[Study on fatigue resistance of mechanical nickel-titanium files by phase-locked infrared flaw detection method].

PURPOSE: The movement trend of the posterior teeth and the distribution of the periodontal membrane stress were studied by using three-dimensional digital technology. METHODS: CBCT data of 88 patients admitted to our hospital from June 2017 to June 2022 were selected, and input into Mimics20.0 software for preliminary extraction of all parts and stored with STL files; then the data were repaired and optimized through Geomagic Studio 2014 software. With the help of normal phase extension, the invisible appliance and periodontal membrane were constructed. Finally, the six FEM models were simulated and observed by the current teeth in different groups. Statistical analysis was performed with SPSS 21.0 software package. RESULTS: The effect force of the largest periodontal membrane was distributed in the neck of the tooth, followed by the apical area, with the maximum effect force value in the NA group. In all accessory groups, the periodontal membrane maximum paradigm isoeffect force values of all patients in the accessory vertical rectangular group were significantly smaller than the values obtained in the horizontal rectangular group. CONCLUSIONS: The design of orthodontic tooth accessories has a strong inhibition effect on the position movement of anterior teeth during recovery, which improves the accuracy of tooth three-dimensional movement to a certain extent. Meanwhile, the normal equivalent stress of the periodontal membrane of patients in the initial application of the invisible appliance without brackets is large.

[Occurrence and Risk Assessment of Microplastics in the Coastal Seawater of Guangdong Province].

Microplastics （MPs） are ubiquitous in the marine environment and have become an emerging pollutant that is attracting great attention. To reveal the pollution characteristics of MPs in surface seawater of coastal waters in Guangdong Province, nine bays （estuaries） were selected from Jiangmen to Shantou. The distribution and compositional characteristics of MPs were investigated through field sampling, oxidation digestion, and visual and compositional identification, and their potential sources were analyzed. The ecological risks were assessed by combining the pollution load index and the polymer risk index. The results showed that MPs were detected in all 30 surface seawater samples from the coastal waters of Guangdong Province, with an abundance range of 70-920 n·m-3 and an average abundance of （295.3 ±175.3） n·m-3. The highest MPs abundance was found in the Pearl River estuary, and the lowest abundance was found in Shenquan bay. The distribution patterns were mainly influenced by human activities and ocean currents. The dominant polymer types included polypropylene （31.2%）, phenol resin （16.0%）, polyethylene terephthalate （15.3%）, and polyethylene （10.9%）. The main shape, color, and size categories of MPs were fiber （57.5%）, transparent （72.0%）, and 0.5-1 mm （32.8%）, respectively. The possible sources of MPs mainly included aquaculture, fishing, navigation, tourism, municipal sewage discharge, and ocean current transportation. The model assessment results showed that the pollution load risk of MPs was relatively low, but the polymer risk was at a medium-high level. This study provides a data basis for the action plan of plastic pollution control in Guangdong Province and supports the prevention and control of marine MPs pollution.

Radiomic signatures associated with tumor immune heterogeneity predict survival in locally recurrent nasopharyngeal carcinoma.

BACKGROUND: The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma is limited because of their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in locally recurrent nasopharyngeal carcinoma. METHODS: This multicenter, retrospective study included 921 patients with locally recurrent nasopharyngeal carcinoma. A machine learning signature and nomogram based on pretreatment magnetic resonance imaging features were developed for predicting overall survival in a training cohort and validated in 2 independent cohorts. A clinical nomogram and an integrated nomogram were constructed for comparison. Nomogram performance was evaluated by concordance index and receiver operating characteristic curve analysis. Accordingly, patients were classified into risk groups. The biological characteristics and immune infiltration of the signature were explored by RNA-sequencing analysis. RESULTS: The machine learning signature and nomogram demonstrated comparable prognostic ability to a clinical nomogram, achieving concordance indexes of 0.729, 0.718, and 0.731 in the training, internal, and external validation cohorts, respectively. Integration of the signature and clinical variables statistically improved the predictive performance. The proposed signature effectively distinguished patients between risk groups with statistically distinct overall survival rates. Subgroup analysis indicated the recommendation of local salvage treatments for low-risk patients. Exploratory RNA-sequencing analysis revealed differences in interferon response and lymphocyte infiltration between risk groups. CONCLUSIONS: A magnetic resonance imaging-based radiomic signature predicted overall survival more accurately. The proposed signature associated with tumor immune heterogeneity may serve as a valuable tool to facilitate prognostic stratification and guide individualized management for locally recurrent nasopharyngeal carcinoma patients.

