The effect of PD-1/PD-L1 signaling axis on the interaction between CD19+B cells and CD4+T cells in peripheral blood of patients with systemic lupus erythematosus

Abstract Background The defect of B cell self-tolerance and the continuous antigen presentation by T cells (TCs) mediated by autoreactive B cells (BCs) play a key role in the occurrence and development of systemic lupus erythematosus (SLE). PD-1/PD-L1 signaling axis negatively regulates the immune response of TCs after activation and maintains immune tolerance. However, the effect of PD-1/PD-L1 signaling axis on the interaction between CD19+B/CD4+TCs in the peripheral blood of patients with SLE has not been studied in detail. Methods PD-1/PD-L1 and Ki-67 levels in peripheral blood (PB) of 50 SLE patients and 41 healthy controls (HCs) were detected through flow cytometry, and then the expression of PD-1+/−cells and PD-L1+/−cells Ki-67 was further analyzed. CD19+B/CD4+TCs were separated for cell culture and the supernatant was collected to determine proliferation and differentiation of TCs. IL-10 and IFN-γ secretion in the supernatant was also determined using ELISA. Results The PD-1, PD-L1, and Ki-67 levels on CD19+B/CD4+TCs in patients with SLE were higher than HCs. In CD19+B/CD4+TCs of SLE patients, the proliferative activity of PD-L1+ cells was higher than that of PD-L1− cells, and the proliferative activity of PD-1+ cells was higher than that of PD-1− cells. In the system co-culturing CD19+B/CD4+TCs from HCs/SLE patients, activated BCs promoted TCs proliferation and PD-L1 expression among TCs. Addition of anti-PD-L1 to co-culture system restored the proliferation of TCs, and inhibited IL-10/IFN-γ level. The addition of anti-PD-L1 to co-culture system also restored Tfh and downregulated Treg in HCs. Conclusions Axis of PD-1/PD-L1 on CD19+B/CD4+TCs in PB of SLE patients is abnormal, and cell proliferation is abnormal. In CD19+B/CD4+TCs of SLE patients, the proliferative activity of PD-L1+ and PD-1+ cells compared with PD-L1− and PD-1− cells in SLE patients, respectively. CD19+B/CD4+TCs in SLE patients can interact through PD-1/PD-L1.

Relationship between the number of peripheral blood endothelial progenitor cells and survival time in individuals aged 75 and older / 中华老年医学杂志

Objective:To investigate the relationship between the number of epithelial progenitor cells(EPCs)in peripheral blood and blood parameter values in order to clarify the relationship between peripheral blood EPCs and the length of survival in elderly individuals aged 75 and beyond.Methods:Analysis was conducted on 114 individuals ≥75 years recruited from the Department of Geriatrics, Tianjin Medical University General Hospital in 2008.Clinical data were collected with December 31, 2020 as the end of the follow-up.Associations between peripheral blood EPC numbers, blood parameter values and all-cause mortality were analyzed.Results:In low and high EPC groups based on orthogonal partial least squares-discriminant analysis(OPLS-DA), D-Dimer was found to be a potential classification marker[the variable importance in projection(VIP)=4.750], out of a panel of blood tests.Blood parameters such as red blood cells(RBC), hemoglobin(HGB), hematocrit(HCT), aspartate aminotransferase(AST), gamma-glutamyl transferase(GGT), lactate dehydrogenase(LDH)and D-Dimer showed statistically significant differences between groups with different levels of EPCs(all P<0.05). Blood EPC numbers were positively correlated with RBC, HGB and HCT and negatively correlated with GGT and D-Dimer in older individuals( r=0.364, 0.343, 0.336, -0.312, -0.312, P<0.05 for all). The number of circulating EPCs had a significant positive correlation with survival time in older individuals( r=0.234, P=0.017). Based on the data of the long-term(12-years)follow-up, Logistic regression analysis suggested that the number of EPCs, age, and HCT were associated with all-cause mortality events in older individuals( OR=0.971, 1.585, 1.231, P=0.013, 0.012, 0.029). Conclusions:EPCs in the peripheral circulation may be involved in the progression of various conditions such as anemia, cardiac, hepatic and renal injury, and coagulation.The number of circulating EPCs may influence the survival of elderly individuals ≥75 years.Age and HCT may be risk factors for all-cause mortality events, whereas the number of EPCs may be a protective factor.

