Prediction of neoadjuvant chemotherapy pathological complete response for breast cancer based on radiomics nomogram of intratumoral and derived tissue.

BACKGROUND: Non-invasive identification of breast cancer (BCa) patients with pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) is critical to determine appropriate surgical strategies and guide the resection range of tumor. This study aimed to examine the effectiveness of a nomogram created by combining radiomics signatures from both intratumoral and derived tissues with clinical characteristics for predicting pCR after NACT. METHODS: The clinical data of 133 BCa patients were analyzed retrospectively and divided into training and validation sets. The radiomics features for Intratumoral, peritumoral, and background parenchymal enhancement (BPE) in the training set were dimensionalized. Logistic regression analysis was used to select the optimal feature set, and a radiomics signature was constructed using a decision tree. The signature was combined with clinical features to build joint models and generate nomograms. The area under curve (AUC) value of receiver operating characteristic (ROC) curve was then used to assess the performance of the nomogram and independent predictors. RESULTS: Among single region, intratumoral had the best predictive value. The diagnostic performance of the intratumoral improved after adding the BPE features. The AUC values of the radiomics signature were 0.822 and 0.82 in the training and validation sets. Multivariate logistic regression analysis revealed that age, ER, PR, Ki-67, and radiomics signature were independent predictors of pCR in constructing a nomogram. The AUC of the nomogram in the training and validation sets were 0.947 and 0.933. The DeLong test showed that the nomogram had statistically significant differences compared to other independent predictors in both the training and validation sets (P < 0.05). CONCLUSION: BPE has value in predicting the efficacy of neoadjuvant chemotherapy, thereby revealing the potential impact of tumor growth environment on the efficacy of neoadjuvant chemotherapy.

KLF5/MDM2 Axis Modulates Oxidative Stress and Epithelial-Mesenchymal Transition in Human Lens Epithelial Cells: The Role in Diabetic Cataract.

Diabetic cataract (DC) is a common cause of visual loss in older diabetic subjects. Krüppel-like factor 5 (KLF5) plays an essential role in migration and the epithelial-mesenchymal transition (EMT) in diverse cells and is involved in oxidative stress. However, the effects of KLF5 on DC remain unknown. This study aimed to examine the biological function of KLF5 in DC and its underlying mechanism. The expression patterns of KLF5 were detected in vivo and in vitro. Then, KLF5 was knocked down in human lens epithelial cells (HLECs) to explore its functional roles and underlying mechanisms. Dual-luciferase reporter assay and chromatin immunoprecipitation analysis were used to detect whether KLF5 could bind the promoter of E3 ubiquitin ligase mouse double minute 2 (MDM2), a key regulator of EMT. Lastly, the regulation of KLF5 in the biological behaviors of HLECs via MDM2 was analyzed. We found a significant increase of KLF5 in the DC lens anterior capsular, diabetic rat lens, and high glucose (HG)-stimulated HLECs. Knockdown of KLF5 inhibited oxidative stress, inflammation, migration, and EMT of HG-stimulated HLECs. KLF5 silencing impeded MDM2 expression and restricted the activation of MARK1/FAK and NF-κB signaling pathways in HLECs under HG condition. Additionally, KLF5 was found to bind the MDM2 promoter and enhance the transcriptional activity of MDM2. The protective effects by silencing KLF5 on HG-cultured HLECs could be offset by MDM2 overexpression. We demonstrated that knockdown of KLF5 alleviated oxidative stress, migration, and EMT of HG-cultured HLECs by regulating MDM2, suggesting a potential therapeutic strategy for DC.

Novel cataract-causing variant c.177dupC in c-MAF regulates the expression of crystallin genes for cell apoptosis via a mitochondria-dependent pathway.

