Serum extracellular vesicle-derived miR-21-5p and miR-26a-5p as non-invasive diagnostic potential biomarkers for gastric cancer: A preliminary study.

PURPOSE: Gastric cancer is the most common malignancy worldwide and is the third leading cause of cancer-related deaths, urgently requiring an early and non-invasive diagnosis. Circulating extracellular vesicles may emerge as promising biomarkers for the rapid diagnosis in a non-invasive manner. METHODS: Using high-throughput small RNA sequencing, we profiled the small RNA population of serum-derived extracellular vesicles from healthy controls and gastric cancer patients. Differentially expressed microRNAs (miRNAs) were randomly selected and validated by reverse transcription-quantitative real-time polymerase chain reaction. Receiver operating characteristic curves were employed to assess the predictive value of miRNAs for gastric cancer. RESULTS: In this study, 193 differentially expressed miRNAs were identified, of which 152 were upregulated and 41 were significantly downregulated. Among the differently expressed miRNA, the expression levels of miR-21-5p, miR-26a-5p, and miR-27a-3p were significantly elevated in serum-derived extracellular vesicles of gastric cancer patients. The miR-21-5p and miR-27a-3p were closely correlated with the tumor size. Moreover, the expression levels of serum miR-21-5p and miR-26a-5p were significantly decreased in gastric cancer patients after surgery. CONCLUSIONS: The present study discovered the potential of serum miR-21-5p and miR-26a-5p as promising candidates for the diagnostic and prognostic markers of gastric cancer.

Surgical Strategy and Application of Robotic-Assisted Benign Sacral Neurogenic Tumor Resection.

BACKGROUND: Robotic surgery may be advantageous in neurogenic sacral tumor resection but only a few studies reported robotic-assisted neurogenic sacral tumor resection. OBJECTIVE: To propose a new surgical strategy for robotic-assisted benign sacral neurogenic tumor resection and introduce the ultrasonic osteotomy surgical system in robotic surgery. METHODS: Twelve patients who had robotic-assisted primary benign sacral neurogenic tumor resection between May 2015 and March 2021 were included. Our surgical strategy divides tumors into 4 types. Type I: Presacral tumors with diameter <10 cm. Type II: Narrow-base tumors involving the sacrum with diameter <10 cm. Type III: Broad-base tumors involving the sacrum with diameter <10 cm. Type IV: Tumors involving sacral nerve roots ≥2 levels and/or with diameter ≥10 cm. RESULTS: Five type I, 5 type II, and 1 type III patients underwent tumor resection via an anterior approach, and 1 type IV patient via a combined approach. The median operation time, blood loss, and postoperative hospital stay of type I and II were much less than those of type IV. The ultrasonic osteotomy surgical system facilitated osteotomy in 2 type II and 1 type III patients. Eleven patients had total resections, and 1 type III patient had a partial resection. During the follow-up period of 7.9 to 70.9 months (median: 28.5 months), no local recurrences or deaths were noted. CONCLUSION: With the largest single-center series to our knowledge, this surgical strategy helped to guide robotic-assisted benign sacral neurogenic tumor resection. The ultrasonic osteotomy surgical system was effective for type II and III.

Treatment of pyogenic liver abscess by surgical incision and drainage combined with platelet-rich plasma: A case report.

BACKGROUND: Pyogenic liver abscesses are insidious in the early stage. Some cases progress rapidly, and the patient's condition can worsen and even become life-threatening if timely treatment is not provided. Surgery and prolonged antibiotic treatment are often required if the abscess is large and liquefied and becomes separated within the lumen. CASE SUMMARY: We report a case of bacterial liver abscess with a poor outcome following pharmacological treatment, review the literature related to the use of platelet-rich plasma (PRP) in the treatment of hepatic impairment and partial hepatectomy in animals, and discuss the prognostic features of surgical incision and drainage combined with PRP in the treatment of bacterial liver abscesses. This is the first case describing the use of PRP in the treatment of a bacterial liver abscess in humans, providing new ideas for the treatment of this condition. CONCLUSION: This case highlights the importance of surgical treatment for bacterial liver abscesses that are well liquefied and poorly managed medically. PRP may produce antimicrobial effects and promote the regeneration and repair of liver tissue.

A Novel Method to Treat Progressive Desmoid Tumors Involving Neurovascular Bundles: A Retrospective Cohort Study.