Correlation of isokinetic thigh muscle asymmetry with gait asymmetry at one year after anterior cruciate ligament reconstruction / 中华创伤杂志

Objective:To investigate the correlation of isokinetic thigh muscle asymmetry with gait asymmetry at one year after anterior cruciate ligament (ACL) reconstruction.Methods:A retrospective case series analysis was made on 25 patients treated by ACL reconstruction in Third Hospital of Peking University from January 2014 to January 2019. All the subjects were male, aged 17-47 years [(29.4±5.2)years]. Standard rehabilitation treatment procedures were conducted after surgery. The isokinetic muscle strength of the thigh was collected at one year after operation to evaluate knee extensor and flexor concentric strength at 60°/s, 180°/s and 300°/s, and knee extensor and flexor eccentric strength at 60°/s. The maximum concentric and eccentric strength of the knee extensor and flexor were analysed between the injured and intact side. The three-dimensional motion information and ground reaction force was collected during the stance phase of gait, and knee kinematic and kinetic parameters were calculated by inverse dynamics analysis, including the peak flexion moment, peak extension moment, first and second peak adduction moment, peak external and internal rotation moment, peak flexion angle, peak extension angle during the terminal stance phase, flexion angle at heel strike, peak abduction angle, and peak external rotation angle during terminal stance phase. Spearman correlation analysis was used to study the correlation between limb symmetry index (LSI) of isokinetic muscle strength and LSI of gait parameters.Results:One year after ACL reconstruction, the maximum concentric strength of the knee extensor and flexor at 60°/s, 180°/s and 300°/s and maximum eccentric strength of the knee flexor and extensor at 60°/s on the injured side were significantly lower than those on the normal side (all P<0.01). Compared with the intact side, the peak knee extension moment on the injured side was significantly lower during the stance phase of gait ( P<0.01), and the extension angle was insufficient during the terminal stance phase ( P<0.01). There were no significant differences between the injured and intact side in terms of peak flexion moment, first and second peak adduction moment, peak external and internal rotation moment, peak flexion angle, flexion angle at heel strike, peak abduction angle, and peak external rotation angle during terminal stance phase (all P>0.05). One year after ACL reconstruction, Spearman correlation analysis during gait stance phase showed that the LSI of 60°/s concentric strength of the isokinetic knee extensor was significantly related to LSI of peak internal rotation moment ( R=0.42, P<0.05), the LSI of 180°/s concentric strength of the isokinetic knee extensor was significantly related to LSI of peak flexion moment ( R=0.45, P<0.05), the LSI of 180°/s concentric strength of the isokinetic knee flexor was significantly correlated with LSI of peak flexion angle ( R=0.46, P<0.05), the LSI of 300°/s concentric strength of the isokinetic knee extensor was significantly correlated with LSI of peak knee flexion angle ( R=0.42, P<0.05), and the LSI of 60°/s eccentric strength of the isokinetic flexor was significantly correlated with LSI of peak knee flexion angle ( R=0.54, P<0.01). Conclusions:For patients following ACL reconstruction at one year postoperatively, a significant correlation of isokinetic thigh extensor strength asymmetry with peak knee flexion and rotation moment and peak knee flexion angle, and that of isokinetic thigh flexor strength asymmetry with peak knee flexion angle are observed during the stance phase of gait, which suggests that patients with ACL reconstruction still need systematic rehabilitation training one year postoperatively to improve muscle strength and motor function so as to reduce the risk of ACL reinjury and secondary injury.

Management algorithm for septic arthritis after anterior cruciate ligament reconstruction / 北京大学学报(医学版)

