Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

Background: Technical aspects of the correct placement of medial support locking screws in the locking plate for proximal humerus fractures remain incompletely understood. This study was to evaluate the clinical relationship between the number of medial support screws and the maintenance of fracture reduction after locked plating of proximal humerus fractures. Methods: We retrospectively evaluated 181 patients who had been surgically treated for proximal humeral fractures (PHFs) with a locking plate between September 2007 and June 2013. All cases were then subdivided into one of four groups as follows: 75 patients in the medial cortical support (MCS) group, 26 patients in the medial multiscrew support (MMSS) group, 29 patients in the medial single screw support (MSSS) group, and 51 patients in the no medial support (NMS) group. Clinical and radiographic evaluations included the Constant-Murley score (CM), visual analogue scale (VAS), complications, and revision surgeries. The neck-shaft angle (NSA) was measured in a true anteroposterior radiograph immediately postoperation and at final follow-up. One-way analysis of variance or Kruskal-Wallis test was used for statistical analysis of measurement data, and Chi-square test or Fisher's exact test was used for categorical data. Results: The mean postoperative NSAs were 133.46° ± 6.01°, 132.39° ± 7.77°, 135.17° ± 10.15°, and 132.41° ± 7.16° in the MCS, MMSS, MSSS, and NMS groups, respectively, and no significant differences were found (F = 1.02, P = 0.387). In the final follow-up, the NSAs were 132.79° ± 6.02°, 130.19° ± 9.25°, 131.28° ± 12.85°, and 127.35° ± 8.50° in the MCS, MMSS, MSSS, and NMS groups, respectively (F = 4.40, P = 0.008). There were marked differences in the NSA at the final follow-up between the MCS and NMS groups (P = 0.004). The median (interquartile range [IQR]) NSA losses were 0.0° (0.0-1.0)°, 1.3° (0.0-3.1)°, 1.5° (1.0-5.2)°, and 4.0° (1.2-7.1)° in the MCS, MMSS, MSSS, and NMS groups, respectively (H = 60.66, P < 0.001). There were marked differences in NSA loss between the MCS and the other three groups (MCS vs. MMSS, Z = 3.16, P = 0.002; MCS vs. MSSS, Z = 4.78, P < 0.001; and MCS vs. NMS, Z = 7.34, P < 0.001). There was also significantly less NSA loss observed in the MMSS group compared to the NMS group (Z = -3.16, P = 0.002). However, there were no significant differences between the MMSS and MSSS groups (Z = -1.65, P = 0.225) or the MSSS and NMS groups (Z = -1.21, P = 0.099). The average CM scores were 81.35 ± 9.79, 78.04 ± 8.97, 72.76 ± 10.98, and 67.33 ± 12.31 points in the MCS, MMSS, MSSS, and NMS groups, respectively (F = 18.68, P < 0.001). The rates of excellent and good CM scores were 86.67%, 80.77%, 65.52%, and 43.14% in the MCS, MMSS, MSSS, and NMS groups, respectively (χ = 29.25, P < 0.001). The median (IQR) VAS scores were 1 (0-2), 1 (0-2), 2 (1-3), and 3 (1-5) points in the MCS, MMSS, MSSS, and NMS groups, respectively (H = 27.80, P < 0.001). Functional recovery was markedly better and VAS values were lower in the MCS and MMSS groups (for CM scores: MCS vs. MSSS, P < 0.001; MCS vs. NMS, P < 0.001; MMSS vs. MSSS, P = 0.031; and MMSS vs. NMS, P < 0.001 and for VAS values: MCS vs. MSSS, Z = 3.31, P = 0.001; MCS vs. NMS, Z = 4.64, P < 0.001; MMSS vs. MSSS, Z = -2.09, P = 0.037; and MMSS vs. NMS, Z = -3.16, P = 0.003). Conclusions Medial support screws might help enhance mechanical stability and maintain fracture reduction when used to treat PHFs with medial metaphyseal comminution or malreduction.
Aged ; Bone Plates ; Bone Screws ; Female ; Fracture Fixation, Internal ; methods ; Humans ; Humerus ; Male ; Middle Aged ; Retrospective Studies ; Shoulder Fractures ; surgery ; Treatment Outcome

OBJECTIVEOsteosarcoma is the most common type of malignant bone tumor in children and adolescents. The role of E3 ligases in tumorigenesis is currently a focus in tumor research. In the present study, we investigated the role of the E3 ligase tripartite motif 21 (TRIM21) in osteosarcoma cell proliferation.

