Introduction of an easy-to-operate arthroscopic test in detecting and treatment of meniscal instability: "suction drift" test.

OBJECTIVE: To explore the surgical guidance value of "suction drift" in osteoarticular meniscal instability. METHODS: The clinical data of 104 patients with significant knee symptoms following surgery were retrospectively analyzed. "Suction drift" was diagnosed in both groups. Depending on the treatment, patients treated with conventional debridement were assigned to group A, and those treated by meniscus suture until the disappearance of the "suction drift" phenomenon were included in group B. All patients were followed up for a minimum of 6 months after surgery. The postoperative Visual Analogue Scale (VAS) score, Lysholm knee score and the occurrence of meniscus-related symptoms were compared between the two groups. RESULTS: After puncture, 78 patients (75.0%) had excessive displacement of the meniscus, with 53 (67.9%) of them being followed-up for at least 6 months. Twenty-five patients in group A and twenty-eight in group B were included in the final analysis (The number of patients with "suction drift" in two groups was tested to be comparable, P>0.05). VAS score was significantly decreased and Lysholm knee score was markedly increased in both groups after treatment, with lower VAS score and higher Lysholm knee score in group B compared with group A. In addition, group A had a significantly higher incidence of meniscus-related symptoms (joint space tenderness, joint clicks, and noose sensation) than group B. CONCLUSIONS: "Suction drift" is a quick and easy-to-operate arthroscopic test, which can not only diagnose meniscus instability due to knee osteoarthrosis-induced meniscus degeneration, but also help determine the recovery of meniscus stability after suture, and significantly relieve symptoms.

Transition metal-free annulative vinylene transfer via the 1,3-dipolar reaction of N-ylides: access to benzo-fused indolizines.

An efficient metal-free annulative vinylene transfer protocol for the synthesis of benzo-fused indolizines via 1,3-dipolar cycloadditions of N-ylides with vinylene carbonate has been developed. Vinylene carbonate serves as an acetylene surrogate without any external oxidant involved. This transformation leads to the direct construction of versatile benzo-fused indolizine derivatives in moderate to good yields.

Screening and verification of prognostic lncRNA markers related to immune infiltration in the metastasis of osteosarcoma.

Background: We sought to screen and verify the long non-coding ribonucleic acids (lncRNAs) related to immune infiltration in metastatic osteosarcoma (OS). Methods: We downloaded the RNA-sequencing expression data from The Cancer Genome Atlas (TCGA) database as the training data set. We downloaded the GSE39055 data set from the National Center for Biotechnology Information, Gene Expression Omnibus as the validation data set. The least absolute shrinkage and selection operator (LASSO) regression algorithm was used to screen the optimized lncRNA combinations. Kaplan-Meier curves were used to evaluate the associations between the lncRNAs and actual prognosis. The independent survival prognosis clinical factors were obtained by univariate and multivariate Cox analyses. A nomogram was established to explore the correlation between survival rate and risk information. The Tumor IMmune Estimation Resource was applied to estimate the composition of 6 subtypes of immune infiltration cells. Results: In total, 1,398 lncRNAs and 14,631 messenger RNAs were screened from TCGA data set, and divided into the low and high immunity groups. The Estimation of STromal and Immune cells in MAlignant Tumour tissues using Expression data (ESTIMATE) scores differed significantly between the samples in the two groups. Additionally, 5 optimized lncRNA combinations were obtained using the LASSO algorithm. Risk factors including age, metastatic tumor, and risk-score (RS) were related to the prognosis of OS patients. The survival rates predicted by the nomogram model were consistent with the actual survival rates of OS patients. Finally, we found that RS was negatively correlated with the proportion of immune cells. Conclusions: In total, 5 feature lncRNAs were identified as novel biomarkers for OS. Next, a RS nomogram model was constructed based on the 5 identified lncRNAs. This model predicted the survival rates and prognoses of OS patients well.

Retracted: The Effects of Ludartin on Cell Proliferation, Cell Migration, Cell Cycle Arrest and Apoptosis Are Associated with Upregulation of p21WAF1 in Saos-2 Osteosarcoma Cells In Vitro.

The authors repeated experiments and found that the results shown in figure 2 were not reproducible. Reference: Shuang-li Zhang, Bao-lin Li, Wei Li, Ming Lu, Lin-ying Ni, Hui-li Ma, Qing-gang Meng. The Effects of Ludartin on Cell Proliferation, Cell Migration, Cell Cycle Arrest and Apoptosis Are Associated with Upregulation of p21WAF1 in Saos-2 Osteosarcoma Cells In Vitro. Med Sci Monit 2018; 24: LBR4926-4933. 10.12659/MSM.909193.

