Design, synthesis, and evaluation of novel quindoline derivatives with fork-shaped side chains as RNA G-quadruplex stabilizers for repressing oncogene NRAS translation.

NRAS mutation is the second most common oncogenic factor in cutaneous melanoma. Inhibiting NRAS translation by stabilizing the G-quadruplex (G4) structure with small molecules seems to be a potential strategy for cancer therapy due to the NRAS protein's lack of a druggable pocket. To enhance the effects of previously reported G4 stabilizers quindoline derivatives, we designed and synthesized a novel series of quindoline derivatives with fork-shaped side chains by introducing (alkylamino)alkoxy side chains. Panels of experimental results showed that introducing a fork-shaped (alkylamino)alkoxy side chain could enhance the stabilizing abilities of the ligands against NRAS RNA G-quadruplexes and their anti-melanoma activities. One of them, 10b, exhibited good antitumor activity in the NRAS-mutant melanoma xenograft mouse model, showing the therapeutic potential of this kind of compounds.

Diagnostic performance of endorectal ultrasound combined with shear wave elastography for rectal tumors staging.

OBJECTIVE: This study aims to analyze the performance of endorectal ultrasound (ERUS) combined with shear wave elastography (SWE) for rectal tumor staging. METHODS: Forty patients with rectal tumors who had surgery were enrolled. They underwent ERUS and SWE examinations before surgery. Pathological results were used as the gold standard for tumor staging. The stiffness values of the rectal tumor, peritumoral fat, distal normal intestinal wall, and distal perirectal fat were analyzed. The diagnostic accuracy of ERUS stage, tumor SWE stage, ERUS combined with tumor SWE stage, and ERUS combined with peritumoral fat SWE stage were compared and evaluated by receiver operating characteristic (ROC) curve to select the best staging index. RESULTS: From T1 to T3 stage, the maximum elasticity (Emax) of the rectal tumor increased gradually (p < 0.05). The cut-off values of adenoma/T1 and T2, T2 and T3 tumors were 36.75 and 85.15kPa, respectively. The diagnostic coincidence rate of tumor SWE stage was higher than that of ERUS stage. Overall diagnostic accuracy of ERUS combined with peritumoral fat SWE Emax restaging was significantly higher than that of ERUS. CONCLUSIONS: ERUS combined with peritumoral fat SWE Emax for tumor restaging can effectively distinguish between stage T2 and T3 rectal tumors, which provides an effective imaging basis for clinical decisions.

The effect of seed location on functional connectivity: evidence from an image-based meta-analysis.

Introduction: Default mode network (DMN) is the most involved network in the study of brain development and brain diseases. Resting-state functional connectivity (rsFC) is the most used method to study DMN, but different studies are inconsistent in the selection of seed. To evaluate the effect of different seed selection on rsFC, we conducted an image-based meta-analysis (IBMA). Methods: We identified 59 coordinates of seed regions of interest (ROIs) within the default mode network (DMN) from 11 studies (retrieved from Web of Science and Pubmed) to calculate the functional connectivity; then, the uncorrected t maps were obtained from the statistical analyses. The IBMA was performed with the t maps. Results: We demonstrate that the overlap of meta-analytic maps across different seeds' ROIs within DMN is relatively low, which cautions us to be cautious with seeds' selection. Discussion: Future studies using the seed-based functional connectivity method should take the reproducibility of different seeds into account. The choice of seed may significantly affect the connectivity results.

[Significance of herbal/botanical monograph in international registration of Chinese medicine].

Herbal/botanical monograph, first emerging abroad, includes the scientific conclusions on safety and effectiveness of herbal medicine/botanical medicine, as it is often compiled by drug regulatory authorities. It is designed to unify the related technologies in this field and evaluation standards for review. Thus, herbal/botanical monograph is vital for the internationalization of Chinese medicine and being inscribed into the herbal/botanical monograph of target country is the first step for drug registration there. At the moment, there are few domestic studies on international herbal/botanical monographs, let alone the importance of the monographs in international registration of Chinese medicine preparations. This study first described international monographs on herbal/botanical medicine, then discussed the similarities and differences between international monographs and Chinese Pharmacopoeia, and finally analyzed the significance and value of the monographs in the international registration of Chinese medicine. On this basis, this study underscored the research on herbal/botanical monographs of key candidate countries for Chinese medicine registration, with a view to enhancing international recognition and laying the foundation for international registration and related policy formulation.

