Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Phenylalanine ammonia lyase (PAL) can catalyze L-phenylalanine to produce trans-cinnamic acid, which is widely used in the fields of pharmacy, food and agriculture. In particular, phenylalanine ammonia lyase from Anabaena variabilis (AvPAL) is the only protein drug for the treatment of phenylketonuria. However, the poor activity and low stability limit the application in industry of AvPAL. In this study, the key amino acids of substrate-binding cavity in AvPAL were identified by screening the single site saturation mutagenesis library. Subsequently, the impact of replacing M222 with the additional 19 amino acids on activity was also evaluated by site-directed mutagenesis. It was found that the k_cat values of mutants M222L and M222V were 90% and 60% higher than that of AvPAL, and the k_cat/K_m was 1.4 and 1.5 times as that of AvPAL. Molecular docking results revealed that the higher activity of M222L and M222V may be due to the increase of hydrophobicity favorable for the substrate-binding cavity. This study is important for elucidating the structure-function relationship of AvPAL.

OBJECTIVE: To observe the clinical effect on spinal low back pain (SLBP) in Air Force crew treated with novel thumbtack needling therapy and to analyze the relevant factors of the therapeutic effect. METHODS: A total of 120 Air Force crew with SLBP were randomized into a thumbtack needling group (40 cases), an external treatment group (40 cases, 1 case dropped off ) and a combined treatment group (40 cases, 1 case dropped off ). In the thumbtack needling group, the thumbtack needling therapy was adopted. The novel thumbtack needles were inserted at the lower No.6 region of the wrist-ankle acupuncture, Yaotongdian (EX-UE 7), Yaoyangguan (GV 3), etc. Each point was pressed and kneaded for 1 min each time, 3 or 4 times a day. The treatment for 3 days was taken as one course. At the interval of 2 days, 3 courses were required totally. In the external treatment group, RESULTS: Compared with the values before treatment, McGill scores and ODI scores were reduced ( CONCLUSION The thumbtack needling therapy is significantly effective on spinal low back pain in Air Force crew and is of the safety. Hence, this therapy is applicable to be promoted in the primary care army hospital.
Acupuncture Points ; Acupuncture Therapy ; Electromyography ; Humans ; Low Back Pain/therapy* ; Needles ; Treatment Outcome

BACKGROUND: Preliminary studies have found that the oral intake of contraceptives reduces the rate of orthodontic tooth movement. This study mainy explores the effects of oral contraceptives on periodontium remodeling during orthodontic tooth movement in a female rat model. OBJECTIVE: To investigate the effects of combined oral contraceptives (COCs) on the expression levels of progesterone receptor and osteoprotegerin, as well as the number of osteoclasts in the periodontium during orthodontic tooth movement. METHODS: Eighty 3-month-old female Sprague-Dawley rats were randomly divided into two groups (n=40 per group), and COCs (marvelon, experimental group) or normal saline (control group) was then given by gavage. At 7 days after administration, the right maxillary first molars were moved mesially under a force of 50 g delivered by nickel-titanium coil springs, and 10 rats were killed on day 7, 14, 21 and 28 after loading, respectively. The expression levels of progesterone receptor and osteoprotegerin in the periodontium were detected by immunohistochemistry, and the number of activated osteoclasts was measured by tartrate-resistant acid phosphatase staining. RESULTS AND CONCLUSION: At 28 days after force loading, the expression level of progesterone receptor in the periodontium in the experimental group (0.307±0.03) was significantly higher than that in the control group (0.194±0.11), (P < 0.01). The number of osteoclasts in the maxillary first molars in the experimental group was significantly less than that in the control group at 7, 14, 21 and 28 days after force loading (P < 0.05). The average absorbance value of osteoprotegerin in the experimental group was significantly higher than that in the control group (P < 0.01). These results show that COCs are able to promote osteogenesis and slow bone absorption during periodontal reconstruction, indicating that the course of orthodontic treatment for female patients with a history of COCs intake may be extended.

