Chemokine platelet factor 4 accelerates peripheral nerve regeneration by regulating Schwann cell activation and axon elongation

Schwann cells in peripheral nerves react to traumatic nerve injury by attempting to grow and regenerate.Howeve r,it is unclear what factors play a role in this process.In this study,we searched a GEO database and found that expression of platelet factor 4 was markedly up-regulated after sciatic nerve injury.Platelet factor is an important molecule in cell apoptosis,diffe rentiation,survival,and proliferation.Further,polymerase chain reaction and immunohistochemical staining confirmed the change in platelet factor 4 in the sciatic nerve at different time points after injury.Enzyme-linked immunosorbent assay confirmed that platelet factor 4 was secreted by Schwann cells.We also found that silencing platelet factor 4 decreased the proliferation and migration of primary cultured Schwann cells,while exogenously applied platelet factor 4 stimulated Schwann cell prolife ration and migration and neuronal axon growth.Furthermore,knocking out platelet factor 4 inhibited the prolife ration of Schwann cells in injured rat sciatic nerve.These findings suggest that Schwann cell-secreted platelet factor 4 may facilitate peripheral nerve repair and regeneration by regulating Schwann cell activation and axon growth.Thus,platelet factor 4 may be a potential therapeutic target for traumatic peripheral nerve injury.

AAV-mediated expression of p65shRNA and bone morphogenetic protein 4 synergistically enhances chondrocyte regeneration

BACKGROUND:Adeno-associated virus(AAV)gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent years.However,given the complexity of osteoarthritis pathogenesis,single gene manipulation for the treatment of osteoarthritis may not produce satisfactory results.Previous studies have shown that nuclear factorκB could promote the inflammatory pathway in osteoarthritic chondrocytes,and bone morphogenetic protein 4(BMP4)could promote cartilage regeneration.OBJECTIVE:To test whether combined application of AAV-p65shRNA and AAV-BMP4 will yield the synergistic effect on chondrocytes regeneration and osteoarthritis treatment.METHODS:Viral particles containing AAV-p65-shRNA and AAV-BMP4 were prepared.Their efficacy in inhibiting inflammation in chondrocytes and promoting chondrogenesis was assessed in vitro and in vivo by transfecting AAV-p65-shRNA or AAV-BMP4 into cells.The experiments were divided into five groups:PBS group;osteoarthritis group;AAV-BMP4 group;AAV-p65shRNA group;and BMP4-p65shRNA 1:1 group.Samples were collected at 4,12,and 24 weeks postoperatively.Tissue staining,including safranin O and Alcian blue,was applied after collecting articular tissue.Then,the optimal ratio between the two types of transfected viral particles was further investigated to improve the chondrogenic potential of mixed cells in vivo.RESULTS AND CONCLUSION:The combined application of AAV-p65shRNA and AAV-BMP4 together showed a synergistic effect on cartilage regeneration and osteoarthritis treatment.Mixed cells transfected with AAV-p65shRNA and AAV-BMP4 at a 1:1 ratio produced the most extracellular matrix synthesis(P<0.05).In vivo results also revealed that the combination of the two viruses had the highest regenerative potential for osteoarthritic cartilage(P<0.05).In the present study,we also discovered that the combined therapy had the maximum effect when the two viruses were administered in equal proportions.Decreasing either p65shRNA or BMP4 transfected cells resulted in less collagen II synthesis.This implies that inhibiting inflammation by p65shRNA and promoting regeneration by BMP4 are equally important for osteoarthritis treatment.These findings provide a new strategy for the treatment of early osteoarthritis by simultaneously inhibiting cartilage inflammation and promoting cartilage repair.

