OBJECTIVETo examine the growth-inhibitory, apoptosis- and necrosis-inducing effects of realgar nano-particles (RNP) in human chronic myelogenous leukemia cell line K562 and acute myeloid leukemia cell line HL-60, and to find out the chemical species with efficacy.

METHODA "solvent-relay" strategy was used for the preparation of RNP suspension. Cell viability was determined by MTT assay. Cell apoptosis and necrosis were characterized with Annexin V-PI double staining in association with flow cytometry and with morphological examination with Hoechst 33258 staining. Parallel experiments with arsenous acid (H3AsO3), the dominant form of arsenic trioxide in the solution, were conducted for comparison.

RESULTThe mean diameter of RNP was 159.0 nm. RNP showed growth-inhibitory effect on both cell lines. The double staining test indicated that RNP induced both apoptosis and necrosis, and this was further confirmed by morphological examination.

CONCLUSIONRNP induced both apoptosis and necrosis in leukemia cell lines K562 and HL-60. Thioarsenite species with both As-O and As-S bonds may be the active intermediates in the RNP.

Antineoplastic Agents ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Arsenicals ; administration & dosage ; pharmacology ; Cell Proliferation ; drug effects ; HL-60 Cells ; pathology ; Humans ; K562 Cells ; pathology ; Materia Medica ; administration & dosage ; pharmacology ; Nanotechnology ; Necrosis ; Particle Size ; Sulfides ; administration & dosage ; pharmacology

Objective:To investigate the independent correlation between serum IL-6 level and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) and to evaluate its predictive value for DCI.Methods:Consecutive patients with aSAH admitted to the Affiliated Hospital of Jining Medical University from June 2017 to June 2019 were enrolled retrospectively. They were divided into DCI group and non-DCI group according to the diagnostic criteria of DCI. Multivariate logistic regression analysis was used to determine the independent correlation between serum IL-6 and DCI. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum IL-6 level for DCI. Results:A total of 160 patients with aSAH were enrolled. They aged 66.1±8.1 years, and 98 were males (61.3%); 76 patients (47.5%) had DCI. Multivariate logistic analysis showed that after adjusting for smoking, hypertension, systolic blood pressure, hyperlipidemia, and drug treatment, serum IL-6 (the first quartile as a reference, and the third quartile: odds ratio[ OR] 3.885, 95% confidence interval [ CI]1.361-7.189; the fourth quartile: OR 9.706, 95% CI 3.412-18.344), Glasgow Coma Scale score ( OR 2.174, 95% CI 1.325-4.538) and Fisher grade ( OR 3.267, 95% CI 1.638-6.725) were independently associated with DCI. The ROC curve showed that the area under the curve of serum IL-6 for predicting DCI was 0.777 (95% CI 0.706-0.849), and the optimal cut-off value was 13.01 ng/L. The sensitivity and specificity of predicting DCI were 72.4% and 71.4%, respectively. Conclusions:Serum IL-6 is an independent risk factor for DCI after aSAH, and has certain predictive value for DCI.

OBJECTIVEThis review focuses on the state-of-the-art of CXCL12/CXCR4 signaling axis in pancreatic cancer and its role in tumor progression.

DATA SOURCESRelevant articles published in English were identified by searching in Pubmed from 1997 to 2013, with keywords "CXCL12", "CXCR4" and "pancreatic cancer". Important references from selected articles were also retrieved.

STUDY SELECTIONArticles about CXCL12/CXCR4 signaling axis in pancreatic cancer and relevant mechanisms were selected.

RESULTSPancreatic cancer has been one of the most lethal human malignancies, with median survival less than one year and overall 5-year survival only 6%. Tumor cells from pancreatic cancer express high level of CXCR4. CXCL12, the ligand for CXCR4, is extensively secreted by neighboring stromal cells and other distant organs. CXCL12 primarily binds to CXCR4, induces intracellular signaling through several divergent pathways, which are involved in progression and metastasis of pancreatic cancer.

