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This study aims to determine the genetic and clinical features of TARDBP-mutated patients in our cohort of Chinese patients with amyotrophic lateral sclerosis (ALS) combined with data in the literature.We performed TARDBP mutation screening in 1258 Chinese ALS patients, including 1204 sporadic ALS (sALS) and 54 familial ALS (fALS) patients. A systematic literature review was conducted by searching TARDBP-mutated patients from China in the online databases.In our cohort, the mutant frequency of TARDBP variants was 0.3% (4/1258), with two recurrent variants (p.G294V, p.G298V) and one novel variant (p.S332G) identified. Combining with data in the literature review, the TARDBP-mutant frequency in the Chinese population was 1.4% (83/5998), with 0.8% (46/5470) in sALS and 7.0% (37/528) in fALS. Most patients had limb onset (63.0%), with an average life expectancy of 4.3 years (range 0.5-13). Disease durations significantly differed (p = 0.002), with p.M337V showing the longest duration (80 months) and p.N378D showing the shortest duration (16.7 months).Our study found that TARDBP mutation was not rare in Chinese fALS patients. Different TARDBP mutations were associated with specific features in phenotypes.

To investigate the factors that influence the occurrence of anorectal malformations (ARMs).From December 2018 to December 2019, 136 children treated for ARMs at the Children's Hospital of Chongqing Medical University were included in the case group. The control group consisted of children with intussusception or perianal abscesses. A uniform questionnaire was filled by the parents of the enrolled children.The birth weight of the cases was significantly lower than that of the controls (p .01), and children with ARMs were more likely to be complicated with single umbilical artery (SUA) (p .001). Maternal upper respiratory tract infection (adjusted odds ratio [ORMaternal infection, anemia during pregnancy, and maternal hazardous substances exposure are possible risk factors for ARMs. Folic acid supplements and multivitamin can reduce the occurrence of ARMs. Meanwhile, paternal drug use may also be a risk factor for ARMs.

Colorectal cancer (CRC) is one of the main causes of cancer-related morbidity and mortality across the globe. Although serum biomarkers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19–9 (CA-199) have been prevalently used as biomarkers in various cancers, they are neither very sensitive nor highly specific. Repeated tissue biopsies at different times of the disease can be uncomfortable for cancer patients. Additionally, the existence of tumor heterogeneity and the results of local biopsy provide limited information about the overall tumor biology. Against this backdrop, it is necessary to look for reliable and noninvasive biomarkers of CRC. Circulating tumor cells (CTCs), which depart from a primary tumor, enter the bloodstream, and imitate metastasis, have a great potential for precision medicine in patients with CRC. Various efficient CTC isolation platforms have been developed to capture and identify CTCs. The count of CTCs, as well as their biological characteristics and genomic heterogeneity, can be used for the early diagnosis, prognosis, and prediction of treatment response in CRC. This study reviewed the existing CTC isolation techniques and their applications in the clinical diagnosis and treatment of CRC. The study also presented their limitations and provided future research directions.

Emergence of antibiotic resistance presents a major setback to global health, and shortage of antibiotic pipelines has created an urgent need for development of alternative therapeutic strategies. Bacteriophage (phage) therapy is considered as a potential approach for treatment of the increasing number of antibiotic-resistant pathogens. Phage-antibiotic synergy (PAS) refers to sublethal concentrations of certain antibiotics that enhance release of progeny phages from bacterial cells. A combination of phages and antibiotics is a promising strategy to reduce the dose of antibiotics and the development of antibiotic resistance during treatment. In this review, we highlight the state-of-the-art advancements of PAS studies, including the analysis of bacterial-killing enhancement, bacterial resistance reduction, and anti-biofilm effect, at both in vitro and in vivo levels. A comprehensive review of the genetic and molecular mechanisms of phage antibiotic synergy is provided, and synthetic biology approaches used to engineer phages, and design novel therapies and diagnostic tools are discussed. In addition, the role of engineered phages in reducing pathogenicity of bacteria is explored.

For reliable downstream molecular analysis, it is crucially important to recover circulating tumor cells (CTCs) from clinical blood samples with high purity and viability. Herein, magnetic nanoparticles coated with an antifouling hydrogel layer based on the polymerization method were developed to realize cell-friendly and efficient CTC capture and recovery. Particularly, the hydrogel layer was fabricated by zwitterionic sulfobetaine methacrylate (SBMA) and methacrylic acid (MAA) cross-linked with N,N-bis(acryloyl)cystamine (BACy), which could not only resist nonspecific adhesion but also gently recover the captured cells by glutathione (GSH) responsiveness. Moreover, the anti-epithelial cell adhesion molecule (anti-EpCAM) antibody was modified onto the surface of the hydrogel to provide high specificity for CTC capture. As a result, 96% of target cells were captured in the mimic clinical blood samples with 5-100 CTCs per mL in 25 min of incubation time. After the GSH treatment, about 96% of the obtained cells were recovered with good viability. Notably, the hydrogel-coated magnetic nanoparticles were also usefully applied to isolate CTCs from the blood samples of cancer patients. The favorable results indicate that the hydrogel-modified magnetic nanoparticles may have a promising opportunity to capture and recover CTCs for subsequent research.

The isolation of specific and sensitive circulating tumor cells (CTCs) is significant for applying them in cancer diagnosis and monitoring. In this work, dual aptamer-modified poly(lactic-co-glycolic acid) (PLGA) nanofiber-based microfluidic devices were fabricated to achieve the highly efficient capture and specific release of epithelial and mesenchymal CTCs of ovarian cancer. Dual aptamer targeting epithelial cell adhesion molecules (EpCAM) and N-cadherin proteins to improve the capture sensitivity, bovine serum albumin (BSA) to guarantee the capture purity and the nanofibers to increase the capture efficiency via synchronously and effectively capturing the epithelial and mesenchymal CTCs with good capture specificity and sensitivity from blood samples were used. We used the target cells including the ovarian cancer A2780 cells (N-cadherin-high, EpCAM-low) and OVCAR-3 cells (EpCAM-high, N-cadherin-low) to test the devices, which exhibited good capture efficiency (91% for A2780 cells, 89% for OVCAR-3 cells), release efficiency (95% for A2780 cells, 88% for OVCAR-3 cells), and sensitivity for rare cells (92% for A2780 cells, 88% for OVCAR-3 cells). Finally, the clinical blood samples of ovarian cancer patients were detected by the PLGA nanofiber-based microfluidic device, and 1 to 13 CTCs were successfully confirmed to be captured with the help of immunofluorescence staining identification. The results exhibited that the dual aptamer-modified PLGA nanofiber-based microfluidic device used as a tool for CTC capture has the potential for clinical application to guide the diagnosis, treatment, and prognosis of ovarian cancer patients.

