A novel in-frame deletion in KIF5C gene causes infantile onset epilepsy and psychomotor retardation.

Motor proteins, encoded by Kinesin superfamily (KIF) genes, are critical for brain development and plasticity. Increasing studies reported KIF's roles in neurodevelopmental disorders. Here, a 6 years and 3 months-old Chinese boy with markedly symptomatic epilepsy, intellectual disability, brain atrophy, and psychomotor retardation was investigated. His parents and younger sister were phenotypically normal and had no disease-related family history. Whole exome sequencing identified a novel heterozygous in-frame deletion (c.265_267delTCA) in exon 3 of the KIF5C in the proband, resulting in the removal of evolutionarily highly conserved p.Ser90, located in its ATP-binding domain. Sanger sequencing excluded the proband's parents and family members from harboring this variant. The activity of ATP hydrolysis in vitro was significantly reduced as predicted. Immunofluorescence studies showed wild-type KIF5C was widely distributed throughout the cytoplasm, while mutant KIF5C was colocalized with microtubules. The live-cell imaging of the cargo-trafficking assay revealed that mutant KIF5C lost the peroxisome-transporting ability. Drosophila models also confirmed p.Ser90del's essential role in nervous system development. This study emphasized the importance of the KIF5C gene in intracellular cargo-transport as well as germline variants that lead to neurodevelopmental disorders and might enable clinicians for timely and accurate diagnosis and disease management in the future.

Diffusion-Weighted MRI of the Fetal Brain in Fetal Growth Restriction With Maternal Preeclampsia or Gestational Hypertension.

BACKGROUND: The fetal neurodevelopmental microstructural alterations of intrauterine exposure to preeclampsia (PE) or gestational hypertension (GH) remain unknown. PURPOSE: To evaluate the differences in diffusion-weighted imaging (DWI) of the fetal brain between normotensive pregnancies and PE/GH pregnancies, with a focus on PE/GH pregnancies with fetal growth restriction (FGR). STUDY TYPE: Retrospective matched case-control study. POPULATION: 40 singleton pregnancies with PE/GH complicated by FGR, and 3 paired control groups (PE/GH without FGR, normotensive FGR, normotensive pregnancies) (28-38 gestational weeks). FIELD STRENGTH/SEQUENCE: DWI with single-shot echo-planar imaging at 1.5 Tesla. ASSESSMENT: The apparent diffusion coefficient (ADC) values were calculated in the centrum semi-ovale (CSO), parietal white matter (PWM), frontal white matter (FWM), occipital white matter (OWM), temporal white matter (TWM), basal ganglia, thalamus (THAL), pons, and cerebellar hemisphere. STATISTICAL TESTS: Student t test or Wilcoxon matched test was used to reveal the difference of ADC values among the investigated brain regions. A correlation between gestational age (GA) and ADC values was determined by linear regression analysis. RESULTS: Compared with fetuses in PE/GH without FGR and those with normotensive pregnancies, fetuses in the PE/GH with FGR group had significantly lower average ADC measurements of supratentorial regions (1.65 ± 0.09 vs. 1.71 ± 0.10 10-3 mm2 /sec; vs. 1.73 ± 0.11 10-3 mm2 /sec, respectively). Regions of significantly decreased ADC values in the fetal brain included CSO, FWM, PWM, OWM, TWM and THAL in cases of PE/GH with FGR. ADC values from supratentorial regions in PE/GH pregnancies were not significantly correlated with GA (P = 0.12, 0.26); however, this trend was statistically significant in the normotensive groups. DATA CONCLUSION: ADC values may indicate fetal brain developmental alterations in PE/GH with FGR fetuses but more microscopic and morphological studies are necessary to provide additional evidence to offer a different interpretation of this trend in fetal brain. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 3.

The role of MRI in the prenatal diagnosis and classification of fetal microtia.

