Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare autosomal recessive neuromuscular disease.It is caused by mutations in the gene immunoglobulin μ-binding protein 2 which resides on chromosome 11 q13.3 and encodes the immunoglobulin μ-binding protein 2.This disorder is characterized by degeneration of anterior horn α-motoneurons and manifesting as irreversible diaphragmatic paralysis,respiratory distress associated with progressive symmetrical muscular weakness,distal lower limbs mainly involved,and muscle atrophy between the first 6 weeks and 6 months of life.Overall,SMARD1 is a poor-prognosis disease that artificial ventilation is needed for the whole life.

Objective To analysis and compare the proteomic differences between neural stem cells and motor neurons in embryonic spinal cord in rat and discover the key different proteins. Methods Separating the protein of cells by the 2-D fluorescence difference gel electrophoresis, and to analyse the differences of protein expression with DeCyder software, and to identify with high performance liquid chromatography-electrospray tandem mass spectrometry. Results About 1 300 protein spots from the cells were gained after gel analysis. Eighty-seven protein spots were selected for mass spectrometry analysis. Fourty-four differently expressed proteins (24 in neural stem cells and 20 in motor neurons) were identified by mass spectrometry analysis.Conclusion Differently expressed proteins between neural stem cells and motor neurons were identified and it is helpful to find the new targets in neural stem cells differentiation into motor neurons.

Objective To investigate the relationship between the expression of ITGAV and the radiosensitivity of NSCLC cells. Methods The expression of ITGAV in NSCLC and its relationship to the prognosis of patients who received radiotherapy were analyzed using bioinformatics methods. Differences in radiosensitivity between radio-resistant cells and parent cells were verified by clone formation experiment, and the protein expression of ITGAV was detected by Western blot. The transfection efficiency of si-ITGAV was determined by Western blot and qRT-PCR analyses. The best ITGAV interference sequence was selected to transfect A549R and H1299R cells. Clone formation experiment and flow cytometry were used to detect clone formation, apoptosis and cell cycle of A549R and H1299R cells. Results The expression of ITGAV in NSCLC tissues was significantly higher than that in normal tissues (P<0.05), and NSCLC patients with high ITGAV expression had poor prognosis. The clonogenic ability of the si-ITGAV group was significantly lower than that of the negative control group at 4, 6, 8Gy irradiation (all P<0.05). After 6 Gy irradiation, the apoptosis of the si-ITGAV group was increased (P_H1299R<0.0001, P_A549R=0.0002), the proportion of G₂/M phase cells to A549-siITGAV and H1299R-siITGAV cells was higher than that in the negative control group (P_H1299R<0.0001, P_A549R=0.0007). Conclusion Interfering with ITGAV expression can increase the radiosensitivity of NSCLC.

Objective To examine whether Tim-3 plays a protective role in paraquat poisoning induced excessive immune response and tissue damage based on the critical roles of Tim-3 controlling inflammatory response.Methods A paraquat poisoning model was established in wild type and in Tim-3 transgenic C57BL/6 mice by intraperitoneal injection of paraquat (40 mg/kg) .In addition, C57BL/6 mice with paraquat poisoning were injected with Tim-3 soluble protein( sTim-3) or control protein to see the effect of Tim-3 blocking on the progression of paraquat poisoning.Samples were collected at 6 and 24 h after paraquat injection respectively and were examined for tissue damage, cytokine expression and paraquat metabolism.Results After paraquat poisoning, there was significantly attenuated tissue damage in the lungs and kidneys and decreased TNF-α,IL-6 and IL-1 beta expression in the PBMCs or in the serum from Tim-3 transgenic mice compared to wild type mice.The serum concentration of paraquat in Tim-3 transgenic mice was also significantly decreased.However, in sTim-3 treated paraquat poisoning mice, there was significantly increased cytokine expression and tissue damage compared to control protein treated mice.The in vitro data showed that Tim-3 signaling negatively regulated macrophages mediated inflammatory response.Conclusion Tim-3 plays a critical role in maintaining the homeostasis after paraquat poisoning. Further investigation on the regulatory roles of Tim-3 in inflammation will shed new light on the pathogenesis of paraquat poisoning and provide new therapeutic strategies.