The associations of secondhand smoke exposure with neurodevelopmental disorders and critical time window identification: A systematic review and meta-analysis.

BACKGROUND: Secondhand smoke (SHS) exposure was harmful for brain development. However, the association between SHS exposure and NDDs diagnosis were unclear. OBJECTIVES: To evaluate associations between SHS exposure and NDDs diagnosis, identify critical time windows, and summarize the strength of evidence. METHODS: To investigate the associations of SHS exposure and the development of NDDs, we searched Ovid, EMBASE, Web of Science, Cochrane Library, and PubMed for all the relevant studies up to 31 March 2023. The risk estimates and standardized mean differences (SMD) for the individuals with any NDDs who were exposed to SHS exposure compared with those unexposed or low-exposed. RESULTS: The results showed that a total of 31,098 citations were identified, of which 54 studies were included. We identified significant associations between SHS exposure and the risks of NDDs including specific types of NDDs like attention deficit hyperactivity disorder (ADHD) and learning disabilities (LD) despite the observed heterogeneity for NDDs and ADHD. We also observed a significant association between cotinine exposure and ADHD. However, inconsistent ratings between the two quality-of-evidence methods for all the meta-analyses indicated the current evidence of the associations and the potential exposure window remained inconclusive. DISCUSSION: Our findings suggested that SHS exposure was associated with a higher risk of developing ADHD and LD, with inconclusive quality-of-evidence. In addition, period-specific associations remained unclear based on current evidence.

Radiomic signatures reveal multiscale intratumor heterogeneity associated with tissue tolerance and survival in re-irradiated nasopharyngeal carcinoma: a multicenter study.

BACKGROUND: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. METHODS: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. RESULTS: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity. CONCLUSIONS: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.

Associations of life course obesity with endometrial cancer in the Epidemiology of Endometrial Cancer Consortium (E2C2).

BACKGROUND: Adult obesity is a strong risk factor for endometrial cancer (EC); however, associations of early life obesity with EC are inconclusive. We evaluated associations of young adulthood (18-21 years) and adulthood (at enrolment) body mass index (BMI) and weight change with EC risk in the Epidemiology of Endometrial Cancer Consortium (E2C2). METHODS: We pooled data from nine case-control and 11 cohort studies in E2C2. We performed multivariable logistic regression analyses to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for BMI (kg/m2) in young adulthood and adulthood, with adjustment for BMI in adulthood and young adulthood, respectively. We evaluated categorical changes in weight (5-kg increments) and BMI from young adulthood to adulthood, and stratified analyses by histology, menopausal status, race and ethnicity, hormone replacement therapy (HRT) use and diabetes. RESULTS: We included 14 859 cases and 40 859 controls. Obesity in adulthood (OR = 2.85, 95% CI = 2.47-3.29) and young adulthood (OR = 1.26, 95% CI = 1.06-1.50) were positively associated with EC risk. Weight gain and BMI gain were positively associated with EC; weight loss was inversely associated with EC. Young adulthood obesity was more strongly associated with EC among cases diagnosed with endometrioid histology, those who were pre/perimenopausal, non-Hispanic White and non-Hispanic Black, among never HRT users and non-diabetics. CONCLUSIONS: Young adulthood obesity is associated with EC risk, even after accounting for BMI in adulthood. Weight gain is also associated with EC risk, whereas weight loss is inversely associated. Achieving and maintaining a healthy weight over the life course is important for EC prevention efforts.

Azonal steatosis correlates with disease severity and poor outcome of nonalcoholic fatty liver disease.

