Single-cell analysis of refractory anti-SRP necrotizing myopathy treated with anti-BCMA CAR-T cell therapy.

Immune-mediated necrotizing myopathy (IMNM) is an autoimmune disorder associated with the presence of autoantibodies, characterized by severe clinical presentation with rapidly progressive muscular weakness and elevated levels of creatine kinase, while traditional pharmacological approaches possess varying and often limited effects. Considering the pathogenic role of autoantibodies, chimeric antigen receptor (CAR)-T cells targeting B cell maturation antigen (BCMA) have emerged as a promising therapeutic strategy. We reported here a patient with anti-signal recognition particle IMNM refractory to multiple available therapies, who was treated with BCMA-targeting CAR-T cells, exhibited favorable safety profiles, sustained reduction in pathogenic autoantibodies, and persistent clinical improvements over 18 mo. Longitudinal single-cell RNA, B cell receptor, T cell receptor sequencing analysis presented the normalization of immune microenvironment after CAR-T cell infusion, including reconstitution of B cell lineages, replacement of T cell subclusters, and suppression of overactivated immune cells. Analysis on characteristics of CAR-T cells in IMNM demonstrated a more active expansion of CD8+ CAR-T cells, with a dynamic phenotype shifting pattern similar in CD4+ and CD8+ CAR-T cells. A comparison of CD8+ CAR-T cells in patients with IMNM and those with malignancies collected at different timepoints revealed a more NK-like phenotype with enhanced tendency of cell death and neuroinflammation and inhibited proliferating ability of CD8+ CAR-T cells in IMNM while neuroinflammation might be the distinct characteristics. Further studies are warranted to define the molecular features of CAR-T cells in autoimmunity and to seek higher efficiency and longer persistence of CAR-T cells in treating autoimmune disorders.

Iodine Adsorption-Desorption-Induced Structural Transformation and Improved Ag+ Turn-On Luminescent Sensing Performance of a Nonporous Eu(III) Metal-Organic Framework.

Posttreatment of pristine metal-organic frameworks (MOFs) with suitable vapor may be an effective way to regulate their structures and properties but has been less explored. Herein, we report an interesting example in which a crystalline nonporous Eu(III)-MOF was transferred to a porous amorphous MOF (aMOF) via iodine vapor adsorption-desorption posttreatment, and the resulting aMOF showed improved turn-on sensing properties with respect to Ag+ ions. The crystalline Eu-MOF, namely, Eu-IPDA, was assembled from Eu(III) and 4,4'-{4-[4-(1H-imidazol-1-yl)phenyl]pyridine-2,6-diyl}dibenzoic acid (H2IPDA) and exhibited a two-dimensional (2D) coordination network based on one-dimensional secondary building blocks. The close packing of the 2D networks gives rise to a three-dimensional supramolecular framework without any significant pores. Interestingly, the nonporous Eu-IPDA could absorb iodine molecules when Eu-IPDA crystals were placed in iodine vapor at 85 °C, and the adsorption capacity was 1.90 g/g, which is comparable to those of many MOFs with large BET surfaces. The adsorption of iodine is attributed to the strong interactions among the iodine molecule, the carboxy group, and the N-containing group and leads to the amorphization of the framework. After immersion of the iodine-loaded Eu-IPDA in EtOH, approximately 89.7% of the iodine was removed, resulting in a porous amorphous MOF, denoted as a-Eu-IPDA. In addition, the remaining iodine in the a-Eu-IPDA framework causes strong luminescent quenching in the fluorescence emission region of the Eu(III) center when compared with that in Eu-IPDA. The luminescence intensity of a-Eu-IPDA in water suspensions was significantly enhanced when Ag+ ions were added, with a detection limit of 4.76 × 10-6 M, which is 1000 times that of pristine Eu-IPDA. It also showed strong anti-interference ability over many common competitive metal ions and has the potential to sense Ag+ in natural water bodies and traditional Chinese medicine preparations. A mechanistic study showed that the interactions between Ag+ and the absorbed iodine, the carboxylate group, and the N atoms all contribute to the sensing performance of a-Eu-IPDA.

The association between sedentary behavior and obstructive sleep apnea: a cross-sectional study from the NHANES (2007-2008 to 2015-2020).

