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Power generation through harvesting human thermal energy provides an ideal strategy for self-powered wearable design. However, existing thermoelectric fibers, films, and blocks have small power generation capacity and poor flexibility, which hinders the development of self-powered wearable electronics. Here, we report a multifunctional superelastic graphene-based thermoelectric (TE) sponge for wearable electronics and thermal management. The sponge has a high Seebeck coefficient of 49.2 μV/K and a large compressive strain of 98%. After 10 000 cyclic compressions at 30% strain, the sponge shows excellent mechanical and TE stability. A wearable sponge array TE device was designed to drive medical equipment for monitoring physiological signals by harvesting human thermal energy. Furthermore, a 4 × 4 array TE device placed on the surface of a normal working Central Processing Unit (CPU) can generate a stable voltage and reduce the CPU temperature by 8 K, providing a feasible strategy for simultaneous power generation and thermal management.

Hyperparathyroidism (HPT) is classified into primary HPT (PHPT), secondary HPT (SHPT), tertiary HPT (THPT), and pseudohyperparathyroidism. Parathyroid surgery is generally reserved for patients with symptomatic PHPT and asymptomatic patients who meet the surgical guideline criteria. However, the risk of complications and mortality after parathyroid gland surgery increases with increasing patient age.This study aimed to review existing research on laser ablation, radiofrequency ablation, microwave ablation, and high-intensity focused ultrasound in the treatment of HPT and analyze its application prospects.Thermal ablation is a good alternative treatment for patients with parathyroid hyperplasia who do not meet the criteria or decline surgery. Being a type of minimally invasive treatment, ultrasound-guided thermal ablation has the advantages of easy operation, rapid recovery, and reusability and is used widely.

To synthetically evaluate the diagnostic accuracy of image features for differentiating benign from malignant gallbladder wall thickening disease with non-contrast MRI and establish the optimal diagnostic indicator. A total of 23 patients with wall thickening type gallbladder carcinoma and 61 patients with benign wall thickening disease were included. The diagnostic performance of six image features including the layered pattern on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) images, T2WI signal intensity, papillary growth, the apparent diffusion coefficient (ADC) value, and the lesion to liver parenchyma ratio (LLR) of gallbladder were evaluated and compared. The receiver operating characteristic (ROC) curve and binary logistic regression analysis were used to construct the optimally combined indicator. All six indicators showed high diagnostic accuracy. The layered pattern on DWI and LLR had the highest area under the curve (AUC) value (0.904), followed by the layered pattern on T2WI (0.883), T2WI signal intensity (0.859), ADC value (0.836), and papillary growth (0.796). There was no statistically significant difference in the AUC among indicators for pairwise comparisons. A combination of layered patterns on DWI and papillary growth was shown to be the optimal indicator by binary logistic regression analysis. The AUC value of the combination (0.972) was higher than the layered pattern on DWI (0.904) and papillary growth (0.796) (P.001). Non-contrast MRI provides several reliable indicators for differentiating benign from malignant gallbladder thickening disease. The combination of layered patterns on DWI and papillary growth is the optimal indicator.

The relationship between outpatient and inpatient care is central to the current healthcare reform debate especially in developing countries. Despite the importance of this relationship to health policy makers, empirical evidence, particularly evidence that can be interpreted as causal is limited and inconclusive. This paper examines the effects of establishing a financing scheme for outpatient care on inpatient utilization and expenditure in China's Urban Employee Basic Medical Insurance scheme. Under a quasi-experimental design, we use a unique administrative insurance claim dataset and conduct a difference-in-differences analysis. Our results indicate that after the policy change, total number of admissions and total inpatient expenditure of the enrollees decreased by 0.47% and 6.05% respectively, which imply outpatient and inpatient care are substitutes, and the reduction in cost-sharing can release the underuse of the outpatient care, so as to reduce those excessive demands for inpatient care. Moreover, we present evidence that the effects on the admissions of Ambulatory Care Sensitive Conditions which should be sensitive to outpatient care intervention are relatively limited because of the lower reimbursement cap, inadequate capacity of the local primary care providers and stickiness in patients' healthcare-seeking behaviors. While the enrollees aged over 55 and retirees are more vulnerable to the medical prices, and the enrollees living in the central districts are more responsive because of the better and more accessible primary care.