OBJECTIVES: In this study we aimed to assess the clinicopathological characteristics and long-term prognosis of patients with nonalcoholic fatty liver disease (NAFLD) having distinct steatosis distribution patterns. METHODS: Clinicopathological data of 238 individuals with biopsy-confirmed NAFLD were collected. Nonalcoholic steatohepatitis-clinical research network (NASH-CRN) and steatosis, activity and fibrosis (SAF)/fatty liver inhibition of progression (FLIP) algorithm were used. Cumulative incidence of liver-related events (LREs) was compared by Kaplan-Meier analysis. Univariate and multivariate logistic regression analyses were used to identify independent predictors for steatosis distribution. RESULTS: Eligible patients were categorized into three groups based on their steatosis distribution, including azonal steatosis (AS) (62 [26.1%]), perivenular steatosis (PVS) (147 [61.8%]), and the pan-acinar steatosis (PAS) groups (29 [12.1%]). There were significantly higher ballooning grade and disease activity (P < 0.05), more severe fibrosis (P < 0.001), and a higher cumulative incidence of LREs (hazard ratio [HR] 8.0, 95% confidence interval [CI] 2.34-27.35, P < 0.0001) in the AS group than in the PVS and PAS groups after a median of 3.6-year follow-up. Multivariate logistic regression analysis revealed age (odds ratio [OR] 1.11, 95% CI 1.06-1.16, P < 0.001) might be independently associated with AS distribution, and PNPLA3 rs738409 CG/GG genotype (OR 3.36, 95% CI 0.98-11.47, P = 0.053) might also play a role. CONCLUSIONS: AS is associated with more severe disease activity and fibrosis stage in NAFLD, and predisposes toward poor prognosis. Age might be an independent predictor for AS in NAFLD, while PNPLA3 rs738409 CG/GG genotype might also play a role.

Pre-conceptional and prenatal exposure to secondhand smoke and autism spectrum disorder: a national multi-center study in China.

BACKGROUND: Despite extensive research evaluating the association between prenatal exposure to secondhand smoke (SHS) and the development of autism spectrum disorders (ASD), no study has investigated the association by considering the pre-conceptional period. This study aimed to investigate the associations of pre-conceptional and prenatal SHS exposure and the development of ASD among toddlers. METHODS: In this cross-sectional study, parents of 6049 toddlers aged 16-30 months were recruited from 7 tertiary hospitals, 21 communities, and 7 kindergartens located in seven cities in six provinces from five geographical regions of China. We analyzed the associations of SHS exposure and the odds of ASD among toddlers in different exposure windows (pre-conceptional and/or prenatal periods). Data were analyzed from November 2021 to January 2022. RESULTS: Among the 6049 toddlers included in the analysis [22.7 (4.1) months; 44.8% girls], 71 were identified and diagnosed with ASD. Compared with the unexposed toddlers, toddlers with pre-conceptional SHS exposure had higher odds of ASD (OR 2.30, 95% CI 1.36-3.84), while we observed a non-significantly positive association regarding prenatal SHS exposure. When considering both pre-conceptional and prenatal periods, toddlers who were continuously exposed to SHS during these two periods had higher odds than those without SHS exposure (OR 2.32, 95% CI 1.24-4.14). CONCLUSION: We reported positive SHS-ASD associations when exposed during the pre-conceptional period and continuously exposed during pre-conceptional and prenatal periods, emphasizing the critical window of pre-conception for targeted intervention on smoking.

Risk stratification system and visualized dynamic nomogram constructed for predicting diagnosis and prognosis in rare male breast cancer patients with bone metastases.

Background: Bone metastases (BM) from malignant tumors could disrupt the balance between osteoclasts and osteoblasts and affect bone homeostasis. Malignant breast cancer (BC) is rare in male patients, and co-occurrence of BM is even rarer. Given its low incidence, there is limited research evaluating risk and prognosis. Despite the widespread application of nomograms to predict uncommon malignancies, no studies have constructed predictive models focusing on the diagnosis and prognosis of male breast cancer with bone metastases (MBCBM). Methods: This study selected all male breast cancer patients (MBC) between 2010 and 2019 in the Surveillance, Epidemiology, and End Results (SEER) database. We used simple and multivariate Logistic regression analyses to identify independent risk factors for BM in MBC patients. Then simple and multivariate Cox regression analyses were employed to determine the independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS) in MBCBM patients. We established and validated three new nomograms based on these independent factors. Result: A total of 4187 MBC patients were included, with 191 (4.56%) having bone metastases at the time of diagnosis. The independent risk factors of BM in MBC patients included age, tumor size, marital status, T stage, and N stage. In MBCBM patients, independent prognostic factors for OS and CSS were both age, T stage, ER status, PR status, and surgery. The concordance index (C-index), the area under the curve (AUC) of the receiver operating characteristic curve (ROC), the calibration curve, and the decision curve analysis (DCA) confirmed that these three nomograms could accurately predict the diagnosis and prognosis of MBCBM patients with excellent discrimination and clinical utility superior to the TNM staging system. We then established two prognostic-based risk stratification systems and three visualized dynamic nomograms that could be applied in clinical practice. Conclusion: In conclusion, this study aimed to establish and validate an accurate novel nomogram to objectively predict the diagnosis and prognosis of MBCBM patients. On this basis, prognostic-based risk stratification systems and visualized dynamic nomograms were constructed to facilitate doctors and patients to quantify individual BM risk probability and survival probability to assist in personalized risk assessment and clinical decision-making.