血清壳多糖酶3样蛋白1和PLT的比值与FIB-4指数在慢性乙型肝炎轻、中度诊断效价的比较

目的比较血清壳多糖酶3样蛋白1(CHI3L1)和PLT的比值(CPR)与FIB-4指数在慢性乙型肝炎轻、中度的诊断效价。方法收集2023年1月至2023年12月在本院就诊的慢性乙型肝炎(CHB)轻、中度患者122例,其中CHB轻度患者30例(CHB轻度组),CHB中度患者92例(CHB中度组)。男78例,女44例;最小年龄12岁,最大年龄68岁,平均38.3±11.1岁。另外选取30例健康体检者为对照组,男16例,女14例;年龄27~57岁,平均41.6±9.8岁。要求被检者在清晨空腹抽血检测PLT、ALT、AST和CHI3L1,计算项目为CPR和FIB-4指数。计量资料符合正态分布采用LSD-t检验、非正态分布采用Mann-Whitney U检验;计数资料组间采用卡方检验。采用MedCalc统计绘制受试者工作特征(ROC)曲线及95%可信区(95%CI)。结果(1)3组中的年龄、CHI3L1、PLT、ALT、AST、FIB-4和CPR差异有统计学意义(U=3.288、10.837、8.627、7.130、8.225、4.485、12.966,P<0.01)。其中CHB中度组中的CHI3L1、ALT、CPR高于CHB轻度组和对照组(P<0.05),且CHB轻度组高于对照组(P<0.05);CHB中度组中的AST、FIB-4高于CHB轻度组和对照组(P<0.05);CHB中度组中的PLT低于轻度组和对照组(P<0.05);CHB中度组的年龄低于轻度组(P<0.05)。(2)CHB轻度组患者的CHI3L1的ROC曲线显示,CHI3L1的AUC=0.774(95%CI 0.645~0.903);FIB-4的AUC=0.551(95%CI 0.401~0.701);CPR的AUC=0.742(95%CI 0.608~0.876)。CHI3L1和CPR的灵敏度和特异性均优于FIB-4。CHI3L1与FIB-4独立诊断比较,差异有统计学意义(Z=2.246,P<0.05);CPR与FIB-4独立诊断比较,差异有统计学意义(Z=2.183,P<0.05)。(3)CHB中度患者的CHI3L1的ROC曲线显示,CHI3L1的AUC=0.793(95%CI 0.717~0.870);FIB-4的AUC=0.722(95%CI 0.629~0.814);CPR的AUC=0.832(95%CI 0.762~0.901)。CHI3L1和CPR的灵敏度和特异性均优于FIB-4。CPR与FIB-4独立诊断比较,差异有统计学意义(Z=2.244,P<0.05)。结论CPR在CHB轻度和中度患者的AUC明显高于同组中FIB-4,且CPR的升高趋势与临床表现严重程度一致,可作为临床评估CHB患者肝脏病程发展的无创检测指标。

TRANSFORMING GROWTH FACTOR-β1 AND SMAD4 SIGNALING PATHWAY DOWN-REGULATES RENAL EXTRACELLULAR MATRIX DEGRADATION IN DIABETIC RATS

Objective To investigate the role of transforming growth factor-131 （TGF-β1）/Smad4 pathway in development of renal fibrosis in streptozotocin （STZ）-induced diabetic nephropathy （DN） rats and explore its possible mechanism. Methods Male Wistar rats weighing 180-220 g were divided into 5 groups： group A （ normal control）, group B [ diabetes mellitus （DM） 2 weeks ], group C （ DM 4 weeks）, group D （ DM 8 weeks）, and group E （ DM 16 weeks）. Except for the normal control group, other groups were induced DM by single injection of STZ （55 mg/kg） respectively. Blood glucose level, serum creatinine, and 24-hour urine protein were examined. Expressions of TGF-β1 and Smad4 protein and mRNA in kidney were detected using immunohistochemical technique, Western blot, and real-time PCR. mRNA expressions of stromelysin-1 （ MMP-3 ）, tissue inhibitor of metalloproteinase-1 （ TIMP-1 ）, and collagen Ⅲ in kidney were also detected by real-time PCR. Results The levels of blood glucose, serum creatinine, and 24-hour urine protein in rats of group B, C, D, and E were higher than those of the control group. With the progression of renal fibrosis, the expressions of TGF-β1 and Smad4 protein and mRNA in kidney of diabetic rats elevated. In addition, the renal MMP-3 mRNA expression diminished in diabetic rats, while TIMP-1 and collagen Ⅲ mRNA increased. Conclusions In STZ-induced diabetic rats, the TGF-β1/Smad4 appears to play an important role in renal fibrosis of DN. The increased expression of TGF-β1 and Smad4 might result in the transcriptional regulation of downstream target genes of TGF-β1/Smad4 pathway, which contributes to the progression of renal fibrosis in diabetic rats.

Prognostic value of hypoxia-inducible factor-1 alpha and prolyl 4-hydroxylase beta polypeptide overexpression in gastric cancer

