Background The excitotoxicity to retinal neurons caused by abnormal elevation of glutamate in retina is a common pathology concomitant with major blind-causing eye diseases.However,an effective approach to protect retinal neurons from glutamate-induced excitotoxicity is still lack.Intraperitoneal administration of α-melanocyte stimulating hormone(α-MSH)has been shown to protect hippocampal neurons from glutamate-induced excitotoxicity.Objective This study was to investigate the protective effect of α-MSH on glutamate-induced excitotoxicity in a chicken embryonic retinal explant culture system.Methods The retinas were isolated from chick embryos at embryonic day 9(E9) and cultured as explants.The explants at 3,5 and 7 days in vitro and the retinas at corresponding embryonic day 12,14 and 16(E12,E14,E16)were collected.The morphology of explant cultures was examined by hematoxylin and eosin staining,and the expression of melanocortin receptors (MCRs)was analyzed by real-time PCR.In the experiment of glutamate-induced excitotoxicity,the retinal explants at 4 days in vitro were treated with glutamate for 48 hours,α-MSH was incubated with the explants 30 minutes before and during the glutamate treatment period.Then the apoptotic cells were detected by TUNEL staining and quantified.The glutamate alone treated-explants and those treated with culture media were included as controls.The expression of glial fibrillary acidic protein(GFAP) at 48 hours after treatment in all retinal explants was analyzed by real-time PCR.Results Hematoxylin and eosin staining showed that the retinal explants exhibited similar morphology to those observed in the retinas from chick embryos at the corresponding developmental stages.The real-time PCR analyses of chick retinas showed that MC1R mRNA level at E9,E12,E14 and E16 was significantly lower than that in post-hatch day 1 (all P=0.000) ;whereas the transcript level of MC5R was significantly increased from E9 to E12 and E14 (both P =0.000),and then gradually decreased from E14 to P1.The expression of these genes showed similar temporal patterns in the retinal explant cultures.TUNEL staining revealed that treatment of the retinal explant cultures with α-MSH substantially and significantly reduced number of apoptotic cells induced by glutamate (P =0.000),which was accompanied by significant suppression of glutamate-induced GFAP up-regulation (P =0.000).Conclusions Application of α-MSH dramatically ameliorated glutamate-induced cell death in retinal explant cultures.This protective effect may be due to α-MSH-mediated suppression of astrogliosis caused by abnormal elevation of glutamate.

12E7 Antigen ; Adolescent ; Adult ; Antigens, CD ; metabolism ; Biomarkers, Tumor ; metabolism ; Brain Neoplasms ; secondary ; Cell Adhesion Molecules ; metabolism ; Child ; Child, Preschool ; Diagnosis, Differential ; Extremities ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Infant ; Ki-67 Antigen ; metabolism ; Male ; Neuroectodermal Tumors, Primitive ; metabolism ; pathology ; Oncogene Proteins, Fusion ; metabolism ; Repressor Proteins ; metabolism ; Sarcoma, Ewing ; metabolism ; pathology ; Sarcoma, Synovial ; diagnosis ; metabolism ; pathology ; surgery ; Soft Tissue Neoplasms ; diagnosis ; metabolism ; pathology ; surgery ; Vimentin ; metabolism ; Young Adult

OBJECTIVETo evaluate the radiosensitivity and toxicity of sodium glycididazole and cisplatin in concurrent chemoradiotherapy for local advanced nasopharyngeal carcinoma (NPC).

METHODSSixty patients with local advanced NPC (T3-4N2-3M0) were randomly divided into chemoradiotherapy group (n=30) and chemoradiotherapy plus sodium glycididazole group (n=30). All the patients received radiotherapy with (60)Co or 6-8 MV linear accelerator and concurrent injection of cisplatin at a weekly dose of 20 mg/m square. In sodium glycididazole group, the patients received injections of sodium glycididazole at 800 mg/m square prior to the radiotherapy 3 times a week.

RESULTSAt the end of the therapy and 3 month after the radiotherapy, a response rate of 100% was achieved in both of the groups. But at the end of the therapy, the chemoradiotherapy plus sodium glycididazole group showed a significantly higher rate of complete tumor remission than the chemoradiotherapy group (93.3% vs 73.33%, chi(2)=4.32, P=0.038). The patients in the two groups showed similar tolerance of the therapy during the observation.