Congenital cataract (CC) is regarded as the most common hereditary ophthalmic disease in children. Mutations in CC-associated genes play important roles in CC formation, which provides the basis for molecular diagnosis and therapy. Among these CC-associated genes, v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (c-MAF) is considered an important transcription factor for eye and lens development. In this study, we recruited a three-generation Chinese Han family with CC. Gene sequencing revealed a novel duplication mutation in c-MAF (NM_005360.5: c.177dup) that caused frameshifting at residue 60 (p. M60fs) of c-MAF. Additionally, in the patient blood samples, the expression levels of related crystallin and noncrystallin genes confirmed that this novel duplication variant impaired the transactivation of c-MAF. Further functional analyses suggested that the c-MAF mutant induces the transcriptional inhibition of CRYAA and CRYGA and subsequently influences ME and G6PD expression levels, ultimately resulting in ROS generation and further leading to cell apoptosis via mitochondria-dependent pathways. In conclusion, we report a novel c-MAF heterozygous mutation that plays a vital role in CC formation in a Chinese family, broadening the genetic spectrum of CC.

Coronary computed tomography angiography imaging features combined with computed tomography-fractional flow reserve, pericoronary fat attenuation index, and radiomics for the prediction of myocardial ischemia.

BACKGROUND: This study aimed to predict myocardial ischemia (MIS) by constructing models with imaging features, CT-fractional flow reserve (CT-FFR), pericoronary fat attenuation index (pFAI), and radiomics based on coronary computed tomography angiography (CCTA). METHODS AND RESULTS: This study included 96 patients who underwent CCTA and single photon emission computed tomography-myocardial perfusion imaging (SPECT-MPI). According to SPECT-MPI results, there were 72 vessels with MIS in corresponding supply area and 105 vessels with no-MIS. The conventional model [lesion length (LL), MDS (maximum stenosis diameter × 100% / reference vessel diameter), MAS (maximum stenosis area × 100% / reference vessel area) and CT value], radiomics model (radiomics features), and multi-faceted model (all features) were constructed using support vector machine. Conventional and radiomics models showed similar predictive efficacy [AUC: 0.76, CI 0.62-0.90 vs. 0.74, CI 0.61-0.88; p > 0.05]. Adding pFAI to the conventional model showed better predictive efficacy than adding CT-FFR (AUC: 0.88, CI 0.79-0.97 vs. 0.80, CI 0.68-0.92; p < 0.05). Compared with conventional and radiomics model, the multi-faceted model showed the highest predictive efficacy (AUC: 0.92, CI 0.82-0.98, p < 0.05). CONCLUSION: pFAI is more effective for predicting MIS than CT-FFR. A multi-faceted model combining imaging features, CT-FFR, pFAI, and radiomics is a potential diagnostic tool for MIS.

Altered local spontaneous brain activity pattern in children with right-eye amblyopia of varying degrees: evidence from fMRI.

PURPOSE: To investigate the abnormal changes of local brain activity in children with right-eye amblyopia of varying degrees. METHODS: Data of resting-state functional magnetic resonance imaging were collected from 16 children with severe amblyopia, 17 children with mild to moderate amblyopia, and 15 children with normal binocular vision. Local brain activity was analyzed using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo). RESULTS: There were extensive ALFF differences among the three groups in 10 brain regions. There were extensive differences in ReHo among the three groups in 11 brain regions. The ALFF and ReHo of the right orbital part of the middle frontal gyrus displayed a significantly positive correlation with the best-corrected visual acuity of the right eye, respectively. The ALFF value and ReHo value of the right orbital part of the middle frontal gyrus followed the pattern of normal control < mild to moderate amblyopia < severe amblyopia. CONCLUSION: This study demonstrated that there were changes in specific patterns of ALFF and ReHo in children with right-eye amblyopia of different degrees in brain regions performing visual sensorimotor and attentional control functions.

MDM2-mediated ubiquitination of LKB1 contributes to the development of diabetic cataract.

