Small Transjugular Intrahepatic Portosystemic Shunt Plus Variceal Embolization for Gastric Varices: A Multicenter Cohort Study.

BACKGROUND & AIMS: The effect of transjugular intrahepatic portosystemic shunt (TIPS) plus variceal embolization for treating gastric varices (GVs) remains controversial. This nationwide multicenter cohort study aimed to evaluate whether adding variceal embolization to a small diameter (8-mm) TIPS could reduce the rebleeding incidence in patients with different types of GVs. METHODS: This retrospective cohort study involved 629 patients who underwent 8-mm TIPS for gastric varices at 7 medical centers. The primary endpoint was all-cause rebleeding, and the secondary endpoints included overt hepatic encephalopathy (OHE) and all-cause mortality. RESULTS: A total of 629 patients were included. Among them, 429 (68.2%) had gastroesophageal varices type 1 (GOV1), 145 (23.1%) had gastroesophageal varices type 2 (GOV2), and 55 (8.7%) had isolated gastric varices type 1 (IGV1). In the entire cohort, adjunctive embolization reduced rebleeding (6.2% vs 13.6%; P = .005) and OHE (31.0% vs 39.4%; P = .02) compared with TIPS alone. However, no significant differences were found in mortality (12.0% vs 9.7%; P = .42). In patients with GOV2 and IGV1, TIPS plus variceal embolization reduced both rebleeding (GOV2: 7.8% vs 25.1%; P = .01; IGV1: 5.6% vs 30.8%; P = .03) and OHE (GOV2: 31.8% vs 51.5%; P = .008; IGV1: 11.6% vs 38.5%; P = .04). However, in patients with GOV1, adjunctive embolization did not reduce rebleeding (5.9% vs 8.7%; P = .37) or OHE (33.1% vs 35.3%; P = .60). CONCLUSIONS: Compared with TIPS alone, 8-mm TIPS plus variceal embolization reduced rebleeding and OHE in patients with GOV2 and IGV1. These findings suggest that patients with GOV2 and IGV1, rather than GOV1, could benefit from embolization with TIPS.

Parallel CNN-Deep Learning Clinical-Imaging Signature for Assessing Pathologic Grade and Prognosis of Soft Tissue Sarcoma Patients.

BACKGROUND: Traditional biopsies pose risks and may not accurately reflect soft tissue sarcoma (STS) heterogeneity. MRI provides a noninvasive, comprehensive alternative. PURPOSE: To assess the diagnostic accuracy of histological grading and prognosis in STS patients when integrating clinical-imaging parameters with deep learning (DL) features from preoperative MR images. STUDY TYPE: Retrospective/prospective. POPULATION: 354 pathologically confirmed STS patients (226 low-grade, 128 high-grade) from three hospitals and the Cancer Imaging Archive (TCIA), divided into training (n = 185), external test (n = 125), and TCIA cohorts (n = 44). 12 patients (6 low-grade, 6 high-grade) were enrolled into prospective validation cohort. FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T/Unenhanced T1-weighted and fat-suppressed-T2-weighted. ASSESSMENT: DL features were extracted from MR images using a parallel ResNet-18 model to construct DL signature. Clinical-imaging characteristics included age, gender, tumor-node-metastasis stage and MRI semantic features (depth, number, heterogeneity at T1WI/FS-T2WI, necrosis, and peritumoral edema). Logistic regression analysis identified significant risk factors for the clinical model. A DL clinical-imaging signature (DLCS) was constructed by incorporating DL signature with risk factors, evaluated for risk stratification, and assessed for progression-free survival (PFS) in retrospective cohorts, with an average follow-up of 23 ± 22 months. STATISTICAL TESTS: Logistic regression, Cox regression, Kaplan-Meier curves, log-rank test, area under the receiver operating characteristic curve (AUC)，and decision curve analysis. A P-value <0.05 was considered significant. RESULTS: The AUC values for DLCS in the external test, TCIA, and prospective test cohorts (0.834, 0.838, 0.819) were superior to clinical model (0.662, 0.685, 0.694). Decision curve analysis showed that the DLCS model provided greater clinical net benefit over the DL and clinical models. Also, the DLCS model was able to risk-stratify patients and assess PFS. DATA CONCLUSION: The DLCS exhibited strong capabilities in histological grading and prognosis assessment for STS patients, and may have potential to aid in the formulation of personalized treatment plans. TECHNICAL EFFICACY: Stage 2.