CONCLUSIONSodium glycididazole plus cisplatin can accelerate the tumor remission and improve the complete remission rate in patients with local advanced NPC without causing severe toxicity.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma ; drug therapy ; radiotherapy ; Cisplatin ; administration & dosage ; Cobalt Radioisotopes ; therapeutic use ; Combined Modality Therapy ; Female ; Humans ; Male ; Metronidazole ; analogs & derivatives ; therapeutic use ; Middle Aged ; Nasopharyngeal Neoplasms ; drug therapy ; radiotherapy ; Radiation-Sensitizing Agents ; therapeutic use

BACKGROUND: Cervical pedicle screw fixation is a reliable method for the treatment of traumatic and non-traumatic cervical instability and cervical disc removal and fixation; however, the operation risks and the failure rate of screw insertion are still high. At present, the digital navigation template with digital computer technology, used in the department of orthopedics, has the advantages of accurate screw insertion and a small error in the screw insertion depth. OBJECTIVE: To observe the clinical efficacy and safety of the digital navigation template combined with cervical pedicle screw implantation. METHODS: This is a prospective, single-center, self-controlled, clinical trial. Thirty-two patients with cervical spondylosis will be recruited from the Harrison International Peace Hospital, Hebei Province, China. Before surgery, a three-dimensional (3D) navigation model of the cervical vertebrae will be designed by 3D reconstruction. The navigation template will be generated by 3D printing. The cervical pedicle screws will be implanted according to preoperatively designed models and the screw positions will be observed by computerized tomography (CT) after surgery. The patients will be followed up for 40 months. The primary outcome measure is the excellent and good rate of screw position 40 months after implantation. The secondary outcome measures include the Visual Analog Scale score, American Spinal Injury Association classification, cervical X-ray and CT images before implantation and 40 months after implantation, and the incidence of adverse reactions 40 months after implantation. The protocols have been approved by the Ethics Committee of the Harrison International Peace Hospital in China (approval number: 20120630). The study protocol has been conducted in accordance with the Declaration of Helsinki,formulated by the World Medical Association.Written informed consent will be obtained from all participants. The recruitment of subjects will begin in December 2017. Samples and data will be collected from December 2017 to April 2019. Outcome measures will be analyzed in October 2020. This trial will be completed in November 2020. The results of the trial will be reported in a scientific conference or disseminated in a peer-reviewed journal. This trial has been registered in the Chinese Clinical Trial Registry (registration number: ChiCTR-ONC-17013481). DISCUSSION: We will verify a high success rate of cervical pedicle screw implantation using the digital navigation template. The operation is simple and quick, with good efficacy and safety.

BACKGROUNDMarked interindividual variation exists in blood pressure response to benazepril, which is considered to have genetic basis. Our objectives were to evaluate whether the E112D polymorphism in the prolylcarboxypeptidase (PRCP) gene has impact on blood pressure response to benazepril.

METHODSHypertensive patients from Huoqiu County and Yuexi County of Anhui Province received daily treatment with an oral dosage of 10 mg benazepril for 15 days. Genotypes of the E112D polymorphism in the PRCP gene were determined by TaqMan SNP genotyping assay. Multivariate linear and Logistic regressions using generalized estimating equation model were performed in a total of 1092 patients to evaluate the association of PRCP genotypes and blood pressure response to benazepril.

RESULTSPatients carrying ED or DD genotype had a less systolic blood pressure reduction (adjusted beta = -3.7 + or - 1.1, P < 0.001), a less diastolic blood pressure reduction (adjusted beta = -3.1 + or - 0.8, P < 0.001) and a lower percentage of reaching target blood pressure defined as SBP lower than 140 mmHg and DBP lower than 90 mmHg (adjusted OR = 0.6, P = 0.005) than those patients carrying EE genotype. In addition, the results from stratified analysis by county (Huoqiu or Yuexi) were similar to those observed in the pooled population.

CONCLUSIONSOur data suggest that the E112D polymorphism in the PRCP gene may be a useful genetic marker to predict the antihypertensive effect of short-term benazepril treatment in hypertensive patients of Anhui Province, China.

Adult ; Aged ; Antihypertensive Agents ; therapeutic use ; Benzazepines ; therapeutic use ; Blood Pressure ; drug effects ; Carboxypeptidases ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Hypertension ; drug therapy ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; genetics ; physiology ; Young Adult

Objective To explore the relationship of chemokines CXCL10-135G/A and CXCL12 -801G/A gene polymorphisms with susceptibility to tuberculosis. Methods CXCL10-135G/A and CXCL12-801G/A polymorphisms of 102 tuberculosis patients(case group)and 115 healthy controls(control group)were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the relationship between the two polymorphisms and susceptibility to tuberculosis were analyzed. Results The genotype analysis of CXCL10-135G/A and CXCL12-801G/A was in accord with the law of Hardy-Weinberg equilibrium in the case group and the control group. The differences of genotype and allele distribution frequency of CXCL10-135G/A were statistically significant between the case group and the control group(all P<0.05).The frequency of G allele distribution was higher in the case group than that in the control group, and the frequency of A allele distribution was lower than that in the control group.There were no significant differences in genotype and allele distribution frequency of CXCL12-801G/A polymorphism between the case group and the control group (all P>0.05).Conclusion Chemokine CXCL10-135G/A gene polymorphism is associated with susceptibility to pulmonary tuberculosis,and CXCL12-801G/A gene polymorphism may not be associated with tuberculosis infection.

Breast Neoplasms ; pathology ; Cell Culture Techniques ; methods ; Cells, Cultured ; Female ; Humans ; Immunohistochemistry ; methods ; Quality Control

OBJECTIVETo analyze the complications and treatment results of intraoperative radiotherapy (IORT) for esophageal carcinoma.