Background:. Reports evaluating the efficacy of transcranial sonography (TCS) for the differential diagnosis of Parkinson disease (PD) and other movement disorders in China are scarce. Therefore, this study aimed to assess the application of TCS for the differential diagnosis of PD, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and essential tremor (ET) in Chinese individuals. Methods:. From 2017 to 2019, 500 inpatients treated at the Department of Dyskinesia, Beijing Tiantan Hospital, Capital Medical University underwent routine transcranial ultrasound examination. The cross-sections at the midbrain and thalamus levels were scanned, and the incidence rates of substantia nigra (SN) positivity and the incidence rates of lenticular hyperechoic area were recorded. The echo of the SN was manually measured. Results:. Of the 500 patients, 125 were excluded due to poor signal in temporal window sound transmission. Among the 375 individuals with good temporal window sound transmission, 200 were diagnosed with PD, 90 with ET, 50 with MSA, and 35 with PSP. The incidence rates of SN positivity differed significantly among the four patient groups (χ2 = 121.061, P 0.017). Conclusion:. SN positivity could effectively differentiate PD from ET, PSP, and MSA in a Chinese population.

The effects of digital Cognitive Behavior Therapy for insomnia (dCBT-i) on sleep quality have been previously demonstrated but the spillover effects on fatigue, flow (a state of immersion in activities of interest), and cognitive flexibility remain unclear. The current study examined the effectiveness of dCBT-i. A total of 97 college students (20.96 ± 1.87 years, 73.1% female students) were randomly selected from a shortlist and divided into sleep intervention (n = 39), conventional education (n = 37), and healthy control (n = 21) groups. Task switching paradigm, Fatigue Severity Scale (FSS), Flow Experience Scale (FES), and the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI) were measured pre- and post-intervention. Results show that the sleep quality of the intervention group improved, and fatigue was relieved. Participants in the sleep intervention group had increased flow experience scores post-intervention and improved cognitive flexibility. The control group’s sleep quality deteriorated and fatigue level increased. dCBT-i can not only achieve a significant improvement in sleep quality and reduce fatigue, but also improve learning abilities, quality of life, flow, and cognitive flexibility. Future research should pay attention to indicators such as work efficiency, sedative use, and the durability and stability of such effects.

Background With improvements in medical technology, the doctor–patient relationship should be further improved. However, disputes between doctors and patients have increased, with the two groups frequently hurting each other. Therefore, we sought to explore the perception of Chinese patients regarding the stimuli of doctor–patient relationships with different valence. Methods We used event-related potential (ERP) to explore the brain electrical activity of 19 undergraduate participants who had a clinical experience in the previous 6 months where they perceived negative, neutral, and positive doctor–patient relationships. The ERPs were recorded, and the early ERP components (P2) and late positive potential (LPP) were measured. Results Compared with the stimuli of negative doctor–patient relationships, those of positive doctor–patient relationships would attract more attention and have larger P2 amplitude; LPP was larger for the stimuli of negative doctor–patient relationships than neutral ones in the 500–800 ms, while in the 1100–1500 ms, the stimuli of neutral doctor–patient relationships elicited larger LPP amplitude than positive ones. Conclusion Patients paid more attention to the stimuli of positive doctor–patient relationships because they expected to have the same positive relationship. Although threatening elements in negative doctor–patient relationships would catch patients’ attention and make them have implicit emotional regulation, neutral stimuli with poker-faced doctors would cause lasting attention. These results illustrate the patients’ real perception of the different valence of doctor–patient relationship stimuli.

A signal-on sandwich-like electrochemical immunosensor was built for determination of cytokeratin 19 fragments 21-1 (CYFRA 21-1) in non-small cell lung cancer (NSCLC) by confining electroactive dye (e.g., methylene blue, MB) as a probe for amplifying signals. Specifically, core-shell gold@rhodium dendritic nanocrystals (Au@Rh DNCs) behaved as a substrate for primary antibody and accelerate interfacial electron transfer. Besides, hollow carbon spheres (HCSs) were subsequently modified with polydopamine (PDA) and PtPd nanoparticles for sequential integration of the secondary antibody and confinement of MB as a label, termed as MB/PtPd/PDA/HCSs for clarity. The built sensors showed a broad linear range (100 fg mL

