An automated method for assessing condyle head changes in patients with skeletal class II malocclusion based on CBCT images.

OBJECTIVES: Currently, there is no reliable automated measurement method to study the changes in the condylar process after orthognathic surgery. Therefore, this study proposes an automated method to measure condylar changes in patients with skeletal class II malocclusion following surgical-orthodontic treatment. METHODS: Cone-beam computed tomography (CBCT) scans from 48 patients were segmented using the nnU-Net network for automated maxillary and mandibular delineation. Regions unaffected by orthognathic surgery were selectively cropped. Automated registration yielded condylar displacement and volume calculations, each repeated three times for precision. Logistic regression and Linear regression were used to analyze the correlation between condylar position changes at different time points. RESULTS: The Dice score for the automated segmentation of the condyle was 0.971. The Intraclass correlation coefficients (ICCs) for all repeated measurements ranged from 0.93 to 1.00. The results of the automated measurement showed that 83.33% of patients exhibited condylar resorption occurring six months or more after surgery. Logistic regression and Linear regression indicated a positive correlation between counterclockwise rotation in the Pitch plane and condylar resorption(p < 0.01). And a positive correlation between the rotational angles in both three planes and changes in the condylar volume at six months after surgery(p ≤ 0.04). CONCLUSIONS: This study's automated method for measuring condylar changes shows excellent repeatability. Skeletal class II malocclusion patients may experience condylar resorption after bimaxillary orthognathic surgery, and this is correlated with counterclockwise rotation in the sagittal plane. ADVANCES IN KNOWLEDGE: This study proposes an innovative multi-step registration method based on CBCT, and establishes an automated approach for quantitatively measuring condyle changes post-orthognathic surgery. This method opens up new possibilities for studying condylar morphology.

Potential risk assessment and occurrence characteristic of heavy metals based on artificial neural network model along the Yangtze River Estuary, China.

Pollution from heavy metals in estuaries poses potential risks to the aquatic environment and public health. The complexity of the estuarine water environment limits the accurate understanding of its pollution prediction. Field observations were conducted at seven sampling sites along the Yangtze River Estuary (YRE) during summer, autumn, and winter 2021 to analyze the concentrations of seven heavy metals (As, Cd, Cr, Pb, Cu, Ni, Zn) in water and surface sediments. The order of heavy metal concentrations in water samples from highest to lowest was Zn > As > Cu > Ni > Cr > Pb > Cd, while that in surface sediments samples was Zn > Cr > As > Ni > Pb > Cu > Cd. Human health risk assessment of the heavy metals in water samples indicated a chronic and carcinogenic risk associated with As. The risks of heavy metals in surface sediments were evaluated using the geo-accumulation index (Igeo) and potential ecological risk index (RI). Among the seven heavy metals, As and Cd were highly polluted, with Cd being the main contributor to potential ecological risks. Principal component analysis (PCA) was employed to identify the sources of the different heavy metals, revealing that As originated primarily from anthropogenic emissions, while Cd was primarily from atmospheric deposition. To further analyze the influence of water quality indicators on heavy metal pollution, an artificial neural network (ANN) model was utilized. A modified model was proposed, incorporating biochemical parameters to predict the level of heavy metal pollution, achieving an accuracy of 95.1%. This accuracy was 22.5% higher than that of the traditional model and particularly effective in predicting the maximum 20% of values. Results in this paper highlight the pollution of As and Cd along the YRE, and the proposed model provides valuable information for estimating heavy metal pollution in estuarine water environments, facilitating pollution prevention efforts.

Inborn errors of immunity and its clinical significance in children with lymphoma in China: a single-center study.

OBJECTIVE: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied. METHOD: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children's Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations. RESULTS: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4 % (p = 0.006). CONCLUSION: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.

Comparison of Two Surgical Approaches for Periacetabular Osteotomy: A Retrospective Study of Patients with Developmental Dysplasia of the Hip.