METHODSSixty patients with thoracic esophageal carcinoma underwent esophagectomy through right thoractomy, 30 patients of whom received IORT of 15 - 25 Gy.

RESULTSIn patients who underwent IORT, 2 cases of pneumonitis, 1 case of anastomotic leak and 1 case of incisional wound infection were found. In patients underwent surgery only, 1 case of thoracic empyema and 1 case of anastomotic leak were found. All the complications ultimately healed. There was no operative mortality. During the follow-up of 3 years, in patients who underwent IORT, 2 of 3 died of radiation pneumonitis 24 and 26 months after IORT with one complicated with bronchoesophageal fistula. One of 3 died of multiple lung metastases. The 3-year survival rate was 88.0% (22/25) in IORT group and 76.0% (19/25) in surgery only group.

CONCLUSIONIntraoperative radiotherapy can reduce locoregional recurrence if performed to thoracic esophageal carcinoma patients without surgical contraindication or distant metastasis. Radiation pneumonitis, a common complication difficult to manage, implies a poor prognosis and, consequently, the lung and bronchus should be protected from the radiation.

Adult ; Aged ; Combined Modality Therapy ; Esophageal Neoplasms ; mortality ; therapy ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Radiotherapy Dosage

PURPOSE: This study was conducted to investigate the prognostic value of lymph node ratio (LNR) in stage II/III breast cancer patients who undergo mastectomy after neoadjuvant chemotherapy. MATERIALS AND METHODS: Clinical and pathological data describing stage II/III breast cancer patients were included in this retrospective study. The primary outcomes were locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS). RESULTS: Among 277 patients, there were 43 ypN0, 64 ypN1, 89 ypN2, and 81 ypN3 cases. Additionally, there were 43, 57, 92 and 85 cases in the LNR 0, 0.01-0.20, 0.21-0.65, and > 0.65 groups, respectively. The median follow-up was 49.5 months. Univariate analysis showed that both ypN stage and LNR were prognostic factors of LRFS, DMFS, DFS, and OS (p < 0.05). Multivariate analysis showed that LNR was an independent prognostic factor of LRFS, DMFS, DFS, and OS (p < 0.05), while ypN stage had no effect on prognosis (p > 0.05). CONCLUSION: The integrated use of LNR and ypN may be suitable for evaluation the prognosis of stage II/III breast cancer patients who undergo mastectomy after neoadjuvant chemotherapy.
Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Drug Therapy* ; Follow-Up Studies ; Humans ; Lymph Nodes* ; Mastectomy* ; Multivariate Analysis ; Neoadjuvant Therapy ; Prognosis* ; Retrospective Studies

BACKGROUND AND OBJECTIVEThe role of postmastectomy radiotherapy (PMRT) in breast cancer patients with T1-T2 tumors and 1-3 positive axillary nodes is still uncertain. This study investigated the value of PMRT for these patients.

METHODSIn the retrospective data of 488 eligible patients, survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using a log-rank test and the Cox proportional hazards model, respectively.

RESULTSThe median observation time was 54 months. The 5- and 10-year locoregional recurrence-free survival (LRFS) rates were 90.8% and 86.9%, respectively. The 5- and 10-year disease-free survival (DFS) rates were 82.0% and 74.3%, respectively. The 5- and 10-year overall survival (OS) rates were 90.7% and 82.7%, respectively. For the 412 patients without PMRT, T2 classification, 2-3 positive nodes, and hormone (estrogen and progesterone) receptor-negative were risk factors for locoregional recurrence in the multivariate analysis. On the basis of these 3 risk factors, the group with 2-3 factors had a 10-year LRFS rate of 63.1% compared with 96.1% for the group with 0-1 factors (P < 0.001). For the group with 2-3 risk factors, LRFS and DFS were significantly improved by PMRT, with the 5- and 10-year LRFS rates without PMRT of 82.4% and 63.1%, respectively, and, with PMRT, of 98.1% at both 5 years and 10 years (P = 0.002). The 5- and 10-year DFS rates without PMRT were 72.0% and 57.6%, respectively, and, with PMRT, the 5- and 10-year DFS rates were 89.4% and 81.7%, respectively (P = 0.007). There was no significant difference in the 10-year OS rates between patients with and without PMRT. However, there is the potential benefit of 15.3% (87.1% vs. 71.8%, P = 0.072). Conversely, the group with 0-1 factors of PMRT had no effect on prognosis.

CONCLUSIONSIn patients receiving mastectomy with T1-T2 breast cancer with 1-3 positive nodes, for the group with 2-3 risk factors, PMRT significantly improved LRFS and DFS and has potential benefit in OS.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; pathology ; radiotherapy ; surgery ; Carcinoma, Lobular ; drug therapy ; pathology ; radiotherapy ; surgery ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Humans ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Radiotherapy, High-Energy ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Retrospective Studies ; Risk Factors ; Survival Rate ; Young Adult