Factors Associated with Dialysis Initiation in Patients with Predialysis Arteriovenous Fistula.

INTRODUCTION: A large proportion of patients initiated hemodialysis with a central vein catheter rather than a permanent vascular access which was recommended by guidelines. One major barrier was the paucity of evidence regarding the optimal timing of vascular access creation in predialysis patients. METHODS: Our study prospectively enrolled 300 patients undergoing predialysis arteriovenous fistula (AVF) creation in our center from 2015 to 2018. Cox proportional hazard regression was performed to identify which demographic and clinical factors were associated with the initiation of hemodialysis after AVF surgery. A receiver operating characteristic area under the curve (AUC) was used to assess the predictive power of preoperative factors for the likelihood of hemodialysis initiation. RESULTS: Overall, 163 (54.3%), 214 (71.3%), and 275 (91.7%) patients initiated hemodialysis within 3 months, 6 months, and 1 year, respectively, after AVF creation. The median time between AVF creation and hemodialysis start was 71.5 days. Using multivariate Cox regression analysis, three factors were associated with hemodialysis initiation within 1 year: serum phosphorus (HR = 1.407, p = 0.021), diabetic kidney disease (DKD) (HR = 1.429, p = 0.039), and cystatin C (HR = 1.179, p = 0.009). Cystatin C alone had a moderate predictive value for dialysis initiation (AUC = 0.746; p < 0.001), whereas the full model had a higher predictive value (AUC = 0.800; p < 0.001). CONCLUSION: DKD, serum cystatin C, and phosphorus at access surgery were associated with hemodialysis initiation within 1 year of the predialysis AVF creation. Our findings provide a basis for a more customized approach to planning AVF placement in patients with chronic kidney disease.

Glucose transporter 3 (GLUT3) promotes lactylation modifications by regulating lactate dehydrogenase A (LDHA) in gastric cancer.

OBJECTIVES: Glucose transporter 3 (GLUT3) plays a major role in glycolysis and glucose metabolism in cancer cells. We aimed to investigate the correlation between GLUT3 and histone lactylation modification in the occurrence and progression of gastric cancer. MATERIALS AND METHODS: We initially used single-cell sequencing data to determine the expression levels of GLUT3 and lactate dehydrogenase A (LDHA) in primary tumor, tumor-adjacent normal, and metastasis tumor tissues. Immunohistochemistry analysis was conducted to measure GLUT3, LDHA, and L-lactyl levels in gastric normal and cancer tissues. Transwell and scratch assays were performed to evaluate the metastatic and invasive capacity of gastric cancer cell lines. Western blotting was used to measure L-lactyl and histone lactylation levels in gastric cancer cell lines. RESULTS: Single-cell sequencing data showed that GLUT3 expression was significantly increased in primary tumor and metastasis tumor tissues. In addition, GLUT3 expression was positively correlated with that of LDHA expression and lactylation-related pathways. Western blotting and immunohistochemistry analyses revealed that GLUT3 was highly expressed in gastric cancer tissues and cell lines. GLUT3 knockdown in gastric cancer cell lines inhibited their metastatic and invasive capacity to various degrees. Additionally, the levels of LDHA, L-lactyl, H3K9, H3K18, and H3K56 significantly decreased after GLUT3 knockdown, indicating that GLUT3 affects lactylation in gastric cancer cells. Moreover, LDHA overexpression in a GLUT3 knockdown cell line reversed the levels of lactylation and EMT-related markers, and the EMT functional phenotype induced by GLUT3 knockdown. The in vivo results were consistent with the in vitro results. CONCLUSIONS: This study suggests the important role of histone lactylation in the occurrence and progression of gastric cancer, and GLUT3 may be a new diagnostic marker and therapeutic target for gastric cancer.

Neutrophil extracellular traps promote angiogenesis in gastric cancer.