Design, synthesis, and evaluation of 9-(pyrimidin-2-yl)-9H-carbazole derivatives disrupting mitochondrial homeostasis in human lung adenocarcinoma.

Since more than 85% of lung cancer cases are non-small cell lung cancer (NSCLC), finding novel agents with anti-tumor activities is meaningful for NSCLC patients. Mitochondria is essential for cellular energy metabolism in cancer, and regulating mitochondrial bioenergetics is emerging as a practical approach for cancer treatment and prevention. The carbazole scaffold is an active structure showing anti-cancer biological activity, and the structural diversity has been expanded through the improvement and optimization of synthesizing methods. To find novel carbazole derivatives with great anti-tumor potential and explore structures variety, we designed and synthesized a series of 9-(pyrimidin-2-yl)-9H-carbazole derivatives based on the previously reported Cp∗Rh(III)/H+ tandem catalytic system. With thoroughly bioactivity exploration, we found benzo[d] [1,3]dioxol-5-yl(9-(pyrimidin-2-yl)-9H-carbazol-1-yl)methanone (compound 5n) showed notable activity in disrupting the mitochondrial homeostasis, induced cell cycle arrest and apoptosis in human adenocarcinoma cells, and finally showed anti-tumor activity in an NSCLC-xenograft mice model.

Use of the RBANS to Evaluate Cognition in Patients with Schizophrenia and Metabolic Syndrome: a Meta-Analysis of Case-Control Studies.

Schizophrenia is associated with an increased risk of metabolic syndrome (MetS), which is an important risk factor for developing cognitive impairment in the general population. A few case-control studies have explored the relationship between MetS and cognitive deficits in individuals with schizophrenia but with inconsistent findings. This meta-analysis of case-control studies was carried out to explore the association between MetS and cognitive performance in patients with schizophrenia. Only case-control studies assessing the association of cognitive function and MetS in patients with schizophrenia were identified. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scale. Six case-control studies (n = 992) comparing cognition between patients with schizophrenia with MetS (n = 426) and those without MetS (n = 566) using the RBANS were identified. Compared to patients with schizophrenia without MetS, patients with schizophrenia and MetS had significantly more impairments in RBANS total scores [standardized mean difference (SMD) = -0.26, 95% confidence interval (CI): -0.51 to -0.02; I2 = 72%; p = 0.03], immediate memory (SMD = -0.32, 95% CI: -0.54 to -0.10; I2 = 66%; p = 0.005), attention (SMD = -0.29, 95% CI: -0.56 to -0.02; I2 = 77%; p = 0.03), and delayed memory (SMD = -0.24, 95% CI: -0.46 to -0.03; I2 = 64%; p = 0.03). No group difference was found regarding visuospatial skills and language (p > 0.05). This meta-analysis found that schizophrenia patients with MetS had worse performance on certain cognitive tasks than non-MetS patients.

Amplitude of Low-Frequency Fluctuation in Multiple Frequency Bands in Tension-Type Headache Patients: A Resting-State Functional Magnetic Resonance Imaging Study.

