Reduced GABA concentration in patients with white matter hyperintensities.

To investigate potential alterations of white matter hyperintensities (WMHs) on J-edited MR spectroscopy (MRS) measures of the primary inhibitory neurotransmitter γ-aminobutyric acid (GABA). Twenty-four WMHs patients and 20 healthy controls (HCs) were recruited to undergo magnetic resonance spectroscopy (MRS) scan at 3T from voxels in left centrum semiovale white matter, using the MEGA point resolved spectroscopy (MEGA-PRESS) technique with the MATLAB-based Gannet tool to estimate GABA+ co-edited macromolecule (GABA+) levels and using Tarquin software to estimate levels of glutamate + glutamine (Glx), total N-acetylaspartate (tNAA), total choline (tCho), and total creatine (tCr). Independent t-tests or Mann-Whitney U-tests were used to test group differences between WMHs and HCs. Additionally, WMHs patients were divided into mild and moderate-severe WMHs subgroup according to the Fazekas scale. Analysis of variance (ANOVA) and post-hoc tests were used among WMHs subgroups and HCs. We found there was a significant reduction in GABA+ levels (p = 0.018) in WMHs patients compared with healthy controls. In subgroup analyses, there was also a significant reduction of GABA+ levels in moderate-severe WMHs subgroup (p = 0.037) and mild WMHs subgroup (p = 0.047) when compared to HCs. Besides, the moderate-severe WMHs subgroup had significantly higher levels of tCho compared with healthy controls (p = 0.019). In conclusion, reduced GABA+ levels in WMHs patients and elevated tCho levels in moderate-severe WMHs were observed when compared with HCs. These results demonstrate that abnormalities of the GABAergic system and choline metabolism may contribute to the pathogenesis of WMHs.

Quantitative Analysis of Whole-Body MRI for Accessing the Degree of Diffuse Infiltration Patterns and Identifying High Risk Cases of Newly Diagnosed Multiple Myeloma.

BACKGROUND: Accurate identification of high-risk multiple myeloma (HRMM) is important for prognostication. The degree of diffuse infiltration patterns on magnetic resonance imaging (MRI) is associated with patient prognosis in multiple myeloma. However, objective indexes to determine the degree of diffuse infiltration patterns are unavailable. PURPOSE: To investigate whether qualitative and quantitative evaluations of diffuse infiltration patterns on MRI could identify HRMM. STUDY TYPE: Retrospective. SUBJECTS: Totally, 180 patients (79 HRMM and 101 standard-risk MM) were assessed. The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, and/or p53 mutations was considered to indicate HRMM. FIELD STRENGTH/SEQUENCE: 3.0 T/diffusion-weighted whole-body imaging with background body signal suppression (DWIBS), modified Dixon chemical-shift imaging Quant (mDIXON Quant), and short TI inversion recovery (STIR). ASSESSMENT: Qualitative analysis involved assessing the degree of diffuse marrow infiltration (mild, moderate, or severe), and quantitative analysis involved evaluating apparent diffusion coefficient (ADC), fat fraction (FF), and T2* values. Clinical data such as sex, age, hemoglobin, serum albumin, serum calcium, serum creatinine, serum lactate dehydrogenase, ß2-microglobulin, and bone marrow plasma cells (BMPCs) were also included. STATISTICAL TESTS: Univariate and multivariate analyses, receiver operating characteristic (ROC) curve. P < 0.05 was considered statistically significant. RESULTS: The high-risk group had significantly higher ADC and T2* and lower FF compared with the standard-risk group. Multivariate analysis indicated BMPCs as a significant independent risk factor for HRMM (odds ratio (OR) = 1.019, 95% CI 1.004-1.033), while FF was a significant independent protective factor associated with HRMM (OR = 0.972, 95% CI 0.946-0.999). The combination of BMPCs and FF achieved the highest areas under the curve (AUC) of 0.732, with sensitivity and specificity of 70.9% and 68.3%, respectively. DATA CONCLUSION: Compared with qualitative analysis, FF value was independently associated with HRMM. The quantitative features of diffuse marrow infiltration on MRI scans are more effective in detecting HRMM. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

FGF9 Recruits ß-Catenin to Increase Hepatic ECM Synthesis and Promote NASH-Driven HCC.