OBJECTIVE: Given the intricate challenges and potential complications associated with periacetabular osteotomy (PAO) for developmental dysplasia of the hip (DDH). Our study aimed to compare the clinical and imaging benefits and drawbacks of two surgical approaches, the modified Stoppa combined iliac spine approach and the modified Smith-Peterson approach, for treating PAO and to provide guidance for selecting clinical approaches. METHODS: A retrospective analysis of 56 patients with 62 DDHs was conducted from June 2018 to January 2022. The experimental group underwent surgery via the modified Stoppa combined iliac spine approach, while the control group underwent surgery via the modified Smith-Peterson approach for periacetabular osteotomy and internal fixation. Basic statistical parameters, including age, sex, BMI, and preoperative imaging data, were analyzed. Differences in surgical time, intraoperative blood loss, and postoperative imaging data were compared, as were differences in preoperative and postoperative imaging data between the two groups. RESULTS: There were 28 hips in the experimental group and 34 in the control group. Moreover, there was no significant difference in the basic parameters between the experimental and control groups. Before and after the operation, for the LCE angle, ACE angle, and Tonnis angle, there was no significant difference in acetabular coverage (p > 0.05). However, there were significant differences between the two groups in terms of the above four indicators before and after the operation (p < 0.05). After the operation, the experimental group exhibited significant increases in both lateral and anterior acetabular coverage of the femoral head. However, the experimental group had longer operation times and greater bleeding volumes than did the control group. Despite this, the experimental group demonstrated significant advantages in protecting the lateral femoral cutaneous nerve compared to the control group. CONCLUSION: The modified Stoppa combined iliac spine approach can be considered a practical approach for PAO and is more suitable for patients with DDH who plan to be treated by one operation than the classic modified Smith-Peterson approach for PAO.

Overexpressing lipid raft protein STOML2 modulates the tumor microenvironment via NF-κB signaling in colorectal cancer.

Colorectal cancer (CRC) is characterized by a complex tumor inflammatory microenvironment, while angiogenesis and immunosuppression frequently occur concomitantly. However, the exact mechanism that controls angiogenesis and immunosuppression in CRC microenvironment remains unclear. Herein, we found that expression levels of lipid raft protein STOML2 were increased in CRC and were associated with advanced disease stage and poor survival outcomes. Intriguingly, we revealed that STOML2 is essential for CRC tumor inflammatory microenvironment, which induces angiogenesis and facilitates tumor immune escape simultaneously both in vitro and in vivo. Moreover, tumors with STOML2 overexpression showed effective response to anti-angiogenesis treatment and immunotherapy in vivo. Mechanistically, STOML2 regulates CRC proliferation, angiogenesis, and immune escape through activated NF-κB signaling pathway via binding to TRADD protein, resulting in upregulation of CCND1, VEGF, and PD-L1. Furthermore, treatment with NF-κB inhibitor dramatically reversed the ability of proliferation and angiogenesis. Clinically, we also observed a strong positive correlation between STOML2 expression and Ki67, CD31, VEGFC and PD-1 of CD8+T cell expression. Taken together, our results provided novel insights into the role of STOML2 in CRC inflammatory microenvironment, which may present a therapeutic opportunity for CRC.

Fibular free flap necrosis after mandibular reconstruction surgery with osteoradionecrosis: Establishment and verification of an early warning model.