OBJECTIVE: To investigate the role of MRI in the diagnosis and classification of fetal microtia. METHODS: Ninety-five fetuses with suspected microtia based on ultrasound and MRI performed within 1 week were enrolled in this study. The diagnosis based on MRI was compared with postnatal diagnosis. Among the microtia cases suspected on the basis of MRI, mild and severe cases were further classified. In addition, external auditory canal (EAC) atresia was evaluated by MRI in 29 fetuses with a gestational age > 28 weeks, and the accuracy of MRI in the diagnosis and classification of microtia was determined. RESULTS: Of 95 fetuses, 83 were considered to have microtia on the basis of MRI, 81 were confirmed to have microtia, and 14 were found to be normal according to postnatal diagnosis. Among 190 external ears in 95 fetuses, 40 ears were suspected to have mild microtia, and 52 ears were suspected to have severe microtia on the basis of MRI. According to the postnatal diagnosis, mild and severe microtia were confirmed in 43 and 49 ears, respectively. Among the 29 fetuses with a gestational age > 28 weeks, 23 ears were suspected to have EAC atresia according to MRI and 21 ears were ultimately confirmed to have EAC atresia. The accuracy of MRI in diagnosing microtia and EAC atresia was 93.68% and 93.10%, respectively. CONCLUSION: MRI shows good performance in diagnosing fetal microtia and has the potential to evaluate its severity on the basis of classification and EAC status. CLINICAL RELEVANCE STATEMENT: This study was aimed at investigating the role of MRI in the diagnosis and classification of fetal microtia. MRI shows good performance and can help evaluate microtia severity and EAC atresia, thus allowing for better clinical management. KEY POINTS: • MRI is a useful adjunct to prenatal ultrasound. • MRI has a higher accuracy rate than ultrasound in diagnosing fetal microtia. • The accurate classification of fetal microtia and the diagnosis of external auditory canal atresia through MRI may help guide clinical management.

Predictive Value of MRI Pelvimetry in Vaginal Delivery and Its Practicability in Prolonged Labour-A Prospective Cohort Study.

BACKGROUND: Pelvic dimensions are crucial variables in the labour process. We used magnetic resonance imaging (MRI) pelvimetry to predict the probability of vaginal delivery and distinguish the cephalopelvic disproportion risk in women with prolonged active labour. METHODS: This prospective cohort study enrolled term nulliparous women willing to undergo MRI pelvimetry and a trial of labour. A nomogram, with vaginal birth as the outcome, was developed and evaluated by calibration curve and decision curve analyses. The pairwise association between maternal and fetal parameters and a prolonged first stage of labour was quantified. RESULTS: Head circumference (HC), abdominal circumference (AC), intertuberous distance (ITD), interspinous diameter (ISD), and body mass index (BMI) were introduced to develop a nomogram with good diagnostic performance (area under the curve = 0.799, sensitivity = 83%, and specificity = 73%). The cephalopelvic index of diameter (CID) in 54 women with a prolonged first stage of labour was much smaller in those who delivered via cesarean section compared with those who delivered vaginally (18.09 ± 1.14 vs. 21.29 ± 1.06; p = 0.046). CONCLUSIONS: An MRI pelvimetry-based nomogram may predict the probability of vaginal delivery. Practitioners should reassess the pelvimetry parameters to decide whether the trial of labour should be continued if it is prolonged.

Comparison of prenatal ultrasound with MRI in the evaluation and prediction of fetal orofacial clefts.

