Surgery is a Viable Treatment Option for Stage IE Primary Thyroid Lymphoma.

BACKGROUND: Stage IE primary thyroid lymphoma (PTL) has been diagnosed in approximately half of patients with PTL; however, the optimal treatment for stage IE PTL has not yet been established. METHODS: Stage IE PTL patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 1998 and 2019. Thereafter, the disease-specific survival (DSS) and treatment modalities (surgery alone, surgery + radiotherapy (RT) and/or chemotherapy (CT), and RT and/or CT) of these patients were compared by Kaplan-Meier curves and log-rank test after propensity score matching (PSM). Additionally, patients with PTL from the Affiliated Sixth People's Hospital of the Shanghai Jiao Tong University and School of Medicine (Shanghai, China) between 2007 and 2022 were retrospectively analyzed as an external cohort. RESULTS: Among the 1596 patients with PTL from the SEER database, 842 were identified as patients with stage IE PTL, with an average follow-up period of 7.8 years. Pairwise analysis after PSM revealed no significant difference between the DSS of the three treatment groups. A total of 38 patients with PTL were identified in the external cohort, with an average follow-up period of 3.4 years. Compared with the RT and/or CT group, the surgery-alone group showed no significant difference in the incidence of hypothyroidism (p = 0.161) but had significantly fewer treatment-related complications (p = 0.021), shorter treatment duration (p < 0.001), and lower treatment costs (p = 0.025). CONCLUSIONS: The results of our study demonstrate that surgery is a viable treatment option for patients with stage IE PTL.

Automated prediction of the neoadjuvant chemotherapy response in osteosarcoma with deep learning and an MRI-based radiomics nomogram.

OBJECTIVES: To implement a pipeline to automatically segment the ROI and to use a nomogram integrating the MRI-based radiomics score and clinical variables to predict responses to neoadjuvant chemotherapy (NAC) in osteosarcoma patients. METHODS: A total of 144 osteosarcoma patients treated with NAC were separated into training (n = 101) and test (n = 43) groups. After normalisation, ROIs for the preoperative MRI were segmented by a deep learning segmentation model trained with nnU-Net by using two independent manual segmentations as labels. Radiomics features were extracted using automatically segmented ROIs. Feature selection was performed in the training dataset by five-fold cross-validation. The clinical, radiomics, and clinical-radiomics models were built using multiple machine learning methods with the same training dataset and validated with the same test dataset. The segmentation model was evaluated by the Dice coefficient. AUC and decision curve analysis (DCA) were employed to illustrate the model performance and clinical utility. RESULTS: 36/144 (25.0%) patients were pathological good responders (pGRs) to NAC, while 108/144 (75.0%) were non-pGRs. The segmentation model achieved a Dice coefficient of 0.869 on the test dataset. The clinical and radiomics models reached AUCs of 0.636 with a 95% confidence interval (CI) of 0.427-0.860 and 0.759 (95% CI, 0.589-0.937), respectively, in the test dataset. The clinical-radiomics nomogram demonstrated good discrimination, with an AUC of 0.793 (95% CI, 0.610-0.975), and accuracy of 79.1%. The DCA suggested the clinical utility of the nomogram. CONCLUSION: The automatic nomogram could be applied to aid radiologists in identifying pGRs to NAC. KEY POINTS: • The nnU-Net trained by manual labels enables the use of an automatic segmentation tool for ROI delineation of osteosarcoma. • A pipeline using automatic lesion segmentation and followed by a radiomics classifier could aid the evaluation of NAC response of osteosarcoma. • A predictive nomogram composed of clinical variables and MRI-based radiomics score provides support for individualised treatment planning.

Interleukin 6 regulates the expression of programmed cell death ligand 1 in thyroid cancer.