OBJECTIVE: Fibular free flap necrosis (FFFN) is the most common complication in patients with osteoradionecrosis (ORN) after mandibular reconstruction surgery. However, there are no effective forecasting tools at present. This research is aimed to establish and verify a nomogram model to predict the risk of FFFN after mandibular reconstruction surgery in ORN patients. METHODS: A total of 193 ORN patients with mandibular reconstruction using fibular free flap (150 cases in the model group and 43 cases in the validation group) were enrolled in this study. In the model group, the variables were optimized by lasso regression. Then the prediction model was established by binary logistic regression analysis, and the nomogram was drawn. The bootstrap self-sampling method was used for internal verification. Moreover, 43 cases in the validation group were used for external validation. RESULTS: The results of lasso regression and binary logistic regression analysis showed that the radiotherapy interval (≤2 years), trismus, diabetes, without deep venous anastomoses, and American society of anesthesiologists (ASA) III were the independent risk factors for FFFN after mandibular reconstruction surgery in ORNJ patients (P<0.05). Based on the above-mentioned risk factors, the nomogram model was established. The AUC values of the model group and the validation group were 0.936 and 0.964, respectively. The curve analysis showed that when the probability thresholds of the model group and the validation group were 5.699%∼98.229% and 0.413%∼99.721%, respectively. So the patient's clinical net profit rate was the highest. CONCLUSION: A nomogram combining the factors of radiotherapy interval (≤2 years), trismus, diabetes, without deep venous anastomoses, and ASA III provided a comparatively effective way to predict the risk of FFFN after mandibular reconstruction surgery in ORN patients, which has distinct applied clinical value.

Development and Validation of Nomograms to Predict Risk and Prognosis in Salivary Gland Carcinoma Patient with Distant Metastases.

Background: Salivary gland carcinoma (SGC) patients with distant metastasis (DM) are rare, and understanding this disease is insufficient. Nomograms can predict the prognostic probability of patients, while few studies have examined diagnostic and prognostic factors in SGC patients with DM. The purpose of this study was to establish and validate the risk and prognostic nomograms of SGC patients with DM. Methods: Based on the SEER database, we analyzed the data of SGC patients between 2004 and 2015. Logistic regression analyses and Cox proportional hazards regression analyses were used to identify risk and prognostic factors for DM in SGC patients. Based on the Akaike information criterion (AIC) value and likelihood ratio test, the best-fitting model was selected to build risk and prognostic nomograms, and the results were evaluated by receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and Kaplan-Meier (K-M) survival curves. ROC curves were also used to compare the nomograms with the American Joint Committee on Cancer (AJCC) staging system. Results: 7418 SGC patients were included in the study, and 307 (4.14%) of them were diagnosed with DM. This study identified that there are variables (age ≥ 80, no-parotid gland primary site, histologic type of mucoepidermoid carcinoma and squamous cell carcinoma, T stage ≥ T2, N staged ≥ N1, histologic grade ≥ III, and tumor size ≥ 41 mm) associated with the occurrence of DM in SGC patients. Therefore, we constructed diagnostic and prognostic nomograms after incorporating these variables. ROC curves illustrated the better predictive efficacy of 2 nomograms over the AJCC staging system. DCA curves, calibration curves, and K-M survival curves showed that 2 nomograms can accurately predict the occurrence and prognosis of DM among SGC patients in training and validation sets. Conclusion: It was shown that the nomograms were highly discriminative in predicting the diagnosis and prognosis of SGC patients with DM, and could identify high-risk patients, thereby providing SGC patients with individualized treatment plans.

An endoplasmic reticulum stress-related signature could robustly predict prognosis and closely associate with response to immunotherapy in pancreatic ductal adenocarcinoma.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors. Endoplasmic reticulum stress (ERS) plays an essential role in PDAC progression. Here, we aim to identify the ERS-related genes in PDAC and build reliable risk models for diagnosis, prognosis and immunotherapy response of PDAC patients as well as investigate the potential mechanism. METHODS: We obtained PDAC cohorts with transcriptional profiles and clinical data from the ArrayExpress, The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Univariate Cox regression, LASSO regression and multivariate Cox regression analyses were used to construct an ERS-related prognostic signature. The CIBERSORT and ssGSEA algorithms were applied to explore the correlation between the prognostic signature and immune cell infiltration and immune-related pathways. The GDSC database and TIDE algorithm were used to predict responses to chemotherapy and immunotherapy, identifying potential drugs for treating patients with PDAC. RESULTS: We established and validated an ERS-related prognostic signature comprising eight genes (HMOX1, TGFB1, JSRP1, GAPDH, CAV1, CHRNE, CD74 and ERN2). Patients with higher risk scores displayed worse outcomes than those with lower risk scores. PDAC patients in low-risk groups might benefit from immunotherapy. Dasatinib and lapatinib might have potential therapeutic implications in high-risk PDAC patients. CONCLUSION: We established and validated an ERS-related prognostic signature comprising eight genes to predict the overall survival outcome of PDAC patients, which closely correlating with the response to immunotherapy and sensitivity to anti-tumor drugs, as well as could be beneficial for formulating clinical strategies and administering individualized treatments.