N-terminal pro-B-type natriuretic peptide is a major cardiac biomarker for early diagnosis and prognosis of heart failure. Herein, a novel label-free electrochemical immunosensor was developed based on home-made branched AuPd nanocrystals/N-doped porous carbon (AuPd NCS/NPC) for ultrasensitive and high-selective detection of N-terminal pro-B-type natriuretic peptide. Specifically, the AuPd NCS/NPC was prepared by a one-pot wet-chemical strategy by using thymine as a green structural directing agent, whose morphology, structures, and properties were strictly examined, showing high-efficiency catalysis towards electro-reduction of hydrogen peroxide. Under the optimized conditions, the fabricated sensor exhibited a dynamic linear range of 0.001 ∼ 10 ng mL

Regulatory authorities, industry peers, and international health policies have emphasized the value of assessing patient-reported outcomes (PROs) in clinical studies. Despite the increase in the number of clinical studies in the last decade in China, little is known about the extent of the use of PROs.To evaluate the application and characteristics of PRO instruments as primary and secondary outcomes in randomized clinical trials in China.A cross-sectional study of interventional clinical trials conducted in China from January 1, 2010, to December 31, 2020, was performed. Data obtained from the Chinese Clinical Trial Registry and ClinicalTrials.gov databases were evaluated.Trials were categorized according to those that (1) precisely listed PRO tools as outcomes, (2) mentioned patient subjective feelings in outcomes but did not clarify which tools were used for assessment, and (3) did not mention any PRO measurements. Data on study phase, setting, participant age, and sex were extracted from trials that considered patient feelings, along with the target diseases and names of the PRO tools.Among a total of 34 033 trials, 6915 (20.3%) listed the explicit PRO instruments used and 3178 (9.3%) included PRO in their outcomes but did not include the names of the assessment tools. From more than 32 million people included in the registered trials, data on 1.5 million (4.7%) patients were scientifically collected by PRO instruments, and subjective feelings were assessed for 693 867 (2.1%) participants. Pain (16.8%), cancer (15.6%), and musculoskeletal symptoms (13.3%) were the most common conditions for which PROs were precisely collected by tools. The most common tools for PRO measurements were the visual analog scale, Short-Form 36, and Hamilton Depression Scale.In this cross-sectional study, the use of PROs increased during the study period in clinical trials conducted in China. However, patient opinion appears to still be rarely measured. The application of PRO is geographically unevenly distributed. Development of PRO instruments, especially those suitable for the Chinese population, may be useful. Further expansion of PROs with respect to the scope of diseases is needed to avoid missing important data.

Obtaining high-quality embryos is one of the key factors to improve the clinical pregnancy rate of assisted reproductive technologies (ART). So far, the clinical evaluation of embryo quality depends on embryo morphology. However, the clinical pregnancy rate is still low. Therefore, new indicators are needed to further improve the evaluation of embryo quality. Several studies have shown that the decrease of sperm-specific protein actin-like 7A (ACTL7A) leaded to low fertilization rate, poor embryo development, and even infertility. The aim of this study was to study whether the different expression levels of ACTL7A on sperm can be used as a biomarker for predicting embryo quality. In this study, excluding the factors of severe female infertility, a total of 281 sperm samples were collected to compare the ACTL7A expression levels of sperms with high and low effective embryo rates and analyze the correlation between protein levels and in-vitro fertilization (IVF) laboratory outcomes. Our results indicated that the ACTL7A levels were significantly reduced in sperm samples presenting poor embryo quality. Furthermore, the protein levels showed a significant correlation with fertilization outcomes of ART. ACTL7A has the potential to be a biomarker for predicting success rate of fertilization and effective embryo and the possibility of embryo arrest. In conclusion, sperm-specific protein ACTL7A has a strong correlation with IVF laboratory outcomes and plays important roles in fertilization and embryo development.