Programmed cell death ligand 1 (PD-L1), inducing T cell exhaustion to facilitate immune escape of tumor cells, is upregulated by interleukin 6 (IL-6) in T cell lymphoma and ovarian cancer. The purpose of this study is to investigate the expression of IL-6 and PD-L1 in thyroid cancer, and whether IL-6 regulates PD-L1 expression. As a result, IL-6 and PD-L1 were highly expressed in thyroid cancer tissues. Multivariate logistic analysis showed that tumor size, distant metastasis, and risk stratification were significantly associated with IL-6 expression (P < .05), and multifocality, lymph node metastasis, distant metastasis, risk stratification, and IL-6 expression were identified as the independent predictors of PD-L1 expression (P < .05). The invasiveness of thyroid cancer was significantly enhanced after IL-6 treatment or PD-L1 overexpression. PD-L1 positive rate correlated with IL-6 expression in cancer tissues (P < .001), and after IL-6 treatment, the PD-L1 expression in TPC-1 and BCPAP significantly increased. The mitogen-activated protein kinase pathway (MAPK) and the Janus-activated kinase (JAK)-signal transducers and activators of transcription 3 (STAT3) signaling pathways were activated by IL-6, and the IL-6-induced PD-L1 expression decreased after treatment with these two signaling pathway inhibitors. Knockdown of transcription factors c-Jun and stat3 suppressed the expression of PD-L1 induced by IL-6, and these two factors could bind to PD-L1 gene promoter directly and promote its transcription. It is concluded that IL-6 and PD-L1 are overexpressed in thyroid cancer and are related to tumor invasiveness. IL-6 upregulates PD-L1 expression through the MAPK and JAK-STAT3 signaling pathways, which function via transcription factors c-Jun and stat3.

Chondromyxoid fibroma-like osteosarcoma: a case series and literature review.

BACKGROUND: Chondromyxoid fibroma-like osteosarcoma (CMF-OS) is an exceedingly rare subtype of low-grade central osteosarcoma (LGCO), accounting for up to 10% of cases and making it difficult to diagnose. CMF-OS is frequently misdiagnosed on a radiological examination and biopsy, even after the initial operation. Its treatment is a controversial issue due to its low-grade classification and actual high-grade behavior. CASE PRESENTATION: We retrospectively reviewed the medical charts of more than 2000 osteosarcoma patients between 2008 and 2019; 11 patients with CMF-OS were identified, of which six patients were treated by our institution with complete clinical characteristics, including treatment and prognosis, radiological and pathological features were reviewed. Three males and three females with a median age of 46 (range 22-56) years were pathologically proven to have CMF-OS. The radiological presentation of CMF-OS is variable, thus radiological misdiagnoses are common. However, one must not ignore a malignant radiologic appearance. The most distinctive pathological feature conferring the diagnosis of CMF-OS is the presence of osteoid production directly by the tumor cells under a chondromyxoid fibroma (CMF)-like background. Differential diagnoses based on comprehensive data from CMF, LGCO, chondrosarcoma (CHS), conventional osteosarcoma (COS), etc., are needed. All patients were treated with an operation and chemotherapy, and one patient received additional radiotherapy. Nevertheless, recurrence and metastasis are common in CMF-OS patients. Relatively invasive biological behavior of CMF-OS is against the low-grade classification of this disease. CONCLUSIONS: It is important to recognize CMF-OS and distinguish it from CMF, CHS, COS and other LGCOs. CMF-OS has a relatively poor prognosis despite its low-grade classification.

Development of Novel Nrf2/ARE Inducers Bearing Pyrazino[2,1-a]isoquinolin Scaffold with Potent In Vitro Efficacy and Enhanced Physicochemical Properties.

Pyrazino[2,1-a]isoquinolin analogues were reported as potent activators of Nrf2/ARE signaling both in vitro and in vivo by our group. In this study, we simplified the ring system to investigate the functions of various parts of the pyrazino[2,1-a]isoquinolin scaffold. We proved that the tetrahydroisoquinoline was not essential for activity and the pyrido[1,2-a]pyrazin analogues 3b and 3g retained the cellular Nrf2/ARE activation activity. Besides, this simplification significantly enhanced water solubility and membrane permeability, indicating that these compounds are more favourable for the further development of therapeutic agents around Nrf2 activation.