CONCLUSIONSCXCL12/CXCR4 signaling axis may play an important role in the communication between pancreatic cancer cells and their microenvironment, which may have effect on tumor proliferation, invasion, angiogenesis, metastasis and chemoresistance. CXCL12/CXCR4 signaling axis may serves as a novel therapeutic target for pancreatic cancer.

Chemokine CXCL12 ; genetics ; metabolism ; Humans ; Pancreatic Neoplasms ; genetics ; metabolism ; Receptors, CXCR4 ; genetics ; metabolism ; Signal Transduction ; genetics ; physiology

OBJECTIVETo study biomechanical changes of newly formed bones 24 weeks after repairing large defects of long bones of goats using heterogeneous deproteinated bone (DPB) prepared by modified methods as an engineering scaffold.

METHODSAccording to a fully randomized design, 18 goats were evenly divided into three groups: normal bone control group (Group A), autologous bone group (Group B) and experimental group (Group C). Each goat in Groups B and C were subjected to the periosteum and bone defect at middle-lower part of the right tibia (20% of the whole tibia in length), followed by autologous bone or DPB plus autologous MSCs + rhBMP2 implantation, respectively and semi-ring slot fixation; while goats in Group A did not perform osteotomy. At 24 weeks after surgery, biomechanical tests were carried out on the tibias.

RESULTSAt 24 weeks after surgery, the results of anti-compression test on tibias in three groups were recorded by a functional recorder presented as linear pressure-deformation curve. The shapes of the curves and their change tendency were similar among three groups. The ultimate pressure values were 10.74 MPa+/-1.23 MPa, 10.11 MPa+/-1.35 MPa and 10.22 MPa+/-1.32 MPa and fracture compression rates were 26.82%+/-0.87%, 27.17%+/-0.75% and 28.22%+/-1.12% in Groups A, B and C, respectively. Comparisons of anti-compression ultimate pressures and fracture compression rates among three groups demonstrated no significant difference (P(AB) equal to 0.415, P(BC) equal to 0.494). Three-point anti-bend test on tibias was recorded as load-deformation curves, and the shapes of the curves and their change tendency were similar among three groups. The ultimate pressure values of the anti-bend test were 481.52 N+/-12.45 N, 478.34 N+/-14.68 N and 475.62 N+/-13.41 N and the fracture bend rates were 2.62 mm+/-0.12 mm, 2.61 mm+/-0.15 mm and 2.81 mm+/-0.13 mm in Groups A, B and C, respectively. There was no significant difference between groups (P(AB) equal to 0.7, P(BC) equal to 0.448). The ultimate anti-torsion torque values were 6.55 Nm+/-0.25 Nm, 6.34 Nm+/-0.18 Nm and 6.42 Nm+/-0.21 Nm and fracture torsion rates were 29.51 degree+/-1.64degree, 28.88 degree+/-1.46 degree and 28.81 degree+/-1.33 degree in Groups A, B and C, respectively. There was no significant difference between groups (P(AB) equal to 0.123, P(BC) equal to 0.346).

CONCLUSIONSThe biomechanical characteristics of newly formed bones from heterogeneous DPB for repairing large segmental long bone defect are comparable to those of normal bones and autologous bones. DPB has the potential for clinical usage as bone graft material.

Animals ; Biomechanical Phenomena ; Female ; Goats ; Male ; Proteins ; Tibia ; physiology ; surgery ; Tissue Engineering ; Torsion, Mechanical

OBJECTIVETo evaluate the value of a new platelet function test PFA P2Y (PFA-200) in monitoring clopidogrel treatment for cardiovascular disease in elderly patients.

METHODSFifty-six elderly patients receiving clopidogrel therapy in the Department of Cardiology of General Hospital of PLA from March to August in 2016 and 85 healthy volunteers were recruited for analysis. All the subjects underwent PFA P2Y, LTA (light transmittance aggregometry) and TEG (Thromboelastograph) tests, and Spearman correlation coefficients were used to test the associations between test results. The agreement among the 3 platelet function test methods was assessed using Cohen's kappa coefficient.