[Evolution of Sichuan Dao-di herbs recorded in ancient works of materia medica of different historical periods].

Sichuan province is very famous for its abundant resources of traditional Chinese medicine(TCM).However, within the scope of administrative division of Sichuan province, the origin records of Dao-di herbs in different historical periods show a dynamic distribution process. On the basis of carefully sorting out the geographical scope of Sichuan province in different historical periods, this article focuses on the textual research of the Dao-di herbs in Sichuan province recorded in the seven mainstream ancient works of materia medica.The results showed that, according to the records of Mingyi bielu and Bencaojing Jizhu, the main distribution areas of Dao-di herbs were mainly in the central and eastern regions of Sichuan province, mainly including Moschus, Coptidis Rhizoma, Zingiberis Rhizoma, Aconiti Lateralis Radix Praeparata and most of the rest materia medica had become unused in the historical process. Qianjin Yifang records that the distribution areas of Dao-di herbs were mainly in the middle and eastern part of Sichuan province.Aconiti Radix, Lateralis Radix Praeparata, Zingiberis Rhizoma, Notopterygii Rhizoma et Radix are still the Dao-di herbs of Sichuan province. According to the book of Bencao Tujing,the main distribution areas of Dao-di herbs are Chengdu Plain, Yibin and Santai, While Toosendan Fructus, Chuanxiong Rhizoma, Zanthoxyli Pericarpium, Aconiti Radix are still the Dao-di herbs of Sichuan province. Ben Cao Gang Mu records the place of origin as Sichuan.Coptidis Rhizoma, Toosendan Fructus, Cyathulae Radix are still the Dao-di herbs of Sichuan pro-vince. Yaowu Chuchanbian and Zengding Weiyao Tiaobian records the place of origin as Sichuan, as well as Kangding, Songpan, Dujiang-yan, Jiangyou, Nanchong, Ya'an, etc. Moschus, Coptidis Rhizoma, Eucommiae Cortex, Phellodendri Chinensis Cortex are still the Dao-di herbs of Sichuan province. The results of this article provide a new understanding of the history and distribution changes of Dao-di herbs in Sichuan province, and can help to further understand the formation connotation of Sichuan Dao-di herbs.

[Research progress on production districts of Sichuan Dao-di herbs].

Dao-di herbs are the Chinese herbs which have high quality and best clinic effects. Sichuan is one of the proviences most rich in Chinese herb resources,which has 7 290 species of Chinese herbs, such as Curcumae Longae Rhizoma, Chuanxiong Rhizoma, Aconiti Lateralis Radix Praeparata, Ophiopogonis Radix, Coptidis Rhizoma, Gentianae Radix, Rhei Radix et Rhizoma, Curcumae Rhizoma, Gardeniae Fructus, ect. After textual research on materia medica of the 7 290 Chinese herbs, we find there are 86 Dao-di herbs in Sichuan, such as Chuanxiong Rhizoma from Dujiangyan, Aconiti Lateralis Radix Praeparata from Jiangyou, Fritillariae Radix, Notoptergii Rhizoma et Radix, Angelicae Dahuricae Radix from Suining, Ophiopogonis Radix from Santai, Salviae Miltiorrhizae Radix et Rhizoma from Zhongjiang, Magnoliae Officinalis Cortex from Pingwu. In China more attention is paid to the production of Dao-di herbs. In 2018, the State Administration of Traditional Chinese Medicine launched the "Construction Plan of national production base of genuine medicinal materials". Developing genuine medicinal materials in genuine production areas is one of the effective ways to ensure the quality of medicinal materials. Based on the study of geographical environment and ecological factors(altitude, climate, soil) in Sichuan province. The Dao-di herbs of Sichuan province are divided into 4 districts, including, Sichuan basin medicinal materials production area, mountain and the basin edge medicinal materials production area, Panxi medicinal materials production area, Plateau Mountain Canyon medicinal materials production area. The suitable regions and best suitable regions of the 86 Dao-di herbs in Sichuan are determined by remote sensing and GIS spatial analysis of the suitable environmental indicators of these Dao-di herbs. Our study is beneficial to the rational distribution of the production and to improvement of the quality of traditional Chinese medicine in Sichuan province.