Purpose: Tension-type headache (TTH), the most prevalent primary headache disorder, imposes an enormous burden on the people of the world. The quest to ease suffering from this neurological disorder has sustained research interest. The present study aimed at evaluating the amplitude of low-frequency oscillations (LFOs) of the brain in multiple frequency bands in patients with TTH. Methods: To address this question, 63 participants were enrolled in the study, including 32 TTH patients and 31 healthy controls (HCs). For all the participants, amplitude of low-frequency fluctuation (ALFF) was measured in six frequency bands (conventional frequency bands, 0.01-0.08 Hz; slow-2, 0.198-0.25 Hz; slow-3, 0.073-0.198 Hz; slow-4, 0.027-0.073 Hz; slow-5, 0.01-0.027 Hz; and slow-6, 0-0.01 Hz), and the differences between TTH patients and HCs were examined. To explore the relationship between the altered ALFF brain regions in the six frequency bands and the Visual Analog Scale (VAS) score in the TTH patients, Pearson's correlation analysis was performed. Results: In all the six frequency bands, a decreased ALFF value was detected, and regions showing reduced ALFF values were mostly located in the middle frontal gyrus and superior gyrus. A frequency-dependent alternating characterization of intrinsic brain activity was found in the left caudate nucleus in the slow-2 band of 0.198-0.25 Hz and in the right inferior frontal orbital gyrus in the slow-5 band of 0.01-0.027 Hz. For the correlation results, both the left anterior cingulate and paracingulate gyri and right superior parietal gyrus showed a positive correlation with the VAS score in the slow-4 frequency band of 0.027-0.073 Hz. Conclusion: The ALFF alterations in the brain regions of TTH patients are involved in pain processing. The altered LFOs in the multiple regions may help promote the understanding of the pathophysiology of TTH. These observations could also allow the future treatment of TTH to be more directional and targeted and could promote the development of TTH treatment.

Association of Decreased Serum BDNF With Restless Legs Syndrome in Parkinson's Disease Patients.

Objective: To objective of the study was to investigate whether serum brain-derived neurotrophic factor (BDNF) levels are associated with the severity of restless legs syndrome (RLS) in Parkinson's disease (PD). Methods: A total of 249 PD patients with (n = 53) and without RLS (n = 196) and 326 age-matched controls were included in this study. All the serum BDNF levels of the participants were measured. The International Restless Legs Syndrome Study Group Rating Scale (IRLSSG-RS) was administered for the severity of RLS. The severity of PD patients were assessed by the Unified PD Rating Scale (UPDRS) and the Hoehn and Yahr (H-Y) stage. Results: The prevalence of RLS was significantly higher in PD patients (21.3%) than in the controls group (7.4%) (p < 0.05). The IRLSSG-RS score in PD patients with RLS (16.25 ± 5.24) was significantly increased than in controls with RLS (12.08 ± 3.99) (p < 0.01). The serum BDNF levels were significantly decreased in PD patients with RLS than in PD patients without RLS, controls without RLS, and controls with RLS (p < 0.001). BDNF levels were negatively associated with IRLSSG-RS in both PD patients with RLS and controls with RLS group (both p < 0.01). Multiple regression analysis confirmed that in either PD with RLS or controls with RLS group, BDNF was an independent contributor to IRLSSG-RS (both p < 0.01). Conclusions: Decreased serum BDNF levels may be involved in the pathophysiology of RLS in PD, suggesting that it may serve as a potential blood biomarker of diagnostic value for RLS in PD.

Performance of Two Trichogrammatid Species from Zambia on Fall Armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae).

The fall armyworm, Spodoptera frugiperda (J.E. Smith), is a noctuid moth native to the tropical and subtropical Americas that has successfully invaded Africa and Asia, where it is has become a serious threat to food security as a pest of cereals and other crops. Biological control is an environmentally friendly means of combating the pest and contributes to an integrated pest management approach. In our study, two egg parasitoid species (Trichogramma mwanzai and Trichogrammatoidea lutea) found in parasitized fall armyworm eggs in Zambia were identified by using a combination of both molecular and morphological characteristics. To evaluate their potential and efficiency on 0- to 2-day-old fall armyworm eggs, we compared their parasitism capabilities with three Trichogramma species native to China (T. ostriniae, T. leucaniae and T. japonicum) under laboratory conditions. The results showed that both parasitoid species would accept 0-, 1- and 2-day-old fall armyworm eggs, and complete their development successfully. Trichogramma mwanzai and T. lutea preferred parasitizing 0- and 1-day-old eggs over 2-day-old eggs. Trichogrammatoidea lutea females supplied with fall armyworm eggs produced the highest parasitism rate of host eggs among the five tested species, while T. mwanzai had the shortest developmental time on all test age eggs. In general, T. lutea was the best performing of the five species when reared on fall armyworm eggs, while T. japonicum was the worst. There were no significant differences, however, in percent emergence in the five test species when reared on fall armyworm eggs.

