Identification of differentially expressed genes associated with the enhancement of X-ray susceptibility by RITA in a hypopharyngeal squamous cell carcinoma cell line (FaDu).

BACKGROUND: Next generation sequencing and bio-informatic analyses were conducted to investigate the mechanism of reactivation of p53 and induction of tumor cell apoptosis (RITA)-enhancing X-ray susceptibility in FaDu cells. MATERIALS AND METHODS: The cDNA was isolated from FaDu cells treated with 0 X-ray, 8 Gy X-ray, or 8 Gy X-ray + RITA. Then, cDNA libraries were created and sequenced using next generation sequencing, and each assay was repeated twice. Subsequently, differentially expressed genes (DEGs) were identified using Cuffdiff in Cufflinks and their functions were predicted by pathway enrichment analyses. Genes that were constantly up- or down-regulated in 8 Gy X-ray-treated FaDu cells and 8 Gy X-ray + RITA-treated FaDu cells were obtained as RITA genes. Afterward, the protein-protein interaction (PPI) relationships were obtained from the STRING database and a PPI network was constructed using Cytoscape. Furthermore, ClueGO was used for pathway enrichment analysis of genes in the PPI network. RESULTS: Total 2,040 and 297 DEGs were identified in FaDu cells treated with 8 Gy X-ray or 8 Gy X-ray + RITA, respectively. PARP3 and NEIL1 were enriched in base excision repair, and CDK1 was enriched in p53 signaling pathway. RFC2 and EZH2 were identified as RITA genes. In the PPI network, many interaction relationships were identified (e.g., RFC2-CDK1, EZH2-CDK1 and PARP3-EZH2). ClueGO analysis showed that RFC2 and EZH2 were related to cell cycle. CONCLUSIONS: RFC2, EZH2, CDK1, PARP3 and NEIL1 may be associated, and together enhance the susceptibility of FaDu cells treated with RITA to the deleterious effects of X-ray.

[Long-term results of personalized treatment in 72 breast cancer patients who failed chemotherapy].

OBJECTIVE: To evaluate the efficacy and prognostic factors of personalized treatment for breast cancer patients who failed chemotherapy. METHODS: Seventy-two patients with breast cancer who failed chemotherapy were treated at the Tumor Hospital of Harbin Medical University from January 2001 to January 2012. Among them, 42 cases received 5.6 cycles (range, 4-8 cycles) of postoperative adjuvant chemotherapy, and 30 cases received 12.2 cycles (range, 6-22 cycles), both postoperative adjuvant and salvage chemotherapy. All of the 72 patients of stage IV were given personalized treatment. Under guidance of the principle that multidisciplinary treatment improves control rate but does not or less damage the normal tissues and host immune function, precise radiotherapy combined with Chinese herbal medicine (CHM), biological agent and others were chosen for the patients. RESULTS: The median survival time was 20 months. Univariate analysis showed that non-invasive ductal carcinoma, less metastasized organs, without brain, liver and lung metastasis, Karnofsky performance scores ≥ 80, not combined with chemotherapy, and multiple courses of Chinese herbal medicine and biolojical agent treatment had significant impact on survival (P < 0.05). Multivariate analysis showed that no brain metastasis, non-invasive ductal carcinoma, and Chinese herbal medicine and biological agent treatment ≥ 7 courses and not combined with chemotherapy had obvious significance (P < 0.05). The rate of grade 3 and 4 treatment-related hematological toxicity was 8.3% (6/72) and 5.6% (4/72), respectively. All the patients with grade 4 hematological toxicity were the cases of grade 3 at hospital admission. No grade 3 and 4 acute radiation damages of the lung and liver were noticed. CONCLUSION: Chinese herbal medicine combined with biological agents and others prolongs survival time in breast cancer patients who failed chemotherapy, and provides an alternative treatment modality for them.

Association between preoperative serum myoglobin and acute kidney injury after Stanford Type A aortic dissection surgery.