BACKGROUND: Orofacial clefts (OFCs) are common craniofacial abnormalities. This study aimed to compare the diagnostic and predictive values of prenatal ultrasonography (US) and magnetic resonance imaging (MRI). METHODS: We reviewed the newborn physical examinations or fetal autopsy data with OFCs. Between January 2013 and December 2018, the diagnoses resulting from prenatal US and MRI examination were compared retrospectively with the postpartum diagnoses. The diagnostic prediction of prenatal imaging was then determined. RESULTS: 334 infants were identified with OFCs by either newborn physical exam or stillborn autopsy. For detection of OFCs by US, the total accuracy (ACC), true positive rate (TPR), true negative rate (TNR), positive predictive value (PPV), and negative predictive value (NPV) were 99.9% (111,178/110,286), 81.9% (230/281), 99.9% (109,948/110,005), 80.1% (230/287), and 99.9% (109,948/109,999), respectively. For MRI, the ACC, TPR, TNR, PPV, and NPV were 99.8% (4,125/4,132), 89.8% (44/49), 99.9% (4,081/4,083), 95.7% (44/46), and 99.9% (4,081/4,086), respectively. When we compared the predictive values between prenatal US and MRI, there were significant differences in the PPV of OFCs (P < 0.05), NPV of OFCs (P < 0.05), TPR of CLO (P < 0.001), PPV of CLP (P < 0.05), and TPR of CPO (P < 0.05). CONCLUSION: Our results suggest that prenatal US could be effective for diagnosing and ruling out fetal OFCs. Diagnostic confidence is significantly improved when fetal MRI is used to assess fetal OFCs as an adjunct to US examination.

Association of Corpus Callosum Development With Fetal Growth Restriction and Maternal Preeclampsia or Gestational Hypertension.

Importance: It remains unknown whether neurodevelopmental impairments are directly associated with the structural development of the brain in offspring with fetal growth restriction (FGR) and mothers with preeclampsia (PE) or gestational hypertension (GH). Objectives: To assess whether fetal corpus callosum (CC) development differed among pregnancies with PE or GH with FGR, pregnancies with PE or GH without FGR, and normotensive pregnancies, particularly the severity of maternal disease and FGR, and to identify the association between adverse perinatal outcomes and structural development of the CC in fetuses with FGR in pregnancies with PE or GH. Design, Setting, and Participants: This retrospective matched case-control study was conducted between January 1, 2014, and January 31, 2021, at Women's Hospital, Zhejiang University School of Medicine in Hangzhou, China. The participant group included cases of singleton pregnancies with PE or GH with FGR; the control groups included cases with PG or GH without FGR and cases with paired normotensive pregnancy. Exposures: Maternal PE or GH and FGR. Main Outcomes and Measures: The length, thickness, total area, subdivision areas, and apparent diffusion coefficient (ADC) values of fetal CC were measured on magnetic resonance imaging (MRI) and analyzed. The association between adverse perinatal outcomes and structural development of CC was further investigated. Results: A total of 56 pregnant individuals with singleton pregnancies and PE or GH and fetuses with FGR were enrolled (maternal median [IQR] age, 29.0 [26.0-34.0] years; mean [SD] gestational age at MRI, 33.6 [2.5] weeks). Significant patterns of decreased median (IQR) fetal CC length (0.4284 [0.4079-0.4470] mm vs 0.4614 [0.4461-0.4944] mm, P < .001, vs 0.4591 [0.4310-0.4927] mm, P < .001) and mean (SD) CC total area (1.0779 [0.1931] mm2 vs 1.1896 [0.1803] mm2, P = .001, vs 1.1438 [0.1935] mm2, P = .02), adjusted for the cephalic index, was observed in cases of PE or GH with FGR compared with cases without FGR and cases with normotensive pregnancy. The splenium region of fetal CC also exhibited the distinct alterations in macrostructural development (with FGR: 0.3149 [0.0697] mm2 vs without FGR: 0.3727 [0.0698] mm2, P < .001, vs normotensive pregnancies: 0.3565 [0.0763] mm2, P < .001) and microstructural development (median [IQR] ADC values: 1.47 [1.38-1.57] × 10-3 mm2/s vs 1.57 [1.53-1.63] × 10-3 mm2/s, P = .009, vs 1.63 [1.50-1.70] × 10-3 mm2/s, P < .001) in all groups. Furthermore, significant associations were found between structural abnormality of the splenium region and adverse perinatal outcomes in the PE or GH with FGR group (mean [SD] ADC value: 1.40 [0.07] × 10-3 mm2/s; P = .04). Conclusions and Relevance: Results of this study suggest that, in fetuses with FGR in pregnancies with PE or GH, decreased structural development of the CC, predominantly the splenium region, may be significantly associated with a higher risk of adverse perinatal outcomes and may be regarded as an MRI-based biomarker for better prenatal counseling and early management decisions.