Although antiangiogenic therapy has been used in gastric cancer, disease progression due to drug resistance remains common. Neutrophils play an important role in the occurrence and progression of cancer via neutrophil extracellular traps (NETs). However, few studies have investigated angiogenic regulation in gastric cancer. We aimed to determine the role of NETs in promoting angiogenesis in gastric cancer. Multiple immunohistochemical staining was used to analyze the spatial distribution of NETs and microvessels in patient tissue samples. A mouse subcutaneous tumor model was established to determine the effect of NETs on tumor growth, and changes in microvessel density were observed via immunohistochemical staining. We screened differentially expressed proteins in HUVECs stimulated by NETs via proteomics. Cell Counting Kit-8, EdU labeling, and tubule formation assays were used to verify the effect of NETs on HUVEC proliferation, migration, and tubule formation. Blocking NETs, which was related to decreased microvessel density, significantly inhibited tumor growth in the murine subcutaneous tumor model. Compared with those of the control group, tumor volume and mass among mice in the inhibition group decreased by 61.3% and 77.9%, respectively. The NET-DNA receptor CCDC25 was expressed in HUVECs, providing a platform for NETs to promote HUVEC proliferation, migration, and tubulation. In an in vitro rat aortic explant model, NETs induced HUVEC proliferation, survival, and chemotaxis, which were not significantly different from those observed in the VEGF stimulation group. Our results confirm that NETs promote angiogenesis in gastric cancer, providing a theoretical basis for identifying new anti-vascular therapeutic targets. Video Abstract.

Neutrophil extracellular traps induced by the hypoxic microenvironment in gastric cancer augment tumour growth.

BACKGROUND: Inflammation-related predisposition to cancer plays an essential role in cancer progression and is associated with poor prognosis. A hypoxic microenvironment and neutrophil infiltration are commonly present in solid tumours, including gastric cancer (GC). Neutrophil extracellular traps (NETs) have also been demonstrated in the tumour immune microenvironment (TIME), but how NETs affect GC progression remains unknown. Here, we investigated the role of NET formation in the TIME and further explored the underlying mechanism of NETs in GC tumour growth. METHODS: Hypoxia-induced factor-1α (HIF-1α), citrulline histone 3 (citH3) and CD66b expression in tumour and adjacent nontumor tissue samples was evaluated by western blotting, immunofluorescence and immunohistochemical staining. The expression of neutrophil-attracting chemokines in GC cells and their hypoxic-CM was measured by qRT‒PCR and ELISA. Neutrophil migration under hypoxic conditions was evaluated by a Transwell assay. Pathway activation in neutrophils in a hypoxic microenvironment were analysed by western blotting. NET formation was measured in vitro by immunofluorescence staining. The protumour effect of NETs on GC cells was identified by Transwell, wound healing and cell proliferation assays. In vivo, an lipopolysaccharide (LPS)-induced NET model and subcutaneous tumour model were established in BALB/c nude mice to explore the mechanism of NETs in tumour growth. RESULTS: GC generates a hypoxic microenvironment that recruits neutrophils and induces NET formation. High mobility group box 1 (HMGB1) was translocated to the cytoplasm from the nucleus of GC cells in the hypoxic microenvironment and mediated the formation of NETs via the toll-like receptor 4 (TLR4)/p38 MAPK signalling pathway in neutrophils. HMGB1/TLR4/p38 MAPK pathway inhibition abrogated hypoxia-induced neutrophil activation and NET formation. NETs directly induced GC cell invasion and migration but not proliferation and accelerated the augmentation of GC growth by increasing angiogenesis. This rapid tumour growth was abolished by treatment with the NET inhibitor deoxyribonuclease I (DNase I) or a p38 MAPK signalling pathway inhibitor. CONCLUSIONS: Hypoxia triggers an inflammatory response and NET formation in the GC TIME to augment tumour growth. Targeting NETs with DNase I or HMGB1/TLR4/p38 MAPK pathway inhibitors is a potential therapeutic strategy to inhibit GC progression. Video Abstract.

The association of serum anti-PLA2R antibody and glomerular PLA2R antigen staining with clinical manifestations and outcomes in membranous nephropathy.