Circulating tumor cells (CTCs) are an important part of liquid biopsy as they represent a potentially rich source of information for cancer diagnosis, monitoring, prognosis, and treatment guidance. It has been proved that the nanotopography interaction between cells and the surface of CTC detection platforms can significantly improve the capture efficiency of CTCs, whereas many mature nanostructure substrates have been developed based on chemistry materials. In this work, a natural biointerface with unique biological properties is fabricated for efficient isolation and nondestructive release of CTCs from blood samples using the cancer cell membranes. The cell membrane interfaces are proved to have a good antiadhesion property for nonspecific cells because of their own electronegativity. A natural surface nanostructure is provided by the cancer cell membrane to nicely match with the surface nanotopography of CTCs. Bovine serum albumin (BSA) as a linker and DNA aptamer against the epithelial cell adhesion molecule (EpCAM) as a specific affinity molecule are then introduced onto the cell membrane interfaces to achieve the highly efficient and specific capture of CTCs. Finally, the captured target cells can be intactly released from the substrate using the complementary DNA sequence with controlling the incubation time. This study provides a smart strategy in the development of a natural biological interface for the isolation and release of CTCs with high purity.

Respiratory syncytial virus (RSV) a leading cause of pediatric and adult morbidity and mortality worldwide. It can cause complications in multiple organs, thus increasing hospital stays and costs. However, RSV-based studies have primarily focused on effects in the lungs and blood, thereby potentially neglecting critical genes and pathways. Hence, studying RSV infection

Heavy metal, organic dyes, and bacterial contamination in water endanger human/animals' health, and therefore, the detection, adsorption, and capturing of contaminants are essential for environmental safety. Ligand-rich membranes are promising for sensors, adsorption, and bacterial decontamination. Herein, tannin (TA)-reinforced 3-aminopropyltriethoxysilane (APTES) crosslinked polycaprolactone (PCL) based nanofibrous membrane (PCL-TA-APTES) was fabricated via electrospinning. PCL-TA-APTES nanofibers possess superior thermal, mechanical, structural, chemical, and aqueous stability properties than the un-crosslinked membrane. It changed its color from yellowish to black in response to Fe

The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that after the treatment, 54.7% (95%CI, 10.3 to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2 to 10.1%) died, and 27.0% (95%CI, 0 to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone.Conclusions: Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines. What is Known:• The efficacy and safety of using potential drugs such as remdesivir, glucocorticoid, and intravenous immunoglobulin (IVIG) in treating children and adolescents with COVID-19/MIS-C are unclear. What is New:• Overall, the current evidence cannot adequately demonstrate the effectiveness and safety of using remdesivir, glucocorticoids, and IVIG in treating children and adolescents with COVID-19 or MIS-C.• We are calling for the publication of high-quality clinical trials and provide substantial evidence for the development of guidelines.

This study aimed to quantitatively assess the incidence of hearing loss in relation to age in individuals with biallelic p.V37I variant in GJB2.Population screening of the biallelic p.V37I variant was performed in 30,122 individuals aged between 0 and 97 years in Shanghai. Hearing thresholds of the biallelic p.V37I individuals and the controls were determined by click auditory brainstem response or pure tone audiometry.Biallelic p.V37I was detected in 0.528% (159/30,122) of the subjects. Of the biallelic p.V37I newborns, 43.91% (18/41) passed their distortion-product otoacoustic emissions-based newborn hearing screening or had hearing thresholds lower than 20 decible above normal hearing level. The older newborns had elevated hearing thresholds, with increasing incidence of 9.52%, 23.08%, 59.38%, and 80.00% for moderate or higher grade of hearing loss in age groups of 7 to 15 years, 20 to 40 years, 40 to 60 years, and 60 to 85 years, respectively. Their hearing deteriorated at a rate of 0.40 dB hearing level per year on average; males were more susceptible, and deterioration occurred preferentially at higher sound frequencies.The biallelic p.V37I variant is associated with steadily progressive hearing loss with increasing incidence over the course of life. Most of the biallelic p.V37I individuals may develop significant hearing loss in adulthood and, can benefit from early diagnosis and intervention through wide-spread genetic screening.

Analysis of circulating tumor cells (CTCs) can provide significant clinical information for tumors, which has proven to be helpful for cancer diagnosis, prognosis monitoring, treatment efficacy, and personalized therapy. However, CTCs are an extremely rare cell population, which challenges the isolation of CTCs from patient blood. Over the last few decades, many strategies for CTC detection have been developed based on the physical and biological properties of CTCs. Among them, nanostructured interfaces have been widely applied as CTC detection platforms to overcome the current limitations associated with CTC capture. Furthermore, aptamers have attracted significant attention in the detection of CTCs due to their advantages, including good affinity, low cost, easy modification, excellent stability, and low immunogenicity. In addition, effective and nondestructive release of CTCs can be achieved by aptamer-mediated methods that are used under mild conditions. Herein, we review some progress in the detection and release of CTCs through aptamer-functionalized nanostructured interfaces.

Objectives We aimed to develop radiomics with attribute bagging, which leverages multimodal ultrasound (US) images to improve the classification accuracy of breast tumors. Methods A retrospective study was conducted. B-mode US, shear wave elastographic, and contrast-enhanced US images of 178 patients with 181 tumors (67 malignant and 114 benign) were included. Radiomics with attribute bagging consisted of extraction of 1226 radiomic features and analysis of them with attribute bagging. Histologic examination results acted as the reference standard. Radiomics with several feature selection algorithms were used for comparison. Cross-validation and a holdout test were performed to evaluate their performances. Results The accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of radiomics with attribute bagging with the multimodal US images were 84.12%, 92.86%, 78.80%, and 0.919, respectively, exceeding all the comparison methods. Conclusions Radiomics with attribute bagging combined with multimodal US images has the potential to be used for accurate diagnosis of breast tumors in the clinic.