AIM To investigate the relationship between hypoxia-inducible factor-1α(HIF-1α), prolyl 4-hydroxylase beta(P4 HB) expression, and clinicopathologic parameters, as well as the prognostic value of these genes for patients with gastric cancer(Gc).METHODS Hypoxia is a critical factor that shapes the Gc microenvironment. In previous reports, we have demonstrated that P4 HB is a potential target of HIF-1α. In the present study, gene expression profiling interactive analysis(GEPIA) was used to analyze the relationship between P4 HB and hypoxia-associated genes. To this end, 428 Gc tissue samples were used to analyze the expression of HIF-1α and P4 HB via immunohistochemical staining. Patient samples were classified as having weak-expression or over-expression both in terms of HIF-1α and P4 HB. Correlations between biomarkers and clinicopathological factors were analyzed to predict survival. RESULTS P4 HB demonstrated a positive correlation with hypoxiaassociated genes(P < 0.05). HIF-1α and P4 HB overexpression have a significant correlation with TNM staging(χ2 = 23.32, P = 0.00; χ2 = 65.64, P = 0.00) and peritoneum cavity metastasis(χ2 = 12.67, P = 0.00; χ2 = 39.29, P = 0.00). In univariate analysis, patients with a high HIF-1α expression trend had a shorter disease-free survival(DFS: 44.80 mo vs 22.06 mo) and overall survival(OS: 49.58 mo vs 39.92 mo). P4 HB overexpression reflected similar results: patients with over-expression of P4 HB had a shorter survival time than those with weak-expression(DFS: 48.03 mo vs 29.64 mo, OS: 52.48 mo vs 36.87 mo). Furthermore, HIF-1α is also a clinicopathological predictor of dismal prognosis according to multivariate analysis(DFS, 95%c I: 0.52-0.88, P < 0.00; OS, 95%c I: 0.50-0.85, P < 0.00). However, P4 HB was meaningful in DFS(95%c I: 0.58-1.00, P < 0.05) but not in OS(95%c I: 0.72-1.23, P > 0.05).CONCLUSION Overexpression of HIF-1α and P4 HB is associated with poor prognosis in patients with Gc. Thus, these genes may be potential prognostic biomarker candidates in GC.

Effects of ω-3 fatty acids on toll-like receptor 4 and nuclear factor-κB p56 in lungs of rats with severe acute pancreatitis

AIM To determine the effects of ω-3 fatty acids(ω-3FA) on the toll-like receptor 4(TLR4)/nuclear factor κB p56(NF-κBp56) signal pathway in the lungs of rats with severe acute pancreatitis(SAP).METHODS A total of 56 Sprague-Dawley rats were randomly divided into 4 groups: control group, SAP-saline group, SAP-soybean oil group and SAP-ω-3FA group. SAP was induced by the retrograde infusion of sodium taurocholate into the pancreatic duct. The expression of TLR4 and NF-κBp56 in the lungs was evaluated by immunohistochemistry and Western blot analysis. The levels of inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in the lungs were measured by enzyme-linked immunosorbent assay. RESULTS The expression of TLR4 and NF-κBp56 in lungs and of inflammatory cytokines in serum significantly increased in the SAP group compared with the control group(P < 0.05), but was significantly decreased in the ω-3FA group compared with the soybean oil group at 12 and 24 h(P < 0.05).CONCLUSION During the initial stage of SAP, ω-3FA can efficiently lower the inflammatory response and reduce lung injury by triggering the TLR4/NF-κBp56 signal pathway.

Effect of stromal cell-derived factor-1/CXCR4 axis in neural stem cell transplantation for Parkinson’s disease

Previous studies have shown that neural stem cell transplantation has the potential to treat Parkinson’s disease,but its specific mechanism of action is still unclear.Stromal cell-derived factor-1 and its receptor,chemokine receptor 4(CXCR4),are important regulators of cell migration.We speculated that the CXCR4/stromal cell-derived factor 1 axis may be involved in the therapeutic effect of neural stem cell transplantation in the treatment of Parkinson’s disease.A Parkinson’s disease rat model was injected with 6-hydroxydopamine via the right ascending nigrostriatal dopaminergic pathway,and then treated with 5μL of neural stem cell suspension(1.5×104/L)in the right substantia nigra.Rats were intraperitoneally injected once daily for 3 days with 1.25 mL/kg of the CXCR4 antagonist AMD3100 to observe changes after neural stem cell transplantation.Parkinson-like behavior in rats was detected using apomorphine-induced rotation.Immunofluorescence staining was used to determine the immunoreactivity of tyrosine hydroxylase,CXCR4,and stromal cell-derived factor-1 in the brain.Using quantitative real-time polymerase chain reaction,the mRNA expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra were measured.In addition,western blot assays were performed to analyze the protein expression of stromal cell-derived factor-1 and CXCR4.Our results demonstrated that neural stem cell transplantation noticeably reduced apomorphine-induced rotation,increased the mRNA and protein expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra,and enhanced the immunoreactivity of tyrosine hydroxylase,CXCR4,and stromal cell-derived factor-1 in the brain.Injection of AMD3100 inhibited the aforementioned effects.These findings suggest that the stromal cell-derived factor-1/CXCR4 axis may play a significant role in the therapeutic effect of neural stem cell transplantation in a rat model of Parkinson’s disease.This study was approved by the Animal Care and Use Committee of Kunming Medical University,China(approval No.SYXKK2015-0002)on April 1,2014.

