[The application value of Gd-EOB-DTPA enhanced MRI based radiomics in the differential diagnosis of iso-or hyperintensity HCC and focal nodular hyperplasia in hepatobiliary phase].

Objective: To investigate the application value of Gd-EOB-DTPA enhanced MRI based radiomics model in the differential diagnosis of iso-or hyperintensity HCC and focal nodular hyperplasia (FNH) in hepatobiliary phase. Methods: A total of 88 patients with HCC or FNH confirmed by surgical or puncture pathology who underwent preoperative Gd-EOB-DTPA enhanced MRI (all lesions showed iso-or hyperintensity in hepatobiliary phase) between January 2015 and February 2023 in The First Affiliated Hospital of Soochow University and Nantong No.3 People's Hospital were retrospectively evaluated, which including 58 males and 30 females, aged [M(Q1, Q3)]56 (40, 67) years, including 61 patients with HCC and 27 patients with FNH. The included cases were divided into training (43 cases of HCC, 19 cases of FNH) and validation cohort (18 cases of HCC, 8 cases of FNH) in the ratio of 7∶3 using the random seeding method. A total of 1 781 radiomics features were extracted from Gd-EOB-DTPA enhanced MRI in the arterial, portal and hepatobiliary phases, respectively. The independent three phase models, combined three phases model and combined clinical-radiomics model was established using Auto-Encoder (AE) and Native Bayes (NB) classifier, respectively. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of these models. DeLong test was used to compare the areas under curve (AUC). Results: In the validation cohort, the combined clinical-radiomics model had the highest AUC (AUC=0.938, 95%CI: 0.828-1.000). The AUC, accuracy, sensitivity, specificity of the clinical-radiomics combined model using AE classifier in the validation cohort were 0.896 (95%CI: 0.760-1.000), 88.5%, 88.9%, 87.5%. The AUC of the clinical-radiomics combined model using NB classifier in the validation cohort were 0.938 (95%CI: 0.828-1.000), 92.3%, 88.9%, 100.0%. Conclusion: Gd-EOB-DTPA enhanced MRI combined clinical-radiomics model has certain value in preoperative differentiation of iso-or hyperintensity in the hepatobiliary phase HCC and FNH, with a high accuracy, sensitivity and specificity.

[Clinical and genetics characteristics of adult-onset cerebrotendinous xanthomatosis: analysis of a Chinese pedigree].

Objective: Clinical manifestations, imaging findings, pathologic features, and genetic mutations of Chinese adult patients with cerebrotendinous xanthomatosis (CTX) were analyzed in order to achieve a greater understanding of CTX that can improve early detection, diagnosis, and treatment. Methods: Clinical data including medical history, neurologic and auxiliary examinations, imaging findings, and genetic profile were collected for an adult patient with CTX admitted to the Sixth Medical Center of Chinese People's Liberation Army General Hospital in August 2020. Additionally, a systematic review of genetically diagnosed Chinese adult CTX cases reported in major databases in China and other countries was performed and age of onset, first symptoms, common signs and symptoms, pathologic findings, imaging changes, and gene mutations were analyzed. Results: The proband was a 39-year-old female with extensive, early-onset nervous system manifestations including cognitive dysfunction and ataxia. Systemic lesions included juvenile cataract and a tendon mass. Cranial magnetic resonance imaging revealed cerebral atrophy, symmetric white matter changes predominantly in the pyramidal tract, and lesions in the cerebellar dentate nucleus. A novel homozygous mutation in the sterol-27-hydroxylase (CYP27A1) gene (c.1477-2A>C) was identified. There were no family members with similar clinical presentation although some were carriers of the c.1477-2A>C mutation. The patient showed a good response to deoxycholic acid treatment. Totally there were 56 cases of adult CTX patients in China, mostly in East China (31/56, 55.4%), at a male-to-female ratio of 1.8 to 1. Multiple organs and tissues including nervous system, tendon, lens, lung, and skeletal muscle were affected in these cases. The most common neurologic manifestations were cognitive dysfunction (44/52, 84.6%) and ataxia (44/51, 86.3%). The cases were characterized by early onset, chronic progressive damage of multiple systems, long disease course, and delayed diagnosis, making the disease difficult to manage clinically and resulting in poor prognosis. The 2 most common genetic mutations in Chinese adult CTX patients were c.1263+1G>A and c.379C>T. Exon 2 of the CYP27A1 gene was identified as a mutation hot spot. Conclusions: Chinese adult patients with CTX have complex clinical characteristics, a long diagnostic cycle, and various CYP27A1 gene mutations. Early diagnosis and intervention can improve the prognosis of these patients.

[A comparison of current guidelines for the management of intrahepatic cholangiocarcinoma worldwide].

