Objective:To characterize the longitudinal and dynamic high-density lipoprotein (HDL) trajectories in critically ill children and explore their correlation with clinical outcomes.Methods:Retrospective cohort study.All critically ill children admitted to the Pediatric Intensive Care Unit (PICU) of West China Hospital, Sichuan University from January 1, 2015 to October 1, 2020 were included in this retrospective study.Group-based trajectory modeling (GBTM) was applied to characterize the HDL trajectories in days 0-6 post-PICU admission and develop HDL trajectory groups.The in-hospital mortality rate was reported as frequency (%) and then compared by the Chi-square test or Fisher′s exact test between HDL trajectory groups.The length of stay (LOS) in the PICU was described by M( Q1, Q3), and its difference between HDL trajectory groups was evaluated by the Kruskal Wallis test.Logistic regression and multiple linear regression were used to determine the correlation between HDL trajectories and clinical outcomes.The primary outcome was in-hospital mortality rate, and the secondary outcome was LOS in the PICU. Results:A total of 4 384 critically ill children were ultimately enrolled in the study, and 6 HDL trajectory groups were developed based on GBTM analyses: group 1 (758 cases), the lowest HDL group; group 2 (1 413 cases), the low HDL group; group 3 (74 cases), the low-to-high HDL group; group 4 (621 cases), the medium HDL group; group 5 (1 371 cases), the high HDL group; and group 6 (147 cases), the highest HDL group.Logistic regression analysis showed that compared with critically ill children in group 1, those belonging to groups 2, 3, 4, 5, and 6 were at lower risks of in-hospital mortality with odds ratio ( OR): 0.475, 95%confidence interval ( CI): 0.352-0.641, P<0.001; OR: 0.093, 95% CI: 0.013-0.679, P=0.019; OR: 0.322, 95% CI: 0.208-0.479, P<0.001; OR: 0.263, 95% CI: 0.185-0.374, P<0.001, and OR: 0.142, 95% CI: 0.044-0.454, P=0.001, respectively.Multiple linear regression analysis revealed that compared with critically ill children in group 1, those belonging to groups 4, 5, and 6 had the trend of shorter LOS in PICU, and the β value and 95% CI were β: -4.332, 95% CI: -5.238- -3.426, P<0.001; β: -3.053, 95% CI: -3.809--2.297, P<0.001; β: -6.281, 95% CI: -7.842--4.721, P<0.001, respectively. Conclusions:The dynamic HDL trajectories during 0-6 days after PICU admission are associated with in-hospital mortality rate of critically ill children.The HDL trajectory at a persistently low level is associated with higher mortality, while the HDL trajectory at a persistently high level or with the trend from a low level rising to a high level shows a lower risk of mortality.It is suggested that the HDL trajectory model may become an indicator to predict the condition and prognosis of critically ill children.

Objective:To investigate the biological behavior spectrum of platelet-derived growth factor alpha receptor (PDGFRA)-mutant gastrointestinal stromal tumor (GIST), and to compare the clinical values of the Zhongshan method of benign and malignant evaluation with the modified National Institutes of Health (NIH) risk stratification.Methods:A total of 119 cases of GIST with PDGFRA mutation who underwent surgical resection at Zhongshan Hospital, Fudan University from 2009 to 2020 were collected. The clinicopathological data, follow-up records, and subsequent treatment were reviewed and analyzed statistically.Results:There were 79 males and 40 females. The patients ranged in age from 25 to 80 years, with a median age of 60 years. Among them, 115 patients were followed up for 1-154 months, and 13 patients progressed to disease. The 5-year disease-free survival (DFS) and overall survival (OS) were 90.1% and 94.1%, respectively. According to the modified NIH risk stratification, 8 cases, 32 cases, 38 cases, and 35 cases were very-low risk, low risk, intermediate risk, and high risk, and 5-year DFS were 100.0%, 95.6%, 94.3%, and 80.5%, respectively. There was no significant difference in prognosis among the non-high risk groups, only the difference between high risk and non-high risk groups was significant ( P=0.029). However, the 5-year OS was 100.0%, 100.0%, 95.0% and 89.0%, and there was no difference ( P=0.221). According to the benign and malignant evaluation Zhongshan method, 43 cases were non-malignant (37.4%), 56 cases were low-grade malignant (48.7%), 9 cases were moderately malignant (7.8%), and 7 cases were highly malignant (6.1%). The 5-year DFS were 100.0%, 91.7%, 77.8%, 38.1%, and the difference was significant ( P<0.001). The 5-year OS were 100.0%, 97.5%, 77.8%, 66.7%, the difference was significant ( P<0.001). Conclusions:GIST with PDGFRA gene mutation shows a broad range of biological behavior, ranging from benign to highly malignant. According to the Zhongshan method, non-malignant and low-grade malignant tumors are common, the prognosis after surgery is good, while the fewer medium-high malignant tumors showed poor prognosis after surgical resection. The overall biological behavior of this type of GIST is relatively inert, which is due to the low proportion of medium-high malignant GIST. The modified NIH risk stratification may not be effective in risk stratification for PDGFRA mutant GIST.