[Clinicopathologic characteristics of primary Schwannoma of the bone].

OBJECTIVE: To evaluate the diagnostic criteria and morphologic difference of primary schwannoma from that of soft tissue schwannoma. METHODS: All neurogenic tumors of the bone in this hospital from 2002 to 2013 were reviewed, four cases of primary schwannoma arising from bone were selected. Their clinical features, radiologic appearance and pathologic findings were evaluated. Immunophenotyping was performed using EnVision method. RESULTS: All four cases had classic morphologic features and immunophenotype of conventional schwannoma. Compared with schwannoma of the soft tissue, primary bone schwannoma had the following features: benign radiological appearance, absence of capsule under light microscope, local infiltration of bone or destruction of bone cortex, occasionally involving extra-osseous soft tissue. Most tumors were solid, with less cystic degeneration. Histologically, the tumors were mainly composed of compact areas of spindle cells (Antoni A), and areas of hypercellularity could often be observed. CONCLUSIONS: Primary schwannoma of the bone is rare, usually arises within the long bones and flat bones. Compared to conventional soft tissue schwannoma, it shows different growth pattern, imaging and pathologic features; thus care should be exercised not to misdiagnose schwannoma of the bone as other primary low-grade malignant spindle cell sarcoma of the bone and to avoid unnecessary over-treatment.

Bivalent inhibitors of the BTB E3 ligase KEAP1 enable instant NRF2 activation to suppress acute inflammatory response.

Most BTB-containing E3 ligases homodimerize to recognize a single substrate by engaging multiple degrons, represented by E3 ligase KEAP1 dimer and its substrate NRF2. Inactivating KEAP1 to hinder ubiquitination-dependent NRF2 degradation activates NRF2. While various KEAP1 inhibitors have been reported, all reported inhibitors bind to KEAP1 in a monovalent fashion and activate NRF2 in a lagging manner. Herein, we report a unique bivalent KEAP1 inhibitor, biKEAP1 (3), that engages cellular KEAP1 dimer to directly release sequestered NRF2 protein, leading to an instant NRF2 activation. 3 promotes the nuclear translocation of NRF2, directly suppressing proinflammatory cytokine transcription. Data from in vivo experiments showed that 3, with unprecedented potency, reduced acute inflammatory burden in several acute inflammation models in a timely manner. Our findings demonstrate that the bivalent KEAP1 inhibitor can directly enable sequestered substrate NRF2 to suppress inflammatory transcription response and dampen various acute inflammation injuries.

Alpha 2-adrenoceptor participates in anti-hyperalgesia by regulating metabolic demand.

The α2-adrenoceptor agonist dexmedetomidine is a commonly used drug for sedatives in clinics and has analgesic effects; however, its mechanism of analgesia in the spine remains unclear. In this study, we systematically used behavioural and transcriptomic sequencing, pharmacological intervention, electrophysiological recording and ultrasound imaging to explore the analgesic effects of the α2-adrenoceptor and its molecular mechanism. Firstly, we found that spinal nerve injury changed the spinal transcriptome expression, and the differential genes were mainly related to calcium signalling and tissue metabolic pathways. In addition, α2-adrenoceptor mRNA expression was significantly upregulated, and α2-adrenoceptor was significantly colocalised with markers, particularly neuronal markers. Intrathecal dexmedetomidine suppressed neuropathic pain and acute inflammatory pain in a dose-dependent manner. The transcriptome results demonstrated that the analgesic effect of dexmedetomidine may be related to the modulation of neuronal metabolism. Weighted gene correlation network analysis indicated that turquoise, brown, yellow and grey modules were the most correlated with dexmedetomidine-induced analgesic effects. Bioinformatics also annotated the involvement of metabolic processes and neural plasticity. A cardiovascular-mitochondrial interaction was found, and ultrasound imaging revealed that injection of dexmedetomidine significantly enhanced spinal cord perfusion in rats with neuropathic pain, which might be regulated by pyruvate dehydrogenase kinase 4 (pdk4), cholesterol 25-hydroxylase (ch25 h) and GTP cyclohydrolase 1 (gch1). Increasing the perfusion doses of dexmedetomidine significantly suppressed the frequency and amplitude of spinal nerve ligation-induced miniature excitatory postsynaptic currents. Overall, dexmedetomidine exerts analgesic effects by restoring neuronal metabolic processes through agonism of the α2-adrenoceptor and subsequently inhibiting changes in synaptic plasticity.

