Evaluation of Kidney Injury Using Arterial Spin Labeling and Blood Oxygen Level-Dependent MRI: An Experimental Study in Rats With Carbon Tetrachloride-Induced Liver Cirrhosis.

BACKGROUND: Serum creatinine (Scr) may be not suited to timely and accurately reflect kidney injury related to chronic liver disease. Currently, the ability of arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) sequences to evaluate renal blood flow (RBF) and blood oxygen in chronic liver disease remains to be verified. PURPOSE: To investigate the value of ASL and BOLD imaging in evaluating hemodynamics and oxygenation changes during kidney injury in an animal model of chronic liver disease. STUDY TYPE: Prospective. ANIMAL MODEL: Chronic liver disease model was established by subcutaneous injection of carbon tetrachloride. Forty-three male Sprague-Dawley rats (8 weeks) were divided into a pathological group (0, 2, 4, 6, 8, 12 weeks, each group: N = 6) and a continuous-scanning group (N = 7). FIELD STRENGTH/SEQUENCE: 3-T, ASL, BOLD, and T2W. ASSESSMENT: Regions of interest in the cortex (CO), outer stripe of the outer medulla (OSOM), and inner stripe of the outer medulla (ISOM) are manually delineated. The RBF and T2* values at each time point (0, 2, 4, 6, 8, 12 weeks) are measured and compared. Hematoxylin-eosin score (HE Score, damage area scoring method), alpha-smooth muscle actin (α-SMA), hypoxia-inducible factor-1alpha (HIF-1α), peritubular capillar (PTC) density, Scr, and neutrophil gelatinase-associated lipocalin were harvested. STATISTICAL TESTS: Analysis of variance, Spearman correlation analysis, Kruskal-Wallis tests, and receiver operating characteristic analysis with the area under the curve (AUC). A P-value <0.05 was considered statistically significant. RESULTS: Renal RBF and T2* values of CO, OSOM, and ISOM were significantly different from baseline. Both RBF and T2* were significantly correlated with HE Score, α-SMA, HIF-1α, and PTC density (|r| = 0.406-0.853). RBF demonstrated superior diagnostic capability in identifying severe kidney injury in this model of chronic liver disease (AUC = 0.964). DATA CONCLUSION: Imaging by ASL and BOLD may detect renal hemodynamics and oxygenation changes related to chronic liver disease early. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 2.

[Clinicopathological features of primary seminal vesicle adenocarcinoma: A report of 4 cases and review of the literature].

OBJECTIVE: To investigate the clinicopathological characteristics, diagnosis, and treatment of primary seminal vesicle adenocarcinoma (SVAC). METHODS: We analyzed the clinical data and clinicopathological characteristics of 4 cases of primary SVAC treated in the Department of Urology of the Second Hospital of Tianjin Medical University and reviewed relevant literature. RESULTS: All the 4 patients were treated by open radical resection of the seminal vesicle and prostate and pathologically diagnosed with SVAC. Preoperative prostatic biopsy had shown 1 of the cases to be negative, while preoperative CT and transrectal ultrasound had revealed a huge pelvic cystic neoplasm in another patient. Immunohistochemistry manifested that the 4 cases were all negative for prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and cytokeratin 20 (CK20), but positive for cancer antigen 125 (CA125) and CK7. All the patients recovered smoothly after surgery and experienced no recurrence or metastasis during 154, 41, 20, and 12 months of follow-up. CONCLUSIONS: Primary seminal vesicle carcinoma is extremely rare and presents in an advanced stage. Immunohistochemistry plays a valuable role in its differential diagnosis. Various combinations of radical surgery, radiotherapy, androgen-deprivation therapy, and chemotherapy are recommended for the treatment of the disease.

Quantitative Analysis of Diffusion-Weighted Imaging for Diagnosis of Puerperal Breast Abscess After Polyacrylamide Hydrogel Augmentation Mammoplasty: Compared with Other Conventional Modalities.