Customed 3D-printed Polyetheretherketone (PEEK) Implant for Secondary Salvage Reconstruction of Mandibular Defects: Case Report and Literature Review.

Given the insufficient height of single-barrel fibula and inadequate bone volume of double-barrel vascularized fibula in mandibular reconstruction, it is a better choice to combine the upper full-thickness vascularized fibula with the lower half-thickness nonvascularized fibula. However, the nonvascularized fibula may fail due to complications, affecting the facial shape and occlusal function. Polyetheretherketone is a thermoplastic polymer used for bone defect reconstruction due to its good mechanical properties and biocompatibility. This case report mainly presents a secondary salvage reconstruction of the mandible by using customed 3-dimensional-printing polyetheretherketone, which restored the continuity and symmetry of the mandible, improved the patient's facial shape, and restored functional occlusion through dental implants. After a 28-month follow-up, no complications occurred, and the patient was satisfied with the final restoration.

Comprehensive analysis, immune, and cordycepin regulation for SOX9 expression in pan-cancers and the matched healthy tissues.

SRY-box transcription factor 9 (SOX9) (OMIM 608160) is a transcription factor. The expression of SOX9 in pan-cancers and the regulation by small molecules in cancer cell lines are unclear. In the current study, we comprehensively analyzed the expression of SOX9 in normal tissues, tumor tissues and their matched healthy tissues in pan-cancers. The study examined the correlation between immunomodulators and immune cell infiltrations in normal and tumor tissues. Cordycepin (CD), an adenosine analog for SOX9 expression regulation, was also conducted on cancer cells. The results found that SOX9 protein is expressed in a variety of organs, including high expression in 13 organs and no expression in only two organs; in 44 tissues, there was high expression in 31 tissues, medium expression in four tissues, low expression in two tissues, and no expression in the other seven tissues. In pan-cancers with 33 cancer types, SOX9 expression was significantly increased in fifteen cancers, including CESC, COAD, ESCA, GBM, KIRP, LGG, LIHC, LUSC, OV, PAAD, READ, STAD, THYM, UCES, and UCS, but significantly decreased in only two cancers (SKCM and TGCT) compared with the matched healthy tissues. It suggests that SOX9 expression is upregulated in the most cancer types (15/33) as a proto-oncogene. The fact that the decrease of SOX9 expression in SKCM and the increase of SOX9 in the cell lines of melanoma inhibit tumorigenicity in both mouse and human ex vivo models demonstrates that SOX9 could also be a tumor suppressor. Further analyzing the prognostic values for SOX9 expression in cancer individuals revealed that OS is long in ACC and short in LGG, CESC, and THYM, suggesting that high SOX9 expression is positively correlated with the worst OS in LGG, CESC, and THYM, which could be used as a prognostic maker. In addition, CD inhibited both protein and mRNA expressions of SOX9 in a dose-dependent manner in 22RV1, PC3, and H1975 cells, indicating CD's anticancer roles likely via SOX9 inhibition. Moreover, SOX9 might play an important role in tumor genesis and development by participating in immune infiltration. Altogether, SOX9 could be a biomarker for diagnostics and prognostics for pan-cancers and an emerging target for the development of anticancer drugs.

Infantile Cranial Fasciitis: A Clinicopathologic Evaluation.