Strain Imaging in the Evaluation of Thyroid Nodules: The Associated Factors Leading to Misdiagnosis.

This study analyzed which imaging characteristics may contribute to misdiagnosis of benign and malignant thyroid nodules (TNs) through strain imaging (SI). We analyzed SI parameters and conventional ultrasound (CUS) characteristics of 264 nodules with histopathology results and we applied binary logistic regression analysis to select independent variables for incorrect SI results. The elastography imaging (EI) score and the virtual touch tissue imaging (VTI) score of malignant TNs were remarkably higher than that in benign TNs. VTI, of which the false-positive rate (FPR), the false-negative rate (FNR), and the cutoff value were 47.6% (39/82), 17.6% (32/182) and 3.5, presented higher diagnostic performance than EI. Aspect ratio (odd ratio [OR]: 14.208) and intra-nodular calcification (OR: 20.384) were significantly associated with false-positive VTI findings, while posterior acoustic feature (OR: 30.424) was significantly associated with false-negative VTI findings. Sex (OR: 0.221) and aspect ratio (OR: 0.268) were negatively associated with false-negative EI findings. In conclusion, sex and aspect ratio significantly affect the accuracy of EI results, while aspect ratio, intra-nodular calcification and posterior acoustic features notably affect the accuracy of VTI results. These CUS features of TNs should not be ignored before explaining SI examination results.

Identification of putative abdominal vibration-related genes through transcriptome analyses in the brown planthopper (Nilaparvata lugens).

The sexually mature female brown planthoppers (BPHs) send out abdominal vibration (AV) signals through the rice so that the males can obtain intraspecific, gender, and localization information to prepare for mating. Destroying vibration signals is an alternative biological method for pest control. However, the regulatory mechanism of AV in female BPHs remains elusive, which presents an obstacle to pest control. We observed that before mating female BHPs emitted abdominal vibration signals that disappeared immediately after mating and reappeared after 6 days. Therefore, ovarian and brain samples of female BPHs from Unmated-6h+ (with AV), Mated-6h- (without AV) and Mated-6d+ (with AV) individuals were collected for transcript analyses. By transcriptional sequencing analyses, 33 candidate genes that might involve in the regulation of female AV were obtained. After selecting 4 candidate genes of them for verification by RNA interference (RNAi), it was found that interference of juvenile hormone binding protein (JHBP) could greatly reduce the probability and frequency of AV for female BPHs. In general, this study identified AV-related candidate genes in female BPHs through transcriptome analyses and provided an important basis for future research on pest control in BPHs.

[Responses of the spatial distribution of Stipa breviflora to stocking rate at different scales.] / ä¸åŒå°ºåº¦ä¸‹è’æ¼ è‰åŽŸå»ºç¾¤ç§çŸ­èŠ±é’ˆèŒ çš„ç©ºé—´åˆ†å¸ƒå¯¹è½½ç•œçŽ‡çš„å“åº”.

We conducted an experiment to test the characteristics and differences of the spatial distribution of constructive species Stipa breviflora at different scales under different stocking rates in the S. breviflora desert steppe in Siziwang Banner, Inner Mongolia. The spatial distribution of S. breviflora under four treatments (control, light grazing, moderate grazing, and heavy grazing) at different scales (small scale as 1 m×1 m and mesoscale as 5 m×10 m) were analyzed. The results showed that the population density of S. breviflora at mesoscale in the control and light grazing was significantly lower than that at the small scale. Grazing significantly increased the population density of S. breviflora in the meso- and small scales. At the small scale, the population distribution of S. breviflora in the control, light grazing, moderate grazing, and heavy grazing treatments conformed to linear, exponential, exponential and exponential models, respectively, and Gaussian, exponential, Gaussian and exponential models at mesoscale fitted by semi-variance function. The spatial distribution pattern at small scales in the control was simple and better but was more complex and poorer under the heavy grazing. At the mesoscale, it was simple and better under the heavy grazing but complex and poor under the moderate grazing. The spatial heterogeneity of S. breviflora population reduced and were more uniform under the moderate and heavy grazing at meso- and small scales. In addition, the trend of population distribution in the enclosure, moderate and heavy grazing were generally the same, while light grazing showed inconsistent trend at different scales.