PURPOSE: Puerperal breast abscess after polyacrylamide hydrogel (PAAG) augmentation mammoplasty can induce breast auto-inflation resulting in serious consequences. Mammography, ultrasound, and conventional MRI are poor at detecting related PAAG abnormality histologically. We evaluated the value of diffusion-weighted imaging (DWI) in the quantitative analysis of puerperal PAAG abscess after augmentation mammoplasty. MATERIALS AND METHODS: This was a retrospective study, and a waiver for informed consent was granted. Sixteen puerperal women with breast discomfort underwent conventional breast non-enhanced MRI and axial DWI using a 3T MR scanner. Qualitative analysis of the signal intensity on DWI and conventional sequences was performed. The apparent diffusion coefficient (ADC) values of the affected and contralateral normal PAAG cysts were measured quantitatively. Paired t test was used to evaluate whether there was significant difference. RESULTS: Both affected and normal PAAG cysts showed equal signal intensity on conventional T1WI and fat saturation T2WI, which were not helpful in detecting puerperal PAAG abscess. However, the affected PAAG cysts had a significantly decreased ADC value of 1.477 ± 0.332 × 10(-3)mm(2)/s and showed obvious hypo-intensity on the ADC map and increased signal intensity on DWI compared with the ADC value of 2.775 ± 0.233 × 10(-3)mm(2)/s of the contralateral normal PAAG cysts. CONCLUSION: DWI and quantitative measurement of ADC values are of great value for the diagnosis of puerperal PAAG abscess. Standardized MRI should be suggested to these puerperal women with breast discomfort or just for the purpose of check up. DWI should be selected as the essential MRI sequence.

Use of Intravoxel Incoherent Motion Diffusion-Weighted Imaging to Assess Mesenchymal Stromal Cells Promoting Liver Regeneration in a Rat Model.

RATIONALE AND OBJECTIVES: Mesenchymal stem cells (MSCs) have the potential to promote liver regeneration, but the process is unclear. This study aims to explore the therapeutic effects and dynamic processes of MSCs in liver regeneration through intravoxel incoherent motion (IVIM) imaging. ANIMAL MODEL: 70 adult Sprague-Dawley rats were randomly divided into either the control or MSC group (n = 35/group). All rats received a partial hepatectomy (PH) with the left lateral and middle lobes removed. Each group was divided into seven subgroups: pre-PH and 1, 2, 3, 5, 7, and 14 days post-PH (n = 5 rats/subgroup). Magnetic resonance imaging (MRI) was performed before obtaining pathological specimens at each time point on postoperative days 1, 2, 3, 5, 7, and 14. The MRI parameters for the pure diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (PF) were calculated. Correlation analysis was conducted for the biochemical markers (alanine transaminase [ALT], aspartate transaminase [AST], and total bilirubin [TBIL]), histopathological findings (hepatocyte size and Ki-67 proliferation index), liver volume (LV) and liver regeneration rate (LLR). RESULTS: Liver D, D* , and PF differed significantly between the control and MSC groups at all time points (all P < 0.05). After PH, the D increased, then decreased, and the D* and PF decreased, then increased in both groups. The hepatocyte Ki-67 proliferation index of the MSC group was lower on day 2 post-PH, but higher on days 3 and 5 post-PH than that of the control group. Starting from day 3 post-PH, both the LV and LLR in the MSC group were greater than those in the control group (all P < 0.05). Hepatocytes were larger in the MSC group than in the control group on days 2 and 7 post-PH. In the MSC group, the D, D* , and PF were correlated with the AST levels, Ki-67 index and hepatocyte size (|r|=0.35-0.71; P < 0.05). In the control group, the D and D* were correlated with ALT levels, AST levels, Ki-67 index, LLR, LV, and hepatocyte size (|r|=0.34-0.95; P < 0.05). CONCLUSION: Bone marrow MSC therapy can promote hepatocyte hypertrophy and prolong liver proliferation post-PH. IVIM parameters allow non-invasively evaluating the efficacy of MSCs in promoting LR.

Estimating pathological prognostic factors in epithelial ovarian cancers using apparent diffusion coefficients of functional tumor volume.