BACKGROUND: Phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN) was manifested as seropositive for PLA2R antibodies (SAb) and/or glomerular PLA2R antigens' (GAg) deposits. According to the test of SAb and GAg, PLA2R-associated MN can be divided into SAb + /GAg-, SAb-/GAg + , and SAb + /GAg + groups. The clinical characteristics and outcomes of the three groups need to be further evaluated. METHODS: 184 PLA2R-associated MN patients were enrolled. SAb was measured by enzyme-linked immunosorbent assay with a cut-off value of 14 RU/mL. GAg was detected by immunofluorescence using a paraffin section of renal biopsy samples. Clinical characteristics and the decline of eGFR were compared among the 3 groups. RESULTS: There were 33 SAb + /GAg-, 46 SAb-/GAg +, and 105 SAb + /GAg + PLA2R-associated MN patients reviewed. Clinical characteristics, such as the level of proteinuria, serum albumin, as well as eGFR, were comparable between the SAb + /GAg- and SAb + /GAg + patients. While SAb-/GAg + patients exhibited mild clinical manifestations as evidenced by higher serum albumin (P < 0.001) and lower proteinuria (p = 0.049) compared with SAb + /GAg + patients. After 21.96 ± 7.39 month follow-up, the eGFR decrease was no difference between the SAb + /GAg- and SAb + /GAg + patients. SAb-/GAg + patients had a lower rate of the > 20% eGFR decline as well as a 50% eGFR decline compared with the SAb + /GAg + patients (10.87% vs 30.48%, p = 0.013; 0.00% vs 4.76%, p = 0.324). CONCLUSIONS: Our study showed that the clinical manifestations of SAb + /Gag- patients were the same as those of double-positive patients, while SAb-/GAg + patients exhibited mild clinical manifestations and slower eGFR decline compared to the double-positive patients.

Deep learning radiomic nomogram to predict recurrence in soft tissue sarcoma: a multi-institutional study.

OBJECTIVES: To evaluate the performance of a deep learning radiomic nomogram (DLRN) model at predicting tumor relapse in patients with soft tissue sarcomas (STS) who underwent surgical resection. METHODS: In total, 282 patients who underwent MRI and resection for STS at three independent centers were retrospectively enrolled. In addition, 113 of the 282 patients received additional contrast-enhanced MRI scans. We separated the participants into a development cohort and an external test cohort. The development cohort consisted of patients from one center and the external test cohort consisted of patients from two other centers. Two MRI-based DLRNs for prediction of tumor relapse after resection of STS were established. We universally tested the DLRNs and compared them with other prediction models constructed by using widespread adopted predictors (i.e., staging systems and Ki67) instead of radiomics features. RESULTS: The DLRN1 model incorporated plain MRI-based radiomics signature into the clinical data, and the DLRN2 model integrated radiomics signature extracted from plain and contrast-enhanced MRI with the clinical predictors. Across both study sets, the two MRI-based DLRNs had relatively better prognostic capability (C index ≥ 0.721 and median AUC ≥ 0.746; p < 0.05 compared with most other models and predictors) and less opportunity for prediction error (integrated Brier score ≤ 0.159). The decision curve analysis indicates that the DLRNs have greater benefits than staging systems, Ki67, and other models. We selected appropriate cutoff values for the DLRNs to divide STS recurrence into three risk strata (low, medium, and high) and calculated those groups' cumulative risk rates. CONCLUSION: The DLRNs were shown to be a reliable and externally validated tool for predicting STS recurrence by comparing with other prediction models. KEY POINTS: • The prediction of a high recurrence rate of STS before emergence of local recurrence can help to determine whether more active treatment should be implemented. • Two MRI-based DLRNs for prediction of tumor relapse were shown to be a reliable and externally validated tool for predicting STS recurrence. • We used the DLRNs to divide STS recurrence into three risk strata (low, medium, and high) to facilitate more targeted postoperative management in the clinic.

Research on imbalance machine learning methods for MR[Formula: see text]WI soft tissue sarcoma data.