Intrahepatic cholangiocarcinoma (ICC) is the second most common human liver malignancy and its incidence rate has been gradually increasing worldwide over the past decades. Surgical resection (R0 resection) is the preferred potentially curative treatment for ICC patients. However, due to its conceal clinical features and high invasiveness, most patients have lost the opportunity for surgical resection at the time of diagnosis. In recent years, with the rapid development of targeted therapy and immunotherapy, which is represented by immune checkpoint inhibitors, clinicians are expected to provide more effective treatment options for patients with mid-stage or advanced ICC. At present, there are still controversial opinions on different guidelines regarding preoperative biliary drainage, the extent of hepatectomy, the definition of R0 resection, the width of the resection margin, lymph node dissection, postoperative recurrence, adjuvant therapy, etc. In this review, 12 guidelines or expert consensus published worldwide from 2012 to 2022 (including 4 Chinese guidelines, 4 European guidelines, 2 American guidelines and 2 Japanese guidelines) were retrieved. Focusing on sorting and comparing the current views on clinical management of ICC in different guidelines, this review aims to provide reference information for ICC clinical management and decision-making.

[Morvan syndrome with positive anti LGI1/CASPR2 antibodies in serum/cerebrospinal fluid:a case report and literature review].

To report a typical case of Morvan syndrome with positive anti-leucine rich glioma-inactivated 1(LGI1) and contactin-associated protein 2 (CASPR2) antibodies in serum and cerebrospinal fluid. A 39-years-old female initially presented weakness of extremeties. The main symptoms included paroxysmal limb pain, wheezing, itching, muscle twitching, epilepsy, hypomnesia, dysphoria, apathy, intractable insomnia, salivation and sweating. Tests of electrolytes found hypokalemia (2.7-3.1 mmol/L) and hyponatremia (130-136 mmol/L). Arterial blood gas analysis showed hypoxemia (oxygen saturation 50%-70%). Total thyroxine (TT4) was elevated to 207 nmol/L with positive thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TG-Ab). LGI1and CASPR2 antibodies (CBA method) were positive in both serum and cerebrospinal fluid, and the remaining antibodies related to autoimmune encephalitis and paraneoplastic syndrome were negative. Head MRI was almost normal, while mild abnormalities were found in electroencephalogram. Electromyography showed slightly increased voltage of left quadriceps motor unit potential. After treated with corticosteroids, IVIG and mycophenolate mofetil, the patient completely improved. Cognitive function scores recovered from MoCA/MMSE (16/24) to MoCA/MMSE (26/29). Positivity of LGI1/CASPR2 antibodies both in serum/cerebrospinal fluid are rarely seen in patients with Morvan syndrome. Steroids and immunosuppressants are suggested for treatment as early as possible.

[The prediction value of enhanced magnetic resonance imaging nomogram model for dual phenotype hepatocellular carcinoma].

Objective: To explore the value of enhanced magnetic resonance imaging nomogram model in the prediction of dual-phenotype hepatocellular carcinoma(DPHCC). Methods: Data of 116 patients of hepatocellular carcinoma (HCC) confirmed by postoperative pathology, who underwent preoperative enhanced MRI between January 2016 and March 2021 in the First Affiliated Hospital of Soochow University were retrospectively evaluated, of these, there are 87 males and 28 females, aged 30-79 (59±10) years, including 31 patients with DPHCC and 85 patients with non-DPHCC. The patients were randomly divided into training set(51 cases of non-DPHCC,19 cases of DPHCC)and validation set(34 cases of non-DPHCC, 12 cases of DPHCC) in a ratio of 6∶4, according to random number table,clinical and imaging characteristics of the two groups were compared. The statistically significant parameters were included in multivariate logistic regression to identify the independent predictors and for the establishment of the nomogram model. The receiver operating characteristic curves were used to evaluate the prediction ability of the models, the corrected curve was used to validate the model. Results: In the training group, the proportions of rim arterial phase hyperenhancement in the DPHCC was significantly higher than that of the non-DPHCC [47.4%(9/19)vs 7.8%(4/51),P<0.001]. Rim arterial phase hyper-enhancement and enhanced capsule were significant predictors for DPHCC[OR=10.17(1.70-60.80),0.17(0.03-0.93),all P<0.05]. In the training group, the area under curve (AUC), sensitivity and specificity of the nomogram were 0.888 (95%CI: 0.806-0.969), 78.9% and 86.3%. In the validation group, the above three indicators were 0.811(95%CI: 0.655-0.968), 75.0% and 82.4%. Conclusion: Enhanced MRI nomogram model has certain value in prediction of DPHCC, with high sensitivity and specificity.

[Value of the application of enhanced CT radiomics and machine learning in preoperative prediction of microvascular invasion in hepatocellular carcinoma].

