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Peripheral nerve injury (PNI) involving the loss of sensory and movement functions is challenging to repair. Although the gold standard of PNI repair is still the use of autologous nerve grafts, the destruction of the donor side is inevitable. In the present study, peripheral nerve tissueoids (PNTs) composed of a Schwann cell (SC)-based neurotrophin-3 (NT-3) delivery system and a decellularized optic nerve (DON) with naturally oriented channels were engineered to investigate the mechanism of PNTs in nerve regeneration. Proteomic analysis and mRNA sequencing revealed that PNTs have the advantage of promoting nerve regeneration by the three mechanisms of chemotaxis, adhesion and intrinsic mobilisation. The results demonstrated that a local NT-3-enriched pool was constructed by laminin γ3 (LAMC3) in PNTs, creating a niche for the colonization of TrkC-positive SCs, attraction of axons to the defect/graft area, and remyelination. In addition, LAMC3 in PNTs can rapidly promote axon adhesion through integrin aVβ6 and can precisely guide long projecting axons to target tissues. Furthermore, the interactions among the NT-3/TrkC, LAMC3/integrin aVβ6 and the scaffold synergistically activate the PI3K-AKT signalling pathway in damaged neurons, further stimulating the intrinsic regenerative drive within the neurons to ultimately achieve the rapid reinnervation and the improvement of sensory and movement functions in the hindlimb., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Phenoxy carboxylic acid herbicides (PCAs) are difficult to degrade and, thus, pose significant threats to the environment and human health. The limit for 2,4-dichlorophenoxyacetic acid is 30 μg/L in China's standards for drinking water quality, 70 μg/L in the United States' drinking water standards, and 30 μg/L in the World Health Organization's guidelines for drinking water quality. Therefore, the development of an effective detection method for trace PCAs in water is a crucial endeavor. Metal-organic frameworks (MOFs) are novel porous materials that possess advantages such as a large specific surface area, adjustable pore size, and abundant active sites. They exhibit excellent adsorption capability for various compounds. However, the applications of MOFs as adsorbents are limited. For example, the process of isolating powdered MOFs from aqueous solutions is laborious, and microporous MOFs exhibit limited surface affinity, which decreases their mass transfer efficiency in the liquid phase. MOF crystals can be embedded in a substrate to overcome these limitations. Aerogels are obtained by drying hydrogels, which are hydrophilic polymers with a three-dimensional crosslinked network structure. Spongy aerogel materials exhibit unique structural properties such as high porosity, large pore volume, ultralow density, and easy tailorability. When MOFs are combined with an aerogel, their efficient and selective adsorption properties are preserved. In addition, MOF aerogels exhibit a hierarchical porous structure, which enhances the affinity and mass transfer efficiency of the MOF for target molecules. At present, MOF aerogels are primarily prepared by freeze-drying or using supercritical carbon dioxide. These drying processes require significant amounts of energy and time. Hence, the development of greener and more efficient methods to prepare skeleton aerogels is urgently needed. In this study, we prepared an environment-friendly aerogel at ambient temperature and pressure without the use of specialized drying equipment. This ambient-dried MOF composite aerogel was then used for the dispersive solid phase extraction (DSPE) of seven PCAs from environmental water, followed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The key parameters affecting the efficiency of DSPE, including the extraction conditions, ratio of MIL-101(Fe)-NH 2 to sodium alginate, pH of the aqueous samples, extraction time, ionic strength (salinity), and elution conditions, such as the elution solvent ratio, elution time, and elution volume, were investigated to obtain optimal extraction efficiency. The adsorbent could adsorb the target contaminants within 12 min, and the analytes could be completely desorbed within 30 s by elution with 4 mL of 1.5% (v/v) formic acid in methanol solution. The water samples could be analyzed without pH adjustment. The main adsorption mechanisms were electrostatic interactions and π-π conjugation. Thus, a new method based on MOF aerogels coupled with UHPLC-MS/MS was developed for the determination of the seven PCA residues in water. The calibration curves for the seven PCAs showed good linearity ( r 2 ≥0.9986), with limits of detection (LODs) and quantification (LOQs) ranging from 0.30 to 1.52 ng/L and from 1.00 to 5.00 ng/L, respectively. Good intra- and inter-day precision values of 6.5%-17.1% and 7.4%-19.4%, respectively, were achieved under low (8 ng/L), medium (80 ng/L), and high (800 ng/L) spiking levels. The developed method was applied to the detection of PCAs in surface water, seawater, and waste leachate, and the detected mass concentrations ranged from 0.6 to 19.3 ng/L. Spiked recovery experiments were conducted at mass concentrations of 8, 80, and 800 ng/L, and the recoveries ranged from 61.7% to 120.3%. The proposed method demonstrates good sensitivity, precision, and accuracy, and has potential applications in the detection of trace PCAs in environmental water.

Drug resistance poses a high risk to human health. Extensive use of non-antibiotic drugs contributes to antibiotic resistance genes (ARGs) transfer. However, how they affect the spread of broad-host plasmids in complex biological systems remains unknown. This study investigated the effect of metoprolol on the transfer frequency and host range of ARGs in both intrageneric and intergeneric pure culture systems, as well as in anammox microbiome. The results showed that environmental concentrations of metoprolol significantly promoted the intrageneric and intergeneric conjugative transfer. Initially, metoprolol induced excessive oxidative stress, resulting in high cell membrane permeability and bacterial SOS response. Meanwhile, more pili formation increased the adhesion and contact between bacteria, and the abundance of conjugation-related genes also increased significantly. Activation of the electron transport chain provided more ATP for this energy-consuming process. The underlying mechanism was further verified in the complex anammox conjugative system. Metoprolol induced the enrichment of ARGs and mobile genetic elements. The enhanced bacterial interaction and energy generation facilitated the high conjugative transfer frequency of ARGs. In addition, plasmid-borne ARGs tended to transfer to opportunistic pathogens. This work raises public concerns about the health and ecological risks of non-antibiotic drugs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