BACKGROUND: Sedentary behavior (SB) may contribute to obesity and lower extremity fluid retention, which may favor the development of obstructive sleep apnea (OSA). However, linking sedentary behavior to OSA is unclear. The purpose of this study was to determine if there is an association between SB and OSA. METHODS: Three typical questions in the NHANES questionnaire(①The frequency of feeling excessively sleepy per month. ②The frequency of gasping, snorting or stopping breathing per week. ③The frequency of snoring per week.) have been used for the assessment of OSA. A physical activity questionnaire(On a typical day, the amount of time you spend sitting or reclining.) was used to assess SB. This secondary analysis included National Health and Nutrition Examination Survey (NHANES) participants (unweighted = 20,115). Weighted sample and multiple logistic regression complex sample analysis techniques were used in this study. RESULTS: After adjustment for confounders, participants with SB(> 8 h/d) had a higher risk of OSA compared to SB(< 4 h/d). Stratified analysis by gender showed that there was no significant association of SB and OSA in men. However, in women, with SB(< 4 h/d) as the reference, participants with(≥ 4 h/d) had an increased risk of OSA. By age-stratified analysis, the association of SB with OSA was stronger among older participants. CONCLUSION: Analysis in this study showed a positive association between SB and OSA, more pronounced in women and participants older than 60 years old.

Asymmetric Carbene-Alkyne Metathesis-Mediated Cascade: Synthesis of Benzoxazine Polychiral Polyheterocycles and Discovery of a Novel Pain Blocker.

This study introduces a novel approach for synthesizing Benzoxazine-centered Polychiral Polyheterocycles (BPCPHCs) via an innovative asymmetric carbene-alkyne metathesis-triggered cascade. Overcoming challenges associated with intricate stereochemistry and multiple chiral centers, the catalytic asymmetric Carbene Alkyne Metathesis-mediated Cascade (CAMC) is employed using dirhodium catalyst/Brønsted acid co-catalysis, ensuring precise stereo control as validated by X-ray crystallography. Systematic substrate scope evaluation establishes exceptional diastereo- and enantioselectivities, creating a unique library of BPCPHCs. Pharmacological exploration identifies twelve BPCPHCs as potent Nav ion channel blockers, notably compound 8 g. In vivo studies demonstrate that intrathecal injection of 8 g effectively reverses mechanical hyperalgesia associated with chemotherapy-induced peripheral neuropathy (CIPN), suggesting a promising therapeutic avenue. Electrophysiological investigations unveil the inhibitory effects of 8 g on Nav1.7 currents. Molecular docking, dynamics simulations and surface plasmon resonance (SPR) assay provide insights into the stable complex formation and favorable binding free energy of 8 g with C5aR1. This research represents a significant advancement in asymmetric CAMC for BPCPHCs and unveils BPCPHC 8 g as a promising, uniquely acting pain blocker, establishing a C5aR1-Nav1.7 connection in the context of CIPN.

Quercetin, Main Active Ingredient of Moutan Cortex, Alleviates Chronic Orofacial Pain via Block of Voltage-Gated Sodium Channel.