Objective: To explore the value of machine learning models in preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) based on dual-phase contrast-enhanced CT radiomics features. Methods: The data of 148 patients [106 males and 42 females, with an average age of (58±11) years] with HCC confirmed by pathology in the First Affiliated Hospital of Soochow University from January 2015 to May 2020 were retrospectively analyzed, including 88 cases of positive MVI and 60 cases of negative MVI. According to the ratio of 7∶3, the patients were randomly divided into the training and validation sets, respectively. The three-dimensional (3D) radiomics features of HCC in arterial phase (AP) and portal venous phase (PP) were extracted by MaZda software, and the optimal feature subset was obtained by combining three feature selection methods (FPM method) and Lasso regression. Then, six machine learning methods were used to build the prediction models. Receiver operating characteristic (ROC) curves were drawn to evaluate the prediction ability of the aforementioned models, and the area under the curve (AUC), accuracy, sensitivity and specificity were calculated. Results: Radiomics features of HCC in AP and PP were extracted by MaZda software, with 239 in each phase. There were 7 optimal features in AP and 14 optimal features in PP selected by FPM method and Lasso regression, respectively. The AUCs of decision tree, extreme gradient boosting, random forest, support vector machine (SVM), generalized linear model, and neural network based on the 7 optimal features in AP in the validation set were 0.736, 0.910, 0.913, 0.915, 0.897, 0.648, respectively. The SVM had the highest AUC in the validation set, with the accuracy, sensitivity and specificity of 95.35%, 95.83% and 94.74%, respectively. Likewise, the AUCs of machine learning models in prediction of MVI in HCC based on the 14 optimal features in PP in the validation set were 0.873, 0.876, 0.913, 0.859, 0.877, 0.834, respectively, and there were no significant differences (all P>0.05). The random forest had the highest AUC in the validation set, with the accuracy, sensitivity and specificity of 90.70%, 87.50% and 94.74%, respectively. Conclusion: Machine learning models based on dual-phase enhanced CT radiomics features can be used in preoperative prediction of MVI in HCC, particularly the SVM and random forest models have high prediction efficiency.

CT-based radiomics model to distinguish necrotic hepatocellular carcinoma from pyogenic liver abscess.

AIM: To investigate the feasibility of a computed tomography (CT)-based radiomics model in distinguishing necrotic hepatocellular carcinoma (nHCC) from pyogenic liver abscess (PLA). MATERIAL AND METHODS: One hundred-four enrolled patients with nHCC (n=56) and PLA (n=48) were divided randomly into a training cohort (n=62) and validation cohort (n=42). ROI (region of interest) of the wall (ROI-wall) and ROI of the necrotic cavity (ROI-necrotic cavity) of the lesion were delineated from each arterial phase (AP) and portal venous phase (PP) image. The least absolute shrinkage and the selection operator logistic regression method was used to select radiomics features, and radiomics scores (R-scores) were calculated. Four radiomics models, including R-score (ROI-wall) in the AP, R-score (ROI-necrotic cavity) in the AP, R-score (ROI-wall) in the PP and R-score (ROI-necrotic cavity) in the PP, were constructed and evaluated by area under the curve (AUC) of receiver operating characteristic curve. RESULTS: The AUCs of R-score (ROI-wall) in the AP, R-score (ROI-necrotic cavity) in the AP, R-score (ROI-wall) in the PP, and R-score (ROI-necrotic cavity) in the PP were 0.935 and 0.917, 0.906 and 0.824, 0.985 and 0.928, 0.899 and 0.850, in the training and validation cohorts, respectively. In the training cohort, the AUC of R-score (ROI-wall) in the PP was higher than that of R-score (ROI-wall) in the AP (p=0.024) or R-score (ROI-necrotic cavity) in the AP (p=0.046) or R-score (ROI-necrotic cavity) in the PP (p=0.044). CONCLUSION: CT-based radiomics models can be used to distinguish nHCC from PLA.

Circular RNA circGFRA1 promotes angiogenesis, cell proliferation and migration of hepatocellular carcinoma by combining with miR-149.

OBJECTIVE: We aimed to explore the effect of circGFRA1 on the progression of hepatocellular carcinoma (HCC) and its underlying mechanism. PATIENTS AND METHODS: First, quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was conducted to detect the level of circGFRA1 in HCC tissues and cells. Survival analysis was applied to detect the effect of highly expressed circGFRA1 on the prognosis of HCC patients. Subsequently, circGFRA1 level was silenced in HCC cells, and proliferative, migration and angiogenesis activity of HCC cells was examined using Cell Counting Kit-8 (CCK-8), transwell test, and angiogenesis experiment. Then, we predicted the binding target of circGFRA1 through the bioinformatics website, and verified it through qRT-PCR and Dual-Luciferase reporter assay. Lastly, the interaction between them was verified through a series of in vitro experiments. RESULTS: qRT-PCR analysis showed that circGFRA1 was abnormally highly expressed in HCC tissues and HCC cells, and the high expression of circGFRA1 may lead to poor prognosis in patients with HCC. After transfecting si-circGFRA1 in HCC cells, CCK-8 and transwell experiments showed that the proliferative ability and migration of HCC cells were inhibited. Moreover, angiogenesis experiments showed that the knockdown of circGFRA1 can inhibit the blood vessels replenishment of HCC cells. The bioinformatics website suggested that miR-149 may be able to bind circGFRA1. MiR-149 was upregulated by the knockdown of circGFRA1 in HCC cells. Pearson analysis suggested that the expression levels of the two genes were negatively correlated. Dual-Luciferase reporter assay further indicated that circGFRA1 can bind to miR-149. Reverse experiment showed that the knockdown of miR-149 can partially restore the inhibited proliferative, migration, and angiogenesis activity of HCC cells caused by circGFRA1 knockdown. CONCLUSIONS: CircGFRA1 is highly expressed in HCC and its level is negatively correlated with miR-149 expression. CircGFRA1 can promote the proliferative, migration and angiogenic activity of HCC by binding miR-149.