BACKGROUND: More effective therapies are needed to treat progressive desmoid tumors when active surveillance and systemic therapy fail. OBJECTIVE: To assess the efficacy and safety of sandwich isolation surgery on the local control of progressive desmoid tumors involving neurovascular bundles. METHODS: A total of 27 patients with progressive desmoid tumors at extremities involving neurovascular bundles who received surgery at our hospital between August 2014 and August 2018 were identified. A total of 13 patients received sandwich isolation surgery, in which R2 resection was performed in neurovasculature-involving regions, and a biomaterial patch was used to envelop involved neurovascular structures and isolate residual tumors. In non-neurovasculature-involving regions, wide resection was performed without isolation. A total of 14 patients received traditional surgery, which included tumor resection without isolation procedure. RESULTS: In sandwich isolation group, tumor progressions and local recurrences occurred in 3 patients outside the isolated neurovasculature-involving regions. However, no progressions or recurrences occurred in any patients in the isolated neurovasculature-involving regions where R2 resection was performed. Sandwich isolation surgery group and traditional surgery group shared similar baseline clinical characteristics. The estimated 3-yr event-free survival rate was 76.9% after sandwich isolation surgery, and 32.7% after traditional surgery (P = .025). Patients who received sandwich isolation surgery were less likely to have local recurrence (hazard ratio: 0.257, P = .040). No complications were noted except intermittent mild pain in operative regions (2 cases). CONCLUSION: Sandwich isolation surgery is effective and safe for local control of desmoid tumors involving neurovascular bundles.

Upgrade of laser pump time-resolved X-ray probes in Beijing synchrotron.

The upgrade of the laser pump time-resolved X-ray probes, namely time-resolved X-ray absorption spectroscopy (TR-XAS) and X-ray diffraction (TR-XRD), implemented at the Beijing Synchrotron Radiation Facility, is described. The improvements include a superbunch fill, a high-efficiency fluorescence collection, an efficient spatial overlap protocol and a new data-acquisition scheme. After upgrade, the adequate TR-XAS signal is now obtained in a 0.3 mM solution, compared with a 6 mM solution in our previous report. Furthermore, to extend application in photophysics, the TR-XAS probe is applied on SrCoO2.5 thin film. And for the first time, TR-XAS is combined with TR-XRD to simultaneously detect the kinetic trace of structural changes in thin film.

Pore-forming toxin-like protein complex expressed by frog promotes tissue repair.

Tissue repair is a highly dynamic process, and the immediate onset of acute inflammation has been considered necessary for repair. Pore-forming proteins are important, both in pathogen invasion and host immunity. However, their roles in wound healing and tissue repair are unclear. ßγ-crystallin fused aerolysin-like protein (α-subunit) and trefoil factor (ß-subunit) complex (ßγ-CAT) is a complex of a bacterial pore-forming toxin aerolysin-like protein and trefoil factor identified in the frog Bombina maxima. In this study, we established mouse cutaneous wound models to explore the effects of ßγ-CAT on skin wound healing. ßγ-CAT accelerated the healing of full-thickness wounds by improving re-epithelialization. This complex relieved dermal edema and promoted scarless healing. ßγ-CAT treatment resulted in a rapid release of IL-1ß, which initiated an acute inflammation response in the early stage of healing. Meanwhile, the expression levels of TGF-ß1, VEGF, and bFGF and the recruitment of M2 macrophages around the wound significantly increased after ßγ-CAT treatment. ßγ-CAT protected skin wounds against methicillin-resistant Staphylococcus aureus by improving neutrophil recruitment at the site of the wound. Overall, our results suggest that ßγ-CAT can promote tissue repair and protect skin wounds against antibiotic-resistant bacterial infection by triggering the acute inflammatory response. This is the first example that aerolysin-like pore-forming proteins widely existing in plants and animals may act in wound healing and tissue repair.-Gao, Z.-H., Deng, C.-J., Xie, Y.-Y., Guo, X.-L., Wang, Q.-Q., Liu, L.-Z., Lee, W.-H., Li, S.-A., Zhang, Y. Pore-forming toxin-like protein complex expressed by frog promotes tissue repair.

Effects of thermal treatment on the properties of defatted soya bean flour and its adhesion to plywood.