BACKGROUND: Acute kidney injury (AKI) is a common complication after Type A aortic dissection (TAAD) surgery, and it is associated with poor outcomes. The nephrotoxic effect of myoglobin was established, but its correlation with AKI following TAAD repair still lacks sufficient evidence. We clarified the correlation between preoperative serum myoglobin (pre-sMyo) concentrations and AKI after TAAD surgery. METHOD: A retrospective analysis was performed on the perioperative data of 382 patients treated with TAAD surgery at Beijing Anzhen Hospital. AKI was defined and classified according to the criteria established by the Kidney Disease: Improving Global Outcomes Acute Kidney Injury Work Group. We attempted to determine the correlation between pre-sMyo concentrations and postoperative AKI. RESULTS: The incidences of Stage 1, 2, and 3 AKI were 37.3 % (57/153), 23.5 % (36/153), and 39.2 % (60/153), respectively. The pre-sMyo concentrations of the AKI group were significantly increased than the non-AKI group [43.1 (21.4, 107.5) vs 26.4 (18.0, 37.2), P < 0.001]. Pre-sMyo concentrations have a linear correlation with preoperative renal function-related indicators. The multivariable logistic regression analysis showed that Ln (pre-sMyo) was an independent risk factor for AKI. When the pre-sMyo concentration was at the fourth quartile [109.3 (64.8, 213.4) ng/ml], the risk of developing any-stage and severe AKI was significantly increased (OR = 4.333, 95 % CI: 2.364-7.943, P < 0.001; OR = 3.862, 95 %, CI: 2.011-7.419, P < 0.001). This difference persisted after adjustment (OR = 3.830, 95 % CI: 1.848-7.936, P < 0.001; OR = 2.330, 95 % CI: 1.045-5.199, P = 0.039). Furthermore, pre-sMyo concentrations were not affected by lower limb malperfusion, myocardial malperfusion, and cardiac tamponade. CONCLUSIONS: Increased pre-sMyo concentrations correlated with postoperative AKI in TAAD, which may increase the risk of developing any-stage AKI and severe AKI after TAAD surgery.

Anzhen Risk Evaluation System for Acute Aortic Syndrome (AZSCORE-AAS): protocol for a multicentre prospective cohort study in northern China.

INTRODUCTION: Acute aortic syndrome (AAS) is a group of acute and critical conditions, including acute aortic dissection (AAD), acute intramural haematoma and penetrating aortic ulcer. High mortality and morbidity rates result in a poor patient prognosis. Prompt diagnoses and timely interventions are paramount for saving patients' lives. In recent years, risk models for AAD have been established worldwide; however, a risk evaluation system for AAS is still lacking in China. Therefore, this study aims to develop an early warning and risk scoring system in combination with the novel potential biomarker soluble ST2 (sST2) for AAS. METHODS AND ANALYSIS: This multicentre, prospective, observational study will recruit patients diagnosed with AAS at three tertiary referral centres from 1 January 2020 to 31 December 2023. We will analyse the discrepancies in sST2 levels in patients with different AAS types and explore the accuracy of sST2 in distinguishing between them. We will also incorporate potential risk factors and sST2 into a logistic regression model to establish a logistic risk scoring system for predicting postoperative death and prolonged intensive care unit stay in patients with AAS. ETHICS AND DISSEMINATION: This study was registered on the Chinese Clinical Trial Registry website (http://www. chictr. org. cn/). Ethical approval was obtained from the human research ethics committees of Beijing Anzhen Hospital (KS2019016). The ethics review board of each participating hospital agreed to participate. The final risk prediction model will be published in an appropriate journal and disseminated as a mobile application for clinical use. Approval and anonymised data will be shared. TRIAL REGISTRATION NUMBER: ChiCTR1900027763.

Blood Transfusion Predicts Prolonged Mechanical Ventilation in Acute Stanford Type A Aortic Dissection Undergoing Total Aortic Arch Replacement.

Background: This research aimed to evaluate the impacts of transfusing packed red blood cells (pRBCs), fresh frozen plasma (FFP), or platelet concentrate (PC) on postoperative mechanical ventilation time (MVT) in patients with acute Stanford type A aortic dissection (ATAAD) undergoing after total arch replacement (TAR). Methods: The clinical data of 384 patients with ATAAD after TAR were retrospectively collected from December 2015 to October 2017 to verify whether pRBCs, FFP, or PC transfusion volumes were associated with postoperative MVT. The logistic regression was used to assess whether blood products were risk factors for prolonged mechanical ventilation (PMV) in all three endpoints (PMV ≥24 h, ≥48 h, and ≥72 h). Results: The mean age of 384 patients was 47.6 ± 10.689 years, and 301 (78.39%) patients were men. Median MVT was 29.5 (4-574) h (h), and 213 (55.47%), 136 (35.42%), and 96 (25.00%) patients had PMV ≥24 h, ≥48 h, and ≥72 h, respectively. A total of 36 (9.38%) patients did not have any blood product transfusion, the number of patients with transfusion of pRBCs, FFP, and PC were 334 (86.98%), 286 (74.48%), and 189 (49.22%), respectively. According to the multivariate logistic regression of three PMV time-endpoints, age was a risk factor [PMV ≥ 24 h odds ratio (OR PMV≥24) = 1.045, p = 0.005; OR PMV≥48 = 1.060, p = 0.002; OR PMV≥72 = 1.051, p = 0.011]. pRBC transfusion (OR PMV≥24 = 1.156, p = 0.001; OR PMV≥48 = 1.156, p < 0.001; OR PMV≥72 = 1.135, p ≤ 0.001) and PC transfusion (OR PMV≥24 = 1.366, p = 0.029; OR PMV≥48 = 1.226, p = 0.030; OR PMV≥72 = 1.229, p = 0.011) were independent risk factors for PMV. FFP had no noticeable effect on PMV [OR PMV≥48 = 0.999, 95% confidence interval (CI) 0.998-1.000, p = 0.039; OR PMV≥72 = 0.999, 95% CI: 0.998-1.000, p = 0.025]. Conclusions: In patients with ATAAD after TAR, the incidence of PMV was very high. Blood products transfusion was closely related to postoperative mechanical ventilation time. pRBC and PC transfusions and age increased the incidence of PMV at all three endpoints.

