Crebanine, an aporphine alkaloid, induces cancer cell apoptosis through PI3K-Akt pathway in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is one of the most prevalent and lethal primary central nervous system malignancies. GBM is notorious for its high rates of recurrence and therapy resistance and the PI3K/Akt pathway plays a pivotal role in its malignant behavior. Crebanine (CB), an alkaloid capable of penetrating the blood-brain barrier (BBB), has been shown to have inhibitory effects on proinflammatory molecules and multiple cancer cell lines via pathways such as PI3K/Akt. This study aims to investigate the efficacy and mechanisms of CB treatment on GBM. It is the first study to elucidate the anti-tumor role of CB in GBM, providing new possibilities for GBM therapy. Through a series of experiments, we demonstrate the significant anti-survival, anti-clonogenicity, and proapoptotic effects of CB treatment on GBM cell lines. Next-generation sequencing (NGS) is also conducted and provides a complete list of significant changes in gene expression after treatment, including genes related to apoptosis, the cell cycle, FoxO, and autophagy. The subsequent protein expressions of the upregulation of apoptosis and downregulation of PI3K/Akt are further proved. The clinical applicability of CB to GBM treatment could be high for its BBB-penetrating feature, significant induction of apoptosis, and blockage of the PI3K/Akt pathway. Future research is needed using in vivo experiments and other therapeutic pathways shown in NGS for further clinical or in vivo studies.

Effects of various functional monomers' reaction on the surface characteristics and bonding performance of polyetheretherketone.

PURPOSE: Polyetheretherketone (PEEK) is a new polymeric material that has received significant attention in dentistry because of its mechanical properties, biocompatibility, and aesthetics. However, the bonding performance of PEEK to other materials is not preferable. This study aimed to analyze the variations in the surface characteristics of PEEK under the chemical action of primers containing different functional monomers or polymers and to evaluate the bonding performance of PEEK and dental cement. METHODS: Disk-shaped PEEK samples were prepared by dental milling, blasting with alumina oxide, and covering with primers containing functional monomers or polymers. The surface characteristics of the samples were analyzed by microscopy and spectroscopy. The shear bond strength (SBS) between PEEK and dental cement, with and without thermocycling, was tested using a universal testing machine. Finally, the data were statistically analyzed and compared. RESULTS: Functional monomers or polymers were successfully bonded to the surface of PEEK. This treatment significantly improved its hydrophilicity and surface free energy (P < 0.05). The primer containing pentaerythritol triacrylate had the highest SBS without thermocycling (13.89 MPa). Meanwhile, the primers containing urethane dimethacrylate (UDMA) and methyl methacrylate (MMA) (abbreviated as the HC group) showed the highest SBS and lowest reduction (25.51%) after thermocycling. Notably, all the testing groups achieved the ISO10477 standard of 5 MPa. After thermocycling, adhesive failure accounted for the largest proportion of failures in all the groups except the HC group. CONCLUSIONS: The chemical priming treatment can significantly improve the SBS of PEEK and dental cement. Moreover, a primer containing both UDMA and MMA can provide improved bonding for PEEK materials.

Whole-mount intramuscular nerve distribution pattern of medial and lateral plantar muscles and its clinical significance / 解剖学报

Objective To reveal the whole-mount distribution pattern of intramuscular nerves in the medial and lateral plantar muscles and to explore its clinical significance. Methods Twenty-four adult cadavers were dissected to remove the medial and lateral groups of the plantar muscles. The distribution pattern of the intramuscular nerves was demonstrated by modified Sihler' s staining. Results The nerve branch for adductor hallucis muscle entered the muscle from the deep surface of the insertion of the muscle, while those nerve branches for abductor hallucis, flexor hallucis brevis, abductor digiti minimi and flexor digiti minimi brevis muscles entered the muscle from the deep side of the origin of the muscle. There were one lunate and one rectangular intramuscular nerve dense regions (INDRs) in the abductor hallucis muscle; two reniform INDRs in the transverse head of the adductor hallucis muscle, one reniform and one rectangular INDRs in the oblique head of the adductor hallucis muscle; there were two rectangle INDRs in the flexor hallucis brevis, abductor digiti minimi and flexor digiti minimi brevis muscles. These five muscles were divided into two neuromuscular compartment, but the percentage position of INDR and the center of INDR on muscle length in each muscle were different. Conclusion These result may provide morphological guidance for surgical operation to avoid nerve injury, the selection and matching of muscle transplantation and the injection of botulinum toxin A to block the spasticity of these muscles.