With an attempt to economically and efficiently improve the water resistance of defatted soya bean flour (DSF)-based wood adhesives, DSF was subjected to thermal treatment at various temperatures (65°C, 80°C, 95°C, 110°C and 125°C) for 30 min. The effects of thermal treatment temperature onto the chemical structure, crystalline degree, water-insoluble content and acetaldehyde value of the thermally treated DSF (T-DSF) were investigated. The thermal stabilities and bonding properties of soya bean adhesives prepared from T-DSF and cross-linker epichlorohydrin-modified polyamide (EMPA) were also investigated. Test results indicated that both the water-insoluble content and the acetaldehyde value of T-DSF increased after thermal treatment, reaching the highest values of 27.28% and 26.81 mg g-1, respectively. All plywood bonded with the T-DSF-based adhesive withstood a 28 h boiling-dry-boiling accelerated ageing treatment, while plywood bonded with the DSF-based adhesive delaminated after 4 h of water boiling, demonstrating the significantly improved water resistance of the T-DSF-based adhesives. Related analyses also confirmed that this improvement was due to: (i) the formation of insoluble cross-linked structures of T-DSF resulting from protein-protein self-cross-linking reactions and the protein-carbohydrate Maillard reaction and (ii) increased cross-linking efficiency between T-DSF and cross-linker EMPA owing to more T-DSF-reactive groups being released after thermal treatment.

Telangiectatic osteosarcoma: Outcome analyses and a diagnostic model for differentiation from aneurysmal bone cyst.

BACKGROUND AND PURPOSE: Telangiectatic osteosarcoma (TOS), a rare variant of osteosarcoma, may be easily misdiagnosed as aneurysmal bone cyst (ABC). The aims of this study were to investigate the diagnostic and prognostic factors of TOS by reviewing our experience with TOS and to develop a diagnostic model that may distinguish TOS from ABC. MATERIALS AND METHODS: We identified 51 cases of TOS treated at the First Affiliated Hospital of Sun Yat-Sen University from March 2001 to January 2016 and reviewed their records, imaging information and pathological studies. A diagnostic model was developed to differentiate TOS and ABC by Bayes discriminant analysis and was evaluated. The log-rank test was used to analyze the prognostic factors of TOS and to compare the outcome differences between TOS and other high-grade osteosarcoma subtypes. RESULTS: The multi-disciplinary diagnostic method employed that combined clinical, imaging, and pathological studies enhanced the diagnostic accuracy. Age 18 years or younger and pathologic fracture were more common among the TOS patients than among the ABC patients (P = .004 and .005, respectively). The average white blood cell (WBC), platelet, lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) values of the TOS patients were higher than those of the ABC patients (P = .002, .003, .007, and .007, respectively). Our diagnostic model, including the aforementioned factors, accurately predicted 62% and 78% of the TOS patients in the training and validation sets, respectively. The 5-year estimates of event-free survival and overall survival of the TOS patients were 52.5 ± 9.4% and 54.9 ± 8.8%, respectively, which were similar to those of patients with other osteosarcoma subtypes (P = .950 and .615, respectively). Tumor volume and the LDH level were predictive prognostic factors (P = .040 and .044) but not the presence of pathologic fracture or misdiagnosis (P = .424 and .632, all respectively). CONCLUSIONS: The multi-disciplinary diagnostic method and diagnostic model based on predictive factors, i.e., age, the presence of pathologic fracture, and platelet, LDH, ALP and WBC levels, aided the differentiation of TOS and ABC. Smaller tumors and normal LDH levels were associated with better outcomes.

Sclerosing angiomatoid nodular transformation of the spleen: A case report and literature review.

Sclerosing angiomatoid nodular transformation (SANT) is a rare benign splenic vascular lesion. Since it was first defined in 2004, a total of 132 cases of SANT have been reported in ~50 studies in the English literature. However, it remains difficult to form a definitive pre-operative differential diagnosis of SANT compared with other splenic tumors or malignant lesions. The present study reports a pathologically proven case of SANT in a 29-year-old man who initially presented with left upper quadrant and back discomfort. The study also provides a review of the current knowledge on the condition, including the clinical profile, imaging features, cytological features, differential diagnosis and treatment of SANT. The most important distinguishing features of SANT are its typical vascular character and lack of other features that are typical of a granuloma. A splenectomy is required and the diagnosis is based on pathological analysis.

Proliferation PET image to characterize pathological spatial features in patients with non-small cell lung cancer: a pilot study.