BC (breast cancer) is the leading cause of cancer death in women. Exosome component 2 (EXOSC2), an RNA exosome component, is elevated in BC tissues and may relate to BC carcinogenesis. In this work, the high EXOSC2 expression was correlated with TNM (Tumor Node Metastasis) stage. Moreover, overexpression of EXOSC2 enhanced tumorigenic capacity of BC cells via facilitating cell proliferation and cell cycle progression, increasing migration and angiogenesis, as well as exacerbating xenograft formation in vivo. Whereas, EXOSC2 knockdown showed anti-cancer effects, including inhibition of cell proliferation and angiogenesis. Mechanistically, EXOSC2 activated the wnt/β-catenin pathway, which was also abolished by EXOSC2 knockdown. In addition, there were m6A methylation modification sites in the mRNA of EXOSC2. WTAP (Wilms tumor 1-associated protein) bound to EXOSC2 mRNA and increased its m6A methylation, resulting in extending the half-life of EXOSC2 mRNA. Luciferase data also confirmed that WTAP enhanced EXOSC2 mRNA stability through binding with the 3'-UTR containing m6A sites. Furthermore, WTAP silencing exhibited cancer-inhibiting effects on cell viability, cell cycle progression and tube formation, which was effectively reversed by EXOSC2 overexpression. In conclusion, our results demonstrate that EXOSC2 promotes the malignant behaviors of BC cells via activating the wnt/β-catenin pathway. In addition, EXOSC2 mediates the function of WTAP which contributes to the m6A modification of EXOSC2. Totally, this study suggested that EXOSC2 mediated the pro-tumor role of WTAP via activating the wnt/β-catenin signal., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Osteoarthritis (OA) is a progressive joint disorder marked by the degradation of cartilage. Elevated concentrations of hypoxia-inducible factor-2α (HIF-2α) are intricately linked to the pathological development of OA. PT2385 has demonstrated effective inhibition of HIF-2α, thereby potentially impeding the initial advancement of OA. Nevertheless, challenges persist, including limited penetration into the deeper layers of cartilage, issues related to charge rejection, and a heightened rate of clearance from the joint. These constraints necessitate further consideration and exploration., Methods: It has been demonstrated that PT2385 exhibits efficient inhibition of HIF-2α expression, thereby contributing to the delay in the progression of osteoarthritis. The pH-responsive attributes of carbon quantum dots, specifically those employing m-phenylenediamine (m-CQDs) coated with bovine serum albumin (BSA), have been systematically evaluated. In both in vitro settings involving cartilage explants and in vivo experiments, the efficacy of BSA-m-CQDs-PT2385 (BCP) has been confirmed in facilitating the transport of PT2385 to the middle and deep layers of cartilage. Furthermore, the BCP system demonstrates controlled drug release contingent upon alterations in environmental pH., Results: While the use of PT2385 alone provides protective effects on chondrocytes within an inflamed environment, there exists an opportunity for further enhancement in its efficacy when administered via intra-articular injection. The BCP formulation, characterized by appropriate particle size and charge, facilitates seamless penetration into cartilage tissue. Additionally, BCP demonstrates the capability to release drugs in response to changes in environmental pH. In vitro experiments reveal that BCP effectively inhibits Hif-2α expression and catabolic factors in chondrocytes. Notably, cartilage explants and in vivo experiments indicate that BCP surpasses PT2385 alone in inhibiting the expression of HIF-2α and matrix metalloproteinase 13, particularly in the middle and deep layers., Conclusions: The BCP drug delivery system exhibits selective release of PT2385 in response to pH changes occurring during the progression of osteoarthritis (OA), thereby inhibiting HIF-2α expression deep within the cartilage. The use of BCP significantly augments the capacity of PT2385 to retard both cartilage degeneration and the progression of osteoarthritis. Consequently, BCP as an innovative approach utilizing m-CQDs to deliver PT2385 into articular cartilage, shows potential for treating osteoarthritis.This strategy opens new avenues for osteoarthritis treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The mechanism of alleviating bleomycin-induced pulmonary fibrosis in mice was compared between Qingqiao(Forsythiae Fructus produced with immature fruits) and Laoqiao(Forsythiae Fructus produced with mature fruits) from the pharmacodynamic correlation and composition differences. Mice were randomized into normal, model, pirfenidone(50 mg·kg~(-1)), low-and high-dose(1.3, 2.6 g·kg~(-1), respectively) Qingqiao, and low-and high-dose(1.3, 2.6 g·kg~(-1), respectively) Laoqiao groups. The mouse model of pulmonary fibrosis was established by intratracheal instillation of bleomycin, during which the survival rate and body weight changes of the mice were measured. After modeling, the lung index was calculated, and the pathological changes in the lung tissue were evaluated by hematoxylin-eosin(HE), Masson, and Sirius red staining. Transmission electron microscopy was employed to observe the ultrastructure of the lung tissue. The biochemical assay was employed to measure the levels of transforming growth factor-β1(TGF-β1), α-smooth muscle actin(α-SMA), E-cadherin, and hydroxyproline(HYP) in the lung tissue and interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in the bronchoalveolar lavage fluid(BALF). The mRNA and protein levels of matrix metalloproteinase 7(MMP7), collagen Ⅰ, E-cadherin, TNF-α, vimentin, TGF-β1, and α-SMA in the lung tissue were determined by RT-qPCR and Western blot, respectively. The expression of α-SMA in the lung tissue was detected by the immunofluorescence assay. Principal component analysis was performed to compare the effects of Qingqiao and Laoqiao in ameliorating pulmonary fibrosis. Molecular docking was employed to analyze the binding between the compounds with high content in Laoqiao and TGF-β1. The cell-counting kit(CCK-8) assay was used to examine the effects of the active compounds on TGF-β1-induced BEAS-2B and HFL1 cell models. The results showed that Qingqiao and Laoqiao increased the survival rate, reduced the lung index, alleviated the pathological damage and collagen deposition in the lung tissue, ameliorated the damage of lamellar bodies in alveolar epithelial type Ⅱ cells, lowered the level of IL-6 and TNF-α in the BALF, down-regulated the expression of HYP, MMP7, vimentin, collagen Ⅰ, TGF-β1, and α-SMA, and up-regulated the expression of E-cadherin in the lung tissue of the mouse model of pulmonary fibrosis. The collagen deposition in the mouse model of pulmonary fibrosis was comprehensively evaluated by principal component analysis, and the effects of different treatments followed the trend of high-dose Laoqiao>low-dose Laoqiao>high-dose Qingqiao>low-dose Qingqiao. Molecular docking showed that hydroxytyrosol, caffeic acid, phillygenin, and(-)-lariciresinol had strong binding affinity with TGF-β1 receptor. The results of cell experiments showed that these compounds significantly attenuated the TGF-β1-induced damage in BEAS-2B cells and inhibited the TGF-β1-induced proliferation of HFL1 cells. In conclusion, both Qingqiao and Laoqiao were effective in ameliorating bleomycin-induced pulmonary fibrosis in mice. Laoqiao was superior to Qingqiao in reducing collagen deposition, which might be attributed to the higher content of hydroxytyrosol, caffeic acid, phillygenin, and(-)-lariciresinol in Laoqiao than in Qingqiao.

