Dynamic changes in gene expression during follicle development and the efficacy of four timed AI protocols in non-suckling female yaks (Bos grunniens).

The objectives of the study were to investigate changes in the mRNA expression levels of five genes during antral follicle development and to assess the efficacy of four timed-artificial insemination (TAI) protocols in female yaks (Bos grunniens). RT-qPCR analysis revealed that expression levels were greater for follicle-stimulating hormone receptor and bone morphogenic protein 15 in the small follicle, luteinizing hormone receptor, and kit ligand in the large follicle, and growth differentiation factor 9 in the medium follicle (p < 0.05). Non-suckling yaks were treated as a 7-d CIDR, and PGF2α + eCG at CIDR withdrawal and TAI with frozen yak semen at 56-58 h after PGF2α (PPe-7d); either a 7-d CIDR (PPG-7d) or a 5-d CIDR (PPG-5d), and PGF2α at CIDR withdrawal and TAI + GnRH at 70-72 h after PGF2α; and GnRH treatment on Day 0, followed by PGF2α on Day 7 and TAI + GnRH on Day 9 (GPG-7d). The results showed that the pregnancy rate (P/AI) was greater in PPG-5d than in GPG-7d (p < 0.05), but the P/AI was not different among the other TAI protocols. In conclusion, the expression levels of these genes in follicles are dynamically changed during antral follicle development in yaks. The PPG-5d protocol achieved a greater P/AI.

Association between Cervical Lymph Node Metastasis and the Incidence of Radiation-Induced Hypothyroidism in Nasopharyngeal Carcinoma.

BACKGROUND: It is controversial and unclear how N-stage would increase the risk of incidence of hypothyroidism (HT) for patients with nasopharyngeal carcinoma (NPC) after radiotherapy. Our study aimed to explore the correlation between cervical lymph node metastasis and the incidence of HT in NPC. MATERIALS AND METHODS: A total of 206 patients with NPC treated at the Cancer Hospital of University of Chinese Academy of Sciences, and their clinical information were retrospectively collected. A series of univariate logistic regression models were performed to explore the association of clinical and lymph node indices with the development of HT. Significant features in univariate analysis were then used to construct three prediction models, for HT prediction using multivariate logistic regression based on Bayesian information criterion. Prediction performance of those models was measured by area under the receiver operating characteristic curve (AUC) using 10-fold cross-validation. RESULTS: A total of 111 patients developed HT, and the incidence of HT in N 2-3 and N 0-1 patients was 58.82% and 44.29%, respectively. Compared to Model 1 (consisted of pretreatment TSH concentration, thyroid volume, and N-stage) whose AUCs were 0.801 and 0.766 in training and validation sets, with N-stage be replaced by shortest distance from thyroid, Model 2 achieved more stable AUCs of 0.824 and 0.801. While with numbers of positive lymph nodes in Level IIb additionally added, Model 3 improved its AUCs to 0.841 and 0.813. CONCLUSION: The shortest distance between the lymph nodes and thyroid gland and the number of lymph nodes in IIb are better predictors of radiation-induced HT than the N-stage.

Research progress of radiation-induced hypothyroidism in head and neck cancer.

This paper reviews the factors related to hypothyroidism after radiotherapy in patients with head and neck cancer to facilitate the prevention of radiation-induced hypothyroidism and reduce its incidence. Hypothyroidism is a common complication after radiotherapy in patients with head and neck cancer, wherein the higher the radiation dose to the thyroid and pituitary gland, the higher the incidence of hypothyroidism. With prolonged follow-up time, the incidence of hypothyroidism gradually increases. Intensity modulated radiotherapy should limit the dose to the thyroid, which would reduce the incidence of hypothyroidism. In addition, the risk factors for hypothyroidism include small thyroid volume size, female sex, and previous neck surgery. The incidence of radiation-induced hypothyroidism in head and neck cancer is related to the radiation dose, radiotherapy technique, thyroid volume, sex, and age. A prospective, large sample and long-term follow-up study should be carried out to establish a model of normal tissue complications that are likely to be related to radiation-induced hypothyroidism.

Hematological Indexes Can Be Used to Predict the Incidence of Hypothyroidism in Nasopharyngeal Carcinoma Patients after Radiotherapy.

