Preoperative contrast-enhanced CT-based radiomics nomogram for differentiating benign and malignant primary retroperitoneal tumors.

OBJECTIVES: This study evaluated the ability of a preoperative contrast-enhanced CT (CECT)-based radiomics nomogram to differentiate benign and malignant primary retroperitoneal tumors (PRT). METHODS: Images and data from 340 patients with pathologically confirmed PRT were randomly placed into training (n = 239) and validation sets (n = 101). Two radiologists independently analyzed all CT images and made measurements. Key characteristics were identified through least absolute shrinkage selection combined with four machine-learning classifiers (support vector machine, generalized linear model, random forest, and artificial neural network back propagation) to create a radiomics signature. Demographic data and CECT characteristics were analyzed to formulate a clinico-radiological model. Independent clinical variables were merged with the best-performing radiomics signature to develop a radiomics nomogram. The discrimination capacity and clinical value of three models were quantified by the area under the receiver operating characteristics (AUC), accuracy, and decision curve analysis. RESULTS: The radiomics nomogram was able to consistently differentiate between benign and malignant PRT in the training and validation datasets, with AUCs of 0.923 and 0.907, respectively. Decision curve analysis manifested that the nomogram achieved higher clinical net benefits than did separate use of the radiomics signature and clinico-radiological model. CONCLUSIONS: The preoperative nomogram is valuable for differentiating between benign and malignant PRT; it can also aid in treatment planning. KEY POINTS: • A noninvasive and accurate preoperative determination of benign and malignant PRT is crucial to identifying suitable treatments and predicting disease prognosis. • Associating the radiomics signature with clinical factors facilitates differentiation of malignant from benign PRT with improved diagnostic efficacy (AUC) and accuracy from 0.772 to 0.907 and from 0.723 to 0.842, respectively, compared with the clinico-radiological model alone. • For some PRT with anatomically special locations and when biopsy is extremely difficult and risky, a radiomics nomogram may provide a promising preoperative alternative for distinguishing benignity and malignancy.

Deep Learning Radiomics Nomogram to Predict Lung Metastasis in Soft-Tissue Sarcoma: A Multi-Center Study.

Objectives: To build and evaluate a deep learning radiomics nomogram (DLRN) for preoperative prediction of lung metastasis (LM) status in patients with soft tissue sarcoma (STS). Methods: In total, 242 patients with STS (training set, n=116; external validation set, n=126) who underwent magnetic resonance imaging were retrospectively enrolled in this study. We identified independent predictors for LM-status and evaluated their performance. The minimum redundancy maximum relevance (mRMR) method and least absolute shrinkage and selection operator (LASSO) algorithm were adopted to screen radiomics features. Logistic regression, decision tree, random forest, support vector machine (SVM), and adaptive boosting classifiers were compared for their ability to predict LM. To overcome the imbalanced distribution of the LM data, we retrained each machine-learning classifier using the synthetic minority over-sampling technique (SMOTE). A DLRN combining the independent clinical predictors with the best performing radiomics prediction signature (mRMR+LASSO+SVM+SMOTE) was established. Area under the receiver operating characteristics curve (AUC), calibration curves, and decision curve analysis (DCA) were used to assess the performance and clinical applicability of the models. Result: Comparisons of the AUC values applied to the external validation set revealed that the DLRN model (AUC=0.833) showed better prediction performance than the clinical model (AUC=0.664) and radiomics model (AUC=0.799). The calibration curves indicated good calibration efficiency and the DCA showed the DLRN model to have greater clinical applicability than the other two models. Conclusion: The DLRN was shown to be an accurate and efficient tool for LM-status prediction in STS.

CT Radiomics Model for Predicting the Ki-67 Index of Lung Cancer： An Exploratory Study.

