Highly tumoricidal efficiency of non-oxidized MXene-Ti3C2Tx quantum dots on human uveal melanoma.

Uveal melanoma (UM) is a highly malignant intraocular tumor with poor prognosis. Current topical ophthalmic therapies purpose to conserve the eye and useful vision. Due to the risks and limited clinical benefits, the topical treatments of UM remain challenging and complex. In this study, newly developed non-oxidized MXene-Ti3C2Tx quantum dots (NMQDs-Ti3C2Tx) are proposed for UM treatment. Surprisingly, NMQDs-Ti3C2Tx shows significant tumor-killing effects on UM cells in a dose-dependent manner and causes severe necrosis near the injection site on the xenograft UM tumor model. Moreover, NMQDs-Ti3C2Tx exhibits excellent biocompatibility with normal retina pigment epithelium (RPE) cells and does not cause any damage in C57BL/6 mice eyes. Mechanistically, NMQDs-Ti3C2Tx inhibits the proliferation, invasion, and migration of UM cells via its desirable reactive oxygen species (ROS) generation ability, which causes lipid peroxidation and mitophagy, triggering cell ferroptosis. Furthermore, NMQDs-Ti3C2Tx is detected accumulating in autolysosomes which exacerbates cell death. This work provides new light on the topical treatment of UM.

Bilateral thoracic Paravertebral block for immediate postoperative pain relief in the PACU: a prospective, observational study.

BACKGROUND: To investigate the feasibility, effectiveness and safety of bilateral thoracic paravertebral block (TPVB) in the post anesthesia care unit (PACU) for pain relief in participants after laparotomy. METHODS: A single shot of bilateral TPVB with 25 ml of 0.2% ropivacaine and 5 mg dexamethasone in combination for both sides at the 8th thoracic transverse level (T8) was performed on 201 participants who complained moderate to severe pain on arrival to PACU after laparotomy. The visual analog scale (VAS) pain scores at rest and on cough, heart rate, blood pressure, and pulse oximetry before and after bilateral TPVB for up to 1 h were recorded. The VAS Pain scores at rest and on cough at 24 h after bilateral TPVB were also recorded. RESULTS: Bilateral TPVB was carried out successfully in all participants. The VAS pain scores at rest and on cough were 7.9 ± 1.6 and 8.7 ± 1.3 respectively pre-bilateral TPVB. The VAS pain scores at rest and on cough were significantly decreased to 1.1 ± 1.2 and 2.1 ± 1.6 respectively (P < 0.001) at 60 min after bilateral TPVB and to 2.1 ± 1.7 and 3.8 ± 1.9 at rest and on cough respectively ((P < 0.001) at 24 h after bilateral TPVB. At 10 min post-bilateral TPVB, only systolic blood pressure was reduced from 122 ± 19 mmHg to 111 ± 18 mmHg (P = 0.007) but then gradually became stable. No complications related to bilateral TPVB were observed. CONCLUSION: Bilateral TPVB can be provided for pain relief to the participants who suffer from moderate to severe pain after upper laparotomy in the PACU. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-ONN-16009229 , Registered on 10 September 2016.

The association and significance of H3K27me3 and a folate metabolic gene ACat2 in neural tube defects.

AIM: To study the association between the expression of H3K27me3 and ACat2 (a folate metabolic protein), in order to elucidate the protective mechanism of folic acid (FA) in neural tube defects (NTDs). METHODS: Eighteen female SD rats were randomly divided into normal, NTD and FA group. NTD group was induced by all-trans retinoic acid (ATRA) at E10d. FA group was fed with FA supplementation since 2 weeks before pregnancy, followed by ATRA induction. At E15d, FA level in the embryonic neural tube was determined by ELISA. Neural stem cells (NSCs) were isolated. Cell proliferation was compared by CCK-8 assay. The differentiation potency was assessed by immunocytochemical staining. H3K27me3 expression was measured by immunofluorescence method and Western blot. ACat2 mRNA expression was detected by qRT-PCR. RESULTS: Cultured NSCs formed numerous Nestin-positive neurospheres. After 5 days, they differentiated into NSE-positive neurons and GFAP-positive astrocytes. When compared with controls, the FA level in NTD group was significantly lower, the ability of cell proliferation and differentiation was significantly reduced, H3K27me3 expression was increased, and ACat2 mRNA expression was decreased (P <0.05). The intervention of FA notably reversed these changes (P <0.05). H3K27me3 expression was negatively correlated with the FA level (rs = -0.908, P <0.01) and ACat2 level (rs = -0.879, P <0.01) in the neural tube. CONCLUSION: The increased H3K27me3 expression might cause a disorder of folate metabolic pathway by silencing ACat2 expression, leading to reduced proliferation and differentiation of NSCs, and ultimately the occurrence of NTD. FA supplementation may reverse this process.