Objective: To compare screw versus Kirschner wire fixation in the treatment of lateral humeral condyle fractures in children., Methods: A systematic search was conducted in PubMed, Embase, the Cochrane library, Web of Science, China National Knowledge Internet(CNKI), Wanfang Datebase from in ception to February 2022. Studies comparing screws and Kirschner wire fixation in the treatment of lateral humeral condyle fractures in children were included. Outcome measures included and excluded by a set of inclusion and exclusion criteria and evaluated for their quality, their excellent and good rate of fracture healing, malunion, delayed union or nonunion, infection, limitation of elbow flexion or extension(>10°) were extracted and analyzed using software Rev Man 5.3., Results: A total of 9 retrospective studies involving 647 patients were included, with 255 patients in the screw fixation group(including screw combined with Kirschner wire) and 392 patients in the Kirschner wire fixation group. Meta analysis showed the following:infection rate in the screw group was significantly lower than that in the Kirschner wire group[ OR =0.22, 95% CI (0.09, 0.56), P =0.001]. There were no significant differences between the 2 groups in excellent and good rate of fracture healing, malunion rate( P >0.05). Subgroup analysis showed that infection rate in the screw-only group was significantly lower than that in the Kirschner wire group[ OR =0.18, 95% CI (0.05, 0.65), P =0.009]., Conclusion: For lateral humeral condyle fractures, Screw fixation alone had a lower infection rate than kirschner wire fixation and screw combined with Kirschner wire fixation. There were no significant differences in the excellent and good rate of fracture healing, malunion. In terms of postoperative efficacy and safety of internal fixation, orthopaedic surgeons are more likely to recommend screws for fixation of lateral humeral condyle fractures in children.

Many novel PET radiotracers have demonstrated potential use in breast cancer. Although not currently approved for clinical use in the breast cancer population, these innovative imaging agents may one day play a role in the diagnosis, staging, management, and even treatment of breast cancer., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Ultrasound elastography (USE) provides complementary information of tissue stiffness and elasticity to conventional ultrasound imaging. It is noninvasive and free of radiation, and has become a valuable tool to improve diagnostic performance with conventional ultrasound imaging. However, the diagnostic accuracy will be reduced due to high operator-dependence and intra- and inter-observer variability in visual observations of radiologists. Artificial intelligence (AI) has great potential to perform automatic medical image analysis tasks to provide a more objective, accurate and intelligent diagnosis. More recently, the enhanced diagnostic performance of AI applied to USE have been demonstrated for various disease evaluations. This review provides an overview of the basic concepts of USE and AI techniques for clinical radiologists and then introduces the applications of AI in USE imaging that focus on the following anatomical sites: liver, breast, thyroid and other organs for lesion detection and segmentation, machine learning (ML) - assisted classification and prognosis prediction. In addition, the existing challenges and future trends of AI in USE are also discussed., Competing Interests: All authors have completed the ICMJE uniform disclosure form. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Wei, Wu, Tang, Pan, Chen, Zhang, Dietrich and Cui.)

Objective: To compare the long-term follow-up effect and complications of ceramic on ceramic (CoC) interface and ceramic on polyethyleneon ceramic (CoP) interface in primary total hip arthroplasty, and provide clinical evidence., Methods: Search PubMed, EMBase, the CoChrane Library databases, Web of science, Wanfang database, and CNKI from January 2000 to September 2021, screening and inclusion of randomized controlled trials (RCTs) comparing the long-term efficacy and complications of CoC interface and CoP interface in total hip arthroplasty. Literature screening, quality evaluation and data extraction were carried out according to the inclusion and exclusion criteria, using Review Manager 5.3 statistical software. The software was used to perform statistical analysis on joint function, revision, prosthesis fracture, abnormal joint noise, and prosthesis wear rate after CoC or CoP., Results: Seven RCTs studies were included, including 390 cases of hips with CoC artificial joints and 384 cases of hips with CoP artificial joints. The long-term joint function improvement of CoC and CoP artificial joints was similar and there was no significant differences, with an average difference was MD =0.63, 95% CI =(-1.81, 3.07), P =0.61. About the postoperative complications, CoC artificial joints have higher incidence rate of abnormal joint noise, with odds ratio ( OR )=11.05, 95% CI =(2.04, 59.84), P =0.005. CoP artificial joints wear faster, with an average MD =-87.11, 95% CI =(-114.40, -59.82), P <0.000 1. There was no significant difference between the two groups in the replacement-related complications such as joint dislocation, prosthesis loosening, osteolysis, and the rate of prosthesis revision caused by various reasons., Conclusion: The clinical function results and complications of CoC artificial joints are comparable to those of CoP artificial joints. Although CoP artificial joint prosthesis has a faster wear rate, it does not affect joint function and increase complications, and there is no abnormal joint noise. CoC is expensive and the long-term efficacy is equivalent to CoP. Clinicians should consider cost performance when choosing CoC.

Physicians have used palpation as a diagnostic examination to understand the elastic properties of pathology for a long time since they realized that tissue stiffness is closely related to its biological characteristics. US elastography provided new diagnostic information about elasticity comparing with the morphological feathers of traditional US, and thus expanded the scope of the application in clinic. US elastography is now widely used in the field of diagnosis and differential diagnosis of abnormality, evaluating the degree of fibrosis and assessment of treatment response for a range of diseases. The World Federation of Ultrasound Medicine and Biology divided elastographic techniques into strain elastography (SE), transient elastography and acoustic radiation force impulse (ARFI). The ARFI techniques can be further classified into point shear wave elastography (SWE), 2D SWE, and 3D SWE techniques. The SE measures the strain, while the shear wave-based techniques (including TE and ARFI techniques) measure the speed of shear waves in tissues. In this review, we discuss the various techniques separately based on their basic principles, clinical applications in various organs, and advantages and limitations and which might be most appropriate given that the majority of doctors have access to only one kind of machine., Competing Interests: None

Objectives: To evaluate the diagnostic value of computer-aided diagnosis (CAD) software on ultrasound in distinguishing benign and malignant breast masses and avoiding unnecessary biopsy., Methods: This prospective, multicenter study included patients who were scheduled for pathological diagnosis of breast masses between April 2019 and November 2020. Ultrasound images, videos, CAD analysis, and BI-RADS were obtained. The AUC, accuracy, sensitivity, specificity, PPV, and NPV were calculated and compared with radiologists., Results: Overall, 901 breast masses in 901 patients were enrolled in this study. The accuracy, sensitivity, specificity, PPV and NPV of CAD software were 89.6%, 94.2%, 87.0%, 80.4%, and 96.3, respectively, in the long-axis section; 89.0%, 91.4%, 87.7%, 80.8%, and 94.7%, respectively, in the short-axis section. With BI-RADS 4a as the cut-off value, CAD software has a higher AUC (0.906 vs 0.734 vs 0.696, all p < 0.001) than both experienced and less experienced radiologists. With BI-RADS 4b as the cut-off value, CAD software showed better AUC than less experienced radiologists (0.906 vs 0.874, p < 0.001), but not superior to experienced radiologists (0.906 vs 0.883, p = 0.057). After the application of CAD software, the unnecessary biopsy rate of BI-RADS categories 4 and 5 was significantly decreased (33.0% vs 11.9%, 37.8% vs 14.5%), and the malignant rate of biopsy in category 4a was significantly increased (11.6% vs 40.7%, 7.4% vs 34.9%, all p < 0.001)., Conclusions: CAD software on ultrasound can be used as an effective auxiliary diagnostic tool for differential diagnosis of benign and malignant breast masses and reducing unnecessary biopsy., Clinical Trial Registration: ClinicalTrials.gov (NCT03887598) KEY POINTS: • Prospective multicenter study showed that computer-aided diagnosis software provides greater diagnostic confidence for differentiating benign and malignant breast masses. • Computer-aided diagnosis software can help radiologists reduce unnecessary biopsy. • The management of patients with breast masses becomes more appropriate., (© 2021. The Author(s), under exclusive licence to European Society of Radiology.)

