Osteoporosis is an important cause of internal fixation loosening after spinal surgery.Cement-augmented pedicle screw instru-mentation(CAPSI)technique is the most widely used technique in clinical practice to improve the stability of pedicle screw,mainly applied in osteoporosis and revision surgery,which included conventional solid pedicles crews and fenestrated/cannulated pedicle screws technique.CAPSI technique may cause cement leakage and pulmonary embolism,and there is no consensus on its indications or technical points.Therefore,this article reviews the research progress of CAPSI,in order to provide relevant reference for clinical practice.

Objective To investigate the preventive effect of schisandrin(SCH)on fetal neural tube defects(NTDs)of mice and its mechanism.Methods C57BL/6 mice were mated with female and male at a ratio of 2:1.Pregnant female mice with vaginal plug after mating were randomly divided into control group,model group,SCH group,and folic acid group,with 9 mice in each group.The NTDs fetal mice model was induced by intraperitoneal injection of all-trans retinoic acid(atRA)(7.5 mg/kg)on embryonic day 7.5(E 7.5 d).During E 0.5 d-E 11.5 d,pregnant rats in folic acid group were given folic acid[61.0 μg/(kg·d)]by gavage once a day,and pregnant rats in SCH group were given SCH[8.0 mg/(kg·d)]by gavage once a day.Fetal mice were removed by cesarean section on E 11.5 d.PC12 cells were divided into control group,model group and SCH group.PC12 cells were treated with atRA(20 μmol/L)for 12 hours to establish cell damage model in model group,and treated with SCH(2.5 μmol/L)for 24 hours in SCH group.Fetuses were identified NTDs by stereoscopic microscopy.HE staining was used to observe the closure of the neural tube.The expression levels of p-PI3K,Akt and p-Akt molecules in PI3K/Akt signaling pathway were detected by Western Blotting.Results Compared with control group,the incidence of NTDs was significantly increased in mice of model group(P<0.01);compared with model group,the incidence of NTDs was decreased in folic acid group and SCH group(P<0.01);compared with folic acid group,SCH group had a lower incidence of NTDs(P<0.01).Western Blotting results showed that compared with control group,the expression of p-PI3K and p-Akt protein in fetal tissues of model group was significantly decreased(P<0.01,P<0.05);compared with model group,there was no significant difference in expression of p-PI3K and p-Akt in fetal tissues of folic acid group(P>0.05),while the expression of p-PI3K and p-Akt protein in SCH group was significantly higher(P<0.05).Compared with control group,PC12 cells in model group showed lower expression levels of p-PI3K and p-Akt(P<0.05);compared with model group,PC12 cells in SCH group showed higher expression levels of p-PI3K and p-Akt(P<0.05).Conclusions SCH can reduce the incidence of atRA-induced NTDs in fetal mice,and its preventive effect is better than folic acid,which may be related to the activation of the PI3K/Akt signaling pathway.

Objective To explore the clinicopathological features and prognosis of the patients newly diagnosed with lung adenocarcinoma with both EGFR mutation and C-MET amplification.Methods The pathological sections were reviewed.EGFR mutation was detected by amplification refractory mutation system-quantitative real-time polymerase chain reaction,and C-MET amplification by fluorescence in situ hybridization.The clinicopathological features and survival data of the patients newly diagnosed with lung adenocarcinoma with both EGFR mutation and C-MET amplification were analyzed retrospectively.Results In 11 cases of EGFR mutation combined with C-MET amplification,complex glands and solid high-grade components were observed under a microscope in 10 cases except for one case with a cell block,the tissue structure of which was difficult to be evaluated.The incidence of lung adenocarcinoma in the patients with EGFR mutation combined with C-MET amplification at clinical stage Ⅳ was higher than that in the EGFR mutation or C-MET amplification group (all P<0.001),whereas the difference was not statistically significant between the EGFR mutation group and C-MET amplification group at each clinical stage (all P>0.05).There was no significant difference in the trend of survival rate between EGFR gene group and C-MET amplification group (χ²=0.042,P=0.838),while the survival of the patients with EGFR mutation combined with C-MET amplification was worse than that of the patients with EGFR mutation (χ²=246.72,P<0.001) or C-MET amplification (χ²=236.41,P<0.001).Conclusions The patients newly diagnosed with lung adenocarcinoma with EGFR mutation plus C-MET amplification demonstrate poor histological differentiation,rapid progress,and poor prognosis.The patients are often in the advanced stage when being diagnosed with cancer.Attention should be paid to this concurrent adverse driving molecular event in clinical work.With increasing availability,the inhibitors targeting C-MET may serve as an option to benefit these patients in the near future.
Humans ; In Situ Hybridization, Fluorescence ; Retrospective Studies ; Prognosis ; Adenocarcinoma of Lung/genetics* ; Mutation ; Lung Neoplasms/genetics* ; ErbB Receptors/genetics*

