Identification and prognostic evaluation of differentially expressed long noncoding RNAs associated with immune infiltration in osteosarcoma.

Osteosarcoma is a malignant bone cancer that originates from the bone with the strongest invasiveness. Tumor formation strongly correlates with immune cell infiltration into the tumor immune microenvironment (TIME). Therefore, we aimed to identify TIME-related biomarkers as potential prognostic markers of osteosarcoma. The mRNA and long noncoding RNA (lncRNA) transcriptome data of 88 patients with osteosarcoma and the expression profile of GSE99671 were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus, respectively. Immune infiltration scores and types were evaluated using ESTIMATE and CIBERSORT. A linear model was established to identify the differentially expressed genes (DEGs) and lncRNAs (DElncRNAs). Functional enrichment analysis of DEGs was conducted by Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis, and gene set variation analysis. DElncRNAs were analyzed using a weighted gene co-expression network. Least absolute shrinkage and selection operator regression was applied to screen for prognostic markers. Patient survival was predicted by the risk score and analyzed by receiver operating characteristic curve. Clinical features affecting patient survival were assessed. Immune infiltration positively correlated with osteosarcoma patient survival. Different immune cell infiltrates in patients with osteosarcma may serve as prognostic indicators and targets for immunotherapy. In total, 1125 DEGs, 80 DElncRNAs, and 11 pairs of co-expressed lncRNA-mRNAs were identified. DEGs in the three modules were associated with immune infiltration into the TIME. Four DElncRNAs, namely AC015819.1, AC015911.3, AL365361.1, and USP30-AS1, showed good prognostic ability for osteosarcoma and were positively correlated with the immune score. Tumor metastasis and risk scores alone were good prognostic indicators, and a combination of the two variables can better predict the prognosis of osteosarcoma. We identified four lncRNAs, AC015819.1, AC015911.3, AL365361.1, and USP30-AS1, as potential biomarkers for osteosarcoma prognosis.

Reversal of cardiac and renal damage in a teenager with hypertension: A case report.

The authors describe the case of a 16-year-old male who was incidentally found to have a blood pressure of 200/? mmHg 6 months previously due to blurred vision and was diagnosed with "high risk of hypertension grade 3, renal insufficiency, hypertensive encephalopathy, hypertensive heart disease, and fundus hemorrhage" after relevant examinations were performed. His blood pressure fluctuated around 120/90 mmHg after beginning antihypertensive treatment. While the diagnostic work-up of his hypertension was inconclusive, he had severe hypertension with brachydactyly type E and short stature on physical examination. The patient's cardiac damage and renal insufficiency ultimately returned to normal after strict blood pressure control, suggesting that hypertension and brachydactyly syndrome alone do not cause cardiac and renal damage.

Argon-helium knife cryoablation plus programmed cell death protein 1 inhibitor in the treatment of advanced soft tissue sarcomas: there is no evidence of the synergistic effects of this combination therapy.

Background: Effective treatment for advanced soft tissue sarcomas (STSs) is necessary for improved outcomes. Previous studies have suggested that cryoablation can have a synergistic effect with programmed cell death protein-1 (PD-1) inhibitor in the treatment of malignancy. This study aimed to clarify the efficacy and safety of argon-helium knife cryoablation in combination with PD-1 inhibitor in the treatment of STSs. Methods: Retrospectively collected and analyzed the clinical data of patients with advanced STS who underwent cryoablation and PD-1 inhibitor between March 2018 and December 2021. Results: This study included 27 patients with advanced STS. In terms of target lesions treated with cryoablation, 1 patient achieved complete response, 15 patients had partial response (PR), 10 patients had stable disease, and 1 patient had progressive disease. This corresponded to an overall response rate of 59.3% and a disease control rate of 96.3%. In terms of distant target lesions untreated with cryoablation, only two patients had a PR compared to the diameter of the lesion before ablation. The combination therapy was relatively well tolerated. None of the patients experienced treatment-related death or delayed treatment due to adverse events. Conclusion: Cryoablation combined with PD-1 inhibitors in the therapy of advanced STS is safe and can effectively shrink the cryoablation-target lesion. However, there is no evidence of the synergistic effects of this combination therapy.