PURPOSE: (18)F-FLT-PET imaging was proposed as a tool for measuring in vivo tumor cell proliferation and detecting sub-volumes to propose escalation in radiotherapy. The aim of this study was to validate whether high FLT uptake areas in (18)F-FLT PET/CT are coincident with tumor cell proliferation distribution indicated by Ki-67 staining in non-small cell lung cancer, thus provide theoretical support for the application of dose painting guided by (18)F-FLT PET/CT. MATERIALS AND METHODS: Twelve treatment naive patients with biopsy proven NSCLC underwent (18)F-FLT PET/CT scans followed by lobectomy were enrolled. The surgical specimen was dissected into 4-7 µm sections at approximately 4-mm intervals. The best slice was sort out to complete Ki-67 staining. Maximum Ki-67 labelling Index and SUVmax of the corresponding PET image was calculated. The correlation between Ki-67 Labelling Index and SUVmax of FLT was determined using Spearman Correlation analysis. High uptake areas and high proliferating areas were delineated on the two images, respectively, and their location was compared. RESULTS: The maximal SUV was 3.26 ± 0.97 (1.96-5.05), maximal Ki-67 labeling index was 49% ± 27.56% (5%-90%). Statistical analysis didn't reveal a significant correlation between them (r = -0.157, P = 0.627, > 0.05). 9 patients can contour high proliferating area on Ki-67 staining slice, and eight can contour the high uptake areas. In 4 patients, we can observe a generally close distribution of high uptake areas and high proliferating areas, in one patient, both the uptake level and proliferation status was low, while the others didn't not find a significant co-localization. CONCLUSION: Noninvasive (18)F-FLT PET assessing the proliferative status may be a valuable aid to guide dose painting in NSCLC, but it needs to be confirmed further.

Local control of giant cell tumors of the long bone after aggressive curettage with and without bone cement.

BACKGROUND: Aggressive curettage has been well established for the treatment of giant cell tumors (GCTs) of the bone. The purpose of this study was to review our experience and evaluate the role of different implant materials in patients with GCTs of the extremities after aggressive curettage. METHODS: A total of 119 patients with GCTs of the long bone were treated at the First Affiliated Hospital of Sun Yat-Sen University between 2004 and 2009. We excluded patients presenting metastases, recurrent tumors, and soft tissue involvement and those with Jaffe pathological grade III. The remaining 65 patients were treated with aggressive curettage using a bone graft or bone cement to fill the cavity. The recurrence rates and functional scores associated with the different fillings were analyzed. RESULTS: Aggressive curettage and bone grafting was performed in 34 cases (52.3%), and aggressive curettage with bone cement was performed in 31 cases (47.7%). The overall recurrence rate after the aggressive intralesional procedures was 35.3% with bone grafting and 12.9% when bone cement was used as an adjuvant filling. The recurrence rate following aggressive curettage and bone grafting was higher than that following aggressive curettage with cement (p = 0.038). The Musculoskeletal Tumor Society (MSTS) score for bone graft patients was 91.1%, which was significantly lower than that for patients treated with bone cement (94.7%). CONCLUSIONS: The use of bone cement was associated with a significantly lower recurrence rate than bone grafting following aggressive intralesional curettage to treat benign giant cell tumors of the long bone. Better MSTS functional results were also observed in the bone cement group compared to the bone graft group.

Preoperative easily misdiagnosed telangiectatic osteosarcoma: clinical-radiologic-pathologic correlations.

PURPOSE: To describe the clinical, imaging, and pathologic characteristics and diagnostic methods of telangiectatic osteosarcoma (TOS) for improving the diagnostic level. MATERIALS AND METHODS: The authors retrospectively reviewed patient demographics, serum alkaline phosphatase (AKP) levels, preoperative biopsy pathologic reports, pathologic materials, imaging findings, and treatment outcomes from 26 patients with TOS. Patient images from radiography (26 cases) and magnetic resonance (MR) imaging (22 cases) were evaluated by 3 authors in consensus for intrinsic characteristics. There were 15 male and 11 female patients in the study, with an age of 9-32 years (mean age 15.9 years). RESULTS: Eighteen of 26 patients died of lung metastases within 5 years of follow-up. The distal femur was affected more commonly (14 cases, 53.8%). Regarding serum AKP, normal (8 cases) or mildly elevated (18 cases) levels were found before preoperative chemotherapy. Radiographs showed geographic bone lysis without sclerotic margin (26 cases), cortical destruction (26 cases), periosteal new bone formation (24 cases), soft-tissue mass (23 cases), and matrix mineralization (4 cases). The aggressive radiographic features of TOS simulated the appearance of conventional high-grade intramedullary osteosarcoma, though different from aneurysmal bone cyst. MR images demonstrated multiple big (16 cases) or small (6 cases) cystic spaces, fluid-fluid levels (14 cases), soft-tissue mass (22 cases), and thick peripheral and septal enhancement (22 cases). Nine of 26 cases were misdiagnosed as aneurysmal bone cysts by preoperative core-needle biopsy, owing to the absence of viable high-grade sarcomatous cells in the small tissue samples. CONCLUSION: The aggressive growth pattern with occasional matrix mineralization, and multiple big or small fluid-filled cavities with thick peripheral, septal, and nodular tissue surrounding the fluid-filled cavities are characteristic imaging features of TOS, and these features are helpful in making the correct preoperative diagnosis of TOS.