Objective To investigate the efficacy of an anti-vascular endothelial growth factor (VEGF) antibody,MIL60,in inhibiting corneal neovascularization (CoNV) formation in a rat model of alkali cauterization and its involved mechanisms.Methods Rat CoNV model induced by alkali burn was founded in the right eyes,and then 72 cases were randomly divided into four groups according to the subconjunctival administration of medicine next day after the successful establishment of this model:25mg· mL-1 MIL60 group,dexamethasone group,MIL60 solvent group and NaCl group.Then CoNV was observed for recording the its length and the involved area using digital photograph.Next the rats were sacrificed on day 7,14,21 and 28,followed by the collection of rats' cornea for HE and immunohistochemical staining to analyze the protein expression of VEGF,VEGF receptor-1 (VEGFR-1),VEGFR-2 and matrix metallopeptidase-9 (MMP-9).Results At each time point,the area and length of CoNV in the 25 mg· mL-1 MIL60 and dexamethasone group were significantly less than those in the MIL60 solvent and NaC1 group,and the differences were statistically significant (all P ＜0.01),and 25 mg· mL-1 MIL60 group had the similar CoNV area and length with the dexamethasone group (all P ＞ 0.05).Moreover,HE and immunohistochemical staining showed that MIL60 could inhibit the protein expression of VEGF,VEGFR-1,VEGFR-2 and MMP-9,which could explain its effective anti-angiogenic activity.Conclusion Subconjunctival administration of MIL60 can significantly inhibit corneal neovascularization formation and alleviate the inflammation in rats suffered from alkali burn.

OBJECTIVETo investigate the effects of silencing ADP-ribosylation factor 6 (Arf6) on the proliferation, migration, and invasion of prostate cancer cell line PC-3 and the possible molecular mechanisms.

METHODSThree Arf6-specific small interfering RNA (siRNA) were transfected into cultured prostate cancer cell line PC-3. Arf6 expression was examined by real-time PCR and Western blotting. MTT assay, wound healing assay, and Transwell migration and invasion assay were used to observe the effect of Arf6 silencing on the proliferation, migration, and invasion ability of PC-3 cells. The levels of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), ERK1/2, p-AKT, AKT and Rac1 were detected by Western blotting.

RESULTSTransfection of siRNA-3 resulted in significantly decreased Arf6 mRNA and protein expression with inhibition rates of (91.88±3.13)% and (86.37±0.57)%, respectively. Arf6 silencing by siRNA-3 markedly suppressed the proliferation, migration and invasion of PC-3 cells and reduced the expression levels of p-ERK1/2 and Rac1.

CONCLUSIONSilencing of Arf6 efficiently inhibits the proliferation, migration, and invasion of PC-3 cells in vitro, and the underlying mechanisms may involve the down-regulation of p-ERK1/2 and Rac1.

ADP-Ribosylation Factors ; genetics ; metabolism ; Cell Line, Tumor ; Cell Movement ; Down-Regulation ; Humans ; Male ; Mitogen-Activated Protein Kinase 1 ; metabolism ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Neoplasm Invasiveness ; Prostatic Neoplasms ; pathology ; RNA Interference ; RNA, Messenger ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; Real-Time Polymerase Chain Reaction ; Transfection ; Wound Healing ; rac1 GTP-Binding Protein ; metabolism

OBJECTIVETo analyze the whole microbial structure in a case of rampant caries to provide evidence for its prevention and treatment.

METHODSClinical samples including blood, supragingival plaque, plaque in the caries cavity, saliva, and mucosal swabs were collected with the patient's consent. The blood sample was sent for routine immune test, and the others samples were stained using Gram method and cultured for identifying colonies and 16S rRNA sequencing. DNA was extracted from the samples and tested for the main cariogenic bacterium (Streptococcus mutans) with qPCR, and the whole microbial structure was analyzed using DGGE.

RESULTSThe patient had a high levels of IgE and segmented neutrophils in his blood. Streptococci with extremely long chains were found in the saliva samples under microscope. Culture of the samples revealed the highest bacterial concentration in the saliva. The relative content of hemolytic bacterium was detected in the samples, the highest in the caries cavity; C. albicans was the highest in the dental plaque. In addition, 33 bacterial colonies were identified by VITEK system and 16S rDNA sequence phylogenetic analysis, and among them streptococci and Leptotrichia wade were enriched in the dental plaque sample, Streptococcus mutans, Fusobacterium nucleatum, and Streptococcus tigurinus in the caries cavity, and Lactobacillus in the saliva. S. mutans was significantly abundant in the mucosal swabs, saliva and plaque samples of the caries cavity as shown by qPCR. Compared to samples collected from a healthy individual and another two patients with rampant caries, the samples from this case showed a decreased bacterial diversity and increased bacterial abundance shown by PCR-DGGE profiling, and multiple Leptotrichia sp. were detected by gel sequencing.

