BACKGROUND: Current research shows that platelet to lymphocyte ratio (PLR) has important prognostic value in renal cell carcinoma, esophageal cancer, gastric cancer, liver cancer and colon cancer. The aim of the study is to evaluate the prognostic value of PLR in non-small cell lung cancer (NSCLC) through meta-analysis. METHODS: Literature search for PubMed, EMBASE, Web of Science, Medline, Cochrane Library, China National Knowledge Internet (CNKI), China Biomedical Medicine disc (CBMdisc), VIP, Wanfang Database using computer electronic system to study the association between PLR and overall survival (OS) and disease-free survival (DFS). Each eligible study data is extracted and a meta-analysis is performed using the hazard risk (HR) and 95% confidence interval (95%CI) to assess the prognostic value of PLR, the time limit for the search is to build the library until November 2018. RESULTS: We include a total of 15 research literatures involving 5,524 patients for meta-analysis. According to the results of the meta-analysis: The OS of the higher PLR group is significantly lower than that of the lower PLR group (HR=1.69, 95%CI: 1.45-1.97, P<0.000,01, I²=46.2%, Pheterogeneity=0.026); the DFS of the higher PLR group is significantly lower than that of the lower PLR group (HR=1.41, 95%CI: 1.14-1.74, P=0.001, I²=46.2%, Pheterogeneity=0.026). Subgroup analysis show that the OS of the higher PLR group is still significantly lower than the lower PLR group (P<0.05) after grouping by ethnicity, sample size, PLR cutoff value and treatment. CONCLUSIONS Increased PLR is associated with poor prognosis in NSCLC, so PLR may be an important biological predictive marker for NSCLC patients, however, its clinical application still needs to be verified through more research in the future.
Blood Platelets ; cytology ; Carcinoma, Non-Small-Cell Lung ; blood ; diagnosis ; pathology ; Humans ; Lung Neoplasms ; blood ; diagnosis ; pathology ; Lymphocytes ; cytology ; Platelet Count ; Prognosis

Zhigancao decoction recorded in Treatise on Febrile Disease by Zhang Zhongjing in the Han dynasty have been widely used in treating palpitation and irregular pulse by traditional Chinese medicine physicians for thousands of years. It is all known that Zhigancao Decoction is used to treat consumptive disease. However,why it has been used to treat exogenous febrile disease? According to studies,Fumai Decoctions in Treatise on Differentiation and Treatment of Epidemic Febrile Disease,that was modified based on Zhigancao Decoction,have their names without reality. Serious defects,including unclear diagnosis,curative effect,and prognosis,have been found in ancient and modern medical records about Zhigancao Decoction. The indications of Zhigancao Decoction include atrial premature beats,ventricular premature beats,and viral myocarditis; tachyarrhythmia( supraventricular tachycardia,atrial fibrillation)with long interval or conduction block,during or after severe infection or high fever; chronic consumptive disease due to tumor after radiotherapy and chemotherapy,malignant fluid state of tumor,hematopathy,terminal stage of heart failure after major operation,and acute hemorrhage after control of severe infection and other major diseases; cough,phlegm and asthma due to chronic obstructive pulmonary disease,pulmonary interstitial fibrosis,lung cancer,after lung cancer surgery; increased heart rate and decreased blood pressure due to insufficient capacity after acute blood loss; the symptoms included palpitation,chest tightness,sweating,lassitude,lacking in strength,shortness of breath,syncope,sudden death,cough,expectoration,excessive phlegm,clear and dilute sputum,emaciation,dry and haggard skin,constipation,haemorrhagic,uterine bleeding,enjoy sweet taste,red tongue without moss,knotted pulse,intermittent pulse,thready rapid pulse,and weak pulse. Besides,Zhigancao Decoction has effect on cardioversion and maintenance of sinus rhythm without thrombosis in persistent atrial fibrillation and permanent atrial fibrillation. Zhigancao Decoction could stop bleeding soon for acute upper gastrointestinal bleeding,and achieve positivity of occult blood test; Zhigancao Decoction could promote thrombocytopenia for idiopathic thrombocytopenic purpura,with the number of platelets 1×109/L. Zhigancao Decoction could promote the rise of granulocytic,erythroid and megakaryocytic hematopoietic lines in unexplained severe anemia,thrombocytopenia,and leukocyte reduction. Zhigancao Decoction could treat cough,asthma,and chest tightness in lung cancer and after lung cancer surgery; chronic consumptive disease due to lung cancer after lung cancer surgery,hematopathy and acute blood loss,which all belonged to the scope of consumptive disease. Zhigancao Decoction could ascend platelets,which was considered as " oriental interleukins" for the ancients. Zhigancao Decoction possesses dual-directional regulation on anticoagulant and hemostasis,which was considered as " oriental low molecular heparin" and " oriental proton pump inhibitors". Large dose of Rehmannia glutinosa is the key of the efficacy of Zhigancao Decoction. This study is expected to enrich the guidelines for modern medical diagnosis and treatment. However,the clinical evidence,relevant genes and targeting network need to be deepened in future studies. In conclusion,it may be a shortcut to restore and explain Zhigancao Decoction formula syndromes based on modern pathophysiology and severe cases of critical care.
Arrhythmias, Cardiac/drug therapy* ; Blood Platelets/cytology* ; Critical Care ; Drugs, Chinese Herbal/pharmacology* ; Electric Countershock ; Hemostasis ; Humans ; Phytotherapy ; Platelet Count ; Treatment Outcome