Abnormal Brain Glucose Metabolism in Papillary Thyroid Cancer Patients 4 Weeks After Withdrawal of Levothyroxine: A Cross-Sectional Study Using 18F-FDG PET/CT.

Background: There is no doubt that thyroid dysfunction is associated with psychiatric disorders. A large amount of thyroid carcinoma patients displayed mood disorders after the withdrawal of levothyroxine (LT4). However, it is unclear whether the disorders are related to the transient withdrawal of LT4, and if yes, what the possible underlying mechanism is. This study aims to investigate the abnormal regional cerebral glucose metabolism (rCMRglu) in a group of papillary thyroid cancer (PTC) patients without LT4 for 4 weeks and prove the relationship between the abnormal rCMRglu with depression and anxiety. Methods: Brain 18F-FDG PET/CT data of 38 consecutive PTC patients with high/intermediate-risk from June 2016 to December 2017 have been analyzed. Of the 38 patients, 23 are in the LT4 withdrawal group (WG) and 15 in the LT4 replacement group (RG). These patients were also evaluated for depressive and anxiety symptoms within 24 h after the scans based on the Hamilton Depression Rating Scale (17 items, HRDS-17) and the Hamilton Anxiety Rating Scale (HAMA) respectively. Results: Thirty-eight patients (12 men, 26 women; age range, 25-69 years; mean age, 45.8 years) were selected in the study. Compared with the RG, patients in WG showed depression and anxiety with higher total scores of HRDS-17 and HAMA (14.7 ± 5.8 vs 3.8 ± 5.5, t = -5.74, p = 0.00; 9.3 ± 4.3 vs 2.7 ± 4.1, t = -4.74, p = 0.00, respectively). In the brain glucose metabolism analysis, the WG patients showed lower rCMRglu in Occipital_Mid_R and Postcentral_L. On the other hand, data illustrated significant rCMRglu increases in the Frontal_Sup_Orb_L. Compared with the healthy group (HG), the rCMRglu of the Postcentral_L and Precuneus_L showed hypoactivity, but the Hippocampus_R and the Temporal_Inf_L showed hyperactivity. This analysis yielded a significant correlation between abnormal rCMRglu with the free thyroxine level, the serum thyroid-stimulating hormone level, HRDS-17, and HAMA scores. Conclusions: The findings showed that more PTC patients exhibited depression and anxiety after LT4 withdrawal for 4 weeks. More attention should be paid to these hypothyroid patients while they were in the hospital. Such a short-term LT4 withdrawal also likely induced abnormal rCMRglu. Our study attempts to explain the possible mechanism of mood disorders related to transient hypothyroidism.

Identify abnormal functional connectivity of resting state networks in Autism spectrum disorder and apply to machine learning-based classification.

Autism spectrum disorder (ASD) patients are often reported altered patterns of functional connectivity (FC) on resting-state functional magnetic resonance imaging (rsfMRI) scans. However, the results in similar brain regions were inconsistent. In this study, we first investigated statistical differences in large-scale resting-state networks (RSNs) on 192 healthy controls (HCs) and 103 ASD patients by using independent component analysis (ICA). Second, an image-based meta-analysis (IBMA) was applied to discover the consistency of spatial patterns from different sites. Last, utilizing these patterns as features, we used Support Vector Machine (SVM) classifier to identify whether a subject was suffering from ASD or not. As a result, six RSNs were obtained with ICA. In each RSN, we identified altered functional connectivity between ASD and HC across the multi-site data. We calculated the area under the receiver operating characteristic curve plots (AUC) to determine the classification performance. The AUC value of classification reaches 0.988. In conclusion, the present study indicates that intrinsic connectivity patterns produced from rsfMRI data could yield a possible biomarker of ASD and contributed to the neurobiology of ASD.