BACKGROUND: Soft tissue sarcoma is a rare and highly heterogeneous tumor in clinical practice. Pathological grading of the soft tissue sarcoma is a key factor in patient prognosis and treatment planning while the clinical data of soft tissue sarcoma are imbalanced. In this paper, we propose an effective solution to find the optimal imbalance machine learning model for predicting the classification of soft tissue sarcoma data. METHODS: In this paper, a large number of features are first obtained based on [Formula: see text]WI images using the radiomics methods.Then, we explore the methods of feature selection, sampling and classification, get 17 imbalance machine learning models based on the above features and performed extensive experiments to classify imbalanced soft tissue sarcoma data. Meanwhile, we used another dataset splitting method as well, which could improve the classification performance and verify the validity of the models. RESULTS: The experimental results show that the combination of extremely randomized trees (ERT) classification algorithm using SMOTETomek and the recursive feature elimination technique (RFE) performs best compared to other methods. The accuracy of RFE+STT+ERT is 81.57% , which is close to the accuracy of biopsy, and the accuracy is 95.69% when using another dataset splitting method. CONCLUSION: Preoperative predicting pathological grade of soft tissue sarcoma in an accurate and noninvasive manner is essential. Our proposed machine learning method (RFE+STT+ERT) can make a positive contribution to solving the imbalanced data classification problem, which can favorably support the development of personalized treatment plans for soft tissue sarcoma patients.

Pulmonary mucosa-associated lymphoid tissue lymphoma: CT findings and pathological basis.

BACKGROUND: Pulmonary mucosa-associated lymphoid tissue lymphoma (MALToma) is the most frequent subset of primary pulmonary lymphoma. This study aimed to identify radiologic characteristics of pulmonary MALToma based on computed tomography (CT) observations and pathologic features, and further investigate its prognosis. METHODS: Sixty-six patients (55.4 ± 10.9 years; 51.5% male) diagnosed as pulmonary MALToma by pathology were retrospectively enrolled. According to distributions and features of lesions shown on CT, patients were divided into three patterns, including single nodular/mass, multiple nodular/mass, and pneumonia-like consolidative. RESULTS: Variety of the location and extent of the lymphomatous infiltration accounted for different characteristics demonstrated at CT. The pneumonia-like consolidative pattern was the most frequent pattern observed in 42 patients (63.6%), followed by single nodular/mass (21.2%) and multiple nodular/mass (15.2%). CT features included air bronchogram (72.7%), well-marginated halo sign (53.0%), coarse spiculate with different lengths (72.7%), angiogram sign (77.1% of 35 patients), peribronchovascular thickening (48.5%), irregular cavitation (16.7%) and pulmonary cyst (7.6%). The estimated 5-year cumulative overall survival rate of pulmonary MALToma was 100.0%. CONCLUSIONS: Pulmonary MALToma demonstrates several characteristics at CT. Identification of the significant pulmonary abnormalities of this indolent disease entity might be helpful for early diagnosis and optimal treatment.

Dynamic Indicators That Impact the Outcomes of Thoracic Endovascular Aortic Repair in Complicated Type B Aortic Dissection.

PURPOSE: To investigate dynamic variables obtained from retrospective computed tomography angiography for ability to predict thoracic endovascular aortic repair (TEVAR) outcomes in patients with complicated type B aortic dissection (cTBAD). MATERIALS AND METHODS: Seventy-nine patients with cTBAD who received TEVAR from March 2009 to June 2018 were retrospectively enrolled. Relative true lumen area (r-TLA) was computed at the level of tracheal bifurcation every 5% of all R-R intervals. Parameters that reflect the state of intimal motion were evaluated, including difference between maximum and minimum r-TLA (D-TLA) and true lumen collapse. The endpoints comprised early (≤ 30 days) and late (> 30 days) outcomes after intervention. RESULTS: Overall early mortality rate was 13.9% (11/79), and early adverse events rate was 24.1% (19/79). Patients who received TEVAR within 2 days of symptom onset demonstrated the worst outcomes. A longer time of r-TLA < 25% in 1 cardiac cycle (P = .049) and larger D-TLA (P < .001) were correlated to an increased early death. In addition, D-TLA was an independent predictor of early mortality. Area under the curve of D-TLA was 0.849 (95% confidence interval 0.730-0.967) for predicting early mortality and 0.742 (95% CI 0.611-0.873) for predicting early adverse events. Survival and event-free survival rates during follow-up were decreased in the D-TLA > 21.5% group compared with the D-TLA ≤ 21.5% group (all P < .001). CONCLUSIONS: Larger D-TLA is correlated with worse postoperative outcomes and might be a crucial parameter for future risk stratification in patients with cTBAD.

MiR-325-3p inhibits renal inflammation and fibrosis by targeting CCL19 in diabetic nephropathy.