Histological assessment based on liver biopsy: the value and challenges in NASH drug development.

Nonalcoholic steatohepatitis (NASH) is increasingly recognized as a serious disease that can lead to cirrhosis, hepatocellular carcinoma (HCC), and death. However, there is no effective drug to thwart the progression of the disease. Development of new drugs for NASH is an urgent clinical need. Liver biopsy plays a key role in the development of new NASH drugs. Histological findings based on liver biopsy are currently used as the main inclusion criteria and the primary therapeutic endpoint in NASH clinical trials. However, there are inherent challenges in the use of liver biopsy in clinical trials, such as evaluation reliability, sampling error, and invasive nature of the procedure. In this article, we review the advantages and value of liver histopathology based on liver biopsy in clinical trials of new NASH drugs. We also discuss the challenges and limitations of liver biopsy and identify future drug development directions.

The diagnostic role of PD-1+ CXCR5+ follicular helper CD8+ T cell in renal allograft dysfunction.

BACKGROUND: The roles of PD-1+ CXCR5+ follicular helper CD8+ T cell were reported in different disease conditions, but their roles in transplantation are unclear. In this study, the association between PD-1+ CXCR5+ follicular helper CD8+ T cell and renal allograft dysfunction in kidney transplant recipients (KTRs) was investigated. METHODS: 82 KTRs were enrolled in this study. 45 KTRs were included in the chronic allograft dysfunction (CAD) group, and 37 KTRs were included in the stable recipients group. Among the CAD group, 12 cases of antibody-mediated rejection (ABMR) and 4 cases of T cell-mediated rejection (TCMR) were diagnosed by biopsy. The percentage of CXCR5+ CD8+ T cells and the co-expression of signal transducers and activators of transcription 4 (STAT4), STAT5, and PD-1 in peripheral blood were determined by flow cytometry. RESULTS: The expression of CXCR5 on CD3+ CD8+ T cells and the percentage of STAT5+ CXCR5+ cells in the CD3+ CD8+ T-cell population were significantly lower in the CAD group (p < 0.05), while the expression of PD-1+ CXCR5+ CD8+ T cells was significantly higher (p < 0.05). Through logistic regression analysis, we concluded that the percentage of PD-1+ CXCR5+ CD8+ T cells was an independent risk factor for renal dysfunction. Grouping by pathological type, PD-1+ CXCR5+ CD8+ T cells showed relatively good diagnostic efficacy for ABMR by ROC analysis. CONCLUSIONS: Our results suggested that PD-1+ CXCR5+ CD8+ T cells were a promising biomarker for distinguishing renal allograft dysfunction and different allograft pathological types. Also, our findings may provide new ways of identifying and treating allograft rejection.

[Effect and mechanism of miR-124 on osteogenic differentiation of dental pulp mesenchymal stem cells].