Tubular cells produce FGF2 via autophagy after acute kidney injury leading to fibroblast activation and renal fibrosis.

Following acute kidney injury (AKI), renal tubular cells may stimulate fibroblasts in a paracrine fashion leading to interstitial fibrosis, but the paracrine factors and their regulation under this condition remain elusive. Here we identify a macroautophagy/autophagy-dependent FGF2 (fibroblast growth factor 2) production in tubular cells. Upon induction, FGF2 acts as a key paracrine factor to activate fibroblasts for renal fibrosis. After ischemic AKI in mice, autophagy activation persisted for weeks in renal tubular cells. In inducible, renal tubule-specific atg7 (autophagy related 7) knockout (iRT-atg7-KO) mice, autophagy deficiency induced after AKI suppressed the pro-fibrotic phenotype in tubular cells and reduced fibrosis. Among the major cytokines, tubular autophagy deficiency in iRT-atg7-KO mice specifically diminished FGF2. Autophagy inhibition also attenuated FGF2 expression in TGFB1/TGF-ß1 (transforming growth factor, beta 1)-treated renal tubular cells. Consistent with a paracrine action, the culture medium of TGFB1-treated tubular cells stimulated renal fibroblasts, and this effect was suppressed by FGF2 neutralizing antibody and also by fgf2- or atg7-deletion in tubular cells. In human, compared with non-AKI, the renal biopsies from post-AKI patients had higher levels of autophagy and FGF2 in tubular cells, which showed significant correlations with renal fibrosis. These results indicate that persistent autophagy after AKI induces pro-fibrotic phenotype transformation in tubular cells leading to the expression and secretion of FGF2, which activates fibroblasts for renal fibrosis during maladaptive kidney repair.Abbreviations: 3-MA: 3-methyladnine; ACTA2/α-SMA: actin alpha 2, smooth muscle, aorta; ACTB/ß-actin: actin, beta; AKI: acute kidney injury; ATG/Atg: autophagy related; BUN: blood urea nitrogen; CCN2/CTGF: cellular communication network factor 2; CDKN2A/p16: cyclin dependent kinase inhibitor 2A; CKD: chronic kidney disease; CM: conditioned medium; COL1A1: collagen, type I, alpha 1; COL4A1: collagen, type IV, alpha 1; CQ: chloroquine; ECM: extracellular matrix; eGFR: estimated glomerular filtration rate; ELISA: enzyme-linked immunosorbent assay; FGF2: fibroblast growth factor 2; FN1: fibronectin 1; FOXO3: forkhead box O3; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HAVCR1/KIM-1: hepatitis A virus cellular receptor 1; IHC: immunohistochemistry; IRI: ischemia-reperfusion injury; ISH: in situ hybridization; LTL: lotus tetragonolobus lectin; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; PDGFB: platelet derived growth factor, B polypeptide; PPIB/cyclophilin B: peptidylprolyl isomerase B; RT-qPCR: real time-quantitative PCR; SA-GLB1/ß-gal: senescence-associated galactosidase, beta 1; SASP: senescence-associated secretory phenotype; sCr: serum creatinine; SQSTM1/p62: sequestosome 1; TASCC: TOR-autophagy spatial coupling compartment; TGFB1/TGF-ß1: transforming growth factor, beta 1; VIM: vimentin.

Single-Cell Transcriptomic Atlas of Parathyroid Adenoma and Parathyroid Carcinoma.