BACKGROUND: This study explored the relationship between thyroid-associated antibodies, immune cells, and hypothyroidism to establish a predictive model for the incidence of hypothyroidism in patients with nasopharyngeal carcinoma (NPC) after radiotherapy. METHODS: A total of 170 patients with NPC treated at the Cancer Hospital of University of Chinese Academy of Sciences between January 2015 and August 2018 were included. The complete blood count, biochemical, coagulation function, immune cells, and thyroid-associated antibodies tested before radiotherapy were evaluated. A logistic regression model was performed to elucidate which hematological indexes were related to hypothyroidism development. A predictive model for the incidence of hypothyroidism was established. Internal verification of the multifactor model was performed using the tenfold cross-validation method. RESULTS: The univariate analysis showed that immune cells had no statistically significant differences among the patients with and without hypothyroidism. Sex, N-stage, antithyroid peroxidase antibody (TPO-Ab), antithyroglobulin antibody (TG-Ab), thyroglobulin (TG), and fibrinogen (Fb) were associated with hypothyroidism. Males and early N-stage were protective factors of thyroid function, whereas increases in TPO-Ab, TG-Ab, TG, and Fb counts were associated with an increased rate of hypothyroidism incidence. The multivariate analysis showed that TPO-Ab, TG-Ab, TG, and Fb were independent predictors of hypothyroidism. The comprehensive effect of the significant model, including TPO-Ab, TG-Ab, TG, and Fb counts, represented the optimal method of predicting the incidence of radiation-induced hypothyroidism (AUC = 0.796). Tenfold cross-validation methods were applied for internal validation. The AUCs of the training and testing sets were 0.792 and 0.798, respectively. CONCLUSION: A model combining TPO-Ab, TG-Ab, TG, and Fb can be used to screen populations at a high risk of developing hypothyroidism after radiotherapy.

Circulating Tumor Cells and Fibronectin 1 in the Prognosis of Nasopharyngeal Carcinoma.

OBJECTIVE: Nasopharyngeal carcinoma is highly endemic in Southeast China. Circulating tumor cell is an important biomarker in the prognosis of variety kinds of cancers. Overexpression of fibronectin 1 was observed in variety kinds of malignancies and may contribute to progress and metastasis of the cancers. The current study was aimed to investigate phenotypes of circulating tumor cell in nasopharyngeal carcinoma blood and fibronectin 1 expression in the circulating tumor cell, and their clinical application in predicting nasopharyngeal carcinoma prognosis. METHODS: Blood samples were obtained from nasopharyngeal carcinoma patients before and after treatment. CanPatrol circulating tumor cell enrichment and RNA in situ hybridization were applied to identify circulating tumor cell and its phenotypes. Fibronectin 1 messenger RNA expression in the cells of circulating tumors was examined by messenger RNA-in situ hybridization. RESULTS: Circulating tumor cell was not associated with tumor characteristics or lymph node metastasis. Patients with >9 circulating tumor cells or >5 mesenchymal phenotype circulating tumor cell per 5-mL blood had poorer progression-free survival (P < .05). Multivariable analysis demonstrated that 2 or more mesenchymal phenotype circulating tumor cells with high fibronectin 1 messenger RNA expression predicted shorter progression-free survival (P < .05). CONCLUSIONS: Circulating tumor cells with high-level fibronectin 1 expression was associated with poor survival in patients with nasopharyngeal carcinoma and could be an independent prognostic factor for nasopharyngeal carcinoma.

Thyroid V50 is a risk factor for hypothyroidism in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy: a retrospective study.

BACKGROUND: We investigated the risk factors of radiation-induced thyroid dysfunction, then combined the clinical factors and optimum thyroid dosimetric parameters to predict the incidence rate of hypothyroidism (HT) and to guide individualized treatment. METHODS: A total of 206 patients with histologically proven nasopharyngeal carcinoma (NPC) treated at the Cancer Hospital of the University of Chinese Academy of Sciences between January 2015 and August 2018 were included. Dose-volume histogram (DVH) data, including mean dose, absolute volume, V20, V25, V30, V35, V40, V45, V50, V55, and V60 were extracted and used as dosimetric parameters. A logistic regression analysis model was built to identify predictors related to HT occurring within 2 years. RESULTS: Sex, N stage, thyroid volume, mean thyroid dose, and thyroid V20 and V50 were significantly different between patients with and without HT. Logistic regression analysis showed that N stage, thyroid volume, and thyroid V50 were independent predictors of HT. The radiosensitivity of the thyroid decreased as the thyroid volume increased. Patients with N stage > 1 had significantly higher HT incidence (37.38%) than patients with N stage ≤1 (13.11%). The incidence of HT was 54.55% in patients with thyroid V50 > 24% and was 34.15% in patients with thyroid V50 ≤ 24%. CONCLUSIONS: The incidence of HT is significantly associated with N stage, thyroid volume, and thyroid V50. More attention should be paid to patients with NPC with thyroid volume ≤ 12.82 cm3 and advanced N stage disease.

Phase II trial of recombinant human endostatin in combination with concurrent chemoradiotherapy in patients with stage III non-small-cell lung cancer.