METHODS3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays were used to assess osteosarcoma cell viability. U2-OS cells stably carrying a recombinant lentivirus expressing tetracycline-regulated TRIM21 were screened. Co-immunoprecipitation was coupled with LCMS/MS analysis to identify novel interacting partners of TRIM21. Co-immunoprecipitation and bimolecular fluorescence complementation (BIFC) were performed to validate the interactions between TRIM21 and its novel partner YWHAZ. A TRIM21-ΔRING construct was generated to test the effects of TRIM21 ligase activity on YWHAZ.

RESULTSTRIM21 positively regulated osteosarcoma cell proliferation. Overexpression of TRIM21 enhanced osteosarcoma cell tolerance toward various stresses. YWHAZ protein was identified as a novel interacting partner of TRIM21 and its expression levels were negatively regulated by TRIM21. The RING domain of TRIM21 was required for TRIM21 negative regulation of YWHAZ expression. However, overexpression of YWHAZ did not affect positive regulation of osteosarcoma cell proliferation by TRIM21.

CONCLUSIONOur results further clarify the molecular mechanisms underlying the pathogenesis of osteosarcoma.

14-3-3 Proteins ; genetics ; metabolism ; Cell Proliferation ; genetics ; Humans ; Osteosarcoma ; genetics ; Ribonucleoproteins ; genetics ; metabolism ; Tumor Cells, Cultured

OBJECTIVETumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance greatly limits the clinical therapeutic efficacy of TRAIL. Elucidating the molecular mechanism underlying TRAIL resistance will be fundamental to resolving this problem.

METHODSNuclear and cytoplasmic protein extraction and immuno？uorescence (IF) assay were used to detect changes in heterogeneous nuclear ribonucleoprotein K (hnRNPK) localization in H1299 cells. The evaluation of cell apoptosis in cells transfected with GFP-hnRNPK, GFP-hnRNPK S284/353A, or GFP-hnRNPK S284/353D mutant was performed using cleaved caspase-3 antibody. The gene expression of XIAP was tested by quantitative RT-PCR.

RESULTSPreviously, we reported that hnRNPK antagonized TRAIL-induced apoptosis through inhibition of PKC-mediated GSK3β phosphorylation. In this study, we further demonstrate that TRAIL treatment induces cytoplasmic accumulation of hnRNPK in H1299 cells. The hnRNPK localized in the cytoplasm has a higher capacity to antagonize TRAIL-induced apoptosis. Both ERK1/2 signaling inhibitor U0126 and ERK-phosphoacceptor-site mutant (GFP-hnRNPK S284/353A) diminish cytoplasmic accumulation of hnRNPK induced by TRAIL. Moreover, we show that XIAP is involved in hnRNPK-mediated TRAIL resistance in H1299 cells.

CONCLUSIONTaken together, these results give new insights into the understanding of the molecular mechanism associated with TRAIL resistance in lung adenocarcinoma.