Primary hyperparathyroidism is typically characterized by monoclonal parathyroid tumors that secrete an excessive amount of parathyroid hormone (PTH). However, the underlying pathogenesis of tumorigenesis remains unclear. We performed single-cell transcriptomic analysis on five parathyroid adenoma (PA) and two parathyroid carcinoma (PC) samples. A total of 63,909 cells were divided into 11 different cell categories; endocrine cells accounted for the largest proportion of cells in both PA and PC, and patients with PC had larger populations of endocrine cells. Our results revealed significant heterogeneity in PA and PC. We identified cell cycle regulators that may play a critical role in the tumorigenesis of PC. Furthermore, we found that the tumor microenvironment in PC was immunosuppressive, and endothelial cells had the highest interactions with other cell types, such as fibroblast-musculature cells and endocrine cells. PC development may be stimulated by fibroblast-endothelial cell interactions. Our study clarifies the transcriptional signatures that underlie parathyroid tumors and offer a potential significant contribution in the study of pathogenesis of PC. © 2023 American Society for Bone and Mineral Research (ASBMR).

Pitfalls and strategies of Sonazoid enhanced ultrasonography in differentiating metastatic and benign hepatic lesions.

OBJECTIVE: This article aims to clarify pitfalls and find strategies for the detecting and diagnosing hyperechoic liver metastases (LMs) using Sonazoid-contrast enhanced ultrasonography (Sonazoid-CEUS). METHODS: This study was a prospective self-controlled study. Patients with hepatic lesions suspected as LMs or benign lesions were included in the study. Baseline ultrasonography (BUS) and Sonazoid-CEUS were performed on every patient. Characteristics of LMs and benign nodules were compared by chi-square test and fisher test. Factors influenced the CEUS were demonstrated by univariate analysis and multivariate logistic regression analysis. RESULTS: 54 patients were included in this study. CEUS found additional 75 LMs from 19 patients in Kupffer phase. We found hyperechoic focal liver lesions and deep seated in liver are main confounding factors in CEUS diagnosis. Sensitivity would be improved from 16.67% to 78.57%, negative predictive value (NPV) would be improved from 28.57% to 76.92% and accuracy would be improved from 37.5% to 87.50% when using rapid "wash-in" and "wash-out" as main diagnostic criteria. CONCLUSIONS: Hyperechoic LMs especially deeply seated ones are usually not shown typical "black hole" sign in Kupffer phase. Quickly "wash-in and wash out" shows high accuracy in diagnosing malignant nodules. We highly recommend CEUS as a routing exam to detect and diagnose LMs.

Genomic Profiling Reveals the Variant Landscape of Sporadic Parathyroid Adenomas in Chinese Population.

OBJECTIVE: To define somatic variants of parathyroid adenoma (PA) and to provide novel insights into the underlying molecular mechanism of sporadic PA. METHODS: Basic clinical characteristics and biochemical indices of 73 patients with PA were collected. Whole-exome sequencing was performed on matched tumor-constitutional DNA pairs to detect somatic alterations. Functional annotation was carried out by ingenuity pathway analysis afterward. The protein expression of the variant gene was confirmed by immunohistochemistry, and the relationship between genotype and phenotype was analyzed. RESULTS: Somatic variants were identified in 1549 genes, with an average of 69 variants per tumor (range, 13-2109; total, 9083). Several novel recurrent somatic variants were detected, such as KMT2D (15/73), MUC4 (14/73), POTEH (13/73), CD22 (12/73), HSPA2 (12/73), HCFC1 (11/73), MAGEA1 (11/73), and SLC4A3 (11/73), besides the previously reported PA-related genes, including MEN1 (11/73), CASR (6/73), MTOR (4/73), ASXL3 (3/73), FAT1 (3/73), ZFX (5/73), EZH1 (2/73), POT1 (2/73), and EZH2 (1/73). Among them, KMT2D might be the candidate driver gene of PA. Crucially, 5 patients carried somatic mutations in CDC73, showed an aggressive phenotype similar to that of parathyroid carcinoma (PC), and had a decreased expression of parafibromin. Pathway analysis of recurrent potential PA-associated driver variant genes revealed functional enrichments in the signaling pathway of Notch. CONCLUSION: Our study expanded the pathogenic variant spectrum of PA and indicated that KMT2D might be a novel candidate driver gene and be considered as a diagnostic biomarker for PA. Meanwhile, CDC73 mutations might be an early developmental event from PA to PC. The results provided insights into elucidating the pathogenesis of parathyroid tumorigenesis and a certain basis for clinical diagnosis and treatment.