Identification of Biomarkers for Osteosarcoma Based on Integration Strategy.

BACKGROUND Osteosarcoma (OS) is the most common primary malignant tumor of bone. The identification of novel biomarkers is necessary for the diagnosis and treatment of osteosarcoma. MATERIAL AND METHODS We obtained 11 paired fresh-frozen OS samples and normal controls from patients between September 2015 and February 2017. We used an integration strategy that analyzes next-generation sequencing data by bioinformatics methods based on the pathogenesis of osteosarcoma. RESULTS One susceptibility lncRNA and 7 susceptibility genes regulated by the lncRNA for osteosarcoma were effectively identified, and real-time PCR and clinical index ALP data were used to test their effectiveness. CONCLUSIONS The results showed that the expression levels of the 7 genes were highly consistent in the training and test sample sets, especially between the expression value of the gene ALPL and the plasma detection value of its encoded protein ALP. In particular, both the expression of gene ALPL and the plasma detection values of protein ALP encoded by gene ALPL showed a high degree of consistency among different data types. The identified lncRNA and genes effectively classified the samples proved so that they could be used as potential biomarkers of osteosarcoma. Our strategy may also be helpful for the identification of biomarkers for other diseases.

Association of high PDPN expression with pulmonary metastasis of osteosarcoma and patient prognosis.

Podoplanin (PDPN) is an important positive regulator of platelet aggregation and functions as a lymphatic endothelial marker. PDPN has been observed to be expressed in human tumor tissues and various cancer cell lines. In the present study, PDPN expression in patients with primary osteosarcoma was assessed at the mRNA and protein levels, and the associations between PDPN expression and pulmonary metastasis (PM) and prognosis were examined. Reverse transcription-quantitative PCR (RT-qPCR) analysis was used to detect the expression levels of PDPN in primary osteosarcoma tissues and paired normal bone tissues (n=20 pairs). In addition, immunohistochemical analysis of PDPN expression was performed in 168 paraffin-embedded osteosarcoma tissue specimens and 23 matched normal tissues. The RT-qPCR results revealed higher mRNA expression levels of PDPN in patients with PM compared with patients without PM. Further survival analyses identified Enneking stage and PM as two independent prognostic indicators. Finally, univariate analysis revealed that high PDPN protein expression was significantly associated with Enneking stage and PM in patients with osteosarcoma.

MiR-128 inhibits the osteogenic differentiation in osteoporosis by down-regulating SIRT6 expression.

Background: MicroRNAs (miRNAs) are involved in the regulation of osteogenic differentiation and chondrification in vivo The purpose of the present study was to explore the potential mechanism of miR-128 in osteoporosis (OP).Methods: Quantitative real-time PCR (qRT-PCR) was used to determine the expression of miR-128 in femoral neck trabecular bones of OP patients (n=40) and non-OP patients (n=40). C2C12 cells were transfected with miR-128 mimic or inhibitor to determine the effect of miR-128 on osteoblastic differentiation of C2C12 cells. Bioinformatics and luciferase reporter genes were used to determine the molecular mechanism of miR-128 in osteoblastic differentiation of C2C12 cells.Results: The qRT-PCR results showed that the expression level of miR-128 in bone samples of OP patients was significantly higher than that of non-OP patients, while miR-128 was significantly down-regulated during the osteogenic differentiation of C2C12 cells. In addition, the results showed that overexpression of miR-128 significantly inhibited the mRNA and protein expression levels of osteocalcin (OC), alkaline phosphatase (ALP) and collagen I type-α1 (COL1A1) in C2C12 cells, while miR-128 inhibitor could reverse this effect. Bioinformatics analysis and dual-luciferase reporter assay found that silencing information regulatory protein 6 (SIRT6) was a direct target of miR-128. The qRT-PCR and Western Blot results found that miR-128 significantly down-regulated the mRNA and protein expressions of SIRT6. Furthermore, silencing SIRT6 significantly inhibited the promoting effect of the miR-128 inhibitor on the expression of osteoblast markers.Conclusion: The above results confirmed that miR-128 inhibited osteoblast differentiation in OP by down-regulating SIRT6 expression, thus accelerating the development of OP.

The Effects of Ludartin on Cell Proliferation, Cell Migration, Cell Cycle Arrest and Apoptosis Are Associated with Upregulation of p21WAF1 in Saos-2 Osteosarcoma Cells In Vitro.