Microstructure and Mechanical Properties of Si_3N_4 Composites Containing SiC Platelet

Hoppressed Si3N4/SiC platelet composites had been investigated with respect to their microstructure and mechanical properties. The results indicate that Vickers hardness, elastic modulus and fracture toughness of the composites were increased by the addition of SiC platelet until the content up to 20 vol pct. A slight decrease in flexural Strength was measured at room temperature with increasing SiC platelet content. The high temperature flexural strength tests at 1150, 1250, and 1350℃ were conducted. It was found that the flexural strength at elevated temperature was degraded with the rising temperature, and the downward trend of flexural strength for the composite containing 10 vol. pct SiC platelet was less. The results indicate that SiC platelet had a positive influence on the high temperature strength. Effects of SiC platelet reinforcement were presented

Diagnostic value of FIB-4, aspartate aminotransferaseto-platelet ratio index and liver stiffness measurement in hepatitis B virus-infected patients with persistently normal alanine aminotransferase

AIM To assess the diagnostic value of FIB-4, aspartate aminotransferase-to-platelet ratio index(APRI), and liver stiffness measurement(LSM) in patients with hepatitis B virus infection who have persistently normal alanine transaminase(PNALT).METHODS We enrolled 245 patients with chronic hepatitis B: 95 in PNALT group, 86 in intermittently elevated alanine transaminase(PIALT1) group [alanine transaminase(ALT) within 1-2 × upper limit of normal value(ULN)], and 64 in PIALT2 group(ALT > 2 × ULN). All the patients received a percutaneous liver biopsy guided by ultrasonography. LSM, biochemical tests, and complete blood cell counts were performed.RESULTS The pathological examination revealed moderate inflammatory necrosis ratios of 16.81%(16/95), 32.56%(28/86), and 45.31%(28/64), and moderate liverfibrosis of 24.2%(23/95), 33.72%(29/86), and 43.75%(28/64) in the PNALT, PIALT1, and PIALT2 groups, respectively. The degrees of inflammation and liver fibrosis were significantly higher in the PIALT groups than in the PNALT group(P < 0.05). No significant difference was found in the areas under the curve(AUCs) between APRI and FIB-4 in the PNALT group; however, significant differences were found between APRI and LSM, and between FIB-4 and LSM in the PNALT group(P < 0.05 for both). In the PIALT1 and PIALT2 groups, no significant difference(P > 0.05) was found in AUCs for all comparisons(P > 0.05 for all). In the overall patients, a significant difference in the AUCs was found only between LSM and APRI(P < 0.05).CONCLUSION APRI and FIB-4 are not the ideal noninvasive hepatic fibrosis markers for PNALT patients. LSM is superior to APRI and FIB-4 in PNALT patients because of the influence of liver inflammation and necrosis.

Platelet factor 4 induces bone loss by inhibiting the integrinα5-FAK-ERK pathway

Background:The effect of platelet factor 4(PF4)on bone marrow mesenchymal stem cells(BMMSCs)and osteoporosis is poorly understood.Therefore,this study aimed to evaluate the effects of PF4-triggered bone destruction in mice and determine the underlying mechanism.Methods:First,in vitro cell proliferation and cell cycle of BMMSCs were assessed using a CCK8 assay and flow cytometry,respectively.Osteogenic differentiation was confirmed using staining and quantification of alkaline phosphatase and Alizarin Red S.Next,an osteoporotic mouse model was established by performing bilateral ovariectomy(OVX).Furthermore,the PF4 concentrations were obtained using enzymelinked immunosorbent assay.The bone microarchitecture of the femur was evaluated using microCT and histological analyses.Finally,the key regulators of osteogenesis and pathways were investigated using quantitative real-time polymerase chain reaction and Western blotting.Results:Human PF4 widely and moderately decreased the cell proliferation and osteogenic differentiation ability of BMMSCs.Furthermore,the levels of PF4 in the serum and bone marrow were generally increased,whereas bone microarchitecture deteriorated due to OVX.Moreover,in vivo mouse PF4 supplementation triggered bone deterioration of the femur.In addition,several key regulators of osteogenesis were downregulated,and the integrinα5-focal adhesion kinase-extracellular signalregulated kinase(ITGA5-FAK-ERK)pathway was inhibited due to PF4 supplementation.Conclusions:PF4 may be attributed to OVX-i nduced bone loss triggered by the suppression of bone formation in vivo and alleviate BMMSC osteogenic differentiation by inhibiting the ITGA5-FAK-ERK pathway.