Probing molecular mechanism of inhibitor bindings to bromodomain-containing protein 4 based on molecular dynamics simulations and principal component analysis.

It is well known that bromodomain-containing protein 4 (BRD4) has been thought as a promising target utilized for treating various human diseases, such as inflammatory disorders, malignant tumours, acute myelogenous leukaemia (AML), bone diseases, etc. For this study, molecular dynamics (MD) simulations, binding free energy calculations, and principal component analysis (PCA) were integrated together to uncover binding modes of inhibitors 8P9, 8PU, and 8PX to BRD4(1). The results obtained from binding free energy calculations show that van der Waals interactions act as the main regulator in bindings of inhibitors to BRD4(1). The information stemming from PCA reveals that inhibitor associations extremely affect conformational changes, internal dynamics, and movement patterns of BRD4(1). Residue-based free energy decomposition method was wielded to unveil contributions of independent residues to inhibitor bindings and the data signify that hydrogen bonding interactions and hydrophobic interactions are decisive factors affecting bindings of inhibitors to BRD4(1). Meanwhile, eight residues Trp81, Pro82, Val87, Leu92, Leu94, Cys136, Asn140, and Ile146 are recognized as the common hot interaction spots of three inhibitors with BRD4(1). The results from this work are expected to provide a meaningfully theoretical guidance for design and development of effective inhibitors inhibiting of the activity of BRD4.

[Impact of gender on hepatic pathology and antibody - mediated immunity caused by Schistosoma japonicum infection in C57BL/6 mice].

OBJECTIVE: To investigate the effect of gender on hepatic pathology and antibody-mediated immunity in Schistosoma japonicum-infected C57BL/6 mice. METHODS: Female and male C57BL/6 mice were infected with S. japonicum, and the hepatic pathological changes were observed using HE and picrosirius red staining in mice 8 weeks post-infection. The serum specific IgG antibody levels against the soluble adult worm antigen (SWA) and soluble egg antigen (SEA) were measured in mice using enzyme-linked immunosorbent assay (ELISA), and the percentages of follicular helper T (Tfh) cells and regulatory T (Treg) cells were detected in mouse spleen and lymph nodes using flow cytometry. RESULTS: HE staining showed no significant difference in the mean area of a single hepatic egg granuloma between female and male mice 8 weeks post-infection with S. japonicum [(28.050 ± 3.576) × 104 µm2 vs. (26.740 ± 4.093) × 104 µm2; t = 0.241, P = 0.821], and picrosirius red staining revealed no statistical differences between female and male mice in terms of the mean proportion of picrosirius red stained hepatic tissues [(7.667 ± 1.856)% vs. (7.667 ± 1.764)%; t = 0, P = 1] or the mean optical density [(0.023 ± 0.003) vs. (0.027 ± 0.007); t = 0.447, P = 0.678]. ELISA detected no significant differences in the serum IgG antibody levels against SWA [(2.098 ± 0.037) vs. (1.970 ± 0.071); t = 1.595, P = 0.162] or SEA [(3.738 ± 0.039) vs. (3.708 ± 0.043); t = 0.512, P = 0.623] between female and male mice 8 weeks post-infection with S. japonicum. Flow cytometry detected significantly greater percentages of Tfh cells in the spleen [female mice, (8.645 ± 1.356)% vs. (1.730 ± 0.181)%, t = 5.055, P = 0.002; male mice, (8.470 ± 1.161)% vs. (1.583 ± 0.218)%, t = 5.829, P = 0.001] and lymph nodes [female mice, (3.218 ± 0.153)% vs. (1.095 ± 0.116)%, t = 11.040, P < 0.001; male mice, (3.673 ± 0.347)% vs. (0.935 ± 0.075)%, t = 8.994, P = 0.001) of both female and male mice 8 weeks post-infection with S. japonicum than in uninfected mice; however, no significant differences were seen between female and male mice 8 weeks post-infection with S. japonicum in terms of the percentages of Tfh cells in the spleen [(8.645 ± 1.356)% vs. (8.470 ± 1.161)%; t = 0.098, P = 0.925] or lymph nodes [(3.218 ± 0.153)% vs. (3.673 ± 0.347)%; t = 1.332, P = 0.241]. There was no significant difference in the proportion of Treg cells in the spleen of male mice between infected and uninfected mice [(10.060 ± 0.361)% vs. (10.130 ± 0.142)%; t = 0.174, P = 0.867], while a higher proportion of Treg cells was seen in the spleen of female mice 8 weeks post-infection with S. japonicum than in uninfected mice [(10.530 ± 0.242)% vs. (9.450 ± 0.263)%; t = 3.021, P = 0.023]. There was no significant difference in the proportion of Treg cells in the spleen between female and male mice infected with S. japonicum [(10.530 ± 0.242)% vs. (10.060 ± 0.361)%; t =1.077, P = 0.323]. In addition, the proportions of Treg cells were significantly greater in the lymph node of S. japonicum -infected female [(17.150 ± 0.805)% vs. (13.100 ± 0.265)%; t = 4.781, P = 0.003] and male mice [(18.550 ± 0.732)% vs. (12.630 ± 0.566)%; t = 6.402, P = 0.001] than in uninfected mice; however, no significant difference was seen between female and male mice 8 weeks post-infection [(17.150 ± 0.805)% vs. (18.550 ± 0.732)%; t = 1.287, P = 0.246]. CONCLUSIONS: There are no gender-specific hepatic pathological changes or antibody-mediated immunity in C57BL/6 mice post-infection with S. japonicum.