Diabetic nephropathy (DN), a common cardiovascular disease, has been a global health threat. MicroRNAs (miRNAs) have been proposed to frequently participate in the occurrence and development of DN, however, the role of miR-325-3p in DN remains uncharacterized. Our research aimed to explore the function and mechanism of miR-325-3p in DN. Bioinformatics analysis (Targetscan, http://www.targetscan.org) and a wide range of experiments including RT-qPCR, CCK-8 assay, western blot, luciferase reporter assay, RNA immunoprecipitation (RIP) assays, urine protein and blood glucose assays, histology analysis and morphometric analysis were used to explore the function and mechanism of miR-325-3p and C-C motif chemokine ligand 19 (CCL19). CCL19 could facilitate the progression of DN by inhibiting cell viability and promoting inflammation and fibrosis in HK-2 and HMC cells. In addition, CCL19 was confirmed to be targeted and negatively regulated by miR-325-3p. Rescue assays validated that the impacts of miR-325-3p mimics on the viability, inflammation and fibrosis of HK-2 and HMC cells were recovered by CCL19 overexpression. To sum up, miR-325-3p inhibits renal inflammation and fibrosis by targeting CCL19 in a DN cell model and mice model, implying miR-325-3p as a possible therapeutic target for DN treatment.

Expression of Vsig4 attenuates macrophage-mediated hepatic inflammation and fibrosis in high fat diet (HFD)-induced mice.

The innate immune response contributes to hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). However, the pathogenic mechanism of NAFLD is still poorly understood. The costimulatory molecule V-set and immunoglobulin domain-containing protein-4 (Vsig4), which is exclusively expressed on macrophages, shows significant role in regulating macrophage-mediated inflammation. Here, we attempted to explore if Vsig4 expression was involved in high fat diet (HFD)-induced NAFLD. The results indicated that Vsig4 expression was markedly down-regulated in fatty livers of NAFLD patients and obese mice. Vsig4 knockout accelerated HFD-induced metabolic dysfunction. In addition, the loss of Vsig4 significantly promoted insulin resistance and lipid deposition in liver samples of HFD-challenged mice. Furthermore, HFD-induced inflammation was apparently accelerated in Vsig4 knockout mice by further activating nuclear factor-κB (NF-κB) signaling pathway. Also, Vsig4 deficient mice exhibited greater collagen accumulation in hepatic samples in HFD-challenged mice compared to the WT mice, which was through promoting transforming growth factor-ß1 (TGFß1) signaling. Importantly, we found that lipopolysaccharide (LPS)- or TGFß1-stimulated inflammation and fibrosis in primary hepatocytes and hepatic stellate cells, respectively, were markedly exacerbated by co-culture with condition medium from bone marrow-derived macrophages (BMDMs) with Vsig4 deficiency. Finally, transplantation of bone marrow cells from control mice to Vsig4-knockout mice restored the severity of steatosis, inflammation and fibrosis after HFD feeding. Therefore, loss of Vsig4 accelerated the severity of lipid deposition, fibrosis and the inflammatory response. Vsig4 could be a therapeutic target for NAFLD treatment.

PD-1 high expression predicts lower local disease control in stage IV M0 nasopharyngeal carcinoma.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) play a critical role in tumor immune surveillance and immune suppression. Understanding tumor infiltrating T cell subset density, location and PD-1/PD-L1 expression might provide insight for the prediction of tumor therapeutic response and clinical outcome. The purpose of this study was to evaluate the expression and localization of CD8, FoxP3, PD-1, and PD-L1 in primary tumor tissues and their effects on prognosis of stage IV M0 locally advanced nasopharyngeal carcinoma (NPC) patients. METHODS: Sixty NPC patients with stage IV M0 locally advanced disease were treated with definitive chemoradiation. Tumor biopsies from primary lesion were analyzed for the expression and localization of CD8, FoxP3, PD-1, and PD-L1 by immunohistochemistry. Their associations with local disease control and survival of NPC were analyzed. RESULTS: The average follow-up time was 43 months (range from 14 to 61 months). High expression of CD8+, FoxP3+, PD-1+ and PD-L1+ was observed in 60, 86.7, 56.7, and 91.7% of patients, respectively. There was no correlation between clinicopathological features and the expression of these immune markers. High PD-1 expression was found to be associated with lower local disease control (5-year LRFS 23.2% vs 96.8%, p < 0.001) and unfavorable clinical outcome (5-year OS 47.4% vs 73.3%, p = 0.014). In multivariate analysis, PD-1 expression was also an adverse prognostic factor for 5-year OS (HR: 3.68, P = 0.023) and LRFS (HR: 16.89, 1.27-11.84, P = 0.007). Those with PD-1 distribution in both stroma and tumor region had the poorest prognosis. However, PD-1 expression has no significant correlation with 5-year RRFS (p = 0.980) and DMFS (p = 0.865). Patients with both PD-1 and PD-L1 high expression had significant poor local disease control (5-year LRFS 96.0% vs 43.0%, p < 0.001) and overall survival (5-year OS 80.8% vs 45.1%, p < 0.001) compared with the others. Other immune markers were not found having corrections with disease control and survival. CONCLUSIONS: PD-1 high expression, especially with PD-L1 co-expression, is associated with high local recurrence and unfavorable clinical outcome for stage IV M0 NPC patients, and might be a potential target for immunotherapy.