OBJECTIVE@#To summarize the experience in the diagnosis and management of septic arthritis after anterior cruciate ligament reconstruction.@*METHODS@#A retrospective review was conducted of all the arthroscopic anterior cruciate ligament reconstructions performed at Department of Sports Medicine, Peking University Third Hospital between January 2001 and December 2020. In the study, 65 of 27 867 patients experienced postoperative septic arthritis. The incidence, presentation, laboratory results, treatment, and outcome of all the infected patients were analyzed. The experiences of diagnosis and management of septic arthritis after anterior cruciate ligament reconstruction were summarized.@*RESULTS@#A total of 27 867 anterior cruciate ligament reconstructions were performed at our department between January 2001 and December 2020. In the study, 65 (0.23%) patients were identified with postoperative septic arthritis. The most common symptoms of the infected patients were fever (38.7±0.5) ℃, knee swelling, pain, and restricted motion. The mean peripheral white blood cell count (WBC) was (9.2±2.6)×109/L (range 4.2×109/L-19.4×109/L), with (72.5±6.3) % (range 54.9%-85.1%) polymorphonuclear neutrophils (N). The mean erythrocyte sedimentation rate (ESR) was (59.9±24.1) mm/h (range 9-108 mm/h), C-reactive protein (CRP) was (10.9±5.7) mg/dL (range 1.2-30.8 mg/dL), and fibrinogen (FIB) level was (7.0±1.6) g/L (range 3.7-10.8 g/L). All of the laboratory results were statistically higher in the infection group compared with the normal postoperative group (P＜0.001). The synovial white blood cell count (SWBC) of aspirated knee joint fluid was (45.0±29.8)×109/L (range 7.1×109-76.5×109/L). Polymorphonuclear cell percentage (PMNC) was (90.27±7.86) % (range 60%-97%). In the study, 45 patients (69.2%) had positive aspirate cultures. Microbiology showed coagulase-negative Staphylococcus (CNS) and Staphylococcus aureus (SA) were the most common bacterium (34 cases and 7 cases, individually). There were 26 methicillin-resistant Staphylococcus. Both conservative (16 patients) and operative (49 patients) treatments were effective, but conservative group had a longer recovery time (5.6 d vs. 1.6 d, P=0.042).@*CONCLUSION@#Septic arthritis after arthroscopic anterior cruciate ligament reconstruction is a rare but potentially devastating complication. The correct diagnosis relies on synovial fluid analysis and bacterial culture. Our proposed treatment protocol is arthroscopic debridement and antibiotic therapy as quickly as possible.

Inhibitory effects of resveratrol on high glucose-induced apoptosis of retinal cells / 中华实验眼科杂志

Objective:To investigate the inhibitory effects of resveratrol (Res) on the apoptosis of retinal neurons of diabetic rats and ARPE-19 cells induced by high glucose.Methods:Streptozotocin was intraperitoneally injected to establish a diabetes model in 25 adult male SD rats, and 20 successful models were randomized into diabetic model group and Res-administered group according to random number table method.Another 10 matched normal rats were served as normal control group.Res was intragastrically given to the rats in the Res-administered group with the dose of 40 mg/(kg·d), and an equivalent volume of normal saline solution was used in the same way in the diabetic model group and normal control group.The body weight and blood glucose level were measured on the 0th, 4th, 8th, 12th week of administration.The rats were sacrificed on the 12th week by over-anesthesia and the eyeballs were enucleated.The ultrastructure of the retinal ganglion cells (RGCs) were examined under the transmission electron microscope.The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay was to assess the apoptosis of retinal neurons.ARPE-19 cells were divided into normal control group, high glucose group and Res-treated group and cultured for 48 hours in medium containing 5.5 mmol/L glucose, 30 mmol/L glucose, 30 mmol/L glucose and 10 mol/L Res, respectively.Apoptosis rate was detected by a flow cytometry.The distribution and expression of bax and bcl-2 in the cells was detected by immunofluorescence and Western blot assay, respectively.This study protocol was approved by an Experimental Animal Ethic Committee of Hubei University of Science and Technology, and the use and care of the animals complied with the Statement of ARVO.Results:Compared with the diabetic model group, the body weight was increased at 4-12 weeks and the blood glucose level was lowered at 8-12 weeks of Res administration in the Res-administered group (both at P<0.01). The chromatin condensation, mitochondrial swelling and vacuolation in cytoplasm were obviously slight and the apoptosis rate was reduced in the Res-administered group in comparison with the diabetic model group.The apoptosis indexes of the retinal ganglion cell layer cells and inner nuclear layer cells in the Res-administered group were (18.36±3.37)% and (23.67±8.98)%, respectively, which were significantly lower than (83.91±9.8)% and (64.26±10.66)% in the diabetic model group (both at P<0.01). The apoptosis rate of the ARPE-19 cells in the normal control group, high glucose group and Res-treated group was (3.11±0.26)%, (11.41±1.06)% and (5.38±0.58)%, respectively, and the apoptosis rate in the Res-treated group was significantly lower than that in the high glucose group (all at P<0.01). Immunofluorescence assay showed that the fluorescence of bax in the cell nucleus of Res-treated group was obviously enhanced in comparison with the normal control group and weaker in comparison with the high glucose group.The fluorescence of bcl-2 protein in the Res-interfered group was weaker in comparison with the normal control group and enhanced in comparison with the high glucose group.The relative expressions level of bax protein in the Res-treated group was 0.21±0.08, which was significantly higher than 0.15±0.06 in the normal control group and lower than 0.31±0.09 in the high glucose group (both at P<0.05). The relative expressions of bcl-2 protein was 0.66±0.25 in the Res-treated group, which was significantly lower than 0.80±0.14 in the normal control group and higher than 0.23±0.09 in the high glucose group (both at P<0.05). The bcl-2/bax ratio in the Res-treated group was significantly higher than that in the high glucose group ( P<0.01). Conclusions:Res can inhibit the apoptosis of RGCs of diabetic rats and high glucose-induced RPE cells in vitro.