RESULTSCorrelation coefficient (r) was -0.701 (P<0.001) between PFA P2Y and LTA, and 0.475 (P<0.001) between PFA P2Y and TEG. The agreement was 75% between PFA P2Y and LTA and 67.9% between PFA P2Y and TEG. The κ value was 0.434 (P=0.001) between PFA P2Y and LTA and 0.242 (P=0.046) between PFA P2Y and TEG. With ADP-induced maximum platelet aggregation rate of LTA >50% as the laboratory clopidogrel resistance, the cut-off value of PFA P2Y was 119 s (AUC=0.733) with a sensitivity of 75.6% and a specificity of 73.3%.

CONCLUSIONPFA P2Y has a moderate correlation and agreement with LTA, but has a poor correlation and agreement with TEG. PFA P2Y can be useful for assessing the effects of clopidogrel therapy and the association of the cut-off value (119 s) with the long-term clinical ischemic events needs be confirmed in further study.

Biological Assay ; Blood Coagulation Tests ; Blood Platelets ; Cardiovascular Diseases ; drug therapy ; Humans ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; therapeutic use ; Platelet Function Tests ; Sensitivity and Specificity ; Ticlopidine ; analogs & derivatives ; therapeutic use

BACKGROUNDMycophenolic acid (MPA) as an anti-proliferative immune-suppressive agent is used in the majority of immunosuppressive regimens in solid organ transplantation. This study aimed to investigate the pharmacokinetic (PK) characteristics of enteric-coated mycophenolate sodium (EC-MPS) and area under the curve (AUC) from 0 to 12 hours with limited sampling strategies (LSSs) in Chinese renal transplant recipients.

METHODSThis study was conducted in 10 Chinese renal transplant patients receiving living donor and treated with EC-MPS, cyclosporine, and corticosteroids. MPA concentrations were measured by enzyme multiplied immunoassay technique (EMIT). Whole 12-hour PK profiles were obtained on Day 4 after operation. LSSs with jackknife technique, multiple stepwise regression analysis, and Bland-Altman analysis were developed to estimate MPA AUC.

RESULTSThe mean maximum plasma concentration, the mean time for it to reach peak (T(max)), and the mean MPA AUC were (11.38 ± 2.49) mg/L, (4.85 ± 3.32) hours, and (63.19 ± 13.54) mg×h×L(-1), respectively. Among the 10 profiles, MPA AUC of four patients was significantly higher than that of the other six patients, and the corresponding T(max) was significantly longer than that of the other six patients. No patient exhibited a second peak caused by enterohepatic recirculation. The best models were as follows: 27.46 + 0.94C(3) + 3.24C(8) + 2.81C(10) (r(2) = 0.972), which was used to predict AUC of fast metabolizer with a mean prediction error (MPE) of -0.21% and a mean absolute prediction error (MAE) of 2.59%; 36.65 + 3.08C(8) + 5.30C(10) - 4.04C(12) (r(2) = 0.992), which was used to predict AUC of slow metabolizer with a MPE of 0.58% and a MAE of 1.95%.

CONCLUSIONSThe PKs of EC-MPS had a high variability among Chinese renal transplant recipients. The preliminary PK data indicated the existence of slow and fast metabolizer. These findings may be associated with the enterohepatic recirculation.