OBJECTIVE: To investigate the clinicopathologic features, immunophenotype, molecular genetic changes, and differential diagnosis of cranial fasciitis (CF). METHODS: The clinical manifestations, imaging, surgical technique, pathologic characteristics, special staining, and immunophenotype, as well as break-apart fluorescence in situ hybridization assay for USP6 of 19 CF cases were analyzed, retrospectively. RESULTS: The patients were 11 boys and 8 girls, aged 5 to 144 months, with a median age of 29 months. There were 5 cases (26.31%) in the temporal bone, 4 cases (21.05%) in the parietal bone, 3 cases (15.78%) in the occipital bone, 3 cases (15.78%) in the frontotemporal bone, 2 cases (10.52%) in the frontal bone, 1 case (5.26%) in the mastoid of middle ear, and 1 case (5.26%) in the external auditory canal. The main clinical manifestations were painless, with the presentation of masses that grew rapidly and frequently eroded the skull. There was no recurrence and no metastasis after the operation. Histologically, the lesion consists of spindle fibroblasts/myofibroblasts arranged in bundles, braided or atypical spokes. Mitotic figures could be seen, but not atypical forms. Immunohistochemical studies showed diffuse strong positive SMA and Vimentin in all CFs. These cells were negative for Calponin, Desmin, ß-catenin, S-100, and CD34. The ki-67 proliferation index was 5% to 10%. Ocin blue-PH2.5 staining showed blue-stained mucinous features in the stroma. The positive rate of USP6 gene rearrangement detected by fluorescence in situ hybridization assay was about 10.52%, and the positive rate was not related to age. All patients were observed for 2 to 124 months and showed no signs of recurrence or metastasis. CONCLUSIONS: In summary, CF was a benign pseudosarcomatous fasciitis that occurs in the skull of infants. Preoperative diagnosis and differential diagnosis were difficult. Computed tomography typing might be beneficial for imaging diagnosis, and pathologic examination might be the most reliable way to diagnose CF.

Kinetics of Hydroxyl Radical Production from Oxygenation of Reduced Iron Minerals and Their Reactivity with Trichloroethene: Effects of Iron Amounts, Iron Species, and Sulfate Reducing Bacteria.

Reactive oxygen species generated during the oxygenation of different ferrous species have been documented at groundwater field sites, but their effect on pollutant destruction remains an open question. To address this knowledge gap, a kinetic model was developed to probe mechanisms of •OH production and reactivity with trichloroethene (TCE) and competing species in the presence of reduced iron minerals (RIM) and oxygen in batch experiments. RIM slurries were formed by combining different amounts of Fe(II) and sulfide (with Fe(II):S ratios from 1:1 to 50:1) or Fe(II) and sulfate with sulfate reducing bacteria (SRB) added. Extents of TCE oxidation and •OH production were both greater with RIM prepared under more reducing conditions (more added Fe(II)) and then amended with O2. Kinetic rate constants from modeling indicate that •OH production from free Fe(II) dominates •OH production from solid Fe(II) and that TCE competes for •OH with Fe(II) and organic matter (OM). Competition with OM only occurs in experiments with SRB, which include cells and their exudates. Experimental results indicate that cells and/or exudates also provide electron equivalents to reform Fe(II) from oxidized RIM. Our work provides new insights into mechanisms and environmental significance of TCE oxidation by •OH produced from oxygenation of RIM. However, further work is necessary to confirm the relative importance of reaction pathways identified here and to probe potentially unaccounted for mechanisms that affect abiotic TCE oxidation in natural systems.

Modeling EDTA-facilitated cadmium migration in high- and low-permeability systems using MODFLOW and RT3D.