BACKGROUND: Chronic orofacial pain (COP) therapy is challenging, as current medical treatments are extremely lacking. Moutan Cortex (MC) is a traditional Chinese medicine herb widely used for chronic inflammatory diseases. However, the mechanism behind MC in COP therapy has not been well-established. The purpose of this study was to identify the active ingredients of MC and their specific underlying mechanisms in COP treatment. METHODS: In this study, the main active ingredients and compound-target network of MC in COP therapy were identified through network pharmacology and bioinformatics analysis. Adult male Sprague-Dawley rats received oral mucosa lipopolysaccharide (LPS) injection to induce COP. Pain behaviors were evaluated by orofacial mechanical nociceptive assessment after intraganglionar injection. In vitro inflammatory cytokines in LPS-pretreated human periodontal ligament stem cells (hPDLSCs) and rat primary cultural trigeminal ganglion (TG) neurons were quantified by real-time quantitative polymerase chain reaction (RT-qPCR). Schrödinger software was used to verify the molecular docking of quercetin and critical targets. Whole-cell recording electrophysiology was used to evaluate the effect of quercetin on voltage-gated sodium (Na v ) channel in rat TG neurons. RESULTS: The assembled compound-target network consisted of 4 compounds and 46 targets. As 1 of the active components of MC correlated with most related targets, quercetin alleviated mechanical allodynia in LPS-induced rat model of COP (mechanical allodynia threshold median [interquartile range (IQR) 0.5 hours after drug administration: vehicle 1.3 [0.6-2.0] g vs quercetin 7.0 [6.0-8.5] g, P = .002). Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that immune response and membrane functions play essential roles in MC-COP therapy. Five of the related targets were identified as core targets by protein-protein interaction analysis. Quercetin exerted an analgesic effect, possibly through blocking Na v channel in TG sensory neurons (peak current density median [IQR]: LPS -850.2 [-983.6 to -660.7] mV vs LPS + quercetin -589.6 [-711.0 to -147.8] mV, P = .006) while downregulating the expression level of proinflammatory cytokines-FOS (normalized messenger RNA [mRNA] level mean ± standard error of mean [SEM]: LPS [2. 22 ± 0.33] vs LPS + quercetin [1. 33 ± 0.14], P = .034) and TNF-α (normalized mRNA level mean ± SEM: LPS [8. 93 ± 0.78] vs LPS + quercetin [3. 77 ± 0.49], P < .0001). CONCLUSIONS: Identifying Na v as the molecular target of quercetin clarifies the analgesic mechanism of MC, and provides ideas for the development of novel selective and efficient chronic pain relievers.

Synthesis and In Vivo Antiarrhythmic Activity Evaluation of Novel Scutellarein Analogues as Voltage-Gated Nav1.5 and Cav1.2 Channels Blockers.

Malignant cardiac arrhythmias with high morbidity and mortality have posed a significant threat to our human health. Scutellarein, a metabolite of Scutellarin which is isolated from Scutellaria altissima L., presents excellent therapeutic effects on cardiovascular diseases and could further be metabolized into methylated forms. A series of 22 new scutellarein derivatives with hydroxyl-substitution based on the scutellarin metabolite in vivo was designed, synthesized via the conjugation of the scutellarein scaffold with pharmacophores of FDA-approved antiarrhythmic medications and evaluated for their antiarrhythmic activity through the analyzation of the rat number of arrhythmia recovery, corresponding to the recovery time and maintenance time in the rat model of barium chloride-induced arrhythmia, as well as the cumulative dosage of aconitine required to induce VP, VT, VF and CA in the rat model of aconitine-induced arrhythmia. All designed compounds could shorten the time of the arrhythmia continuum induced by barium chloride, indicating that 4'-hydroxy substituents of scutellarein had rapid-onset antiarrhythmic effects. In addition, nearly all of the compounds could normalize the HR, RR, QRS, QT and QTc interval, as well as the P/T waves' amplitude. The most promising compound 10e showed the best antiarrhythmic activity with long-term efficacy and extremely low cytotoxicity, better than the positive control scutellarein. This result was also approved by the computational docking simulation. Most importantly, patch clamp measurements on Nav1.5 and Cav1.2 channels indicated that compound 10e was able to reduce the INa and ICa in a concentration-dependent manner and left-shifted the inactivation curve of Nav1.5. Taken together, all compounds were considered to be antiarrhythmic. Compound 10e even showed no proarrhythmic effect and could be classified as Ib Vaughan Williams antiarrhythmic agents. What is more, compound 10e did not block the hERG potassium channel which highly associated with cardiotoxicity.

Regulating the Porosity and Iodine Adsorption Properties of Metal-Organic Framework Glass via an Ammonia-Immersion Approach.

Metal-organic framework (MOF) glass is a new type of glass material, but it usually lacks sufficient porosity. Thus, regulating the pore structure of MOF glass to improve its adsorption performance is very important. Herein, we found that the porosity of MOF glasses agZIF-62 and agZIF-76 can be regulated via an ammonia-immersion approach. After ammonia immersion, the resulting agZIF-62-NH3 and agZIF-76-NH3 could be maintained in their glass states or converted to their amorphous states, respectively. Their porosity changed according to the gas adsorption experiments. Notably, compared with agZIF-62 and agZIF-76, the iodine uptake capacities for agZIF-62-NH3 and agZIF-76NH3 increased by 12 and 21 times, respectively. This work shows that the subsequent treatment of MOF glass can regulate their adsorption performance.

