Pathologic fracture does not influence prognosis in stage IIB osteosarcoma: a case–control study

OBJECTIVE: This study tested the implication of pathologic fractures on the prognosis in stage IIb osteosarcoma. METHODS: A single center retrospective evaluation of clinical management and oncologic outcome was conducted with 15 pathological fracture patients (M:F = 10:5; age: mean 23.2, range 12–42) and 50 non-fracture patients between April 2002 and December 2010. These stage IIB osteosarcoma patients were matched for age, tumor site (femur, tibia, and humerus), and osteosarcoma subtype (i.e., control patients with osteosarcoma in the same sites as the fracture patients). All osteosarcoma patients with pathological fractures underwent brace or cast immobilization, adjuvant chemotherapy, and limb salvage surgery or amputation. Musculoskeletal Tumor Society (MSTS) functional scores were assessed. The mean follow-up time was 34.7 months (range, 8–47 months). RESULTS: Following limb salvage surgery, no statistical differences were observed in major complications (fracture = 20.0%, control = 12.0%, P = 0.43) or local recurrence complications (fracture = 26.7%, control = 14.0%, P = 0.25). Overall 3-year survival rates of the fracture and control groups (66.7% and 75.3%, respectively) were not statistically different (P = 0.5190). Three-year disease-free survival rates of the fracture and control groups were 53.3% and 66.5%, respectively (P = 0.25). CONCLUSIONS: Pathologic fracture was not a prognostic indicator of recurrence or overall survival in localized osteosarcoma patients. Limb salvage can be achieved by and maintaining adequate surgical margins and applying adjuvant chemotherapy

Associations of triglyceride levels with longevity and frailty: A Mendelian randomization analysis.

Observational studies suggest associations of triglyceride levels with longevity and frailty. This study aimed to test whether the associations are causal. We used data from the Rugao Longevity and Ageing Study, a population-based cohort study performed in Rugao, China. A variant in the APOA5 gene region (rs662799) was used as the genetic instrument. Mendelian randomization (MR) analyses were performed to examine the associations of genetically predicted triglycerides with two ageing phenotypes - longevity ( ≥95 years) and frailty (modified Fried frailty phenotype and Rockwood frailty index). C allele of rs662799 was robustly associated with higher triglyceride levels in the comparison group (β = 0.301 mmol/L per allele, p < 0.001), with an F statistic of 95.3 and R2 = 0.040. However MR analysis did not provide strong evidence for an association between genetically predicted triglyceride levels and probability of longevity (OR: 0.61; 95% CI: 0.35, 1.07 per 1 mmol/L increase in triglycerides). In the ageing arm (70-84 years), genetically predicted triglyceride levels were not associated with the frailty index (β = 0.008; 95% CI: -0.013, 0.029) or the frailty phenotype (OR: 1.91; 95% CI: 0.84, 4.37). In conclusion, there is currently a lack of sufficient evidence to support causal associations of triglyceride levels with longevity and frailty in elderly populations

An integrative multi-platform analysis for discovering biomarkers of osteosarcoma

<p>Abstract</p> <p>Background</p> <p>SELDI-TOF-MS (Surface Enhanced Laser Desorption/Ionization-Time of Flight-Mass Spectrometry) has become an attractive approach for cancer biomarker discovery due to its ability to resolve low mass proteins and high-throughput capability. However, the analytes from mass spectrometry are described only by their mass-to-charge ratio (<it>m</it>/<it>z</it>) values without further identification and annotation. To discover potential biomarkers for early diagnosis of osteosarcoma, we designed an integrative workflow combining data sets from both SELDI-TOF-MS and gene microarray analysis.</p> <p>Methods</p> <p>After extracting the information for potential biomarkers from SELDI data and microarray analysis, their associations were further inferred by link-test to identify biomarkers that could likely be used for diagnosis. Immuno-blot analysis was then performed to examine whether the expression of the putative biomarkers were indeed altered in serum from patients with osteosarcoma.</p> <p>Results</p> <p>Six differentially expressed protein peaks with strong statistical significances were detected by SELDI-TOF-MS. Four of the proteins were up-regulated and two of them were down-regulated. Microarray analysis showed that, compared with an osteoblastic cell line, the expression of 653 genes was changed more than 2 folds in three osteosarcoma cell lines. While expression of 310 genes was increased, expression of the other 343 genes was decreased. The two sets of biomarkers candidates were combined by the link-test statistics, indicating that 13 genes were potential biomarkers for early diagnosis of osteosarcoma. Among these genes, cytochrome c1 (CYC-1) was selected for further experimental validation.</p> <p>Conclusion</p> <p>Link-test on datasets from both SELDI-TOF-MS and microarray high-throughput analysis can accelerate the identification of tumor biomarkers. The result confirmed that CYC-1 may be a promising biomarker for early diagnosis of osteosarcoma.</p

CYP2A6 activity and cigarette consumption interact in smoking-related lung cancer susceptibility.