The pedicled sartorius flap and mesh (PSM) technique vs no reconstruction in repairing the defect after type III pelvic bone tumor resection: a retrospective study.

BACKGROUND: Type III pelvic bone tumor resections are often accompanied by postoperative complications. In order to reduce complications, we developed a novel pedicled sartorius flap and mesh (PSM) technique to reconstruct the pelvic ring defect. In this study, we evaluated the efficacy and risks of this PSM technique in type III pelvic bone tumor resections by comparing outcomes between patients that underwent PSM reconstruction and patients that did not receive any reconstruction. METHODS: We retrospectively reviewed a consecutive set of patients that underwent type III pelvic bone tumor surgeries in our center from January 2020 to January 2021 with either PSM reconstruction (designated as the PSM group) or without any reconstruction (designated as the control group). General information such as age, gender, tumor type, tumor size, and surgical-related information such as duration of surgery, blood loss, and the surgical margins was collected. Outcome data recorded included wound complications such as infection and dehiscence, local recurrence, and Musculoskeletal Tumor Society (MSTS) scores for postoperative functional evaluation. Statistical analysis between both groups was performed with GraphPad Prism v7. RESULTS: A total of 20 patients were included in this study (PSM group n = 12, control group n = 8). While no herniation was found in the PSM group, it occurred in 6 of 8 cases in the control group. The control group showed a significantly higher rate of bacterial infection (p = 0.03) and wound dehiscence (p = 0.02) but lower MSTS scores (p < 0.05) compared to the PSM group. CONCLUSIONS: The use of the PSM technique can significantly reduce postoperative complication rates and enhance postoperative function following type III pelvic bone tumor resection.

Efficacy and safety of sintilimab plus doxorubicin in advanced soft tissue sarcoma: A single-arm, phase II trial.

Background: Chemoimmunotherapy is safe and efficacious in treating many types of malignant tumors. However, clinical data demonstrating the effect of this combination treatment in patients with metastatic soft tissue sarcoma (STS) are currently limited. This study evaluated the safety and efficacy of a programmed cell death protein 1 (PD-1) inhibitor plus doxorubicin in patients with advanced STS who failed previous systemic therapy. Methods: This was a single-center, single-arm, open-label phase II trial. Patients with unresectable or metastatic STS who had previously failed systemic therapy were enrolled. Patients received up to six cycles of doxorubicin and sintilimab (a PD-1 inhibitor), while sintilimab treatment continued for up to 2 years. Primary outcomes were objective response rate (ORR) and safety. Univariate Cox proportional hazards model was used to analyze the relationship between clinicopathological parameters and progression-free survival (PFS). Results: A total of 38 patients (20 men and 18 women) were enrolled in this study. The overall ORR was 39.5%, disease control rate was 71.1%, and the median PFS was 4.5 months [95% confidence interval (CI), 3.0-8.5 months]. The adverse events (AEs) associated with the combined treatment were mild, manageable, and well-tolerated. The most common grade 3 or higher AEs were hematologic, including leukopenia (21.1%), anemia (18.4%), and thrombocytopenia (18.4%). Patients with undifferentiated pleomorphic sarcoma (UPS) or dedifferentiated liposarcoma had a significantly longer PFS than those with other pathological subtypes [hazard ratio (HR) = 0.42, 95% CI 0.21-0.83; p = 0.013]. There was no significant difference in the median PFS between patients who had previously received anthracycline-based chemotherapy and those who had not (HR = 0.74, 95% CI 0.34-1.58, p = 0.43). Conclusion: Sintilimab plus doxorubicin is a safe and promising treatment for patients with advanced STS who have failed previous systemic therapy (including anthracycline-based chemotherapy). The efficacy of this combination therapy in UPS and dedifferentiated liposarcoma is superior to that in other sarcomas. Clinical Trial Registration: https://www.chictr.org.cn, registration number: ChiCTR1900027009.

[Application of three-dimensional printed customized prosthesis with preserved epiphysis and articular surface in the reconstruction of large bone defects in treatment of adolescent femoral malignant tumors].