Reversal of Peripheral Neuropathic Pain by the Small-Molecule Natural Product Narirutin via Block of Nav1.7 Voltage-Gated Sodium Channel.

Neuropathic pain is a refractory chronic disease affecting millions of people worldwide. Given that present painkillers have poor efficacy or severe side effects, developing novel analgesics is badly needed. The multiplex structure of active ingredients isolated from natural products provides a new source for phytochemical compound synthesis. Here, we identified a natural product, Narirutin, a flavonoid compound isolated from the Citrus unshiu, showing antinociceptive effects in rodent models of neuropathic pain. Using calcium imaging, whole-cell electrophysiology, western blotting, and immunofluorescence, we uncovered a molecular target for Narirutin's antinociceptive actions. We found that Narirutin (i) inhibits Veratridine-triggered nociceptor activities in L4-L6 rat dorsal root ganglion (DRG) neurons, (ii) blocks voltage-gated sodium (NaV) channels subtype 1.7 in both small-diameter DRG nociceptive neurons and human embryonic kidney (HEK) 293 cell line, (iii) does not affect tetrodotoxin-resistant (TTX-R) NaV channels, and (iv) blunts the upregulation of Nav1.7 in calcitonin gene-related peptide (CGRP)-labeled DRG sensory neurons after spared nerve injury (SNI) surgery. Identifying Nav1.7 as a molecular target of Narirutin may further clarify the analgesic mechanism of natural flavonoid compounds and provide an optimal idea to produce novel selective and efficient analgesic drugs.

Nickel-Catalyzed Asymmetric Hydroaryloxy- and Hydroalkoxycarbonylation of Cyclopropenes.

The asymmetric Reppe carbonylation reactions provide a straightforward access to α-chiral carbonyl compounds. The reported paradigms predominantly adopted precious palladium as the catalyst. Here we report a nickel-catalyzed asymmetric carbonylation of cyclopropenes with phenyl formate and CO/ROH, respectively. This asymmetrical synthetic protocol features high atom economy, good functional group tolerance, which rapidly constructs polysubstituted cyclopropanecarboxylic derivatives with excellent diastereo- and enantioselectivity. The synthetic utility is demonstrated by facile conversion of the chiral products into bioactive molecules such as (-)-Tranylcypromine and (-)-Lemborexant.

Perfusion-based functional magnetic resonance imaging for differentiating serous borderline ovarian tumors from early serous ovarian cancers in a rat model.

BACKGROUND: Differentiation of borderline tumors from early ovarian cancer has recently received increasing attention, since borderline tumors often affect young women of childbearing age who desire to preserve fertility. However, previous studies have demonstrated that non-enhanced magnetic resonance imaging (MRI) sequences cannot sufficiently differentiate these tumors. PURPOSE: To investigate the value of dynamic contrast-enhanced MRI (DCE-MRI) and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in differentiating serous borderline ovarian tumors (SBOT) from early serous ovarian cancers (eSOCA). MATERIAL AND METHODS: Twenty SBOT and 20 eSOCA rat models were performed with DCE-MRI and IVIM-DWI at 3.0-T MR scanner. Qualitative and quantitative parameters of DCE-MRI were acquired and compared between two groups and correlated with the microvessel density (MVD). The receiver operating characteristic (ROC) curve analyses were conducted to determine their differentiating performances. RESULTS: SBOTs presented significantly lower values of the initial area under the enhancement curve (iAUC), volume transfer constant (Ktrans), and extracellular extravascular volume fraction (ve) (P < 0.05) and a significantly higher value of true diffusion (D) (P = 0.001) compared with eSOCAs. The diagnostic effectiveness of ve combined with D was significantly better than that of ve or Ktrans alone (P ≤ 0.039). CONCLUSION: DCE-MRI may represent a promising tool for differentiating SBOTs from eSOCAs and may not be replaced by IVIM-DWI. Combining DCE-MRI with DWI may improve the diagnostic performance of ovarian tumors.

