Intelligent identification system of gastric stromal tumors based on blood biopsy indicators.

BACKGROUND: The most prevalent mesenchymal-derived gastrointestinal cancers are gastric stromal tumors (GSTs), which have the highest incidence (60-70%) of all gastrointestinal stromal tumors (GISTs). However, simple and effective diagnostic and screening methods for GST remain a great challenge at home and abroad. This study aimed to build a GST early warning system based on a combination of machine learning algorithms and routine blood, biochemical and tumour marker indicators. METHODS: In total, 697 complete samples were collected from four hospitals in Gansu Province, including 42 blood indicators from 318 pretreatment GST patients, 180 samples of gastric polyps and 199 healthy individuals. In this study, three algorithms, gradient boosting machine (GBM), random forest (RF), and logistic regression (LR), were chosen to build GST prediction models for comparison. The performance and stability of the models were evaluated using two different validation techniques: 5-fold cross-validation and external validation. The DeLong test assesses significant differences in AUC values by comparing different ROC curves, the variance and covariance of the AUC value. RESULTS: The AUC values of both the GBM and RF models were higher than those of the LR model, and this difference was statistically significant (P < 0.05). The GBM model was considered to be the optimal model, as a larger area was enclosed by the ROC curve, and the axes indicated robust model classification performance according to the accepted model discriminant. Finally, the integration of 8 top-ranked blood indices was proven to be able to distinguish GST from gastric polyps and healthy people with sensitivity, specificity and area under the curve of 0.941, 0.807 and 0.951 for the cross-validation set, respectively. CONCLUSION: The GBM demonstrated powerful classification performance and was able to rapidly distinguish GST patients from gastric polyps and healthy individuals. This identification system not only provides an innovative strategy for the diagnosis of GST but also enables the exploration of hidden associations between blood parameters and GST for subsequent studies on the prevention and disease surveillance management of GST. The GST discrimination system is available online for free testing of doctors and high-risk groups at https://jzlyc.gsyy.cn/bear/mobile/index.html .

The prognostic role of circulating tumor cells in gastric cancer: A meta-analysis.

Objective: We conducted a meta-analysis to evaluate the relationship between circulating tumor cells (CTC) and the prognosis of patients with gastric cancer. Materials and methods: The cohort studies reporting on the relationship between CTC and prognosis of gastric cancer were collected from Pubmed, Cochrane, Embase, CNKI, WanFang Data, and VIP databases. The two researchers independently screened the literature, extracted the data, and evaluated the bias risk of the included literature. The data were analyzed by Revman software (Review Manager version 5.4). Result: A total of 14 retrospective cohort studies with 1053 patients were included. The results showed that the overall survival time (OS) and progression-free survival time (PFS) of CTC-positive patients were shorter compared to CTC-negative patients. Taking into consideration the critical value of CTC positive patients, country of origin, sample size, treatment mode, and study time, the subgroup analysis showed that CTC-positive was related to the shortening of OS in patients with gastric cancer. Based on the subgroup analysis of the factors such as CTC positive critical value < 2.8, sample size ≥ 75, mixed therapy, longer study duration, country, and immunofluorescence detection of CTC, it was found that OS in CTC positive group was shorter than that in CTC-negative group (all P<0.05), while the critical value of positive CTC ≥ 2.8, sample size ≥ 75, choice of treatment only for operation or non-operation, short study time and molecular detection of CTC were not associated with OS (all P>0.05). In addition, CTC-positive patients had a more advanced TNM staging, poorer tumor differentiation, and earlier distant metastasis. Conclusion: CTC can be used as a prognostic indicator of gastric cancer. Gastric cancer patients with positive CTC may have a poorer prognosis compared to those with CTC-negative tumors. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022323155.

3D Bioprinting of Biomimetic Bilayered Scaffold Consisting of Decellularized Extracellular Matrix and Silk Fibroin for Osteochondral Repair.