Anorectal malformation (ARM) is known to be associated with maldevelopment of the enteric nervous system (ENS), and vitamin A (VA) and its metabolite retinoic acid (RA) play important roles in ENS development. Thus, our aim was to investigate serum VA levels in ARM newborns and RA receptor (RAR) expression in the rectum of ARM patients and animal models. Serum VA concentrations were detected in newly diagnosed ARM neonates (n = 32) and neonates with non-alimentary tract malformations (n = 30). Intestinal specimens were divided into three groups: rectum from ARM patients (n = 30), colon from a stoma (n = 30) and rectum from controls (n = 4). RAR mRNA expression was evaluated by RT-qPCR. Rectum specimens from ARM patients were divided into two groups by postoperative pathology: the normal and lesion ganglion cell groups. Immunohistochemistry and Western blot were employed to detect RARα protein expression in rectum specimens. In addition, the ARM mouse model was induced by all-trans retinoid acid (ATRA), and the expression levels of RARα and the neuronal marker NeuN in the rectum of mice on embryonic day 16.5–18.5 (E16.5–18.5) were investigated. The serum concentration of VA in ARM neonates was lower than that in control neonates (P

We performed a systematic review and meta-analysis to investigate the effects of vitamin D (VitD) supplementation on children with allergic diseases. MEDLINE, Embase, Web of Science, the Cochrane library, and three Chinese databases were searched up to 15 August 2022. Randomized controlled trials (RCTs) comparing a VitD supplementation versus a placebo for children with allergic diseases were included. Thirty-two RCTs with 2347 participants were included. VitD supplementation did not reduce the risk of asthma exacerbations in children compared with placebo overall (risk ratio (RR) = 0.84, 95% confidence interval (CI): 0.65 to 1.08, p = 0.18), but reduced the risk of asthma exacerbation in children with baseline serum 25(OH)D of

Background POU3F4 is the causative gene for X-linked deafness-2 (DFNX2), characterized by incomplete partition type III (IP-III) malformation of the inner ear. The purpose of this study was to investigate the clinical characteristics and molecular findings in IP-III patients by Sanger or nanopore single-molecule sequencing. Methods Diagnosis of IP-III was mainly based on clinical characteristics including radiological and audiological findings. Sanger sequencing of POU3F4 was carried out for these IP-III patients. For those patients with negative results for POU3F4 Sanger sequencing, nanopore long-read single-molecule sequencing was used to identify the possible pathogenic variants. Hearing intervention outcomes of hearing aids (HAs) fitting and cochlear implantation (CI) were also analyzed. Aided pure tone average (PTA) was further compared between two groups of patients according to their different locations of POU3F4 variants: in the exon region or in the upstream region. Results In total, 18 male patients from 14 unrelated families were diagnosed with IP-III. 10 variants were identified in POU3F4 by Sanger sequencing and 6 of these were reported for the first time (p.Gln181*, p.Val215Gly, p.Arg282Gln, p.Gln316*, c.903_912 delins TGCCA and p.Arg205del). Four different deletions that varied from 80 to 486 kb were identified 876–1503 kb upstream of POU3F4 by nanopore long-read single-molecule sequencing. De novo genetic mutations occurred in 21.4% (3/14) of patients with POU3F4 mutations. Among these 18 patients, 7 had bilateral HAs and 10 patients received unilateral CI. The mean aided PTA for HAs and CI users were 41.1 ± 5.18 and 40.3 ± 7.59 dB HL respectively. The mean PTAs for patients with the variants located in the exon and upstream regions were 39.6 ± 6.31 versus 43.0 ± 7.10 dB HL, which presented no significant difference (p = 0.342). Conclusions Among 14 unrelated IP-III patients, 28.6% (4/14) had no definite mutation in exon region of POU3F4. However, possible pathogenic deletions were identified in upstream region of this gene. De novo genetic mutations occurred in 21.4% (3/14) of patients with POU3F4 mutation. There was no significant difference of hearing intervention outcomes between the IP-III patients with variants located in the exon region and in the upstream region.

Objectives This study aimed to screen the significant sonographic features for differentiation of benign and malignant superficial lymph nodes (LNs) by logistic regression analysis and fit a model to diagnose LNs. Methods A total of 204 pathological LNs were analyzed retrospectively. All the LNs underwent conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) examinations. A total of 16 suspicious sonographic features were used to assess LNs. All variables that were statistically related to the diagnosis of LNs were included in the logistic regression analysis in order to ascertain the significant features of diagnosing LNs, and to establish a logistic regression analysis model. Results The significant features in the logistic regression analysis model of diagnosing malignant LNs were absence of echogenic hilus, age, and absence of hilum after enhancement. According to the results of logistic regression analysis, the formula to predict whether LNs were malignant was established. The area under the receiver operating curve (ROC) was 0.908 and the accuracy, sensitivity, and specificity were 85.0%, 92.9%, and 85.3%, respectively. Conclusion The logistic regression model for the significant sonographic features of conventional US and CEUS is an effective and accurate diagnostic tool for differentiating malignant and benign LNs.

Breast tumor segmentation is an important step in the diagnostic procedure of medical physicians and computer-aided diagnosis systems. We propose a two-step deep learning framework for breast tumor segmentation in breast ultrasound (BUS) images which requires only a few manual labels. The first step is breast anatomy decomposition handled by a semi-supervised semantic segmentation technique. The input BUS image is decomposed into four breast anatomical structures, namely fat, mammary gland, muscle and thorax layers. Fat and mammary gland layers are used as constrained region to reduce the search space for breast tumor segmentation. The second step is breast tumor segmentation performed in a weakly-supervised learning scenario where only image-level labels are available. Breast tumors are first recognized by a classification network and then segmented by the proposed class activation mapping and deep level set (CAM-DLS) method. For breast anatomy decomposition, the proposed framework achieves Dice similarity coefficient (DSC) of 83.0 ± 11.8%, 84.3 ± 10.0%, 80.7 ± 15.4% and 91.0 ± 11.4% for fat, mammary gland, muscle and thorax layers, respectively. For breast tumor recognition, the proposed framework achieves sensitivity of 95.8%, precision of 92.4%, specificity of 93.9%, accuracy of 94.8% and F1-score of 0.941. For breast tumor segmentation, the proposed framework achieves DSC of 77.3% and intersection-over-union (IoU) of 66.0%. In conclusion, the proposed framework could efficiently perform breast tumor recognition and segmentation simultaneously in a weakly-supervised setting with anatomical constraints.

The majority of current methods of isolating circulating tumor cells (CTCs) rely on a biomarker. However, the isolation efficiency may be compromised due to the heterogeneity of CTCs. In this work, a simple and broad-spectrum method is established to efficiently isolate the heterogeneous CTCs from patient blood samples using tannic acid (TA)-functionalized magnetic nanoparticles (MNPs). The TA-functionalized MNPs (MNPs-TA) inhibit the nonspecific adhesion of peripheral blood mononuclear cell (PBMC) and enhance cancer cell capture, resulting from the unique interaction between TA and glycocalyx on cancer cells. The MNPs-TA was demonstrated to effectively capture seven kinds of cancer cells (HeLa, PC-3, T24, MAD-MB-231, MCF-7, HT1080, A549) from artificial samples (62.3-93.7%). Moreover, this epithelial cell adhesion molecule (EpCAM)-independent CTC isolation method was also tested using clinical blood samples from patients with different cancers (21 patients), which may provide a universal tool to detect CTCs in the clinic.