Magnetic Resonance Imaging-Based Nomogram to Antenatal Predict Cesarean Delivery for Cephalopelvic Disproportion in Primiparous Women.

BACKGROUND: Cephalopelvic disproportion (CPD)-related obstructed labor is associated with maternal and neonatal morbidity and mortality. Accurate prediction of whether a primiparous woman is at high risk of an unplanned cesarean delivery would be a major advance in obstetrics. PURPOSE: To develop and validate a predictive model assessing the risk of cesarean delivery in primiparous women based on MRI findings. STUDY TYPE: Prospective. POPULATION: A total of 150 primiparous women with clinical findings suggestive of CPD. FIELD STRENGTH/SEQUENCE: T1-weighted fast spin-echo sequences, single-shot fast spin-echo (SSFSE) T2-weighted sequences at 1.5 T. ASSESSMENT: Pelvimetry and fetal biometry were assessed independently by two radiologists. A nomogram model combined that the clinical and MRI characteristics was constructed. STATISTICAL TESTS: Univariable and multivariable logistic regression analyses were applied to select independent variables. Receiver operating characteristic (ROC) analysis was performed, and the discrimination of the model was assessed by the area under the curve (AUC). Calibration was assessed by calibration plots. Decision curve analysis was applied to evaluate the net clinical benefit. A P value below 0.05 was considered to be statistically significant. RESULTS: In multivariable modeling, the maternal body mass index (BMI) before delivery, bilateral femoral head distance, obstetric conjugate, fetal head circumference, and fetal abdominal circumference was significantly associated with the likelihood of cesarean delivery. The discrimination calculated as the AUC was 0.838 (95% confidence interval [CI]: 0.774-0.902). The sensitivity and specificity of the nomogram model were 0.787 and 0.764, and the positive predictive and negative predictive values were 0.696 and 0.840, respectively. The model demonstrated satisfactory calibration (calibration slope = 0.945). Moreover, the decision curve analysis proved the superior net benefit of the model compared with each factor included. DATA CONCLUSION: Our study might provide a nomogram model that could identify primiparous women at risk of cesarean delivery caused by CPD based on MRI measurements. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Outcomes of sonographically-suspected fetal intra-abdominal cysts: Surgical intervention, conservative management and spontaneous regression.

Objective: The prenatal diagnosis of fetal intra-abdominal cysts is challenging. This study aimed to evaluate the diagnostic ability of prenatal ultrasound for fetal intra-abdominal cysts and to develop a predictive method for pre- and postnatal outcomes. Methods: We retrospectively reviewed fetuses with ultrasound-detected intra-abdominal cysts between January 2013 and January 2020. The maternal-fetal clinical characteristics and ultrasound parameters were integrated into a model of pre- or postnatal outcomes. Results: The study enrolled 190 eligible fetuses, including 94 cases of spontaneous regression, 33 cases of conservative management and 63 cases of surgical intervention. For the 63 cases of surgical intervention, prenatal ultrasound was found to identify fetal intra-abdominal cysts with 80.00% sensitivity (95% CI: 67.03%-89.57%), 37.50% specificity (95% CI: 8.52%-75.51%), 89.80% positive predictive value (95% CI: 83.51%-93.86%), 21.43% negative predictive value (95% CI: 8.80%-43.53%) and 74.60% accuracy (95% CI: 62.06%-84.73%). The predictive model of prenatal spontaneous regression was as follows: y = -3.291 + 0.083 × gestational age + 1.252 × initial diameter, with an area under the curve (AUC) of 0.819 (95% CI: 0.739-0.899) and an optimal cut-off value of 0.74. The large cyst diameter before delivery was an independent predictor of postnatal surgical intervention (p < 0.001), with an AUC of 0.710 (95% CI: 0.625-0.794) and an optimal cut-off value of 3.35 cm. Conclusion: Although ultrasound has a limited ability in the accurate diagnosis of fetal abdominal cysts, a simple method of measuring the diameter can predict fetal outcomes and identify the cases that may require surgical intervention or spontaneous regression.