Cytokine-induced killer cell infusion combined with conventional treatments produced better prognosis for hepatocellular carcinoma patients with barcelona clinic liver cancer B or earlier stage: A systematic review and meta-analysis.

BACKGROUND AIMS: To investigate the clinical benefits of cytokine-induced killer (CIK) cell infusions on hepatocellular carcinoma (HCC) patients, combined with other conventional treatments. METHODS: This was a systematic review and meta-analysis conducted among phase II and III randomized control trials worldwide. Review manager 5.2 version was used to pool the effect size across studies. Sensitivity analyses and risk of bias were estimated among included studies. Egger's test was used to characterize the publication bias. RESULTS: Eight randomized controlled trials and 945 patients with HCC were included in the study. CIK infusion reduced cancer recurrence risk to 0.74 (95% confidence interval [CI] 0.5-0.92), I2 75% (P <0.001), and reduced cancer death risk to 0.76 (95% CI 0.65-0.88), I2 50% (P = 0.09). Among studies blinded for outcome assessment and Barcelona Clinic Liver Cancer stages of 0, A and B, CIK infusion reduced recurrence risk by 18% (relative risk [RR] = 0.82, 95% CI 0.70-0.96) and death risk by 37% (RR = 0.63, 95% CI 0.47-0.85); heterogeneity was 0% and 39%, respectively (P > 0.05). The intercepts of linear regressions for recurrence and death were -2.17 and -2.07, respectively, but the P value was 0.17 and 0.38; no significant publication bias was observed with Egger's test. DISCUSSION: Among hepatocellular carcinoma patients with Barcelona Clinic Liver Cancer score of B or less, CIK cell infusions combined with conventional treatments significantly prolonged recurrence-free and overall survival. This adoptive immunotherapy could be recommended to HCC patients.

Effects of phosphatidylinositol-3 kinase/protein kinase b/bone morphogenetic protein-15 pathway on the follicular development in the mammalian ovary / 中国医学科学院学报

In mammals, ovarian follicle is made of an oocyte with its surrounding granulosa cells and theca cells. Follicular growth and development is a highly coordinated programmable process, which guarantees the normal oocyte maturation and makes it having the fertilizing capacity. The paracrine and autocrine between oocytes and granulosa cells are essential for the follicular development to provide a suitable microenvironment. Phosphatidylinositol-3 kinase /protein kinase B is one of these important regulatory signaling pathways during this developmental process, and bone morphogenetic protein-15 an oocyte-specific secreted signal molecule, which regulates the follicular development by paracrine in the mammalian ovary. The present article overviewed the role of phosphatidylinositol-3 kinase / protein kinase B signaling during the follicular development based on our previous investigation about protein kinase B /forkhead transcription factor forkhead family of transcription factors -3a, and then focused on the regulatory effects of bone morphogenetic protein-15, as a downstream signal molecule of phosphatidylinositol-3 kinase / forkhead family of transcription factors -3a pathway, on ovarian follicular development, which helped to further understand the molecular mechanism regulating the follicular development and to treat ovarian diseases like infertility.

Aetiological Analysis of Chronic Obstructive Pulmonary Disease Complicated with Ventilator-associated Pneumonia / 上海第二医科大学学报

Objective To analyze the aetiological characteristics and bacterial susceptibility in chronic obstructive pulmonary disease (COPD) complicated with ventilator-associated pneumonia (VAP) after mechanical ventilation. Methods To review the clinical characteristics, aetiological flora and bacterial susceptibility in 28 patients complicated with VAP in the ICU in recent years. Results The incidence rate of VAP was 66.7％. 91 clinical bacteria and 10 mycete isolates were collected, 64 (80.3％) were Gram-negative bacteria (GNB) and 27(29.7％) Gram- positive bacteria (GPC). The dominant bacteria was Xanthomonas maltophilia in COPD complicated VAP. Conclusion The main kind of bacteria in COPD complicated VAP after mechanical ventilation was GNB, and all kinds of the bacteria showed high tolerance. More attention should be paid to the cultivate aetiological bacteria and bacterial susceptibility and select the most suitable antibiotics in the treatment of VAP.