[The predictive value of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid enhanced MRI imaging features combined with quantitative parameters for the pathologic grading of hepatocellular carcinoma].

Objective: To investigate the predictive value of gadolinium-ethoxybenzyl- diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI imaging features combined with quantitative parameters for the pathologic grading of hepatocellular carcinoma (HCC). Methods: Eighty patients (65 males, 15 females; range 30-74 years,average age (59±11) years old) with HCC who underwent curative resection or biopsy from June 2016 to June 2019 in the First Affiliated Hospital of Soochow University after Gd-EOB-DTPA-enhanced MRI were evaluated retrospectively.According to the pathological results of the postoperative pathology, eighty patients were divided into poorly differentiated group (26 cases, 22 males, 4 females) and moderately-well differentiated group (54 cases, 43 males, 11 females). In Gd-EOB-DTPA-enhanced MRI, qualitative parameters were assessed. Quantitative parameters including tumor size, tumor-to-liver signal intensity ratio(SIR) of arterial phase (AP), portal vein phase (PP), equilibrium phase (EP) and hepatobiliary phase (HBP), contrast enhancement ration AP (CER-AP)were measured and calculated. Clinical data and qualitative parameters between poorly differentiated group and moderately-well differentiated group were analyzed by using χ(2) test.Quantitative parameters were analyzed by using independent sample t test. Statistically significant qualitative parameters, quantitative parameters, qualitative combined with quantitative parameters and AFP combined with qualitative and quantitative parameters were included in binary logistic regression model. The receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the four prediction model for the pathologic grading of HCC. Results: There was a statistical difference between poorly differentiated group and moderately-well differentiated group in AFP, arterial peritumoral enhancement, arterial rim enhancement, peritumoral hypointensity on HBP and tumor signal (all P<0.05). In two groups, tumor size, SIR-AP and SIR-PP were (7.0±3.7) vs (3.9±2.4)cm,1.11±0.29 vs 1.31±0.32 and 0.89±0.21 vs 1.03±0.27 (all P<0.05). AUC of qualitative parameters, quantitative parameters, qualitative combined with quantitative parameters and AFP combined with qualitative and quantitative parameters were 0.805, 0.804, 0.855, 0.892.There was a statistical difference between qualitative parameters and qualitative combined with quantitative parameters in sensitivity(80.8% vs 92.3%, P<0.05). Conclusion: Gd-EOB-DTPA-enhanced MRI imaging features combined with quantitative parameters can be used to predict the pathologic grading of HCC preoperatively, which has a great applicative value.

[The value of CT radiomics in the prediction of EGFR mutation in lung cancer].

Objective: To explore the value of CT radiomics quantitative features in the prediction of epidermal growth factor receptor (EGFR) mutation in lung cancer. Methods: The data of 144 patients, 75 males, 69 females, median age 54 (25-68 years), with EGFR gene test results in lung cancers diagnosed in the First Affiliated Hospital of Soochow University were retrospectively analyzed, including 81 patients, 39 males, 42 females, median age 52 (25-64)years old, with EGFR mutations and 63 patients,36 males,27 females,median age 56(32-68) years old,with EGFR wild types. According to a ratio of 2︰1, patients were randomly assigned to the training group and validation group. MaZda software was used to extract radiomics features including the gray level histogram (GLH), absolute gradient (GRA), gray-level co-occurrence matrix (GLCM), gray-level run-length matrix (GLRLM), auto-regressive model (ARM) and wavelets transform (WAV), and so on. Fisher coefficients (Fisher), classification error probability combined average correlation coefficients (POE+ACC) and mutual information (MI) were used to select 10 optimal features making up the optimal feature subsets. The optimal feature subsets were analyzed by using linear discriminant analysis (LDA) and nonlinear discriminant analysis (NDA) to calculate the accuracy, sensitivity and specificity in the differential diagnosis of EGFR mutant types and wild types in lung cancers. The prediction model was established using the optimal feature subsets with the highest accuracy in the training group with artificial neural network (ANN). The established prediction model was used to differentiate EGFR mutant types from wild types in the validation group. Results: MaZda software extracted a total of 301 quantitative features in the CT images for the patients with EGFR mutant types and EGFR wild types in the training group. The optimal feature subsets obtained from Fisher-NDA and (POE+ACC)-NDA had the highest accuracy of 93.8%, in the differential diagnosis of the EGFR mutant types and EGFR wild types of lung cancer in the training group. The optimal feature subset prediction model obtained from Fisher-NDA had the accuracy, sensitivity and specificity of 83.3%, 86.7% and 77.8%, respectively, in the differential diagnosis of the EGFR mutant types and EGFR wild types of lung cancer in the validation group. Conclusion: The optimal subset of CT radiomics features has high accuracy in predicting EGFR mutations in lung cancer, providing a new method for predicting gene expression of lung cancer.