Virtual reality-based exposure therapy for anxiety disorders: A meta-analysis for randomized controlled trials / 中国心理卫生杂志

Objective:To review the efficacy of virtual reality-based exposure therapy (VRET) for anxiety disorders. Methods: Through literature search, 31 studies that used randomized controlled trial design to examine the efficacy of VRET for anxiety disorders between 1995 and 2017 were recruited. The sample size was 1231. The data of these studies were converted to effect sizes in order to conduct the meta-analysis. Results: Comparing to the waiting list, VRET group showed lower level of anxiety (Hedge's g = 1.027, 95％ CI:0.75 - 1.30) and subjective distress (Hedge's g = 1.018, 95％ CI:0.18 -1.84). VRET group gained more improvements in cognition (Hedge's g=1.092, 95％ CI:0.34 -1.84), behavior (Hedge's g =0.550, 95％ CI: 0.19 -0.91) and psychophysiological index (Hedge's g =0.652, 95％ CI:0.11 -1.42). The effects of VRET remained 6 months or 1 year after the treatment. The random effects analysis showed that traditional treatment was not significantly more effective than VRET(Hedge's g= -0.028, 95％ CI: -0.21 -0.15). Conclusion:It suggests that virtual reality-based exposure therapy tends to be a viable treatment option for anxiety disorders.

Effect of resveratrol on the expression of Bcl-2 and Bax and in the retina of diabetic rats / 实用医学杂志

Objective To observe the effect of resveratrol(Res)on the expression of Bcl-2 and Bax in the retina of streptozotocin(STZ)induced diabetic rats.Methods Among 35 adult healthy male SD rats,10 were ran-domly divided into normal control group(Control),25 were used for the diabetic animal model with STZ.Success-fully modeled 20 rats were randomly divided into diabetes mellitus group(DM group)and resveratrol treated group (DM+Res group)equally. The DM+Res group were administrated with intragastric Res daily. After 12 weeks of Res administration,the eyes of three groups were dissected. Retinal histology was examined,and the thickness of the retina was measured.And the expression of Bcl-2 and Bax in the retinal tissues was determined by immunohisto-chemical staining. Results Compared with the control group,the thickness of the retina in DM group significant-ly decreased(P < 0.01),while the thickness of the retina in DM+Res group significantly increased(P < 0.05) compared with the DM group.Consistent with these effects,Res treatment increased the Bcl-2 level and decreased Bax expression level,at the same time,increased the ratio of Bcl-2-to-Bax(P<0.01). Conclusion Res is able to reduce apoptosis in retinal neurons caused by diabetes through up-regulating Bcl-2 expression and inhibiting Bax expression,as a result of increasing the ratio of Bcl-2-to-Bax.

Distribution of pathogens and their drug resistance in aged patients with community-acquired pneumonia / 中华老年医学杂志

Objective To investigate the distribution of pathogens and their drug resistance in elderly patients with community-acquired pneumonia. Methods A total of 222 elderly patients with community-acquired pneumonia admitted to our hospital from February 2017 to January 2018 were enrolled in this study.Lower respiratory tract secretions or morning sputum were collected by using the sterile culture method. According to the clinical microbiological examination procedures ,pathogenic bacteria were cultured and identified. The pathogenic bacteria strains and the drug resistance were analyzed. Results The bacteria examination rate of the patients was 100.0% (222/222 patients) , and the rate of positive cultures was 64.9% (144/222 ).216 strains of pathogenic bacteria were identified ,and 75 strains(34.7% )were Gram-positive bacteria ,of which the most common pathogenic bacteria were Staphylococcus aureus ,Streptococcus pneumoniae and Staphylococcus epidermidis. And 127 strains(58.8% )were Gram-negative bacteria ,of which the most common pathogenic bacteria were Klebsiella pneumoniae ,patina Pseudomonas ,Escherichia coli ,Stenotrophomonas maltophilia and Haemophilus influenza. The drug susceptibility test showed that Gram-positive bacteria were sensitive to nitrofurantoin ,cotrimoxazole ,vancomycin and teicoplanin ,and Gram-negative bacteria were sensitive to piperacillin ,tazobactam ,cefepime ,amikacin ,levofloxacin and imipenem cilastatin. Conclusions The pathogenic bacteria are mainly Gram-negative bacteria in the elderly patients with community-acquired pneumonia ,but the majority of pathogenic bacteria have higher resistance to antibacterial drugs. The analyses of distribution of pathogens and their drug resistance are of great significance for the reasonable selection of antimicrobial agents and for the obvious decrease of lung infection and mortality rate.