Diabetic cataract (DC) is a common complication of diabetes mellitus. The epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is a crucial event in the development of DC. Murine double minute 2 (MDM2) is an E3 ubiquitin ligase that promotes EMT by regulating diverse targets. However, little is known about how MDM2 is involved in the pathogenesis of DC. We found the mRNA and protein levels of MDM2 were up-regulated in the lens of DC patients and rats. Thus, high glucose (HG)-induced human lens epithelial cells (HLECs) were constructed for further investigation. The results showed that the level of MDM2 was increased in HG-cultured HLECs, and the MDM2 knockdown alleviated HG-induced abnormal migration, EMT, and oxidative stress damage. Moreover, co-immunoprecipitation and ubiquitination assays demonstrated that MDM2 down-regulated LKB1 expression by ubiquitination degradation. LKB1 was found to be lower expressed in human and rat DC lenses, and HG-stimulated HLECs. Also, LKB1 overexpression mitigated HG-induced dysfunction of HLECs. Finally, our data showed that the changes related to EMT and oxidative stress induced by MDM2 knockdown were restored by down-regulation of LKB1. Together, MDM2 may involve in the pathogenesis of DC through down-regulating LKB1. MDM2 might be an effective therapeutical target of DC.

LncRNA GAS5 regulates migration and epithelial-to-mesenchymal transition in lens epithelial cells via the miR-204-3p/TGFBR1 axis.

Diabetic cataract (DC) is a major ocular complication secondary to diabetes mellitus. The epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is an important event in DC progression. Long non-coding RNAs (lncRNAs) and microRNAs are involved in various biological processes and disorders. The aim of this study was to investigate the roles of lncRNA growth arrest-specific transcript 5 (GAS5) and microRNA-204-3p (miR-204-3p) deregulation in the pathogenic mechanism of high glucose (HG)-stimulated LECs. The results show that GAS5 was up-regulated, whereas miR-204-3p was down-regulated in anterior lens capsule tissues of DC patients and in HG-treated LECs compared to their controls, respectively. Functional experiments suggest that the lentivirus-mediated depletion of GAS5, as well as overexpression of miR-204-3p, suppressed migration and EMT in HG-treated LECs. Further mechanistic studies revealed that lncRNA GAS5/miR-204-3p/type 1 receptor of transforming growth factor-beta (TGFBR1) has a regulatory role in the process. Collectively, we demonstrated that dysregulation of GAS5 affects lens epithelial cell migration and EMT under HG conditions via the miR-204-3p/TGFBR1 axis. The current findings may provide new insights into the molecular mechanisms of DC development.

Circ-GGA3 promotes the biological functions of human lens epithelial cells depending on the regulation of miR-497-5p/SMAD4 axis.

The cause of posterior capsular opacification (PCO) is the dysfunction of lens epithelial cells (LECs). Circular RNA (circRNA) was found to regulate cell biological functions, including LECs. However, the role of circ-GGA3 in PCO formation is unclear. Quantitative real-time PCR was used to measure the expression of circ-GGA3, miR-497-5p and SMAD4. Cell proliferation, invasion and migration were determined via MTT assay, EdU staining, transwell assay and wound healing assay. The protein expression of epithelial-mesenchymal transition (EMT) markers, fibrosis markers, TGF-ß/SMAD pathway markers and SMAD4 were determined by western blot assay. The interaction between miR-497-5p and circ-GGA3 or SMAD4 was confirmed using dual-luciferase reporter assay. Circ-GGA3 was highly expressed in PCO patients, and its silencing inhibited the proliferation, invasion, migration, EMT process and fibrosis of TGF-ß2-induced LECs. Circ-GGA3 could sponge miR-497-5p to regulate SMAD4. Further experiments revealed that miR-497-5p inhibitor recovered the negative regulation of circ-GGA3 knockdown on the biological functions of TGF-ß2-induced LECs, and SMAD4 overexpression also abolished the suppressive effect of miR-497-5p. In addition, circ-GGA3/miR-497-5p/SMAD4 axis could activate the TGF-ß/SMAD pathway. Our results indicated that circ-GGA3 could enhance the biological functions of LECs, suggesting that circ-GGA3 might be a potential target for PCO therapy.

Circ-POLR3A accelerates TGF-ß2-induced promotion in cell viability, migration, and invasion of lens epithelial cells via miR-31/TXNIP signaling cascade.