Preparation and Characterization of Bi_4Ti_3O_(12) Platelets by a Novel Low-temperature Molten Salt System

Bismuth titanate （Bi4Ti3O12） platelets were prepared by molten salt method in a new salt system of CaCl2·NaCl at 650-750℃, using bismuth nitrate pentahydrate （Bi （NO3）3·H2O） and titanium butoxide （Ti （OC4H9）4） as raw materials. The synthesis temperature of Bi4Ti3O12 platelets was decreased to 650℃ from 900-1100℃. The phase compositions and crystalline morphology of Bi4Ti3O12 platelets were investigated by XRD and SEM. The experimental results indicate that Bi4Ti3O12 platelets containing tetragonal and orthorhombic phase with the size of 1-3μm can be synthesized at 650℃ for 2 h, and the orthorhombic phase becomes the dominant phase at 750℃ for 5 h. The size and proportion of Bi4Ti3O12 platelets increase with the increment of the calcining temperature and holding time. The proportion of platelets increases to about ninety percent, and the platelets grow up to about 3-10μm at 750℃ for 5 h from 1-2μm at 650℃ for 2 h. This technical route provides a new low-temperature molten salt system for preparing platelets by molten salt methods.

Effects of Platelet Factor 4 on Expression of Bone Marrow Heparan Sulfate in Syngenic Bone Marrow Transplantation Mice

To explore the effects of platelet factor 4(PF4) on hematopoietic reconstitution and its mechanism in syngenic bone marrow transplantation (BMT). The syngenic B MT mice models were established. 20 and 26 h before irradiation, the mice were injected 20 μg/kg PF4 or PBS twice into abdominal cavity, then the donor bone marrow nuclear cells (BMNC) were transplanted. On the 7th day, spleen clone forming units (CFU S) were counted. On the 7th, 14th and 21st day after BMT, the BMNC and megakaryoryocytes in bone marrow tissue were counted and the percentage of hematopoietic tissue and expression level of heparan sulfate in bone marrow tissue were assessed. In PF4 treated groups, the CFU S counts on the 7th day were higher than those in BMT groups after BMT. The BMNC and megakaryoryocyte counts and the percentage of hematopoietic tissue and heparan sulfate expression level were higher than those in BMT group on the 7th, 14th and 21st day after BMT ( P <0.01 or P <0.05). PF4 could accelerate hematopoietic reconstitution of syngenic bone marrow transplantation. The promotion of the heparan sulfate expression in bone marrow may be one of mechanisms of PF4.

4℃冷藏保存血小板输注对大鼠失血性休克/复苏致急性肾损伤的影响研究

目的研究4℃冷藏保存血小板(cold storage platelets,CSP)对大鼠失血性休克/复苏(HS/R)导致急性肾损伤的影响。方法健康雄性SD大鼠40只,随机选取20只用以制备血小板制剂,剩余大鼠随机分为4组:假手术组(空白组)、HS/R模型组(模型组)、CSP输注组、22℃±2℃振荡保存血小板输注组(RTP输注组)。容量复苏后24 h处死动物,采集血和肾组织标本。检测各组血清中血肌酐(Scr)、尿素氮(BUN)、血清胱抑素C(CysC)及肾组织中白细胞介素1β(IL-1β)、白细胞介素18(IL-18)含量。Western Blot法检测各组大鼠肾组织中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、肾损伤因分子1(KIM-1)表达量,HE染色观察肾组织病理学改变。结果①四组大鼠基线状态体质量、MAP、SCr、BUN等指标无明显差异(P>0.05)。②复苏后24 h,模型组大鼠SCr(P<0.05)、BUN(P<0.01)、CysC(P<0.01)水平均高于其他三组;CSP输注组BUN(P<0.01)、SCr(P=0.037)、CysC(P=0.020)水平低于RTP输注组。③与模型组比较,CSP输注组和RTP输注组血清IL-1β和IL-18水平均显著降低。较于RTP输注组,CSP输注组血清IL-1β水平有所降低(P=0.041)。④与模型组相比,CSP输注组NGAL蛋白表达明显下降(P<0.01),CSP输注组和RTP输注组KIM-1蛋白表达均显著下降(P<0.01)。肾组织病理学结果示,CSP输注可减轻肾细胞变性、坏死及炎性细胞浸润程度。结论较于RTP,CSP输注可减轻SD大鼠HS/R急性肾损伤。