Initiatory Application of Three-dimensional Asymmetry on Anterior-cruciate-ligament Rupture Gait Analysis / 中国康复理论与实践

@#Objective Gait analysis plays an important role in the description of the site and degree of injury in the lower limbs, and symmetry is an important indicator of gait characteristics. The aim of this study is to quantitatively describe gait information and its asymmetry in three-dimensional space, dig deeper into gait information and improve the analysis of abnormal gait characteristics.Methods The information about the change of coronal-sagittal plane angle in different parts was obtained based on the inertial gait sensor, and the gait space vector was inverted to build the movement curve and form a motion symmetry detection method based on three-dimensional space angle vector distance. The characteristics of normal subjects (control group) and the anterior cruciate ligament (ACL) rupture patients (patients group) were analyzed from July, 2017 to January, 2018, and its effectiveness was verified.Results There was a better discrimination effect in the calf, thigh and knee asymmetry, etc., between the control group and the patient group (P<0.05). The characteristics of the calf space motion vector were highest among the control group and the patient group, and the discrimination was relatively stable, and not various with gender, age, height or body mass index.Conclusion The time-coronal-sagittal vector diagrams of left and right limbs were obtained by inertial sensor and the average of the square of the Euclidean distances in space at the selected gait cycle time points was calculated in three-dimensional space, which could be used as a gait asymmetry analysis method.

EGFR mutations detection in non-small cell lung cancer liquid based cytology samples by ARMS method / 临床与实验病理学杂志

Purpose To explore the application and characteristics of liquid-based cytology samples of non-small cell lung cancer for detection of EGFR mutations by ARMS method.Methods The positive samples of liquid-based cytology were collected and the DNA of samples was extracted to detect the EGFR mutations by ARMS method and the analyze the association with clinical features,types of samples,pathological types and the contents of tumor cells,etc.Results There were 117 genetic mutations detected in 279 liquid-based cytology specimens,with the mutation rate of 41.9％.The mutation rate of adencarcinoma was 44.7％ and the other was 11.3％.When the tumor ceils in cytology samples were abundant,medium,small clusters and few,EGFR gene mutation rate were 53％,44％,45％ and 44％ respectively.19Del was 51.9％.Exon 21L858R missense mutation occurred at 39.4％ of EGFR mutations.Conclusion All liquid-based cytology of non-small cell lung cancer samples are adequate for EGFR mutation analysis.In the tumor cell-rich samples EGFR gene mutation rate is higher than that of the less tumor cells samples.19Del is the most common type of EGFR mutations.

Biochemical and molecular biological characteristics of Yersinia pestis in Chengduo County of Qinghai Province / 中华地方病学杂志

Objective To study the biological characteristics and epidemiological significance of Yersinia pestis in Chengduo County of Qinghai Province,in order to provide scientific basis for plague prevention and control in this area.Methods Thirty one strains of Yersinia pestis isolated from Chengduo County of Qinghai Province from 1980 to 2011 were selected as study subjects.Biochemical test,virulence factors evaluation [Fra1 (F1),pesticin Ⅱ (Pst Ⅱ),virulence antigen (VW),pigmentation (Pgm)] and different region (DFR) genotyping were carried out.Nineteen of the 31 strains Yersinia pestis were selected according to different time,different areas and different hosts to determine their toxicity in mice,MLD ≤ 10 000 was strong toxic strain,10 000 ＜ MLD ＜ 100 000 was moderate toxic strain.Results Among thirty one strains of Yersinia pestis,23 strains were isolated from human,the Himalaya marmot and its fleas and lice,and their biological type was classical,biochemical type was Qinghai-Tibet plateau;21 strains genotype was type 5,1 was type 16,1 was type 32,and they contained all four kinds of virulence factors (F1,Pgm,Pst Ⅱ,VW),and toxicity test showed all strains (14) were strong toxic strains.The rest 8 strains of Yersinia pestis isolated from the Microtus fuscus and its fleas,and their biological type was Microtus,biochemical type was Chuanqing plateau;they could produce F1 and Pgm,of which 87.5％ (7/8) strains could produce Pst Ⅱ,but could not produce VW antigen factor,the genotype was 14,and the toxicity results showed that they were strong (3)and moderate (2) toxic strains.Conclusion The strains separated in Chengduo County of Qinghai Province from 1980 to 2011 have the pathogen characteristics of Qinghai-Tibet plateau plague,they are mainly strong toxic strains;the work on prevention and control of plague should not be neglected.