Child ; Humans ; Pneumonia, Mycoplasma/epidemiology* ; Macrolides/therapeutic use* ; Singapore/epidemiology* ; Child, Hospitalized ; Mycoplasma pneumoniae ; Anti-Bacterial Agents/therapeutic use* ; Drug Resistance, Bacterial ; Community-Acquired Infections/drug therapy*

This study showed a case of a patient with central dislocation of the femoral head without involvement of anterior or posterior column of the acetabulum. The patient was associated with endocrine disorders caused by pituitectomy, severe osteoporosis caused by a long-term gulucocorticoids intake history, and poor bone quality of the quadrilateral plate. The direct impact of the femoral head on the quadrilateral plate after trauma resulted in purely central dislocation of the femoral head. 3D printing technique was used to print the fracture model for observation of the fracture morphology and the simulated operation before surgery. The variable-angle locking acetabular plate with a propeller-like shape was designed on the basis of the mirror of the ipsilesional semi-pelvis. This fracture was reduced via the lateral-rectus approach under direct vision. The quadrilateral surface fractures were fixed by the variable-angle locking acetabular plate which was used as a template for reduction. The follow up after surgery showed good reduction and fixation, equal length of double lower limbs, good positive and passive motion of the injured hip joint and without perioperative complications. This report describes an isolated quadrilateral plate fracture that has not yet been classified. It was effectively treated by using a customized variable-angle locking acetabular plate with a propeller-like shape via the lateral rectus approach.

Objective To investigate the effect of exposure to lead oxide nanoparticles (PbO NPs) on the polarization of microglia in mouse hippocampus. Methods i) Specific pathogen-free male C57 mice were randomly divided into control group, low-, medium- and high-dose groups, with 10 mice in each group. Mice in these three dose groups were intraperitoneally injected with PbO NPs suspension at doses of 5, 10 and 20 mg/kg per day, respectively, and mice in the control group were intraperitoneally injected with the same volume of 0.9% sodium chloride solution, five days per week for four weeks. ii) BV-2 cells were treated with PbO NPs at doses of 0.0, 2.5, 5.0 and 10.0 mg/L for 24 hours. iii) BV-2 cells were randomly divided into control group, PbO NPs group and triggering receptor expressed on myeloid cells 2 (TREM2) high expression + PbO NPs group. The cells in the control group received no treatment. The cells in PbO NPs group were exposed to 10.0 mg/L PbO NPs suspension for 24 hours. Cells in TREM2 high expression + PbO NPs group were transfected with Trem2 high expression plasmid, and then exposed to 10.0 mg/L PbO NPs suspension for 24 hours. iv) The mRNA expression of M1 markers ［nitric oxide synthase (iNos), cyclooxygenase 2 (Cox2), chemokine receptor 7 (Ccr7)］, M2 markers ［arginin-1 (Arg-1), transforming growth factor-β (Tgf-β), chemokine receptor 2 (Ccr2)］ and Trem2 of microglia was detected by real-time fluorescent quantitative polymerase chain reaction. The protein expression of iNOS, ARG-1 and TREM2 was detected by Western blotting. Results i) During the experiment, there was no significant difference in body weight of mice among these four groups (P>0.05). The relative expression of Cox2 and Ccr7 mRNA in the hippocampus of the mice increased in the low-dose group and the iNos, Cox2 and Ccr7 mRNA increased in the medium- and high-dose groups, compared with the control group (all P<0.05). The relative mRNA expression of Tgf-β in the hippocampus of the mice of low-dose group and Arg-1, Tgf-β and Ccr2 in the medium- and high-dose groups was decreased compared with the control group (all P<0.05). The mRNA relative expression of iNos, Cox2 and Ccr7 was increased (all P<0.05), while the mRNA relative expression of Arg-1, Tgf-β and Ccr2 was decreased (all P<0.05) in the hippocampus of the mice of high-dose group compared with the low-dose group. The relative expression of Trem2 mRNA and TREM2 protein in the hippocampus of mice of the medium- and high-dose groups was lower than those in the control group (all P<0.05). The relative expression of Trem2 mRNA and TREM2 protein in the hippocampus of mice of the high dose group was lower than those in the low- and the medium-dose groups (all P<0.05). With the increase of PbO NPs exposure dose, the relative expression of iNOS protein in hippocampus tissues of mice increased (P<0.01), and the relative expression of ARG-1 protein decreased (P<0.01). ii) With the increase of PbO NPs exposure dose, the relative expression of iNOS protein increased (P<0.01), and the relative expression of ARG-1 protein decreased (P<0.01) in BV-2 cells. The relative expression of iNOS protein in BV-2 cells of PbO NPs group and TREM2 high expression + PbO NPs group was increased (all P<0.05), and the relative expression of ARG-1 protein decreased (all P<0.05) compared with the control group. The relative expression of iNOS protein decreased (P<0.05), and the relative expression of ARG-1 protein increased (P<0.05) in BV-2 cells of TREM2 high expression + PbO NPs group compared with the PbO NPs group. Conclusion Exposure to PbO NPs could increase the M1 polarization and decrease the M2 polarization of microglia, with a dose-effect relationship. The M1 polarization of microglia decreased and M2 polarization increased after overexpression of Trem2 gene. The regulation of microglia polarization by TREM2 may be involved in the neurotoxic effects of PbO NPs.