Adrenal Cortex Hormones ; therapeutic use ; Adult ; Aged ; Cyclosporine ; therapeutic use ; Female ; Humans ; Kidney Transplantation ; methods ; Male ; Middle Aged ; Mycophenolic Acid ; analogs & derivatives ; pharmacokinetics ; therapeutic use ; Young Adult

Objective This study aimed to explore the potential effects of terahertz (THz) waves on primary cultured neurons from 4 rat brain regions (hippocampus,cerebral cortex,cerebellum,and brainstem)and 3 kinds of neuron-like cells (MN9D,PC12,and HT22 cells) under nonthermal conditions.Methods THz waves with an output power of 50 (0.16 THz) and 10 (0.17 THz) mW with exposure times of 6 and 60 min were used in this study.Analysis of temperature change,neurite growth,cell membrane roughness,micromorphology,neurotransmitters and synaptic-related proteins (SYN and PSD95) was used to evaluate the potential effects.Results Temperature increase caused by the THz wave was negligible.THz waves induced significant neurotransmitter changes in primary hippocampal,cerebellar,and brainstem neurons and in MN9D and PC12 cells.THz wave downregulated SYN expression in primary hippocampal neurons and downregulated PSD95 expression in primary cortical neurons.Conclusion Different types of cells responded differently after THz wave exposure,and primary hippocampal and cortical neurons and MN9D cells were relatively sensitive to the THz waves.The biological effects were positively correlated with the exposure time of the THz waves.

Objectives: To evaluate the positive rate of left posterior lymph nodes of the superior mesenteric artery (14cd-LN) in patients undergoing pancreaticoduodenectomy for pancreatic head carcinoma,to analyze the impact of 14cd-LN dissection on lymph node staging and tumor TNM staging. Methods: The clinical and pathological data of 103 consecutive patients with pancreatic cancer who underwent pancreaticoduodenectomy at Pancreatic Center,the First Affiliated Hospital of Nanjing Medical University from January to December 2022 were analyzed,retrospectively. There were 69 males and 34 females,with an age(M (IQR))of 63.0 (14.0) years (range:48.0 to 86.0 years). The χ² test and Fisher's exact probability method was used for comparison of the count data between the groups,respectively. The rank sum test was used for comparison of the measurement data between groups. Univariate and multivariate Logistic regression analyzes were used for the analysis of risk factors. Results: All 103 patients underwent pancreaticoduodenectomy successfully using the left-sided uncinate process and the artery first approach. Pathological examination showed pancreatic ductal adenocarcinoma in all cases. The location of the tumors was the pancreatic head in 40 cases,pancreatic head-uncinate in 45 cases,and pancreatic head-neck in 18 cases. Of the 103 patients,38 cases had moderately differentiated tumor and 65 cases had poorly differentiated tumor. The diameter of the lesions was 3.2 (0.8) cm (range:1.7 to 6.5 cm),the number of lymph nodes harvested was 25 (10) (range:11 to 53),and the number of positive lymph nodes was 1 (3) (range:0 to 40). The lymph node stage was stage N0 in 35 cases (34.0%),stage N1 in 43 cases (41.7%),and stage N2 in 25 cases (24.3%). TNM staging was stage ⅠA in 5 cases (4.9%),stage ⅠB in 19 cases (18.4%),stage ⅡA in 2 cases (1.9%),stage ⅡB in 38 cases (36.9%),stage Ⅲ in 38 cases (36.9%),and stage Ⅳ in 1 case (1.0%). In 103 patients with pancreatic head cancer,the overall positivity rate for 14cd-LN was 31.1% (32/103),and the positive rates for 14c-LN and 14d-LN were 21.4% (22/103) and 18.4% (19/103),respectively. 14cd-LN dissection increased the number of lymph nodes (P<0.01) and positive lymph nodes (P<0.01). As a result of the 14cd-LN dissection,the lymph node stage was changed in 6 patients,including 5 patients changed from N0 to N1 and 1 patient changed from N1 to N2. Similarly,the TNM stage was changed in 5 patients,including 2 patients changed from stage ⅠB to ⅡB,2 patients changed from stage ⅡA to ⅡB,and 1 patient changed from stage ⅡB to Ⅲ. Tumors located in the pancreatic head-uncinate (OR=3.43,95%CI:1.08 to 10.93,P=0.037) and the positivity of 7,8,9,12 LN (OR=5.45,95%CI:1.45 to 20.44,P=0.012) were independent risk factors for 14c-LN metastasis; while tumors with diameter >3 cm (OR=3.93,95%CI:1.08 to 14.33,P=0.038) and the positivity of 7,8,9,12 LN (OR=11.09,95%CI:2.69 to 45.80,P=0.001) were independent risk factors for 14d-LN metastasis. Conclusion: Due to its high positive rate in pancreatic head cancer,dissection of 14cd-LN during pancreaticoduodenectomy should be recommended,which can increase the number of lymph nodes harvested,provide a more accurate lymph node staging and TNM staging.
Male ; Female ; Humans ; Pancreaticoduodenectomy/methods* ; Retrospective Studies ; Prognosis ; Lymph Node Excision/methods* ; Lymph Nodes/pathology* ; Pancreatic Neoplasms/pathology* ; Neoplasm Staging

