Progress in the development of nanosensitizers for X-ray-induced photodynamic therapy.

In recent years, photodynamic therapy has been applied in cancer treatment because of its high selectivity and marginal invasion properties. However, the excitation light used has limited ability to penetrate tissue, which creates a stumbling block for its future development. To overcome this, X-rays have been introduced to transmit energy to deeper tissues. Given that a large number of X-ray-induced sensitizers have been designed to facilitate X-ray excitation and generate reactive oxygen species (ROS), this has led to the concept of X-ray-induced photodynamic therapy (X-PDT). After 10 years of development, this treatment now shows good therapeutic effects as well as shortcomings. Going forward, it will be important to improve tumor targeting and a standard deep-seated tumor model should be established.

Tissue-specific significance of BAP1 gene mutation in prognostic prediction and molecular taxonomy among different types of cancer.

BAP1 is an emerging tumor suppressor whose inactivating mutations have been found to play critical roles in tumor development. This study was conducted to elucidate the potential value of BAP1 mutation in guiding prognostic prediction and clinical stratification. We conducted a comprehensive analysis of relevant studies from multiple databases, to determine the impact of BAP1 mutation on the overall survival and disease-free survival of patients in various cancers. A total of 2457 patients from 21 studies were included in the final analysis. Although the pooled results demonstrated that BAP1 mutation was a negative indicator of overall survival (hazard ratio = 1.73; 95% confidence interval = 1.23-2.42) and disease-free survival (hazard ratio = 2.25; 95% confidence interval = 1.47-3.45), this prognostic value was only applicable to uveal melanoma and clear cell renal cell carcinoma, but not to malignant pleural mesothelioma or cholangiocarcinoma. Consistently, BAP1 mutation was correlated with critical clinicopathological features only in uveal melanoma and clear cell renal cell carcinoma. In uveal melanoma, BAP1 mutation and SF3B1/EIF1AX mutations were negatively correlated, and BAP1-mutant tumors indicated significant worse prognosis than SF3B1/EIF1AX-mutant tumors ( p = 0.028). While in clear cell renal cell carcinoma, BAP1 mutation was mutually exclusive with PBRM1 mutations, and BAP1-mutant clear cell renal cell carcinomas also showed significantly worse prognosis than PBRM1-mutant clear cell renal cell carcinomas ( p = 0.001). Our study revealed a unique tissue-specific significance of BAP1 mutation in prognostic prediction among different types of cancer. Clinically, combining detection of BAP1 mutation and other driver mutations may further allow for a more precise molecular taxonomy to stratify patients into distinct subgroups in uveal melanoma and clear cell renal cell carcinoma.

[Isoflurance-based intravenous and inhalation combined anesthesia versus low-dose-ketamine-based total intravenous anesthesia for valvuloplasty in minipigs].

OBJECTIVE: To compare the effectiveness of anesthesia between Isoflurane-based intravenous and inhalant combined approach and low-dose-ketamine-based total intravenous approach for valvuloplasty in minipigs. METHODS: Twenty four minipigs were given 3-5 mg/kg ketamine intramuscularly and 15-20 mg/kg pentobarbital intravenously for anesthetic induction and intubation. They were then randomly divided into two groups, each with 12 minipigs. In group I (isoflurane), the minipigs received isoflurane 1.0-2.0 minimum alveolar concentration (MAC), fentanyl 20-25 microg/(kg x h), midazolam 0.1-0.2 mg/(kg x h) and pipecuronium 0.10-0.15 mg/(kg x h) for maintenance. In group K (ketamine), the minipigs were given ketamine 3-5 mg/(kg x h), pentobarbital 8-10 mg/(kg x h) and pipecuronium 0. 10-0.15 mg/(kg x h) intravenously. The general peri-operation characteristics were recorded. Hemodynamics, blood gas and respirations were monitored. Anesthetic complications were observed. RESULTS: Two minipigs died from causes other than anesthesia. The minipigs in group I had lower mean aortic pressure (MAP) than those in group K during cardiopulmonary bypass (CPB), but without a statistical significance. The minipigs in group I had significantly lower levels of lactic acid than those in group K after CPB cessation (P < 0.05). The times on analepsia were (21.6 +/- 4.1) min and (67.8 +/- 8.5) min for group I and group K, respectively. The times on ventilator were (281.3 +/- 34.7) min and (330.4 +/- 27.0) min for group I and group K, respectively. The differences were significant (P < 0.05). One minipig in group K was intubated for espiratory depression after surgery. CONCLUSION: The isoflurane-based intravenous and inhalant combined anesthesia was preferable for valvular reparation in minipigs. However, low-dose-ketamine-based total intravenous anesthesia is also a good choice in the circumstance of limited resources.