PURPOSE: To assess the utility of apparent diffusion coefficients (ADCs) of whole tumor volume (WTV) and functional tumor volume (FTV) in determining the pathologicalprognostic factors in epithelial ovarian cancers (EOCs). METHODS: A total of 155 consecutive patients who were diagnosed with EOC between January 2017 and August 2022 and underwent both conventional magnetic resonance imaging and diffusion-weighted imaging were assessed in this study. The maximum, minimum, and mean ADC values of the whole tumor (ADCwmax, ADCwmin, and ADCwmean, respectively) and functional tumor (ADCfmax, ADCfmin, and ADCfmean, respectively) as well as the WTV and FTV were derived from the ADC maps. The univariate and multivariate logistic regression analyses and receiver operating characteristic curve (ROC) analysis were used to assess the correlation between these ADC values and the pathological prognostic factors, namely subtypes, lymph node metastasis (LNM), Ki-67 index, and p53 expression. RESULTS: The ADCfmean value was significantly lower in type II EOC, LNM-positive, and high-Ki-67 index groups compared to the type I EOC, LNM-negative, and low-Ki-67 index groups (p ≤ 0.001). Similarly, the ADCwmean and ADCfmean values were lower in the mutant-p53 group compared to the wild-type-p53 group (p ≤ 0.001). Additionally, the ADCfmean showed the highest area under the ROC curve (AUC) for evaluating type II EOC (0.725), LNM-positive (0.782), and high-Ki-67 index (0.688) samples among the given ROC curves, while both ADCwmean and ADCfmean showed high AUCs for assessing p53 expression (0.694 and 0.678, respectively). CONCLUSION: The FTV-derived ADC values, especially ADCfmean, can be used to assess preoperative prognostic factors in EOCs.

Squamous cell carcinoma of ear and temporal bone: A retrospective study on clinicopathological predictors.

BACKGROUND: Ear and temporal bone squamous cell carcinoma (ETBSCC) is a rare and aggressive malignant tumor with minimal clinicopathological studies. The object of this study was to retrospectively evaluate the predictive effect of clinicopathological variables on the 5-year overall survival (OS) rate of ETBSCC patients in a single tertiary medical center in Tianjin, China. METHODS: A cohort of 44 patients with diagnosed ETBSCC from December 2012 to August 2022 were retrospectively studied. Univariate and multivariate analysis were, respectively, performed for the assessment of clinicopathological predictors, including sex, age, history of chronic suppurative otitis media (CSOM), lesion side, diameter, the choice of surgical approach, parotidectomy, neck dissection, adjuvant therapies, T stage, lymph node metastasis, tumor grade, margin, perineural invasion (PNI), and Ki-67 index. RESULTS: Seventeen females and 27 males were included, with the mean age of 65 years old, ranging from 36 to 89 years. The 5-year OS rate was 43% (mean 51 months, 95% confidence interval [CI] = 39-64). Significant prediction of a worse prognosis for 5-year OS rate was observed under univariate analysis for advanced T stage, positive margin, identified PNI, and higher Ki-67 index, respectively. Advanced T stage was confirmed to be an independent prognostic factor strongly affecting 5-year OS rate among this cohort of patients using a multivariate cox proportional hazard model. CONCLUSION: We found that clinicopathological parameters, especially postoperative pathological parameters, play a critical role in predicting the prognosis of ETBSCC patients.

3-O-Methyl-D-Glucose Blunts Cold Ischemia Damage in Kidney via Inhibiting Ferroptosis.

BACKGROUND: The glucose derivative 3-O-methyl-D-glucose (OMG) is used as a cryoprotectant in freezing cells. However, its protective role and the related mechanism in static cold storage (CS) of organs are unknown. The present study aimed to investigate the effect of OMG on cod ischemia damage in cold preservation of donor kidney. METHODS: Pretreatment of OMG on kidney was performed in an isolated renal cold storage model in rats. LDH activity in renal efflux was used to evaluate the cellular damage. Indicators including iron levels, mitochondrial damage, MDA level, and cellular apoptosis were measured. Kidney quality was assessed via a kidney transplantation (KTx) model in rats. The grafted animals were followed up for 7 days. Ischemia reperfusion (I/R) injury and inflammatory response were assessed by biochemical and histological analyses. RESULTS: OMG pretreatment alleviated prolonged CS-induced renal damage as evidenced by reduced LDH activities and tubular apoptosis. Kidney with pCS has significantly increased iron, MDA, and TUNEL+ cells, implying the increased ferroptosis, which has been partly inhibited by OMG. OMG pretreatment has improved the renal function (p <0.05) and prolonged the 7-day survival of the grafting recipients after KTx, as compared to the control group. OMG has significantly decreased inflammation and tubular damage after KTx, as evidenced by CD3-positive cells and TUNEL-positive cells. CONCLUSION: Our study demonstrated that OMG protected kidney against the prolonged cold ischemia-caused injuries through inhibiting ferroptosis. Our results suggested that OMG might have potential clinical application in cold preservation of donor kidney.