Recently, three-dimensional (3D) bioprinting technology is becoming an appealing approach for osteochondral repair. However, it is challenging to develop a bilayered scaffold with anisotropic structural properties to mimic a native osteochondral tissue. Herein, we developed a bioink consisting of decellularized extracellular matrix and silk fibroin to print the bilayered scaffold. The bilayered scaffold mimics the natural osteochondral tissue by controlling the composition, mechanical properties, and growth factor release in each layer of the scaffold. The in vitro results show that each layer of scaffolds had a suitable mechanical strength and degradation rate. Furthermore, the scaffolds encapsulating transforming growth factor-beta (TGF-ß) and bone morphogenetic protein-2 (BMP-2) can act as a controlled release system and promote directed differentiation of bone marrow-derived mesenchymal stem cells. Furthermore, the in vivo experiments suggested that the scaffolds loaded with growth factors promoted osteochondral regeneration in the rabbit knee joint model. Consequently, the biomimetic bilayered scaffold loaded with TGF-ß and BMP-2 would be a promising strategy for osteochondral repair.

Hyaluronate-Based Self-Stabilized Nanoparticles for Immunosuppression Reversion and Immunochemotherapy in Osteosarcoma Treatment.

Immunotherapy is regarded as a potential strategy to combat cancer, especially when immunotherapy is combined with appropriate chemotherapy. However, the immunosuppressive tumor microenvironment (TME) and serious side effects extremely limit the application of immunotherapy. Herein, a self-stabilized hyaluronic acid nanoparticle is synthesized for tumor-targeted delivery of doxorubicin (DOX), cisplatin (CDDP), and resiquimod (R848) in osteosarcoma immunochemotherapy, which is referred to as CDDPNPDOX&R848. CDDPNPDOX&R848 exhibits sufficient stability, great pH responsibility, and brilliant tumor-targeting accumulation in vivo, which make it suitable for further in vivo applications. After intravenous injection, CDDPNPDOX&R848 can release the loaded cargoes under the acidic TME continuously. DOX can induce tumor cell apoptosis in combination with CDDP and trigger immunogenic cell death. More importantly, the immune-activated TME created by R848 can facilitate tumor-associated antigen presentation and antitumor immunity elicitation. Benefiting from the synergistic effect of chemotherapy and immunotherapy, the growth of tumors and lung metastasis was greatly inhibited by CDDPNPDOX&R848 in the K7M2 orthotopic osteosarcoma mouse model. Thus, this intelligent codelivery platform might be a competitive candidate for osteosarcoma immunochemotherapy.

Injectable Ultrasonication-Induced Silk Fibroin Hydrogel for Cartilage Repair and Regeneration.

Articular cartilage lacks both a nutrient supply and progenitor cells. Once damaged, it has limited self-repair capability. Cartilage tissue engineering provides a promising strategy for regeneration, and the use of injectable hydrogels as scaffolds has recently attracted much attention. Silk fibroin (SF) is an advanced natural material used to construct injectable hydrogels that are nontoxic and can be used efficiently in crosslinking applications. The objective of the present work was to develop an injectable hydrogel using SF in a novel one-step ultrasonication crosslinking method. Gelation kinetics and the characteristics of ultrasonication-induced SF (US-SF) hydrogels were systematically evaluated. The cytocompatibility of US-SF hydrogels was evaluated using rabbit chondrocytes, the Cell Counting Kit-8 testing, and immunofluorescence staining. Furthermore, the in vivo cartilage regenerative ability of US-SF hydrogels was confirmed following subcutaneous administration in nude mice and in situ injections in rabbit osteochondral defect models. These results suggest that US-SF hydrogels could be potential candidates for cartilage repair and regeneration. Impact statement Injectable silk fibroin hydrogel is a promising strategy for cartilage tissue engineering. The transition from solution state to gel state can be fabricated by both physical and chemical methods. However, the complexing protocol and toxicity of these methods remain hindrances to further application. In this study, a one-step ultrasonication method was developed. The novel ultrasonication-induced silk fibroin hydrogel showed satisfactory physicochemical and biomechanical properties. In vitro and in vivo experiments proved that it could promote cartilage regeneration, indicating that it may be a potential solution for cartilage repair and regeneration.