Objective: In addition to the split hand sign, other split phenomena of different muscles also exist in amyotrophic lateral sclerosis (ALS). We analyzed the incidence of split phenomena in multiple antagonistic muscle groups in ALS patients and explored whether clinical factors affected their occurrence. Methods: 618 ALS patients were included from a single ALS center. Muscle strength in upper and lower limbs was evaluated using the modified Medical Research Council (MRC) scoring system (range from 1 to 13). Split phenomena between different antagonistic muscle groups were summarized, and the correlations with clinical factors were analyzed. Results: Split phenomena were detected in 22.3% antagonistic muscles for flexion and extension of the elbow, 11.9% for the wrist, 23.9% for fingers, 18.2% for the ankle, and 14.7% for toes. These manifestations were characterized by preferential wasting of the elbow, wrist, and finger extensor muscles compared with the flexor muscles, and the ankle and toe dorsiflexor muscles compared with the plantar flexor muscles. The presence of muscle wasting was more common when the muscle strength was stronger than a modified MRC grade 6. No definite correlation was found between split phenomena and clinical factors, including age-at-onset, gender, disease duration, the region of onset, and pyramidal tract damage. Discussion: Split phenomena of antagonistic muscle groups widely exist in ALS patients. No definitive and consistent clinical factors were observed that affected the occurrence of these phenomena.

Circulating tumor cells (CTCs) acquire mesenchymal markers (e.g., N-cadherin) and lose epithelial markers (e.g., epithelial cell adhesion molecule, EpCAM) during the epithelial-mesenchymal transition (EMT) and are therefore ideal biomarkers of tumor metastasis. However, it is still a challenge to efficiently capture and detect circulating tumor cells with different phenotypes simultaneously. In this work, to obtain aptamers targeting N-cadherin in the native conformation on live cells, we established stable N-cadherin overexpressing cells (N-cadherin cells) and used these cells to identify a panel of N-cadherin-specific aptamers through the cell-SELEX approach. Two aptamer candidates obtained after 12 rounds of selection showed a low equilibrium dissociation constant in the nanomolar range, indicating high binding affinity. The truncated aptamer candidate NC3S showed the highest binding affinity to N-cadherin cells with a low Kd value of 20.08 nM. The SYL3C aptamer was reported to target cancer cell surface biomarker EpCAM. Then, we synthesized two kinds of aptamer-modified magnetic nanoparticles (SYL3C-MNPs and NC3S-MNPs). Both SYL3C and NC3S aptamers possess excellent capture specificity and efficiency for the target cells. The aptamer-MNP cocktail exhibits a considerable capture efficiency and sensitivity for rare cancer cells of epithelial and mesenchymal phenotypes. Furthermore, no CTCs were found in blood samples from healthy donors, while CTCs were successfully isolated by using the aptamer-MNP cocktail for 15 out of 16 samples collected from patients. In summary, the two kinds of aptamer-modified MNPs could be utilized as a promising tool for capturing CTCs from clinical samples.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive injury of both upper and lower motor neurons. Recently, protein-truncating and missense mutations of

Aptamers have become the most promising recognition reagents in terms of early diagnosis and effective treatment of cancers. In this study, using cervical cancer as a model, we have identified a DNA aptamer specifically binding to cervical cancer cells with high affinity using the cell-SELEX (systematic evolution of ligands by exponential enrichment) method, in which a negative selection was carried out using normal epithelial cells as control. The binding abilities of 6 selected truncated aptamers were determined by laser confocal fluorescence microscopy and flow cytometry, while most of them only recognize the target cells and do not bind the control cells, and the aptamer C-9S with 51-mer shows the best binding affinity to Ca Ski cells (target cells) with a dissociation constant value of 19.3 ± 2.9 nM. Moreover, at physiological temperature, C-9S remains its specific recognition capability to Ca Ski cells as well. Meanwhile, C-9S shows a similar binding ability to another cervical cancer cells (HeLa). Therefore, on the basis of its excellent targeting properties and inherent functional versatility of aptamer, C-9S holds great potential to be a molecular probe for early detection, in vivo imaging, and targeted delivery for further researches in cancer.

Ovarian cancer (OC) is a lethal disease occurring in women worldwide. Due to the lack of obvious clinical symptoms and sensitivity biomarkers, OC patients are often diagnosed in advanced stages and suffer a poor prognosis. Circulating tumor cells (CTCs), released from tumor sites into the peripheral blood, have been recognized as promising biomarkers in cancer prognosis, treatment monitoring, and metastasis diagnosis. However, the number of CTCs in peripheral blood is low, and it is a technical challenge to isolate, enrich, and identify CTCs from the blood samples of patients. This work develops a simple, effective, and inexpensive strategy to capture and identify CTCs from OC blood samples using the folic acid (FA) and antifouling-hydrogel-modified fluorescent-magnetic nanoparticles. The hydrogel showed a good antifouling property against peripheral blood mononuclear cells (PBMCs). The FA was coupled to the hydrogel surface as the targeting molecule for the CTC isolation, held a good capture efficiency for SK-OV-3 cells (95.58%), and successfully isolated 2–12 CTCs from 10 OC patients’ blood samples. The FA-modified fluorescent-magnetic nanoparticles were successfully used for the capture and direct identification of CTCs from the blood samples of OC patients.

Background: Ongoing efforts have been made to identify new neuroimaging markers to track amyotrophic lateral sclerosis (ALS) progression. This study aimed to explore the monitoring value of multimodal magnetic resonance imaging (MRI) in the disease progression of ALS. Methods: From September 2015 to March 2017, ten patients diagnosed with ALS in Peking Union Medical College Hospital completed head MRI scans at baseline and during follow-up. Multimodal MRI analyses, including gray matter (GM) volume measured by voxel-based morphometry; cerebral blood flow (CBF) evaluated by arterial spin labeling; functional connectivity, including low-frequency fluctuation (fALFF) and regional homogeneity (ReHo), measured by resting-state functional MRI; and integrity of white-matter (WM) fiber tracts evaluated by diffusion tensor imaging, were performed in these patients. Comparisons of imaging metrics were made between baseline and follow-up using paired t-test. Results: In the longitudinal comparisons, the brain structure (GM volume of the right precentral gyri, left postcentral gyri, and right thalami) and perfusion (CBF of the bilateral temporal poles, left precentral gyri, postcentral gyri, and right middle temporal gyri) in both motor and extramotor areas at follow-up were impaired to different extents when compared with those at baseline (all P < 0.05, false discovery rate adjusted). Functional connectivity was increased in the motor areas (fALFF of the right precentral gyri and superior frontal gyri, and ReHo of right precentral gyri) and decreased in the extramotor areas (fALFF of the bilateral middle frontal gyri and ReHo of the right precuneus and cingulate gyri) (all P < 0.001, unadjusted). No significant changes were detected in terms of brain WM measures. Conclusion: Multimodal MRI could be used to monitor short-term brain changes in ALS patients. Key words: Amyotrophic Lateral Sclerosis; Disease Progression; Monitoring Value; Multimodal Magnetic Resonance Imaging