Most nonalcoholic steatohepatitis (NASH) patients develop severe fibrosis through extracellular matrix (ECM) accumulation, which can lead to hepatocellular carcinoma (HCC). Fibroblast growth factor 9 (FGF9) is involved in serial types of cancer; however, the specific role of FGF9 in NASH-driven HCC is not fully understood. This study finds that FGF9 is increased in patients with NASH-associated HCC. Furthermore, NASH-driven HCC mice models by feeding wildtype mice with high-fat/high-cholesterol (HFHC) diet and low dose carbon tetrachloride (CCl4 ) treatment is established; and identified that hepatic FGF9 is increased; with severe fibrosis. Additionally, AAV-mediated knockdown of FGF9 reduced the hepatic tumor burden of NASH-driven HCC mice models. Hepatocyte-specific FGF9 transgenic mice (FGF9Alb ) fed with a HFHC diet without CCl4 treatment exhibited an increased hepatic ECM and tumor burden. However, XAV-939 treatment blocked ECM accumulation and NASH-driven HCC in FGF9Alb mice fed with HFHC diet. Molecular mechanism studies show that FGF9 stimulated the expression of ECM related genes in a ß-catenin dependent manner; and FGF9 exerts its effect on ß-catenin stability via the ERK1/2-GSK-3ß signaling pathway. In summary, the data provides evidence for the critical role of FGF9 in NASH-driven HCC pathogenesis; wherein it promotes the tumors formation through the ECM pathway.

Identifying Key Factors of Hazardous Materials Transportation Accidents Based on Higher-Order and Multilayer Networks.

This paper focuses on the application of higher-order and multilayer networks in identifying critical causes and relationships contributing to hazardous materials transportation accidents. There were 792 accidents of hazardous materials transportation that occurred on the road from 2017 to 2021 which have been investigated. By considering time sequence and dependency of causes, the hazardous materials transportation accidents causation network (HMTACN) was described using the higher-order model. To investigate the structure of HMTACN such as the importance of causes and links, HMTACN was divided into three layers using the weighted k-core decomposition: the core layer, the bridge layer and the peripheral layer. Then causes and links were analyzed in detail. It was found that the core layer was tightly connected and supported most of the causal flows of HMTACN. The results showed that causes should be given hierarchical attention. This study provides an innovative method to analyze complicated accidents, which can be used in identifying major causes and links. And this paper brings new ideas about safety network study and extends the applications of complex network theory.

Preliminary Study of Confounder-Corrected Fat Fraction and R2* Mapping of Bone Marrow in Children With Acute Leukemia.

BACKGROUND: The bone marrow (BM) evaluation of acute leukemia (AL) mainly depends on invasive BM puncture biopsy. Noninvasive and accurate MR examination technology has potential clinical application value in the BM evaluation of AL patients. Multi-gradient-echo (MGRE) has been found useful to evaluate changes in BM fat and iron content, but has not yet been applied in AL. PURPOSE: To explore the diagnostic capability of BM infiltration of quantitative BM fat fraction (FF) and R2* values obtained from a 3D MGRE sequence in children with primary AL. STUDY TYPE: Prospective. POPULATION/SUBJECTS: Sixty-two pediatric patients with untreated AL and 68 healthy volunteers. AL patients were divided into acute lymphoblastic leukemia (ALL) (n = 39) and acute myeloid leukemia (AML) (n = 23) groups. FIELD STRENGTH/SEQUENCE: 3T, 3D chemical-shift-encoded multi-gradient-echo, T1WI, T2WI, T2_STIR. ASSESSMENT: BM FF and R2* values were assessed by manually drawing regions of interest at the L3, L4, ilium, and 1 cm below the bilateral trochanter of the femur (upper femur). STATISTICAL TESTS: Independent sample t-tests, variance analysis, Spearman correlation. RESULTS: BM FF and R2* at L3, L4, ilium, and upper femur, FFtotal and R2*total were significantly lower in the AL than control group. BM FF did not significantly differ between ALL and AML groups (PL3 = 0.060, PL4 = 0.086, Pilium = 0.179, Pupper femur = 0.149, and Ptotle = 0.097, respectively). The R2* was significantly lower in ALL group than AML group for L3, L4, and R2*total . BM FF was moderately positively correlated with R2* in ALL group, and strongly positively correlated in AML group. Area under the receiver operating characteristic curves showed that BM FF had higher AUC in AL, ALL, and AML (all AUC = 1.000) than R2* (0.976, 0.996, and 0.941, respectively). DATA CONCLUSION: MGRE-MRI mapping can be applied to measure BM FF and R2* values, and help evaluate BM infiltration and iron storage in children with AL. EVIDENCE LEVEL: 1 Technical Efficacy: 2.