PURPOSE: The objective of this study was to evaluate the efficacy and safety of Endostar combined with concurrent chemoradiotherapy (CCRT) in patients with stage III non-small-cell lung cancer (NSCLC). METHODS: Patients with unresectable stage III NSCLC were treated with Endostar (7.5mg/m(2)/d) for 7days at weeks 1, 3, 5, and 7, while two cycles of docetaxel (65mg/m(2)) and cisplatin (65mg/m(2)) were administered on days 8 and 36, with concurrent thoracic radiation to a dose of 60-66Gy. Primary end points were short-term efficacy and treatment-related toxicity. RESULTS: Fifty patients were enrolled into the study, and 48 were assessable. Of the 48 patients, 83% had stage IIIB and 65% had N3 disease. Median follow-up was 25.0months. Overall response rate was 77%. The estimated median progression-free survival (PFS) was 9.9months, and the estimated median overall survival (OS) was 24.0months. The 1-, 2-, and 3-year local control rates were 75%, 67%, and 51%, PFS rates were 48%, 27%, and 16%, and OS rates were 81%, 50%, and 30%, respectively. All toxicities were tolerable with proper treatment. CONCLUSIONS: The combination of Endostar with CCRT for locally advanced NSCLC patients was feasible and showed promising survival and local control rates.

Five miRNAs as novel diagnostic biomarker candidates for primary nasopharyngeal carcinoma.

MicroRNAs (miRNAs) play an essential role in the development and progression of nasopharyngeal carcinomas (NPC). Despite advances in the field of cancer molecular biology and biomarker discovery, the development of clinically validated biomarkers for primary NPC has remained elusive. In this study, we investigated the expression and clinical significance of miRNAs as novel primary NPC diagnostic biomarkers. We used an array containing 2, 500 miRNAs to identify 22 significant miRNAs, and these candidate miRNAs were validated using 67 fresh NPC and 25 normal control tissues via quantitative real-time PCR (qRT-PCR). Expression and correlation analyses were performed with various statistical approaches, in addition to logistic regression and receiver operating characteristic curve analyses to evaluate diagnostic efficacy. qRT-PCR revealed five differentially expressed miRNAs (miR-93-5p, miR-135b-5p, miR-205-5p and miR-183-5p) in NPC tissue samples relative to control samples (p<0.05), with miR-135b-5p and miR-205-5p being of significant diagnostic value (p<0.01). Moreover, comparison of NPC patient clinicopathologic data revealed a negative correlation between miR-93-5p and miR- 183-5p expression levels and lymph node status (p<0.05). These findings display an altered expression of many miRNAs in NPC tissues, thus providing information pertinent to pathophysiological and diagnostic research. Ultimately, miR-135b-5p and miR-205-5p may be implicated as novel NPC candidate biomarkers, while miR- 93-5p, miR-650 and miR-183-5p may find application as relevant clinical pathology and diagnostic candidate biomarkers.

[Late course conformal radiotherapy combined with chemotherapy for stage III and IV a nasopharyngeal carcinoma].

OBJECTIVE: To evaluate the effect and acute toxicity of late course conformal radiotherapy combined with chemotherapy for stage III and IV a nasopharyngeal carcinoma (NPC). METHODS: Ninety-six patients with stage III and IV a NPC were randomly divided into 2 groups: test group (n = 46, undergoing late course conformal radiotherapy combined with chemotherapy) and control group (n = 50, undergoing conventional radiotherapy). Both groups were treated with one-period chemotherapy, including cisplantin, 5-fluouracil, and calcium folinate, before and after the radiotherapy. The radiotherapy of the test group consisted of 2 phases: 36.0 approximately 40.0 Gy in 18 approximately 20 fractions over 3.5-4 weeks as the first phase using conventional technique was delivered with 2 lateral opposing faciocervical fields, and then 30.0-46.0 Gy in 15-23 fractions over 3-4.5 weeks as the second phase using three-dimensional conformal radiotherapy (3D-CRT). RESULTS: The rates of complete remission (CR), partial remission (PR), and no change (NC) of the test group were 95.65%, 4.35%, and 0, not significantly different from those in the control group (90.00%, 10.00%, and 0, P = 0.287). The 1-year survival rate of the test group was 100%, not significantly different from that of the control group (96.00%, P = 0.170). The nasopharyngeal 1 year control rate of the test group was 97.83%, significantly higher than that of the control group (78.00%, P = 0.03). The distant metastasis rate of the test group was 8.70%, not significantly different from that of the control group (12.00%, P = 0.596). The incidence rates of radiological caries and irradiation-induced otitis media in the test group was 4.25% and 17.39% respectively, both significantly lower than those in the control group (26.00% and 42.00% respectively, P = 0.004 and P = 0.000). There was no significant difference in the incidence of nausea, vomiting, leukopenia, and severity of acute mucositis between these 2 groups. CONCLUSION: Late course conformal radiotherapy combined with chemotherapy effectively improves the disease control, delays the distant metastasis, and alleviates radioactivity damnification.