OBJECTIVE: To examine the anti-inflammatory effect of grape seed extract (GSE) in animal and cellular models and explore its mechanism of action. METHODS: This study determined the inhibitory effect of GSE on macrophage inflammation and Th1 and Th17 polarization in vitro. Based on the in vitro results, the effects and mechanisms of GSE on multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE) mice model were further explored. The C57BL/6 mice were intragastrically administered with 50 mg/kg of GSE once a day from the 3rd day to the 27th day after immunization. The activation of microglia, the polarization of Th1 and Th17 and the inflammatory factors such as tumor necrosis factor- α (TNF- α), interleukin-1 β (IL-1 β), IL-6, IL-12, IL-17 and interferon-γ (IFN-γ) secreted by them were detected in vitro and in vivo by flow cytometry, enzyme linked immunosorbent assay (ELISA), immunofluorescence staining and Western blot, respectively. RESULTS: GSE reduced the secretion of TNF-α, IL-1 β and IL-6 in bone marrow-derived macrophages stimulated by lipopolysaccharide (P<0.01), inhibited the secretion of TNF-α, IL-1 β, IL-6, IL-12, IL-17 and IFN-γ in spleen cells of EAE mice immunized for 9 days (P<0.05 or P<0.01), and reduced the differentiation of Th1 and Th17 mediated by CD3 and CD28 factors (P<0.01). GSE significantly improved the clinical symptoms of EAE mice, and inhibited spinal cord demyelination and inflammatory cell infiltration. Peripherally, GSE downregulated the expression of toll-like-receptor 4 (TLR4) and Rho-associated kinase (ROCKII, P<0.05 or P<0.01), and inhibited the secretion of inflammatory factors (P<0.01 or P<0.05). In the central nervous system, GSE inhibited the infiltration of CD45⁺CD11b⁺ and CD45⁺CD4⁺ cells, and weakened the differentiation of Th1 and Th17 (P<0.05). Moreover, it reduced the secretion of inflammatory factors (P<0.01), and prevented the activation of microglia (P<0.05). CONCLUSION GSE had a beneficial effect on the pathogenesis and progression of EAE by inhibiting inflammatory response as a potential drug and strategy for the treatment of MS.
Mice ; Animals ; Encephalomyelitis, Autoimmune, Experimental/pathology* ; Grape Seed Extract/therapeutic use* ; Interleukin-17 ; Interleukin-1beta ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Th1 Cells ; Mice, Inbred C57BL ; Interferon-gamma/therapeutic use* ; Th17 Cells/metabolism* ; Interleukin-12/therapeutic use* ; Cytokines/metabolism*

Aim To explore the protective effect of proanthocyanidin B2 (PC-B2) on oxidative damage of PC 12 cells induced by hydrogen peroxide (H

Aim To explore the mechanism of grape seed proanthocyanidins (GSPs) targeting astrocytes (AS), so as to regulate the phenotype and function of AS and maximize their neuroprotective effect. Methods The effects of GSPs on the phenotype, secretion of pro-inflammatory factors and neurotrophic factors of Al AS induced by TNF-α, IL-1α and Clq were investigated by RT-PCR, Elisa and Western blot in vitro. And JNK phosphorylation was determined using Western blot. Results GSPs significantly reduced the expression of C3d and Clq of Al AS markers and inhibited the phosphorylation of JNK. Moreover, compared with the model group, GSPs could significantly inhibit the release of pro-inflammatory cytokines IL-6, IL-1 α, IL-17 and H

Cervical cancer mainly caused by human papillomavirus (HPV) infection has become a public health issue, which seriously threatens women 's health. To prevent HPV infection, the currently used prophylactic vaccines mainly induce a humoral immune response in the host, thereby generating neutralizing antibodies. In contrast, the design goal of therapeutic HPV vaccines is to induce a cell-mediated immune response in the host, primarily driven by Th1 cells, aiming to clear existing viral infections and slow down or inhibit tumor progression. Currently, several therapeutic HPV vaccines based on different mechanisms and techniques have entered clinical trials. This review will summarize the progress of these clinical trials, providing reference for the research and development of therapeutic HPV vaccines.
Female ; Humans ; Papillomavirus Vaccines/therapeutic use* ; Papillomavirus Infections/prevention & control* ; Uterine Cervical Neoplasms ; Immunity, Cellular ; Papillomaviridae