Purpose To explore the surgical effects of endoscopic facial nerve decompression in Bell's palsy. Materials and methods This retrospective study included 15 patients with Bell's palsy. All had grade VI (House-Brackmann grading system) complete unilateral facial paralysis before surgery and a >95% reduction in amplitude on electroneurography testing compared to the unaffected side. Their MRI results indicated perineural edema in the geniculate ganglion area. Endoscopic decompression surgery was performed soon after they presented at our hospital. The time between onset of facial paralysis and surgery ranged from 25 to 93 days. All patients had no relevant surgical history or ear diseases. Results At 1-year follow-up, 13 of the 15 (87%) patients had recovered to normal or near-normal facial function (House-Brackmann grade I-II), and all patients had reached House-Brackmann grade III or lower facial function. No obvious air-bone gap or sensorineural hearing loss occurred after surgery, and there were no severe complications or synkinesis. Conclusions Endoscopic transcanal facial nerve decompression provides a less traumatic and improved exposure of the geniculate ganglion, and may also help prevent permanent severe facial sequela. Results of intraoperative facial nerve stimulation may be related to the length of time required for recovery. The optimal time of surgery after onset of paralysis needs to be investigated further, to identify a post-drug surgical therapy which may be more acceptable for patients. Patients' response to conservative treatments should be assessed as soon as possible so as not to delay surgery.

Herein, we developed an inexpensive titanium dioxide (TiO

Extreme rarity and inherent heterogeneity of circulating tumor cells (CTCs) result in a tremendous challenge for the CTC isolation from patient blood samples with high efficiency and purity. Current CTC isolation approaches mainly rely on the epithelial cell adhesion molecule (EpCAM), which may significantly reduce the ability to capture CTCs when the expression of EpCAM is lost or down-regulated in epithelial-mesenchymal transition. Here, a rapid and highly efficient method is developed to isolate and identify heterogeneous CTCs with high efficiency from patient blood samples using the fluorescent-magnetic nanoparticles (F-MNPs). A dual-antibody interface targeting EpCAM and N-cadherin is fabricated onto the F-MNPs to capture epithelial CTCs as well as mesenchymal CTCs from whole blood samples. The poly(carboxybetaine methacrylate) brushes of excellent antifouling properties are employed to decrease nonspecific cell adhesion. Moreover, the F-MNPs provide a prompt identification strategy for heterogeneous CTCs (F-MNPs+, Hoechst 33342+, and CD45-) that can directly identify CTCs in a gentle one-step processing within 1 h after isolation from patient blood samples. This has been demonstrated through artificial samples as well as patient samples in details.

Objective: Split-hand sign is a useful clinical and electrophysiological feature in the diagnosis of amyotrophic lateral sclerosis (ALS). We proposed a novel split-hand index (SI) using F-wave pers...

Objectives To explore the cause of long survival but early onset and other prognostic factors among Chinese sporadic amyotrophic lateral sclerosis (ALS) patients. Methods Patients with ALS were recruited and followed up from Jan 2013 to Jan 2017. Phenotype and survival were compared among different age-at-onset groups. Candidate prognostic factors were analyzed by Kaplan-Meier method, Cox regression and Royston Parmar (RP) model dealing with breaches of proportional hazard assumption. Results In the cohort of 531 patients, mean age-at-onset was 53.68 years (SD:10.85) and overall estimated median survival time was 59 months (95% CI: 48.29–69.71). Pairwise comparison showed that patients above 65 years at onset were more frequently bulbar onset (adjusted residual: 3.0), less frequently lumbosacral onset (adjusted residual: −3.0), and had shorter survival compared with other age groups (p = 0.002). Cox and RP model demonstrated independent prognostic variables including age at onset, bulbar onset, diagnostic delay, MRC-score at first diagnosis and region of residence. Conclusions This clinic-based study suggested that Chinese sporadic ALS patients had relatively long survival probably due to young age and less bulbar onset cases. Short diagnostic delay, low MRC-score and northern residence were also predicative of short survival. Reallocation of resources is needed to optimize quality care and prolong survival time.

Delayed antimicrobial therapy is associated with poor outcomes in sepsis, but the optimal antibiotic administration time remains unclear. We aimed to investigate the effects of the time of antimicrobial administration on outcomes and evaluate an optimal empirical antibiotic administration time window for children with Streptococcus pneumoniae sepsis. This retrospective study enrolled children with S. pneumoniae sepsis who presented to the Children’s Hospital of Chongqing Medical University from May 2011 to December 2018. Classification and regression tree (CART) analysis was used to determine the time-to-appropriate-therapy (TTAT) breakpoint. Outcomes were compared between patients receiving early or delayed therapy, defined by CART-derived TTAT breakpoint. During the study period, 172 patients were included. The CART-derived TTAT breakpoint was 13.6 h. After adjustment for confounding factors, a TTAT of ≥13.6 hours was found to be an independent predictor of sepsis-related in-hospital mortality (odds ratio [OR] = 39.26; 95% confidence interval [CI] = 6.10 to 252.60), septic shock (OR = 4.58; 95% CI = 1.89 to 11.14), and requiring mechanical ventilation (OR = 2.70; 95% CI = 1.01 to 7.35). A Pediatric Risk of Mortality (PRISM) III score of ≥10 was independently associated with delayed therapy. Delayed antibiotic therapy was associated with poor outcomes in children with S. pneumoniae sepsis. The optimal empirical antibiotic administration time window in children with S. pneumoniae sepsis was within 13.6 h. Efforts should be made to ensure timely and appropriate therapy.

Over the last decade, significant progress has been made to develop sensitive devices for the capture of circulating tumor cells (CTCs) from blood of cancer patients. However, simple capture and counting of CTCs cannot provide effective information for understanding the biology of them. In this work, a functional biointerface is fabricated for specific capture and nondestructive release of CTCs from blood samples. A nanostrucure of porous network based on chitosan nanofibers is fabricated by electrospinning, to mimic the function of extracellular matrices, and then the poly(carboxybetaine methacrylate) (pCBMA) brushes integrating onto nanofiber interface provide the effect of interfacial properties to control nonspecific cell adhesion and the multivalent immobilization of aptamers to induce high efficient and specific CTC capture. Furthermore, a complementary sequence is used to efficiently hybridize with the aptamer to achieve nondestructive release of the captured target cells, assisted by the flexible space provided by pCBMA brushes. This work also shows how nanostructure and the interface molecules regulate the morphology of the captured CTCs, and reveals the importance of the controllable cell morphology on biointerface for an effective nondestructive release of the captured CTCs.