Splenectomy does not affect mouse behaviors.

The spleen is critical for immunity. It is the largest immune organ and immune center in the peripheral system. While the relationship between behavior and immunity has been demonstrated in physiology and diseases, the role of the spleen in behavior is not clear. To investigate the effects of the spleen on behaviors, we performed a refined splenectomy procedure on C57BL/6J mice and performed an open field test, circadian rhythm test, elevated plus maze, sucrose preference test, and Barnes maze test. Splenectomy did not induce changes in general locomotion, circadian rhythms, learning and memory, or depression/anxiety-related behaviors. To further investigate the effects of spleen on stress susceptibility, we established mouse models of depression through chronic unpredictable mild stress. The behavioral performances of mice subjected to splenectomy showed no differences from control animals. These findings suggest that splenectomy does not cause changes in baseline behavioral performance in mice.

Decreasing pancreatic leak after distal pancreatectomy: bovine pericardium wrapping stump in a porcine model.

BACKGROUND: Despite marked improvements in pancreatic surgery, the high incidence and morbidity of pancreatic leak after resection has remained unchanged. The current study investigated the safety and efficacy of bovine pericardium wrapping stump after distal pancreatectomy in a porcine model. METHODS: Thirty-two swine were randomly assigned to control and experiment groups to undergo conventional scalpel transection with single hand-sewn closure of the pancreatic remnant (control) or bovine pericardium wrapping stump combined with hand-sewn closure (experiment). Closed-suction drainage was collected and measured daily. Animals were necropsied at 3 weeks postoperatively, and the pancreatic remnants were examined for histology. Primary end points were the development of a pancreatic fistula defined as greater than threefold drain/serum amylase after the 3rd postoperative day, and the presence of undrained amylase-rich fluid collections/abscess. RESULTS: The incidence of pancreatic leak in the wrapping group was 6.3 versus 46.7% in the control group (p < 0.05). The amount of drainage fluid was higher in the control group than the experiment group during the postoperative days. There were no differences in operative time or other clinical parameters measured. No other significant differences were found in macroscopic changes between groups at reexploration. Histological examination demonstrated focal, chronic inflammation with necrosis in all animals. CONCLUSIONS: Bovine pericardium wrapping stump effectively reduced the incidence of pancreatic leakage after the distal pancreatectomy.

Severe 25-Hydroxyvitamin D Deficiency May Predict Poor Renal Outcomes in Patients With Biopsy-Proven Diabetic Nephropathy.

Aims: This study aims to investigate the role of 25-hydroxyvitamin D (25(OH)D) levels in predicting renal survival in biopsy-proven diabetic nephropathy (DN) with type 2 diabetes mellitus (DM). Methods: In this retrospective study, a total of 161 biopsy-proven DN patients were enrolled and divided into four groups (normal group: 25(OH)D>20ng/ml; mild group: 10<25(OH)D ≤ 20ng/ml; moderate group: 5<25(OH)D ≤ 10 ng/ml; severe group: 25(OH)D ≤ 5 ng/ml). The effect of the 25(OH)D level on renal survival was evaluated by multivariate Cox regression. Results: A total of 161 type 2 DM patients with biopsy-proven DN were enrolled in this study. Patients with lower 25(OH)D levels had higher serum creatinine, urinary albumin creatinine ratio (UACR), total cholesterol, and parathyroid hormone levels as well as lower estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and calcium levels and were more prone to diabetic retinopathy (DR). Rather than proteinuria and renal function, glomerular class and interstitial fibrosis and tubular atrophy (IFTA) had a significant correlation with 25(OH)D levels. Multivariate Cox regression indicated that severe deficiency of 25(OH)D levels was associated with adverse renal outcomes. Compared to the level in the normal group, after adjusting for clinicopathological characteristics, a lower 25(OH)D level remained a risk factor for renal outcomes. The HRs were 3.446 (95% CI 0.366-32.406, p=0.279) for the mild group, 8.009 (95% CI 0.791-81.102, p=0.078) for the moderate group, and 14.957(95%CI 1.364-163.995, P=0.027) for the severe group. Conclusion: Levels of 25(OH)D less than 5 ng/ml were correlated with worse renal function, more pathological injury and poorer renal prognosis in patients with biopsy-proven DN.