Scopoletin Activates Adenosine Monophosphate-Activated Protein Kinase/Mammalian Target of Rapamycin Signaling Pathway and Improves Functional Recovery after Spinal Cord Injury in Rats.

BACKGROUND: Scopoletin (SPT) is known to exert neuroprotective autophagy effect. However, the efficacy of SPT in the treatment of spinal cord injury (SCI) has yet not been explored. The investigation was intended to elucidate whether SPT can exert neuroprotective effect by triggering neuronal autophagy after SCI. The study was also directed to investigate the role of adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway in the autophagy facilitated by SPT. MATERIALS AND METHODS: The SCI was developed in female Sprague-Dawley rats by damaging the T10 spinal level using an impounder impact. Three animals groups were investigated - Sham group, SCI group, and SCI + SPT group. The SCI + SPT group was administered with SPT (100 mg/kg) intraperitoneally. Basso, Beattie, and Bresnahan scores and angle of incline test revealed that SPT administration improved the movement of hind limbs after SCI induction. RESULTS: Results indicated that SPT imparted neuronal protection, alleviated neuronal apoptosis, and improved neuronal autophagy. SPT-induced autophagy was identified by increased Beclin-1 expression and LC3B-positive neuronal cells. Further investigations revealed that SPT triggers the pathway involving AMPK/mTOR signaling, thereby stimulating autophagy in SCI-induced rat model. CONCLUSION: The findings of the present investigation strongly advocate the beneficial effects of SPT in the treatment of the SCI. SPT ameliorates the AMPK/mTOR signaling-induced autophagy and thereby improves functional recovery in SCI-induced rats.

Homochiral Cu(I) Coordination Polymers Based on a Double-Stranded Helical Building Block from Achiral Ligands: Symmetry-Breaking Crystallization, Photophysical and Photocatalytic Properties.

A pair of homochiral coordination polymers, [Cu(DPT)]n (1M and 1P, HDPT = 3,5-di-4-pyridinyl-2H-tetrazole), were assembled from achiral precursors. Crystal structure analysis showed that they are chiral three-dimensional (3D) coordination polymers based on a new double-stranded helical building block that is composed of two different 1D helices. Interestingly, rare symmetry-breaking crystallization was observed, in which the possibility of obtaining enantio-enriched bulk product with excessive M enantiomers (1-A) was obviously higher than that for P enantiomers (1-B) as demonstrated in multiple, repeated experiments with single-crystal diffraction and vibrational circular dichroism (VCD) spectra. Moreover, compound [Cu(DPT)]n shows good chemical stability in water, with pH values ranging from 3 to 13, as well as in many common organic solvents. Photophysical properties, including thermochromic properties and two-photon excited luminescence, were studied, and the potential for applications in temperature sensing was exhibited. In addition, the photocatalytic degradation of methylene blue in water indicated that compound [Cu(DPT)]n can be used as a photocatalyst.

Hydrolytically Stable Nanotubular Cationic Metal-Organic Framework for Rapid and Efficient Removal of Toxic Oxo-Anions and Dyes from Water.

Cationic framework materials capable of removing anionic pollutants from wastewater are highly desirable but relatively rarely reported. Herein, a cationic MOF (SCNU-Z1-Cl) possessing tubular channels with diameter of 1.5 nm based on Ni(II) and a nitrogen-containing ligand has been synthesized and applied to capture hazardous anionic contaminants from water. The SCNU-Z1-Cl exhibits high BET surface area of 1636 m2/g, and shows high hydrolytically stability in pH range from 4 to 10. Owing to the large tubular channels and the uncoordinated anions in the framework, the aqueous-phase anion-exchange applications of SCNU-Z1-Cl were explored with environmentally toxic oxo-anions including CrO42-, Cr2O72-, MnO4-, and ReO4-, and organic dyes. The adsorption of oxoanions exhibits high uptake kinetics and the adsorption capacities of CrO42-, Cr2O72-, MnO4-, and ReO4- are 126, 241, 292, and 318 mg/g, respectively, which were some of the highest values in the field of MOF/COF. In additional, the selectively is high when other concurrent anions are exist. The anionic dyes with different sizes including methyl orange, acid orange A, congo red, as well as methyl blue can be adsorbed by SCNU-Z1-Cl in few minutes to about 1 h. The adsorption capacities for them are 285, 180, 585, and 262 mg/g, respectively. In contrast, the adsorption kinetics for catinionic dyes with different sizes is obviously lower and exhibit a size-selectively adsorption that only cationic dye with suitable size (rhodamine B) can be adsorbed by SCNU-Z1-Cl. Consequently, SCNU-Z1-Cl can sepearate organic dyes in three different modes: size-dependent, charge-dependent, and kinetics-dependent selective adsorption. The excellent adsorption and separation properties of SCNU-Z1-Cl is attribute to the cationic framework, large tubular channel, as well as the high positive Zeta potential.