Objective:To investigate the efficacy and safety of encephalo-duro-arterio-synangiosis (EDAS) for intracranial atherosclerotic steno-occlusive disease (ICASD).Methods:Patients with symptomatic ICASD received EDAS treatment in the Department of Neurosurgery, the PLA General Hospital from January 2018 to January 2019 were retrospectively included. The baseline information, perioperative complications, primary endpoint events, and changes in modified Rankin Scale (mRS) scores before and after surgery were collected. The primary endpoint event was any stroke/death that occurred within 30 d after enrollment. The secondary endpoint events were any stroke/death, non-stroke bleeding (subdural or epidural bleeding), and clinical functional improvement after 30 d. The clinical functional improvement was defined as a decrease of ≥1 in the mRS score compared to before surgery.Results:A total of 40 patients were included, including 30 males and 10 females, aged 53.9±8.6 years old. The clinical symptoms were mainly limb weakness and dizziness. One case of ischemic stroke and one case of hemorrhagic stroke occurred during the perioperative period. The primary endpoint event incidence was 2.5%. The patients were followed up for 49.75±2.99 months after surgery. One patient died of cerebral hemorrhage 31 months after surgery, and one patient developed acute ischemic stroke 35 months after surgery. The postoperative mRS scores of 34 patients decreased compared to before surgery, and the clinical function improvement rate was 85%. The mRS score increased in 2 cases after surgery compared to before surgery and 4 cases had no change.Conclusion:EDAS can improve the clinical function of patients with symptomatic ICASD and reduce the incidence of long-term stroke.

Objective:To explore the mechanism of Xijiao Dihuang Ddecoction (XJDHT) against sepsis-induced liver injury based on transcriptomics.Methods:Sixty C57BL/6 mice were randomly (random number) divided into the sepsis group, sepsis treatment with XJDHT and control group, with 20 mice in each group. The sepsis mouse model was established by intraperitoneal (i.p.) injection of lipopolysaccharide (LPS). The control group was intraperitoneally injected with the same amount of normal saline. The sepsis treatment with XJDHT group was injected with XJDHT (crude drug 187.5 mg) twice a day 2 days before modeling. After modeling, gastric feeding was continued twice a day, while the control group and sepsis group were gavaged with the same amount of normal saline. At 72 h after LPS intervention, 9 mice in each group were randomly selected. After anesthesia, part of the liver were taken for small RNA and RNA sequencing and analysis, and part of the liver were taken for pathological examination.Results:XJDHT could improve the histopathological changes of liver in septic mice, and alleviate some abnormally expressed microRNAs (mmu-mir-292a-5p, mmu-mir-871-3p, mmu-mir-653-5p, mmu-mir-293-5p, mmu-mir-155-3p, mmu-mir-346-5p, mmu-mir-187-5p, mmu-mir-3090-3p) and their target genes.Conclusions:XJDHT can reduce the liver histopathological changes in septic mice, and its mechanism may be related to XJDHT regulating the expression of important key genes of liver of sepsis like mmu-mir-187-5p and its target genes such as ADAM8, irak3 and PFKFB3

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.