Clinical and Histological Predictors of Renal Survival in Patients with Biopsy-Proven Diabetic Nephropathy.

INTRODUCTION: Clinical indicators or pathological features alone cannot reliably predict renal survival in patients with biopsy-confirmed diabetic nephropathy (DN). Therefore, this analysis sought to develop and validate a predictive model incorporating both clinical and pathological markers to predict renal outcomes in patients with biopsy-confirmed DN. METHODS: A predictive nomogram was developed based upon data pertaining to 194 patients with biopsy-confirmed DN. The prognostic relevance of individual clinicopathological variables was assessed through univariate and multivariate Cox regression analyses. A prognostic nomogram was then developed and validated based upon concordance (C)-index values and calibration curves. Internal validation was conducted through bootstrap resampling, while the clinical utility of this model was assessed via a decision curve analysis (DCA) approach. RESULTS: Nephrotic-range 24-h proteinuria, late-stage CKD, glomerular classification III-IV, and IFTA score 2-3 were all identified as independent predictors of poor renal outcomes in DN patients and were incorporated into our final nomogram. Calibration curves revealed good agreement between predicted and actual 3- and 5-year renal survival in DN patients with the C-index value for this nomogram at 0.845 (95% CI: 0.826-0.864). DCA revealed that our nomogram was superior to models based solely upon clinical indicators. CONCLUSION: A predictive nomogram incorporating clinical and pathological indicators was developed and validated for the prediction of renal survival outcomes in patients with biopsy-confirmed DN. This model will be of value to clinicians, as it can serve as an easy-to-use and reliable tool for physicians to guide patient management based on individualized risk.

Pseudobronchial crista-like change in children: A case report.

Pseudobronchial crista-like change is an unusual type of inflammatory granulation tissue hyperplasia in the endobronchial membrane caused by chronic retention of bronchial foreign bodies. Here, we report a case of pseudobronchial crista-like change in a 4-year-old boy who required admission for intermittent cough for >10 days and wheezing for 2 days. The main manifestation was persistent and non-healing lobar pneumonia. Initial electronic bronchoscopy showed cristae at the distal left main bronchus, which was misdiagnosed as bronchial opening stenosis. Repeat electronic bronchoscopy was performed after standard antibiotic treatment proved ineffective. Foreign bodies were observed at the opening of the basal branch of the left lower lobe. The left main bronchial cristae were clamped. The cristae appeared to be a pseudobronchial crista-like change caused by long-term retention of bronchial foreign bodies. After CT-confirmation of no abnormal blood supply at the cristae, the bronchial foreign bodies were removed, and the distal cristae of the left main bronchus were cut-off by laser, followed by balloon dilatation. To our knowledge, no similar cases have been reported so far in our review of domestic and foreign literature. Insufficient clinical understanding of Pseudobronchial Crista-like Change increase the risk of misdiagnosis and missed diagnosis. Detailed exploration and careful identification under bronchoscopy are helpful for the timely diagnosis and treatment of Pseudobronchial Crista-like Change.

Protocol of Kupffer phase whole liver scan for metastases: A single-center prospective study.