Objective: This study aimed to explore the value of elasticity score (ES) and strain ratio (SR) combined with conventional ultrasound in distinguishing benign and malignant breast masses and reducing biopsy of BI-RADS (Breast Imaging Reporting and Data System) 4a lesions., Methods: This prospective, multicenter study included 910 patients from nine different hospitals. The acquisition and analysis of conventional ultrasound and strain elastography (SE) were obtained by radiologists with more than 5 years of experience in breast ultrasound imaging. The diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under curve (AUC) of conventional ultrasound alone and combined tests with ES and/or SR were calculated and compared., Results: The optimal cutoff value of SR for differentiating benign from malignant masses was 2.27, with a sensitivity of 60.2% and a specificity of 84.8%. When combined with ES and SR, the AUC of the new BI-RADS classification increased from 0.733 to 0.824 ( p < 0.001); the specificity increased from 48.1% to 68.5% ( p < 0.001) without a decrease in the sensitivity (98.5% vs . 96.4%, p = 0.065); and the PPV increased from 52.2% to 63.7% ( p < 0.001) without a loss in the NPV (98.2% vs . 97.1%, p = 0.327). All three combinations of conventional ultrasound, ES, and SR could reduce the biopsy rate of category 4a lesions without reducing the malignant rate of biopsy (from 100% to 68.3%, 34.9%, and 50.4%, respectively, all p < 0.001)., Conclusions: SE can be used as a useful and non-invasive additional method to improve the diagnostic performance of conventional ultrasound by increasing AUC and specificity and reducing the unnecessary biopsy of BI-RADS 4a lesions., Competing Interests: Author CD was employed by company Hirslanden Clinic. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wei, Yan, Wu, Ye, Jiang, Liu, Wang, Wang, Wang, Pan, Hu, Song, Dietrich and Cui.)

Computer-aided diagnosis (CAD) systems have attracted extensive attention owing to their performance in the field of image diagnosis and are rapidly becoming a promising auxiliary tool in medical imaging tasks. These systems can quantitatively evaluate complex medical imaging features and achieve efficient and high-diagnostic accuracy. Deep learning is a representation learning method. As a major branch of artificial intelligence technology, it can directly process original image data by simulating the structure of the human brain neural network, thus independently completing the task of image recognition. S-Detect is a novel and interactive CAD system based on a deep learning algorithm, which has been integrated into ultrasound equipment and can help radiologists identify benign and malignant nodules, reduce physician workload, and optimize the ultrasound clinical workflow. S-Detect is becoming one of the most commonly used CAD systems for ultrasound evaluation of breast and thyroid nodules. In this review, we describe the S-Detect workflow and outline its application in breast and thyroid nodule detection. Finally, we discuss the difficulties and challenges faced by S-Detect as a precision medical tool in clinical practice and its prospects.

Purpose: This study aimed to develop a radiomics nomogram based on contrast-enhanced ultrasound (CEUS) for preoperatively assessing microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients., Methods: A retrospective dataset of 313 HCC patients who underwent CEUS between September 20, 2016 and March 20, 2020 was enrolled in our study. The study population was randomly grouped as a primary dataset of 192 patients and a validation dataset of 121 patients. Radiomics features were extracted from the B-mode (BM), artery phase (AP), portal venous phase (PVP), and delay phase (DP) images of preoperatively acquired CEUS of each patient. After feature selection, the BM, AP, PVP, and DP radiomics scores (Rad-score) were constructed from the primary dataset. The four radiomics scores and clinical factors were used for multivariate logistic regression analysis, and a radiomics nomogram was then developed. We also built a preoperative clinical prediction model for comparison. The performance of the radiomics nomogram was evaluated via calibration, discrimination, and clinical usefulness., Results: Multivariate analysis indicated that the PVP and DP Rad-score, tumor size, and AFP (alpha-fetoprotein) level were independent risk predictors associated with MVI. The radiomics nomogram incorporating these four predictors revealed a superior discrimination to the clinical model (based on tumor size and AFP level) in the primary dataset (AUC: 0.849  vs . 0.690; p < 0.001) and validation dataset (AUC: 0.788  vs . 0.661; p = 0.008), with a good calibration. Decision curve analysis also confirmed that the radiomics nomogram was clinically useful. Furthermore, the significant improvement of net reclassification index (NRI) and integrated discriminatory improvement (IDI) implied that the PVP and DP radiomics signatures may be very useful biomarkers for MVI prediction in HCC., Conclusion: The CEUS-based radiomics nomogram showed a favorable predictive value for the preoperative identification of MVI in HCC patients and could guide a more appropriate surgical planning., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a conflict of interest., (Copyright © 2021 Zhang, Wei, Wu, Zhang, Lu, Lv, Liao, Cui, Ni and Dietrich.)

The precious rare edible fungus Morchella conica is popular worldwide for its rich nutrition, savory flavor, and varieties of bioactive components. Due to its high commercial, nutritional, and medicinal value, it has always been a hot spot. However, the molecular mechanism and endophytic bacterial communities in M. conica were poorly understood. In this study, we sequenced, assembled, and analyzed the genome of M. conica SH. Transcriptome analysis reveals significant differences between the mycelia and fruiting body. As shown in this study, 1,329 and 2,796 genes were specifically expressed in the mycelia and fruiting body, respectively. The Gene Ontology (GO) enrichment showed that RNA polymerase II transcription activity-related genes were enriched in the mycelium-specific gene cluster, and nucleotide binding-related genes were enriched in the fruiting body-specific gene cluster. Further analysis of differentially expressed genes in different development stages resulted in finding two groups with distinct expression patterns. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment displays that glycan degradation and ABC transporters were enriched in the group 1 with low expressed level in the mycelia, while taurine and hypotaurine metabolismand tyrosine metabolism-related genes were significantly enriched in the group 2 with high expressed level in mycelia. Moreover, a dynamic shift of bacterial communities in the developing fruiting body was detected by 16S rRNA sequencing, and co-expression analysis suggested that bacterial communities might play an important role in regulating gene expression. Taken together, our study provided a better understanding of the molecular biology of M. conica SH and direction for future research on artificial cultivation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lü, Wu, Sun, Zhang, Wu, Jiang, Li, Huang, Wang, Zhao, Liu, Song, Mo, Pan, Yang, Long, Cui, Zhang, Wang and Tang.)