Objective:To assess the diagnostic and prognostic value of lymphocyte subtyping for invasive candidiasis infection (ICI) in critically ill patients with non-neutropenic sepsis.Methods:A prospective observational cohort study was performed at Peking Union Medical College Hospital (PUMCH), 377 patients with non-neutropenic sepsis admitted to Department of Critical Care Medicine from January 2017 to November 2019 were enrolled. There were 9.0% (34/377) patients diagnosed as ICI. Vital signs, supportive care therapy and microbiological specimens were collected. Peripheral blood lymphocyte subtypes, serum globulin, complements, inflammatory factors such as interleukin(IL)-6, IL-8, IL-10 and tumor necrosis factor were detected within 24 hours after sepsis was diagnosed. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value and prognostic significance of immunological indicators for ICI. Multiple logistic regression was used to analyze the independent risk factors for ICI. Kaplan-Meier analysis was used to analyze survival.Results:The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score was 17.0 (13.0, 21.0) in all 377 patients. The sequential organ failure score (SOFA) was 11.0 (8.0, 13.0), and the 28-day mortality rate was 27.6% (104/377). Peripheral blood CD8 +absolute T lymphocyte count≤177 cells/μl, CD28 +CD8 +T-cell count≤81 cells/μl and 1, 3-β-D-glucan (BDG) ≥88.20 ng/L were closely correlated with the diagnosis of ICI (AUC=0.793,95 %CI 0.749-0.833, P<0.000 1;AUC=0.892,95 %CI 0.856-0.921, P<0.000 1;AUC=0.761, 95 %CI 0.715-0.803, P<0.000 1, respectively), with sensitivity of diagnosis 94.12%, 100.00%, and 88.24%; the specificity of diagnosis 81.34%, 62.39%, 63.56% respectively. Multivariate logistic regression analysis identified CD8 +T-cell count≤139 cells/μl ( OR=7.463, 95 %CI 1.300-42.831, P=0.024) and CD28 +CD8 +T-cell counts≤52 cells/μl ( OR=57.494, 95 %CI 3.986-829.359, P=0.003) as independent risk factors for higher mortality. Kaplan-Meier survival analysis suggested that CD8 +T-cell count ≤139 cells/μl ( P=0.0159) and CD28 +CD8 +T-cell count≤52 cells/μl ( P=0.000 1) were associated with higher mortality within 28 days (68.8%, 91.7%). Conclusions:Low CD28 +CD8 +T cell count in peripheral blood is closely related to the development and clinical outcome of ICI in sepsis patients, which could be used as an effective indicator for the diagnosis and prognosis prediction of ICI.