OBJECTIVE: To establish a radiomics signature and a nomogram model based on enhanced CT images to predict the Ki-67 index of lung cancer. METHODS: From January 2014 to December 2018, 282 patients with lung cancer who had undergone enhanced CT scans and Ki-67 examination within 2 weeks were retrospectively enrolled and analyzed. The clinical data of the patients were collected, such as age, sex, smoking history, maximum tumor diameter and serum tumor markers. Our primary cohort was randomly divided into a training group (n=197) and a validation group (n=85) at a 7:3 ratio. A Ki-67 index ≤ 40% indicated low expression, and a Ki-67 index > 40% indicated high expression. In total, 396 radiomics features were extracted using AK software. Feature reduction and selection were performed using the lasso regression model. Logistic regression analysis was used to establish a multivariate predictive model to identify high and low Ki-67 expression in lung cancer. A nomogram integrating the radiomics score was established based on multiple logistic regression analysis. Area under the curve (AUC) was used to evaluate the prediction efficiency of the radiomics signature and nomogram. RESULTS: The AUC,sensitivity, specificity and accuracy of the radiomics signature in the training and validation groups were 0.88 (95% CI: 0.82~0.93),79.2%,84.3%,81.2% and 0.86 (95% CI: 0.78~0.94),74.6%,88.1%,79.8%, respectively. A nomogram combining radiomics features and clinical risk factors (smoking history and NSE) was developed. The AUC, sensitivity, specificity and accuracy were 0.87 (95% CI: 0.80~0.95), 75.0%, 90.2% and 83.5% in the validation group, respectively. CONCLUSION: The radiomics signature and nomogram based on enhanced CT images provide a way to predict the Ki-67 expression level in lung cancer.

LncRNA POU3F3 Contributes to Dacarbazine Resistance of Human Melanoma Through the MiR-650/MGMT Axis.

Background: Alkylating agents are critical therapeutic options for melanoma, while dacarbazine (DTIC)-based chemotherapy showed poor sensitivity in clinical trials. Long non-coding RNAs (lncRNAs) were highlighted in the progression of malignant tumors in recent years, whereas little was known about their involvement in melanoma. Methods: The functional role and molecular mechanism of lncRNA POU3F3 were evaluated on DTIC-resistant melanoma cells. Further studies analyzed its clinical role in the disease progression of melanoma. Results: We observed elevated the expression of lncRNA POU3F3 in the DTIC-resistant melanoma cells. Gain-of-function assays showed that the overexpression of lncRNA POU3F3 maintained cell survival with DTIC treatment, while the knockdown of lncRNA POU3F3 restored cell sensitivity to DTIC. A positive correlation of the expression O6-methylguanine-DNA-methyltransferase (MGMT) was observed with lncRNA POU3F3 in vitro and in vivo. Bioinformatic analyses predicted that miR-650 was involved in the lncRNA POU3F3-regulated MGMT expression. Molecular analysis indicated that lncRNA POU3F3 worked as a competitive endogenous RNA to regulate the levels of miR-650, and the lncRNA POU3F3/miR-650 axis determined the transcription of MGMT in melanoma cells to a greater extent. Further clinical studies supported that lncRNA POU3F3 was a risk factor for the disease progression of melanoma. Conclusion: LncRNA POU3F3 upregulated the expression of MGMT by sponging miR-650, which is a crucial way for DTIC resistance in melanoma. Our results indicated that lncRNA POU3F3 was a valuable biomarker for the disease progression of melanoma.

[Clinical features of Enterococcus faecium meningitis in children].

OBJECTIVE: To summarize the clinical features of Enterococcus faecium meningitis in children. METHODS: The clinical data of nine children with Enterococcus faecium meningitis were analyzed. RESULTS: In all the nine children, Enterococcus faecium was isolated from blood, cerebrospinal fluid, or peripherally inserted central catheters; 6 (67%) patients were neonates, 2 (22%) patients were younger than 6 months, and 1 (11%) patient was three years and four months of age. In those patients, 56% had high-risk factors before onset, which included intestinal infection, resettlement of drainage tube after surgery for hydrocephalus, skull fracture, perinatal maternal infection history, and catheter-related infection. The main symptoms were fever and poor response. In those patients, 22% had seizures; no child had meningeal irritation sign or disturbance of consciousness. The white blood cell count and level of C-reactive protein were normal or increased; the nucleated cell count in cerebrospinal fluid was normal or mildly elevated; the protein level was substantially elevated; the glucose level was decreased. The drug sensitivity test showed that bacteria were all sensitive to vancomycin and the vancomycin treatment was effective. Only one child had the complication of hydrocephalus. CONCLUSIONS: Enterococcus faecium meningitis occurs mainly in neonates and infants. The patients have atypical clinical features. A high proportion of patients with Enterococcus faecium meningitis have high-risk factors. Enterococcus faecium is sensitive to vancomycin.