PURPOSE X-ray grating interferometry (XGI) provides substantially increased contrast over conventional absorption-based imaging methods and therefore shows great potential for future biomedical applications. In this work, we propose a single-shot phase retrieval method for synchrotron-based high-energy x-ray grating interferometry. Contrary to existing retrieval methods, the presented novel approach enables direct retrieval of the object's phase map quantitatively from a single projection image, thus significantly simplifying the experimental procedure and reducing data acquisition times. METHODS The phase retrieval method is analytically derived, based on the phase-attenuation duality of soft tissues when being imaged with high-energy x rays. The sensitivity of the retrieved phase map, quantified by the standard deviation, is evaluated as a function of the photon number. Numerical experiments are performed to validate the proposed method and provide some quantitative insight. RESULTS The numerical results show that the method can provide high-quality phase images, where the well-known streak artifacts are significantly suppressed. Moreover, the retrieved phase maps confirm that the method is highly stable with respect to statistical noise. CONCLUSIONS Thanks to simplified experimental procedure and reduced acquisition time and dose deposition to the sample, we believe that this new method can find its potential in biomedical imaging and in vivo studies. Future work will focus on the adaptation of the method to polychromatic x ray from tube source and to computed tomography.

Background Residential instability during pregnancy has been linked to poor health outcomes. As a first step toward providing better health care to pregnant migrant women, the size and characteristics of this population and factors associated with mobility during pregnancy should be studied. Methods Using the “Monitoring Data of Chinese Migrants” for 2012, from the Chinese National Population and Family Planning Commission, this study explored mobility patterns during pregnancy and associated factors among migrants within China. From a library of 158,556 participants, two subsamples were selected. Percentages, with chi-squared tests, and means and standard deviations, with ANOVAs, were adopted to describe mobility patterns during pregnancy (always staying in sending area, mainly staying in sending area, mainly staying in receiving area, and always staying in receiving area) and delivery location choice. Logistic regression analysis was used to explore the associated factors. Results We found that the percentage of migrants always or mainly staying in receiving areas during pregnancy rose from nearly 40% in 1985 to more than 80% in 2012, while the percentage of migrants who were mobile between receiving and sending areas during pregnancy fluctuated between 30 and 40% before 1995, and between 40 and 45% after 1995, decreasing to around 40% after 2008. The percentage of respondents who chose to deliver in receiving areas fluctuated but increased from 10% in 1985 to more than 50% in 2011. Among respondents who had delivered during the last year of the survey period, families with older pregnant women (OR = 1.09, 95% CI 1.05–1.13), their own housing (OR = 5.66, 95% CI 2.45–13.05), longer time in the receiving area (OR = 1.14, 95% CI 1.09–1.20), and strong will to integrate (OR = 1.32, 95% CI 1.15–1.51) always stayed in the receiving area during pregnancy, rather than the sending area, and families with broadly similar characteristics were inclined to choose the receiving area for their delivery. Conclusions The mobility patterns of pregnant migrant women in China have been changing in recent years, with the percentage of them staying in receiving areas during pregnancy and delivering there increasing. Individual and family characteristics were also associated with mobility patterns and delivery location choice. Electronic supplementary material The online version of this article (10.1186/s12884-018-1813-2) contains supplementary material, which is available to authorized users.

We report a specific light-up fluorescent probe for i-motif DNA for the first time. Compared with the previously reported probes, neutral red could selectively interact with an i-motif and show a significant increase in its fluorescence. This feature makes it advantageous for designing label-free fluorescent sensing systems.

In this paper, we develop a low-cost size-based microfluidic chip using conventional polycarbonate membrane to isolate CTCs from blood, and propose a strategy to increase the capture efficiency before cell filtration by a size enlargement method utilizing modified microbeads specifically binding to CTCs. Up to 91% of target cells were isolated from whole blood samples using our microfluidic capture system at a flow rate of 1mL/min. Moreover, a WBC depletion process is introduced which greatly decreases the WBC retaining on the filter membrane. The tests of immunofluorescence analysis of cells captured on the membrane were performed, which demonstrates that the device could provide a dependable CTC identification and CTC count in whole blood samples. Finally, the device was further validated in the detection of CTCs from blood samples of cancer patients, and it indicates a promising capability to detect CTC response to treatment.

It is one of the ultimate goals in cell biology to understand the complex spatio-temporal interplay of biomolecules in the cellular context. To this end, there have been great efforts on the development of various probes to detect and localize specific biomolecules in cells with a variety of microscopic imaging techniques. In this Research News, we first summarize several types of microscopy for visualizing specific biomolecular targets. Then we focus on recent advances in the design of X-ray sensitive nanoprobes for applications in synchrotron-based cellular imaging. With the availability of advanced synchrotron techniques, there has been rapid progress toward high-resolution and multi-color X-ray imaging in cells with various types of functional nanoprobes.

To determine the risk of stroke in patients with subclavian steal syndrome (SSS). We identified 165 patients with imaging-provenSSS from two hospitals. Demographic, clinical and imaging data were retrospectively collected. Patients were followed up for stroke events. Stroke occurred in 43 patients with a median follow-up of 28months. Seven of these cases were identified prospectively and 36 cases retrospectively. On multivariate analysis, presence of symptoms at presentation (p=0.029) was a significant predictor of stroke. Presence of symptoms at presentation predicted stroke in imaging-proven SSS.

Mutations in the low-complexity domain (LCD) of T cell–restricted intracellular antigen-1 (TIA1) was recently identified to be associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in non-Hispanic white populations. We sequenced the TIA1 exons 11-13 encoding LCD in a series of 588 Chinese ALS/ALS-FTD patients (Familial ALS = 29; Sporadic ALS = 546; ALS-FTD = 13) and 500 neurologically normal control subjects. We found a novel heterozygous missense mutation (c.973A>G, p.N325D) in a sporadic ALS patient, which suggests that TIA1 LCD mutations are not common in Chinese ALS/ALS-FTD.

We have previously demonstrated that mutated DNA derived from the circulation can be detected in urine and predominantly exists as DNA fragments < 1 kb. To preferentially isolate the trans-renal DNA from urine, we developed a method using carboxylated beads to separate high-MW (1 kb or larger) from low-MW DNA in urine. A primer set for 18s rRNA (generating a PCR product of 872 bp) was designed and optimized for real-time PCR quantification of high-MW DNA templates. To evaluate the method, urine samples from 5 volunteers with no known diseases and 36 patients with various colorectal diseases were collected and tested. It was found that the average removal efficiency of high-MW DNA from total urine DNA using carboxylated beads is 92.72% ± 1.42%. Furthermore, compared with using total urine DNA, our method provides a greater ability to detect mutated K-ras in the urine of colorectal cancer patients. The concurrence of K-ras mutations detected in disease tissue and the corresponding urine specimen is significantly higher (P = 0.0015) when the samples were enriched in low-MW DNA.