[Clinical effects of surgical treatment of high myopic strabismus fixus by modified Yokoyama's surgery combined with medial rectus muscle recession].

Objective: To analyze clinical effects of modified Yokoyama's surgery combined with medial rectus muscle recession for treatment of high myopic strabismus fixus. Methods: Retrospective analysis of records of 9 patients (14 eyes) with high myopic strabismus fixus treated from February 2013 to December 2016 in the Department of Ophthalmology, Xiangya Hospital, Central South University. All patients underwent modified Yokoyama's surgery. The temporal 1/2 of the superior rectus (SR) and the superior 1/2 of the lateral rectus (LR) were united 12 to 14 mm, combined with medial rectus muscle recession. The angle of deviation of primary position, the mobility of the affected eye, and the change of CT imaging were observed and analyzed before and 6 months after surgery. Statistical analysis was performed by Mann-Whitney U test. Results: The patients were 5 females and 4 males with an average age of (60±10) years. The duration of high myopia was (33.33±6.61) years. The refractive power was (-23.32±5.95) D, and the axial length was (33.04±2.63) mm. The recession mount of medial rectus was (7.2±2.1) mm (4.0-10.0 mm) intraoperatively. At 6 months, the median esotropia improved from 130 (80-140) prism diopter (PD) to 0 (0-10) PD, and the hypotropia from 20 (15-25) PD to 0 (0-5) PD. The median abduction limitation decreased from -3 (-4--1) to -1 (-2-0), and the median limitation of elevation decreased from -2 (-4--1) to 0 (-1-0). The angle of esotropia and hypotropia significantly improved (Z=-2.67, -2.70; P=0.008, 0.007), and the restriction of abduction and elevation decreased (Z=-3.35, -3.24; both P=0.001). Only 3 patients' CT images were enrolled in a comparative study. Preoperative orbital CT scans showed inferior LR displacement and medial SR displacement with the posterior portion of the eyeball to the superotemporal quadrant of the orbit. After surgery, the mean reduction ratio of dislocation degree of the 3 patients was 28.97%, the dislocation of LR and SR was reduced, and the posterior global part was correctly positioned within the orbit. Conclusions: The modified Yokoyama's surgery combined with medial rectus muscle recession can effectively correct high myopic strabismus fixus, recover the eyeball anatomical position, and evidently improve eye mobility. The clinical effects are satisfactory. (Chin J Ophthalmol, 2019, 55: 670-676).

[Regulation of hypoxia inducible factor-1α on permeability of vascular endothelial cells and the mechanism].