An Anionic Nanotubular Metal-Organic Framework for High-Capacity Dye Adsorption and Dye Degradation in Darkness.

A metal-organic framework (MOF), named SCNU-Z2, based on a new heterotopic tripodal nitrogen-containing ligand, has been constructed. Due to the replacement of one imidazole group in the reported ligand with one tetrazole group, the charge of the framework is changed from cationic to anionic but retains the same framework structure. The framework consists of tubular channels with a diameter of 1.5 nm and exhibits satisfactory stability in water with a pH range of 3-11. The anionic nature of the framework allows the effective adsorption of the cationic dyes MLB, CV, and RhB with capacities of 455.6, 847.4, and 751.8 mg/g, respectively. Among them, the adsorption capacities for SCNU-Z2 on CV and RhB rank as the highest when compared with other reported MOFs. In contrast, SCNU-Z2 exhibits an extremely low capacity for anionic dyes MO and AO, making it useful for the separation of anionic and cationic dyes based on a charge-dependent mode. Interestingly, SCNU-Z2 can be used to degrade an anionic dye, MB, within 30 min under darkness at room temperature. The apparent activation energy of the dye degradation reaction is calculated to be approximately 18.96 kJ·mol-1, implying that the catalytic reaction of MB can be considered as a low-temperature thermocatalytic reaction in the dark/SCNU-Z2 system.

Cholestane-3ß, 5α, 6ß-triol suppresses neuronal hyperexcitability via binding to voltage-gated sodium channels.

Neuronal hyperexcitability is identified as a critical pathological basis of epileptic seizures. Cholestane-3ß, 5α, 6ß-triol (Triol) is a major metabolic oxysterol of cholesterol. Although its neuroprotective effect on ischemia-induced neuronal injury and negative modulation of voltage-gated sodium (Nav) channels were well established, the physical binding site of triol to sodium channels and its effects on neuronal hyperexcitability have not yet been explored. In this study, we utilized molecular docking and molecular dynamics simulation to investigate the interaction between triol and Nav Channels. Our results demonstrated that triol binds to the indole ring of Trp122 of the Nav Channel in silico with a high biological affinity. We further found that triol negatively modulates the action potentials bursts of hippocampal neurons by cell-attached patch recording. Moreover, triol significantly inhibits low Mg2+-induced hyperexcitability in vitro. In addition, triol attenuates pentylenetetrazole (PTZ)-induced convulsive-form behavioral deficits in vivo. Together, our results suggest that triol suppresses neuronal hyperexcitability via binding to Nav channel, indicating that triol might be an attractive lead compound for the treatment of neuronal hyperexcitability-related neurological disorders, especially epileptic seizures.

Epidemiological Features of Hand, Foot and Mouth Disease during the Period of 2008-14 in Wenzhou, China.

This study aimed to analyze the epidemiological characteristics of hand, foot and mouth disease (HFMD) during 2008-14 in Wenzhou, China. The epidemiological data of HFMD retrieved from the Wenzhou Center for Disease Control and Prevention were retrospectively analyzed. HFMD infections with enterovirus 71 (EV71), Cox A16 or other pathogens were further verified by polymerase chain reaction (PCR) and real-time PCR. A total of 213 617 cases of HFMD were reported between 2008 and 2014 in Wenzhou. The average incidence was 384.31 of 100 000, and the fatality rate was 0.14‰. The incidence of HFMD peaked between April and July, and it occurred more frequently in males than in females. Approximately 92.68% of the HFMD patients were children aged <5 years. Nearly 80% of the cases were diagnosed within 2 days after onset. The major HFMD pathogen was EV71. This study suggested that appropriate comprehensive prevention and control measures should be taken to avoid the spread of HFMD.