Altered static and dynamic spontaneous neural activity in patients with ischemic pontine stroke.

Objective: The purpose of the study was to investigate the abnormality both of static spontaneous brain activity and dynamic temporal variances following a pontine infarction. Methods: Forty-six patients with chronic left pontine infarction (LPI), thirty-two patients with chronic right pontine infarction (RPI), and fifty healthy controls (HCs) were recruited for the study. The static amplitude of low-frequency fluctuations (sALFF), static regional homogeneity (sReHo), dynamic ALFF (dALFF), and dynamic ReHo (dReHo) were employed to detect the alterations in brain activity induced by an infarction. The Rey Auditory Verbal Learning Test and Flanker task were used to evaluate the verbal memory and visual attention function, respectively. Receiver operating characteristic curve analysis was used to reveal the potential capacity of these metrics to distinguish the patients from HCs. Results: There were significant variations of these static and dynamic metrics in patients with chronic pontine infarction. The altered regions involved the supratentorial regions, including cortex and subcortical. Moreover, the altered metrics were significantly correlated with verbal memory and visual attention. In addition, these static and dynamic metrics also showed potential in distinguishing stroke patients with behavior deficits from HCs. Conclusion: The pontine infarction-induced cerebral activation changes are observed in both motor and cognitive systems, indicating the functional damage and reorganization across the global cerebral level in these patients with subtentorial infarction, and there is a reciprocal effect between motor and cognitive impairment and repair.

Knocking Down Gm16685 Decreases Liver Granuloma in Murine Schistosomiasis Japonica.

Long noncoding RNAs (lncRNAs) can regulate key genes and pathways in liver disease development. Moreover, macrophages are speculated to play an important role in regulating granulomatous inflammation during schistosomiasis. However, the role of lncRNAs in the formation of liver granulomas by influencing the polarization of macrophages in Schistosoma japonicum infection is unclear. Our study aimed to determine whether lncRNAs can play a role in S. japonicum-induced hepatic egg granulomas and elucidate their effect on macrophages. We established S. japonicum infection models and screened the target lncRNA Gm16685 highly expressed in schistosomiasis mice using high-throughput sequencing. Hematoxylin and eosin staining revealed that the knockdown of Gm16685 reduced the area of egg granulomas. Moreover, M1 macrophage factor genes were significantly downregulated in Gm16685 knockdown livers. Meanwhile, M2 macrophage factor genes were significantly upregulated, which was consistent with the protein detection results. Hepatocytes, hepatic stellate cells, and macrophages were isolated from mouse models infected with S. japonicum, with Gm16685 being significantly upregulated in macrophages. Moreover, the knockdown of Gm16685 in RAW264.7 cells revealed similar results to in liver tissue. RNA fluorescence in situ hybridization (FISH) and nucleocytoplasmic separation experiments revealed that Gm16685 was predominantly localized in the cytoplasm of cells. We found that miR-205-5p was upregulated after Gm16685 was knocked down. After overexpression of miR-205-5p, the expression of Gm16685 and inflammatory factors was significantly downregulated. These results indicate that Gm16685 can participate in the pathogenesis of hepatic disease in schistosomiasis and promote M1 macrophage polarization by regulating miR-205-5p. Thus, our study may provide a new target for schistosomiasis japonica treatment.