Objective: To investigate the regulation of hypoxia-inducible factor-1α (HIF-1α) on permeability of rat vascular endothelial cells and the mechanism. Methods: Twelve male Sprague-Dawley rats aged 35 to 38 days were collected and vascular endothelial cells were separated and cultured. The morphology of cells was observed after 4 days of culture, and the following experiments were performed on the 2nd or 3rd passage of cells. (1) Rat vascular endothelial cells were collected and divided into blank control group, negative control group, HIF-1α interference sequence 1 group, HIF-1α interference sequence 2 group, and HIF-1α interference sequence 3 group according to the random number table (the same grouping method below), with 3 wells in each group. Cells in negative control group, HIF-1α interference sequence 1 group, HIF-1α interference sequence 2 group, and HIF-1α interference sequence 3 group were transfected with GV248 empty plasmid, recombinant plasmid respectively containing HIF-1α interference sequence 1, interference sequence 2, and interference sequence 3 with liposome 2000. Cells in blank control group were only transfected with liposome 2000. After transfection of 24 h, expression levels of HIF-1α mRNA and protein of cells in each group were respectively detected by reverse transcription real-time fluorescent quantitative polymerase chain reaction and Western blotting (the same detecting methods below) . The sequence with the highest interference efficiency was selected. (2) Another batch of rat vascular endothelial cells were collected and divided into blank control group, negative control group, and HIF-1α low expression group, with 3 wells in each group. Cells in blank control group were only transfected with liposome 2000, and cells in negative control group and HIF-1α low expression group were respectively transfected with GV248 empty plasmid and low expression HIF-1α recombinant plasmid selected in experiment (1) with liposome 2000. After 14 days of culture, the mRNA and protein expressions of HIF-1α in each group were detected. (3) Another batch of rat vascular endothelial cells were collected and divided into blank control group, negative control group, and HIF-1α high expression group, with 3 wells in each group. Cells in blank control group were transfected with liposome 2000, and cells in negative control group and HIF-1α high expression group were respectively transfected with GV230 empty plasmid and HIF-1α high expression recombinant plasmid with liposome 2000. After 14 days of culture, the mRNA and protein expressions of HIF-1α of cells in each group were detected. (4) After transfection of 24 h, cells of three groups in experiment (1) and three groups in experiment (2) were collected, and mRNA and protein expressions of myosin light chain kinase (MLCK), phosphorylated myosin light chain (p-MLC), and zonula occludens 1 (ZO-1) of cells were detected. Data were processed with one-way analysis of variance and t test. Results: After 4 days of culture, the cells were spindle-shaped, and rat vascular endothelial cells were successfully cultured. (1) The interference efficiencies of HIF-1α of cells in HIF-1α interference sequence 1 group, HIF-1α interference sequence 2 group, and HIF-1α interference sequence 3 group were 47.66%, 45.79%, and 62.62%, respectively, and the interference sequence 3 group had the highest interference efficiency. After transfection of 24 h, the mRNA and protein expression levels of HIF-1α of cells in interference sequence 3 group were significantly lower than those in blank control group (t=18.404, 9.140, P<0.01) and negative control group (t=15.099, 7.096, P<0.01). (2) After cultured for 14 days, the mRNA and protein expression levels of HIF-1α of cells in HIF-1α low expression group were significantly lower than those in blank control group (t=21.140, 5.440, P<0.01) and negative control group (t= 14.310, 5.210, P<0.01). (3) After cultured for 14 days, the mRNA and protein expression levels of HIF-1α of cells in HIF-1α high expression group were significantly higher than those in blank control group (t=19.160, 7.710, P<0.01) and negative control group (t= 19.890, 7.500, P<0.01). (4) After transfection of 24 h, the mRNA expression levels of MLCK and p-MLC of cells in HIF-1α low expression group were significantly lower than those in blank control group (t=2.709, 4.011, P<0.05 or P<0.01) and negative control group (t=2.373, 3.744, P<0.05 or P<0.01). The mRNA expression level of ZO-1 of cells in HIF-1α low expression group was significantly higher than that in blank control group and negative control group (t=4.285, 5.050, P<0.01). The mRNA expression levels of MLCK and p-MLC of cells in HIF-1α high expression group were significantly higher than those in blank control group (t=9.118, 11.313, P<0.01) and negative control group (t=9.073, 11.280, P<0.01). The mRNA expression level of ZO-1 of cells in HIF-1α high expression group was significantly lower than that in blank control group and negative control group (t=2.889, 2.640, P<0.05). (5) After transfection of 24 h, the protein expression levels of MLCK and p-MLC of cells in HIF-1α low expression group were significantly lower than those in blank control group (t=2.652, 3.983, P<0.05 or P<0.01) and negative control group (t=2.792, 4.065, P<0.05 or P<0.01). The protein expression of ZO-1 of cells in HIF-1α low expression group was significantly higher than that in blank control group and negative control group (t=3.881, 3.570, P<0.01). The protein expression levels of MLCK and p-MLC of cells in HIF-1α high expression group were 1.18±0.24 and 0.68±0.22, which were significantly higher than 0.41±0.21 and 0.35±0.14 in blank control group (t=5.011, 3.982, P<0.05 or P<0.01) and 0.43±0.20 and 0.36±0.12 in negative control group (t= 4.880, 3.862, P<0.05 or P<0.01). The protein expression level of ZO-1 of cells in HIF-1α high expression group was 0.08±0.06, which was significantly lower than 0.20±0.09 in blank control group and 0.19±0.09 in negative control group (t=4.178, 3.830, P<0.05 or P<0.01). Conclusions: HIF-1α up-regulates expressions of MLCK and p-MLC and down-regulates expression of ZO-1, thereby increasing the permeability of rat vascular endothelial cells.

[Evaluation of the diagnosis value of carcinoembryonic antigen in malignant pleural effusion].