Evaluation of thyroid nodules with coexistent Hashimoto's thyroiditis according to various ultrasound-based risk stratification systems：A retrospective research.

PURPOSES: To investigate the efficiency of Thyroid Imaging Reporting and Data System (TI-RADS) proposed by KWAK, the American College of Radiology, and the 2015 American Thyroid Association (ATA) guidelines for thyroid nodules with Hashimoto's thyroiditis (HT) and to determine whether HT influence the diagnostic performance of these risk-stratification systems. METHODS: A total of 101 nodules with HT and 101 nodules with non-HT were retrospectively analyzed by ultrasound-based diagnostic classifications and compared with histopathological results. The areas under the receiver operating characteristic curve (AUCs) were calculated for comparative analysis. RESULTS: In the HT group, KWAK TI-RADS has the best sensitivity (91.67%), while ACR TI-RADS has the highest specificity (82.93%) and accuracy (81.19%). The AUCs of ACR TI-RADS, ATA guidelines, and KWAK TI-RADS were 0.844, 0.782, and 0.830, respectively. In the non-HT group, the sensitivity and specificity of three risk-stratification systems had no significant difference. The AUCs of ACR TI-RADS, ATA guidelines, and KWAK TI-RADS were 0.872, 0.839, and 0.874, respectively. No significant difference was found in diagnostic effectiveness of the same systems with both contexts. CONCLUSIONS: ACR TI-RADS performed the most effective for thyroid nodules in HT, whereas KWAK TI-RADS was the best for those in non-HT. Both of TI-RADS (ACR and KWAK) provided higher diagnostic effectiveness than ATA guidelines in HT or in non-HT. Moreover, HT could not affect the diagnostic performance of these risk-stratification systems.

Comparison of Supersonic Shear Wave Imaging-Derived Renal Parenchyma Stiffness Between Diabetes Mellitus Patients With and Without Diabetic Kidney Disease.

This study aims to evaluate the difference in renal parenchyma stiffness assessed by measuring Young's modulus (YM) using a supersonic shear wave imaging (SSI) technique among healthy patients and patients with type 2 diabetes mellitus (DM) with and without diabetic kidney disease (DKD). We analyzed the correlations of YM with clinical information and conventional ultrasound parameters. All patients (N = 124) were divided into three groups: (i) healthy patients (patients without kidney disease or type 2 DM, N = 31); (ii) patients with type 2 DM without kidney disease (N = 38); and (iii) patients with DKD (N = 55). Conventional and SSI ultrasound examinations were performed in all individuals for both kidneys. Then, we recorded renal length, width, parenchyma thickness, interlobar arterial resistive index (RI) and values of mean, mininum and maximum YM. The mean values of these parameters for the left and right kidneys were calculated for statistical analysis. Statistical significance was considered at p < 0.05. Among all ultrasound parameters, the mean YM demonstrated the largest area under the receiver operating characteristic (ROC) curve (0.860). The areas under the ROC curve (AUCs) for renal length, width, parenchyma thickness, interlobar arterial RI, minimum YM and maximum YM were 0.493, 0.616, 0.507, 0.733, 0.848 and 0.794, respectively. The corresponding cutoff value of mean YM was 31.73 kPa, with a sensitivity of 85.5% and a specificity of 71.0%. The mean YM in patients with type 2 DM without kidney disease (31.44 ± 3.83 kPa) was significantly higher than that in the healthy group (26.45 ± 4.32 kPa) and lower than that in the DKD group (37.60 ± 6.56 kPa). Patients with type 2 DM without kidney disease were considered as stage 0 of DKD. Thus, the mean YM in the control group was significantly lower than that in the stage 0, 2, 3, 4 and 5 subgroups. The mean YM in the stage 0-2 subgroups was lower than that in the stage 5 group, and the mean YM in the stage 0 group was lower than that in the stage 4 group. In the DKD group, the mean YM had a positive correlation with cystine-c (r = 0.634), urea (r = 0.596), creatine (r = 0.690), uric acid (r = 0.263), albumin/creatinine ratio (r = 0.428) and the presence or absence of diabetic retinopathy (r = 0.354). The mean YM also had a negative correlation with the estimated glomerular filtration rate (r = -0.657). SSI is a non-invasive method with which to diagnose DKD and has a performance superior to that of conventional ultrasound. In addition, SSI may provide a secondary index for the staging of DKD and the monitoring of renal damage in type 2 DM patients.