Efficacy of tigecycline on serum procalcitonin and its efficacy in elderly COPD and nosocomial infection / 中国生化药物杂志

Objective To investigate the effect of tigecycline on serum procalcitonin and its efficacy in the treatment of elderly chronic obstructive pulmonary disease (COPD) and nosocomial infection. Methods 82 elderly patients with COPD with nosocomial infection were selected and randomly divided into two groups with 41 cases of each group, the control group received routine treatment combined with cefoperazone and sulbactam, and the experimental group received routine treatment combined with tigecycline, 2 weeks for a course of treatment. The serum inflammatory factors and laboratory related indexes, clinical efficacy and bacterial clearance were compared after the treatment. Results Compared with control group, the levels of serum high-sensitivity C-reactive protein (hs-CRP), interluekin 6(IL-6) and tumor necrosis factorα(TNF-α) were significantly lower, and the serum levels of PCT and NO were lower(P < 0.05). The total efficacy of experimental group was 90.24%, which was higher than 70.73% in control group (P<0.05). The bacterial clearance rate in the control group was 63.42%, which was lower than the experimental group of 87.80% (P < 0.05). Conclusion Tigecycline in the treatment of COPD and nosocomial infection in elderly patients is curative effective and it can reduce the serum levels of PCT, NO and inflammatory factors with high safety.

The value of preoperative magnetic resonance imaging in predicting postoperative recovery in patients with cervical spondylosis myelopathy: a meta-analysis

This meta-analysis was designed to elucidate whether preoperative signal intensity changes could predict the surgical outcomes of patients with cervical spondylosis myelopathy on the basis of T1-weighted and T2-weighted magnetic resonance imaging images. We searched the Medline database and the Cochrane Central Register of Controlled Trials for this purpose and 10 studies meeting our inclusion criteria were identified. In total, 650 cervical spondylosis myelopathy patients with (+) or without (-) intramedullary signal changes on their T2-weighted images were examined. Weighted mean differences and 95g% confidence intervals were used to summarize the data. Patients with focal and faint border changes in the intramedullary signal on T2 magnetic resonance imaging had similar Japanese Orthopaedic Association recovery ratios as those with no signal changes on the magnetic resonance imaging images of the spinal cord did. The surgical outcomes were poorer in the patients with both T2 intramedullary signal changes, especially when the signal changes were multisegmental and had a well-defined border and T1 intramedullary signal changes compared with those without intramedullary signal changes. Preoperative magnetic resonance imaging including T1 and T2 imaging can thus be used to predict postoperative recovery in cervical spondylosis myelopathy patients.

Inhibitory Effect and Mechanism of Fluorofenidone on the Proliferation of Rat Pulmonary Fibroblasts / 医药导报

Objective To study the inhibitory effect and mechanism of fluorofenidone on the proliferation of the rat lung fibroblasts induced by TGF-β1 . Methods Pulmonary fibroblasts cell were cultured and purified by using differentially adherent method, the third generation was used in the experiment. Cells were pretreated with 1,3,10 mmol?L-1 fluorofenidone, respectively. Pulmonary fibroblasts were identified by immunocytochemistry, and interfered by transient transfection. Cell proliferation was measured by BrdU marking. The mRNA and protein expression of eIF3α and p27 were analyzed by real-time PCR and Western blot. Results Immunocytochemistry staining identification of vimentin was positive in the third generation of pulmonary fibroblasts .TGF-β1 could obviously promote the eIF3α expression and proliferation of pulmonary fibroblasts. EIF3a siRNA was transfected with lipofectamine into cells, which obviously inhibit eIF3α expression induced by TGF-β1 , reversed cell proliferation induced by TGF-β1 , and could obviously promote p27mRNA expression induced by TGF-β1 . Fluorofenidone (3, 10 mmol?L-1 )could obviously inhibit cell proliferation induced by TGF-β1 and reduce eIF3α expression of pulmonary fibroblasts promoted by TGF-β1 . The inhibition rate was 66.7% and 78.8% respectively. Fluorofenidone (3 mmol?L-1 ,10 mmol?L-1 ) could also obviously reverse p27 expression inhibited by TGF-β1 , the reverse rate was 75. 5% and 71. 3% respectively. Conclusion eIF3α/ p27 signal pathway involves in pulmonary fibroblasts proliferation induced by TGF-β1 .Fluorofenidone can inhibit pulmonary fibroblasts proliferation induced by TGF-β1 by inhibiting eIF3α expression, enhancing p27 expression and/ or increasing p27 directly.