Sterility of Aedes albopictus by X-ray Irradiation as an Alternative to γ-ray Irradiation for the Sterile Insect Technique.

The mosquito Aedes albopictus can transmit various arboviral diseases, posing a severe threat to human health. As an environmentally friendly method, sterile insect technology (SIT) is considered an alternative to traditional methods such as chemical pesticides to control Ae. albopictus. In SIT, the sterility of male mosquitoes can be achieved by γ-ray or X-ray radiation. Compared with γ-rays, X-rays are easier to obtain, cheaper, and less harmful. However, there is a lack of comparative assessment of these two types of radiation for SIT under the same controlled conditions. Here, we compared the effects of X-ray and γ-ray radiation on the sterility of Ae. albopictus males under laboratory-controlled conditions. Neither type of radiation affected the number of eggs but significantly reduced the survival time and hatch rate. The same dose of γ-rays caused a higher sterility effect on males than X-rays but had a more significant impact on survival. However, X-rays could achieve the same sterility effect as γ-rays by increasing the radiation dose. For example, X-rays of 60 Gy induced 99% sterility, similar to γ-rays of 40 Gy. In the test of male mating competitiveness, the induced sterility and the male mating competitiveness index were also identical at the same release ratio (sterile males/fertile males). At a release ratio of 7:1, nearly 80% of eggs failed to hatch. Sterile males produced by X-ray and γ-ray radiation had similar male competitiveness in competition with field males. In conclusion, a higher dose of X-rays is required to achieve the same sterility effect, compared to γ-rays. When γ-rays are not readily available, high-dose X-rays can be used instead. This study provides data supporting the selection of more suitable radiation for the field release of sterile male mosquitoes.

Dual-gene detection in a single-tube system based on CRISPR-Cas12a/Cas13a for severe fever thrombocytopenia syndrome virus.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease, which is caused by severe fever with thrombocytopenia syndrome virus (SFTSV). The disease results in high mortality and increased morbidity and threatens global public health. Rapid detection of SFTSV is crucial for epidemic prevention in low-resource settings. Here we developed deployable, sensitive and rapid detection methods based on CRISPR/Cas12a or Cas13a technologies. The CRISPR/Cas12a-based detection assay could stably detect the SFTSV L or M genes at 10 cp/µl. The Cas13a-based method could detect the L gene as low as 0.75 cp/µl. For point-of-care testing, we combined fluorescence visualization and lateral flow detection with CRISPR/Cas-based assays. Furthermore, using the orthogonal DNA/RNA collateral activity of the Cas12a/Cas13a system, we present the dual-gene detection platform for SFTSV, which can simultaneously detect the L and M genes in a single tube. Based on the dual-gene detection, we designed multiplexed test strips to detect SFTSV. All our methods were initially validated using 52 clinical samples, showing 100% sensitivity and specificity. These new CRISPR/Cas-based detection methods are promising candidates for on-site detection of SFTSV.

Understanding Hazardous Materials Transportation Accidents Based on Higher-Order Network Theory.

In hazardous materials transportation systems, accident causation analysis is important to transportation safety. Complex network theory can be effectively used to understand the causal factors of and their relationships within accidents. In this paper, a higher-order network method is proposed to establish a hazardous materials transportation accident causation network (HMTACN), which considers the sequences and dependences of causal factors. The HMTACN is composed of 125 first- and 118 higher-order nodes that represent causes, and 545 directed edges that denote complex relationships among causes. By analyzing topological properties, the results show that the HMTACN has the characteristics of small-world networks and displays the properties of scale-free networks. Additionally, critical causal factors and key relationships of the HMTACN are discovered. Moreover, unsafe tank or valve states are important causal factors; and leakage, roll-over, collision, and fire are most likely to trigger chain reactions. Important higher-order nodes are discovered, which can represent key relationships in the HMTACN. For example, unsafe distance and improper operation usually lead to collision and roll-over. These results of higher-order nodes cannot be found by the traditional Markov network model. This study provides a practical way to extract and construct an accident causation network from numerous accident investigation reports. It also provides insights into safety management of hazardous materials transportation.