[Correction of shortened and broaden prolabium deformity with double flag-shaped flaps following bilateral cleft lip repair].

OBJECTIVE: To explore the correction for shortened and broaden prolabium deformity following bilateral cleft lip repair. METHODS: We designed the upper lip double flag-shaped flaps. The quadrilateral original surgical scar (flap flag pole part) was resected and the incision was made along the direction of nasolabial groove at the nostrils bottom to form two flag-shaped flaps (the section of the flag face). Lip tubercle were tracted and blunt dissection of upper philtrum were performed to form a wound, 4-6 mm in width. The flag-shaped flaps on both sides were rotated to the central, in order to form a new nasal base and new prolabium, followed by V-Y or Z plasty procedure to correct the defect of tubercle and vermilion. RESULTS: 10 cases were enrolled for the clinical application from January 2008 to December 2012. The height of the prolabium was lengthened by 4-6 mm after operation, which fundamentally corrected shortened and broaden prolabium deformity after bilateral cleft lip operation. The procedure can also correct the depression or defect of tubercle, too wide philtrum, philtrum column scar and the deformity of vermilion border continuity. The patients were followed up for a period of 3 months to 3 years with satisfactory results. CONCLUSION: Double flag-shaped flaps of the upper lip at the nostrils bottom is a simple and good surgery method to correct the shortened and broaden prolabium deformity following bilateral cleft lip repair.

[Gene expression of transforming growth factor beta receptor II in the epidermis of pathological scar].

OBJECTIVE: To study the gene expression of transforming growth factor beta receptor II (TbetaR II) in pathological scar. METHODS: Twenty samples of pathological scar were collected from 20 burn or trauma patients hospitalized in the General Hospital of Ji'nan Military Command from 2007 to 2009. Twenty specimens of epidermal layer were obtained from the middle portion and the edge of pathological scars. Twenty normal skin specimens which were located more than 10 cm away from the lesion sites of 20 patients were collected as self-controls. Serum from 1-2 mL whole blood were obtained from each of the 20 patients for second self-control. Eight normal skin specimens from 8 patients without pathological scar, discarded from un-related operations, were also collected as negative-control. Positive expressions of TbetaR II in three different skin specimens were determined with biotin-streptavidin-peroxidase staining. Gene expressions of TbetaR II in all specimens were compared with PCR-single strand conformation polymorphism analysis and gene sequencing. Data were processed with Fisher's exact test. RESULTS: Positive expression of TbetaR II in pathological scar epidermis was lower than that in normal skin specimen of patients with pathological scar or normal skin specimen of patients without pathological scar, and TbetaR II was mainly located in the basal layer of epidermis. Positive expressions of TbetaR II were seldom found in acanthocytes, granular cells, and cuticle or even non-existing. No abnormality of TbetaR II was found in normal skin epidermis or serum samples of pathological scar patients or normal skin epidermis of patients without pathological scar. TbetaR II expressing in 8 specimens of epidermis of pathological scar showed abnormal electrophoresis pattern at poly A fragments hand and loss of one A base in DNA fragment (P = 0.044). CONCLUSIONS: There may he abnormal gene expression of TbetaR II in pathological scar epidermis. Replantation of epidermis of scar may increase the risk of scar recurrence, while replantation of normal skin of patients with scar on wound may not increase the risk of scar recurrence.

FSCB phosphorylation in mouse spermatozoa capacitation.

