Objective To study the characteristic of inhibition on platelet P2Y12 and short-term change after clopidogrel intake in patients with cardiovascular disease. Methods Thirty-two patients with cardiovascular disease were enrolled. Samples at baseline, 10 h and 36 h after 300 mg loading dose and 75 mg/d maintenance dose of clopidogrel with 100 mg/d Aspirin intake were measured respectively. Platelet aggregation (PAgT) was measured on thromboelastograph(TEG) induced by ADP/AA. INH was detected and calculated activated by Kaolin, AA, ADP and Activator((R)) in the TEG reagent. CD62p and VASP phosphorylation (PRI), platelet activation markers were tested with FACSCalibur Flow Cytometry, and platelet secretion activity and suppression of P2Y12 receptor were detected respectively. The changes of indicators were compared before and after clopidogrel intake, and evaluate their function in platelet receptor activation. Results INHADP at baseline was (11.5 ±9.3)%, and increased to (42.5 ±29.1)% statistically (t =3.155, P<0.05) after taking the P2Y12 at 10 h, but decreased to (20.4±13.1)% at 36 h, non-statistical to baseline (t = 2.078, P > 0. 05) , INHAA increases from baseline level (56. 6 ± 36. 6) % to (83.0 ±27. 3)% at 10h(t=2.086,P>0.05) and (85. 4 ±20. 8)% at 36 h (t= 1. 888, P>0.05), no statistical defferences were found. Inhibition on platelet activativation induced by ADP function well till 36 h after 300 mg loading dose. PAgTADP decrease from (53. 7 ± 14. 1)% at baseline to (49. 2 ±22. 8)% at 10 h non-statistically (t=0.656, P>0.05), and (40.7±12.8)% at 36 h statistically (t=2.418, P<0.05), however PAgTAA decrease at both 10 h and 36 h statiscally, from (34. 3 ± 18. 1) % to (17.4 ± 13. 1) % , (t=3.134, P<0.05) and (14.6±5.1)%, (t=2.532, P<0.05), respectively. Data of PAgT was not corresponding to that from TEG for the difference in sample type partly. PRI in VASP assay was (78. 6 ± 22.3)% before loading dose, and decreased to (70.7 ±9.4)% at 10 h without significance (t = l. 194, P>0.05) and (59.6 ±28.0)% at 36 h (t=1.930,P<0.05) statistically, similarly to INHADP,indicating that within 36 h clopidogrel did not have strong inhibitory effect on the ADP receptor. On the contrary, CD62p changed from (7. 5 ± 1. 4) % at baseline to (4. 2 ± 1. 1) % statistically (10 h, t = 18. 027, P < 0. 05) and ( 4. 3 ± 0. 2 ) % non-statistically (36 h, t = 2. 908, P > 0. 05 ). Inhibition of secretion activity reflected by CD62p was significant. In contrast, it was more obvious inhibition in COX-1 passway, while the inhibition of P2Y12 receptor varied due to assay difference. Conclusions AA-induced platelet activation is significantly decreased in the inhibition of clopidogrel and aspirin, while ADP receptor is significantly inhibited until 36 h after the loading dose of clopidogrel. Platelet function in whole blood reflects total activity of platelet interaction with other components, in which no significant inhibition could be witnessed within 10 h.