Objective:To explore the serum tenascin-C levels in patients with acute ST-segment elevation myocardial infarction (STEMI) and its impact on the long-term prognosis.Methods:One hundred and thirteen STEMI patients who were admitted to the Department of Cardiology of the First Affiliated Hospital of Dalian Medical University and successfully underwent emergency PCI from June 2015 to June 2016 were included in this prospective study. The serum tenascin-C levels were measured during hospitalization, and the patients were divided into tenascin-C ≥ 120 μg/L group and tenascin-C<120 μg/L group according to the serum tenascin-C level. Major adverse cardiovascular events (MACE) were observed during the 5 years follow up in all patients. According to the incidence of MACE, the patients were divided into MACE group and non-MACE group, and the predictive factors of MACE were analyzed. Continuous variables were presented as the mean±standard deviation and compared with the Student′s t-test. Categorical variables were presented as percentages and compared with the Chi-square test or Fisher′s exact test. Receiver operating characteristic (ROC) curve was used to analyze the value of serum tenascin-C level in predicting MACE in STEMI patients. Kaplan Meier survival analysis was used to compare the incidence of MACE between two groups. Cox proportional hazards regression model was used to analyze the risk factors of MACE during the 5 years follow up.Results:The serum tenascin-C levels in the STEMI patients increased on the first day after the onset of disease (46.5±24.8 μg/L), peaked on the third day (97.5±41.2 μg/L), and then gradually decreased. All patients were followed up for 5 years. There were 37 cases of MACE, including 4 cases of cardiac death (3.5%), 14 cases of heart failure (12.4%), 14 cases of recurrent myocardial infarction or revascularization (12.4%), and 5 cases of stroke (4.4%). For prediction of MACE, the area under the curve of the serum TN-C level was 0.953 (95% CI 0.918-0.988, P<0.05), which was thus a valuable biomarker in predicting MACE for STEMI patients. The incidence of MACE in the group of tenascin-C≥120 μg/L group was higher than that in the group of tenascin-C<120 μg/L group (86.4% [19/22] vs 19.8% [18/91]), and Kaplan-Meier survival analysis showed that the difference was statistically significant ( P<0.05). Cox proportional hazards model analysis showed that serum tenascin-C level was an independent predictor of MACE for STEMI patients during the 5 years follow-up ( HR=1.007, 95% CI 1.001-1.012, P<0.05). In addition, other variables including high sensitivity C-reactive protein ( HR=1.028, 95% CI 1.007-1.049, P<0.05), and cardiac troponin Ⅰ ( HR=1.004, 95% CI 1.000-1.008, P<0.05) were also found to be the independent predictors of MACE. Conclusions:The serum tenascin-C levels in STEMI patients increased significantly during the acute disease phase. Detecting the serum tenascin-C levels is valuable for predicting MACE in STEMI patients, and serum tenascin-C is an independent predictor of MACE in STEMI patients during the long-term follow-up period after acute myocardial infarction.

Objective:To investigate the effect of optimized construction of green channel under plan-do-check-action (PDCA) on shortening the door-to-needle time (DNT) and improving early neurological improvement in patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis.Methods:The clinical data of 120 patients with AIS treated with intravenous thrombolysis from June 2018 to September 2019 in Liangxiang Teaching Hospital of Capital Medical University were retrospectively analyzed. Among them, 60 patients were admitted to hospital before optimized as non-optimized group, and 60 patients were admitted to hospital after optimized as optimized group. The time from visit to CT examination completion, time from CT examination completion to informed consent, time from informed consent to intravenous thrombolysis, DNT, DNT ≤ 60 min ratio, National Institutes of Health stroke scale (NIHSS) score 2 h after intravenous thrombolysis and at discharge from hospital, early neurological improvement (ENI) rate, hospital stays, adverse outcomes and mortality were compared between 2 groups.Results:The time from CT examination completion to informed consent and DNT in optimized group were significantly shorter than those in non-optimized group: 29 (14, 36) min vs. 37 (21, 54) min, 55 (45, 67) min vs. 76 (54, 93) min, the DNT ≤ 60 min ratio was significantly higher than that in non-optimized group: 68.3% (41/60) vs. 35.0% (21/60), the ENI rate was significantly lower than that in non-optimized group: 28.3% (17/60) vs. 46.7% (28/60), and there were statistical differences ( P<0.05 or<0.01). There were no statistical differences in the time from visit to CT examination completion, time from informed consent to intravenous thrombolysis, NIHSS score 2 h after intravenous thrombolysis, hospital stays, NIHSS score at discharge from hospital, adverse outcomes rate and mortality between 2 groups ( P>0.05). Conclusions:The optimized construction of green channel under PDCA can effectively shorten the DNT of intravenous thrombolysis in patients with AIS, and may be significantly important for improving the long-term prognosis of patients.