MRI for differentiating primary fallopian tube carcinoma from epithelial ovarian cancer.

PURPOSE: To compare potential discriminatory magnetic resonance imaging (MRI) features of primary fallopian tube carcinoma (PFTC) and primary epithelial ovarian cancer (EOC). MATERIALS AND METHODS: MRI features (the laterality, shape, size, signal intensity, enhancement of solid portion, amount of ascites, peritoneal planting, lymph nodes, or distant metastasis) of 27 tumors in 23 patients with PFTC confirmed by surgery and pathology were compared with 42 tumors in 37 patients with EOC. RESULTS: The mean maximum diameter was 6.1 ± 0.7 cm in PFTC versus 10.2 ± 0.6 cm in EOC. MRI features of PFTC were sausage-like shape (19/27, 70%), or irregular (8/27, 30%) shape; solid (20/27, 74%) or cystic-solid (7/27, 26%) mass; homogeneous (21/27, 78%) or heterogeneous (6/27, 22%) signal on T2 -weighted images; mild (8/27, 30%), moderate (13/27, 48%), or prominent (6/27, 22%) enhancement; associated hydrosalpinx (13/27, 48%) or intrauterine fluid accumulation (7/23, 30%). Significant differences between PFTC and EOC were found in the size, shape, configuration, signal homogeneity, and enhancement pattern, associated hydrosalpinx, and intrauterine fluid accumulation (P < 0.001, < 0.001, 0.015, 0.001, < 0.001, < 0.001, and 0.001, respectively). CONCLUSION: PFTC often appears as a small-sized solid mass, with a sausage-like shape, homogeneous signal, mild or moderate enhancement, hydrosalpinx, or intrauterine fluid accumulation. Our preliminary study shows that MRI can identify the characteristic features of PFTC and differentiate PFTC from EOC.

MR Spectroscopy for Differentiating Benign From Malignant Solid Adnexal Tumors.

OBJECTIVE: The purpose of this article is to investigate the proton MR spectroscopy ((1)H-MRS) features of solid adnexal tumors and to evaluate the efficacy of (1)H-MRS for differentiating benign from malignant solid adnexal tumors. MATERIALS AND METHODS: Sixty-nine patients with surgically and histologically proven solid adnexal tumors (27 benign and 42 malignant) underwent conventional MRI and (1)H-MRS. Single-voxel spectroscopy was performed using the point-resolved spectroscopy localization technique with a voxel size of 2 × 2 × 2 cm(3). Resonance peak integrals of choline, N-acetyl aspartate (NAA), creatine, lactate, and lipid were analyzed, and the choline-tocreatine, NAA-to-creatine, lactate-to-creatine, and lipid-to-creatine ratios were recorded and compared between benign and malignant tumors. RESULTS: A choline peak was detected in all 69 cases (100%), NAA peak in 67 cases (97%, 25 benign and 42 malignant), lipid peak in 47 cases (17 benign and 30 malignant), and lactate peak in eight cases (four benign and four malignant). The mean (± SD) choline-tocreatine ratio was 5.13 ± 0.6 in benign tumors versus 8.90 ± 0.5 in malignant solid adnexal tumors, a statistically significant difference (p = 0.000). There were no statistically significant differences between benign and malignant tumors in the NAA-to-creatine and lipid-to-creatine ratios (p = 0.263 and 0.120, respectively). When the choline-to-creatine threshold was 7.46 for differentiating between benign and malignant tumors, the sensitivity, specificity, and accuracy were 94.1%, 97.1%, and 91.2%, respectively. CONCLUSION: Our preliminary study shows that the (1)H-MRS patterns of benign and malignant solid adnexal tumors differ. The choline-to-creatine ratio can help clinicians differentiate benign from malignant tumors.

Primary fallopian tube carcinoma: correlation between magnetic resonance and diffuse weighted imaging characteristics and histopathologic findings.