Objective: To investigate the functional changes of key gut microbiota (GM) that produce lipopolysaccharide (LPS) in atrial fibrillation (AF) patients and to explore their potential role in the pathogenesis of AF. Methods: This was a prospective cross-sectional study. Patients with AF admitted to Beijing Chaoyang Hospital of Capital Medical University were enrolled from March 2016 to December 2018. Subjects with matched genetic backgrounds undergoing physical examination during the same period were selected as controls. Clinical baseline data and fecal samples were collected. Bacterial DNA was extracted and metagenomic sequencing was performed by using Illumina Novaseq. Based on metagenomic data, the relative abundances of KEGG Orthology (KO), enzymatic genes and species that harbored enzymatic genes were acquired. The key features were selected via the least absolute shrinkage and selection operator (LASSO) analysis. The role of GM-derived LPS biosynthetic feature in the development of AF was assessed by receiver operating characteristic (ROC) curve, partial least squares structural equation modeling (PLS-SEM) and logistic regression analysis. Results: Fifty nonvalvular AF patients (mean age: 66.0 (57.0, 71.3), 32 males(64%)) were enrolled as AF group. Fifty individuals (mean age 55.0 (50.5, 57.5), 41 males(82%)) were recruited as controls. Compared with the controls, AF patients showed a marked difference in the GM genes underlying LPS-biosynthesis, including 20 potential LPS-synthesis KO, 7 LPS-biosynthesis enzymatic genes and 89 species that were assigned as taxa harbored nine LPS-enzymatic genes. LASSO regression analysis showed that 5 KO, 3 enzymatic genes and 9 species could be selected to construct the KO, enzyme and species scoring system. Genes enriched in AF group included 2 KO (K02851 and K00972), 3 enzymatic genes (LpxH, LpxC and LpxK) and 7 species (Intestinibacter bartlettii、Ruminococcus sp. JC304、Coprococcus catus、uncultured Eubacterium sp.、Eubacterium sp. CAG:251、Anaerostipes hadrus、Dorea longicatena). ROC curve analysis revealed the predictive capacity of differential GM-derived LPS signatures to distinguish AF patients in terms of above KO, enzymatic and species scores: area under curve (AUC)=0.957, 95%CI: 0.918-0.995, AUC=0.940, 95%CI 0.889-0.991, AUC=0.972, 95%CI 0.948-0.997. PLS-SEM showed that changes in lipopolysaccharide-producing bacteria could be involved in the pathogenesis of AF. The key KO mediated 35.17% of the total effect of key bacteria on AF. After incorporating the clinical factors of AF, the KO score was positively associated with the significantly increased risk of AF (OR<0.001, 95%CI:<0.001-0.021, P<0.001). Conclusion: Microbes involved in LPS synthesis are enriched in the gut of AF patients, accompanied with up-regulated LPS synthesis function by encoding the LPS-enzymatic biosynthesis gene.
Aged ; Atrial Fibrillation/complications* ; Cross-Sectional Studies ; Gastrointestinal Microbiome ; Humans ; Lipopolysaccharides ; Male ; Middle Aged ; Prospective Studies