Platelets have long been known to play critical roles in hemostasis by clumping and clotting blood vessel injuries. Recent experimental evidence strongly indicates that platelets can also interact with tumor cells by direct binding or secreting cytokines. For example, platelets have been shown to protect circulating cancer cells in blood circulation and to promote tumor metastasis. In-depth understanding of the role of platelets in cancer progression and metastasis provides promising approaches for platelet biomimetic drug delivery systems and functional platelet-targeting strategies for effective cancer treatment. This review highlights recent progresses in platelet membrane-based drug delivery and unique strategies that target tumor-associated platelets for cancer therapy. The paper also discusses future development opportunities and challenges encountered for clinical translation.
Animals ; Antineoplastic Agents ; chemistry ; pharmacology ; Biomimetic Materials ; chemistry ; Blood Platelets ; cytology ; Drug Carriers ; chemistry ; Humans ; Models, Animal ; Nanomedicine ; methods ; Nanostructures ; chemistry ; Neoplasms ; drug therapy

To determine whether platelet-rich fibrin lysate (PRF-L) could restore the function of chronically ultraviolet-A (UVA)-irradiated human dermal fibroblasts (HDFs), we isolated and sub-cultured HDFs from six different human foreskins. HDFs were divided into two groups: those that received chronic UVA irradiation (total dosages of 10 J cm-2) and those that were not irradiated. We compared the proliferation rates, collagen deposition, and migration rates between the groups and between chronically UVA-irradiated HDFs in control and PRF-L-treated media. Our experiment showed that chronic UVA irradiation significantly decreased (p<0.05) the proliferation rates, migration rates, and collagen deposition of HDFs, compared to controls. Compared to control media, chronically UVA-irradiated HDFs in 50% PRF-L had significantly increased proliferation rates, migration rates, and collagen deposition (p<0.05), and the migration rates and collagen deposition of chronically UVA-irradiated HDFs in 50% PRF-L were equal to those of normal fibroblasts. Based on this experiment, we concluded that PRF-L is a good candidate material for treating UVA-induced photoaging of skin, although the best method for its clinical application remains to be determined.
Blood Platelets/*cytology/*metabolism ; Cell Movement/radiation effects ; Cell Proliferation/radiation effects ; Cells, Cultured ; Collagen/metabolism ; Fibrin/*metabolism ; Fibroblasts/*cytology/metabolism/*radiation effects ; Humans ; Skin/*cytology ; Time Factors ; Ultraviolet Rays/*adverse effects