CONCLUSIONThe outgrowth of such pathogenic microorganisms as S. mutans and Leptotrichia sp., and dysbiosis of oral microbial community might contribute to the pathogenesis of rampant caries in this case.

Abnormalities, Multiple ; Dental Caries ; microbiology ; Dental Plaque ; microbiology ; Fusobacterium ; isolation & purification ; Humans ; Immunoglobulin E ; blood ; Lactobacillus ; isolation & purification ; Leptotrichia ; isolation & purification ; Limb Deformities, Congenital ; Microbiota ; Mouth Mucosa ; microbiology ; Neutrophils ; cytology ; Phylogeny ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S ; genetics ; Saliva ; microbiology ; Streptococcus ; isolation & purification ; Tooth Abnormalities

Toxicity of different processed was evaluated Polygoni Multiflori Radix by determining the hepatotoxic potency for selecting processing technology. Process Polygoni Multiflori Radix using high pressure steamed, Black Bean high pressure steamed, atmospheric steamed for different time. Using normal human hepatocytes (L02) as evaluation model, hepatotoxic potency as index to evaluate hepatotoxic potency of different processed Polygoni Multiflori Radix. Analysis chemical composition of some processed products by UPLC-MS. Hepatotoxic bioassay method cloud evaluate the toxicity of different Polygoni Multiflori Radix samples. Different processing methods can reduce the toxicity of Polygoni Multiflori Radix, high pressure steamed three hours attenuated was better. Different processing methods have different effects on chemical constituents of Polygoni Multiflori Radix. Comparing with crude sample, the contents of gallic acid, 2,3,5,4-tetrahydroxyl diphenylethylene-2-O-glucoside, emodin-8-O-beta glucoside and emodin were decreased in processed products with 3 kinds of different methods. The change trend of 2,3,5,4-tetrahydroxyl diphenylethylene-2-O-glucoside content was similar with hepatotoxic potency. Different processing methods can reduce the toxicity of Polygoni Multiflori Radix. Processing methods and time attenuated obvious impact on toxicity. Recommended further research on the attehuated standard control of Polygoni Multiflori Radix concocted.
Biological Assay ; Cell Line ; Chemistry, Pharmaceutical ; methods ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; toxicity ; Fallopia multiflora ; chemistry ; toxicity ; Hepatocytes ; drug effects ; Humans ; Plant Roots ; chemistry ; toxicity

This article summarizes the pathogenesis of hypercoagulability in β thalassemia patients, including platelet activation, alteration of red blood cell membranes, abnormal expression of adhesion molecules on vascular endothelial cells and iron overload. Clinical evidence, clinical manifestations of hypercoagulable state and thrombosis in β thalassemia and the effect of splenectomy on hypercoagulable state were reviewed. Strategies to prevent and treat the thromboembolic events in β-thalassemia intermedia are also discussed, including transfusion therapy to raise hemoglobin levels, avoidance or delay of splenectomy and a number of treatments in the exploration.
Erythrocyte Aggregation ; Humans ; Thrombophilia ; etiology ; prevention & control ; beta-Thalassemia ; complications

Objective To study the relationship between resting heart rate and blood lipid level.
Methods A total of 9 415 subjects aged≥40 years were included in the present study. Their resting heart rate was monitored and their serum levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were measured to define dyslipidemia according to the 2007 Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults.
Results The subjects were divided into group A with their resting heart rate<70 beats/min, group B with their resting heart rate=70-79 beats/min, group C with their resting heart rate=80-89 beats/min, and group D with their resting heart rate≥90 beats/min. High TG, TC, and LDL-C were presented across the resting heart rate (Ptrend<0.01). Multiple logistic regression analysis revealed that the risk of high TG and TC was higher in subjects with their resting heart rate≥90 beats/min than in those with their resting heart rate<70 beats/min (OR=1.42;95%CI:1.16-1.74 and OR=1.33;95%CI:1.09-1.64, respectively).
Conclusion Elevated resting heart rate is associated with high TG and TC in middle-aged and elderly Chinese subjects.