Cadmium (Cd) has impacted groundwater resources and can pose a serious threat to human health and the environment. Its fate in groundwater is complex and challenging to predict, as it is affected by adsorption to sediments, complexation with aqueous phase ligands, and variations in hydraulic conductivity. In this study, a 2D reactive transport model based on MODFLOW and RT3D is used to simulate published experimental results of cadmium migration without and with EDTA present in a flow cell containing high- and low-permeability zones (i.e., HPZs and LPZs). The model is then extended to conceptual flow cells with more complex LPZ configurations. Simulation results generally match the experimental data well, and analysis of experimental and simulated Cd effluent concentration profiles shows that EDTA enhances Cd removal from LPZs relative to water alone. Simulation results indicate that faster Cd removal is due to EDTA complexation with adsorbed Cd in LPZs, which enhances its solubilization and subsequent back diffusion. Lastly, simulation results show that with increasing LPZ heterogeneity more Cd is retained in flow cells, and EDTA is more effective in enhancing Cd removal relative to water alone; these results are attributed to more LPZ-HPZ interfaces that enhance Cd mass transfer into LPZs during contamination, and enhance EDTA mass transfer into LPZs to promote cleanup. Overall, the results highlight the promise of using EDTA to remove Cd from heterogeneous sites, but caution is advised due to model simplicity and lack of consideration of changes in solution pH, redox potential, or competing cations.

DNMT3A low-expression is correlated to poor prognosis in childhood B-ALL and confers resistance to daunorubicin on leukemic cells.

BACKGROUND: Little is known about DNMT3A expression and its prognostic significance in childhood B cell acute lymphoblastic leukemia (B-ALL). METHODS: We determined DNMT3A mRNA expression in 102 children with B-ALL. Correlations with relapse-free survival (RFS) and common clinical characteristics were analyzed. DNMT3A was stably knocked out by CRISPR/Cas9 gene editing technology in Reh and 697 B-ALL cell lines. Cell proliferation activity after treated with daunorubicin (DNR) was determined by CCK8 assay in DNMT3A KO Reh and 697 cell lines. RESULTS: DNMT3A expression in B-ALL patients who were in continuous complete remission (CCR) was higher than in those who got relapse (P = 0.0111). Receiver operating characteristic curve showed prognostic significance of DNMT3A expression (P = 0.003). Low expression of DNMT3A (≤ 0.197) was significantly correlated with poor RFS (P < 0.001) in children with B-ALL. Knock-out of DNMT3A in Reh and 697 cell lines significantly increased IC50 of DNR (P = 0.0201 and 0.0022 respectively), indicating elevated resistance to DNR. CONCLUSION: Low expression of DNMT3A associates with poor prognosis in children with B-ALL. Knock-out of DNMT3A confers resistance to DNR on leukemic cells.

USP1 promotes the aerobic glycolysis and progression of T-cell acute lymphoblastic leukemia via PLK1/LDHA axis.

The effect of aerobic glycolysis remains elusive in pediatric T-cell acute lymphoblastic leukemia (T-ALL). Increasing evidence has revealed that dysregulation of deubiquitination is involved in glycolysis, by targeting glycolytic rate-limiting enzymes. Here, we demonstrated that upregulated deubiquitinase ubiquitin-specific peptidase 1 (USP1) expression correlated with poor prognosis in pediatric primary T-ALL samples. USP1 depletion abolished cellular proliferation and attenuated glycolytic metabolism. In vivo experiments showed that USP1 suppression decreased leukemia progression in nude mice. Inhibition of USP1 caused a decrease in both mRNA and protein levels in lactate dehydrogenase A (LDHA), a critical glycolytic enzyme. Moreover, USP1 interacted with and deubiquitinated polo-like kinase 1 (PLK1), a critical regulator of glycolysis. Overexpression of USP1 with upregulated PLK1 was observed in most samples of patients with T-ALL. In addition, PLK1 inhibition reduced LDHA expression and abrogated the USP1-mediated increase of cell proliferation and lactate level. Ectopic expression of LDHA can rescue the suppressive effect of USP1 silencing on cell growth and lactate production. Pharmacological inhibition of USP1 by ML323 exhibited cell cytotoxicity in human T-ALL cells. Taken together, our results demonstrated that USP1 may be a promising therapeutic target in pediatric T-ALL.