Objective To elucidate the immunologic mechanism and clinical effect of high intensity focused ultrasound (HIFU) combined with dendritic cell and cytokine induced killer cell (DC-CIK) immunotherapy on patients with pancreatic cancer.Methods Seventy-two pancreatic cancer patients were divided randomly into 2 equal groups,one treated with HIFU only the other treated with HIFU and DC-CIK immunotherapy.Ultrasound imaging and a variety of immunological indexes were recorded before and after treatment and the clinical effects in the two groups were compared.Moreover,autogenous tumor cells were isolated from the combination therapy group and the killing activity of DC-CIK which loaded tumor antigen processed by HIFU on autogenous tumor cells was observed.Results Tumor antigen processed by HIFU can improve the killing activity of DC-CIK on autogenous tumor cells.After treatment,the immunological indexes,of all patients were better than before treatment.(58.26 ± 17.97 versus 52.15 ± 14.22 pg/ml with IL-12 22.14 ± 6.39 versus 17.36 ± 5.73 ng/ml with HSP70 and 0.94 ± O.34 versus 1.32 ± O.61 ng/ml with TGF-β,P ＜ 0.05 ) ; The combination group was significantly better than the HIFU group with regard to the average scores of quality of life (75.89 ± 19.65 versus 67.22 ± 16.34,P＜0.05),pain (3.15 ±0.82 versus 3.59 ± 1.04,P ＜0.05),tumor markers (107.55 ±27.58 versus 123.63 ±34.12 U/ml) and survival time (18.92±6.47 versus 13.36 ±5.78 mos).Conclusion HIFU can improve the immunologic status and anti-tumor response in patients with pancreatic cancer.HIFU combined with DC-CIK has good synergistic therapeutic effect for treating pancreatic cancer.

Objective To explore the immune effects of high intensity focused ultrasound (HIFU) in the treatment of pancreatic carcinoma and to investigate the imaging methods to evaluate HIFU's efficacy.Methods A total of 32 patients with pancreatic carcinoma treated by HIFU were enrolled.The freeze-thaw antigen was prepared by freezing and thawing the cancer cells.HIFU antigen was prepared by cancer cells sonicated by HIFU.The killing effects of no antigen activated dendritic cells (DC) induced T lymphocyte (DC-T),freeze-thaw antigen activated DC induced T lymphocyte (freeze-thaw antigen-DC-T) and HIFU activated DC induced T lymphocyte (HIFUantigen-DC-T) in autologous pancreatic cancer cells were detected by lactic dehydrogenase kit.The changes of immune indexes [heat shock protein 70 (HSP70),T helper lymphocyte Thl/Th2 and transforming growth factor-β (TGF-β)] before and after H IFU treatment were determined by enzymelinked immunosorbnent assay (ELISA) method.The changes of clinical efficacy indexes [visual analogue scale (VAS),performance status (PS) and carbohydrate antigen (CA) 19-9] before and after HIFU treatment were compared.The instant and recent (two months) efficacy of HIFU treatment were evaluated by contrast enhanced ultrasonograph (CEUS) and computed tomography (CT).The line q test was performed for comparision between groups.t-test was applied for comparision before and after treatment.Results Compared with freeze-thaw antigen,the killing effect of HIFU antigen-DC-T in autologous pancreatic cancer cells was higher (40.24％ ± 10.56％ vs 46.93％±13.26％,q=3.44,P＜0.05).HSP70 [(17.31±4.75) ng/mlvs (22.84±5.56) ng/ml],Th1/Th2 (1.24±0.36 vs 1.47±0.31),TGF-β [(1.39±0.41) ng/ml vs (1.04±0.38) ng/ml],VAS (3.97±1.32 vs 3.26±1.18),PS (2.76± 1.02 vs 2.21±0.86) and CA19-9 level[(135.39±37.45) U/ml vs (114.82±30.51) U/ml] improved after HIFU treatment compared with those before treatment (t=4.278,2.739,3.542,2.268,2.332 and 2.409,allP＜0.05).CEUS and CT showed that blood supply and the volume of the tumors reduced after HIFU treatment.Conclusions HIFU is effective in treating pancreatic carcinoma,improving immune status of patients and enhancing antitumor response.CEUS can real-time evaluate the efficacy of HIFU treatment.

