Nickel-Catalyzed Hydroamination and Hydroalkoxylation of Enelactams with Unactivated Amines and Alcohols.

Nickel-catalyzed hydroamination and hydroalkoxylation of enelactams with unactivated amines and alcohols are reported. This method showed good functional group tolerance and delivered the corresponding hydrofunctionalized products in good to excellent yields (≤98%). Furthermore, an intramolecular hydroalkoxylation of an enelactam was also realized, giving a cyclization product in a good yield. Mechanistic studies indicated that tBuI acts as a hydride donor and radical precursor, which is crucial for the success of the reaction.

Efficacy and safety of transarterial chemoembolization with CalliSpheres® Microspheres in head and neck cancer.

Objective: Transarterial chemoembolization with CalliSpheres® Microspheres (CSM-TACE) presents favorable efficacy and tolerable safety in several cancers, while its application in head and neck cancer (HNC) is unclear. Thus, the current pilot study aims to evaluate the efficacy and safety of CSM-TACE in treating HNC. Methods: A total of 15 HNC patients receiving CSM-TACE at the Second Affiliated Hospital of Dalian Medical University from March 2017 to December 2021 were enrolled in this study. Moreover, treatment information, treatment response, progression-free survival (PFS), overall survival (OS), changes in liver and renal function indices, and adverse events were recorded. Results: There were nine patients receiving CSM-TACE as first-line treatment and six patients receiving CSM-TACE as second- or above-line treatment; meanwhile, there were seven, seven, and one patient undergoing one time, two times, and three times of CSM-TACE, respectively. Furthermore, the objective response rate (ORR) and the disease control rate (DCR) were 60.0% and 100%, respectively, at the first month; meanwhile, the ORR and the DCR were 53.3% and 73.3%, respectively, at the second month. Moreover, the 1-year PFS rate was 34.1%, and the 1-year OS rate was 38.9%. Additionally, no change in liver function indices (namely, total protein, albumin, total bilirubin, alanine aminotransferase, and aspartate aminotransferase) or in renal function indices (namely, creatinine and blood urea nitrogen) was found before and 1 month after treatment (all P > 0.05). Meanwhile, no severe adverse events were found during and after CSM-TACE. Conclusion: CSM-TACE illustrates favorable treatment response and survival benefits as well as a tolerable safety profile in HNC patients.

Clinical Effect of Digital Subtraction Angiography Combined with Neurointerventional Thrombolysis for Acute Ischemic Cerebrovascular Disease and Its Influence on Vascular Endothelial Function and Oxidative Stress.

Objective: Ischemic cerebrovascular disease is a commonly seen vascular disorder in clinical practice. Given the difficulty of drug therapy to achieve ideal curative effects, interventional therapy has gradually become the preferred treatment for the disease. This research primarily discusses the short-term efficacy of digital subtraction angiography- (DSA-) guided neurointerventional thrombolysis for acute ischemic cerebrovascular disease (AICVD) and its influence on vascular endothelial function (VEF) and oxidative stress (OS). Methods: All the clinical data of 162 patients diagnosed with AICVD and treated between June 2019 and December 2021 were collected and analyzed retrospectively. They were assigned to two cohorts according to the difference in interventional methods: a conventional group (CG) given recombinant tissue plasminogen activator (rt-PA) therapy and an observation group (OG) intervened by DSA-guided neurointerventional thrombolysis. The two groups were compared with respect to short-term treatment efficacy, the National Institutes of Health Stroke Scale (NIHSS) score, cerebral hemodynamics, and VEF and OS indexes. Results: The short-term efficacy was better in OG (93.98%) than in CG (82.28%). After treatment, the NIHSS score decreased in both cohorts with obvious differences within the group at different time points, and the posttreatment NIHSS score was lower in OG as compared to CG. OG had higher Q m and V m while lower W v, Z cv, and R v than CG. Higher endothelial-dependent flow-mediated dilatation (FMD) was observed in OG, as well as lower ankle-brachial index (ABI) and pulse wave velocity (PWV). And the posttreatment MDA was lower while SOD, GSH-Px, and TAC were higher in OG compared with those on CG. All the above differences were of statistical significance (P < 0.05). Conclusions: DSA-guided neurointerventional thrombolysis is highly effective in the treatment of AICVD, which can not only effectively improve patients' neurological function and cerebral hemodynamics but also mitigate VEF injury and help to alleviate patients' OS.

Study on the expression of p53 and MMP-2 in patients with lung cancer after interventional therapy.