Crosslinker-free silk/decellularized extracellular matrix porous bioink for 3D bioprinting-based cartilage tissue engineering.

As cartilage tissue lacks the innate ability to mount an adequate regeneration response, damage to it is detrimental to the quality of life of the subject. The emergence of three-dimensional bioprinting (3DBP) technology presents an opportunity to repair articular cartilage defects. However, widespread adoption of this technique has been impeded by difficulty in preparing a suitable bioink and the toxicity inherent in the chemical crosslinking process of most bioinks. Our objective was to develop a crosslinker-free bioink with the same biological activity as the original cartilage extracellular matrix (ECM) and good mechanical strength. We prepared bioinks containing different concentrations of silk fibroin and decellularized extracellular matrix (SF-dECM bioinks) mixed with bone marrow mesenchymal stem cells (BMSCs) for 3D bioprinting. SF and dECM interconnect with each other through physical crosslinking and entanglement. A porous structure was formed by removing the polyethylene glycol from the SF-dECM bioink. The results showed the SF-dECM construct had a suitable mechanical strength and degradation rate, and the expression of chondrogenesis-specific genes was found to be higher than that of the SF control construct group. Finally, we confirmed that a SF-dECM construct that was designed to release TGF-ß3 had the ability to promote chondrogenic differentiation of BMSCs and provided a good cartilage repair environment, suggesting it is an ideal scaffold for cartilage tissue engineering.

Low-Temperature Three-Dimensional Printing of Tissue Cartilage Engineered with Gelatin Methacrylamide.

Low-concentration gelatin methacryloyl (GelMA) hydrogels have been found to be promising cell-laden bioinks with excellent cell viability. Herein, we report a strategy that accurately deposits cell-containing bioinks at 5% (w/v) GelMA using extrusion three-dimensional (3D) bioprinting technology by utilizing its photo-crosslinkable and thermosensitive properties without the need for any sacrificial materials. During the 3D printing process, regular, smooth microfibers were formed without any discontinuity of extrusion or clogging, and photo-crosslinking was then used to stabilize the printed GelMA structure. After printing, the scaffolds were cultured in a chondrogenic medium to evaluate their significant roles in directing the behaviors of bone mesenchymal stem cells (BMSCs). Evidence of chondrogenic differentiation was demonstrated by Alcian blue staining and immunofluorescence (Col2a1) as well as the expression of chondrogenic genes. Finally, after platelet-rich plasma treatment, the in vivo effects of the BMSCs on cartilage regeneration on the thigh muscles of female nude mice were measured by using immunohistochemical techniques. The results showed that with this strategy, GelMA bioink displays excellent printability and a high cell survival rate. In vitro and in vivo, the cell-laden scaffold successfully regenerated mature cartilage via a cartilage-specific extracellular matrix, which seems to be suitable for cartilage regeneration and repair.

Addition of Platelet-Rich Plasma to Silk Fibroin Hydrogel Bioprinting for Cartilage Regeneration.