Objective: To investigate the clinical application and effectiveness of three-dimensional (3D) printed customized prosthesis with preserved epiphysis and articular surface in the reconstruction of large bone defects in treatment of adolescent femoral malignant tumors. Methods: The clinical data of 10 adolescent patients with femoral primary malignant tumor who met the selection criteria and underwent limb salvage surgery with 3D printed customized prosthesis with preserved epiphysis and articular surface between January 2020 and October 2021 were retrospectively analyzed. There were 6 males and 4 females with an average age of 12.5 years ranging from 7 to 18 years. There were 8 cases of osteosarcoma and 2 cases of Ewing's sarcoma. Enneking stage was Ⅱb. The length of the lesions ranged from 76 to 240 mm, with an average of 138.0 mm. The length of osteotomy (i. e. length of customized prosthesis) ranged from 130 to 275 mm, with an average of 198.5 mm; the distance between distal osteotomy end and epiphyseal line ranged from 0 to 15 mm, with an average of 8.8 mm; the bone defect after osteotomy accounted for 37.36% to 79.02% of the total length of the lesion bone, with a mean of 49.43%. The operation time, intraoperative blood loss, complications, tumor outcome (refered to RESIST1.1 solid tumor efficacy evaluation criteria), and limb length discrepancy were recorded. The Musculoskeletal Cancer Society (MSTS) 93 score was used to evaluate the function at 6 months after operation, and visual analogue scale (VAS) score was used to evaluate the pain before and after operation. Results: The operation was successfully performed in all the 10 patients, and the postoperative pathological results were consistent with the preoperative pathological results. The operation time was 165-440 minutes, with an average of 263 minutes; and the intraoperative blood loss was 100-800 mL, with an average of 350 mL. All patients were followed up 7-26 months, with an average of 11.8 months. No tumor was found on the osteotomy surface; the customized prosthesis were firmly installed and closely matched with the retained articular surface. The tumor outcome of neoadjuvant chemotherapy was stable in 4 cases and partial remission in 6 cases. No local recurrence or distant metastasis was found in 9 cases after postoperative adjuvant chemotherapy; pulmonary metastasis was found in 1 case at 12 months after operation. Two patients had local incision fat liquefaction, superficial infection, and delayed healing at 14 days after operation; 1 patient had local bone absorption at the contact surface of the prosthesis, and the screw and prosthesis did not loosen at 7 months after operation; the other patients had good incision healing, with no infection, prosthesis loosening, fracture, or other complications. At 6 months after operation, the MSTS93 score was 19-28, with an average of 24.1; 8 cases were excellent and 2 cases were good. The VAS score was 0.9±1.0, which significantly improved when compared with before operation (5.9±1.0) ( t=23.717, P<0.001). The height of the patients increased by 1-12 cm, with an average of 4.6 cm. At last follow-up, 4 patients had limb length discrepancy, with a length difference of 1 cm in 2 cases and 2 cm in 2 cases. Conclusion: The application of 3D printed customized prosthesis in the resection and reconstruction of adolescents femoral primary malignant tumors can achieve the purpose of preserving epiphysis and articular surface, and obtain good effectiveness.

Experience in utilizing a novel 3D digital model with CT and MRI fusion data in sarcoma evaluation and surgical planning.

OBJECTIVE: To assess sarcoma margins with more accuracy and aid surgical planning, we constructed three-dimensional (3D) digital models with computed tomography(CT) and magnetic resonance imaging (MRI) image fusion data and validated the preciseness of the models by comparing them with 3D models constructed with CT only data. MATERIALS AND METHODS: We retrospectively reviewed a consecutive set of patients treated in our center who were preoperatively evaluated with the fusion image model. Models based on fusion images or CT-only data were constructed. Volumes of both tumors were calculated and the tumors were overlapped to see the location of differences between the two models. RESULTS: A consecutive 12 cases (4 male vs. 8 female) were included in this study. Most of the tumors were located in the pelvic bone or spine. The volume of the two tumor models was different and the differences were mainly in the peripheral region of the tumor. CONCLUSION: CT and MRI fusion image 3D models are more accurate than models with CT-only data and can be very helpful in preoperative planning of sarcoma patients.

Disruption of the primary salicylic acid hydroxylases in rice enhances broad-spectrum resistance against pathogens.