PURPOSE: To evaluate the effect of microRNA (miR)-124 on osteogenic differentiation of dental pulp mesenchymal stem cells (DPSCs) and to explore the possible mechanism. METHODS: Logarithmic DPSCs were collected and divided into blank group, no-load group, miR-124 inhibitor group, miR-124 inhibitor combined with N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-ph (DAPT, Notch signaling pathway inhibitor) group. The blank group was not treated, the empty group was transfected with negative control vector inhibitor-NC, the miR-124 inhibitor group was transfected with miR-124 inhibitor, the miR-124 inhibitor combined with DAPT group was transfected with miR-124 inhibitor, and DAPT was added to make the final concentration of 5 µmol/L. The proliferation ability was tested by CCK-8 method 48 h after transfection. Alkaline phosphatase (ALP) activity was tested by p-nitrophenyl phosphate (P-NPP) method after 2 weeks of induction. The area of calcified nodules was tested by alizarin red staining method. The protein expression of hair-like division-related enhancer 1 (HEY1), hair-like division-related enhancer 2 (HEY2), and cyclin D1 gene (CCND1) were tested by Western blot. The data was analyzed by SPSS 19.0 software package. RESULTS: Compared with the blank group and no-load group, the A450 value at 24, 48, 72 h detected by CCK-8 experiment, A450 value of ALP activity, the area composition ratio of calcified nodules, and expression of HEY1, HEY2, and CCND1 in the miR-124 inhibitor group were increased (P<0.05). Compared with miR-124 inhibitor group, the A450 value at 24, 48, 72 h detected by CCK-8 experiment, A450 value of ALP activity, the area composition ratio of calcified nodules, and the expression of HEY1, HEY2, and CCND1 in the miR-124 inhibitor combined with DAPT group were significantly decreased(P<0.05). CONCLUSIONS: Down-regulation of miR-124 can promote osteogenic differentiation of DPSCs. It is speculated that the mechanism of action is related to the activation of Notch signaling pathway.

[Mandibular secretory carcinoma: a case report].

Secretory carcinoma, a low-grade malignant tumor, occurs mainly in parotid, submandibular gland, and small salivary glands in the mouth. It has not yet been reported in the mandible. Now we report a case occurred in the right mandibular angle of secretory carcinoma, accompanying with its diagnosis, treatment and prognosis.

Multicenter prospective study to validate a new transient elastography device for staging liver fibrosis in patients with chronic hepatitis B.

OBJECTIVES: To validate the operational and diagnostic performances of a new device for transient elastography (TE), FibroTouch, for liver fibrosis in patients with chronic hepatitis B (CHB). METHODS: In this prospective multicenter study, adult patients with CHB and valid liver pathological results were recruited to validate the operational and diagnostic performance of a TE device by FibroTouch for staging liver fibrosis. RESULTS: In total, 517 patients with histologically proven CHB were enrolled. All had achieved at least 10 successful liver stiffness measurements (LSM), resulting in a success rate of 99.1% and reliable evaluations of 95.2%. Altogether 412 patients were included to analyze the diagnostic performance of FibroTouch. The area under the receiver operating characteristic curve for the LSM was 0.846 (95% confidence interval [CI] 0.808-0.880) for fibrosis stage ≥ F1, 0.850 (95% CI 0.811-0.883) for ≥ F2, 0.908 (95% CI 0.876-0.934) for ≥ F3 and 0.874 (95% CI 0.836-0.903) for F4. The diagnostic accuracy of LSM was superior to that of gamma-glutamyl transpeptidase-to-platelet ratio (GPR), aminotransferase-to-platelet ratio index (APRI), or fibrosis index based on 4 factors (FIB-4) index in staging fibrosis F2-F4 (P = 0.007 to < 0.0001). Optimal LSM cut-off values for diagnosing fibrosis stage ≥ F1, ≥ F2, ≥ F3, and F4 were 5.5 kPa, 7.85 kPa, 10.0 kPa, and 12.7 kPa, respectively. CONCLUSION: FibroTouch has a high success rate and good reliability in staging liver fibrosis in patients with CHB.

Serum Procalcitonin Level Predicts Acute Kidney Injury After Traumatic Brain Injury.