Upregulation of stromal cell-derived factor-1 alpha/CXCR4 axis-induced migration of human neural progenitors by tumor necrosis factor-alpha and interleukin-8

BACKGROUND： Studies of several animal models of central nervous system diseases have shown that neural progenitor cells （NPCs） can migrate to injured tissues. Stromal cell-derived factor 1 alpha （SDF-la）, and its primary physiological receptor CXCR4, have been shown to contribute to this process. OBJECTIVE： To investigate migration efficacy of human NPCs toward a SDF-1α gradient, and the regulatory roles of tumor necrosis factor-α （TNF-α） and interleukin-8 （IL-8） in SDF-1α/CXCR4 axis-induced migration of NPCs. DESIGN, TIME AND SETTING： An in vitro, randomized, controlled, cellular and molecular biology study was performed at the Laboratory of Department of Cell Biology, Medical College of Soochow University between October 2005 and November 2007. MATERIALS： SDF-1α and mouse anti-human CXCR4 fusion antibody were purchased from R＆D Systems, USA. TNF-αwas purchased from Biomyx Technology, USA and IL-8 was kindly provided by the Biotechnology Research Institute of Soochow University. METHODS： NPCs isolated from forebrain tissue of 9 to 10-week-old human fetuses were cultured in vitro. The cells were incubated with 0, 20, and 40 ng/mL TNF-α, or 0, 20, and 40 ng/mL IL-8, for 48 hours prior to migration assay. For antibody-blocking experiments, cells were further pretreated with 0, 20, and 40 μg/mL mouse anti-human CXCR4 fusion antibody for 2 hours. Subsequently, the transwell assay and CXCR4 blockade experiments were performed to evaluate migration of human NPCs toward a SDF-1α gradient. Serum-free culture medium without SDF-1α served as the negative control. MAIN OUTCOME MEASURES： The transwell assay was performed to evaluate migration of human NPCs toward a SDF-1α gradient, which was blocked by fusion antibody against CXCR4. In addition, CXCR4 expression in human NPCs stimulated by TNF-α and IL-8 was measured by flow cytometry. RESULTS： Results from the transwell assay demonstrated that SDF-1α was a strong chemoattractant for human NPCs （P 〈 0.01）, and 20 ng/mL produced the highest levels of migration. Anti-human CXCR4 fusion antibody significantly blocked the chemotactic effect （P 〈 0.05）. Flow cytometry results showed that treatment with TNF-α and IL-8 resulted in increased CXCR4 expression and greater chemotaxis efficiency of NPCs towards SDF-1α（P 〈 0.01）. CONCLUSION： These results demonstrated that SDF-la significantly attracted NPCs in vitro, and neutralizing anti-CXCR4 antibody could block part of this chemotactic function. TNF-α and IL-8 increased chemotaxis efficiency of NPCs towards the SDF-1αgradient by upregulating CXCR4 expression in NPCs.

天冬氨酸氨基转移酶与血小板比值指数与纤维化-4指数对肝癌切除术后患者预后的预测价值

目的探讨肝硬化血液生化指标天冬氨酸氨基转移酶与血小板比值指数(APRI)、纤维化-4指数(FIB-4)对肝癌切除术后患者预后的预测价值。方法回顾性收集2005年2月至2017年7月在复旦大学附属中山医院行肝癌根治性切除300例患者的临床病理资料、肝癌复发和生存情况,分析APRI、FIB-4与肝癌患者术后复发、生存的关系,应用ROC曲线评价APRI、FIB-4对肝癌切除术后患者预后的预测价值。结果300例患者的中位随访时间为61个月。单因素Cox回归分析显示,APRI、FIB-4、血管侵犯是影响肝癌患者术后无复发生存期(DFS)、总生存期(OS)的危险因素;多因素Cox回归分析显示,血管侵犯是影响肝癌患者术后DFS(HR=1.518,95%CI 1.024~2.252,P=0.038)、OS(HR=2.301,95%CI 1.270~4.167,P=0.006)的独立危险因素。时间依赖ROC(time-ROC)结果显示,APRI、FIB-4预测术后1年、3年和5年DFS的曲线下面积(AUC)为0.555~0.596,预测术后1年、3年和5年OS的AUC为0.600~0.679。结论基于血液生化检测的肝硬化指标APRI与FIB-4对肝癌患者术后预后的预测价值有限。