Posterior capsular opacification (PCO) is the major complication after cataract surgery and can result in secondary vision loss. Circular RNAs (circRNAs) are reported to play critical regulatory roles in multiple cell biological processes. The most common working mechanism of circRNAs is by acting as microRNA sponges. Here, we analyzed the role and mechanism of circRNA RNA polymerase III subunit A (POLR3A) in PCO. Cell viability was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell motility was assessed by transwell and wound healing assays. Dual-luciferase reporter and RNA-pull-down assays were performed to verify the interaction between microRNA-31 (miR-31) and circ-POLR3A or thioredoxin interacting protein (TXNIP). PCO cell model was established by treating SRA01/04 cells with transforming growth factor-ß2 (TGF-ß2). We found that TGF-ß2 enhanced SRA01/04 cell viability, migration, and invasion abilities. Circ-POLR3A expression was upregulated in PCO tissues and TGF-ß2-induced SRA01/04 cells. TGF-ß2 promoted the viability and motility of SRA01/04 cells largely by upregulating circ-POLR3A. Circ-POLR3A negatively regulated the miR-31 level by directly interacting with it. Circ-POLR3A absence-induced influences in TGF-ß2-induced SRA01/04 cells were partly reversed by silencing miR-31. miR-31 is directly bound to the 3'-untranslated region of TXNIP. TXNIP overexpression largely attenuated miR-31 overexpression-mediated effects in TGF-ß2-induced SRA01/04 cells. Circ-POLR3A could elevate the protein expression of TXNIP by sponging miR-31. Exosomes were involved in mediating the delivery of circ-POLR3A in SRA01/04 cells. In conclusion, circ-POLR3A contributed to TGF-ß2-induced promotion of cell viability, migration, and invasion of SRA01/04 cells by targeting miR-31/TXNIP axis.

Exosome-transmitted circ-CARD6 facilitates posterior capsule opacification development by miR-31/FGF7 axis.

BACKGROUND: Posterior capsular opacification (PCO) is the major vision-disrupting complication arising after cataract surgery. Circular RNAs (circRNAs) are biological active RNAs which were involved in various physiological functions. So far, the role of circRNA caspase recruitment domain family member 6 (circ-CARD6) in PCO is still unclear. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression of circ-CARD6, microRNA 31 (miR-31) and fibroblast growth factor 7 (FGF7) message RNA (mRNA). Western blot was used to analyze the protein expression. Transmission electron microscopy (TEM) was employed to capture the exosome image. The proliferation and metastasis were analyzed by cell counting kit-8 (CCK8), transwell and wound healing assays. The potential binding sequences between miR-31 and circ-CARD6 or FGF7 were respectively predicted by Circinteractome and Targetscan online tool, and verified by dual-luciferase reporter and RNA binding protein immunoprecipitation (RIP) assays. RESULTS: Exosome-transmitted circ-CARD6 was highly expressed in PCO tissues and TGF-ß2-treated SRA01/04 cells. Circ-CARD6 deletion repressed the proliferation, metastasis, EMT process and MAPK pathway, which was reversed by anti-miR-31 in TGF-ß2-treated SRA01/04 cells. Meanwhile, circ-CARD6 sponged miR-31 which directly targeted FGF7 in TGF-ß2-treated SRA01/04 cells. FGF7 overexpression allayed miR-31 overexpression-induced suppression in proliferation, metastasis, EMT process and MAPK pathway. Besides, circ-CARD6 regulated FGF7 expression by sponging miR-31. CONCLUSION: Circ-CARD6 promoted PCO development via miR-31/FGF7 axis. This finding might contribute to the development of the targeted therapy for PCO.

LncRNA NEAT1 promotes proliferation, migration, invasion and epithelial-mesenchymal transition process in TGF-ß2-stimulated lens epithelial cells through regulating the miR-486-5p/SMAD4 axis.