Peritoneal Dialysis Treatment in Small Children with Acute Kidney Injury: Experience in Northwest China.

BACKGROUND: Peritoneal dialysis (PD) is a kind of renal replacement therapy (RRT), which can be employed to treat pediatric acute kidney injury (AKI) as it is safe, simple, and cost-effective. The studies of PD treatment in pediatric AKI in China have rarely been reported in English literature. OBJECTIVE: To investigate the efficacy and the outcome of PD in pediatric patients with AKI. METHODS: We performed a retrospective study of children who received PD as RRT for AKI in a teaching hospital in northwest China from 2003 to 2013. Demographic characteristics and laboratory data were collected, and the prognostic factors of renal recovery were identified. RESULTS: There were 24 children (62.5% male) identified, with the mean age of 22.4 ± 18.7 months (3 months to 5 years old). The most common causes of AKI were drug induced (25.0%), glomerulonephritis (20.9%), and obstructive nephropathy (16.7%). The mean duration of PD was 11.3 ± 7.8 days (2-39 days). PD treatment was highly effective in attenuation of toxics, improvement of fluid overload, and correction of electrolyte disturbances (p < 0.001). One catheter outflow obstruction was noted, and no major complication was identified. In total, 18 children (75.0%) recovered and had the catheter successfully removed, 2 (8.3%) needed further PD treatment, and 4 (16.7%) died. The albumin level was significantly higher in patients who recovered with PD treatment (33.7 ± 6.2 vs. 21.5 ± 4.8 g/L, p = 0.002). CONCLUSIONS: PD can be performed safely and efficiently for the treatment of pediatric AKI. Low albumin level may be associated with poor prognosis of pediatric AKI.

High precision calibration of optical lattice depth based on multiple pulses Kapitza-Dirac diffraction.

The precise calibration of optical lattice depth is an important step in the experiments of ultracold atoms in optical lattices. The Raman-Nath diffraction method, as the most commonly used method of calibrating optical lattice depth, has a limited range of validity and the calibration accuracy is not high enough. Based on multiple pulses Kapitza-Dirac diffraction, we propose and demonstrate a new calibration method by measuring the fully transfer fidelity of the first diffraction order. The high sensitivity of the transfer fidelity to the lattice depth ensures the highly precision calibration of the optical lattice depth. For each lattice depth measured, the calibration uncertainty is further reduced to less than 0.6% by applying the Back-Propagation Neural Network Algorithm. The accuracy of this method is almost one order of magnitude higher than that of the Raman-Nath diffraction method, and it has a wide range of validity applicable to both shallow lattices and deep lattices.

Targeted next generation sequencing identified clinically actionable mutations in patients with esophageal sarcomatoid carcinoma.