Comparison of fine-needle aspiration and core-needle biopsy in the pathological evaluation on thyroid lesions: A single-center experience on 407 Chinese patients.

BACKGROUND: The object of this study was to compare the diagnosis performance of US-guided fine-needle aspiration (FNA) and core-needle biopsy (CNB) for patients with thyroid nodules, in aspects of sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV). MATERIALS AND METHODS: Four hundred seven Chinese patients from July 2019 to June 2022 were retrospectively recruited in this study. Cytological diagnoses were categorized into six categories based on the 2017 Bethesda System for Reporting Thyroid Cytopathology (BSRTC), and histological specimens were drawn a diagnosis by means of an analogy with the Bethesda system. RESULTS: All patients incorporated were proceed with surgical excision (SE) and received final surgical diagnoses. The rate of malignancy (ROM) was comparable between two methods, with the exception that the test-negative category of the FNA group was significantly higher than that of the CNB group (39.25% vs. 23.86%, p = .022). Sensitivity and accuracy were higher in CNB group (82.50% and 87.83%, respectively) than that in FNA group (72.00% and 79.36%, respectively), as well as NPV (76.14% in CNB vs. 60.75% in FNA), but not in terms of the specificity and PPV (95.59% and 97.30% in FNA vs. 97.10% and 98.02% in CNB). CONCLUSION: CNB displayed a higher sensitivity and accuracy than FNA in malignant lesions of thyroid. Both FNA and CNB exhibit excellent performance with the understanding that both need to be applied under the most appropriate conditions to maximize their benefits.

Assessment of Fibrotic Liver Regeneration After Partial Hepatectomy With Intravoxel Incoherent Motion Diffusion-Weighted Imaging: An Experimental Study in a Rat Model With Carbon Tetrachloride Induced Liver Injury.

PURPOSE: To determine whether intravoxel incoherent motion (IVIM) parameters correlate with liver regeneration and function recovery after partial hepatectomy (PH) in rats with carbon tetrachloride (CCl4)-induced liver fibrosis. METHODS: Sixty-two adult Sprague-Dawley rats were divided into the control group and the fibrosis group with CCl4 injection for 8 weeks. At the end of the 8th week, all rats received left lateral lobe liver resection. Within each group, IVIM imaging (n = 10/group) and histologic and biochemical analyses (n = 3/group/time point) were performed pre- and post-PH (on days 1, 2, 3, 5, 7, 14, and 21). Differences in liver IVIM parameters and correlation between IVIM parameters and Ki-67 indices, hepatocyte diameter, alanine transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil) values were analyzed. RESULTS: Post-PH, liver true diffusion coefficient (D) values decreased and pseudodiffusion coefficient (D*) and perfusion fraction (PF) values increased, then recovered to pre-PH levels gradually in both fibrosis and control rats. PF in fibrosis group were significantly higher than in controls from 3 to 21 days (P < 0.05). In fibrosis rats, both Ki-67 indices and hepatocyte diameters increased, and a strong correlation was found between PF and Ki-67 indices (r = -0.756; P = 0.03), D* and PF values and ALT, AST, and TBil values (r = -0.762 to -0.905; P < 0.05). In control rats, only hepatocyte diameters increased, and all IVIM parameters correlated well with hepatocyte diameters, ALT, AST and TBil values (r = 0.810 to -1.000; P < 0.05). CONCLUSION: The regeneration pattern in fibrotic liver tissue was different compared with control livers. IVIM parameters can monitor liver regeneration and functional recovery non-invasively after PH.

KIF11 Promotes Proliferation of Hepatocellular Carcinoma among Patients with Liver Cancers.