BACKGROUND: Abnormal proliferation, metastasis and epithelial-mesenchymal transformation (EMT) of lens epithelial cells (LECs) are direct factors of posterior capsular opacification (PCO). Nuclear enriched abundant transcript 1 (NEAT1) has been shown to promote cell proliferation, metastasis and EMT, but whether it affects the progression of PCO is unclear. METHODS: The expression of NEAT1, microRNA-486-5p (miR-486-5p) and Drosophila mothers against decapentaplegic 4 (SMAD4) was determined using quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation of cells was measured via 3-(4, 5-dimethyl-2 thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Transwell assay was employed to detect the migration and invasion of cells. The levels of EMT marker proteins, SMAD4 protein and transforming growth factor-ß (TGF-ß)/SMAD signaling pathway-related proteins were assessed by western blot (WB) analysis. Further, the relationship between miR-486-5p and NEAT1 or SMAD4 was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and biotin-labeled RNA pull-down assay. RESULTS: NEAT1 is upregulated and miR-486-5p is downregulated in the posterior capsular tissues of PCO patients and TGF-ß2-induced LECs. Interference of NEAT1 reverses the promoting effect of TGF-ß2 on the proliferation, migration, invasion and EMT of LECs. MiR-486-5p can be sponged by NEAT1, and its inhibitor reverses the suppression effect of NEAT1 silencing on the progression of TGF-ß2-induced LECs. SMAD4 functions as a target of miR-486-5p, and its overexpression recovers the inhibition effect of miR-486-5p overexpression on the progression of TGF-ß2-induced LECs. The activity of the TGF-ß/SMAD signaling pathway is regulated by the NEAT1/miR-486-5p/SMAD4 axis. CONCLUSION: Our study shows that NEAT1 has a positive effect on the progression of PCO and is expected to become a new target for PCO treatment.

Matched beam-intensity processing for a deep vertical line array.

A vertical line array can be deployed in deep water below the critical depth, the depth where the sound speed equals the sound speed at the surface, to take advantage of the lower ambient noise level (compared with above the critical depth) for target detection. To differentiate a submerged source from a surface source, a Fourier transform based method [McCargar and Zurk, J. Acoust. Soc. Am. 133, EL320-325 (2013)] was proposed for a narrowband signal that exploits the depth-related harmonic (oscillation) feature of the beam power time series associated with the target arrival. In this paper, incoherent matched beam processing is used to estimate the target depth. Where the replica (calculated) beam intensity or amplitude time series best matches that of the data is used to estimate the source depth. This method is shown, based on simulated data, to provide a better depth resolution in general and better ability to estimate the depth of a very shallow source (say at 10 m) and can be used to complement the Fourier transform based method. It can be extended to process (random) broadband signals and to environments where the Lloyd's mirror theory is not valid.

[Analysis of disease-causing gene mutation in three Chinese families with congenital inherited cataract].

OBJECTIVE: To identify the disease-causing gene mutations in three Chinese pedigrees affected with congenital inherited cataract, in ordre to provide genetic counseling and prenatal diagnosis. METHODS: Using exons combined target region capture sequencing chip to screen the candidate disease-causing mutations, Sanger sequencing was used to confirm the disease-causing mutations. RESULTS: Family 1 was polymorphic cataract, family 2 was cerulean cataract, family 3 was coralliform cataract. The inheritance mode of the three pedigrees consisted with autosomal dominant inheritance. In family 1, a nonsense mutation of CRYßB2 gene c.463C>T in exon 6 result in a p.Q155X amino acid change. In family 2, a missense mutation of of CRYGD gene c.43C>T in exon 2 result in a p.R14C amino acid change. In family 3, a missense mutation of CRYGD gene c.70C>A in exon 2 result in a p.P23T amino aid change. No above-mentioned mutations were found in normal individuals. CONCLUSION: The nonsense mutation c.463C>T (p.Q155X) of CRYßB2 gene, the heterozygous mutations c.43C>T(p.R14C) of CRYGD gene and c.70C>A( p.P23T) of CRYGD gene was the disease-causing gene mutation in family 1, 2 and 3 respectively, our results provid genetic counseling and prenatal diagnosis for these three families.

Sound speed, attenuation, and reflection in gassy sediments.

