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Background To investigate the treatment failure pattern and factors influencing locoregional recurrence of esophageal squamous cell carcinoma (ESCC) and examine patient survival with re-irradiation (re-RT) after primary radiotherapy. Methods We retrospectively analyzed 87 ESCC patients treated initially with radiotherapy. Failure patterns were classified into regional lymph node recurrence only (LN) and primary failure with/without regional lymph node recurrence (PF). Patients received either re-RT or other treatments (non-re-RT group). Baseline covariates were balanced by a propensity score model. Overall survival (OS) and toxicities were assessed as outcomes. Results The median follow-up time was 87 months. Thirty-nine patients received re-RT. Failure pattern and re-RT were independent prognostic factors for OS ( P  = 0.040 and 0.015) by Cox multivariate analysis. Re-RT with concomitant chemotherapy showed no survival benefit over re-RT alone ( P  = 0.70). No differences in characteristics were found between the groups by Chi-square tests after propensity score matching. The Cox model showed that failure pattern and re-RT were prognostic factors with hazard ratios (HR) of 0.319 ( P  = 0.025) and 0.375 ( P  = 0.002), respectively, in the matched cohort. Significant differences in OS were observed according to failure pattern ( P  = 0.004) and re-RT ( P  < 0.001). In the re-RT and non-re-RT groups, 9.09% and 3.03% of patients experienced tracheoesophageal fistulas, and 15.15% and 3.03% of patients developed pericardial/pleural effusion, respectively ( P  > 0.05). The incidence of radiation pneumonitis was higher in the re-RT group (24.24% vs. 6.06%, P  = 0.039), but no cases of pneumonia-related death occurred. Conclusions Re-RT improved long-term survival in patients with locoregional recurrent ESCC. Despite a high incidence of radiation pneumonitis, toxicities were tolerable.

To evaluate whether high biologically effective dose (BED) radiotherapy improves local control and survival outcomes for patients with brain metastases (BMs) from small-cell lung cancer (SCLC) and to determine possible prognostic factors. From January 1998 to June 2018, 250 patients with BM from SCLC were retrospectively analyzed. The Cutoff Finder program was used to classify patients by BED. Overall survival (OS) and BM progression-free survival (BM-PFS) were analyzed using the Kaplan-Meier method and log-rank test. A Cox regression model was used to calculate the hazard ratio and 95% CI for prognostic factors for OS among the study population and propensity score (PS)–matched patients. A BED of 47.4 was taken as the optimal cutoff value. Both OS and BM-PFS were significantly improved in the high-BED (>47.4 Gy) than in the low-BED (≤47.4 Gy) group (median OS: 17.5 months vs 9.5 months, P < .001, median BM-PFS: 14.4 months vs 8.3 months, P < .001). Biologically effective dose (P < .001), Eastern Cooperative Oncology Group performance status (P = .047), smoking (P = .005), and pleural effusion (P = .004) were independent prognostic factors for OS. Propensity score matching with a ratio of 1:2 resulted in 57 patients in the high-BED group and 106 patients in the low-BED group. In the PS-matched cohort, OS and BM-PFS were significantly prolonged in the high-BED group compared with the low-BED group (P < .001). Biologically effective dose >47.4 Gy improves survival among patients with BM from SCLC. Eastern Cooperative Oncology Group score, smoking, and pleural effusion independently affect OS of SCLC patients with BM.

Purpose To characterize the pattern of post-mastectomy supraclavicular lymph node (LN) metastases in patients with breast cancer (BC) and to provide insights for individualized clinical target volume delineation for radiotherapy. Methods We retrospectively analyzed 88 patients with BC who developed post-mastectomy regional LN metastases. The affected regional LNs were categorized as the ipsilateral medial supraclavicular LN area (IMSC-LN), ipsilateral lateral supraclavicular LN area (ILSC-LN), ipsilateral infraclavicular LN area (IIC-LN), and ≥2 groups in the ipsilateral clavicular LN area (MMIC-LN). Clinical characteristics were included in a multivariate analysis to identify risk factors for clavicular LN metastases. Results The ILSC-LNs (68.2%) were the most common metastatic site. IMSC-LN metastases showed a significant association with estrogen-receptor (ER) negative status, left-sided BC, and positive axillary LNs. Tumor size ≥2.4 cm and Her2 type were predictors of ILSC-LN metastases. Additionally, tumor size ≥2.4 cm, and level I ipsilateral axillary metastases were associated with MMIC-LN metastasis. Conclusion ILSC-LN was the most frequently affected group of supraclavicular lymph nodes. ER-negative status, left-sided BC, tumor size, and positive ipsilateral axillary LNs are potentially associated with the pattern of supraclavicular LN metastatic involvement.