It is generally accepted that spermatozoa capacitation is associated with protein kinase A-mediated tyrosine phosphorylation. In our previous study, we identified the fibrous sheath CABYR binding protein (FSCB), which was phosphorylated by PKA. However, the phosphorylation status of FSCB protein during spermatozoa capacitation should be further investigated. To this aim, in this study, we found that phosphorylation of this 270-kDa protein occurred as early as 1 min after mouse spermatozoa capacitation, which increased over time and remained stable after 60 min. Immunoprecipitation assays demonstrated that the tyrosine and Ser/Thr phosphorylation of FSCB occurred during spermatozoa capacitation. The extent of phosphorylation and was closely associated with the PKA activity and spermatozoa motility characteristics. FSCB phosphorylation could be induced by PKA agonist DB-cAMP, but was blocked by PKA antagonist H-89.Therefore, FSCB contributes to spermatozoa capacitation in a tyrosine-phosphorylated format, which may help in further elucidating the molecular mechanism of spermatozoa capacitation.

[Clinical study on the repair of extensive deep burn wounds with autogenous fat granules and autologous microskin grafts in mixed grafting].

OBJECTIVE: To observe the effects of autologous fat granules in mixed grafting microskin grafts on repair of extensive deep burn wounds in patients. METHODS: Twenty patients hospitalized in our ward were enrolled for autogenous self-control test in wounds on both or symmetrical parts of wounds of the trunk, and they were randomly divided into experimental (E) trol (C) groups, the wounds in E group were repaired with autologous fat granules together with microskin in mixed grafting (volume ratio 1 : 1), and in C group only autologous microskin grafting was given. Wound healing rate was measured on 30th, 45th, and 60th day after operation. Wound specimens harvested for HE staining and PCNA immunohistochemistry examination on 7th, 14th, 21st, and after operation. RESULTS: (1) The mean wound healing rate on 30th, 45th, and 60th day after E group was (56.3 +/- 3.1)%, (76.4 +/-6.1)%, (96.2 +/- 1.5)%, which were respectively higher C group [(28.3 +/-2.0)%, (47.3 +/-4.8)%, (85.4 +/- 2.2)%, P < 0.01]. HE staining showed epithelization in E group was earlier than that in C group, with regular arrangement of collagen fibers. The quantity NA positive cells in E group were larger than that in C group, and PCNA was mainly expressed cells of basal layer . CONCLUSION: Autologous fat granules in mixed grafting with autologous microskin promote wound healing.

[Atrial natriuretic factor's effects on the reperfusion process after cochlea ischemia].

OBJECTIVE: To investigate the effects of atrial natriuretic peptide (ANP) on ischemia and reperfusion cochlea in guinea pigs. METHODS: The guinea pigs were randomly allocated into four groups: experiment groups (A1 and B1) and control groups (A2 and B2). Cochlear ischemia and reperfusion was induced by thrombus and thrombolysis method. In experiment group A1, ANP was administered 10 min before the ischemic insult. In experiment group B1, ANP was administered at the beginning of reperfusion. In control groups, instead of ANP, normal sodium was injected. The blood flow of cochlea (CoBF) was monitored continuously with laser Doppler flow meter and the threshold of auditory brainstem response (ABR) was measured. RESULTS: Before the induction of ischemia, the CoBF of experiment group A1 was higher than that of the control group A2. From the reperfusion moment to the end of the experiment, there was no difference between the CoBF of the two groups. In B1 and B2 groups, no difference could be seen between the two groups before the induction of ischemia. After reperfusion, the blood flow of control group B2 recovered to 70% of the base level, while the CoBF of experiment group B1 restored to almost the same level of the beginning. Before ischemia, the ABR threshold of the four groups had no difference. At 30 min of ischemia, the threshold of experiment group Al was lower than that of control group A2. And there was no difference in experiment group B1 and control group B2. At 30 min and 60 min of reperfusion, the threshold of experiment group B1 was significantly lower than that of control group B2. No difference could be seen between experiment group A1 and control group A2. CONCLUSIONS: Administration of ANP at the beginning of reperfusion protects the cochlea from ischemia and reperfusion injury. The administration can not only increase the CoBF, but lower the ABR threshold.

[Expression of substance P receptor positive cells in the Corti's organ with acute middle ear infection in guinea pigs].