A predictive model for acoustic dispersion and attenuation in gassy sediments is proposed. The model combines the linear solution for gas-bubble pulsations in a viscoelastic medium with corrected Biot equations involving gas-bubble pulsations. Numerical results for sound speed and attenuation are compared with predictions from Anderson and Hampton's model to demonstrate the advantages of the proposed model. The most important advantage of the current model is that it combines the dispersion regimes associated with gas-bubble pulsations and relative motion between the pore water and solid framework. The reflection coefficient at the water/gassy-sediment interface is derived based on the current model, and numerical results show that gas-bubble resonance can lead to the highest reflection. This model can also be used with a full acoustic inversion to estimate gas-bubble size distributions.

A corrected effective density fluid model for gassy sediments.

A corrected effective density fluid model is developed for predicting sound speed dispersion and attenuation coefficient in gassy sediments. An acoustic experiment was undertaken to measure the attenuation coefficient in a frequency band of 600 to 3000 Hz in gassy unsaturated sand. The measured frequency spectra of the attenuation coefficient show four peaks due to bubble resonance. Then a method of using several modified Gaussian functions to model bubble size distribution is proposed to fit measured attenuation data, which shows that the magnitudes of the fitted model attenuation coefficients are broadly in agreement with those measured attenuation data.

[Protective effect of Salidroside on oxidative damage to human lens epithelial cells].

OBJECTIVE: The aim of the experiment was to investigate the effects of salidroside (Sal) on oxidative damage to human lens epithelial cells (HLEC). METHODS: Experimental study. The cultured HLECwas intervened with hydrogen peroxide (H2O2) which created oxidative damage model to observe the effect of Sal on HLECs. The cultured cells during the logarithmic phase were interposed by different concentrations Sal (0 µmol/L, 10 µmol/L, 30 µmol/L, 50 µmol/L, 100 µmol/L, 200 µmol/L) for 24 h. Then the viability of cells was detected by cell counting Kit-8 (CCK-8) assay. The cells were divided into 5 groups:control group, H2O2 group, Sal low dose group (30 µmol/L Sal+ H2O2 group), Sal middle dose group (50 µmol/L Sal+H2O2 group), Sal high dose group (100 µmol/L Sal+ H2O2 group). The effects of Sal on the apoptosis of the HLEC were determined by Hoechst 33258 staining and flow cytometry assay.Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect B cell lymphoma-2 associated X protein (Bax), B-cell lymphoma-2 (Bcl-2) and Cysteinyl aspartate specific proteinase 3 (Caspase-3) expression. Data between groups were analyzed using one-way analysis of variance (ANOVA), while LSD-t test was used for further comparison between every two groups. RESULTS: CCK-8 result showed that when the concentration of H2O2 was 200 µmol/L, the survival of HLEC inhibition rate was 49.56% ± 7.07%, which was close to the half of the cell survival inhibition rate (IC50). So 200 µmol/L was chosen as the concentration of H2O2 in follow-up experiments. Different concentrations of Sal had no inhibitive influence on HLEC viability. After 24 hours cultivated with Sal (10 µmol/L, 30 µmol/L, 50 µmol/L, 100 µmol/L, 200 µmol/L), the survival rate of HLEC were 100.24% ± 2.07%, 101.18% ± 2.14%, 101.32% ± 2.48%, 101.76% ± 1.93% and 99.28% ± 1.74% correspondingly. There was no significant difference comparing with that of the control group 99.84% ± 2.21% (F = 1.044, P = 0.415; all P > 0.05). Hoechst 33258 staining showed that the chromatin of H2O2 group aggregated and concentrated obviously. And Sal could reduce the aggregation of chromatin of HLEC obviously. FCM results indicated that the apoptosis rate of HLEC was 2.26% ± 0.29% in control group and 44.56% ± 4.28% in H2O2 group. After interposal with Sal (30 µmol/L, 50 µmol/L, 100 µmol/L), the apoptosis rate of HLEC reduced to 31.52% ± 3.05%, 24.06% ± 4.25% and 17.16% ± 2.75%. The differences of apoptosis rates had statistical significance between the five groups (F = 117.082, P < 0.001). The HLEC apoptosis rate decreased with higher Sal concentreations (F = 117.082, P < 0.01). The expression of Bax and Caspase-3 in H2O2 group were higher and the expression of Bcl-2 were lower than that in the control group (P < 0.01). Compared with the control group, the expression of Bcl-2 in three Sal dose groups was higher and the expression of Bax, Caspase-3 was lower, especially the high dose Sal group (Bax:F = 493.554, P < 0.01; Bcl-2:F = 827.820, P < 0.01; Caspase-3:F = 537.237, P < 0.01). CONCLUSIONS: The Sal takes the protective effect on the oxidative damage to HLEC.It could decrease the apoptosis of HLEC.