Diffusion MRI Based Myometrium Tractography for Detection of Placenta Accreta Spectrum Disorder.

BACKGROUND: Prenatal diagnosis of placenta accreta spectrum (PAS) disorders is difficult. Magnetic resonance imaging (MRI) has been shown to be a useful supplementary method to ultrasound. PURPOSE: To investigate diffusion MRI (dMRI) based tractography as a tool for detecting PAS disorders, and to evaluate its performance compared with anatomical MRI. STUDY TYPE: Prospective. POPULATION: Forty-seven pregnant women in the third trimester with risk factors for PAS. FIELD STRENGTH/SEQUENCE: Using fast imaging employing steady-state acquisition and high-angular resolution dMRI at 1.5 Tesla. ASSESSMENT: Diagnosis of PAS was performed by three radiologists based on the dMRI-based feature of myometrial fiber discontinuity and on commonly used anatomical features including presence of dark band, discontinuous myometrium and bladder wall interruption. We evaluated the sensitivity, specificity, accuracy, and area-under-the-curve (AUC) of the individual features and established an integrated model with random forest analysis. STATISTICAL TESTS: Maternal age and gestational age at scan were compared between PAS and control group using a t-test, and childbearing history was compared using a chi-squared test. The random forest model was employed to combine the anatomical and dMRI features with 5-fold cross-validation, and the weight of each feature was normalized to evaluate its importance in predicting PAS. RESULTS: Based on surgical pathology reports, 16 out of 47 patients had confirmed PAS. The anatomical feature of dark bands and tractography marker achieved the highest AUC of 0.842 for predicting PAS, and the integrated anatomical and tractography features further improved the AUC of 0.880 with an accuracy of 87.2%. The tractography feature contributed most (30.1%) to the integrated model. DATA CONCLUSION: Myometrial tractography demonstrated superior performance in detecting PAS. Moreover, the combination of dMRI-based tractography and anatomical MRI could potentially improve the diagnosis of PAS disorders in clinical practice. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Prussian Blue/Calcium Peroxide Nanocomposites-Mediated Tumor Cell Iron Mineralization for Treatment of Experimental Lung Adenocarcinoma.

Current lung cancer diagnosis methods encounter delayed visual confirmation of tumor foci and low-resolution metrics in imaging findings, which delays the early treatment of tumors. Here, we developed a potent lung cancer imaging and treatment strategy centered around a nanotransformational concept of tumor iron mineralization in situ, which employs Prussian blue/calcium peroxide nanocomposites as a precursor. The resultant iron mineralization in tumor cells greatly facilitates the early and differential diagnosis of lung carcinoma from benign nodules via medical imaging, meanwhile introducing oxidative stress to activate the cellular apoptosis and ferroptosis pathways, resulting in inhibition of the malignant behavior of tumor cells. Tumor-microenvironment-triggered iron mineralization enables integration of the detection and prevention of tumor metastasis at its early stages with no assistance of toxic drugs, which offers a potential solution for the precise management of lung cancer with ideal outcomes.

Measurement of the Brain Volume/Liver Volume Ratio by Three-Dimensional MRI in Appropriate-for-Gestational Age Fetuses and Those With Fetal Growth Restriction.

