Hepatocellular carcinoma (HCC) is a lethal disease, and recurrence and metastasis are the major causes of death in HCC patients. Cancer-associated fibroblasts (CAFs), a major stromal cell type in the HCC microenvironment, promote HCC progression, and have gradually become a hot research topic in HCC-targeted therapy. This review comprehensively describes and discusses the heterogeneous tissue distribution, cellular origin, phenotype, and biological functions of HCC-associated fibroblasts. Furthermore, the possible use of CAFs for predicting HCC prognosis and in targeted therapeutic strategies is discussed, highlighting the critical roles of CAFs in HCC progression, diagnosis, and therapy.
Osteoarthritis not only results in cartilage lesion, but also is accompanied with subchondral bone damage caused by the inflammatory response. It is of great significance to treat osteoarthritis by regulating the immune response. As copper (Cu) plays an essential role in immune response and anti-arthritis, a copper-incorporated bioactive glass-ceramics (Cu-BGC) may achieve the aim of healing cartilage lesion and reducing inflammatory response caused by osteoarthritis. We hypothesized that the Cu2+ released from Cu-BGC scaffolds may satisfy the requirements of cartilage regeneration and anti-arthritis.Methods: 3D-printing method was employed to prepare Cu-BGC scaffolds. The stimulating effect on the chondrocytes and macrophages cultured with Cu-BGC extracts was investigated. Furthermore, the in vivo regenerative effect of Cu-BGC scaffolds on osteochondral defects was studied.Results: The incorporation of Cu2+ into BGC considerably promoted the proliferation and maturation of chondrocytes, and induced macrophages shifting to anti-inflammatory phenotype. Histological analysis demonstrated that the Cu-BGC scaffolds meaningfully improved the regeneration of cartilage and elevated the recovery of the osteochondral interface as compared with the CTR and BGC groups. The potential mechanism is related to Cu2+ ions triggering the immune response of cartilage via activating HIF signaling pathway and inhibiting the inflammatory response in osteochondral tissue.Conclusion: These results demonstrated that Cu-BGC scaffolds significantly facilitated the regeneration of cartilage and osteochondral interface, as well as inhibited inflammatory response, which may prevent the development of osteoarthritis associated with osteochondral defects.
Post-operative IMRT following narrow-margin hepatectomy may be a favourable therapy for both its safety profile and clinical benefit in patients with HCC located close to the major vessels.
Background and AimHepatocellular carcinoma (HCC) is one of the most deadly tumors. Transarterial chemoembolization (TACE) is effective for unresectable HCC. In recent years, miRNAs have been proposed as novel diagnostic and prognostic tools for HCC. This study aimed to identify whether microRNAs (miRNAs) can serve as biomarkers to reliably predict outcome before HCC patients are treated with TACE.MethodsEleven miRNAs (miR-, miR-19a, miR-101-3p, miR-199a-5p, miR-200a, miR-21, miR-214, miR-221, miR-222, miR-223 and miR-, -5p) were quantified by quantitative real-time PCR (qRT-PCR) in 136 HCC patients’ serum before they received TACE therapy. Univariate and multivariate analysis were used to identify the prognostic value of clinical parameters and miRNAs. Area under the receiver operating characteristic curve (AUC) was used to evaluate the prediction potency.ResultsThe levels of some miRNAs were dramatically associated with clinicopathologic features regarding Child-Puge class, AFP, tumor size and satellite nodules. Univariate analysis revealed that miR-200a, miR-21, miR-122 and miR-224-5p were significantly associated with patients’ survival. Multivariate analysis demonstrated that AFP, satellite nodules and miR-200a were the independent prognostic factors associated with survival in this cohort (p = 0.000, 0.001, 0.000, respectively). The probability of the prognostic accuracy of miR-200a was 81.64% (74.47% specificity and 88.76% sensitivity), which was higher than the classifier established by combination of AFP and satellite nodules (76.87% probability, 70.21% specificity and 69.66% sensitivity). Furthermore, the combination of AFP, satellite nodules and miR-200a demonstrated as a classifier for HCC prognosis, yielding a ROC curve area of 88.19% (93.62% specificity and 68.54% sensitivity).ConclusionsOur study indicated that serum miR-200a may prognosticate disease outcome in HCC patients with TACE therapy. Therefore, miR-200a can potentially guide individualized treatment for HCC patients with a high risk of TACE treatment failures.
Background: Persistent descending mesocolon (PDM) is a rare colonic anatomical variant. However, PDM's impact on the technical aspects and outcomes of laparoscopic colorectal cancer resection are unclear. Patients and Methods: This retrospective clinical cohort study was conducted at a high-volume cancer center in Japan to evaluate intra-and postoperative outcomes of laparoscopic colorectal cancer surgery in patients with (PDM+) or without (PDM-) PDM over the past 7 years. Results: Between January 2012 and September 2019, 2,775 patients underwent laparoscopic colorectal cancer resection at our center, including 60 (2.1%) cases of PDM. Preoperative detection was achieved in only 5 patients (8.3%), 39 patients were men, and 21 patients were women. The average age was 67 years. Twenty patients had a history of prior abdominal surgery (33.3%), with little or no subsequent adhesions. The average duration of sigmoidectomy in PDM+ patients (n=17; 217.7±14.2 min) was significantly longer than that in 176.2±2.4 min; p=0.003), as was average blood loss (32.3±10.6 ml vs. 16.7±2.8 ml; p=0.03). Likewise, average operative time for high anterior resection in PDM+ patients (n=11; 227.1±20.2 min) was significantly longer than that in 195.6±3.0 min; p=0.048). Rates of postoperative anastomotic leakage and postoperative recurrence did not differ in both groups. In PDM+ patients, retention of left colic artery had no impact on proximal specimen margins or occurrences of anastomotic leakage. Conclusion: PDM prolongs operative times and increases bleeding in laparoscopic colorectal cancer surgery and should be considered a risk factor when encountered.
The study aims to investigate the techniques of design and construction of CT 3D reconstructional data-based polycaprolactone (PCL)-hydroxyapatite (HA) scaffold. Femoral and lumbar spinal specimens of eight male New Zealand white rabbits were performed CT and laser scanning data-based 3D printing scaffold processing using PCL-HA powder. Each group was performed eight scaffolds. The CAD-based 3D printed porous cylindrical stents were 16 piece × 3 groups, including the orthogonal scaffold, the Pozi-hole scaffold and the triangular hole scaffold. The gross forms, fiber scaffold diameters and porosities of the scaffolds were measured, and the mechanical testing was performed towards eight pieces of the three kinds of cylindrical scaffolds, respectively. The loading force, deformation, maximum-affordable pressure and deformation value were recorded. The pore-connection rate of each scaffold was 100 % within each group, there was no significant difference in the gross parameters and micro-structural parameters of each scaffold when compared with the design values (P > 0.05). There was no significant difference in the loading force, deformation and deformation value under the maximum-affordable pressure of the three different cylinder scaffolds when the load was above 320 N. The combination of CT and CAD reverse technology could accomplish the design and manufacturing of complex bone tissue engineering scaffolds, with no significant difference in the impacts of the microstructures towards the physical properties of different porous scaffolds under large load.
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