Systemically sustained thrombin generation in vivo is the hallmark of disseminated intravascular coagulation (DIC). Typically, this is in response to a progressing disease state that is associated with significant cellular injury. The etiology could be infectious or noninfectious, with the main pathophysiological mechanisms involving cross-activation among coagulation, innate immunity, and inflammatory responses. This leads to consumption of both pro- and anticoagulant factors as well as endothelial dysfunction and disrupted homeostasis at the blood vessel wall interface. In addition to the release of tissue plasminogen activator (tPA) and soluble thrombomodulin (sTM) following cellular activation and damage, respectively, there is the release of damage-associated molecular patterns (DAMPs) such as extracellular histones and cell-free DNA. Extracellular histones are increasingly recognized as significantly pathogenic in critical illnesses through direct cell toxicity, the promotion of thrombin generation, and the induction of neutrophil extracellular trap (NET) formation. Clinically, high circulating levels of histones and histone–DNA complexes are associated with multiorgan failure, DIC, and adverse patient outcomes. Their measurements as well as that of other DAMPs and molecular markers of thrombin generation are not yet applicable in the routine diagnostic laboratory. To provide a practical diagnostic tool for acute DIC, a composite scoring system using rapidly available coagulation tests is recommended by the International Society on Thrombosis and Haemostasis. Its usefulness and limitations are discussed alongside the advances and unanswered questions in DIC pathogenesis.
Blood Platelets/cytology/pathology ; Disseminated Intravascular Coagulation/*diagnosis/pathology ; Fibrin Fibrinogen Degradation Products/analysis ; Humans ; Immunity, Innate ; Laboratories, Hospital ; Partial Thromboplastin Time ; Prothrombin Time ; Thrombelastography

OBJECTIVEWe explored the expressions of the Notch and Wnt signaling pathways and their significance in the repair process of alveolar bone defects by establishing animal models with a composite of autologous bone marrow mesenchymal stem cells (BMSCs) and platelet-rich fibrin (PRF) to repair bone defects in the extraction sockets of rabbits.

METHODSA total of 36 two-month-old male New Zealand white rabbits were randomly divided into four groups, and the left mandibular incisors of all the rabbits were subjected to minimally invasive removalunder general anesthesia. BMSC-PRF compounds, single PRF, and single BMSC were implanted in Groups A, B, and C. No material was implanted in Group D (blank control). The animals were sacrificed at 4, 8 and 12 weeks after surgery, the bone defect was immediately drawn, and the bone specimens underwent surgery after four, eight, and twelve weeks, with three rabbits per time point. The expressions of Notch1 and Wnt3a in the repair process of the bone defect were measured via immunohistochemical and immunofluorescence detection.

RESULTSImmunohistochemistry showed that the expressions of Notch1 and Wnt3a in Groups A, B, and C were higher than that in Group D at the fourth and eighth week after operation (P<0.05). By contrast, the expressions of Notch1 and Wnt3a in Group D were higher than those in Groups A, B, and C at the twelfth week (P<0.05). Immunofluorescence showed that the expressions of both Notch1 and Wnt3a reached their peaks in the new bone cells of the bone defect after four weeks following surgery and gradually disappeared when the bone was repaired completely.

CONCLUSIONNotch1 and Wnt3a signaling molecules are expressed in the process of repairing bone defects using BMSC-PRF composites and can accelerate the healing by regulating the proliferation and differentiation of BMSCs. Moreover, the expressions of Notch and Wnt are similar, and a crosstalk between them may exist it.

Alveolar Bone Grafting ; methods ; Animals ; Blood Platelets ; Bone Marrow Cells ; cytology ; Bone Transplantation ; methods ; Bone and Bones ; abnormalities ; Cell Differentiation ; Fibrin ; administration & dosage ; Male ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; Platelet-Rich Plasma ; Rabbits ; Random Allocation ; Receptor, Notch1 ; metabolism ; Tissue Engineering ; Wnt Signaling Pathway ; Wnt3A Protein ; metabolism ; Wound Healing

OBJECTIVETo explore the function of a novel nonsense mutation c.1476G>A of ITGB3 gene using an in vitro expression system.

METHODSAn eukaryotic expression vector containing ITGB3 c.1476G>A cDNA was generated by site-directed mutagenesis and transformed into E.coli. Plasmid DNA was extracted and sequenced to confirm the target mutations. Wild-type and mutant recombination plasmids were transfected into Chinese hamster ovarian cancer (CHO) cells by nonliposome method, and the stable expression cells were harvested by G418 screening. The ITGB3 gene mRNA transcription and GPIIIa expression level in CHO cells were detected with real-time quantitative PCR, Western blotting and flow cytometry, respectively.