Clinical, biological, and outcome features of P2RY8-CRLF2 and CRLF2 over-expression in pediatric B-cell precursor acute lymphoblastic leukemia according to the CCLG-ALL 2008 and 2018 protocol.

OBJECTIVES: CRLF2 alterations are associated with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). This study aimed to explore the clinical, biological, and outcome features of pediatric BCP-ALL with CRLF2 abnormalities. METHODS: This study enrolled 630 childhood BCP-ALLs treated on CCLG-ALL 2008 or 2018 protocol. P2RY8-CRLF2 was determined by Sanger sequencing and CRLF2 expression was evaluated by qRT-PCR. The correlation between clinical, biological features and outcomes with P2RY8-CRLF2 or CRLF2 over-expression were analyzed. RESULTS: P2RY8-CRLF2 and CRLF2 over-expression were found in 3.33% and 5.71% respectively. P2RY8-CRLF2 was associated with male, higher frequency of CD7 expression, high WBC and MRD before consolidation. CRLF2 over-expression showed ETV6-RUNX1- , higher frequency of CD22, CD34, CD66c, CD86 expression, hyperdiploidy and high MRD at early treatment. The lower overall survival (OS) was found in patients with P2RY8-CRLF2 and confined only in IR group. Furthermore, adverse event-free survival and OS of P2RY8-CRLF2 were discovered comparing to those without known fusions or treated on CCLG-ALL 2008 protocol. However, P2RY8-CRLF2 was not confirmed as independent prognostic factors and no prognostic impact of CRLF2 over-expression was found. CONCLUSIONS: These findings indicate P2RY8-CRLF2 identifies a subset of patients with specific features and adverse outcomes that could be improved by risk-directed treatment.

Combination of external fixation using digital six-axis fixator and internal fixation to treat severe complex knee deformity.

BACKGROUND: Severe knee valgus/varus or complex multiplanar deformities are common in clinic. If not corrected in time, cartilage wear will be aggravated and initiate the osteoarthritis due to lower limb malalignment. Internal fixation is unable to correct severe complex deformities, especially when combined with lower limb discrepancy (LLD). Based on the self-designed digital six-axis external fixator Q spatial fixator (QSF), which can correct complex multiplanar deformities without changing structures, accuracy of correction can be improved significantly. METHODS: This retrospective study included 24 patients who suffered from complex knee deformity with LLD treated by QSF and internal fixation at our institution from January 2018 to February 2021. All patients had a closing wedge distal femoral osteotomy with internal fixation for immediate correction and high tibia osteotomy with QSF fixation for postoperative progressive correction. Data of correction prescriptions were computed by software from postoperative CT scans. RESULTS: Mean discrepancy length of operative side was 2.39 ± 1.04 cm (range 0.9-4.4 cm) preoperatively. The mean difference of lower limb was 0.32 ± 0.13 cm (range 0.11-0.58 cm) postoperatively. The length of limb correction had significant difference (p < 0.05). The mean MAD and HKA decreased significantly (p < 0.05), and the mean MPTA and LDFA increased significantly (p < 0.05). There were significant increase (p < 0.05) in the AKSS-O, AKSS-F and Tegner Activity Score. The lower limb alignment was corrected (p < 0.05). The mean time of removing external fixator was 112.8 ± 17.9 days (range 83-147 days). CONCLUSIONS: Complex knee deformity with LLD can be treated by six-axis external fixator with internal fixation without total knee arthroplasty. Lower limb malalignment and discrepancy can be corrected precisely and effectively by this approach.

Impact of BSG/CD147 gene expression on diagnostic, prognostic and therapeutic strategies towards malignant cancers and possible susceptibility to SARS-CoV-2.