IL-37 alleviates liver granuloma caused by Schistosoma japonicum infection by inducing alternative macrophage activation.

BACKGROUND: Hepatic macrophages regulate liver granuloma formation and fibrosis caused by infection with Schistosoma japonicum, with the manner of regulation dependent on macrophage activation state. Interleukin (IL)-37 may have immunomodulatory effects on macrophages. However, whether IL-37 can affect liver granuloma formation and fibrosis by affecting the polarization of macrophages in S. japonicum infection remains unclear. The aim of this study was to investigate IL-37-affected macrophage polarization in liver granuloma formation and fibrosis in S. japonicum infection. METHODS: An enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of IL-37 in the serum of patients with acute S. japonicum infection and in the serum of healthy people. Recombinant IL-37 (rIL-37), CPP-IgG2Fc-IL-37 and no CPP-IgG2Fc-IL-37 proteins were injected into S. japonicum-infected mice every 3 days for a total of 6 times from day 24 post infection onwards. Subsequently, ELISA, quantitative reverse transcription-PCR, fluorescence-activated cell sorting and western blot were used to analyze whether IL-37 inhibits the formation of liver granulomas and the development of liver fibrosis by regulating the phenotypic transition of macrophages. Finally, the three IL-37 proteins and SIS3, a Smad3 inhibitor, were co-cultured in mouse peritoneal macrophages to explore the mechanism underlying the promotion of the polarization of M0 macrophages to the M2 phenotype by IL-37. RESULTS: Serum IL-37 levels were upregulated in schistosomiasis patients, and this increased level of IL-37 protein apparently alleviated the liver granuloma of mice in infection models. It also could induce liver and peritoneal macrophages to polarize to the M2 phenotype in S. japonicum-infected mice. The S. japonicum-infected mice injected with CPP-IgG2Fc-IL-37 group exhibited the most obvious improvement in inflammatory reaction against the liver granuloma. The number and ratio of M2 macrophages in the liver and peritoneal cavity were significantly higher in the three IL-37 protein groups, especially in the CPP-IgG2Fc-IL-37 group, compared to the controls. Similar results were also found regarding liver function damage. IL-37 induced macrophage M2 polarization by promoting AMP-activated protein kinase (AMPK) phosphorylation in vitro. Among all groups, the activation of AMPK was most significant in the CPP-IgG2Fc-IL-37 group, and it was found that SMAD3 could enhance the anti-inflammatory function of IL-37. CONCLUSIONS: The results show that IL-37 was able to promote the polarization of macrophages to the M2 phenotype, thereby inhibiting the development of schistosomiasis. In comparison to the rIL-37 protein, the CPP-IgG2Fc-IL-37 protein has the advantages of being effective in small doses and having fewer side effects and a better efficacy.

JQ-1 ameliorates schistosomiasis liver granuloma in mice by suppressing male and female reproductive systems and egg development of Schistosoma japonicum.