Objective: The purpose of this study was to improve the differentiation between malignant and benign thyroid nodules using deep learning (DL) in category 4 and 5 based on the Thyroid Imaging Reporting and Data System (TI-RADS, TR) from the American College of Radiology (ACR)., Design and Methods: From June 2, 2017 to April 23, 2019, 2082 thyroid ultrasound images from 1396 consecutive patients with confirmed pathology were retrospectively collected, of which 1289 nodules were category 4 (TR4) and 793 nodules were category 5 (TR5). Ninety percent of the B-mode ultrasound images were applied for training and validation, and the residual 10% and an independent external dataset for testing purpose by three different deep learning algorithms., Results: In the independent test set, the DL algorithm of best performance got an AUC of 0.904, 0.845, 0.829 in TR4, TR5, and TR4&5, respectively. The sensitivity and specificity of the optimal model was 0.829, 0.831 on TR4, 0.846, 0.778 on TR5, 0.790, 0.779 on TR4&5, versus the radiologists of 0.686 ( P =0.108), 0.766 ( P =0.101), 0.677 ( P =0.211), 0.750 ( P =0.128), and 0.680 ( P =0.023), 0.761 ( P =0.530), respectively., Conclusions: The study demonstrated that DL could improve the differentiation of malignant from benign thyroid nodules and had significant potential for clinical application on TR4 and TR5., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wu, Lv, Yin, Xu, Yan, Chen, Wang, Zhang, Cui and Dietrich.)

Objectives: This study aimed to explore associations between plasma free amino acids (PFAA) and risk of cardiovascular disease (CVD) in Chinese with Type 2 diabetes (T2D)., Methods: We retrieved 741 inpatients with T2D consecutively from tertiary hospital. Twenty-three PFAA were measured. CVD was defined as having coronary heart disease (CHD) or stroke. Principal component analysis was used to extract factors of PFAA. Factors and their components were introduced into binary logistic regressions as continuous and tertiles to obtain OR (odds ratio) and 95% confidence interval (CI) for CVD (or its components) risk., Results: Of 741 inpatients, 282 (38.1%) had CVD (CHD alone: 122, stroke alone: 109, both: 51). Five factors were extracted, accounting for 65% of the total variance. Factor 3 composed of glutamate and tryptophan was associated with increased CVD risk (ORs, 95%CI of top vs. bottom tertiles: 1.60, 1.02-2.50 for CVD; 2.19, 1.17-4.07 for stroke, 1.51, 0.83-2.73 for CHD); the ORs (top vs. bottom tertiles) of glutamate were 2.62 (95%CI, 1.18-5.84) for stroke and 1.44 (0.80-2.61) for CHD; the ORs (top vs. bottom tertiles) of tryptophan were 1.50 (0.81-2.75) for stroke and 1.07 (0.58-1.97) for CHD. Comparable results were observed according to important confounders (all P for interaction >0.05)., Conclusions: Elevated factor 3 composed of glutamate and tryptophan was associated with increased CVD, especially stroke in T2D in China., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Luo, Feng, Bai, Fang, Wu and Wu.)

Objective: To study two novel CD36 gene mutations at the CD36 splicing sites found in Guangxi population, as well as the molecular basis and population incidence of them., Methods: DNA sequencing and cDNA clonal sequencing were used to detect CD36 exon sequence and the protein coding region sequence of CD36 mRNA for 2 CD36 deficient individuals (HHC and WGM) found in Guangxi population. Eukaryotic expression cell lines were established for the discovery of CD36 mRNA abnormal transcripts and Western blot assay was used to verify the effect of abnormal CD36 mRNA transcripts on CD36 expression. A DNA PCR-SSP genotyping method was established for the two CD36 novel mutations, and the population distribution was investigated among 110 CD36 deficient individuals in Guangxi region and 296 random individuals in Guangxi population., Results: Novel mutation of c.430 -1G>C was found at the CD36 splicing site in HHC and WGM individuals, and novel mutation of c.1006 +2T>G at the CD36 splicing site was also found in the WGM individual. CD36 cDNA clonal sequencing showed that CD36 c.430 -1G>C could lead to the production of the two CD36 mRNA transcript variants: c.429&#95;430ins［430-17&#95;430-2;C］(p.Ala144fsTer1) and c.430&#95;609del(p.Ala144&#95;Pro203del)(GenBank:HM 217023.1); and CD36 c.1006 +2T>G could lead to the production of CD36 mRNA transcript variant of c.819&#95;1006 del (p.Ser274GlufsTer16) (GenBank: HM217025.1). It was verified that all the three transcript variants could lead to CD36 deficiency by establishment of eukaryotic expression cell lines and Western blot assay. A study of the population incidence of two novel CD36 splicing site mutations found showed that in 110 CD36 deficient individuals and in 296 random individuals in Guangxi region, the mutation rate of CD36 c.430 -1G>C was 10.91% (12/110) and 1.35% (4/296), respectively, while CD36 c.1006 +2T>G was 2.73% (3/110) and 0 (0/296), respectively., Conclusion: This study identifies two novel CD36 mutations at CD36 splicing site, and preliminary clarified their molecular basis for the CD36 deficiency and the distribution characteristics in Guangxi population as well. It provides an experimental and theoretical basis for studying the molecular mechanism and characteristics of CD36 deficiency in Chinese population.

Background Deep learning (DL) algorithms are gaining extensive attention for their excellent performance in image recognition tasks. DL models can automatically make a quantitative assessment of complex medical image characteristics and achieve increased accuracy in diagnosis with higher efficiency. Purpose To determine the feasibility of using a DL approach to predict clinically negative axillary lymph node metastasis from US images in patients with primary breast cancer. Materials and Methods A data set of US images in patients with primary breast cancer with clinically negative axillary lymph nodes from Tongji Hospital (974 imaging studies from 2016 to 2018, 756 patients) and an independent test set from Hubei Cancer Hospital (81 imaging studies from 2018 to 2019, 78 patients) were collected. Axillary lymph node status was confirmed with pathologic examination. Three different convolutional neural networks (CNNs) of Inception V3, Inception-ResNet V2, and ResNet-101 architectures were trained on 90% of the Tongji Hospital data set and tested on the remaining 10%, as well as on the independent test set. The performance of the models was compared with that of five radiologists. The models' performance was analyzed in terms of accuracy, sensitivity, specificity, receiver operating characteristic curves, areas under the receiver operating characteristic curve (AUCs), and heat maps. Results The best-performing CNN model, Inception V3, achieved an AUC of 0.89 (95% confidence interval [CI]: 0.83, 0.95) in the prediction of the final clinical diagnosis of axillary lymph node metastasis in the independent test set. The model achieved 85% sensitivity (35 of 41 images; 95% CI: 70%, 94%) and 73% specificity (29 of 40 images; 95% CI: 56%, 85%), and the radiologists achieved 73% sensitivity (30 of 41 images; 95% CI: 57%, 85%; P = .17) and 63% specificity (25 of 40 images; 95% CI: 46%, 77%; P = .34). Conclusion Using US images from patients with primary breast cancer, deep learning models can effectively predict clinically negative axillary lymph node metastasis. Artificial intelligence may provide an early diagnostic strategy for lymph node metastasis in patients with breast cancer with clinically negative lymph nodes. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Bae in this issue.