Application value of conventional ultrasound and real-time shear wave elastography in patients with type 2 diabetic polyneuropathy.

PURPOSE: To explore the application value of conventional ultrasound and real-time shear wave elastography (SWE) to the tibial nerve (TN) and the common peroneal nerve (CPN) in diabetic peripheral neuropathy (DPN). MATERIALS AND METHODS: Thirty-three healthy volunteers, 33 diabetic patients without DPN, and 30 diabetic patients with DPN were enrolled in this study. The anteroposterior diameter (APD), the cross-sectional area (CSA), and the perimeter of the TN and the CPN were measured by conventional ultrasound, and the stiffness of the nerves was measured by SWE. RESULTS: The conventional ultrasound parameters and stiffness of the TN in patients with DPN were significantly larger than those of the other two groups (P < 0.01). The conventional ultrasound parameters of the CPN were significantly higher in patients with DPN than in the other two groups (P < 0.01).The patients with DPN demonstrated a greater stiffness of the CPN compared to the control group (P < 0.05). The comparison of all parameters for the left and right TNs and CPNs among the three groups showed no significant difference. The area under the curve (AUC) of TN stiffness for the diagnosis of DPN was significantly greater than that of conventional ultrasound parameters. CONCLUSION: The conventional ultrasound parameters and the stiffness of the TN and the CPN were significantly higher in patients with DPN. The stiffness of the TN could better diagnose DPN than conventional ultrasound parameters. In short, conventional ultrasound and SWE of nerves are of good application value in the diagnosis of DPN.

Percent amplitude of fluctuation: A simple measure for resting-state fMRI signal at single voxel level.

The amplitude of low-frequency fluctuation (ALFF) measures resting-state functional magnetic resonance imaging (RS-fMRI) signal of each voxel. However, the unit of blood oxygenation level-dependent (BOLD) signal is arbitrary and hence ALFF is sensitive to the scale of raw signal. A well-accepted standardization procedure is to divide each voxel's ALFF by the global mean ALFF, named mALFF. Although fractional ALFF (fALFF), a ratio of the ALFF to the total amplitude within the full frequency band, offers possible solution of the standardization, it actually mixes with the fluctuation power within the full frequency band and thus cannot reveal the true amplitude characteristics of a given frequency band. The current study borrowed the percent signal change in task fMRI studies and proposed percent amplitude of fluctuation (PerAF) for RS-fMRI. We firstly applied PerAF and mPerAF (i.e., divided by global mean PerAF) to eyes open (EO) vs. eyes closed (EC) RS-fMRI data. PerAF and mPerAF yielded prominently difference between EO and EC, being well consistent with previous studies. We secondly performed test-retest reliability analysis and found that (PerAF ≈ mPerAF ≈ mALFF) > (fALFF ≈ mfALFF). Head motion regression (Friston-24) increased the reliability of PerAF, but decreased all other metrics (e.g. mPerAF, mALFF, fALFF, and mfALFF). The above results suggest that mPerAF is a valid, more reliable, more straightforward, and hence a promising metric for voxel-level RS-fMRI studies. Future study could use both PerAF and mPerAF metrics. For prompting future application of PerAF, we implemented PerAF in a new version of REST package named RESTplus.