Schistosomiasis is a serious and widespread parasitic disease caused by infection with Schistosoma. Because the parasite's eggs are primarily responsible for schistosomiasis dissemination and pathogenesis, inhibiting egg production is a potential approach to control the spread and severity of the disease. The bromodomain and extra-terminal (BET) proteins represent promising targets for the development of epigenetic drugs against Schistosoma. JQ-1 is a selective inhibitor of the BET protein family. In the present study, JQ-1 was applied to S. japonicum in vitro. By using laser confocal scanning microscopy and EdU incorporation assays, we showed that application of JQ-1 to worms in vitro affected egg laying and the development of both the male and female reproductive systems. JQ-1 also inhibited the expression of the reproductive-related genes SjPlk1 and SjNanos1 in S. japonicum. Mice infected with S. japonicum were treated with JQ-1 during egg granuloma formation. JQ-1 treatment significantly reduced the size of the liver granulomas and levels of serum alanine aminotransferase and aspartate aminotransferase in mice and suppressed both egg laying and the development of male and female S. japonicum reproductive systems in vivo. Moreover, the mRNA expression levels of some proinflammatory cytokines were decreased in the parasites. Our findings suggest that JQ-1 treatment attenuates S. japonicum egg-induced hepatic granuloma due at least in part to suppressing the development of the reproductive system and egg production of S. japonicum. These findings further suggest that JQ-1 or other BET inhibitors warrant additional study as a new approach for the treatment or prevention of schistosomiasis.

Cerebral blood flow alterations specific to freezing of gait in Parkinson's disease.

BACKGROUND: Freezing of gait (FOG) have been associated with deficits in the cortico-basal ganglia-thalamic network. However, the resting-state cerebral blood flow (CBF) alterations specific to FOG in Parkinson's disease (PD) remain unknown. METHODS: In total, sixty PD individuals, including 30 PD with FOG (PD-FOG) and 30 PD without FOG (PD-NFOG), and 30 healthy controls (HC) underwent arterial spin labeling magnetic resonance image. The CBF were voxel-wise compared among the three groups and validated in a different cohort of PD-FOG and PD-NFOG. RESULTS: The results revealed that patients with PD-FOG had increased CBF in bilateral thalamus and the left caudate nucleus and decreased CBF in the left inferior parietal cortex compared to patients with PD-NFOG. The inter-group differences of CBF between PD-FOG and PD-NFOG was confirmed in a different cohort in the validation analysis. Moreover, the CBF in left caudate nucleus was positively correlated with severity of FOG in PD-FOG patients. CONCLUSIONS: Perfusion alterations in both cortical and subcortical regions in the cortico-basal ganglia-thalamic network are related to the development of FOG in PD patients.

Respiratory Mucosal Immunity: Kinetics of Secretory Immunoglobulin A in Sputum and Throat Swabs From COVID-19 Patients and Vaccine Recipients.

While IgM and IgG response to SARS-CoV-2 has been extensively studied, relatively little is known about secretory IgA (sIgA) response in respiratory mucosa. Here we report IgA response to the SARS-CoV-2 in sputum, throat swabs, and serum with nucleocapsid protein (NP) enzyme-linked immunosorbent assays (ELISA) in a cohort of 28 COVID-19 patients and 55 vaccine recipients. The assays showed sIgA in respiratory mucosa could be detected on the first day after illness onset (AIO), and the median conversion time for sIgA in sputum, throat swabs, and serum was 3, 4, and 10 days, respectively. The positive rates of sIgA first week AIO were 100% (24/28) and 85.7% (24/28) in sputum and throat swabs, respectively, and were both 100% during the mid-onset (2-3 weeks AIO). During the recovery period, sIgA positive rates in sputum and throat swabs gradually decreased from 60.7% (17/28) and 57.1% (16/28) 1 month AIO and the sIgA antibodies were all undetectable 6 months AIO. However, serum IgA positive rate was still 100% at 4 months and 53.6% (15/28) at 6 months. Throat swabs obtained from volunteers who received inactivated SARS-CoV-2 vaccines by intramuscular delivery all showed negative results in IgA ELISA. These findings will likely improve our understanding of respiratory mucosal immunity of this emerging disease and help in containing the pandemic and developing vaccines.

Differentiation of Diffuse Infiltration Pattern in Multiple Myeloma From Hyperplastic Hematopoietic Bone Marrow: Qualitative and Quantitative Analysis Using Whole-Body MRI.