Salicylic acid (SA) is a crucial hormone involved in plant immunity. Rice (Oryza sativa) maintains high SA levels that are not induced by pathogens. However, the roles of SA in rice immunity and yield remain largely unknown. Here, we identified SA 5-hydroxylases 1 (OsS5H1) and 2 (OsS5H2) as the primary enzymes engaged in catalysing SA to 2,5-dihydroxybenzoic acid (2,5-DHBA) in rice. SA levels were significantly increased in the oss5h mutants, while they were dramatically decreased in the OsS5H1 and OsS5H2 overexpression lines. The mutants were resistant, whereas the overexpression lines were susceptible to Pyricularia oryzae and Xanthomonas oryzae pv. Oryzae. Moreover, the pathogen-associated molecular patterns-triggered immunity responses, including reactive oxygen species burst and callose deposition, were enhanced in all the mutants and compromised in the overexpression lines. Quantification of the agronomic traits of the oss5h mutants grown in the paddy fields demonstrated that the grain number per panicle was decreased as the SA levels increased; however, the tiller number and grain size were enhanced, resulting in no significant yield penalty. Collectively, we reveal that mildly increasing SA content in rice can confer broad-spectrum resistance without yield penalty and put new insights into the roles of SA in immunity and growth.

Nanoparticle albumin-bound paclitaxel and PD-1 inhibitor (sintilimab) combination therapy for soft tissue sarcoma: a retrospective study.

BACKGROUND: There is increasing evidence that combination therapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and programmed cell death protein 1 (PD-1) inhibitor is safe and efficacious in treating many types of malignant tumors. However, clinical data demonstrating the effect of this treatment combination for patients with metastatic soft tissue sarcoma (STS) are currently limited. METHODS: The clinical data of patients with metastatic STS who received nab-paclitaxel plus PD-1 inhibitor (sintilimab) therapy between January 2019 and February 2021 were retrospectively analyzed. The effectiveness and safety of the combined treatment were evaluated in terms of the median progression-free survival (PFS), estimated using the Kaplan-Meier method. The univariate Cox proportional hazards model was used to analyze the relationship between clinicopathological parameters and PFS. All statistical analyses were two-sided; P < 0.05 was considered statistically significant. RESULTS: A total of 28 patients treated with nab-paclitaxel plus sintilimab were enrolled in this study. The objective response rate was 25%, the disease control rate was 50%, and the median PFS was 2.25 months (95% CI = 1.8-3.0 months). The most common grade 1 or 2 adverse events (AEs) were alopecia (89.3%; 25/28), leukopenia (25.0%; 7/28), fatigue (21.4%; 6/28), anemia (21.4%; 6/28), and nausea (21.4%; 6/28). The most common grade 3 AEs were neutropenia (10.7%; 3/28) and peripheral neuropathy (10.7%; 3/28). No grade 4 AEs were observed. Among the present study cohort, patients with angiosarcoma (n = 5) had significantly longer PFS (P = 0.012) than patients with other pathological subtypes, including undifferentiated pleomorphic sarcoma (n = 7), epithelioid sarcoma (n = 5), fibrosarcoma (n = 4), synovial sarcoma (n = 3), leiomyosarcoma (n = 2), pleomorphic liposarcoma (n = 1), and rhabdomyosarcoma (n = 1); those who experienced three or more AEs had significantly longer median PFS than those who experienced less than three AEs (P = 0.018). CONCLUSION: Nab-paclitaxel plus PD-1 inhibitor is a promising treatment regimen for advanced STS. Randomized controlled clinical trials are required to further demonstrate its efficacy and optimal application scenario.

Clinical Experience with Apatinib and Camrelizumab in Advance Clear Cell Sarcoma: A Retrospective Study.