To investigate the correlation between the expressions of human telomerase reverse transcriptase (hTERT) and vascular endothelial growth factor (VEGF) in prostate cancer (PCa) and benign prostatic hyperplasia (BPH), and to determine if hTERT was correlated with VEGF-promoted tumor cell proliferation in prostate cancer.Immunohistochemistry was used to analyze the expressions of hTERT and VEGF in 60 cases of PCa and 60 cases of benign prostatic hyperplasia (BPH). Then their correlation in PCa was analyzed by Spearman correlative analysis.The expressions of hTERT were detected in 38 cases of PCa and 10 cases of BPH. The expressions of VEGF were detected in 46 cases of PCa and 28 cases of BPH. The expressions of hTERT and VEGF in PCa were significantly higher than those in BPH (P0.05). As a result of correlation analysis, it was found that with an increase of the expression of VEGF, the expression of hTERT also increased in PCa. Significant correlation was observed between the expressions of hTERT and VEGF in PCa (r = 0.8333, P0.05). But there was no significant correlation between the expressions of hTERT and VEGF in BPH (r = 0.3156, P0.05).All experiences above indicate that hTERT was one of the important proteins in the proliferation-promoting effect of VEGF on tumor cells in PCa.

Enamel cannot heal by itself if damaged. Hydroxyapatite (HAP) is main component of human enamel. Formation of enamel-like materials for healing enamel defects remains a challenge. In this paper, we successfully isolated the abalone water-soluble matrix (AWSM) with 1.53wt% the abalone water-soluble protein (AWSPro) and 2.04wt% the abalone water-soluble polysaccharide (AWSPs) from abandoned abalone shell, and self-healing biomineralization of tooth defects was successfully achieved in vitro. Based on X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), hot field emission scanning electron microscopy (HFESEM) and energy dispersive spectrometer (EDS) analysis, the results showed that the AWSM can efficiently induce remineralization of HAP. The enamel-like HAP was successfully achieved onto etched enamel's surface due to the presence of the AWSM. Moreover, the remineralized effect of eroded enamel was growing with the increase of the AWSM. This study provides a solution to the resource waste and environmental pollution caused by abandoned abalone shell, and we provides a new method for self-healing remineralization of enamel defects by AWSM and develops a novel dental material for potential clinical dentistry application.

A couple with a proband child of GJB2 (encoding the gap junction protein connexin 26)-associated hearing impairment and a previous pregnancy miscarriage sought for a reproductive solution to bear a healthy child. Our study aimed to develop a customized preconception-to-neonate care trajectory to fulfill this clinical demand by integrating preimplantation genetic diagnosis (PGD), noninvasive prenatal testing (NIPT), and noninvasive prenatal diagnosis (NIPD) into the strategy. Auditory and genetic diagnosis of the proband child was carried out to identify the disease causative mutations. The couple then received in-vitro-fertilization treatment, and eight embryos were obtained for day 5 biopsy. PGD was performed by short-tandem-repeat linkage analysis and Sanger sequencing of GJB2 gene. Transfer of a GJB2c.235delC heterozygous embryo resulted in a singleton pregnancy. At the 13th week of gestation, genomic DNA (gDNA) from the trio family and cell-free DNA (cfDNA) from maternal plasma were obtained for assessment of fetal chromosomal aneuploidy and GJB2 mutations. NIPT and NIPD showed the absence of chromosomal aneuploidy and GJB2-associated disease in the fetus, which was later confirmed by invasive procedures and postnatal genetic/auditory diagnosis. This strategy successfully prevented the transmission of hearing impairment in the newborn, thus providing a valuable experience in reproductive management of similar cases and potentially other monogenic disorders.

We read with interest a recent paper by Almenawer et al.1 The authors performed a meta-analysis on biopsy versus partial versus gross total resection (GTR) in older patients with high-grade gliomas (HGGs). The authors compared patients undergoing overall resection (of any extent) with patients undergoing biopsy and found significantly longer overall survival and progression-free-survival, higher postoperative Karnofsky performance status (KPS), and lower morbidity and mortality. GTR was found to be superior to subtotal resection in terms of overall survival, postoperative KPS, and progression-free survival with no difference in morbidity and mortality. The authors concluded that maximum resections are safe and are associated with longer survival time, delayed tumor progression rates, and improved functional recovery. We would like to commend the authors on their efforts to examine the impact of extent of resection on survival and functional outcomes for elderly patients with HGG. The benefit of maximal resection is uncertain in this age group since older patients tend to have more comorbidities, higher complication rates, and poorer prognosis overall. In addition, fundamental differences in tumor biology may explain some of the correlation between age and outcome.1 However, we have some doubts about the methodology and the conclusions reached by the authors. First, it is quite possible that biopsy was used for diagnostic purposes only in some of the studies included in the meta-analysis. In fact, this was clearly stated in the methods section of 3 studies.2–4 We believe it is not meaningful to include these studies in the meta-analysis since the goal of the paper was to compare outcomes in elderly patients who underwent different extents of resection, not between patients who had surgery versus those who did not. Secondly, the authors admitted that the greatest limitation in their meta-analysis was the inability to account for similar distribution of patient' characteristics. We agree with the authors that variables such as patient age, brain tumor location and size, adjuvant therapy, and preoperative baseline functional status should be taken into account when performing meta-analyses. Without looking at these factors, the conclusion reached (ie, that increasing extents of tumor resection are associated with improved outcomes) suffers from selection bias. However, these variables were presented in such a way in the individual studies that it is almost impossible to incorporate them into the meta-analysis (eg, using meta-regression). Therefore, we attempted to compare age, preoperative KPS, tumor location and size, and adjuvant treatment between biopsy and resection cohorts in the individual studies via qualitative analysis (Table 1). In the 12 studies that separated the age groups for the biopsy and resection patients, 11 reported either a higher proportion of older patients undergoing biopsy,2,5–8 or a higher mean age for the biopsy group.4,9–12 The biopsy group had a lower preoperative KPS score in 5 of the 9 studies that reported this information.2,6,12–14 The resection group was associated with a larger tumor size in the 2 studies that listed tumor size separately for the resection and biopsy groups.8,13 In the 4 studies that compared tumor location between biopsy and resection groups, patients with corpus callosum, deep lesions (eg, brainstem), and bilateral lesions were more likely to undergo biopsy,8,13,15 while endangerment of the eloquent area seemed to play little role in the decision-making process.14 In the 6 studies that reported number of patients receiving chemotherapy in the 2 groups, the proportion of patients receiving chemotherapy was higher in the resection group than that in the biopsy group in all 6 studies,2,10,11,13,14,16 while the proportion of patients receiving radiotherapy was higher in only 4 studies.2,10,11,13 Table 1. Biopsy versus resection in elderly patients with high-grade glioma In summary, even among the elderly, older patients tended to undergo biopsy rather than resection of their HGGs. Tumors located in the corpus callosum, deep lesions, and bilateral lesions were more likely to be biopsied than resected. Elderly patients undergoing resection of their HGG were more likely to receive chemotherapy than those who underwent biopsy. Consequently, the favorable outcomes associated with greater extent of resection in elderly patients may be influenced by the patient selection factors listed above and should be interpreted with caution.