OBJECTIVE: The aim of this study was to investigate the magnetic resonance (MR) and diffusion-weighted (DW) imaging characteristics of primary fallopian tube carcinoma (PFTC). METHODS: The clinical, MR, and DW imaging characteristics and pathologic findings of 23 patients with 27 tumors were studied retrospectively. The MR and DW imaging appearance of tumors including laterality, size and shape, architecture, signal intensity, apparent diffusion coefficient (ADC) value, enhancement pattern, hydrosalpinx, and intrauterine fluid collection were evaluated and correlated with pathologic findings. RESULTS: Histopathologically, all 27 tumors were serous carcinoma with a unilateral tumor in 19 patients and bilateral tumors in 4 patients. Thirteen patients (57%) with PFTC were misdiagnosed preoperatively, 10 of which as epithelial ovarian carcinoma. The mean (SD) largest diameter was 61 (7) mm. The tumor shape was fusiform, sausagelike, or serpentine in 19 patients (70%) and nodular or irregular in 8 patients (30%). Twenty (74%) of the 27 tumors were solid, and 7 (26%) were cystic-solid. The solid components showed hypointensity to isointensity on T1-weighted imaging, and isointensity to slight hyperintensity on T2-weighted imaging. There were obvious hyperintensity on DW imaging; obvious hypointensity on ADC maps with a mean (SD) ADC value of 0.79 (0.22) × 10 mm; and mild (8/27, 30%), moderate (13/27, 48%), and marked (6/27, 22%) enhancement on contrast-enhanced imaging. Ipsilateral hydrosalpinx, intrauterine fluid collection, and ascites were found in 14 tumors (52%) and 7 (30%) and 5 (22%) patients, respectively. CONCLUSIONS: The PFTC has some characteristic MR imaging features. The DW imaging, ADC maps, and ADC values are helpful for the detection and differentiation of PFTC from other pelvic masses.

Primary ovarian endometrioid adenocarcinoma: magnetic resonance imaging findings including a preliminary observation on diffusion-weighted imaging.

OBJECTIVE: This study aimed to investigate the magnetic resonance imaging (MRI) features of ovarian endometrioid adenocarcinoma (OEC) and to evaluate conventional MRI and diffusion-weighted imaging (DWI) for diagnosing OEC. MATERIALS AND METHODS: Twenty patients with OEC proven by surgery and pathology underwent MRI. The MRI features of the tumors evaluated included laterality, shape, size, configuration, mural nodules, signal intensity, apparent diffusion coefficient (ADC) values, enhancement, peritoneal implants, ascites, and synchronous primary cancer (SPC) of the ovary and endometrium. RESULTS: Unilateral ovarian masses were observed in 18 (90%) of the 20 patients with 22 OEC lesions, whereas the remaining 2 (10%) patients had bilateral masses. Oval, lobulated, and irregular shapes were observed in 13 (59%), 6 (27%), and 3 (14%) tumors, respectively. The maximum diameter of the tumors ranged from 3.7 to 22.5 cm, with a mean of 11.2 ± 5.1 cm. Fifteen (68%) masses were mainly cystic with mural nodules, 5 (23%) were mixed cystic-solid, and 2 (9%) were solid. The solid components of tumors showed isointensity (100%) on T1-weighted imaging (T1WI), heterogeneous hyperintensity on T2-weighted imaging (T2WI) (86%), and hyperintensity on DWI (82%), with a mean ADC value of (0.96 ± 0.20) × 10 mm/s. The cystic components showed isointensity or hyperintensity (85%) on T1WI, hyperintensity on T2WI (100%), and hypointensity on DWI (63%), with a mean ADC value of (2.27 ± 0.27) × 10 mm/s. Ten (50%) of the patients were SPC. The mean ADC values of the solid components were (0.85 ± 0.19) × 10 mm/s and (1.08 ± 0.15) × 10 mm/s in only-OEC and SPC, respectively, with a statistically significant difference (P = 0.012). CONCLUSIONS: Ovarian endometrioid adenocarcinoma usually appears as a large, oval, or lobulated cystic mass with mural nodules. Cystic components show isointensity or hyperintensity on T1WI, solid components and hyperintensity on T2WI and DWI. Synchronous primary cancer of the ovary endometrium is another characteristic feature of OEC.