The impact of adjuvant radiotherapy in pT3N0 rectal cancer is controversial. We aimed to determine the risk factors for cancer‐specific survival (CSS) among these patients and to develop a risk‐stratification system to identify which of these patients would benefit from adjuvant radiotherapy. In this review of the Surveillance, Epidemiology, and End Results database (2010‐2014), we analyzed the data of pT3N0 rectal cancer patients who had not undergone neoadjuvant radiotherapy. Prognostic factors were identified using the Cox proportional hazards model, and risk scores were derived according to the β regression coefficient. A total of 1021 patients were identified from the database search. The overall 5‐year CSS was 86.31%. Multivariate analysis showed that age (P < 0.001), tumor differentiation (P = 0.044), number of nodes resected (P = 0.032), marital status (P = 0.005), and radiotherapy (P = 0.006) were independent prognostic factors for CSS. A risk‐stratification system composed of age, tumor differentiation, and number of nodes resected was generated. Low‐risk patients had better CSS than high‐risk patients (92.13% vs 72.55%, P < 0.001). The addition of radiotherapy to surgery doubled the CSS among the high‐risk patients (42.06% vs 91.26%, P = 0.001) but produced no survival benefit among the low‐risk patients (93.36% vs 96.38%, P = 0.182). Our risk‐stratification model based on age, tumor differentiation, and number of nodes resected predicted the outcomes of pT3N0 rectal cancer patients. This model could help identify patients who may benefit from adjuvant radiotherapy. We define the risk factors for the cancer‐specific survival (CSS) of patients with pT3N0 rectal cancer and develop a risk‐stratification model that would be able to identify which of these patients might benefit from adjuvant radiotherapy.

Pancreatic cancer is characterized by a hypoxic microenvironment and resistance to most currently available treatment modalities. Prolyl hydroxylase domain 3 (PHD3) is a rate-limiting enzyme that regulates the degradation of hypoxia-inducible factors (HIFs) and is deregulated in pancreatic cancer cells. Whether such alteration of PHD3 expression contributes to the sustained growth and radioresistance of pancreatic cancer cells remains largely unknown. PHD3 was overexpressed in pancreatic cancer Mia-paca2 cells via lentiviral expression. Cell cycle progression and apoptosis were assayed by flow cytometry. HIF-1α, EGFR, and PHD3 protein expression was assessed by Western blotting. Cell survival was determined in a colony formation assay. PHD3 overexpression suppressed HIF-1α protein expression and EGFR phosphorylation and enhanced the 2 Gy irradiation-mediated reductions in HIF-1α and phosphorylated (p)-EGFR under either normoxic or hypoxic conditions. PHD3 overexpression inhibited the growth and colony formation of Mia-paca2 cells in response to irradiation under either normoxic or hypoxic conditions. PHD3 overexpression exacerbated irradiation-induced apoptosis, with a greater effect under hypoxia than normoxia. Cell cycle distribution analysis demonstrated that PHD3 overexpression resulted in further shortened S phase and lengthened G2/M phase in response to irradiation. PHD3 expression may contribute to the radiotherapy efficacy of pancreatic cancer cells and serve as a novel biomarker for improving radiotherapy efficacy in pancreatic cancer.

ObjectiveTo evaluate the preventive effect of salvianolate (Sal B) on glucose metabolism disorders of dimethylnitrosamine (DMN)-induced cirrhotic rats.MethodsFifty-five Wistar rats were randomly divided into a control group (n=10) and a cirrhotic group (n=45) according to a random number table. Liver cirrhosis was induced by intraperitoneal administration of DMN. The cirrhotic rats were divided into model, Sal B and metformin groups (n=15), respectively. Rats in the model group were given saline, two treatment groups were given Sal B (50 mg/kg), metformin (150 mg/kg) respectively for 28 consecutive days, while rats in the control group were injected 0.9% saline with same volume of vehicle. Body weight was measured everyday. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp. Organ index, glucose tolerance test (OGTT), and fasting plasma glucose (FPG), fasting insulin (FINS), hepatic glycogen, hydroxyproline (HYP) and liver function were detected at the end of the treatment. Area under the curve (AUC) for OGTT was calculated. Liver and pancreas histology were determined by histopathological examination with hematoxylin and eosin staining (HE), Sirius Red staining and Masson’s trichrome staining, respectively. Hepatic expression of α-smooth muscle actin (α-SMA) and collagen (Col I) were evaluated by immunohistochemical staining.ResultsCompared with the model group, Sal B significantly increased body and liver weight, liver-body ratio, glucose infusion rate (GIR), FPG, FINS levels and hepatic glycogen at the end of administration (P<0.05 or P<0.01). Meanwhile, Sal B significantly decreased AUC for OGTT, spleen weight, spleen-body ratio, aminotransferase and HYP level (P<0.05 or P<0.01). Sal B was also effective in alleviating necrosis of liver tissue, suppressing fibrosis progression and inhibiting the expression of α-SMA and Col I in liver. Compared with the metformin group, Sal B had advantages in ameliorating FPG, hepatic glycogen, spleen weight, organ index, liver function and cirrhosis (P<0.05). Metformin increased insulin sensitivity more potently than Sal B (P<0.05).ConclusionsSal B could improve glucose metabolism in cirrhotic rats by protecting hepatic glycogen reserve, increasing insulin sensitivity, and alleviating pancreatic morphology abnormalities. Sal B was clinically potential in preventing glucose metabolism anomalies accompanied with cirrhosis.