Apoptosis ; physiology ; Cell Line, Tumor ; Gene Expression Regulation ; physiology ; Heterogeneous-Nuclear Ribonucleoprotein K ; genetics ; metabolism ; Humans ; Mitogen-Activated Protein Kinase 1 ; genetics ; metabolism ; Mitogen-Activated Protein Kinase 3 ; genetics ; metabolism ; TNF-Related Apoptosis-Inducing Ligand ; genetics ; metabolism ; Up-Regulation ; physiology ; X-Linked Inhibitor of Apoptosis Protein ; genetics ; metabolism

Objective To design a novel double-leaf proximal humeral locking plate for fixing greater and lesser tuberosities in complex proximal humeral fractures, and evaluate its fixing stability by biomechanical tests. Methods Twelve fresh-frozen humerus specimens with intact rotator cuff were randomly divided into two groups (Group A and Group B) to establish the same greater and lesser tuberosities fracture models. Specimens in Group A were fixed with the double-leaf proximal humeral locking plate, while specimens in Group B were fixed with the proximal humeral internal locking system (PHILOS) and tension band suture, and a 3.5-mm cannulated screw was added to stabilize the lesser tuberosity. The tensile test on subscapularis, infraspinatus and teres, supraspinatus as well as the load-to-failure test on greater and lesser tuberosities were performed on specimens in two groups. Results For subscapularis tensile tests, displacements under 150 N tensile stretch and after fatigue test in Group A were both significantly smaller than those in Group B (P<0.05). For infraspinatus and teres tensile tests, there were no statistical differences between Group A and B in displacements under 150 N tensile stretch and after fatigue test (P>0.05). For supraspinatus tensile tests, there were no statistical differences between Group A and B in displacements under 90 N tensile stretch and after fatigue test (P>0.05). For load-to-failure tests on lesser tuberosity, the failure load in Group A was significantly greater than that in Group B (P<0.05), and the failure displacement in Group A was significantly smaller than that in Group B (P<0.05). For load-to-failure tests on greater tuberosity, there were no statistical differences between Group A and B in both the failure load and failure displacement (P>0.05). Conclusions Compared with the ordinary tension band suture plus cannulated screw for fixing lesser tuberosity, the novel double-leaf proximal humeral locking plate shows more obvious biomechanical stability, with the advantage of simultaneously fixing greater and lesser tuberosities. The research findings provide a new choice for the clinical treatment of complex proximal humeral fractures.

Objective To design a novel double-leaf proximal humeral locking plate for fixing greater and lesser tuberosities in complex proximal humeral fractures,and evaluate its fixing stability by biomechanical tests.Methods Twelve fresh-frozen humerus specimens with intact rotator cuff were randomly divided into two groups (Group A and Group B) to establish the same greater and lesser tuberosities fracture models.Specimens in Group A were fixed with the double-leaf proximal humeral locking plate,while specimens in Group B were fixed with the proximal humeral internal locking system (PHILOS) and tension band suture,and a 3.5-mm cannulated screw was added to stabilize the lesser tuberosity.The tensile test on subscapularis,infraspinatus and teres,supraspi natus as well as the load-to-failure test on greater and lesser tuberosities were performed on specimens in two groups.Results For subscapularis tensile tests,displacements under 150 N tensile stretch and after fatigue test in Group A were both significantly smaller than those in Group B (P ＜ 0.05).For infraspinatus and teres tensile tests,there were no statistical differences between Group A and B in displacements under 150 N tensile stretch and after fatigue test (P ＞ 0.05).For supraspinatus tensile tests,there were no statistical differences between Group A and B in displacements under 90 N tensile stretch and after fatigue test (P ＞ 0.05).For load-to-failure tests on lesser tuberosity,the failure load in Group A was significantly greater than that in Group B (P ＜ 0.05),and the failure displacement in Group A was significantly smaller than that in Group B (P ＜ 0.05).For load-to-failure tests on greater tuberosity,there were no statistical differences between Group A and B in both the failure load and failure displacement (P ＞ 0.05).Conclusions Compared with the ordinary tension band suture plus cannulated screw for fixing lesser tuberosity,the novel double-leaf proximal humeral locking plate shows more obvious biomechanical stability,with the advantage of simultaneously fixing greater and lesser tuberosities.The research findings provide a new choice for the clinical treatment of complex proximal humeral fractures.