PURPOSE: Advanced clear cell sarcoma (CCS) is a rare subtype of sarcoma with few effective treatments. Evidence shows that apatinib is efficacious and safe for CCS. This study aimed to assess the safety and efficacy of apatinib and/or camrelizumab (a PD-1 inhibitor) in treating advanced CCS. METHODS: We retrospectively reviewed 12 patients with advanced CCS who received apatinib and/or camrelizumab therapy between November 2018 and July 2021. Standard descriptive statistics were employed for continuous variables and categorical variables (number and percentage). RESULTS: Of the 12 CCS patients, 3 had a partial response (PR), and 4 had stable disease (SD). Among the 5 patients treated with apatinib monotherapy, 1 PR and 2 SD were found, and the addition or replacement of camrelizumab after progressive disease (PD) did not work. In the 4 patients who received apatinib plus camrelizumab combination therapy, 1 PR and 1 SD were found. All 3 patients who received camrelizumab first had PD, and 1 PR and 1 SD were found after adding apatinib. Grade 3 or 4 adverse events were significantly more common in the apatinib plus camrelizumab combination therapy than in the apatinib or camrelizumab monotherapy, and these included increased aspartate aminotransferase and increased alanine aminotransferase levels. CONCLUSION: Apatinib has promising effectiveness for CCS. Camrelizumab efficacy for the treatment of clear cell sarcoma is inconclusive. The efficacy of apatinib and PD-1 inhibitors in CCS need to be further investigated in prospective clinical trials.

Undifferentiated Pleomorphic Sarcoma with Neoplastic Fever: A Retrospective Study.

BACKGROUND: Although the annual incidence of undifferentiated pleomorphic sarcoma (UPS) is extremely low, it can be subdivided into different subtypes. UPS with fever of unknown origin (also known as neoplastic fever) is a specific subtype of UPS, which shows certain clinical features that differentiate it from other UPS subtypes. However, no studies have focused on this rare UPS subtype. This study retrospectively analyzed the clinical data of patients with UPS to provide a reference for the diagnosis and treatment of UPS with neoplastic fever. METHODS: This study included patients with UPS who were diagnosed and treated between June 2012 and June 2018. We examined whether these patients had a history of neoplastic fever. The characteristics of patients with UPS with neoplastic fever were summarized and analyzed. RESULTS: We reviewed the medical records of 183 patients with UPS. Seven (3.83%) of these patients had neoplastic fever. In patients with UPS with neoplastic fever, the primary lesions were located in the extremities and across the muscle space. In these patients, magnetic resonance imaging showed necrosis within the tumor body and extensive soft tissue edema around the tumor body. Patients with UPS with neoplastic fever had a lower metastasis rate (14.29% vs 44.94%) and a higher 3-year survival rate (85.71% vs 59.55%) than those without neoplastic fever. CONCLUSION: UPS with neoplastic fever is characterized by intratumoral necrosis and extensive edema of the surrounding soft tissues. Patients with UPS with neoplastic fever may have a better prognosis than those without neoplastic fever.

High-Quality Genome Sequence Resource of a Rice False Smut Fungus Ustilaginoidea virens Isolate, UV-FJ-1.

Ustilaginoidea virens is the fungal pathogen causing rice false smut, resulting in not only yield lost but also grain pollution with toxic mycotoxins. Here we deployed PacBio Sequel II HIFI-read sequencing technology to generate a near-complete genome assembly for the U. virens isolate UV-FJ-1 (38.48 Mb), which was isolated from Fujian province, China. The genome assembly contains 116 contigs with N50 of 0.65 Mb and a maximum length of 2.10 Mb, and the genome completeness is ≥98% assessed by benchmarking universal single-copy orthologs (BUSCOs) and the mapping rate of Illumina short reads. Excluding 35.78% repeat sequences, we identified a total of 7,164 protein-coding genes, of which 5,818 were functionally annotated and 223 encode putative effector proteins. Moreover, 21 secondary metabolite biosynthesis gene clusters were found in UV-FJ-1 genome. Taken together, this high-quality genome assembly and gene annotation resource will provide a better insight for characterizing the biological and pathogenic mechanisms of U. virens.

Plant Virology Delivers Diverse Toolsets for Biotechnology.

Over a hundred years of research on plant viruses has led to a detailed understanding of viral replication, movement, and host-virus interactions. The functions of vast viral genes have also been annotated. With an increased understanding of plant viruses and plant-virus interactions, various viruses have been developed as vectors to modulate gene expressions for functional studies as well as for fulfilling the needs in biotechnology. These approaches are invaluable not only for molecular breeding and functional genomics studies related to pivotal agronomic traits, but also for the production of vaccines and health-promoting carotenoids. This review summarizes the latest progress in these forefronts as well as the available viral vectors for economically important crops and beyond.