BACKGROUND: Hepatocellular carcinoma (HCC) lacks effective treatments and has a poor prognosis. Therefore it is needed to develop more effective drug targets. Kinesin family member 11 (KIF11) has been reported to affect the progression of several cancers, and its high expression associates with the prognosis of patients. However, the relevant mechanisms of KIF11 in HCC progression have not been studied. METHOD: Through the cancer genome atlas (TCGA) database and immunohistochemical (IHC) staining of patients' specimens, we determined that KIF11 was highly expressed in HCC tissues and associated with prognosis. We established a KIF11 stably depleted hepatoma cell line, through cell-cloning experiments and cell counting kit-8 (CCK-8) assays to detect the effects on proliferation in vitro. The role of KIF11 in promoting cell proliferation was verified in mice. RESULT: The expression of KIF11 was negatively correlated with the overall survival (OS) and disease-free survival (DFS) and positively correlated with tumor size of HCC patients. KIF11 depletion inhibits cell proliferation and tumor growth in vitro and in vivo. Conclusion. KIF11 can be used as a positive correlation marker for HCC prognosis and served as a potential therapeutic target.

MCOLN1 Promotes Proliferation and Predicts Poor Survival of Patients with Pancreatic Ductal Adenocarcinoma.

BACKGROUND: MCOLN1 (mucolipin subfamily, member 1) was first identified as an autophagic regulator, which was essential for efficient fusion of both autophagosomes and late endosomes with lysosomes. This study is aimed at investigating the role of MCOLN1 in the development of pancreatic ductal adenocarcinoma (PDAC). METHODS: Immunohistochemistry (IHC) assay was conducted to evaluate the expression level of MCOLN1 in 82 human PDAC tumor tissues. Overall survival (OS) and recurrence-free survival (RFS) analysis was performed to assess the prognosis of patients. Colony formation and MTT assays [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide] were performed to measure the proliferation capacity of tumor cells. The expression level of related genes was measured by RT-PCR (reverse transcription polymerase chain reaction) and western blot assays. The animal model was used to examine the effects of indicated protein on tumorigenesis in vivo. RESULTS: The results of IHC showed that a high level of MCOLN1 expression was associated with the poor clinical characteristics of PDAC patients. OS and RFS were significantly worse in patients with high MCOLN1 expression. Silencing of MCOLN1 dramatically blocked the proliferation of PDAC cells. Mechanism studies confirmed that knockdown of MCOLN1 decreased the expression of Ki67 and PCNA (proliferating cell nuclear antigen), two markers of cell proliferation. In vivo, MCOILN1 depletion reduced the formation and growth of tumors in mice. CONCLUSION: The high level of MCOLN1 expression was associated with poor clinical outcomes of PDAC patients. MCOLN1 ablation could inhibit PDAC proliferation of both in vitro and in vivo, which provide a new insight and novel therapeutic target for the treatment of PDAC.

A six-gene-based prognostic signature for hepatocellular carcinoma overall survival prediction.

AIMS: The purpose of this study was to propose a pipeline to identify prognostic signature for HCC overall survival (OS) prediction based on HCC gene expression datasets from The Cancer Genome Atlas (TCGA). RESULTS: Differential expression analysis identified 3573 genes aberrantly expressed (DEGs) in HCC samples. Univariate cox regression analysis obtained 1605 and 1067 HCC OS and relapse free survival (RFS) related genes, which are abbreviated as OS-Gene and RFS-Gene respectively. Besides, there are 55 overlaps among DEGs, OS-Genes and RFS-Genes. Further prioritization of the 55 overlapping genes through Sure Independence Screening (SIS) resulted in 6 genes, including SRL, TTC26, CPSF2, TAF3, C16orf46 and CSN1S1, and the prognostic signature is the weighted combination of their expression values. Kaplan-Meier analysis based on the prognostic score (PS) of every sample indicates higher PS is associated with better HCC OS. Robustness of the prognostic signature was evaluated through another HCC gene expression datasets from the Gene Expression Omnibus (GEO). What's more, univariate and multivariate cox regression analysis indicate significant associations between stage/PS and HCC OS. CONCLUSIONS: Our study provides a pipeline for the identification of prognostic signature for HCC OS prediction, which should also be suit for other types of cancers.