OBJECTIVE: To analyze the correlation between four vessel regulate factors and vibration-induced white finger( VWF) evaluating in workers exposed to hand-arm vibration,and discuss the value of regulate factors for VWF screening.METHODS: Using typical sampling method,77 male workers exposed to hand-arm vibration with more than 1 year of polish work from a metalwork factory were selected as the study subjects. Based on the workers' self-report,they were divided into VWF group( 43 workers) and non-VWF group( 34 workers). The venous blood from center elbow was collected and plasma was separated. The plasma level of endothelin( ET) was detected by radioimmunoassay. The plasma levels of transforming growth factor beta( TGF-β),soluble intercellular adhesion molecule-1( s ICAM-1) and 5-hydroxytryptamine( 5-HT) were detected by enzyme-linked immunosorbent assay. The regulate factors for evaluating VWF were screened and the new multivariable model index ^y was built by logistic regression. The related factors were analyzed according to the receiver operating characteristic( ROC) curve. RESULTS: Compared with the non-VWF group,the plasma level of ET in VWF group was decreased( P < 0. 01),and the plasma level of TGF-β was increased( P < 0. 01). Both the levels of s ICAM-1 and 5-HT between the two groups showed no significant difference( P > 0. 05). The logistic regression analysis results showed that after adjusting the confounding factors of age,smoking,alcohol and symptoms in hands,there was a negative correlation found between the ET plasma level and VWF( P < 0. 01) and a positive correlation between the TGF-βplasma level and VWF( P < 0. 01). The VWF incidence was not correlated with plasma levels of s ICAM-1 and 5-HT( P >0. 05). According to ROC curve analysis,the area under the curve( AZ) value of the plasma levels of ET and TGF-β were0. 787 and 0. 691,respectively( P < 0. 01); the sensitivity were 70. 60% and 53. 49%,and the specificity were 79. 10%and 85. 29% respectively. The multivariable model index ^y built with ET and TGF-β by logistic regression was used to judge the AZvalue of VWF to be 0. 821( P < 0. 01),with the 72. 09% of sensitivity and 76. 47% of specificity. The AZ values among ET and TGF-β,^y and ET showed no statistical significance( P > 0. 05). The AZvalue of ^y was larger than that of TGF-β( P < 0. 05). CONCLUSION: The plasma levels of ET and TGF-β are correlation with VWF in hand-arm vibration exposure workers,which can be used in the reseach of screening VWF. The correlation between VWF and SICAM as well as 5-HT needs to be further research.

Objective To investigate the effect of acupuncture combined with antidepressant on behavioral changes and 5-hydroxytryptamine 1A and 2A receptor ( 5-HT1AR and 5-HT2AR) mRNA expression in nucleus raphes dorsalis (NRD) of sleep deprivation depression (SDD) rats. Methods Eight normal Sprague Dawley (SD) rats were caged together without any stimulus or treatment, serving as the normal group. Thirty-two SD rats were given solitary raise for 21 days, together with chronic unpredictable mild stress ( CUMS) and rapid eye movement ( REM) sleep deprivation to establish the model. Twenty-eight rats completed the modeling successfully, and were divided into model group, acupuncture group, medicine group, and combination group, 7 rats in each group. Rats in the model group were given modeling treatment but without any intervention. Rats in the acupuncture group were given acupuncture on acupoint Yintang, Shenting and bilateral Taichong, acupuncture stimulation lasting 15 s every 10 min and acupuncture retention for 20 min in each day. Rats in the medicine group were given gastric gavage of Zoloft solution (0.83 mg·kg-1·d-1) and Alprazolam solution (0.067 mg· kg-1·d-1) , and rats in the combination group were given both acupuncture and medicine intervention. The intervention for the three intervention groups lasted for 7 days. Results Compared with the normal group, body weight, Open-field scores and sucrose preference of the model rats were significantly decreased on modeling day 7, 14, 21 (P<0.05). On modeling day 28, body weight and Open-field scores of each intervention group were significantly increased compared with those of the model group (P<0.05), and Open-field scores of combination group differed from those of acupuncture group and medicine group ( P<0.05). Only sucrose preference of combination group was improved significantly compared with the model group (P<0.05). Compared with the model group, NRD 5-HT1AR mRNA expression level was increased in the combination group (P<0.05), and NRD 5-HT2AR mRNA expression level was down-regulated in all of the three intervention groups ( P<0.05). Conclusion Acupuncture and antidepressant treatment covering 7 days can evoke rapid effect on SDD rats, which can improve the slow effect of antidepressant.