Early and Long-Term Follow-Up for Chronic Type B and Type Non-A Non-B Aortic Dissection Using the Frozen Elephant Trunk Technique.

Background: This study aimed to evaluate the early and long-term outcomes of a single center using a frozen elephant trunk (FET) procedure for chronic type B or non-A non-B aortic dissection. Methods: From February 2009 to December 2019, 79 patients diagnosed with chronic type B or non-A non-B aortic dissection who underwent the FET procedure were included in the present study. We analyzed operation mortality and early and long-term outcomes, including complications, survival and interventions. Results: The operation mortality rate was 5.1% (4/79). Spinal cord injury occurred in 3.8% (3/79), stroke in 2.5% (2/79), and acute renal failure in 5.1% (4/79). The median follow-up time was 53 months. The overall survival rates were 96.2, 92.3, 88.0, 79.8, and 76.2% at 1/2, 1, 3, 5 and 7 years, respectively. Moreover, 79.3% of patients did not require distal aortic reintervention at 7 years. The overall survival in the subacute group was superior to that in the chronic group (P = 0.047). Conclusion: The FET technique is a safe and feasible approach for treating chronic type B and non-A non-B aortic dissection in patients who have contraindications for primary endovascular aortic repair. The technique combines the advantages of both open surgical repair and endovascular intervention, providing comparable early and long-term follow-up outcomes and freedom from reintervention.

Comparison of Open Repair vs. the One-Stage Hybrid Extra-Anatomic Technique for Distal Aortic Arch Disease Treatment: Mid-term Outcomes With a Risk-Adjusted Analysis.

Objective: This study aims to compare the short- and mid-term outcomes of the stented elephant trunk (SET) procedure combined with supra-arch branch reconstruction and one-stage hybrid arch repair combined thoracic endovascular aortic repair (TEVAR) with extra-anatomic bypass in the management of distal arch disease. Methods: From January 2009 to January 2019, 97 patients underwent one-stage hybrid arch repair combined with TEVAR with extra-anatomic bypass (HAR group), and 206 patients underwent the SET procedure with supra-arch branch reconstruction (SET group). We used inverse-probability-of treatment weighting (IPTW) to adjust baseline differences. Results: Before IPTW adjustment, there was no significant difference in operative mortality between the two groups (5.2 vs. 1.0%, P = 0.064). The incidences of stroke, spinal cord injury (SCI), acute kidney injury (AKI), and endoleak also showed no significant differences (4.1 vs. 0.5%, P = 0.066; 2.1 vs. 1.5%, P = 1.000; 0 vs. 1.0%, P = 0.831; 6.2 vs. 1.9%, P = 0.113, respectively). After IPTW adjustment, the incidences of stroke, SCI, and AKI showed no significant differences between the two groups (1.8 vs. 1.1%, P = 0.138; 0.8 vs. 1.6%, P = 0.448; and 0 vs. 0.7%, P = 0.148, respectively). However, the HAR group tended to have higher operative mortality and incidence of endoleak than the SET group (12.4 vs. 1.3%, P = 0.01; 9.9 vs. 1.8%, P = 0.031, respectively). In the multivariate analysis, open repair decreased the risks of endoleak (odds ratio [OR], 0.171, 95% CI, 0.060-0.401; P < 0.001) and operative mortality (OR, 0.093, 95% CI, 0.027-0.238; P < 0.001). The overall survival and event-free survival of the HAR group were significantly lower than those of the SET group (P < 0.001). Conclusion: One-stage hybrid arch repair combined TEVAR with extra-anatomic bypass and the SET procedure with supra-arch branch reconstruction both provided good postoperative treatment outcomes for distal arch disease. However, hybrid arch repair increased the risks of endoleak and operative mortality. The SET procedure provided better mid-term survival than hybrid arch repair without increasing operative mortality. Carefully selecting the indications for the procedure, while receiving close long-term follow-up, may improve the survival rate of patients undergoing hybrid arch repair.