Studying on resistance specificity of human acupoints is one of the major subjects in the research on acupoint specificity. Even since a long time ago, many methods have been put forward in the detection of acupoint resistance specificity. From the vertical lengthways of the acupoint structure, the methods and means are put forward to detect the acupoint resistance in a series of studies. In the studies, some peculiar phenomena are found out in the detection of the acupoint resistance, and some phenomena are interrelated with the volume conductor characteristics of the human body, and some phenomena might be interrelated with the detecting methods and means. By the summary and analysis of those peculiar phenomena, references are offered to the relevant researchers engaged in the detection of the acupoint resistance.

Purpose: Pancreatic cancer is characterized by a hypoxic microenvironment and resistance to most currently available treatment modalities. Prolyl hydroxylase domain 3 (PHD3) is a rate-limiting enzyme that regulates the degradation of hypoxia-inducible factors (HIFs) and is deregulated in pancreatic cancer cells. Whether such alteration of PHD3 expression contributes to the sustained growth and radioresistance of pancreatic cancer cells remains largely unknown. Materials and methods: PHD3 was overexpressed in pancreatic cancer Mia-paca2 cells via lentiviral expression. Cell cycle progression and apoptosis were assayed by flow cytometry. HIF-1[alpha], EGFR, and PHD3 protein expression was assessed by Western blotting. Cell survival was determined in a colony formation assay. Results: PHD3 overexpression suppressed HIF-1[alpha] protein expression and EGFR phosphorylation and enhanced the 2 Gy irradiation-mediated reductions in HIF-1 [alpha] and phosphorylated (p)-EGFR under either normoxic or hypoxic conditions. PHD3 overexpression inhibited the growth and colony formation of Mia-paca2 cells in response to irradiation under either normoxic or hypoxic conditions. PHD3 overexpression exacerbated irradiation-induced apoptosis, with a greater effect under hypoxia than normoxia. Cell cycle distribution analysis demonstrated that PHD3 overexpression resulted in further shortened S phase and lengthened G2/M phase in response to irradiation. Conclusion: PHD3 expression may contribute to the radiotherapy efficacy of pancreatic cancer cells and serve as a novel biomarker for improving radiotherapy efficacy in pancreatic cancer. Keywords: pancreatic cancer, PHD3, radiotherapy efficacy, HIF-1[alpha], p-EGFR

MicroRNAs （miRNAs） are endogenous noncoding RNAs （-22 nt） that regulate target gene expression at the posttranscriptional level in the cytoplasm. Recent discoveries of the presence of miRNAs and miRNA function-required argonaute family proteins in the cell nucleus have prompted us to hypothesize that miRNAs may also have regulatory functions in the cell nucleus. In this study, we demonstrate that mouse miR-709 is predominantly located in the nucleus of various cell types and that its nuclear localization pattern rapidly changes upon apoptotic stimuli. In the cell nucleus, miR-709 directly binds to a 19-nt miR-709 recognition element on pri-miR-15a/16-1 and prevents its processing into pre-miR-15a/16-1, leading to a suppression of miR-15a/16-1 maturation. Furthermore, nuclear miR- 709 participates in the regulation of cell apoptosis through the miR-15a/16-1 pathway. In summary, the present study provides the first evidence that one miRNA can control the biogenesis of other miRNAs by directly targeting their primary transcripts in the nucleus.

Previous studies of animal models of chronic mechanical compression of the spinal cord have mainly focused on cervical and thoracic lesions, but few studies have investigated thoracolumbar injury. The specific pathophysiological mechanism of chronic thoracolumbar cord injury has not yet been elucidated. The purpose of this study was to improve animal models of chronic thoracolumbar cord compression using the progressive screw. A custom-designed flat plastic screw was implanted in the spinal cord between thoracic vertebrae 12 and lumbar 1 of rats. The screw was tightened one complete turn（0.5 mm） every 7 days for 4 weeks to create different levels of chronic spinal cord compression. Following insertion of the screw, there was a significant decline in motor function of the hind limbs, and severe stenosis of micro-computed tomography parameters in the spinal cord. Cortical somatosensory evoked potential amplitudes were reduced remarkably, and latencies were prolonged at 30 minutes after surgery. The loss of motor neurons in the gray matter was marked. Demyelination and cavitation were observed in the white matter. An appropriate rat model of chronic thoracolumbar cord compression was successfully created using the progressive screw compression method, which simulated spinal cord compression injury.