BACKGROUND: BSG (CD147) is a member of the immunoglobulin superfamily that shows roles for potential prognostics and therapeutics for metastatic cancers and SARS-CoV-2 invasion for COVID-19. The susceptibility of malignant cancers to SARS-CoV-2 as well as the correlations between disease outcome and BSG expression in tumor tissues have not been studied in depth. METHODS: In this study, we explored the BSG expression profile, survival correlation, DNA methylation, mutation, diagnostics, prognostics, and tumor-infiltrating lymphocytes (TILs) from different types of cancer tissues with corresponding healthy tissues. In vitro studies for cordycepin (CD), N6-(2-hydroxyethyl) adenosine (HEA), N6, N6-dimethyladenosine (m62A) and 5'-uridylic acid (UMP) on BSG expression were also conducted. RESULTS: We revealed that BSG is conserved among different species, and significantly upregulated in seven tumor types, including ACC, ESCA, KICH, LIHC, PAAD, SKCM and THYM, compared with matched normal tissues, highlighting the susceptibility of these cancer patients to SARS-CoV-2 invasion, COVID-19 severity and progression of malignant cancers. High expression in BSG was significantly correlated with a short OS in LGG, LIHC and OV patients, but a long OS in KIRP patients. Methylation statuses in the BSG promoter were significantly higher in BRCA, HNSC, KIRC, KIRP, LUSC, PAAD, and PRAD tumor tissues, but lower in READ. Four CpGs in the BSG genome were identified as potential DNA methylation biomarkers which could be used to predict malignant cancers from normal individuals. Furthermore, a total of 65 mutation types were found, in which SARC showed the highest mutation frequency (7.84%) and THYM the lowest (0.2%). Surprisingly, both for disease-free and progression-free survival in pan-cancers were significantly reduced after BSG mutations. Additionally, a correlation between BSG expression and immune lymphocytes of CD56bright natural killer cell, CD56dim natural killer cell and monocytes, MHC molecules of HLA-A, HLA-B, HLA-C and TAPBP, immunoinhibitor of PVR, PVRL2, and immunostimulators of TNFRSF14, TNFRSF18, TNFRSF25, and TNFSF9, was revealed in most cancer types. Moreover, BSG expression was downregulated by CD, HEA, m62A or UMP in cancer cell lines, suggesting therapeutic potentials for interfering entry of SARS-CoV-2. CONCLUSIONS: Altogether, our study highlights the values of targeting BSG for diagnostic, prognostic and therapeutic strategies to fight malignant cancers and COVID-19. Small molecules CD, HEA, m62A and UMP imply therapeutic potentials in interfering with entry of SARS-CoV-2 and progression of malignant cancers.

An innovative pyroptosis-related long-noncoding-RNA signature predicts the prognosis of gastric cancer via affecting immune cell infiltration landscape.

Background: Gastric cancer (GC) is a worldwide popular malignant tumor. However, the survival rate of advanced GC remains low. Pyroptosis and long non-coding RNAs (lncRNAs) are important in cancer progression. Thus, we aimed to find out a pyroptosis-related lncRNAs (PRLs) signature and use it to build a practical risk model with the purpose to predict the prognosis of patients with GC. Methods: Univariate Cox regression analysis was used to identify PRLs linked to GC patient's prognosis. Subsequently, to construct a PRLs signature, the least absolute shrinkage and selection operator regression, and multivariate Cox regression analysis were used. Kaplan-Meier analysis, principal component analysis, and receiver operating characteristic curve analysis were performed to assess our novel lncRNA signature. The correlation between risk signature and clinicopathological features was also examined. Finally, the relationship of pyroptosis and immune cells were evaluated through the CIBERSORT tool and single-sample lncRNA set enrichment analysis (ssGSEA). Results: A PRLs signature comprising eight lncRNAs was discerned as a self-determining predictor of prognosis. GC patients were sub-divided into high-risk and low-risk groups via this risk-model. Stratified analysis of different clinical factors also displayed that the PRLs signature was a good prognosis factor. According to the risk score and clinical characteristics, a nomogram was established. Moreover, the difference between the groups is significance in immune cells and immune pathways. Conclusion: This study established an effective prognostic signature consist of eight PRLs in GC, and constructed an efficient nomogram model. Further, the PRLs correlated with immune cells and immune pathways.