Objective:To evaluate and compare the inpatient medical services of secondary public and private general hospitals by using disease risk adjustment model, and to explore the application of disease risk adjustment model in medical service evaluation of different ownership hospitals.Methods:Based on 1 032 865 front pages of medical records in Chengdu in 2017 and 2018, a regression model with mortality, average length of stay, total hospitalization expenses, medical service fees, drug costs and surgical consumables costs as dependent variables and related influencing factors as independent variables was established by using disease management intelligent analytic and evaluation system. The risk adjusted case mix index(ACMI) was calculated. The mortality, average length of stay, hospitalization expenses and other indicators were predicted. The ratio of observed value to expected value(O/E value) of each index in public and private secondary general hospitals was obtained and compared.Results:The ACMI value of secondary public general hospital was 4.63, slightly higher than that of private hospitals(4.55). The technical difficulty and resource consumption of the public hospitals were slightly higher than that of the private hospitals.From the O/E value, the management of disease mortality, medical service fees and inpatient drug costs of secondary public hospitals was generally good, and the O/E values of hospitalization expenses of each secondary private general hospital were quite different, and there was a possibility that the costs were unreasonable. The O/E value of surgical consumables cost in secondary public general hospital was 1.54, and there was room for improvement in cost management.Conclusions:The disease risk adjustment model fully considers the characteristics of different types and severity of diseases in different institutions, which can not be simply compared. Based on individual cases, it realizes the comparability of different ownership hospitals, and provides a new means for the evaluation of medical service ability and quality.

PURPOSE: Tripartite-motif-containing protein 56 (TRIM56) has been found to exhibit a broad antiviral activity, depending upon E3 ligase activity. Here, we attempted to evaluate the function of TRIM56 in multiple myeloma (MM) and its underlying molecular basis. MATERIALS AND METHODS: TRIM56 expression at the mRNA and protein level was measured by qRT PCR and western blot analysis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry analysis was performed to investigate the effect of TRIM56 on MM cell proliferation and apoptosis. The concentrations of interferon (IFN)-β, interleukin (IL)-6, and tumor necrosis factor-α in MM cell culture supernatants were detected with respective commercial ELISA kits. Western blot was employed to determine the effect of TRIM56 on toll-like receptor 3 (TLR3)/toll-IL-1 receptor (TIR) domain-containing adaptor inducing IFN-β (TRIF) signaling pathway. RESULTS: TRIM56 expression was prominently decreased in MM cells. Poly (dA:dT)-induced TRIM56 overexpression in U266 cells suppressed proliferation, induced apoptosis, and enhanced inflammatory cytokine production, while TRIM56 knockdown improved growth, diminished apoptosis, and inhibited inflammatory cytokine secretion in RPMI8226 cells. Moreover, TRIM56 knockdown blocked TLR3 signaling pathway. Furthermore, poly (I:C), a TLR3 agonist, markedly abolished TRIM56 depletion-induced increase of proliferation, decrease of apoptosis, and reduction of inflammatory factor in MM cells. CONCLUSION: TRIM56 may act as a tumor suppressor in MM through activation of TLR3/TRIF signaling pathway, contributing to a better understanding of the molecular mechanism of TRIM56 involvement in MM pathogenesis and providing a promising therapy strategy for patients with MM.
Adaptor Proteins, Vesicular Transport/metabolism ; Apoptosis/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cytokines/secretion ; Disease Progression ; Down-Regulation/drug effects ; Gene Knockdown Techniques ; Humans ; Multiple Myeloma/metabolism ; Multiple Myeloma/pathology ; Poly I-C/pharmacology ; Signal Transduction/drug effects ; Toll-Like Receptor 3/metabolism ; Tripartite Motif Proteins/deficiency ; Tripartite Motif Proteins/metabolism ; Ubiquitin-Protein Ligases/deficiency ; Ubiquitin-Protein Ligases/metabolism

Objective To evaluate the feasibility and accuracy of virtual navigation contrast enhanced sonography in accurately location of small liver tumors which cannot be detected by conventional sonography during microwave ablation therapy. Methods Twenty-three patients with 28 small liver tumors,which could not be detected by conventional sonography but CT/MRI,underwent microwave ablation with virtual navigation contrast enhanced sonography from January 2015 to March 2017 at Nanfang Hospital. After fusion of images from both sonography and CT/MRI,small liver tumors were ablated under the real-time monitoring of navigated sonography. Virtual navigation contrast enhanced sonography was also utilized to evaluate the efficacy of ablation after the ablation.All patients underwent CT/MRI examination at one month post-ablation to evaluate the efficacy of ablation. Results Virtual navigation system successfully provided image fusion for all patients and all lesions(image fusion efficacy was 100%). All patients underwent virtual navigation contrast enhanced sonography monitored microwave ablation.Only one patient received extra ablation since a small proportion of residual tumor checked after the initial ablation. No severe complications occurred in the present study. One-month after ablation,all patients showed complete ablation by further CT/MRI examinations.Conclusion Virtual navigation sonography can precisely target small liver tumors which are undetected by conventional sonography.Evaluation of lesions and ablation efficacy can be performed with the help of virtual navigation contrast enhanced sonography during the ablation period,which have shown satisfactory clinical efficacy.