OBJECTIVE: To investigate the expression of substance P receptor(SPR), SPR positive cells in the Corti's organ with acute middle ear infection in guinea pigs using the polyclonal antibody of SPR. METHODS: Twelve healthy guinea pigs were employed in the experiment. After general anesthesia, by injecting 1 x 10(8)/L staphylococcosis aureus into the middle cavity of right ear with the left ear serving as control, the acute middle ear infection model was established. Then three days later, immunohistochemical staining of SPR was performed in the Cochlear base membrane preparation. RESULTS: Microscopic examination of whole cochlear preparation revealed a number of SPR positive cells expression in the cochlear base membrane, these labeled cells usually did not exist in normal cochlear tissue. Obvious difference in morphology and distribution could be identified with inner hair cells, outer hair cells vascular endothelial cell and spiral ganglion neurons. Labeled SP receptor positive cells were similar to "neurons", scattering distributed in the free margin of cochlear base membrane, with larger size and multiple projections which was 6-12 times than the erythrocyte. There were the vesicle and granular substances in the cytoplasm of the labeled cells. CONCLUSIONS: Acute middle ear infection could induce the expression of SP receptor positive nonspecific cells in the Corti's organ of guinea pigs. These cells did not exist in the normal base membrane and might participate in initiating or inducing the immune response of inner ear.

[Human antisense-vascular endothelial growth factor gene therapy for laryngeal tumor by cationic liposome-mediated transfection].

OBJECTIVE: To observe the effect of cationic liposome mediated antisense-vascular endothelial growth factor (VEGF) gene transfection on the growth of laryngeal cancer Hep-2 cells in the nude mice. METHODS: The VEGF-cDNA gene was cloned by reverse transcriptase polymerase chain reaction (RT-PCR) from human laryngeal cancer, and its eukaryotic expression vector pcDNA3-VEGF (-) with antisense-VEGF gene was constructed and identified by PCR and double-enzyme digestion. The pcDNA3-VEGF (-) was transfected into laryngeal cancer Hep-2 cell line by using cationic liposome (LP 2000). Then, the transfected Hep-2 cells were injected into nude mice and the size of tumor from different groups was observed while establishing laryngeal cancer xenografts in nude mice, and then treating the tumor-bearing mice with liposome-plasmid complex, observing the size of tumor from different groups. The expression of VEGF mRNA in different groups was observed by RT-PCR. The transfected cell ultranstructure was observed by transmission electron microscopy. RESULTS: The human VEGF-cDNA was successfully cloned and its eukaryotic expression vector with antisense-VEGF pcDNA3-VEGF (-) was constructed. The antisense-VEGF gene was transfected into Hep-2 cell line by using cationic liposome (LP2000). The size of tumor transfected with pcDNA3-VEGF (-) was significantly smaller than that of control groups. While the size of tumor treated with liposome-pcDNA3-VEGF (-) complex was significantly smaller than that of control groups. Many apoptic tumor cells were observed by transmission electron microscopy and the structure of microvessel was also changed. The expression of VEGF mRNA was evidently weaker than that of the control groups. CONCLUSION: The growth of Hep-2 cells could be inhibited significantly by antisense-VEGF gene transfection.

[Culture of neural stem cells from rat olfactory bulb].

OBJECTIVE: To establish the method of in vitro culture of neural stem cells (NSC) from rat olfactory bulb and investigate the characteristics of its proliferation and differentiation. METHODS: NSC from postnatal one-day (P1) and adult rat olfactory bulb were isolated and cultured in serum free media with epidermal growth factor (EGF) and fibroblast growth factor-basic (bFGF). Antibodies against NSC (nestin), neuronal (neuronal specific enolase, NSE), astrocytic (glial fibrillary acidic protein, GFAP) and oligodendrocytic (galactocerebroside, GalC) markers were used to identify NSC and specific neural cells differentiated from NSC with immunocytochemical staining. Growth curve of olfactory bulb NSC was measured using MTT method. RESULTS: Nestin immuno-positive NSC were isolated and cultured from P1 and adult rat olfactory bulb which could differentiate into neurons, astrocytes and oligodendrocytes. The forming rates of neurosphere from P1 and adult rat olfactory bulb were 20% approximately 30% and 0.1% respectively. The proliferation of olfactory bulb NSC depended on EGF and bFGF, in which EGF increased proliferation of cells stronger than bFGF. CONCLUSIONS: NSC with self-renewal capacity and potential multi-differentiation were cultured from P1 and adult rat olfactory bulb.