BACKGROUND: Fetal growth restriction (FGR) is associated with a high fetal brain volume/liver volume (FBV/FLV) ratio. Ultrasound may not always be reliable, which has prompted further investigation of MRI techniques. PURPOSE: To determine the relationship between FBV/FLV ratio, as measured by MRI, and gestational age (GA) in normal fetuses and those with FGR. STUDY TYPE: Retrospective. POPULATION: One hundred and forty seven singleton pregnancies including 105 appropriate-for-gestational age (AGA) fetuses and 42 FGR fetuses. FIELD STRENGTH/SEQUENCE: Three-dimensional fast imaging employing steady-state acquisition at 1.5 T. ASSESSMENT: The FBV and FLV were measured by three radiologists. The inter- and intraobserver agreements, the correlation between FBV/FLV ratio, and advancing GA were evaluated; the diagnostic value of FBV/FLV ratio was evaluated and compared with head circumference/abdominal circumference (HC/AC) ratio measured by ultrasound. STATISTICAL TESTS: Intraclass correlation coefficient (ICC) was used to determine inter- and intraobserver agreements. Regression analysis was used to assess the correlation between FBV/FLV ratio and advancing GA. The diagnostic value of the FBV/FLV ratio was examined by the area under the receiver operating characteristic (ROC) curve. RESULTS: The inter- and intraobserver agreements were excellent with an interobserver ICC of 0.984 and intra-observer ICCs of 0.989, 0.994, and 0.995. The FBV/FLV ratio in AGA fetuses decreased significantly with advancing GA (Pearson correlation coefficient = -0.844). The FBV/FLV ratio in FGR fetuses was significantly higher than that in AGA fetuses. To identify fetuses at high risk for FGR using the FBV/FLV ratio, the area under the ROC curve was 0.978, with an optimal cut-off value of 4.10. The sensitivity of FBV/FLV ratio in identifying FGR was significantly higher than that of HC/AC ratio (0.929 vs. 0.529). DATA CONCLUSION: An inverse correlation exists between FBV/FLV ratio and advancing GA in normal fetuses. A high FBV/FLV ratio may be used to ascertain fetuses at high risk for FGR. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 3.

Prenatal Diagnosis and Classification of Fetal Hypospadias: The Role and Value of Magnetic Resonance Imaging.

BACKGROUND: Prenatal diagnosis and classification of hypospadias are difficult and of value for management during perinatal and neonatal periods. The conventional approach for prenatal diagnosis of hypospadias is ultrasound; however, this technique may be inconclusive in certain cases, which prompts for further exploration with magnetic resonance imaging (MRI). PURPOSE: To investigate the role of MRI in the prenatal diagnosis and classification of fetuses with hypospadias. STUDY TYPE: Retrospective. POPULATION: Thirty-five fetuses (median gestational age = 37, range 24-39 weeks) with possible hypospadias. FIELD STRENGTH/SEQUENCE: Single-shot fast spin echo T2-weighted imaging, fast imaging employing steady-state acquisition (FIESTA), and three-dimensional FIESTA acquired at 1.5 T. ASSESSMENT: Diagnosis and classification of hypospadias using MRI were performed by three experienced radiologists based on MRI features, including a short penile shaft, abnormal penile tip, penile curvature, bifid scrotum, "tulip sign," and penoscrotal transposition. The accuracy of MRI in the diagnosis and classification of hypospadias was assessed in comparison to postnatal clinical diagnosis. The interobserver agreement between radiologists was also assessed. STATISTICAL TESTS: Kendall's W test was applied to assess the interobserver agreement between radiologists. Taking postnatal clinical diagnosis as the reference standard, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated. RESULTS: Of the 35 fetuses, 24 cases were confirmed as hypospadias through postnatal clinical diagnosis. The interobserver agreement between radiologists was substantial (Kendall's W = 0.781, P < 0.001). Of the 24 confirmed cases (13 cases of severe hypospadias and 11 cases of mild hypospadias), 22 cases were correctly diagnosed by MRI. The accuracy of MRI in the diagnosis of hypospadias, severe hypospadias, and mild hypospadias was 85.71%, 82.86%, and 80.00%, respectively. DATA CONCLUSION: MRI has good performance in the diagnosis of fetal hypospadias. In addition, MRI could help evaluate the severity of fetal hypospadias. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Role of prenatal imaging in the diagnosis and management of fetal facio-cervical masses.