The glycogen synthase kinase-3ß/nuclear factor-kappa B pathway is involved in cinobufagin-induced apoptosis in cultured osteosarcoma cells.

Cinobufagin, a major component of cinobufacini (huachansu), is an important cardenolidal steroid. Several studies have suggested that cinobufagin has potent anti-cancer effects. The present study examines the apoptosis-inducing activity and the underlying mechanism of action of cinobufagin in osteosarcoma (OS) cells. Our results showed that cinobufagin potently inhibited the proliferation of U2OS, MG63 and SaOS-2 cells. Significant increases in G2/M cell-cycle arrest and apoptosis in OS cells were also observed. The expression levels of several apoptotic proteins were assessed after cinobufagin treatment in U2OS cells. Among them, xIAP, cIAP-1, survivin and Bcl-2 levels decreased remarkably, while the levels of Bax and cleaved-PARP increased. Furthermore, we validated the inhibition of GSK-3ß/NF-κB signaling following cinobufagin treatment. Western blots showed a decrease in nuclear p65 protein expression after exposure to different concentrations of cinobufagin, while the phosphorylation of GSK-3ß was simultaneously increased. Transduction with constitutively active forms of GSK-3ß could protect against the downregulation of p65 and upregulation of cleaved-PARP that are induced by cinobufagin treatment. However, combined treatment with cinobufagin and SB216367 resulted in a significant reduction in p65 and an increase in cleaved-PARP in U2OS cells. Altogether, these results show that cinobufagin is a promising agent for the treatment of OS. These studies are the first to reveal the involvement of the GSK-3ß/NF-κB pathway in cinobufagin-induced apoptosis.

Critical role of heat shock protein 27 in bufalin-induced apoptosis in human osteosarcomas: a proteomic-based research.

Bufalin is the primary component of the traditional Chinese herb "Chan Su". Evidence suggests that this compound possesses potent anti-tumor activities, although the exact molecular mechanism(s) is unknown. Our previous study showed that bufalin inhibited growth of human osteosarcoma cell lines U2OS and U2OS/MTX300 in culture. Therefore, this study aims to further clarify the in vitro and in vivo anti-osteosarcoma effects of bufalin and its molecular mechanism of action. We found bufalin inhibited both methotrexate (MTX) sensitive and resistant human osteosarcoma cell growth and induced G2/M arrest and apoptosis. Using a comparative proteomics approach, 24 differentially expressed proteins following bufalin treatment were identified. In particular, the level of an anti-apoptotic protein, heat shock protein 27 (Hsp27), decreased remarkably. The down-regulation of Hsp27 and alterations of its partner signaling molecules (the decrease in p-Akt, nuclear NF-κB p65, and co-immunoprecipitated cytochrome c/Hsp27) were validated. Hsp27 over-expression protected against bufalin-induced apoptosis, reversed the dephosphorylation of Akt and preserved the level of nuclear NF-κB p65 and co-immunoprecipitated Hsp27/cytochrome c. Moreover, bufalin inhibited MTX-resistant osteosarcoma xenograft growth, and a down-regulation of Hsp27 in vivo was observed. Taken together, bufalin exerted potent anti-osteosarcoma effects in vitro and in vivo, even in MTX resistant osteosarcoma cells. The down-regulation of Hsp27 played a critical role in bufalin-induced apoptosis in osteosarcoma cells. Bufalin may have merit to be a potential chemotherapeutic agent for osteosarcoma, particularly in MTX-resistant groups.