Artificial intelligence (AI) is gaining extensive attention for its excellent performance in image-recognition tasks and increasingly applied in breast ultrasound. AI can conduct a quantitative assessment by recognizing imaging information automatically and make more accurate and reproductive imaging diagnosis. Breast cancer is the most commonly diagnosed cancer in women, severely threatening women's health, the early screening of which is closely related to the prognosis of patients. Therefore, utilization of AI in breast cancer screening and detection is of great significance, which can not only save time for radiologists, but also make up for experience and skill deficiency on some beginners. This article illustrates the basic technical knowledge regarding AI in breast ultrasound, including early machine learning algorithms and deep learning algorithms, and their application in the differential diagnosis of benign and malignant masses. At last, we talk about the future perspectives of AI in breast ultrasound., Competing Interests: Conflict-of-interest statement: We declare that we do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

Artificial intelligence (AI), particularly deep learning algorithms, is gaining extensive attention for its excellent performance in image-recognition tasks. They can automatically make a quantitative assessment of complex medical image characteristics and achieve an increased accuracy for diagnosis with higher efficiency. AI is widely used and getting increasingly popular in the medical imaging of the liver, including radiology, ultrasound, and nuclear medicine. AI can assist physicians to make more accurate and reproductive imaging diagnosis and also reduce the physicians' workload. This article illustrates basic technical knowledge about AI, including traditional machine learning and deep learning algorithms, especially convolutional neural networks, and their clinical application in the medical imaging of liver diseases, such as detecting and evaluating focal liver lesions, facilitating treatment, and predicting liver treatment response. We conclude that machine-assisted medical services will be a promising solution for future liver medical care. Lastly, we discuss the challenges and future directions of clinical application of deep learning techniques., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors who contributed their efforts in this manuscript.

Objective: To analyse the cases of platelet transfusion refractoriness after received HLA-matched unrelated donor hematopoietic stem cell transplantation, to analyze and identify the phenotype and genotype of CD36 in both the patient and stem cell donor, as well as the characteristic of antibody induced platelet transfusion refractoriness, and to analyse the efficacy of matched CD36-deficiency platelets transfusions., Methods: The CD36 expression on platelet and monocyte was analyzed by flow cytometry (FCM) in both patient and donor. Polymerase chain reaction sequence-based typing (PCR-SBT) was used to analyze the exons sequence of CD36 and HPA. Fast monoclonal antibody-specific immobilization of platelet antigen (F-MAIPA) and FCM were used to identify platelet antibodies in the patient. Short tandem repeat polymerase chain reaction (STR-PCR) was applied to monitor engraftment evidence. The platelet level was monitored. CD36- deficiency donor's platelets were selected from CD36- deficiency donor blood bank., Results: The donor was CD36 positive and the patient was typed I CD36 deficiency. The anti-CD36 antibody was identified in patient's serum (after transplantation), while the HLA and HPA-related antibodies were excluded. Sequence analysis of CD36 exon in the patient showed Exon 6 -1G>C(Change in splicing site) homozygote, which was a novel CD36 mutation. STR, HPA and CD36 of the patient (complete chimerism) were conversed to that of donor gene types on day 18 after allo-HSCT. The positive CD36 expression on platelet and monocyte in the patient was observed on day 96 after allo-HSCT. The patient showed the platelet transfusion refractoriness which was significantly improved after platelets transfusions from CD36 deficiency donors., Conclusion: Stem cell transplants resulted in anti-CD36 and caused platelet transfusion refractoriness, that was first reported in China. To ensure the efficacy of platelet transfusion, the CD36-deficiency patient should receive CD36 deficiency platelets for transfusion.

Background: Chronic kidney disease (CKD) is a leading cause of morbidity and mortality. Biomarkers that predict end-stage renal disease (ESRD) and/or mortality could usher in new therapeutics to halt this onslaught. While fibroblast growth factor (FGF)23 can predict both ESRD and mortality, it has not been studied in North American CKD patients of Asian ethnicity., Method: This is a prospective investigation about the role of FGF23 in 998 Canadian patients of Asian descent with CKD defined by an estimated glomerular filtration rate (eGFR) <60 mL/min/m2 and followed up for 3 years., Results: The mean age of patients was 68.9 years and 68.3% were males. The mean (range) eGFR, and median FGF23 were 40.2 (11.0-59.0) mL/min and 154.1 (7.0-7,823.0) RU/mL, respectively. Over the 3 years, higher values of FGF23 levels at baseline were associated with higher risk of ESRD (hazard ratio [HR] for log[Fgf23] = 2.16 [95% CI 1.20-3.89]). Despite the short follow-up, 42 patients died due to cardiovascular diseases (38.8%), cancer (14.9%), and infections (12.7%). Log-FGF23 levels were independently associated with death, HR 1.94, 95% CI 1.24-3.03. Mortality risk increased in FGF23 subgroups from <100 to >400 RU/mL. In a time-changing covariate analysis, serial log-FGF23 levels over the 3 years predicted mortality with a HR of 2.66 (95% CI 1. 79-3.95)., Conclusion: In a Canadian Asian population with CKD, FGF23 levels obtained at 6-monthly intervals for 3 years predicted ESRD and mortality suggesting that it is also a risk marker in Asians., (© 2017 S. Karger AG, Basel.)

HLA-A*33:88 differs from HLA-A*33:03:01 by one nucleotide exchange at position 475, G>A (codon 135 GCG>ACG)., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To identify a novel human leukocyte antigen (HLA) allele HLA-B*13:92 and analyze 3D model of HLA molecule., Methods: Polymerase chain reaction sequencing-based (PCR-SBT) was used in routine HLA typing, the B locus typing results of one sample was one base mismatch with B*13:01:01, B*58:01:01 at locus 189, The Group Specific Sequencing Products (GSSP) which target at B*13 and B*58 were used to confirm difference between the new allele and highest homologous allele, then the new allele was modeled by Swiss-model to its 3D structure., Results: The sequencing results showed that the new allele with highest homologous allele B*13:01:01 was the difference in the second exon at position 189 C>A (codon 39 GAC>GAA), 39 Asp (D) was changed to Glu (E). The amino acid substitution at residue 39 of the HLA polypeptide was located in α-helices of antigenic peptide-biding region., Conclusion: This allele is a new HLA-B allele found in Chinese Guangxi Zhang population and has been designated as HLA-B*13:92 by the World Health Organization (WHO) HLA Nomenclature Committee.

