The present study investigated the inhibitory effects of apatinib on the proliferation of the SMMC-7721 hepatocellular carcinoma cell line to explore the possible mechanism. The MTT assay was used to detect the inhibitory effects of the different concentrations of apatinib on the proliferation of SMMC-7721 cells. Annexin V/PI double staining was performed to investigate the effects of apatinib on the apoptosis of SMMC‑7721 cells. Expression of the apoptosis-related genes Bcl-2, Bax and caspase-9 after apatinib treatment was detected by reverse transcription‑quantitative PCR (RT-qPCR) and western blot analysis. Expression of the PI3K, p-PI3K, Akt and p-Akt proteins after apatinib treatment was detected using western blot analysis. The MTT results showed that apatinib inhibited the in vitro proliferation of SMMC-7721 cells. Annexin V/PI double staining showed that apatinib induced the apoptosis of SMMC‑7721 cells in a concentration-dependent manner. Results of RT-qPCR and western blot analysis showed that apatinib was able to induce the expression of pro-apoptotic genes Bax and caspase-9 and inhibited the expression of anti-apoptotic gene Bcl-2. In addition, the western blot analysis revealed that p-PI3K and p-Akt was significantly decreased following apatinib treatment, while no significant differences were found in the total protein levels of PI3K and Akt. The results of the present show that apatinib is capable of promoting the apoptosis of SMMC-7721 cells by inhibiting the PI3K/Akt signal transduction pathway, upregulating the expression of pro-apoptotic genes Bax and caspase-9, and downregulating the expression level of the anti-apoptotic gene Bcl-2.

Increasing awareness of chronic pain due to both injury and disease have encouraged drug companies and pharmaceutical researchers alike to design and fabricate better, more specific drugs for pain relief. However, overuse of clinically available pain medication has caused a multitude of negative repercussions, including drug tolerance, addiction, and other severe side effects, which can prolong suffering and reduce pain mediation. Applications of nanotechnology to the field of drug delivery has sought to enhance the treatment efficiency, lower side effects, and mitigate the formation of tolerance. The use of nanomaterials has several advantages for chronic pain relief, such as controlled release, prolonged circulation time, and limited side effects. With the development of nanotechnology, strategies for chronic pain relief have also bourgeoned utilizing a variety of nanomaterials and targeting surface modifications. In addition to using these materials as carriers for drug delivery, nanomaterials can also be designed to have inherent properties that relieve chronic pain. This minireview covers the current status of designed nanomaterials for pain relief and provides a discussion of future considerations for nanotechnology designed for relieving chronic pain.

BACKGROUND AND PURPOSE: Efficient detection of metastases is important for patient’ treatment. This prospective study was to explore the clinical value of contrast-enhanced T2 FLAIR in imaging brain metastases using half-dose gadobenate dimeglumine. MATERIALS AND METHODS: In vitro signal intensity of various gadolinium concentrations was explored by spin-echo T1-weighted imaging and T2 FLAIR. Then, 46 patients with lung cancer underwent nonenhanced T2 FLAIR before administration of half-dose gadobenate dimeglumine and 3 consecutive contrast-enhanced T2 FLAIR sequences followed by 1 spin-echo T1WI after administration of half-dose gadobenate dimeglumine. After an additional dose of 0.05 mmol/kg, 3D brain volume imaging was performed. All brain metastases were classified as follows: solid-enhancing, ≥ 5 mm (group A); ring-enhancing, ≥ 5 mm (group B); and lesion diameter of <5 mm (group C). The contrast ratio of the lesions on 3 consecutive phases of contrast-enhanced T2 FLAIR was measured, and the percentage increase of contrast-enhanced T2 FLAIR among the 3 groups was compared. RESULTS: In vitro, the maximal signal intensity was achieved in T2 FLAIR at one-eighth to one-half of the contrast concentration needed for maximal signal intensity in T1WI. In vivo, the mean contrast ratio values of metastases on contrast-enhanced T2 FLAIR for the 3 consecutive phases ranged from 63.64% to 83.05%. The percentage increase (PI) values of contrast-enhanced T2 FLAIR were as follows: PI_A < PI_B (P = .001) and PI_A < PI_C (P < .001). The degree of enhancement of brain metastases on contrast-enhanced T2 FLAIR was lower than on 3D brain volume imaging (P < .001) in group A, and higher than on 3D brain volume imaging (P < .001) in group C. CONCLUSIONS: Small or ring-enhancing metastases can be better visualized on delayed contrast-enhanced T2 FLAIR using a half-dose high-relaxivity contrast agent.

Interest in cancer immunotherapy has rapidly risen since it offers many advantages over traditional approaches, such as high efficiency and prevention of metastasis. Efforts have primarily focused on two major strategies for regulating the body's antitumor immune response mechanisms: “enhanced immunotherapy” that aims to amplify the immune activation, and “normalized immunotherapy” that corrects the defective immune mechanism in the tumor immune microenvironments (TIMEs), which returns to the normal immune trajectory. However, due to the complexity and heterogeneity of the TIMEs, and lack of visualization research on the immunotherapy process, cancer immunotherapy has not been widely used in clinical setting. Recently, through the design and modification of nanomaterials, intelligent TIME-responsive nanoplatforms were developed from which encouraging results in many aspects of immunotherapy have been achieved. In this mini review, the status of designed nanomaterials for nanoplatform-based immune regulation of TIMEs has been emphasized, particularly with respect to the aforementioned approaches. It is envisaged that future prospects will focus on a combination of multiple immunotherapies for more efficient cancer inhibition and elimination.