Objective: To investigate the diagnostic value of serum and pleural fluid carcinoembryonic antigen (CEA) for malignant pleural effusion (MPE). Methods: The concentration of CEA in serum and pleural fluid of 286 patients with the diagnosis confirmed by pleural biopsy through medical thoracoscopy were retrospectively analyzed. MPE was confirmed in 171 cases which were divided into two groups (adenocarcinoma group with 121cases and non-adenocarcinoma group with 50 cases) and benign pleural effusion in 115 cases. The optimal cutoff for MPE and MPE caused by adenocarcinoma were determined by using the ROC curve. Results: The concentration of serum CEA 12.27(3.80, 58.45) µg/L was significantly higher in MPE caused by adenocarcinoma than that of non-adenocarcinoma 1.91(1.08, 4.55) µg/L and benign effusion 1.32(0.86, 2.27) µg/L (both P<0.001), but there was no statistically significant difference between benign and non-adenocarcinoma effusion (P=0.728). The concentration of pleural fluid CEA 160.70(30.48, 1 000.00) µg/L was significantly higher in MPE caused by adenocarcinoma than that of non-adenocarcinoma 1.77(0.51, 11.39) µg/L and benign effusion 1.09(0.60, 1.68) µg/L (both P<0.001), and higher in non-adenocarcinoma effusion than that of benign effusion (P<0.05). The cutoff value of serum and pleural fluid CEA for MPE was 3.10 and 5.83 µg/L, the sensitivity respectively was 67.3% and 74.3%, the specificity respectively was 87.8% and 98.3%, positive predictive value respectively was 89.2% and 98.5%, negative predictive value respectively was 64.3% and 72.0%. The cutoff value of serum and pleural fluid CEA for MPE caused by adenocarcinoma was 3.54 and 7.30 µg/L, the sensitivity respectively was 76.0% and 91.7%, the specificity respectively was 74.0% and 72.0%, positive predictive value respectively was 87.6% and 88.8%, negative predictive value respectively was 56.1% and 78.3%. Conclusions: The concentration of serum and pleural fluid CEA have diagnostic significance to MPE, especially MPE caused by adenocarcinoma. The diagnostic value of pleural fluid CEA is superior to serum CEA.

[Value of spectral CT-based quantitative analysis in differential diagnosis of liver cancer and liver abscess].

Objective: To investigate the value of spectral CT-based quantitative analysis in the differential diagnosis of liver cancer and liver abscess. Methods: A total of 70 patients with space-occupying lesions in the liver(45 with liver cancer and 25 with liver abscess)underwent spectral CT scans to obtain spectral images in the arterial phase and portal venous phase. The solid constituents of lesions and the iodine and water concentrations in necrotic or cystic parts of lesions, normal hepatic tissue, and abdominal aorta in the arterial phase and portal venous phase were measured, and the normalized iodine concentration(NIC)and lesion-to-normal hepatic tissue ratio(LNR)of iodine concentration were calculated. The two samples t-test and the receiver operating characteristic(ROC)curve analysis were performed for the quantitative indices above. Results: The patients with liver cancer had higher NIC and LNR in solid constituents in the arterial phase than those with liver abscess(NIC: 0.15±0.06 mg/ml vs 0.14±0.02 mg/ml, P > 0.05; LNR: 2.78±0.65 vs 1.45±0.88, P < 0.001). The patients with liver abscess had significantly higher NIC and LNR in solid constituents in the portal venous phase than those with liver cancer(NIC: 0.65±0.08 mg/ml vs 0.52±0.08 mg/ml, P≤0.001; LNR: 1.22±0.23 vs 0.95±0.15, P≤0.001). There were no significant differences in NIC in the arterial phase or NIC and LNR in the portal venous phase in necrotic or cystic parts of lesions between the patients with liver cancer and liver abscess(P > 0.05). The optimal quantitative value for the differential diagnosis of liver cancer and liver abscess was LNR in arterial phase, and the cut-off value of 1.53 had a sensitivity of 100% and a specificity of 92%. Conclusion: Quantitative iodine concentration analysis in spectral CT imaging has a certain value in the differential diagnosis of liver cancer and liver abscess and can improve the accuracy of diagnosis.

Protective effects of tumor necrosis factor-α blockade by adalimumab on articular cartilage and subchondral bone in a rat model of osteoarthritis.

We aimed to investigate the effects of an anti-tumor necrosis factor-α antibody (ATNF) on cartilage and subchondral bone in a rat model of osteoarthritis. Twenty-four rats were randomly divided into three groups: sham-operated group (n=8); anterior cruciate ligament transection (ACLT)+normal saline (NS) group (n=8); and ACLT+ATNF group (n=8). The rats in the ACLT+ATNF group received subcutaneous injections of ATNF (20 µg/kg) for 12 weeks, while those in the ACLT+NS group received NS at the same dose for 12 weeks. All rats were euthanized at 12 weeks after surgery and specimens from the affected knees were harvested. Hematoxylin and eosin staining, Masson's trichrome staining, and Mankin score assessment were carried out to evaluate the cartilage status and cartilage matrix degradation. Matrix metalloproteinase (MMP)-13 immunohistochemistry was performed to assess the cartilage molecular metabolism. Bone histomorphometry was used to observe the subchondral trabecular microstructure. Compared with the rats in the ACLT+NS group, histological and Mankin score analyses showed that ATNF treatment reduced the severity of the cartilage lesions and led to a lower Mankin score. Immunohistochemical and histomorphometric analyses revealed that ATNF treatment reduced the ACLT-induced destruction of the subchondral trabecular microstructure, and decreased MMP-13 expression. ATNF treatment may delay degradation of the extracellular matrix via a decrease in MMP-13 expression. ATNF treatment probably protects articular cartilage by improving the structure of the subchondral bone and reducing the degradation of the cartilage matrix.