Objective To observe the brain activation of interictal epiletiform discharges(IEDs) and to localize the epileptogenic foci of epilepsy.Methods The electroencephalogram(EEG)and functional MRI data of 12 focal epileptic patients were acquired using a combination of EEG and functional MRI simultaneously.The IEDs onset time detected with EEG were set as the time parameters in an event- related paradigm of functional MRI analysis.The spatial and temporal characters of IEDs activation were analyzed in detail.In order to confirm the consistency of this method,all patients were scanned repeatedly and the results were correlated with clinical evaluation.Results Of the 12 patients,valid data from EEG- fMRI were obtained from 10 patients in a total of 18 sessions..Compared with the structural foci,the epileptic foci localization results of eleven sessions were good,five sessions were fairly good,and two sessions were poor.The results obtained from six patients in two separate sessions were concordant.respectively.Moreover,thalamic activation was detected in ten sessions,cerebellar activation was detected in all sessions,and the deactivation was found in the default mode loci in nine sessions. Conclusion The method of performing EEG and fMRI simultaneously can potentially be a useful tool in epilepsy research.

Serum levels of soluble MHC class I-related chain A (sMICA) are related with the prognosis of various types of cancer; however, few studies on the prognostic value of sMICA in hepatocellular carcinoma (HCC) have been reported. In this study, we retrospectively investigated the relationship between sMICA levels and clinical features of advanced HCC, and we assessed the prognostic value of sMICA in advanced HCC. Furthermore, the relationship of serum sMICA levels and natural killer group 2, member D (NKG2D) expression on natural killer (NK) cells was also evaluated. We detected sMICA levels in the serum of 60 advanced HCC patients using enzyme-linked immunosorbent assay (ELISA) and measured expression levels of NKG2D on NK cells using flow cytometry. We found that serum sMICA levels in HCC patients were in the range of 0.10-6.21 ng/mL. Chi-square analyses showed that sMICA level was significantly related with only tumor size. Survival analysis showed that a high sMICA level was significantly related with poor prognosis among HCC patients. Multivariate analyses indicated that sMICA was an independent prognostic factor. In addition, the levels of CD56+NKG2D+ NK cells were within the range of 11.2%-55.4%, and correlation analyses indicated that sMICA level was negatively correlated with the level of NKG2D+ NK cells. Our results suggest that serum sMICA levels may be an independent prognostic factor for advanced HCC.
Adult ; Carcinoma, Hepatocellular ; blood ; immunology ; pathology ; Female ; Histocompatibility Antigens Class I ; blood ; Humans ; Killer Cells, Natural ; immunology ; metabolism ; Liver Neoplasms ; blood ; immunology ; pathology ; Male ; Middle Aged ; Multivariate Analysis ; NK Cell Lectin-Like Receptor Subfamily K ; metabolism ; Neoplasm Staging ; Retrospective Studies ; Survival Rate ; Tumor Burden

Objective To explore developmental states on the preterm and term neonatal brain white matter based on the co-variation of metrics derived from diffusion tensor imaging(DTI).Methods This work enrolled 66 neonates,consisting of 33 preterm(21 males and 12 females;gestational age:30.143-36.286 weeks)and 33 full-term neonates(22 males and 11 females;gestational age:37.000 -41.429 weeks).DTI derived metrics included axial diffusivity(AD),radial diffusivity(RD),and fractional anisotropy(FA).Spearman's rank correlation between metrics and postmenstrual age was analyzed in the preterm and term neonates.Developmental states were evaluated according to the method proposed by Dubois:fiber organization was associated with increased AD, decreased RD and increased FA;pre-myelination was related to decreased AD,decreased RD and unchanged/increased FA;myelination was revealed by unchanged AD,decreased RD and increased FA.Mann-Whitney U test was used to compare DTI metrics between the preterm and term neonates.Results According to the method proposed by Dubois,posterior limb of internal capsule and corpus callosum underwent myelination in the preterm-neonate period.Cerebral peduncle started myelination in the term-neonate period.Superior corona radiate,inferior fronto-occipital fasciculus and external capsule underwent pre-myelination on preterm and term neonates.FA values were higher in term neonates than those in preterm neonates in all the selected regions(P＜0.05).AD and RD values were lower in term neonates than those in preterm neonates in the selected regions except for cerebral peduncle(P＜0.05).Conclusion Changes in DTI metrics and the method of Dubois can be used to quantitatively evaluate developmental states of the neonatal brain white matter.The changes coincided with DTI variations associated with pre-myelination and myelination.White matter development is delayed in preterm neonates compared with term neonates.