BACKGROUND: Esophageal sarcomatoid carcinoma (ESC) is a rare disease with a mixture of both carcinomatous and sarcomatous components in the tumor. Its genetic background and mechanisms of oncogenesis remain largely unknown. METHODS: Here we performed targeted next generation sequencing (NGS) on a pan-cancer gene panel in 15 ESC tumors to explore their genetic alterations, and aimed to identify clinically actionable mutations for future treatment instructions. RESULTS: TP53 alterations were identified in all patients. Alterations in receptor tyrosine kinases (RTK) were identified in 10 out of 15 patients. Members of downstream RAS and PI3-kinase pathways are also mutated in 10 patients, and PIK3CA is the top mutated gene in these pathways. In addition, we identified mutations on histone modification genes in 5 patients, including histone acetyltransferase gene EP300 and its homologue CREBBP, lysine methyltransferase genes KMT2A and KMT2B, and lysine demethylase gene KDM5A. Finally, mismatch repair (MMR) genes and proofreading gene POLE all together were mutated in one third of the ESC patients. CONCLUSIONS: This is the first study to unravel the mutational profile of ESC tumors. Our findings could match 9 patients to the targeted therapies currently available in clinical practice or in active clinical trials, suggesting the potential utility of targeted therapies for this rare disease in the future.

Breast osteoblastoma and recurrence after resection: Demonstration by color Doppler ultrasound.

Osteoblastoma is a rare benign primary bone tumor, which occurs in any part of the skeleton. Extraskeletal osteoblastoma is rather rare. We presented an extremely rare case of extraskeletal osteoblastoma located in the breast. The tumor recurred 7 months later after resection and transformed to aggressive osteoblastoma. The histopathological features, ultrasonic manifestations and ultrasonic differential diagnoses of the primary and recurrent tumors were discussed. The recommended treatment of the tumor is surgical excision. Due to its tendency of recurrence and potential malignant transformation, adequate resection and careful follow up is essential.

Two-stage crossed beam cooling with 6Li and ¹³³Cs atoms in microgravity.

Applying the direct simulation Monte Carlo (DSMC) method developed for ultracold Bose-Fermi mixture gases research, we study the sympathetic cooling process of 6Li and 133Cs atoms in a crossed optical dipole trap. The obstacles to producing 6Li Fermi degenerate gas via direct sympathetic cooling with 133Cs are also analyzed, by which we find that the side-effect of the gravity is one of the main obstacles. Based on the dynamic nature of 6Li and 133Cs atoms, we suggest a two-stage cooling process with two pairs of crossed beams in microgravity environment. According to our simulations, the temperature of 6Li atoms can be cooled to T = 29.5 pK and T/TF = 0.59 with several thousand atoms, which propose a novel way to get ultracold fermion atoms with quantum degeneracy near pico-Kelvin.

Risk factors for suspected pulmonary embolism in children: Complication of Mycoplasma pneumoniae pneumonia.

PURPOSE: Pulmonary embolism (PE) is not a rare complication of Mycoplasma pneumoniae pneumonia (MPP) in children. We sought to determine the incidence of PE in children with MPP who underwent clinically indicated CT pulmonary angiography (CTPA) and to evaluate the risk factors for PE. METHODS: All 106 children with MPP who were clinically suspected of having PE and who underwent CTPA were retrospectively enrolled from June 2018 to December 2021. The clinical features, laboratory data, and radiological parameters were recorded (e.g., lung consolidation involved and the Qanadli score). A Cox proportional hazards model and area under the receiver operating characteristic (ROC) curve were used to evaluate the risk factors and prognostic discriminatory capacity for PE. RESULTS: PE was detected in 26 of 106 (24.5 %) children (mean age, 6.2 years ± 3.3 years; 53 boys). Sixteen of the 26 (61.5 %) children with PE were boys. The mean age of the children with PE was 8.1 ± 2.9 years, and the mean Qanadli score was 15.3 ± 10.2. Children with PE had higher D-dimer levels (9.3 ± 7.1 mg/Lvs. 3.6 ± 3.8 mg/L) and a greater frequency of lung lobe consolidation (25 (96.2 %) vs. 64 (80.0 %)) (all P < 0.05). For children with MPP, age (hazard ratio (HR) = 1.96 (95 % CI1.04, 3.71; P = 0.037), D-dimer level (HR = 1.52, 95 % CI: 1.03, 2.24; P = 0.029), and bilateral lung consolidation (HR = 2.41, 95 % CI: 1.03, 5.58; P = 0.043) were found to be independent predictors of PE. CONCLUSION: Clinical and CT radiological predictors could be used to predict PE in children with MPP. The use of risk factor assessment as a tool has the potential to guide more appropriate use of CTPA in children.