The anti-malarial drug, artemisinin, is quite expensive as a result of its slow content in Artemisia annua. Recent investigations have suggested that genetic engineering of A. annua is a promising approach to improve the yield of artemisinin. In this study, the transgenic A. annua strain GYR, which has high artemisinin content, was evaluated in an environmental release trial. First, GYR plants were compared with the wild-type variety NON-GYR, with regard to phenotypic characters (plant height, crown width, stem diameter, germination rate, leaf dry weight, 1000-seed weight, leave shape). Second, stress resistance in the two varieties (salt, drought, herbicide, and cold resistance) was evaluated under different experimental conditions. Finally, gene flow was estimated. The results indicated that there were significant differences in several agronomic traits (plant height, stem diameter, and leave dry weight) between the transgenic GYR and NON-GYR plants. Salt stress in transgenic and control plants was similar, except under high NaCl concentrations (1.6%, w/w). Leaf water, proline, and MDA content (increased significantly) were significantly different. Transgenic A. annua GYR plants did not grow better than NON-GYR plants with respect to drought and herbicide resistance. The two varieties maintained vitality through the winter. Third, gene flow was studied in an environmental risk trial for transgenic GYR. The maximum gene flow frequency was 2.5%, while the maximum gene flow distance was 24.4 m; gene flow was not detected at 29.2 m at any direction. Our findings may provide an opportunity for risk assessment in future commercialization of transgenic A. annua varieties., Competing Interests: : The authors declare no conflict of interest.

This study was aimed to investigate the detection and diagnosis of the neonatal alloimmune thrombocytopenia purpura (NAITP) caused by anti-HPA-5b antibody. The platelet count and clinical manifestation in the newborn were examined. The HPA-1-21bw genotypes of the newborn and her parents were detected by multiple-PCR and DNA sequencing. The HPA-specific antibody in the sera of newborn and her mother were detected and identified by flow cytometry (FCM) and monoclonal antibody-specific immobilization of platelet antigens (MAIPA). The results indicated that the clinical manifestations of the newborn were lighter. The HPA genotyping showed that the genotype of the newborn was HPA-5ab, while that of her mother and father were HPA-5aa and HPA-5ab, respectively. The antibody against the platelet of newborn's father existed in the newborn's mother sera. The HPA antibody of the mother was identified as anti-HPA-5b. It is concluded that the newborn with neonatal alloimmune thrombocytopenia purpura was caused by the antibody against HPA-5b.

Hepatocellular carcinoma (HCC) is one of the most common human malignancies and the third leading cause of cancer mortality worldwide. The development and progression of HCC is a complicated process, involving the deregulation of multiple genes that are essential to cell biological processes. Recently, microRNAs (miRNAs) have been suggested to be closely associated with tumorigenesis. Our study showed that miR-184 is upregulated in HCC cell lines and tissues. Overexpression of miR-184 in HCC cells increased cell proliferation, tumorigenicity, and cell cycle progression, whereas inhibition of miR-184 reduced cell proliferation, tumorigenicity, and cell cycle progression. Additionally, we identified SOX7 as a direct target of miR-184. Ectopic expression of miR-184 led to downregulation of the SOX7 protein, resulting in upregulation of c-Myc, Cyclin D1, and phosphorylation of Rb. Our findings suggested that miR-184 represents a potential onco-miR and plays an important role in HCC progression by suppressing SOX7 expression.

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide and a leading cause of cancer related death. Although the mortality rate of CRC is decreasing, finding novel targets for its therapy remains urgent. Carboxypeptidase E (CPE), a member of the pro-protein convertases, which are involved in the maturation of protein precursors, has recently been reported as elevated in many types of cancer. However, its role and mechanisms in tumor progression are poorly understood., Methods: In the present study, we investigated expression of CPE in CRC cell lines and tumor tissues using Western blot and real-time qRT-PCR. Plasmids for overexpression and depletion of CPE were constructed and analyzed by Western blot, MTT and colony formation assays and bromodeoxyuridine incorporation assays. The relative expression of p21, p27, and cyclin D1 were analyzed by Real-time qRT-PCR in the indicated cells., Results: Our study showed that CPE was significantly upregulated in CRC cell lines and tumor tissues. MTT and colony formation assays indicated that overexpression of CPE enhanced cell growth rates. BrdU incorporation and flow-cytometry assays showed that ectopic expression of CPE increased the S-phase fraction cells. Soft agar assay proved enhanced tumorigenicity activity in CPE over-expressing CRC cells. Further studies of the molecular mechanisms of CPE indicated that is promoted cell proliferation and tumorigenicity through downregulation of p21 and p27, and upregulation of cyclin D1., Conclusions: Taken together, these data suggest that CPE plays an important role in cell cycle regulation and tumorigenicity, and may serve as a potential target for CRC therapeutics.

Objective: To explore the diagnosis and treatment of a case of neonatal alloimmune thrombocytopenia purpura (NAITP) caused by anti HPA-3a antibody., Methods: The platelet counts and purpuric symptom in the newborn were clinical examined. The HPA-1-21bw genotypes of the newborn and his parents were detected by multiple DNA-PCR, gene sequencing and genotyping. The HPA specificity antibody in the sera of newborn and his mother were detected by flow cytometry (FCM), and the HPA specificity antibody was identified by monoclonal antibody-specific immobilization of platelet antigens (MAIPA)., Results: The newborn had the typical symptom of NAITP, multiple subcutaneous petechia, hematuria and coffee-like vomitus. The HPA genotype of the newborn was HPA-3ab, while that of his mother and his father were HPA-3bb and HPA-3aa, respectively. The sera of newborn and his mother existed antibody against the platelet of newborn's father. The HPA antibody of the newborn and his mother were identified as anti HPA-3a. The newborn was approved a patient of NAITP caused by anti HPA-3a antibody., Conclusion: The diagnosis and treatment for NAITP newborn caused by anti HPA-3a antibody in this study was the first domestic report. It could provide successful experiences and references for the similar cases.

There are two independent mol-ecules in the asymmetric unit of the title compound, C(30)H(44)O(5). They comprise a triterpenoid skeleton of five six-membered rings and a five-membered lactone ring. The five six-membered rings are all trans-fused. In both independent mol-ecules the D rings adopt a slightly distorted half-chair conformation due the presence of the lactone ring while the other four six-membered rings all adopt chair conformations. The characteristic carbon-carbon double bond of the oleanoic skeleton is absent. Inter-molecular O-H⋯O hydrogen bonds between the hy-droxy and carbonyl groups occur in the crystal structure.

A novel iodide-catalyzed reduction method using hypophosphorous and/or phosphorus acids was developed to reduce both diaryl ketones and nitroarenes chemoselectively in the presence of chloro and bromo substituents in high yield. This efficient and practical method has been successfully applied to a large scale production of a potential anticancer agent., (© 2011 American Chemical Society)

Human lymphocyte antigen (HLA) is the most complicated human dominant polymorphic genetic system. Accurate HLA genotyping is clinically important for hematopoietic stem cell (HSC) transplantation, also important for research on many human diseases. Polymerase chain reaction-sequence based typing (PCR-SBT) provides the highest resolution level and defines new alleles, so it is widely used for HLA typing. One great disadvantage of PCR-SBT method is the fact that it cannot resolve sequences of heterozygous samples in diploid genomes, leading to ambiguous typing results which make much trouble to the accurate definition of HLA genotype. This article reviewed the occurring reasons and solution method of ambiguous allele combinations in the HLA high resolution genotyping as well as the research prospect in this field.