Objective:To compare the early therapeutic effects of internal fixation with percutaneous minimally invasive hollow nail assisted by electromagnetic navigation robot and guided by C-arm in the treatment of Tile type C pelvic fracture.Methods:A retrospective cohort study was conducted to analyze the clinical data of 32 patients with Tile type C pelvic fracture admitted to Weihai Central Hospital from January 2020 to March 2022, including 18 males and 14 females; aged 36-60 years [(44.1±3.9)years]. Among them, 17 patients were treated with internal fixation with percutaneous minimally invasive hollow nail assisted by electromagnetic navigation robot (electromagnetic navigation group), and 15 with internal fixation with percutaneous minimally invasive hollow nail guided by C-arm (C-arm guidance group). Operative time, intraoperative blood loss, sacroiliac screw placement time, pubic branch screw placement time, ambulation time and fracture healing time were compared between the two groups. Visual analog scale (VAS), Majeed function score and complication rate at 1 day, 6 months, 12 months after surgery and at the last follow-up were compared between the two groups.Results:All the patients were followed up for 12-24 months [(15.4±0.5)months]. The operative time and intraoperative blood loss in the electromagnetic navigation group were (42.0±2.5)minutes and (10.9±2.6)ml, shorter or less than (50.0±3.5)minutes and (14.9±3.1)ml in the C-arm guidance group (all P<0.01). The placement time of sacroiliac screw and pubic branch screw in the electromagnetic navigation group was (12.4±0.2)minutes and (10.1±0.3)minutes, shorter than (15.3±0.3)minutes and (13.2±0.3)minutes in the C-arm guidance group (all P<0.01). The ambulation time was (3.2±0.4)weeks in the electromagnetic navigation group, earlier than (3.5±0.4)weeks in the C-arm guidance group ( P<0.05). There was no significant difference in fracture healing time between the two groups ( P>0.05). VAS scores of the electromagnetic navigation group were (4.4±0.3)points and (1.1±0.1)points at 1 day and 6 months after surgery respectively, lower than those of the C-arm guidance group [(4.8±0.4)points and (1.2±0.3)points] ( P<0.05 or 0.01). Majeed function scores of the electromagnetic navigation group were (37.3±1.1)points and (88.5±1.4)points at 1 day and 6 months after surgery respectively, higher than those of the C-arm guidance group [(30.7±4.2)points and (82.6±1.8)points] (all P<0.01). There were no significant differences in VAS and Majeed scores at 12 months after surgery and at the last follow-up between the two groups (all P>0.05). There was no significant difference in the incidence of postoperative complications between the two groups ( P>0.05). Conclusion:Compared with C-arm guidance, electromagnetic navigation robot-assisted internal fixation with percutaneous minimally invasive hollow nail for Tile type C pelvic fracture can reduce operative time and intraoperative blood loss, shorten screw placement time and ambulation time, relieve pain and improve functional recovery at early stage.

Objective:To analyze the clinical efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced NSCLC.Methods:We collected 23 cases of NSCLC advanced patients, who were treated in the affiliated Cancer Hospital of Guangzhou Medical University from January 2015 to March 2020. And these 23 cases of patients with first-generation EGFR-TKIs resistance were treated with the third-generation EGFR-TKI drugs. We analyzed their clinicopathological characteristics, studied their therapeutic effects, and followed up their progression-free survival (PFS).Results:It is showed that 16 of 23 cases (69.56%) were got local progression and 7 of 23 cases (31.43%) were found with systemic progression. Briefly, the median PFS of the 23 patients was 17.5 months. A total of 7 cases occurred rashes after taking EGFR-TKI, and 3 cases got abnormal liver function. Fortunately, they were all improved after symptomatic treatments. Additionally, no bone marrow suppression (granulocytes, neutropenia, thrombocytopenia, anemia) and digestive tract reactions (nausea, vomiting, diarrhea) were occurred in 23 cases of NSCLC patients. The mental and physical improvement of EGFR-TKI in the third generation of 19 patients was more obvious than that in the first generation of EGFR-TKI. Among them, 15 cases showed more obvious lesion shrinkage after third-generation EGFR-TKI treatment. 4 patients with GGO had cleaner disappearance than that of the first-generation EGFR-TKI.Conclusions:Compared with traditional chemotherapy, the first-generation EGFR-TKI resistance treatment with three-generation EGFR-TKI treatment has better efficacy with reduced toxic and side effects, and significantly improved the life quality of advanced NSCLC patients.