The implication of HDAC2 in diagnosis and treatment patients with acute exacerbation of chronic obstructive pulmonary disease / 预防医学

Objective To explore the correlation among the concentration of peripheral blood histone deacetylase 2 (HDAC2),C -reactive protein (CRP),proealeitonin (PCT)and lung function among patients with acute exacerbation period of chronic obstructive pulmonary disease (AECOPD).Methods A total of 60 patients with AECOPD were selected as the test group,and 40 healthy subjects in the same medical examination center were selected as the control group.The HDAC2,CRP,PCT,lung function testing and blood gas analysis were measured on Day 0,3,7,1 0.Results Along with the process of AECOPD patients,in the treatment of 0 d,3 d,7 d,1 0 d,the average level of CRP and PCT in peripheral blood of patients was decreased gradually,while the average level of HDAC2 was gradually increased (P<0. 05 ).In patients treated with 0 d,3 d,7 d,1 0 d,HDAC2 levels were negatively correlated with CRP and PCT at the same time (rCRP was-0. 31 6,-0. 435,-0. 495,-0. 547,respectively,and rPCT was -0. 41 4,-0. 332,-0. 481 ,-0. 523,respectively, P<0. 01 ).The level of HDAC2 was positively correlated with lung function in the same period (rFEV1 was 0. 594,and rFEV1/Expected value was 0. 561 ,P<0. 01 ).Conclusion HDAC2 may be a negative regulator of the inflammatory response among the patients with AECOPD,and is associated with the degree of airflow obstruction of the patients.

Nano-hydroxyapatite/polyamide 66 composite for repair of early femoral head necrosis / 中国组织工程研究

BACKGROUND:Nano-hydroxyapatite/polyamide 66 composite has good material-cel interface and three-dimensional porous network structure, and it can also be gradualy degraded over time after implantation in the human body. OBJECTIVE:To explore the effect of nano-hydroxyapatite/polyamide 66 in early repair of femoral head necrosis. METHODS:A retrospective analysis was performed on clinical data of 62 cases of early osteonecrosis of the femoral head, including 32 males and 30 females, aged 34-51 years. These patients were divided into control group (31 cases) and observation group (31 cases) according to treatment methods. Core decompression with nano-hydroxyapatite/polyamide 66 implantation and core decompression with bone graft were respectively performed in the observation and control groups. Incidence of pain in the two groups was compared at 1 day after treatmen; and during the 12-month folow-up, the Harris score of the hip function in the two groups was compared. RESULTS AND CONCLUSION:There was no significant difference in the visual analog scale scores between two groups at 1 day after treatment. The Harris scores in the observation group were significantly higher than those in the control group at 3 and 12 months after treatment (P < 0.05). There was no adverse reaction in the two groups. These findings indicate that nano-hydroxyapatite/polyamide 66 material for repair of early femoral head necrosis has good biocompatibility, and can obtain good effects on limb function recovery.

Application of nanohydroxyapatite/collagen basal bone materials in lumbar posterolateral bone graft fusion：evaluation of pain scores and bone graft fusion effects / 中国组织工程研究