BACKGROUND The aim of this study was investigate the effects of the sesquiterpene lactone, ludartin, on cell proliferation, cell migration, apoptosis, and the cell cycle in osteosarcoma cell lines, compared with a normal osteoblast cell line. MATERIAL AND METHODS Osteosarcoma cell lines, MG-63 Saos-2 U-2OS, T1-73 143B, and HOS, and normal hFOB 1.19 osteoblasts, were cultured and treated with increasing doses of ludartin, The MTT colorimetric assay was used to measure cell metabolic activity and viability. Apoptosis was studied by fluorescence-activated cell sorting (FACS) using 4',6-diamidino-2-phenylindole (DAPI) nuclear staining and Annexin-V/propidium iodide (PI) staining. Cell cycle was studied using flow cytometry. Cell migration and invasion were studied using wound healing and Boyden chamber assays. Protein expression was measured by Western blotting. RESULTS Ludartin inhibited cell viability, cell migration, cell proliferation, and increased cell apoptosis, in all osteosarcoma cell lines, with an IC50 dose ranging from 15-30 µM. The greatest effects were on the Saso-2 osteosarcoma cells, with an IC50 of 15 µM. However, ludartin showed minor cytotoxic effects of the normal hFOB 1.19 osteoblasts (IC50 >100 µM). Ludartin exerted its anti-proliferative effects on Saos-2 cells via induction of apoptosis and cell cycle arrest at the G2/M checkpoint, associated with reduced expression of Cdc25c (Ser216), Cdc25c, pCdc2 (Tyr15), and Cdc2 and increased expression of p21WAF1. Ludartin inhibited cell migration and invasion of the Saos-2 cells. CONCLUSIONS The dose-dependent effects of ludartin on cell proliferation, migration, apoptosis, cell cycle arrest at the G2/M checkpoint involved p21WAFI in Saos-2 osteosarcoma cells.

Effects of connective tissue growth factor on prostate cancer bone metastasis and osteoblast differentiation.

Previous studies have demonstrated that connective tissue growth factor (CTGF) is expressed at increased levels in prostate cancer bone metastasis mouse models and patients with prostate cancer which metastasizes to the bone; however, the underlying molecular mechanism(s) remain unknown. The present study investigated the function of CTGF in osteoblast differentiation and its effect on prostate cancer bone metastasis by analyzing CTGF gene expression and transcription at different levels of invasion, metastasis of prostate cancer cells, and the influence of CTGF on proliferation and xenotransplantation. A mouse model demonstrating bone metastasis was used to investigate the function(s) of CTGF in bone metastasis and osteoblast differentiation. Results demonstrated that CTGF expression was increased in association with high bone metastasis in prostate cancer cells, and its expression was significantly decreased in whole cell lysates. CTGF expression in prostate cancer cells with high levels of bone metastasis was increased 1.9-fold compared with prostate cancer cells with low levels of bone metastasis. The expression of CTGF in mesenchymal cells was markedly increased compared with epithelial cells. Results indicated that the increased expression of CTGF does not affect the proliferation of tumor cells and possesses no influence on tumor volume. Control and CTGF plasmids were transfected into RM1 cells and led to 4 and 17% bone lesions, respectively. Increased expression of CTGF significantly enlarged the tumor area in the bone metastatic position compared with the control. Positive areas of alkaline phosphatase were significantly decreased as the concentration of CTGF increased. The results of the present study demonstrated that CTGF promotes prostate carcinoma to metastasize in the bone by dysregulating osteoblast differentiation.

Up-Regulation of MiR-300 Promotes Proliferation and Invasion of Osteosarcoma by Targeting BRD7.

Increasing reports suggest that deregulated microRNAs (miRNAs) might provide novel therapeutic targets for cancers. However, the expression and function of miR-300 in osteosarcoma is still unknown. In our study, we found that the expression of miR-300 was up-regulated in osteosarcoma tissues and cells compared with paired adjacent non-tumor bone tissues and osteoblastic cells using RT-qPCR. The enforced expression of miR-300 could promote cell proliferation, invasion and epithelial-mesenchymal transition (EMT). Moreover, we identified that bromodomain-containing protein 7 (BRD7), a new tumor suppressor gene, was a direct target of miR-300. Ectopic expression of BRD7 could significantly inhibit miR-300-promoted proliferation, invasion and EMT. Therefore, our results identify an important role for miR-300 in osteosarcoma through regulating BRD7 expression.