Introduction: As the presence of hepatic metastases is very important to cancer patients' clinical stage which would directly affect the selection and application of anti-cancer treatments. Although conventional ultrasound is commonly performed as a screening tool, most of the examinations have relatively poor sensitivity and specificity for detecting liver metastases. Contrast-enhanced ultrasound (CEUS) with Sonazoid has been reported to have the advantage of the diagnosis and therapeutic support of focal hepatic lesions and its specific Kupffer phase whole liver scan (KPWLS) is believed to be sensitive to detect liver metastases. And the purpose of this study is to determine the number, size, location and diagnosis of metastatic lesions, and to compare the results with conventional ultrasound and contrast-enhanced computed tomography (CECT), thus to clarify the application value, indications of Sonazoid-CEUS in screening liver metastasis. Methods and analysis: Kupffer phase whole liver scan for metastases (KPWLSM) is a self-control, blind map-reading, single-center, prospective superiority trial. Approved by the institutional review committee, the study period is planned to be from 1 January 2022 to 31 December 2025. Our study will include 330 patients with history of malignant tumors that cling to metastasize to liver. All patients will undergo the examinations of conventional ultrasound, Sonazoid-CEUS, and contrast-enhanced magnetic resonance imaging (CEMRI), and 65 of them should have additional CECT scans. The primary endpoint is the comparative analysis of the numbers of detected liver metastatic lesions among Sonazoid-CEUS, conventional ultrasound and CECT in screening liver metastases. Subjective conditions of patient after injection of Sonazoid will be followed up 3 and 30 days after KPWLSM, and any short-term and long-term adverse events are to be recorded with telephone interviews. Ethics and dissemination: This study has been granted by the Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People's Hospital (Approval No: 2021-197). When the KPWLSM is completed, we will publish it in an appropriate journal to promote further widespread use. Registration: Trial Registration Number and Date of Registration: Chinese Clinical Trial Registry, ChiCTR2100054385, December 16, 2021.

Primary Thyroid NUT Carcinoma With High PD-L1 Expression and Novel Massive IGKV Gene Fusions: A Case Report With Treatment Implications and Literature Review.

BACKGROUND: Nuclear protein in testis (NUT) carcinoma (NC) is a rare and aggressive undifferentiated carcinoma that typically arises from midline supradiaphragmatic structures. It is uniquely driven by a NUT gene rearrangement on chromosome 15q14. Few thyroid NCs have been reported and there are no established treatment guidelines for NUT carcinoma. METHOD: Ultrasound-guided fine needle aspiration smear was performed for the preoperative diagnosis of thyroid lesions. Cytopathology, histology, and immunochemical staining all indicated NC. Fluorescence in situ hybridization (FISH), qRT-PCR, and next-generation sequencing (NGS) were used to analyze the genetic characteristics of NC. RESULTS: We describe a rare case of thyrogenic NC in a 38-year-old male with cytological, histological, immunohistochemical, and genetic features. Cytological smears and histopathological specimens showed typical features of NC. Immunohistochemistry confirmed strong immunoreactivity with NUT, EMA, P63, TTF-1, and c-myc. CK19 was positive exclusively in sudden keratosis. No immunoreactivity was found for neuroendocrine markers. FISH was applied to isolate the NUT gene on chromosome 15q14. The NGS results revealed a BRD4-NUT gene fusion, which was further confirmed by RT-qPCR. Structural variation (SV) of NUTM1 occurred in the exon region, and the mutation site was 15q14. Moreover, BRD4 single-nucleotide variation (SNV) occurs in the 3' UTR at mutation site 19p13.12. The PD-L1 combined predictive score was over 30%. The patient received chemotherapy, followed by programmed cell death 1 (PD-1) inhibition with camrelizumab, and died 10 months after surgery. CONCLUSION: Thyroid NC is an extremely rare and fatal malignant tumor. It is necessary to consider NC when squamous differentiation is observed cytologically or histologically. NGS is an effective tool for obtaining the final diagnosis and obtaining a better understanding of tumor pathogenesis. A large number of IGKV gene fusions in addition to the BRD4-NUT fusion may play a role in the pathogenesis and immunotherapy response of NC. Immunotherapy for NC remains to be explored due to the rarity of this aggressive malignancy.