The recent advent of 3D bioprinting of biopolymers provides a novel method for fabrication of tissue-engineered scaffolds and also offers a potentially promising avenue in cartilage regeneration. Silk fibroin (SF) is one of the most popular biopolymers used for 3D bioprinting, but further application of SF is hindered by its limited biological activities. Incorporation of growth factors (GFs) has been identified as a solution to improve biological function. Platelet-rich plasma (PRP) is an autologous resource of GFs, which has been widely used in clinic. In this study, we have developed SF-based bioinks incorporated with different concentrations of PRP (12.5%, 25%, and 50%; vol/vol). Release kinetic studies show that SF-PRP bioinks could achieve controlled release of GFs. Subsequently, SF-PRP bioinks were successfully fabricated into scaffolds by bioprinting. Our results revealed that SF-PRP scaffolds possessed proper internal pore structure, good biomechanical properties, and a suitable degradation rate for cartilage regeneration. Live/dead staining showed that 3D, printed SF-PRP scaffolds were biocompatible. Moreover, in vitro studies revealed that tissue-engineered cartilage from the SF-PRP group exhibited improved qualities compared with the pure SF controls, according to histological and immunohistochemical findings. Biochemical evaluations confirmed that SF-PRP (50% PRP, v/v) scaffolds allowed the largest increases in collagen and glycosaminoglycan concentrations, when compared with the pure SF group. These findings suggest that 3D, printed SF-PRP scaffolds could be potential candidates for cartilage tissue engineering. Impact statement Three-dimensional bioprinting of silk fibroin (SF) hydrogel as bioinks is a promising strategy for cartilage tissue engineering, but it lacks biological activities, which favors proliferation of seeded cells and secretion of the extracellular matrix. In this study, we have successfully added platelet-rich plasma (PRP) into SF-based bioinks as an autologous source of growth factors. The 3D, printed SF-PRP scaffold showed an enhanced biological property, thus aiding in potential future development of novel cartilage tissue engineering applications.

Fixation of os acromiale using polyester sutures: a novel surgical treatment.

BACKGROUND: Patients with unstable os acromiale often complain of shoulder pain. Numerous surgical treatment options have been introduced with inconsistent clinical results. In this study, a novel surgical treatment using polyester sutures to fix unstable os acromiale was introduced, and clinical results were reported. METHODS: We retrospectively studied 10 shoulders that were diagnosed with os acromiale from January 2014 to January 2016. All 10 cases were of the meso-acromion type. Except for the first case in our series, cases of os acromiale were fixed using polyester sutures arthroscopically. The standardized scores and visual analog scale (VAS) were recorded preoperatively and at each follow-up. A computed tomography (CT) scan was ordered at the follow-up of 12 months. RESULTS: The average follow-up length was 28.7 months, ranging from 26 to 33 months. The average Constant score before surgery was 40.50±4.53 points, which significantly improved to 75.60±5.17 points after surgery. The average VAS score was reduced from 5.20±1.14 points to 1.60±0.84. At the follow-up of 12 months, a CT scan was ordered. All the patients showed a bony union of the os acromiale. On the CT scan, two small pits could be seen on the medial and lateral side of the acromion, which indicated the level of the os acromiale. The position of the os acromiale was good, and no evident sclerosis was found on the edges of the fragments. CONCLUSIONS: Polyester sutures could provide reliable strength for the fixation of os acromiale without any irritation from hardware.

Clinical outcomes after absorbable suture fixation of patellar osteochondral fracture following patellar dislocation.

BACKGROUND: Osteochondral fracture (OCF) is one of the severe complications following a patellar dislocation. The appropriate fixation method for patients with OCF remains controversial. METHODS: Eighteen patients who had undergone surgery after a patellar dislocation were recruited retrospectively. Patellar OCF was fixed with an absorbable suture in an unreported method. The medial patellofemoral ligament (MPFL) was repaired or reconstructed if necessary. The Lysholm and Kujala knee scoring systems were used to evaluate the knee function. Imaging examinations were used to confirm the fracture healing. RESULTS: The mean period of follow-up was 36 months. All patients recovered well postoperatively without symptomatic complications. The Lysholm score and the Kujala score improved significantly from 37.6 (SD =6.8) and 45.9 (SD =6.4) preoperatively to 80.9 (SD =7.4) and 89.4 (SD =6.8) postoperatively at the latest follow-up, respectively. Imaging evidence including X-ray and MRI revealed good healing of the OCFs. CONCLUSIONS: This study showed satisfactory mid-term outcomes of OCF fixation using absorbable suture, which supports this method's potential to be a novel surgical method in the treatment of patellar OCF caused by a patellar dislocation.