Advances in two-photon absorption photodynamic therapy of glioma based on porphyrin-based metal-organicframework composites.

Gliomas of the brain are characterised by high aggressiveness, high postoperative recurrence rate, high morbidity and mortality, posing a great challenge to clinical treatment. Traditional treatments include surgery, radiotherapy and chemotherapy; they also have significant associated side effects, leading to difficulties in tumour resection and recurrence. Photodynamic therapy has been shown to be a promising new strategy to help treat malignant tumours of the brain. It irradiates the tumour site at a specific wavelength to activate a photosensitiser, which selectively accumulates at the tumour site, triggering a photochemical reaction that destroys the tumour cells. It has the advantages of being minimally invasive, highly targeted and with few adverse reactions, and is expected to be well used in anti-tumour therapy. However, the therapeutic effect of traditional PDT is limited by the weak tissue penetration ability of photosensitiser, hypoxia and immunosuppression in the tumour microenvironment. This paper reviews the current research status on the therapeutic principle of photodynamic therapy in glioma and the mechanism of tumour cell injury, and also analyses the advantages and disadvantages of the current application in glioma treatment, and clarifies the analysis of ideas to improve the tissue penetration ability of photosensitizers. It aims to provide a feasible direction for the improvement of photodynamic therapy for glioma and a reference for the clinical treatment of deep brain tumours.

Effects of lung-protective ventilation strategy on lung aeration loss and postoperative pulmonary complications in moderate-risk patients undergoing abdominal surgery.

BACKGROUND: There is a controversy about whether the use of a lung-protective ventilation strategy(LPVS) can reduce the incidence of postoperative pulmonary complications (PPCs) and improve the clinical outcomes in moderate-risk patients were assessed by the Assess Respiratory Risk in Surgical Patients in Catalonia(ARISCAT). METHODS: One hundred moderate-risk patients predicted by the ARISCAT, scheduled to undergo abdominal surgery were randomized into two groups: conventional ventilation strategy group (G0) and lung-protective ventilation strategy group (G1). Lung ultrasonography (LUS) and the LUS score were performed before induction of anesthesia (T0), 30min after extubation (T1), and 24h (T2), 72h (T3) after surgery. The incidence and severity of PPCs within the postoperative 7 days, the duration of postoperative oxygen supplementation, and postoperative hospital stay (PHS) were recorded. RESULTS: The LUS score of both groups at T1-3 was higher than those at T0 (P<0.05), moreover, the LUS score of G1 was lower than that of G0 at T1-3. The incidence of PPCs of G1 (10.9%) was lower than that of G0 (29.8%) (relative risk, 0.37; 95% confidence interval [CI], 0.14 to 0.93; P=0.02) and the severity of PPCs of G1 were lower than those of G0 (P<0.05). The PHS of G1 was less than that of G0 (8[7-10] vs. 9[8-11], P<0.05). CONCLUSIONS: The LPVS can decrease lung aeration loss assessed by LUS and reduce the incidence of PPCs in moderate-risk patients.

Sedative effect of dexmedetomidine in spinal-epidural anesthesia on hysteromyomectomy.

To investigate the sedative effect of dexmedetomidine in spinal-epidural anesthesia on hysteromyomectomy a total of 100 hysteromyomectomy patients were randomly divided into the control group and the observation group with 50 in each group. Patients in the control group received the general anesthesia, while those in the observation group received spinal-epidural anesthesia, and intravenous injection of dexmedetomidine. For maintenance of anesthesia, ropivacaine was adopted for both groups. Before anesthesia, at 30 min and 60 min after anesthesia, we measured the heart rate (HR), bispectral index (BIS) and sedative effect. Before anesthesia, HR, BIS and Ramsay scores were compared between two groups, and the results showed that differences had no statistical significance (p>0.05); but at 30 min after anesthesia, HR and BIS of patients in the observation group were significantly lower than those in the control group (p<0.05), and Ramsay score was higher than the control group (p<0.05). No statistical significance was found in differences of the incidence rate of adverse reactions between two groups (p>0.05). Application of dexmedetomidine in spinal-epidural anesthesia gains promising sedative effect and safety in hysteromyomectomy, which is worthy of being promoted in clinical treatment.

Up-regulation of miR-370-3p restores glioblastoma multiforme sensitivity to temozolomide by influencing MGMT expression.

MicroRNAs (miRNA) are believed to play an important role in glioblastoma multiforme (GBM)chemotherapy. Our study aims to investigate potential miRNA biomarkers in GBM. Sixty GBM patients, which were given temozolomide (TMZ) chemotherapy and recurrent radiotherapy, were recruited. miRNA array was performed in cancerous and in paired normal tissues. Microarray results were further validated by a quantitative real-time PCR in selected tissues and GBM cell lines. TMZ resistance cells were developed and cell proliferation along with colony formation assays was determined. Our study employed H2AX formation and flow cytometry to analyse the role of miRNA in DNA damage and apoptosis. Our study illustrated 16 miRNA in which 9 were up-regulated and 7 down-regulated. and their differential expression were demonstrated in a recurrent GBM tissue. Among them, miRNA-370-3p demonstrated the highest level of down- regulation in tissues and in TMZ resistance cells. miRNA-370-3p mimic increased its expression and sensitivity of GBM cells to TMZ by suppressing the self-reparative ability of tumour cell DNA. O(6)-methylguanine-DNA methyltransferase (MGMT) was identified as the direct target gene of miR-370-3p, and it was found to be inversely correlated with miR-370-3p expression in tissue samples obtained. Thus, our study demonstrated a critical clinical role of an up-regulated miR-370-3p expression in glioblastoma multiforme chemotherapy sensitivity.

Cisplatin targets the stromal cell-derived factor-1-CXC chemokine receptor type 4 axis to suppress metastasis and invasion of ovarian cancer-initiating cells.

In ovarian cancer, CD44+/CD117+ stem cells, also known as cancer-initiating cells (CICs), are highly proliferative and invasive. Therefore, the CD44+/CD117+ subpopulation is thought to be an important target for novel therapeutic strategies. In this study, we investigated the effects of cisplatin (CDDP) on metastasis and invasion suppression of ovarian CICs by targeting the CXC chemokine receptor-4 (CXCR4) signaling pathway in vitro and in vivo. CD44+/CD117+ ovarian CICs were enriched from human primary ovarian tumor tissues and confirmed by flow cytometry sorting. A 3-(4,5-dimethylthiazol-2-yl)-2.5-dipheny-tetrazolium bromide (MTT) assay revealed significant inhibition of proliferation of ovarian CICs with increasing CDDP drug concentrations. Moreover, colony formation and transwell migration assays indicated that CDDP significantly suppressed the invasive capacity of ovarian CICs in vitro. The expression levels of stromal cell-derived factor (SDF)-1, CXCR4, matrix metalloproteinase (MMP) 2, and MMP9 mRNA and protein levels were significantly reduced in CDDP-treated cells compared to untreated ovarian CICs. Furthermore, xenograft experiments confirmed that CDDP suppressed the growth of xenograft tumors formed by ovarian CICs in vivo. In addition, CXCR4 agonist (diprotin A) treatment of ovarian CICs weakened the effects of CDDP and enhanced SDF-1-CXCR4 axis expression in ovarian CICs. Thus, the SDF-1-CXCR4 axis is an important mediator of proliferation and invasion in CXCR4-overexpressing ovarian cancer-initiating cells (OCICs). Furthermore, CDDP inhibits invasion and metastasis of OCICs by targeting SDF-1-CXCR4 axis expression.