Congenital facio-cervical masses can be a developmental anomaly of cystic, solid, or vascular origin, and have an inseparable relationship with adverse prognosis. This retrospective cross-sectional study aimed at determining on the prenatal diagnosis of congenital facio-cervical masses, its management and outcome in a large tertiary referral center. We collected information on prenatal clinical data, pregnancy outcomes, survival information, and final diagnosis. Out of 130 cases of facio-cervical masses, a total of 119 cases of lymphatic malformations (LMs), 2 cases of teratoma, 2 cases of thyroglossal duct cyst, 4 cases of hemangioma, 1 case of congenital epulis, and 2 cases of dermoid cyst were reviewed. The accuracy of prenatal ultrasound was 93.85% (122/130). Observations of diameters using prenatal ultrasound revealed that the bigger the initial diameter is, the bigger the relative change during pregnancy. Magnetic resonance imaging (MRI) revealed that 2 cases of masses were associated with airway compression. In conclusion, ultrasound has a high overall diagnostic accuracy of fetal face and neck deformities. Prenatal US can enhance the management of ambulatory monitoring and classification. Furthermore, MRI provided a detailed assessment of fetal congenital malformations, as well as visualization of the trachea, presenting a multi-dimensional anatomical relationship.

Targeted GSH-exhausting and hydroxyl radical self-producing manganese-silica nanomissiles for MRI guided ferroptotic cancer therapy.

Ferroptosis, a cell death path induced by the generation of reactive oxygen species (ROS), will cause the accumulation of lipid peroxides (PL-PUFA-OOH) and achieve potent tumor-regression. However, glutathione (GSH)-dependent glutathione peroxidase 4 (GPx4) can reduce PL-PUFA-OOH and antagonize the ferroptosis inducing effect of ROS. Herein, folate-PEG modified dihydroartemisinin (DHA) loaded manganese doped mesoporous silica nanoparticles (described as nanomissiles) were constructed for integrating the effect of GSH exhaustion and ROS generation. After endocytosis by tumor cells, intracellular GSH triggered the degradation of nanomissiles, which allowed the simultaneous release of DHA and Fenton catalytic Mn2+ due to the redox reaction between the manganese-oxygen bonds and GSH. The degradation would lead to GSH exhaustion, activation of Mn2+-based magnetic resonance imaging (MRI), and DHA-driven ˙OH generation. The GSH-free environment inhibited the activity of GPx4 and enhanced the accumulation of PL-PUFA-OOH oxidized by ˙OH. Furthermore, the cooperative effects suppressed tumor metastasis by destroying the structure of polyunsaturated fatty acids in the cell membranes and showed potent antitumor activity. This innovative ferroptotic therapy integrating the GSH exhaustion and ROS generation will be a promising strategy for cancer therapy.

The prenatal diagnosis and classification of cleft palate: the role and value of magnetic resonance imaging.

OBJECTIVE: The aim of this study was to evaluate the value of MRI in the prenatal diagnosis and classification of cleft palate (CP). METHODS: We collected 94 fetal cases that were suspected of cleft palate with or without cleft lip by prenatal ultrasound (US) and then carried out further MRI to examine the entire body of each fetus within 1 week. The diagnoses resulting from MRI and US examination were compared separately with the final diagnoses obtained from postnatal physical examination or fetal autopsy. The diagnostic accuracy between MRI and US was then determined. RESULTS: During the follow-up period, the results for 6 fetuses (6.38%) were lost. Of the remaining 88 cases, the final diagnoses identified 23 cases of cleft lip (CL), 45 cases of unilateral cleft lip with cleft palate (UCLP), 4 cases of median cleft lip with cleft palate (MCLP), 12 cases of bilateral cleft lip with cleft palate (BCLP), 3 cases of unilateral cleft lip and cleft alveolus (CLA), and 1 case of isolated cleft palate (CPO). The total accuracy rate of US was 59.09%, while that of MRI was 92.05%. More importantly, 81 cases were accurately identified by MRI; the accuracy rate for CL, UCLP, MCLP, BCLP, CLA, and CPO was 86.96%, 95.56%, 100%, 91.67%, 66.67%, and 100%, respectively. CONCLUSION: Our results suggest that MRI could be a useful adjunct to US examination in the prenatal diagnosis of fetuses with cleft palate, and further demonstrates the classification and degree of involvement of the cleft palate. KEY POINTS: • MRI is a useful adjunct to prenatal ultrasound. • MRI has a higher accuracy rate for CP. • The accurate classification of CP diagnosed by MRI can guide clinical management.