BACKGROUND: A common non-neurologic complication after traumatic brain injury (TBI), acute kidney injury (AKI) is a risk factor of mortality. Some studies confirmed the predictive value of procalcitonin (PCT) on AKI in several clinical settings. We designed this study to explore the predictive value of PCT on AKI after TBI. METHODS: We retrospectively enrolled patients with TBI admitted to our hospital from February 2015 to June 2019. Multivariate logistic regression analysis was performed to find the risk factors of AKI and construct a predictive model for AKI. Receiver operating characteristics curves were drawn to compare the predictive value of PCT and the constructed model. RESULTS: A total of 214 patients were included in this study. The incidence of AKI after TBI was 25.70% in this study. Compared with the non-AKI group, the AKI group had higher age (P = 0.031), lower Glasgow Coma Scale (P < 0.001), and higher incidence of coagulopathy (P < 0.001) and shock (P < 0.001). Moreover, patients complicated with AKI had higher in-hospital mortality (P < 0.001) and worse 90-day outcome (P < 0.001). Multivariate logistic regression analysis indicated that age (P = 0.033), PCT (P = 0.002), serum chlorine (P = 0.011), and creatinine (P < 0.001) were independent risk factors of AKI. We constructed a predictive model using these 4 risk factors. The area under receiver operating characteristics curves of the predictive model was 0.928, which was significantly higher than that of a single PCT value (area under receiver operating characteristics curves = 0.833) (Z = 2.395, P < 0.05). CONCLUSIONS: PCT is valuable in predicting AKI after TBI. To avoid AKI after TBI, physicians can adjust treatment strategies according to the level of PCT.

Non-obese patients with nonalcoholic fatty liver disease may use a lower liver stiffness cut-off to assess fibrosis stages.

OBJECTIVE: We aimed to estimate the optimal cut-off values of liver stiffness measurement (LSM) for diagnosing and staging fibrosis in non-obese and obese patients with nonalcoholic fatty liver disease (NAFLD). METHODS: NAFLD patients diagnosed by liver biopsy according to the Nonalcoholic Steatohepatitis Clinical Research Network scoring system were enrolled in this study. Non-obesity was defined as a body mass index (BMI) less than 25 kg/m2 . LSM was performed by experienced physicians within 2 weeks before or after liver biopsy. RESULTS: A total of 158 patients were included. Average BMI of the non-obese (n = 68) and obese (n = 90) groups was 23.2 ± 1.6 and 27.9 ± 2.5 kg/m2 , respectively. After adjusted for age, fibrosis stage, steatosis grade and type 2 diabetes mellitus, the obese group had a LSM of 3.522 kPa higher than the non-obese patients (P = 0.003). LSM values of the non-obese patients had a lower trend when stratified by fibrosis stage, especially in cirrhosis (F4; P = 0.021). Applying separate cut-off values for patients with NAFLD in individual fibrosis stage, 5.8 vs 7.5 kPa (≥ F1), 7.6 vs 8.5 kPa (≥ F2), 9.1 vs 11.2 kPa (≥ F3), and 12.5 vs 14.3 kPa (F4), improved their diagnostic odds ratios compared with overall cut-off values. In the non-obese NAFLD group, using a separate cut-off avoided underestimating 9.1% of patients with cirrhosis. CONCLUSIONS: Non-obese NAFLD group had lower LSM than the obese group. Different cut-off values should be used to measure liver fibrosis stage in non-obese and obese NAFLD patients.

Synchronous bilateral clear cell renal cell carcinoma and prostate gland carcinoma on 18F-FDG PET/CT in one patient.

We present a case of synchronous bilateral renal cell carcinoma and prostate carcinoma in a 62 year old man. In a fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) scan, the left renal mass showed intense 18F-FDG uptake with maximum standardized uptake volume (SUVmax) of 8.12, while uptake in the right renal mass was minimal with SUVmax of 2.99. Fluorine-18-FDG uptake in the prostate gland lesion was moderate with SUVmax of 4.19. Histopathologically, both renal tumors were clear cell renal cell carcinoma with International Society of Urological Pathology (ISUP) Grade 2 and 3 for the right and left kidney, respectively and prostate gland lesion was typical prostate gland carcinoma.

Alteration of liver-infiltrated and peripheral blood double-negative T-cells in primary biliary cholangitis.