RESULTSThe eukaryotic expression vectors of wild ITGB3 cDNA and c.1476G>A mutant were successfully constructed. CHO cells with stable expression were obtained after transfection and screening. Compared with the wild-type transfected cells, the amount of CD61 antigen expression was 37% and mRNA transcription level was only 6% in the mutant-transfected cells. Full length GPIIIa protein was found only in the stably wild-type-transfected cells, but not in mutant-transfected cells by Western blotting analysis.

CONCLUSIONThe ITGB3 c.1476G>A mutation can decrease the transcription level and further affect GPIIIa synthesis and CD61 antigen expression.

Animals ; Base Sequence ; Blood Platelets ; cytology ; metabolism ; CHO Cells ; Cloning, Molecular ; Codon, Nonsense ; genetics ; Cricetinae ; Cricetulus ; Humans ; Integrin beta3 ; genetics ; metabolism ; Molecular Sequence Data ; Plasmids ; genetics ; metabolism ; Point Mutation

OBJECTIVETo investigate the effect and mechanism of Factor Xa on the differentiation of Meg-01 cells into platelet-like particles.

METHODSThe Meg-01 cells were used as experimental object, Factor Xa was used as agonist. Cell proliferation was detected by CCK-8 assay. The viability of platelet-like particles was analyzed by AlamaBlue kit. MAPK/ERK pathway and PI3K/AKT pathway were assayed by Western blot. The expression of CD41b was analyzed by Western blot and flow cytometry. Cell cycle and apoptosis were detected by flow cytometry.

RESULTSThe Factor Xa (1 µg/ml) inhibited cell viability, induced apoptosis. Factor Xa triggered cell arrest at the G(2)/M stage and down-regulated the expression of SKP2. After Meg-01 cells were stimulated by Factor Xa, the expression of CD41b was up-regulated and the MAPK/ERK pathway and PI3K/AKT pathway were activated. The platelets-like particles stimulated by FXa activation were viable.

CONCLUSIONThe Factor Xa maybe display some effect on the differentiation of megakaryocytes into platelets.

Apoptosis ; Blood Platelets ; cytology ; drug effects ; Cell Cycle Checkpoints ; Cell Differentiation ; drug effects ; Cell Line ; Cell Proliferation ; Cell Survival ; Factor Xa ; pharmacology ; Humans ; MAP Kinase Signaling System ; Megakaryocytes ; cytology ; drug effects ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism

OBJECTIVETo investigate the predictive value of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) for the patients with diffuse large B-cell lymphoma (DLBCL).

METHODSThe clinical data of 57 DLBCL patients admitted in the First Affiliated hospital of Anhui Medical University were analyzed retrospectively. According to ROC curve, the cut-off value for NLR and PLR was deterimined, and the patients were divided into high and low NLR/PLR groups before first chamotherapy. Then the relation of NLR and PLR with overall survival (OS) and progression-free survival (PFS) was analyzed by univariate and multivariate COX regression.

RESULTSThe optimal cut-off value for NLR and PLR was 2.915 and 270.27, respectively. NLR at the diagnosis was found to be an independent predictor for OS and PFS by univariate and multivariate analysis, while the PLR was an independent predictor for PFS, but did not affect the OS.

CONCLUSIONNLR and PLR may provide additional prognostic information for DLBCL patients.

Blood Platelets ; cytology ; Disease-Free Survival ; Humans ; Lymphocyte Count ; Lymphocytes ; cytology ; Lymphoma, Large B-Cell, Diffuse ; diagnosis ; Multivariate Analysis ; Neutrophils ; cytology ; Prognosis ; Retrospective Studies

Platelet-enriched plasma (PRP) contains high concentration of platelets and abundant growth factors, which is made by centrifuging of blood and separating of blood elements. PRP promotes tendon repair by releasing various cytokines to enhance cell proliferation, tenogenic differentiation, formation and secretion of matrix; meantime, it can reduce pain by inhibiting the expression of pain-associated molecules. A number of clinical studies demonstrated that PRP was effective in treatment of tendinopathy, including patellar tendinopathy, lateral epicondylitis and plantar fasciopathy. However, some studies did not support this conclusion, because of disparity of PRP types, therapeutic courses and injections protocols in clinical application. Based on its safety, PRP can be a choice of treatment for tendinopathy, in case other non-surgical therapies are of no effect.
Blood Platelets ; cytology ; Cytokines ; metabolism ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Platelet-Rich Plasma ; Tendinopathy ; therapy