Objective To compare the stability of greater tuberosity fractures of humerus treated by three different fixation techniques (screws, tension band, locking plate, respectively) through biomechanical testing, so as to provide the biomechanics basis for choosing a better fixation in the clinical treatment for greater tuberosity fractures of humerus. Methods Standardized fracture models of the greater tuberosity from 18 fresh-frozen proximal humeri with intact rotator cuffs were created. The specimens were randomly assigned to 3 groups and treated by screws, tension band and locking plates, respectively. An increasing force was applied to the supraspinatus tendon. The force displacement curve and two parameters: LtYP(Load to 5 mm yield point) and Ltf(load to failure) were recorded. Results LtYP from the screw group, tension band group and locking plate group was (377±86), (499±90), (793±52) N, respectively, with significant differences among the three groups (P<0.01). Significant differences were also found between the groups as locking plate group (only 3 cases in locking plate group reached to 5 mm displacement before LtF in this study ) and screw group, locking plate group and tension band group, tension band group and screw group (P<0.01). LtF of screw group, tension band group and locking plate group was (744±112), (908±93), (979±143) N, respectively, showing significant differences among them, and which were also found between locking plate group and screw group, tension band group and screw group (P<0.01), but no significant differences were found between locking plate group and tension band group (P>0.05). Conclusions Locking plates show more obvious biomechanical stability than screws and tension band, which provides a new and better choice for treatment of isolated greater tuberosity fractures of humerus.

Objective To analyze the stress distribution and peak stress on midshaft clavicular fractures fixed by titanium elastic nail (TEN) or reconstruction plate, respectively. Methods CT data of the clavicle was adopted to reconstruct the intact clavicle model and the midshaft clavicular fracture models with the TEN and reconstruction plate fixation by using Mimics software. All the three dimensional finite element models were analyzed using Abaqus 6.9 software. The distal displacement, the peak stress and stress distribution on the distal clavicle under the axial load (250 N) and vertical load (250 N) were calculated for the three models. Results The axial displacement of the distal clavicle under the axial load showed TEN (0.23 mm)>intact clavicle (0.14 mm)>reconstruction plate (0.11 mm), respectively. While the vertical displacement of the distal clavicle under the vertical load was 5.12 mm for TEN, 3.71 mm for intact clavicle and 2.25 mm for reconstruction plate, respectively. But the peak stress of the clavicle under the axial load was 33.1 MPa for TEN, 18.7 MPa for reconstruction plate, and 15.5 MPa for intact clavicle model, respectively. And the peak stress under the vertical load was 146.3, 64.1, 56.1 MPa in the TEN, intact clavicle model, and reconstruction plate model, respectively. The stress distribution in TEN model under both kinds of loads was similar to that in intact clavicle model, while under the vertical load, the stress distribution in reconstruction plate model was clearly different with that in intact clavicle model. For the implants under the axial load, the peak stresses were 191.5, 52.3 MPa in the TEN model and reconstruction plate model, respectively, and the peak stress on implants under the vertical load was 1 248.0, 421.7 MPa in the TEN model and reconstruction plate model, respectively. Conclusions The TEN for treating midshaft clavicular fractures showed a stress distribution similar to the intact clavicle, with a higher peak stress and a higher peak implant stress at the fracture site. The reconstruction plate fixation for midshaft clavicular fractures was shown to be more stable, but with obvious stress shielding. Therefore, TEN is generally preferable for treating the simple displaced fractures of midshaft clavicle. However, the ipsilateral shoulder should avoid excessive exercise and weight bearing in the early postoperative period.