Cigarette smoke, containing both nicotine and carcinogens, causes lung cancer. However, not all smokers develop lung cancer, highlighting the importance of the interaction between host susceptibility and environmental exposure in tumorigenesis. Here, we aimed to delineate the interaction between metabolizing ability of tobacco carcinogens and smoking intensity in mediating genetic susceptibility to smoking-related lung tumorigenesis. Single-variant and gene-based associations of 43 tobacco carcinogen-metabolizing genes with lung cancer were analyzed using summary statistics and individual-level genetic data, followed by causal inference of Mendelian randomization, mediation analysis, and structural equation modeling. Cigarette smoke-exposed cell models were used to detect gene expression patterns in relation to specific alleles. Data from the International Lung Cancer Consortium (29,266 cases and 56,450 controls) and UK Biobank (2,155 cases and 376,329 controls) indicated that the genetic variant rs56113850 C>T located in intron 4 of CYP2A6 was significantly associated with decreased lung cancer risk among smokers [odds ratio (OR) = 0.88, 95% confidence interval = 0.85-0.91, P = 2.18×10-16], which might interact (Pinteraction = 0.028) with and partially be mediated (ORindirect = 0.987) by smoking status. Smoking intensity accounted for 82.3% of the effect of CYP2A6 activity on lung cancer risk but entirely mediated the genetic effect of rs56113850. Mechanistically, the rs56113850 T allele rescued the downregulation of CYP2A6 caused by cigarette smoke exposure, potentially through preferential recruitment of transcription factor HLTF. Together, this study provides additional insights into the interplay between host susceptibility and carcinogen exposure in smoking-related lung tumorigenesis

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

All-arthroscopic versus mini-open repair of small to large sized rotator cuff tears: a meta-analysis of clinical outcomes.

The purpose of this study was to compare clinical outcomes of patients with full-thickness small to large sized tears undergoing all-arthroscopic versus mini-open rotator cuff repair.A literature search for electronic databases and references for eligible studies was conducted through Medline, Embase and Cochrane library between 1969 and 2013.A total of 12 comparative studies (n = 770 patients) were included. Pooled results showed: there were no differences in function outcome, pain scores, retear rate or the incidence of adhesive capsulitis between all arthroscopic and mini-open repair groups.There were no differences in outcomes between the arthroscopic and mini-open rotator cuff repair techniques, they should be considered alternative treatment options.Level IV, Meta analysis

Mesenchymal stem cells in the osteosarcoma microenvironment: their biological properties, influence on tumor growth, and therapeutic implications

Abstract During tumorigenesis and development, participation of the tumor microenvironment is not negligible. As an important component in the tumor microenvironment, mesenchymal stem cells (MSCs) have been corroborated to mediate proliferation, metastasis, and drug resistance in many cancers, including osteosarcoma. What’s more, because of tumor site tropism, MSCs can be engineered to be loaded with therapeutic agents so that drugs can be precisely delivered to tumor lesions. In this review, we mainly discuss recent advances concerning the functions of MSCs in osteosarcoma and their possible clinical applications in the future

Laparoscopic parenchyma-sparing resections for solid pseudopapillary tumors located in the head of pancreas

Abstract Background Solid pseudopapillary tumor (SPT) of the pancreas is a rare low-grade malignant tumor. Here, we aimed to determine the safety and feasibility of laparoscopic parenchyma-sparing pancreatectomy for SPT located in the pancreatic head. Methods From July 2014 to February 2022, 62 patients with SPT located in the pancreatic head were operated laparoscopically in two institutions. These patients were divided into two groups according to the operative strategy: laparoscopic parenchyma-sparing pancreatectomy (27 patients, group 1) and laparoscopic pancreaticoduodenectomy (35 patients, group 2). The clinical data were retrospectively collected and analyzed in terms of demographic characteristics, perioperative variables, and long-term follow-up outcomes. Results The demographic characteristics of the patients in the two groups were comparable. Compared to the patients in group 2, those in group 1 required less operative time (263.4 ± 37.2 min vs. 332.7 ± 55.6 min, p < 0.001) and experienced less blood loss (105.1 ± 36.5mL vs. 188.3 ± 150.7 mL, p < 0.001). None of the patients in group 1 had tumor recurrence or metastasis. However, 1 (2.5%) patient in group 2 showed liver metastasis. Conclusion Laparoscopic parenchyma-sparing pancreatectomy is a safe and feasible approach for SPT located in the pancreatic head, with favorable long-term functional and oncological results

Effect of Impregnation with Maltodextrin and 1,3-Dimethylol-4,5-Dihydroxyethyleneurea on Poplar Wood

Modification of poplar (Populus adenopoda Maxim) wood by using maltodextrin (MA) combined with 1,3-dimethylol-4,5-dihydroxyethyleneurea (DM) resin was investigated in this study. The weight percent gain, dimensional stability, mechanical strength, and microscopic chemical change were determined before and after impregnation. Results indicated that the composite modifier was impregnated into the wood cell lumen, as verified by scanning electron microscopy and a change in weight percent gain. Anti-swelling efficiency was significantly improved compared with the untreated sample; however, the sample treated with MA obtained an anti-swelling efficiency that was slightly lower than that of the sample treated with sucrose. The flexural strength, flexural modulus, and compressive strength perpendicular to the grain increased with an increase in MA concentration, but the compressive modulus and impact strength were reduced. Fourier-transform infrared spectroscopy demonstrated that MA delayed the cross-linking of the DM resin cell wall, and X-ray diffraction analysis showed that the crystallinity of the cellulose crystalline region was reduced to a certain extent. In general, the poplar wood treated with combined MA and DM resin exhibited enhanced properties relative to those of the poplar wood treated with sucrose