Objective To understand the current situation of health education contents as well as the differences in their requirements between clinical medical students and clinicians,and to provide reference for the optimization of health education curricula for medical students.Methods A stratified sampling method was adopted to select 511 medical students (303 females and 208 males) from a medical university,and the survey results of 436 clinicians (144 females and 292 males) were taken as reference.Differences in the degrees of need between clinical medical students and clinicians were compared by chi-square tests.Results There were statistical differences in needs between clinical medical students and clinicians regarding drug compliance,smoking cessation intervention,balanced diet,application of Chinese traditional rehabilitation medicine,mobile health technology education,exercise rehabilitation guidance,and theory of health promotion (P＜0.01).With regard to drug compliance,smoking cessation intervention,and exercise rehabilitation guidance,the proportions of clinical medical students' needs were just 87.1％,82.2％,and 81.2％,respectively,but for clinicians the proportions reached up to 96.3％,93.8％,and 92.8％,respectively.Whereas,there were no statistical differences for mental stress management,chronic infectious disease health education,and acute infectious disease health education (P＞0.05).Conclusion There is still a big gap between medical students and clinical doctors when it comes to the knowledge of chronic disease management and healthy lifestyles;clinical medical students have not yet realized the importance of such knowledge and skills.Therefore,the strengthening of course construction for clinical medical students is suggested.

Objective: To evaluate clinical efficacy and surgical techniques of customized variable-angle locking acetabular wing plates in treatment of complex acetabular fractures in the elderly through the lateral-rectus approach. Methods: Data of 11 elder patients of complex acetabular fractures (mean age 75 y, range: 60-93 y; 8 males, 3 females) admitted to our department from March 2016 to March 2017 were retrospectively analyzed. According to Judet-Letournel classification of acetabular fractures, there were 2 cases of anterior column and posterior hemitransverse fractures, 9 cases of both-column fractures. The customized variable-angle locking acetabular wing plates were designed by mimics software and then produced before surgery. During the operation, the customized variable-angle locking acetabular wing plate was applied to reduction and fixation via the anterior lataral-rectus approach. The effect of fracture reduction was assessed by Matta's criteria. The clinical effect was assessed by Harris Hip score and the modified Merle d' Aubigné-Postal score at the 6th month of postoperative follow-up. Results: The average time of designing and producing customized variable-angle locking acetabular wing plates was 4 d (3-5 d), the average operation time was 95 min (45-150 min), and the average intraoperative bleeding was 600 ml (250-1 400 ml). All patients were followed up, with an average follow-up of 18 m (6-24 m). All fractures were healed, with an average healing time of 8 weeks (6-12 weeks). Reduction quality: excellent in 8 cases, good in 2 cases, poor in 1 case, with an overall excellent and good rate of 90.9%. The result of Harris Hip scoring: excellent in 7 cases, good in 3 cases, and acceptable in 1 case, with a total excellent and good rate of 90.9%; Modified Merle d' Aubigné-Postal soring: excellent in 6 cases, good in 3 cases, and acceptable in 2 cases, with an overall excellent and good rate of 81.8%. There were 2 cases of obturator nerve injury, 1 case of fat liquefaction of incision, 3 cases of traumatic hip arthritis. During the follow-up, no complications such as ectopic ossification, plate fracture and screw loosening were found. Conclusion The customized variable-angle locking acetabular wing plates in treatment of complex acetabular fractures in the elderly via the lateral-rectus approach can achieve satisfactory reduction and firm fixtation.