FIB-4、总胆红素及GPRI水平与肝癌切除术后肝功能衰竭并发症的相关性

目的 探究纤维化指数(FIB-4)、总胆红素及γ-谷氨酰转肽酶与血小板比值指数(GPRI)水平与肝癌切除术后肝功能衰竭并发症的相关性。方法 回顾性选取2018年3月至2023年3月在长治医学院附属和平医院接受肝癌切除术治疗的肝癌患者,记录患者术后是否并发肝功能衰竭,将发生肝功能衰竭的患者纳入研究组(n=32),并按照1∶2的比例随机抽取64例术后未发生肝功能衰竭的肝癌患者纳入对照组。比较两组患者的一般资料(年龄、性别、体重指数、肿瘤大小、病灶数目、乙肝表面抗原、淋巴结转移情况、术前Child分级、腹水)情况、实验室指标[总胆红素、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)、γ-谷氨酰转肽酶(GGT)]水平,计算并对比两组FIB-4、GPRI水平,分析影响患者术后并发肝功能衰竭的因素。结果 两组在平均年龄、年龄段、性别、体重指数、肿瘤大小、病灶数目、乙肝表面抗原、有无淋巴结转移、腹水方面比较差异均无统计学意义(P>0.05),研究组患者术前Child B级占46.88%,高于对照组(17.19%),差异有统计学意义(P<0.05)。研究组FIB-4、总胆红素及GPRI水平分别为2.73±0.35、(18.55±1.04)μmol/L、4.45±0.51,均高于对照组[1.76±0.28、(14.22±1.56)μmol/L、2.11±0.34],差异均有统计学意义(P<0.05)。研究组和对照组患者的LDH水平比较,差异无统计学意义(P>0.05),研究组患者的ALT、AST、GGT水平分别为(39.55±2.45)、(58.98±2.33)、(122.48±12.21) U/L,均高于对照组[(33.23±2.13)、(36.15±2.38)、(76.89±15.49) U/L],差异均有统计学意义(P<0.05)。多因素Logistic回归分析结果显示,FIB-4、总胆红素、GPRI水平均是肝癌患者术后并发肝功能衰竭的危险因素(P<0.05)。经受试者工作特征(ROC)曲线分析,可知FIB-4、总胆红素、GPRI均对患者术后肝功能衰竭存在较高的预测价值,其曲线下面积(AUC)值分别为0.809、0.846、0.839(P<0.05)。结论 FIB-4、总胆红素、GPRI水平均是肝癌患者术后并发肝功能衰竭的危险因素,且FIB-4、总胆红素、GPRI对预测肝癌切除术后并发肝功能衰竭具有一定应用价值。

基于血清HE4、PLR、RLX、KPNA2构建晚期卵巢上皮性癌术后复发风险预测模型的临床研究

目的探讨基于血清人附睾蛋白4(HE4)、血小板计数/淋巴细胞计数比值(PLR)、血清松弛素(RLX)、核转运蛋白α2(KPNA2)构建晚期卵巢上皮性癌术后复发风险预测模型。方法选取2016年1月至2019年1月苏州市立医院(东区)诊治的124例晚期卵巢上皮性癌患者作为研究对象,根据晚期卵巢上皮性癌患者是否复发分为复发组和无复发组。HE4水平采用电化学发光免疫分析法检测,根据血常规结果计算PLR,酶联免疫吸附试验检测RLX、KPNA2水平。晚期卵巢上皮性癌患者术后复发的影响因素采用多因素Logistic回归分析,并建立晚期卵巢上皮性癌术后复发风险预测模型。采用受试者工作特征(ROC)曲线评估晚期卵巢上皮性癌术后复发风险预测模型的预测效能,利用Hosmer-Lemeshow检验分析患者晚期卵巢上皮性癌术后复发风险预测模型的拟合度。结果复发组与无复发组在肿瘤国际妇产科联盟(FIGO)分期及血清糖类抗原125、HE4、PLR、RLX、KPNA2水平比较,差异有统计学意义(P<0.05)。肿瘤FIGO分期Ⅳ期及血清HE4、PLR、RLX、KPNA2升高是晚期卵巢上皮性癌患者术后复发的危险因素(P<0.05)。ROC曲线分析显示,晚期卵巢上皮性癌术后复发风险预测模型的曲线下面积为0.859,均明显高于HE4、PLR、RLX、KPNA2单一指标检测。通过Hosmer-Lemeshow检验分析,晚期卵巢上皮性癌术后复发风险预测模型有较好的拟合度(χ^(2)=7.869,P=0.437)。结论基于血清HE4、PLR、RLX、KPNA2及肿瘤FIGO分期构建的晚期卵巢上皮性癌术后复发风险预测模型对于评估患者晚期卵巢上皮性癌术后复发具有较高的预测价值,值得临床关注。

Effects of IL-4 on cyclooxygenase-2 and platelet-derived growth factor in the lungs of COPD rats