BACKGROUND & AIMS: Double-negative (DN) T-cell is a unique regulatory T-cell, which is essential for maintaining immune system homoeostasis. However, the role of DN T-cells in the pathogenesis of primary biliary cholangitis (PBC) is still unknown. METHODS: We investigated the number and function of DN T-cells in peripheral blood and liver biopsy specimens of PBC patients. RESULTS: The number and frequency of DN T-cells significantly decreased in peripheral blood and liver tissue of PBC patients. Furthermore, the frequency of DN T-cells in PBC was negatively correlated with disease severity and positively correlated with ursodeoxycholic acid response. In vitro assays showed that perforin expression and the suppressive capability of DN T-cells on the proliferation of CD4+ and CD8+ T-cells were impaired in PBC. Finally, lithocholic acid, the most hydrophobic acid, could downregulate the proliferation and perforin expression of DN T-cells. CONCLUSIONS: Decreased quantity and function of DN T-cells in PBC may result in the loss of immune regulations on effector CD4+ and cytotoxic CD8+ T-cells, and thereby may break the immune tolerance and promote the pathogenesis of PBC.

Remediation of organochlorine pesticides contaminated lake sediment using activated carbon and carbon nanotubes.

Organochlorine pesticides (OCPs) in sediment were a potential damage for humans and ecosystems. The aim of this work was to determine the effectiveness of carbon materials remedy hexachlorocyclohexane (HCH) and dichlorodiphenyltrichloroethanes (DDTs) in sediment. Two different carbon materials including activated carbon (AC) and multi-walled carbon nanotubes (MWCNTs) were used in the present research. Sediment treated with 2 wt% AC and MWCNTs after 150 d contact showed 97%, and 75% reduction for HCH, and 93% and 59% decrease for DDTs in aqueous equilibrium concentration, respectively. Similarly, the reduction efficiencies of DDT and HCH uptake by semipermeable membrane devices (SPMDs) treated with AC (MWCNTs) were 97% (75%) and 92% (63%), respectively under the identical conditions. Furthermore, for 2 wt% AC (MWCNTs) system, a reduction of XAD beads uptake up to 87% (52%) and 73% (67%) was obtained in HCH and DDT flux to overlying water in quiescent system. Adding MWCNTs to contaminated sediment did not significantly decrease aqueous equilibrium concentration and DDTs and HCH availability in SPMDs compared to AC treatment. A series of results indicated that AC had significantly higher remediation efficiency towards HCH and DDTs in sediment than MWCNTs. Additionally, the removal efficiencies of two organic pollutants improved with increasing material doses and contact times. The greater effectiveness of AC was attributed to its greater specific surface area, which was favorable for binding contaminants. These results highlighted the potential for using AC as in-situ sorbent amendments for sediment remediation.

Up-Regulation of PKR Signaling Pathway by Ethanol Displays an Age of Onset-Dependent Relationship.

BACKGROUND: Ethanol (EtOH) neurotoxicity can result in devastating effects on brain and behavior by disrupting homeostatic signaling cascades and inducing cell death. One such mechanism involves double-stranded RNA activated protein kinase (PKR), a primary regulator of protein translation and cell viability in the presence of a virus or other external stimuli. EtOH-mediated up-regulation of interferon-gamma (IFN-γ; the oxidative stress-inducible regulator of PKR), PKR, and its target, p53, are still being fully elucidated. METHODS: Using Western blot analysis, immunofluorescence, and linear regression analyses, changes in the IFN-γ-PKR-p53 pathway following chronic EtOH treatment in the frontal cortex of rodents were examined. The role of PKR on cell viability was also assessed in EtOH-treated cells using PKR overexpression vector and PKR inhibitor (PKRI). RESULTS: In rats chronically fed EtOH, PKR, phosphorylated PKR (p-PKR), IFN-γ, and p53 were significantly increased following chronic EtOH exposure. Linear regression revealed a significant correlation between IFN-γ and p-PKR protein levels, as well as p-PKR expression and age of EtOH exposure. Overexpression of PKR resulted in greater cell death, while use of PKRI enhanced cell viability in EtOH-treated cells. CONCLUSIONS: Chronic EtOH exposure activates the IFN-γ-PKR-p53 pathway in the frontal cortex of rodents. p-PKR expression is greater in brains of rodents exposed to EtOH at earlier ages compared to later life, suggesting a mechanism by which young brains could be more susceptible to EtOH-related brain injury. PKR and p-PKR were also colocalized in neurons and astrocytes of rats. This study provides additional insight into biochemical mechanisms underlying alcohol use disorder related neuropathology and warrants further investigation of PKR as a potential pharmacotherapeutic target to combat EtOH-related neurotoxicity, loss of protein translation and brain injury.