BACKGROUND: The visual assessment used for diffuse infiltration of multiple myeloma (MM) is inadequate. It can be difficult to differentiate MM from hyperplastic hematopoietic bone marrow (HHBM) because the MRI signal characteristics overlap. PURPOSE: To analyze the bone marrow diffuse signal changes on whole-body MRI caused by MM and HHBM. STUDY TYPE: Retrospective. SUBJECTS: Thirty Four patients with MM (21 men and 13 women), 22 patients with HHBM (9 men and 13 women), and 15 healthy controls (9 men and 6 women). FIELD STRENGTH/SEQUENCE: A 3.0 T MRI; diffusion-weighted whole-body imaging with background body signal suppression (DWIBS), modified Dixon T1 fast field echo, and T2 STIR. ASSESSMENT: Three radiologists analyzed the whole-body MRI alone and in combination with apparent diffusion coefficient (ADC) and fat fraction (FF) with qualitative and quantitative analysis. Normalized T1 and T2 signal intensities (nT1 and nT2) and signal-to-noise ratio (SNR) were obtained. STATISTICAL TESTS: Kruskal-Wallis and chi-square tests. RESULTS: The MM group had significantly higher ADC and significantly lower FF than HHBM and control groups. There was no significant difference in nT1, nT2 or SNR between MM and HHBM (P = 0.932, P = 0.097, and P = 0.110, respectively). Receiver operating characteristic (ROC) analysis using ADC and FF cut-off values of 0.47 × 10-3  mm2 /sec and 20.63%, respectively. The AUC was 0.866 for ADC and 0.886 for FF. The quantitative analysis yielded better specificity (observer 1: 81.8% vs. 27.3%; observer 2: 68.2% vs. 22.7%; and observer 3: 72.7% vs. 18.2%) and a higher diagnostic accuracy (observer 1: 82.1% vs. 51.8%; observer 2: 80.4% vs. 50.0%; observer 3: 76.8% vs. 44.6%) than the qualitative analysis. DATA CONCLUSION: Whole-body MRI combined with DWIBS and mDIXON could be used to differentiate between MM and HHBM. Combining the quantitative ADC and FF with the whole-body MRI improved the specificity and accuracy in differentiating these conditions. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Evaluation of Diffuse Bone Marrow Infiltration Pattern in Monoclonal Plasma Cell Diseases by Quantitative Whole-body Magnetic Resonance Imaging.

RATIONALE AND OBJECTIVES: To analyze diffuse infiltration pattern in monoclonal plasma cell diseases by diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) and quantitative chemical-shift encoded MRI. MATERIALS AND METHODS: Ninety-nine patients with monoclonal plasma cell diseases and 15 healthy control subjects were retrospectively analyzed. All patients underwent whole-body MRI (including DWIBS and mDIXON Quant) and were divided into three groups: monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma (MM). Apparent diffusion coefficient (ADC), fat fraction (FF), and T2* values for each group were calculated then analyzed by one-way ANOVA and receiver operating characteristic curve. Correlations of ADC, FF, and T2* with clinical indices were analyzed with Spearman correlation test. RESULTS: The ADC and T2* values of MM were significantly higher than those of the healthy control, MGUS and SMM (ADC: p = 0.003, p = 0.003, and p = 0.042; T2*: all with p < 0.001). The FF values of MM were significantly lower than those of the healthy control, MGUS and SMM (p < 0.001, p < 0.001 and p = 0.034). The ADC, FF, and T2* thresholds for recognizing MM and MGUS+SMM were 0.51 × 10-3 mm2/s, 31.14%, and 10.53 ms, respectively. The ADC, FF, and T2* values were identified to be significantly associated with bone marrow plasma cells and hemoglobin in patients (all with p < 0.001). CONCLUSION: ADC, FF, and T2* were significantly correlated with clinical indices related to monoclonal plasma cell diseases. MM with the diffuse infiltration pattern can be distinguished more objectively from MGUS and SMM by quantitative functional MRI parameters.