Prolonged ischemia elicits acute allograft rejection involved in CXCR3 activation in rat kidney transplants.

BACKGROUND: Acute rejection is a major obstacle in patients with prolonged ischemia in deceased-donor renal transplantation. Chemokines and their receptors play a critical role in leukocyte trafficking, resulting in allograft rejection; therefore, the role of chemokine receptor CXCR3 in acute rejection induced by prolonged ischemia in rat kidney transplantation models was evaluated. METHODS: Syngeneic and allogeneic renal transplantations were performed. For cold ischemia, grafts were stored in 4.0°C University of Wisconsin solution for 12 or 16 h. Serum and renal tissues were harvested 7.0 d after surgery and serum TNF-α, IL-6, and renal function were measured. Graft histology was stained with periodic acid-Schiff and immunohistochemical staining and further evaluated for signs of acute rejection. CXCR3 proteins were quantified by Western blot. The transplanted rats were divided into 4 groups as follows: iso-12-h = isogeneic transplant with 12-h CIT graft; iso-16-h = isogeneic kidney transplant with 16-h CIT graft; allo-12-h = allogeneic renal transplant with 12-h CIT graft; allo-16 h = allogeneic renal transplant with 16-h CIT graft; and 16 h+T = allogeneic 16-h CIT graft received tacrolimus. RESULTS: Prolonged cold ischemia time (CIT; 16 h) enhanced acute glomerular damage, interstitial inflammation, and tubulointerstitial cellular infiltration in allografts with and without immunosuppressant tacrolimus; but it was not apparent in the isografts. The expression of CXCR3 protein and the proportion of CXCR3-positive cells were significantly higher in the allo-16 h and 16 h +T groups than that in the allo-12 h group 7d post-surgery. CONCLUSIONS: CIT triggered acute rejection in allogeneic, but not in isogeneic, kidney transplants, accompanied by an elevation of leukocyte recruitment and damaged graft function. The upregulated expression of chemokine receptor CXCR3 promoted inflammatory infiltration and acute allograft rejection.

Liver transplantation for a giant mesenchymal hamartoma of the liver in an adult: Case report and review of the literature.

Mesenchymal hamartomas of the liver (MHLs) in adults are rare and potentially premalignant lesions, which present as solid/cystic neoplasms. We report a rare case of orthotopic liver transplantation in a patient with a giant MHL. In 2013, a 34-year-old female sought medical advice after a 2-year history of progressive abdominal distention and respiratory distress. Physical examination revealed an extensive mass in the abdomen. Computed tomography (CT) of her abdomen revealed multiple liver cysts, with the diameter of largest cyst being 16 cm × 14 cm. The liver hilar structures were not clearly displayed. The adjacent organs were compressed and displaced. Initial laboratory tests, including biochemical investigations and coagulation profile, were unremarkable. Tumor markers, including levels of AFP, CEA and CA19-9, were within the normal ranges. The patient underwent orthotopic liver transplantation in November 2013, the liver being procured from a 40-year-old man after cardiac death following traumatic brain injury. Warm ischemic time was 7.5 min and cold ischemic time was 3 h. The recipient underwent classical orthotopic liver transplantation. The recipient operative procedure took 8.5 h, the anhepatic phase lasting for 1 h without the use of venovenous bypass. The immunosuppressive regimen included intraoperative induction with basiliximab and high-dose methylprednisolone, and postoperative maintenance with tacrolimus, mycophenolate mofetil, and prednisone. The recipient's diseased liver weighed 21 kg (dry weight) and measured 41 cm × 32 cm × 31 cm. Histopathological examination confirmed the diagnosis of an MHL. The patient did not experience any acute rejection episode or other complication. All the laboratory tests returned to normal within one month after surgery. Three months after transplantation, the immunosuppressive therapy was reduced to tacrolimus monotherapy, and the T-tube was removed after cholangiography showed no abnormalities. Twelve months after transplantation, the patient remains well and is fulfilling all normal activities. Adult giant MHL is extremely rare. Symptoms, physical signs, laboratory results, and radiographic imaging are nonspecific and inconclusive. Surgical excision of the lesion is imperative to make a definite diagnosis and as a cure. Liver transplantation should be considered as an option in the treatment of a non-resectable MHL.