The aim of the study was to investigate the expression of tumor suppressor gene p53 and MMP-9 in non-small cell lung cancer (NSCLC) before and after chemotherapy, and investigate its association with the effect of chemotherapy and prognosis. Fifty-eight elderly NSCLC patients comprised the observation group. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of p53 and MMP-9 in lung cancer tissues before and after chemotherapy. Immunohistochemistry and western blot analysis were used to detect the expression of p53 and MMP-9 proteins in NSCLC tissue before and after chemotherapy. Terminal deoxynucleotidyl transferase nick end-labeling (TUNEL) was used to detect apoptotic cells. The association between the effect of chemotherapy and the expression of p53 and MMP-9 in lung cancer tissues was analysed. RT-qPCR results showed that the expression of p53 and MMP-2 mRNA in the tumor tissue after chemotherapy was significantly lower than that in the tumor tissue before chemotherapy. Western blot analysis revealed that the expression of p53 and MMP-2 protein in the tumor tissue after chemotherapy was significantly decreased. The positive expression of p53 and MMP-2 in lung cancer tissues before chemotherapy was 76.25 and 71.25%, respectively, and were reduced to 27.50 and 23.75%, respectively, after chemotherapy. After chemotherapy, the positive rates of p53 and MMP-2 were significantly lower than those before chemotherapy. TUNEL results showed that the apoptosis index increased significantly after chemotherapy. Efficiency of chemotherapy in patients with a negative expression of p53 and MMP-2 in lung cancer before chemotherapy was significantly higher than that in patients with a positive p53 and MMP-2 expression. A significant difference was found in the expression levels of p53 and MMP-2 in lung cancer before and after chemotherapy. The findings of the present study indicate that the expression levels of p53 and MMP-2 can be used as a predictor of chemotherapy sensitivity.

4-Hydroxybenzoic acid (4-HBA) enhances the sensitivity of human breast cancer cells to adriamycin as a specific HDAC6 inhibitor by promoting HIPK2/p53 pathway.

Breast cancer is reported a very complex disease along with heterogeneous morphological characteristics and unrelated clinical behavior, and is a leading cancer among female. Nevertheless, chemo-resistance is frequently observed. Adriamycin (ADM) is a always employed drug to treat clinical breast cancer. However, strong resistance to ADM limited its clinical efficacy. Deregulation of HDAC6 activity is linked to various diseases including cancer resulting in accumulating interest for developing HDAC6 inhibitors. In the present study, for the first time, we found that 4-Hydroxybenzoic acid (4-HBA), as histone deacetylase 6 (HDAC6) inhibitor, could successfully reverse ADM resistance in human breast cancer cells. 4-HBA significantly promoted the anticancer effect of ADM on apoptosis induction, as evidenced by the increased expressions of Caspase-3 and PARP cleavage, which was associated with the promotion p53 and homeodomain interacting protein kinase-2 (HIPK2) expressions in ADM-resistant breast cancer cells. Furthermore, the suppressive effect of ADM on drug-resistant breast cancer cells was accelerated by 4-HBA through increasing the number of cells distributed in G2/M phase of cell cycle arrest. Inhibiting HIPK2/p53 pathway could abolish 4-HBA/ADM co-treatment-induced apoptosis and G2/M cell cycle arrest. Importantly, HDAC6 expressions were also significantly down-regulated in ADM-resistance breast cancer cells co-treated with ADM and 4-HBA. Additionally, 4-HBA clearly potentiated the anticancer role of ADM in the MCF-7 breast cancer animal model with low toxicity. Therefore, 4-HBA could be applied as an effective HDAC6 inhibitor to reverse human breast cancer resistance. Herein, the 4-HBA and ADM combination might represent as a useful therapeutic strategy to prevent human breast cancer.

Endovascular stent graft repair of aortogastric fistula caused by peptic ulcer after esophagectomy: A case report.

RATIONALE: Aortogastric fistula (AGF) is a rare but devastating clinical complication after esophagectomy. In a recent report, nearly all AGF patients died of massive hemorrhage or aspiration of massive hematemesis. Therefore, timely appropriate treatment of AGF remains a challenge.Herein, we report a case of AGF that resulted from peptic ulceration after esophagectomy and was successfully treated with endovascular stent graft placement. PATIENT CONCERNS: A 59-year-old man had undergone video-assisted thoracoscopic esophagectomy for squamous cell carcinoma and esophageal reconstruction using a gastric tube 14 months previously. He suddenly experienced massive hematemesis and unstable circulatory dynamics, Infusion was performed to treat critical hemorrhagic shock but was ineffective. We informed the patient and his family members of the situation, and once written informed consent to treatment was provided, we rushed him to the operating room. DIAGNOSES: Contrast medium permeated into the gastric cavity through a fistula between the abdominal aorta and gastric tube at the 11th thoracic level, Based on this, we made a diagnosis of AGF resulting from a peptic ulcer, and this diagnosis was further confirmed by high pressure angiography combined with computed tomography (CT) imaging. INTERVENTIONS: An endovascular stent graft was placed under the guidance of digital subtraction angiography and followed by antibiotic therapy to prevent infection and proton pump inhibitor therapy to inhibit gastric acid secretion. OUTCOMES: The patient recovered uneventfully after the procedure. Four months after surgery, the patient died of organ failure caused by retroperitoneal lymph node metastasis and multiple intrahepatic metastases, with no postoperative bleeding linked to the endovascular stent graft repair. LESSONS: Our case supports the notion that endovascular stent graft repair is a feasible alternative in treatment of AGF with several advantages in addition to surgical intervention, although more such cases should be collected and analyzed in the future to corroborate our observations.