ZPK (zipper protein kinase)/MUK/DLK/MAP3K12, a member of mixed-lineage kinases (MLKs), is expressed in a tissue-specific manner, particularly in developing brain, and likely to contribute to cytodifferentiation, apoptotic elimination, and migration. To understand the preferential expression of ZPK in neuronal tissues, we have analyzed the putative core promoter region upstream of the first exon of the human ZPK gene. The core promoter region is TATA-less, but contains several potential transcription factor-binding motifs such as a GC-box, all of which are well conserved between human and mouse. Reporter assays and 'gel-shift' analysis using SH-SY5Y cells revealed that a xenobiotic responsive element (XRE)-like motif (GGGCGTGTCC) was preferentially recognized by Sp3, and enhanced the core promoter activity. However, the core promoter activity was still potent even in HeLa cells which barely express ZPK. Our results suggest that, for the selective expression of ZPK gene, cell-specific negative regulatory element(s) which locate outside of the core promoter region repress the potent basic promoter activity.

Ultrasonography, the preferred imaging modality for breast diseases, has merits such as absence of radiation, high diagnostic accuracy, and convenience for follow-up, thus playing an important role in clinical diagnosis and management. The American College of Radiology (ACR) proposed Breast Imaging-Reporting and Data System (BI-RADS ) and has updated for several times. Gradually, the BI-RADS has been accepted and adopted by ultrasound physicians at all levels of hospitals in China, and it has played a certain role in improving the diagnostic level of breast ultrasound in China. In order to standardize breast ultrasound application and raise the status of ultrasound in clinical decision-making of breast diseases, based on the latest edition of ACR BI-RADS Atlas 2013, the committee has reached the “Expert Consensus on Clinical Frequently Asked Questions in Breast Ultrasonography”on a number of controversial Frequently Asked Questions (FAQs) in clinical practice (hereafter referred to as “Consensus”), and will be dedicated to updating the contents of the “Consensus”, through further experience in clinical practice and the advent of new information from further studies. This consensus is only for reference purposes for medical personnel, and the processes outlined are not mandatory by law.

We read with interest a recent paper published by Chen et al on building a multivariable model to predict the likelihood of an IDH1/2 mutation in diffuse gliomas.1 Incorporating patient age, glioblastoma diagnosis, and prior history of grade II or III gliomas, the model was shown to have high sensitivity and specificity for predicting the presence of an IDH1/2 mutation, either with or without an immunostain, and high accuracy for predicting the presence of a less common IDH1 or IDH2 mutation when the immunostain was negative. The authors suggested that the model will help triage diffuse gliomas that would benefit from mutation testing in both clinical and research settings. We commend the authors for their effort to create such a model since IDH1/2 mutation has been shown to have both diagnostic and prognostic implications in diffuse gliomas. IDH1 in adult patients is associated with younger age at diagnosis, TP53 mutation, combined 1p/19q deletion, MGMT promoter hypermethylation, and favorable patient survival.2 Detection of an IDH mutation has also been shown to be reliable for differentiating glioma from reactive gliosis.2 There are even proposals to include IDH mutation status in the next version of the WHO classification of gliomas (Gupta 2011).3 However, the utility of such a model to predict IDH mutation status in both clinical and research settings must be interpreted in the context of sensitivity and specificity of the 2 most common methods currently being used in the laboratory to detect this mutation: immunohistochemistry (IHC) and Sanger sequencing. We identified 8 studies in the literature that directly compared IHC and sequencing in their detection of IDH1/2 mutation in gliomas (Table 1). The number of samples ranged from 49 to 343. Six studies included gliomas of all grades,4–9 while 2 studies focused only on oligodendrogliomas.10,11 The antibody used for IHC was DIA-H09 in 6 studies4,5,8–11 and Imab in one study;7 another study used both antibodies.6 The concordance rate between IHC and sequencing ranged from 88% to 99%. In 5 of 8 studies, the number of mutations detected by IHC was greater than those detected by sequencing.4,6–8,10 This was explained by the fact that only IHC can detect the mutation if there is only a small population of IDH1-R132H mutation-possessing tumor cells in the sample. Under model B proposed by Chen et al the predicted probability of IDH1 is 100% if IHC is positive. This makes the implicit assumption that as long as there are a few cells in the sample that stain positive for IDH-1 on IHC, the sample should be considered IDH1 positive. However, there is no study in the literature showing that glioma samples with only a small population of IDH1-R132H mutation-possessing tumor cells exhibit the same properties as those that are unequivocally IDH1 positive. In the remaining 3 studies, in which the number of mutations detected by sequencing was greater than those detected by IHC,5,9,11 the most frequently cited reason for false negatives was that IHC had failed to detect the other types of IDH1 mutations including R132C (4%), R132L (1%), R132S (2%), R132G (2%), and IDH2 mutations.2 To some extent in cases where immunostain is negative, the model proposed by Chen et al will generate the possibility of harboring a less common mutation Table 1. Comparison of immunohistochemistry with sequencing for IDH1 testing in gliomas At our institution, we first test all diffuse glioma samples with IHC and only sequence the negative samples. If the model given by Chen et al predicts only a 20% likelihood of an IDH1 mutation in a negative IHC sample, will that change our decision to sequence the sample? The answer will be “no” if we believe that accurate assessment of the IDH1 status will factor significantly into how we prognosticate and manage the patient. The answer will only be “yes” if we are so resource constrained that the cost of sequencing outweighs the benefit provided by the information gained from accurate IDH mutation testing. Similarly, in a research setting, it is highly unlikely that any researcher would base the decision to immunostain or sequence the sample on what the model predicts. In conclusion, we suggest that the models proposed by Chen et al demonstrating the clinical and pathological factors, which can be important for predicting IDH1/2 mutation in diffuse gliomas, currently have limited utility in both the clinical and research settings.