Prediction of postoperative liver metastasis in pancreatic ductal adenocarcinoma based on multiparametric magnetic resonance radiomics combined with serological markers: a cohort study of machine learning.

OBJECTIVE: To construct and validate a multi-dimensional model based on multiple machine leaning algorithms to predict PCLM using multi-parameter magnetic resonance (MRI) sequences with clinical and imaging parameters. METHODS: A total of 148 PDAC retrospectively examined patients were classified as metastatic or non-metastatic based on results at 3 months after surgery. The radiomics features of the primary tumor were extracted from T2WI images, followed by dimension reduction. Then, multiple machine learning methods were used to construct models. Independent predictors were also screened using multifactor logistic regression and a nomogram was constructed in combination with the radiomics model. Area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used to assess the accuracy and reliability of the nomogram. RESULTS: The diagnostic efficacy of the radiomics model in the training and test set was 0.822 and 0.803, sensitivity was 0.742 and 0.692, and specificity was 0.792 and 0.875, respectively. The diagnostic efficacy of the nomogram in the training and test set was 0.866 and 0.832. CONCLUSION: A radiomics nomogram based on machine learning improved the accuracy of predicting PCLM and may be useful for early preoperative diagnosis.

Integrative neurovascular coupling and neurotransmitter analyses in anisometropic and visual deprivation amblyopia children.

The association between visual abnormalities and impairments in cerebral blood flow and brain region potentially results in neural dysfunction of amblyopia. Nevertheless, the differences in the complex mechanisms of brain neural network coupling and its relationship with neurotransmitters remain unclear. Here, the neurovascular coupling mechanism and neurotransmitter activity in children with anisometropic amblyopia (AA) and visual deprivation amblyopia (VDA) was explored. The neurovascular coupling of 17 brain regions in amblyopia children was significantly abnormal than in normal controls. The classification abilities of coupling units in brain regions differed between two types of amblyopia. Correlations between different coupling effects and neurotransmitters were different. The findings of this study demonstrate a correlation between the neurovascular coupling and neurotransmitter in children with AA and VDA, implying their impaired neurovascular coupling function and potential molecular underpinnings. The neuroimaging evidence revealed herein offers potential for the development of neural therapies for amblyopia.

Predicting pathological complete response to neoadjuvant chemotherapy in breast cancer patients: use of MRI radiomics data from three regions with multiple machine learning algorithms.

OBJECTIVE: To construct a multi-region MRI radiomics model for predicting pathological complete response (pCR) in breast cancer (BCa) patients who received neoadjuvant chemotherapy (NACT) and provide a theoretical basis for the peritumoral microenvironment affecting the efficacy of NACT. METHODS: A total of 133 BCa patients who received NACT, including 49 with confirmed pCR, were retrospectively analyzed. The radiomics features of the intratumoral region, peritumoral region, and background parenchymal enhancement (BPE) were extracted, and the most relevant features were obtained after dimensional reduction. Then, combining different areas, multivariate logistic regression analysis was used to select the optimal feature set, and six different machine learning models were used to predict pCR. The optimal model was selected, and its performance was evaluated using receiver operating characteristic (ROC) analysis. SHAP analysis was used to examine the relationship between the features of the model and pCR. RESULTS: For signatures constructed using three individual regions, BPE provided the best predictions of pCR, and the diagnostic performance of the intratumoral and peritumoral regions improved after adding the BPE signature. The radiomics signature from the combination of all the three regions with the XGBoost machine learning algorithm provided the best predictions of pCR based on AUC (training set: 0.891, validation set: 0.861), sensitivity (training set: 0.882, validation set: 0.800), and specificity (training set: 0.847, validation set: 0.84). SHAP analysis demonstrated that LZ_log.sigma.2.0.mm.3D_glcm_ClusterShade_T12 made the greatest contribution to the predictions of this model. CONCLUSION: The addition of the BPE MRI signature improved the prediction of pCR in BCa patients who received NACT. These results suggest that the features of the peritumoral microenvironment are related to the efficacy of NACT.

