monocytes. There were significant differences in the median overall survival time and event-free survival time among the low-, medium-, and high-risk FCSS groups (P<0.05). Among the low-, medium-, and high-risk FCSS groups, the low-risk FCSS group had the highest 2-year overall survival rate, while there was no significant difference between the medium- and high-risk FCSS groups (P>0.05). The three groups had a 2-year event-free survival rate of 95%, 60%, and 46% respectively (P<0.05). FCSS score was positively correlated with MDS type, IPSS score, and IPSS-R score (P<0.05).

CONCLUSIONSMFC and FCSS help with the diagnosis and prognostic evaluation of childhood MDS.

OBJECTIVETo evaluate the expression of HMGB1 protein in tissue specimens of laryngeal squamous cell carcinoma (LSCC) and adjacent normal mucosa, and explore the correlation of HMGB1 protein expression with clinicopathologic features and prognosis in LSCC.

METHODSNinty-three cases of LSCC and 5 cases of adjcent mucosal tissue samples were included in this study. Immunohistochemical staining was performed on paraffin-embedded tissue specimens to examine the HMGB1 protein expression. The data were futher correlated with the clinicopathological features and prognosis of the LSCC patients.

RESULTSThe positive rates of HMGB1 expression in LSCC specimens was 87.1%, significantly higher than that in the adjcent normal mucosa samples (46.7%, P = 0.001), and its overexpresion was closely correlated with T stage (Chi2 = 10.878, P = 0.004), clinical stage (Chi2 = 21.115, P < 0.01), metastasis (Chi2 = 28.298, P < 0.01) and recurrence (Chi2 = 14. 923, P = 0.001) in patients with LSCC. Patients with HMGB1 overexpression had both poorer disease-free survival and poorer overall survival compared with that in patients with low HMGB1 expression (Chi2 = 13.815, Chi2 = 11.912; Both P < 0.01). Univariate and multivariate Cox regression analyses revealed that HMGBI expression is an independent prognostic factor for patients with LSCC.

CONCLUSIONSThe results of this study demonstrate that HMGB1 protein expression is significantly increased in LSCC tissues, and HMGB1 protein overexpression is associated with a poorer prognosis in patients with LSCC. These results suggest that HMGB1 may play a critical role in the initiation and progression of LSCC, implicating HMGB1 may become a valuable marker for the prediction of prognosis in patients with LSCC.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; metabolism ; pathology ; surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; HMGB1 Protein ; metabolism ; Humans ; Laryngeal Neoplasms ; metabolism ; pathology ; surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Proportional Hazards Models ; Survival Rate

Fatal Outcome ; Humans ; Inflammation ; immunology ; metabolism ; mortality ; Lymphoma, T-Cell ; immunology ; metabolism ; mortality ; Male ; Middle Aged

BACKGROUND: The current deep learning diagnosis of breast masses is mainly reflected by the diagnosis of benign and malignant lesions. In China, breast masses are divided into four categories according to the treatment method: inflammatory masses, adenosis, benign tumors, and malignant tumors. These categorizations are important for guiding clinical treatment. In this study, we aimed to develop a convolutional neural network (CNN) for classification of these four breast mass types using ultrasound (US) images. METHODS: Taking breast biopsy or pathological examinations as the reference standard, CNNs were used to establish models for the four-way classification of 3623 breast cancer patients from 13 centers. The patients were randomly divided into training and test groups (n = 1810 vs. n = 1813). Separate models were created for two-dimensional (2D) images only, 2D and color Doppler flow imaging (2D-CDFI), and 2D-CDFI and pulsed wave Doppler (2D-CDFI-PW) images. The performance of these three models was compared using sensitivity, specificity, area under receiver operating characteristic curve (AUC), positive (PPV) and negative predictive values (NPV), positive (LR+) and negative likelihood ratios (LR-), and the performance of the 2D model was further compared between masses of different sizes with above statistical indicators, between images from different hospitals with AUC, and with the performance of 37 radiologists. RESULTS: The accuracies of the 2D, 2D-CDFI, and 2D-CDFI-PW models on the test set were 87.9%, 89.2%, and 88.7%, respectively. The AUCs for classification of benign tumors, malignant tumors, inflammatory masses, and adenosis were 0.90, 0.91, 0.90, and 0.89, respectively (95% confidence intervals [CIs], 0.87-0.91, 0.89-0.92, 0.87-0.91, and 0.86-0.90). The 2D-CDFI model showed better accuracy (89.2%) on the test set than the 2D (87.9%) and 2D-CDFI-PW (88.7%) models. The 2D model showed accuracy of 81.7% on breast masses ≤1 cm and 82.3% on breast masses >1 cm; there was a significant difference between the two groups (P < 0.001). The accuracy of the CNN classifications for the test set (89.2%) was significantly higher than that of all the radiologists (30%). CONCLUSIONS: The CNN may have high accuracy for classification of US images of breast masses and perform significantly better than human radiologists. TRIAL REGISTRATION Chictr.org, ChiCTR1900021375; http://www.chictr.org.cn/showproj.aspx?proj=33139.
Area Under Curve ; Breast/diagnostic imaging* ; Breast Neoplasms/diagnostic imaging* ; China ; Deep Learning ; Humans ; ROC Curve ; Sensitivity and Specificity

OBJECTIVE: To explore the DNA methylation sites correlated with blood pressure (systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse pressure) in adult twin population. METHODS: A total of 476 twins from the Chinese National Twin Registry were selected as the research population. Questionnaires were used to collect demographic characteristics, lifestyle, disease status and other information, and blood pressure, height, weight and other anthropometric indicators were measured. The genome-wide DNA methylation of whole blood samples was detected by using Infinium HumanMethylation450 BeadChip. The DNA methylation sites correlated with blood pressure were analyzed by constructing mixed effect model with adjusting potential confounding factors, and the significant level was false discovery rate <0.05. RESULTS: After data quality control, 465 twins (122 pairs of monozygotic twins, 104 pairs of dizygotic twins, 13 individuals from 13 pairs of twins) aged (44.8±13.2) years were finally enrolled. There were more males and more monozygotic twins, and the current smokers and current regular drinkers both accounted for more than 30%. No significant CpG site was found after multiple testing in the correlation study between genome-wide DNA methylation and blood pressure by using the collected twins. However, the cg07761116 located on chromosome 10 had low P value in the correlation analysis of 3 blood pressure indices (systolic blood pressure, diastolic blood pressure, mean arterial pressure), suggesting that this site might be correlated with blood pressure. The other 7 sites had low P value in the correlation analysis of the two blood pressure indices, respectively, which pointed to genes involved in neurological development, protein homeostasis, inflammatory reaction and other pathways. CONCLUSION There is no sufficient evidence to support any DNA methylation site correlated with blood pressure, which may be caused by insufficient sample size and other reasons. This study could provide a reference for subsequent similar twin studies, and subsequent studies can focus on the cg07761116 located on chromosome 10 and other sites with low P values.
Adult ; Blood Pressure ; Body Weight ; CpG Islands ; DNA Methylation ; Female ; Humans ; Male ; Middle Aged ; Twins, Monozygotic

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.