This study was aimed to investigate the influence of different platelet membrane glycoprotein monoclonal antibodies (McAb) which are common used in laboratories on the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) technique according to the request of 14th International Society of Blood Transfusion Platelet Immunology Workshop. 30 participant laboratories were provided with 10 known human platelet antigen (HPA) antibodies, 1 normal serum, 9 different McAbs (against GPIIb/IIIa, GPIa/IIa, GPIb/IX and GPIV respectively), and the same protocol. Each participant laboratory carried out the test as the protocol to compare the results of different McAbs against the same glycoprotein and submitted the data to organizer. The results indicated that in McAbs against GPIIb/IIIa, AP2, Gi-5 and PL2-73 showed higher mean S/CO than that of others; in GPIa/IIa, MBC202.2 and 143.1 showed higher mean S/CO than that of others; in GPIb/IX, 142.11 and CLB-MB45 (CD42b) showed higher mean S/CO than that of others; as to GPIV, 131.4 showed higher mean S/CO. In conclusion, capture effects of various McAbs are different, so that different products of McAbs exert influences on the sensitivity of MAIPA. To use a panel of McAbs against the same glycoprotein may avoid the false negative results.

Although several DNA-based human platelet antigens (HPA) typing techniques, such as PCR-SSP and PCR-SSO, have been established, the typing errors and the lack of interlaboratory reproducibility are still the issues of concerns. In the present study, polymerase chain reaction primers were designed for identification of all the phenotypically different HPA-1 to HPA-17w types by sequencing-based typing (SBT) method using genomic DNA samples. No discrepancies were observed between PCR-SSP typing and SBT typing in typing a panel of HPA-typed platelet donors that included all common HPA types and the rare HPA-1b, 2b, 3b, and 6bw homozygous donors.

This study was aimed to investigate the polymorphism of D2S1338 and D19S433 loci in Southern Chinese Han nationality population, and to evaluate its forensic application. The DNA was extracted by chromatography on che-lex-100. Fifteen STR loci (D2S1338, D19S433 etc.) were amplified by Identifiler kit and analyzed by 3100 genetic analyzer. The softwares of analysis were GeneScan 3.0 and Genetype 3.7. The results indicated that the allele frequencies of H, DP, PIC, PE of D2S1338 and D19S433 loci were obtained. The allele frequency of samples were in Hardy-Weinberg equilibrium by chi2 test. No mutation was found on D2S1338 and D19S433 loci in 370 cases of meiosis. It is concluded that the D2S1338 and D19S433 loci are high polymorphic and their mutation rates in Southern Chinese Han nationality population are low. Their good distribution is suitable for forensic individual identification and paternity testing.

Objective: To study the genetic polymorphisms of 9 Y-chromosome specific STR loci that the allele size is less than 180 bp in length in the southern Chinese Han population, and to utilize the studied result to forensic science., Methods: Nine Y-STR loci were amplified by single multiplex PCR, and the PCR products were sequenced by using ABI Prism 3100 DNA Sequencer. The allele and haplotype frequencies at 9 Y-STR loci were determined in a total of 213 unrelated males from southern Chinese Han population. Eighty-four father/son pairs with demonstrated paternity and thirty-six non-paternity father/son pairs were detected by using our Y-STR multiplex system., Results: Three Y-STR alleles for DYS426, five alleles for DYS393, DYS460, DYS391 and DYS389 I respectively, six alleles for DYS456, seven alleles for both H4 and DYS388, and eight alleles for DYS458 loci were detected in 213 unrelated male individuals. Except for the DYS426 locus with a low GD value of 0.1489, the GD values for other 8 Y-STR loci ranged from 0.5064 to 0.9133. A total of 178 haplotypes were found at 9 Y-STR loci, of which 154 haplotypes were observed only once, and the haplotype diversity was 0.9983. None of Y-STR allele mutation was observed in the 84 father/son pairs with demonstrated paternity. Among the 36 non-paternity father/son pairs, two cases could get the paternity exclusions at 2 Y-STR loci; and the paternity of 33 cases could be ruled out by 3 or more Y-STR loci; only one case was found no exclusion of paternity regardless of detecting 9 Y-STR loci., Conclusion: This result indicates that the 9 Y-STR loci with short fragment size alleles are highly polymorphic. The fluorescent multiplex amplification system that we developed is suitable for personal identification and paternity testing.

Objective: To study the ABO allele molecular characteristics of Ael blood subgroup., Methods: Five individuals of diagnosed as Ael blood subgroup were subjected to PCR amplify ABO alleles using four pairs of sequence-specific primers. Exon 6 and exon 7 at ABO locus of all samples were sequenced. An individual with AelB phenotype was chosen for further analysis of transcript structure of ABO gene., Results: Sequence analysis indicated one Ael phenotype sample with reported Ael01 allele, one Ael phenotype sample with an Ael05 allele, and two AelB and one Ael individuals did not contain referred A allele, but contain O01 or O02 allele with 261G deletion., Conclusion: Molecular bases for the Ael have highly polymorphism. The mechanism responsible for the express weak A antigen of O allele with 261G deletion awaits to be elucidated.

The ABO blood group is one of the main blood group systems, and it plays an important role in transfusion medicine and transplantation. To date, most of the many ABO subgroups with a weak expression of the A or B antigen on red blood cells have been elucidated to have specific molecular genetic background with respect to the ABO gene. The ABO*B(A) allele or CisAB allele is a type of dual ABO allele which can encode glycosyltransferases responsible for the conversion of H substance to both A and B antigen. We report here our characterization of a novel B(A) allele which differs from those reported previously.

Background and Objectives: To elucidate the molecular genetic background of the Ax phenotype in the Chinese population., Materials and Methods: The ABO genes of eight Ax phenotype samples, four Ax and four AxB, were amplified by polymerase chain reaction (PCR) and were cloned, along with those of 10 random A(1) Chinese subjects. We analysed the ABO gene transcript structure and the sequences of two exons and one intron at the ABO locus., Results: Among the four Ax phenotype samples, we identified one Ax02, two Ax03 and one novel Ax allele with the 543G > T mutation in the A102 background. Two of five family members also carry the allele. Of the four AxB phenotypes, one was designated as cis-AB-1/B101; the other three were shown to carry one B allele and one O with the nt261G deletion. The B alleles of the latter three were identical to B101 except for single point mutation at nt700C > G, nt640A > G and nt641T > C, respectively. The novel B101-like alleles were first associated with A(weak)B phenotypes., Conclusions: Two ABO*B(A) alleles and an Ax allele clearly differ from all previously reported ABO alleles, suggesting that the molecular genetic background of Ax is heterogeneous in the Chinese population.