[Evaluation of calcium dobesilate for its anti-cataract potential in experimental rat models].

OBJECTIVE: To investigate the preventive and therapeutic effects of agent calcium dobesilate(CDO) with different doses on the galactose cataract of rats. METHODS: We chose fifty Wistar rats at 20- day old. Then, they were divided into 3 groups at random. Choose 10 rats as the control group and gave normal diet; 10 rats as the model group and fed with Gal solution ( drink 12.5% Gal solution from 1 to 7 days and 10%Gal solution from 8 to 21 days except for normal diet ) ; 30 rats as the treatment group and fed with the same Gal solution as the model group, besides they were divided into high dosage group, medium dosage group and low dosage group equally and gave 300 mg×kg(-1)×d(-1), 150 mg×kg(-1)×d(-1), 75 mg×kg(-1)×d(-1) dose of calcium dobesilate respectively from the first day to the end of experiment. The experiment lasts 21 days. Lens opacity were observed and recorded by slit-lamp examination regularly. Activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) and content of malondialdehyde (MDA) were determined to estimate the effect of CDO . Lens fibers changes and Histological changes were observed by scanning electron microscope (SEM) and light microscope (LM) separately. The apoptosis rate of lens epithelium were determined by TUNEL assay. RESULTS: The appearance of Lens opacity in model group was more quickly than that in treatment group in model group, 3 eyes in degree IV, 7 eyes in degree V, while in treatment group, 5 eyes in degree III, 3 eyes in degree IV, 2 eyes in degree V (H = 7.12, P < 0.05). The activity of SOD and GSH-px in treatment group is higher than mode group, but lower than control group on 8th day, there was difference noticed in the activity of SOD (50.01 ± 1.19), (39.39 ± 1.70) , treatment group (46.57 ± 1.09, 46.42 ± 0.87, 45.70 ± 1.46) U/mgProt (F = 88.70, P < 0.05) and the activity of GSH-px (42.92 ± 0.97) , (12.70 ± 1.17) , treatment group (29.16 ± 1.05, 29.08 ± 0.98, 28.25 ± 0.98) nmol/mgprot (F = 1071.89, P < 0.05) ]in 3 groups. The content of MDA in model group (3.43 ± 0.15)nmol/mgprot is higher than treatment group (2.89 ± 0.11, 2.99 ± 0.12, 2.99 ± 0.09)nmol/mgprot (F = 64.62; P < 0.05). There were no statistic significant differences among high dosage group, medium dosage group and low dosage group . The texture of lens fibres detected by SEM in the rats of model was more disorder than treatment group. After HE staining, Lens epithelial cell detected by LM in control group have a clear structure, however, Lens epithelial cell both in model group and treatment group have changed from the initial single layer to multi-storey. Junction between lenses fibers became decreased even disappeared . The apoptosis rate of lens epithelium in treatment group[(2.37 ± 0.17)%, (2.46 ± 0.26)%, (2.79 ± 0.41)%] is higher than control group (0.23 ± 0.07) %, but is much fewer than model group (4.99 ± 0.51) % (χ(2) = 40.41;P < 0.05). CONCLUSION: CDO with different doses could protect lens of rats against galactose damage and there were no significant differences among the different doses of groups.