BACKGROUND:Nanohydroxyapatite/colagen basal bone materials have a porous structure which is very close to natural bone. After implanting to the human body, it can be gradualy degraded and absorbed over time to play a strongly guiding and bridging role. OBJECTIVE:To investigate the clinical effect of nanohydroxyapatite/colagen basal bone materials on lumbar posterolateral bone graft fusion. METHODS: Fifty-eight patients with lumbar disease, including 28 males and 30 females, aged 47to81 years were included and were performed lumbar laminectomyvia posterior midline approach, or simultaneously performed discectomy and lumbar posterolateral bone graft fusion between transverse process. The bone graft material was nanohydroxyapatite/colagen basal bone repair material. Pedicle screw system was used to make the internal fixation. Patients were folowed up for 18 months after treatment. Pain relief and bone graft fusion condition were observed. RESULTS AND CONCLUSION: Fifty-eight patients had successfuly completed the treatment. The incisions healed by first intention. The clinical symptoms and signs were significantly improved compared with before treatment. The complications such as infection, screws shifting and loosening, spondylolisthesis and displacement of adjacent vertebral in fixed segments, and the adverse reactions associated with bone graft material were not occurred during the folow-up. At the 1st, 6th, 12th and 18th months after implanting nanohydroxyapatite/colagen basal bone materials, the visual analog scale scores of the lower limbs and waist were al lower than those before implantation (P < 0.05). At the 12thand 18th months of folow-up, the bone graft rates were 84% and 90%, respectively. These results demonstrate that the application of nanohydroxyapatite/colagen basal bone materials in the process of lumbar posterolateral bone graft fusion can ease the symptoms of lower limb pain and lower back pain, which is conducive to bone graft fusion.

Meta-analysis on the relationship between sleep apnea-hypopnea syndrome and liver injury / 天津医药

Objective To provide an comprehensive evaluation of the correlation between sleep apnea hypopnea syn?drome (SAHS) and nonalcoholic fatty liver disease (NAFLD). Methods The various case-control studies on the relation?ship between SAHS and NAFLD were retrieved from all kinds of large-scale databases at home and abroad (including Web of science, EMbase, Pubmed, Springer Link, EBSCO Databases, CNKI, CQVIP, Wanfang Data). The quality evaluation of in?cluded studies was made by two independent researchers. RevMan 5.1 and stata 12.0 software were used for meta-analysis. Results A total of 11 qualified documents were included in this study. Meta analysis showed that the relative risk of NAFLD was increased in SAHS patients than non-SAHS patients (RR=2.82, 95%CI:2.03-3.92, P<0.01). The serum ala?nine aminotransferase (ALT) increased in SAHS patients (SMD=0.53, 95% CI:0.02-1.05, P < 0.05). Compared with non-SAHS patients, the apnea-hypopnea index (AHI) was significantly higher in SAHS patients combined with severe NAFLD than those combined with mild NAFLD (SMD=1.42, 95%CI:0.12-2.72, P < 0.05). Conclusion The risk of NAFLD in?creases in SAHS patients. The severity of NAFLD is relatively higher with the severity of intermittent hypoxia.

Effects of different doses of dexmedetomidine on lung injury in pediatric patients undergoing open heart surgery under cardiopulmonary bypass / 中华麻醉学杂志

Objective To evaluate the effects of different doses of dexmedetomidine on lung injury in pediatric patients undergoing open heart surgery under cardiopulmonary bypass (CPB).Methods Forty-eight pediatric patients,aged 7 months-3 yr,of ASA physical status Ⅱ or Ⅲ,scheduled for elective repair of ventricular septal defect under CPB,were randomly divided into 4 groups (n =12 each) using a random number table:control group (group C) and 3 different doses of dexmedetomidine groups (D1-3 groups).Anesthesia was induced with midazolam,fentanyl and vecuronium.The patients were endotracheally intubated and mechanically ventilated.In D1-3 groups,dexmedetomidine 0.5μg/kg (initial dose) was given over more than 10 min,followed by continuous infusion at 0.1,0.3 and 0.5 μg· kg-1 · h-1,respectively,until the end of operation.The equal volume of normal saline was given instead of dexmedetomidine in group C.Before administration (T1),and at 2,6 and 12 h after termination of CPB (T2-4),blood samples were collected for determination of plasma tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6) and IL-8 concentrations and for blood gas analysis.Respiratory index (RI),oxygenation index (OI) and lung compliance (CL) were calculated.Results The plasma concentrations of TNF-α and IL-8 at T2-4 and IL-6 at T3,4 were significantly lower in D2,3 groups than in group C.Compared with group D1,the plasma concentrations of TNF-α,IL-8 and RI were significantly decreased,and OI and CL were increased at T2-4 in D2-3 groups,and the plasma IL-6 concentrations at T3,4 in group D2 and at T2-4 in group D3 were decreased.The plasma concentrations of TNF-α and IL-6 were significantly lower,while OI and CL were higher at T2,3,and the plasma concentrations of IL-8 and RI were lower at T2-4 in group D3 than in group D2.Conclusion Dexmedetomidine can reduce lung injury in pediatric patients undergoing open heart surgery under CPB and promote the lung function after CPB possibly through inhibiting inflammatory responses to CPB dosedependently.