JQ-1 ameliorates schistosomiasis liver fibrosis by suppressing JAK2 and STAT3 activation.

Schistosomiasis is a serious parasitic infection caused by Schistosoma. The parasite deposits eggs in the host liver, causing inflammation that activates hepatic stellate cells (HSCs), which leads to liver fibrosis. Currently, there is no effective therapy for liver fibrosis; thus, treatments are urgently needed. Therefore, in the present study, mice infected with Schistosoma japonicum were treated with JQ-1, a small-molecule bromodomain inhibitor with reliable anti-tumor and anti-inflammatory activities. The fibrotic area of the liver measured by computer-assisted morphometric analysis and the expression levels of the cytoskeletal protein alpha smooth muscle actin (α-SMA) and of collagen assessed by quantitative PCR, Western blot and immunohistochemistry were significantly decreased in the liver following JQ-1 treatment compared with vehicle-treated controls. Total RNA was extracted from the liver of JQ-1-treated Schistosoma-infected mice for RNA-sequencing analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that JQ-1 affected biological processes and the expression of cellular components known to play key roles in the transdifferentiation of HSCs to myofibroblasts. In vitro treatment with JQ-1 of JS-1 cells, a mouse HSC line, indicated that JQ-1 significantly inhibited JS-1 proliferation but had no effect on JS-1 activity, senescence, or apoptosis. Western blot results showed that JQ-1 inhibited the expression levels of phosphorylated JAK2 and phosphorylated STAT3 without altering expression levels of these non-phosphorylated proteins. Taken together, these findings suggested that JQ-1 treatment ameliorated S. japonicum egg-induced liver fibrosis, at least in part, by suppressing HSC activation and proliferation through the inhibition of JAK2/STAT3 signaling. These results lay a foundation for the development of novel approaches to treat and control liver fibrosis caused by S. japonicum.

Quantitative whole-body MR imaging for assessment of tumor burden in patients with multiple myeloma: correlation with prognostic biomarkers.

BACKGROUND: To assess the quantification of tumor burden in multiple myeloma (MM) patients using whole-body magnetic resonance imaging (MRI) and to identify the correlation between MRI parameters and prognostic biomarkers. METHODS: We retrospectively analyzed 95 newly diagnosed MM patients treated at our hospital from June 2018 to March 2020. All patients underwent whole-body MRI examination, including diffusion-weighted whole-body imaging with background body signal suppression (DWIBS), modified Dixon chemical-shift imaging (mDIXON), and short TI inversion recovery (STIR) sequences. The MRI presentation was used to determine MM infiltration patterns and calculate apparent diffusion coefficient (ADC) and a fat fraction (FF). The one-way ANOVA and Kruskal-Wallis test were used to compare the differences of these values between DS, ISS, and R-ISS stages in different MM infiltration patterns. Spearman correlation test was used for correlation analysis of ADC and FF against prognostic biomarkers, and two independent sample t-test was used to evaluate the differences of ADC and FF in different free light-chain ratio groups. RESULTS: The MRI presentation was classified into normal pattern (36 patients; 37.9%), diffuse (27 patients; 28.4%), and focal (32 patients; 33.7%) infiltration patterns. Statistically significant ADC and FF differences between different DS, ISS, and R-ISS stages were observed in normal/diffuse infiltration patterns but not in focal infiltration patterns. The ADC and FF of the normal/diffuse infiltration pattern showed correlations with hemoglobin, ß2-microglobulin, bone marrow plasma cells, flow cytometry of bone marrow cells, and serum monoclonal protein. In contrast, ADC in focal infiltration patterns was negatively correlated with ß2-microglobulin and C-reactive protein. The FF of patients with a normal/diffuse infiltration pattern was higher in the low free light-chain ratio group than that in the high free light-chain ratio group (P=0.023). CONCLUSIONS: Our observations indicate that quantitative whole-body functional MRI examination may serve as an effective complement to imaging diagnosis based on morphology and provide further information on the tumor burden of patients with MM.