Cervical cancer mainly caused by human papillomavirus (HPV) infection has become a public health issue, which seriously threatens women 's health. To prevent HPV infection, the currently used prophylactic vaccines mainly induce a humoral immune response in the host, thereby generating neutralizing antibodies. In contrast, the design goal of therapeutic HPV vaccines is to induce a cell-mediated immune response in the host, primarily driven by Th1 cells, aiming to clear existing viral infections and slow down or inhibit tumor progression. Currently, several therapeutic HPV vaccines based on different mechanisms and techniques have entered clinical trials. This review will summarize the progress of these clinical trials, providing reference for the research and development of therapeutic HPV vaccines.
Female ; Humans ; Papillomavirus Vaccines/therapeutic use* ; Papillomavirus Infections/prevention & control* ; Uterine Cervical Neoplasms ; Immunity, Cellular ; Papillomaviridae

The immune checkpoint programmed cell death-ligand 1(PD-L1)-mediated immunosuppression is among the important features of tumor. PD-L1, an immunosuppressant, can induce T cell failure by binding to programmed cell death-1(PD-1). Thus, the key to restoring the function of T cells is inhibiting the expression of PD-L1. The Chinese medicinal Atractylodis Macrocephalae Rhizoma(AMR) has the anti-tumor, anti-inflammatory, antioxidant, and hypoglycemic activities, and the polysaccharide in AMR(PAMR) plays a crucial role in immunoregulation, but the influence on the immune checkpoints which are closely related to immunosuppression has not been reported. MicroRNA-34 a(miR-34 a) expression in esophageal carcinoma tissue is significantly lower than that in normal tissue. This study aims to investigate the inhibitory effect of PAMR on esophageal carcinoma cells, and the relationship between its inhibitory effect on PD-L1 expression and miR-34 a, which is expected to clarify the anti-tumor mechanism of PAMR. Firstly, different human esophageal carcinoma cell lines(EC9706, EC-1, TE-1, EC109 cells) were screend out, and expression of PD-L1 was determined. Then, EC109 cells, with high expression of PD-L1, were selected for further experiment. The result showed that PAMR suppressed EC109 cell growth. According to the real-time quantitative PCR(qPCR) and Western blot, it significantly suppressed the mRNA and protein expression of PD-L1, while promoting the expression of tumor suppressor miR-34 a. The confocal microscopy and luci-ferase assay proved that PAMR alleviated the inhibitory effect of PD-L1 while blocked miR-34 a. Additionally, the expression of PD-L1 was controlled by miR-34 a, and the combination of miR-34 a inhibitor with high-dose PAMR reversed the inhibitory effect of PAMR on PD-L1 protein expression. Thus, the PAMR may inhibit PD-L1 by increasing the expression of miR-34 a and regulating its downstream target genes. In conclusion, PAMR inhibits the expression of PD-L1 mainly by inducing miR-34 a.
B7-H1 Antigen/pharmacology* ; Carcinoma ; Cell Proliferation ; Humans ; MicroRNAs/metabolism* ; Polysaccharides/pharmacology*

Precious Tibetan medicine formula is a characteristic type of medicine commonly used in the clinical treatment of central nervous system diseases. Through the summary of modern research on the precious Tibetan medicine formulas such as Ratnasampil, Ershiwuwei Zhenzhu Pills, Ershiwewei Shanhu Pills, and Ruyi Zhenbao Pills, it is found that they have obvious advantages in the treatment of stroke, Alzheimer's disease, epilepsy, angioneurotic headache, and vascular dementia. Modern pharmacological studies have shown that the mechanisms of precious Tibetan medicine formulas in improving central nervous system diseases are that they promote microcirculation of brain tissue, regulate the permeability of the blood-brain barrier, alleviate inflammation, relieve oxidative stress damage, and inhibit nerve cell apoptosis. This review summarizes the clinical and pharmacological studies on precious Tibetan medicine formulas in prevention and treatment of central nervous system diseases, aiming to provide a reference for future in-depth research and innovative discovery of Tibetan medicine against central nervous diseases.
Blood-Brain Barrier ; Brain ; Central Nervous System Diseases ; Humans ; Medicine, Tibetan Traditional ; Stroke/drug therapy*