OBJECTIVETo investigate the lymph nodes distribution and metastatic pattern of the ultra-low rectal cancer after neoadjuvant therapy.

METHODSA total of 21 rectal cancer gross specimen after neoadjuvant therapy and 23 rectal cancer gross specimen without neoadjuvant therapy were investigated by whole mount section and tissue microarray techniques with CK20. All the patients were treated by abdominoperineal resection.

RESULTSThere were 138 lymph nodes retrieved from the mesorectum in the neoadjuvant group including 39 metastatic lymph nodes and 12 micro-metastatic lymph nodes. Among these nodes, there were 7 rectal cancer cases with lymph nodes and 2 cases with micro-metastatic lymph nodes, and 6 cases had pathological complete remission. There were 415 lymph nodes retrieved from the mesorectum in the group without neoadjuvant therapy including 169 metastatic lymph nodes and 59 micro-metastatic lymph nodes. Among these nodes, there were 12 rectal cancer cases with lymph nodes and 4 cases with micro-metastatic lymph nodes. The proportions of metastatic lymph nodes in outer zone between the two groups were 21.5% and 29.0%, and those in pre-zone were 17.6% and 17.2% respectively. The ratio of metastatic lymph nodes in ischiorectal fossa between the two groups were 25.0% vs. 22.2% respectively. The rate of metastatic or micro-metastatic lymph nodes cases between the two groups were 4.8% vs. 13.0% respectively.

CONCLUSIONSThe lymph nodes distribution and metastatic pattern of the ultra-low rectal cancer are affected by neoadjuvant therapy. The proportions of the anal sphincter invasion and metastatic or micro-metastatic lymph nodes in ischiorectal fossa are lower after neoadjuvant therapy. Abdominoperineal resection as the standard treatment of the ultra-low rectal cancer after neoadjuvant therapy should be re-evaluated.

Biopsy ; Digestive System Surgical Procedures ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Neoadjuvant Therapy ; Rectal Neoplasms ; pathology ; therapy

OBJECTIVETo study the radiobiological characteristic of human nasopharyngeal carcinoma cell lines CNE1 and CNE2 and the changes in expression MRN (Mre11-Rad50-Nbs1) complex in the cell lines exposed to irradiation.

METHODSCNE1 and CNE2 were irradiated by a linear accelerator. Radiobiological characteristics were detected by colony assay and MTT assay. MRN complex expression were examined by Western blot.

RESULTSSurviving fraction at 2 Gy (SF2), quasi-threshold Dose (Dq), and mean lethal dose (Do) of CNE1 were 0.56, 1.449 Gy and 1.480 Gy; SF2, Dq, and Do of CNE2 were 0.44, 0.776 Gy and 1.685 Gy, respectively. Survival fraction of CNE1 at the day 6 after 4 Gy irradiation was 0.59 and that of CNE2 was 0.79 when compared with control, with the up-regulated expressions of Rad50 in CNE1 and Mre11, Rad50 and Nbs1 in CNE2 (P < 0.05).

CONCLUSIONSCNE1 and CNE2 were sensitive to radiation, but there were radioresistance cells in CNE2. The expressions of some components of MRN complex were up-regulated to repair DNA lesions induced by radiation.

Carcinoma ; Cell Cycle Proteins ; metabolism ; Cell Line, Tumor ; radiation effects ; DNA Repair ; DNA Repair Enzymes ; metabolism ; DNA-Binding Proteins ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; MRE11 Homologue Protein ; Nasopharyngeal Neoplasms ; pathology ; radiotherapy ; Nuclear Proteins ; metabolism ; Radiation Tolerance