Cancer-associated fibroblasts (CAFs) are a major contributor to tumor stromal crosstalk in the tumor microenvironment (TME) and boost tumor progression by promoting angiogenesis and lymphangiogenesis. This study aimed to identify prognostic genes associated with CAFs that lead to high morbidity and mortality in ovarian cancer (OC) patients. We performed bioinformatics analysis in 16 multicenter studies (2,742 patients) and identified CAF-associated hub genes using the weighted gene co-expression network analysis (WGCNA). A machine learning methodology was used to identify COL16A1, COL5A2, GREM1, LUM, SRPX, and TIMP3 and construct a prognostic signature. Subsequently, a series of bioinformatics algorithms indicated risk stratification based on the above signature, suggesting that high-risk patients have a worse prognosis, weaker immune response, and lower tumor mutational burden (TMB) status but may be more sensitive to routine chemotherapeutic agents. Finally, we characterized prognostic markers using cell lines, immunohistochemistry, and single-cell sequencing. In conclusion, these results suggest that the CAF-related signature may be a novel pretreatment guide for anti-CAFs, and prognostic markers in CAFs may be potential therapeutic targets to inhibit OC progression.
Purpose This study was undertaken to elucidate the clinical significance of widening of the popliteal hiatus on magnetic resonance imaging (MRI), and to document the clinical results and technical aspects of arthroscopic repair of this finding. Methods Included are 82 knees after arthroscopic surgery, divided according to arthroscopic diagnosis into group A, hypermobility of lateral meniscus, 8 knees; group B, tear of the anterior horn of the lateral meniscus, 32 knees; and group C, no abnormality of the lateral meniscus, 36 knees with medial meniscal tears and 6 with other conditions. Popliteal hiatus diameter was measured and the popliteal hiatus/lateral tibial plateau (LTP) ratio was calculated on preoperative sagittal and coronal MRI. At arthroscopy, the widened popliteal hiatus in group A was tightened anteriorly by outside-in or all-inside suture and posteriorly with all-inside suture. Outcomes were evaluated with MRI, Lysholm, Tegner and VAS scores. ResultsThe preoperative diameter of the popliteal hiatus and the popliteal hiatus/LTP ratio were significantly larger in group A than in groups B and C (p < 0.05) on both views. Threshold popliteal hiatus/LTP values of 0.16 and 0.18 on the sagittal and coronal views demonstrated diagnostic discrimination, and these values were significantly reduced after arthroscopy in Group A. Lysholm and Tegner scores were improved after tightening of the popliteal hiatus, while VAS scores reduced (all p < 0.05). Conclusion Widening of the popliteal hiatus on MRI may lead to recurrent subluxation of the lateral meniscus. Arthroscopic anterior and posterior tightening of the popliteal hiatus was a safe and effective treatment. Level of evidence II.
Background: The ketogenic diet (KD) has been reported to play an important role in the development of cancer by an abundance of pre-clinical experiments; however, their conclusions have been controversial. We therefore aimed to perform a systematic review and meta-analysis of animal studies evaluating the effects of KD on cancer.Methods: Relevant studies were collected by searching PubMed, Embase, and Web of Science. Outcome measures comprised tumor weight, tumor volume, and survival time. Meta-analysis was performed using the random-effect model according to heterogeneity.Results: The search resulted in 1,254 references, of which 38 were included in the review and 17 included in the meta-analysis. Pooled results indicated that KD supplementation significantly prolonged survival time [standardized mean difference (SMD) = 1.76, 95% CI (0.58, 2.94), p = 0.003], and reduced tumor weight [SMD = −2.459, 95% CI (−4.188, −0.730), p = 0.027] and tumor volume [SMD = −0.759, 95% CI (−1.349, −0.168), p = 0.012]. Meta-regression and subgroup analysis results suggested that KD supplementation at a ratio of 4:1 was associated with remarkable prolongation of survival time in animals with limited tumor types.Conclusion: In summary, the pre-clinical evidence pointed toward an overall anti-tumor effect of the KD in animals studies currently available with limited tumor types.
We investigated whether the implantation of juvenile allograft and minced meniscal fragments could improve the healing of avascular meniscal injuries, which cannot heal spontaneously. Concentric cylindrical explants were excised from the inner two-thirds of swine medial menisci. The inner cylinder consisted of a "sandwich" structure, with minced juvenile meniscal fragments, juvenile meniscal columns, minced mature meniscal fragments, or mature meniscal columns implanted in the middle. The explants were cultured in vitro for 2, 4, or 6 weeks. Interfacial meniscal repair was assessed by histology, immunohistochemistry, biomechanical testing, and confocal laser scanning microscopy. Histology and confocal microscopy results revealed that tissue repair and cell accumulation at the interface were best at all time points in the juvenile meniscal fragments group, followed by the juvenile columns, minced mature fragments, and mature columns groups, respectively. At 6 weeks, the implantation of juvenile allograft and minced meniscal fragments increased the shear strength, peak force, and energy to failure in the peripheral interface. Picosirius red/polarized light microscopy and immunohistochemistry results showed concurrent expression of type I and II collagen in the interfacial repair tissue. In conclusion, implantation of juvenile allograft and minced meniscal fragments could increase the healing of avascular meniscal injury in vitro. ß
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