Objective： To explore the role of interleukin 4（IL-4）, expressions of cyclooxygenase-2 （COX-2） and platelet-derived growth factor （PDGF） in the model of chronic obstructive pulmonary disease （COPD）, in the lungs of rats. Methods： Male Wistar rats were used to build up the model of COPD. Rats were randomly divided into the control group and model group, the IL-4 group and the dexamethasone group. The expressions of COX-2, PDGF-A and PDGF-B in the lung tissue were detected by western blotting and RT-PCR. Results： The expressions of COX-2, PDGF-A and PDGF-B in the model group were increased significantly. Those expressions in the IL-4 and dexamethasone group were notably decreased. Conclusion： IL-4 and dexamethasone could interfere in the establishment of COPD. The expressions of COX-2 and PDGF in the lung tissue of COPD were increased significantly and IL-4 and dexamethasone could decrease those expressions.

Prognostic role of the stromal cell derived factor-1 in patients with hepatitis B virus-related acute-on-chronic liver failure

BACKGROUND Stromal cell derived factor-1(SDF-1)plays a pivotal role in the recruitment of stem cells to injured livers.However,the changes of SDF-l in patients with hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF)have yet to be elucidated.AIM To study the SDF-1 changes in patients with HBV-related ACLF.METHODS 30 patients with HBV-related ACLF,27 patients with chronic hepatitis B and 20 healthy individuals are involved in our study.The SDF-l mRNA expression in liver tissue was detected by quantitative real-time polymerase chain reaction.Immunohistochemical staining was performed to illustrate the expression of SDFl,CXC receptor 4(CXCR4)and Ki67.The serum SDF-l concentrations were also detected by enzyme-linked immunosorbent assays.RESULTS The expression of SDF-1 mRNA from ACLF patients was remarkably higher than that from other patients(both P<0.05).The expression of SDF-l,CXCR4 and Ki67 from ACLF were the highest among the three groups(all P<0.01).The serum SDF-l levels in ACLF patients were significantly lower than that in other patients(both P<0.01).Moreover,in ACLF patients,the serum SDF-1 Levels were positively correlated with serum total bilirubin and international normalized ratio.In addition,the serum SDF-l levels in survival were significantly lower compared with the non-survivals(P<0.05).The area under the curve for the serum SDF-1 level in predicting 28-d mortality was 0.722(P<0.05).CONCLUSION This study provides the SDF-1 changes in patients with HBV-related ACLF.The SDF-1 Level at admission may serve as a promising prognostic marker for predicting short-term prognosis.

血清sTLR4、IL-22 R1、PAF与胎膜早破合并绒毛膜羊膜炎及早发型败血症的关系

目的 探讨血清可溶性Toll样受体4(sTLR4)、白介素22受体1(IL-22R1)、血小板激活因子(PAF)水平在胎膜早破合并绒毛膜羊膜炎(CAM)中的变化及对早发型败血症(EONS)的预测价值。方法 选择郑州大学附属郑州中心医院妇产科的122例胎膜早破的产妇作为研究对象,根据胎盘病理结果为CAM组与非CAM组,分析sTLR4、IL-22 R1、PAF水平在胎膜早破合并绒毛膜羊膜炎中的变化;根据随访结果分为EONS组与非EONS组,分析sTLR4、IL-22 R1、PAF水平对EONS发生的预测价值。结果122例胎膜早破产妇中有46例合并CAM,发生率为37.70%,有76例产妇未合并CAM,占62.30%。CAM组WBC、PLT、CRP、sTLR4、IL-22 R1、PAF水平均高于非CAM组,差异有统计学意义(t=23.063、15.534、17.763、8.988、12.588、6.352,P<0.05)。多因素logistic回归分析显示:IL-22 R1、PAF水平增高与胎膜早破合并CAM发生密切相关(P<0.05)。122例胎膜早破产妇中有16例发生EONS,发生率为13.11%,有106例产妇未发生EONS,占86.89%。EONS组CAM比例、sTLR4、IL-22 R1、PAF水平均高于非EONS组,差异有统计学意义(χ^(2)=4.820,t=6.935、4.938、3.577,P<0.05)。多因素logistic回归分析显示:CAM及sTLR4、IL-22 R1水平增高与胎膜早破产妇发生EONS密切相关(P<0.05)。sTLR4、IL-22 R1、PAF三者联合预测的AUC为0.851(0.770~0.933),灵敏度为81.3%,特异度为79.2%,高于单一检测(P<0.05)。结论 血清sTLR4、IL-22 R1、PAF在胎膜早破合并CAM中明显增高,与CAM及EONS发生密切相关,三指标联合检测对EONS发生有良好的临床预测价值。