Background The aim of this study is to propose a new TI-RADS and compare it with the American College of Radiology (2017 ACR)-TI-RADS and the 2020 Chinese (2020 C)-TI-RADS. Methods A retrospective analysis of 749 thyroid nodules was performed. Based on the calculated odds ratio of ultrasonic signs between benign and malignant nodules, a new thyroid nodule score and malignancy rate were calculated. A receiver operating characteristic curve was drawn to analyze the new system’s effectiveness in the differential diagnosis of benign and malignant thyroid nodules and was compared with the 2020 C-TI-RADS and 2017 ACR-TI-RADS. Five ultrasound physicians with different qualifications graded another 123 thyroid nodules according to the 2017ACR-TI-RADS, 2020 C-TI-RADS, and the newly proposed TI-RADS. Intergroup and intragroup consistency was evaluated using the Kappa test and intraclass correlation coefficient (ICC) test. Results 1) The new thyroid nodule score was divided into 0, 1, 2, 3, 4, and 5 points, with malignancy rates of 1.52%, 7.69%, 38.24%, 76.00%, 90.75%, and 93.75%, respectively. Using 3 points as the cutoff value to diagnose benign and malignant thyroid nodules, the sensitivity and specificity were 94.03% and 67.39%, respectively, which were higher than those of the 2017 ACR-TI-RADS and 2020 C-TI-RADS. The simplified TI-RADS, namely, sTI-RADS, was established as follows: sTI-RADS 3 (0 points), malignancy rate 90%. 2) Five ultrasound doctors graded thyroid nodules by the 2017 ACR-TI-RADS, 2020C-TI-RADS and sTI-RADS. Intragroup consistency was good among all tests; ICC were 0.86 (0.82–0.90), 0.84 (0.78–0.88), and 0.88 (0.84–0.91), respectively, while only sTI-RADS had good intergroup consistency. Conclusion In summary, we proposed a new TI-RADS, namely, sTI-RADS, which was obtained using a simple assignment method with higher specificity, accuracy, positive predictive value, and Youden index than the 2017 ACR-TI-RADS and 2020 C-TI-RADS.

Preeclampsia (PE) is a pregnancy complication characterized by severe hypertension and multiple organ damage. Gut microbiota has been linked to PE by previous amplicon sequencing studies. To resolve the PE gut microbiota in a higher taxonomy resolution, we performed shotgun metagenomic sequencing on the fecal samples from 40 early-onset PE and 37 healthy pregnant women. We recovered 1,750 metagenome-assembled genomes (representing 406 species) from the metagenomic dataset and profiled their abundances. We found that PE gut microbiota had enriched in some species belonging to Blautia, Pauljensenia, Ruminococcus, and Collinsella and microbial functions such as the bacitracin/lantibiotics transport system, maltooligosaccharide transport system, multidrug efflux pump, and rhamnose transport system. Conversely, the gut microbiome of healthy pregnant women was enriched in species of Bacteroides and Phocaeicola and microbial functions including the porphyrin and chlorophyll metabolism, pyridoxal-P biosynthesis, riboflavin metabolism, and folate biosynthesis pathway. PE diagnostic potential of gut microbial biomarkers was developed using both species and function profile data. These results will help to explore the relationships between gut bacteria and PE and provide new insights into PE early warning.

BackgroundFew studies have described the relationship between the type of infertility and live birth in patients treated with intrauterine insemination (IUI). We focused on this issue and attempted to explore it.MethodsThis retrospective study enrolled 2,256 infertile patients who underwent their first IUI cycle and were subsequently diagnosed with a clinical pregnancy at Ji’an Women and Child Health Care Hospital between 2007 and 2018. Inductees were divided into primary infertility (1,680 patients) and secondary infertility groups (876 patients). Following 1:1 propensity score matching to obtain balanced data, the COX proportional hazards model, landmark analysis, and subgroup analysis were used to assess the association between infertility types and live birth rates. Subsequently, a sensitivity analysis was employed to evaluate the potential effect of unmeasured confounding on outcomes.ResultsOf the 1,486 patients who were identified as a matched cohort, 743 were in the primary infertility group and the remaining patients were in another group. A total of 1,143 patients had live births during 431,009 person-days of follow-up (average 290.0 days). Throughout the follow-up period, patients with secondary infertility demonstrated more live births than patients with primary infertility (hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.04 to 1.30; P = .007). More details were observed in the landmark analysis. Live birth rates were similar in both groups within 316 days of follow-up (HR, 0.84; 95% CI, 0.62 to 1.14; P = .269), whereas the opposite was found between 316 days of follow-up and delivery day (HR, 1.19; 95% CI, 1.06 to 1.34; P = .004). This was also obtained in a subgroup analysis of patients younger than 35 years old and patients treated with natural cycles (NCs) and IUIs.ConclusionAmong the infertile patients who underwent a single natural or stimulated cycle followed by IUI and had later pregnancies, full-term young secondary infertility mothers (

Background Risk stratification of asymptomatic carotid plaque remains an issue in stroke prevention in clinical practice. Purpose To investigate whether a multimodal ultrasound (MMU) model would help plaque risk stratification in patients with asymptomatic carotid stenosis. Material and Methods A prospective study was conducted of symptomatic and asymptomatic patients with > 50% proximal internal carotid artery (ICA) stenosis. All patients underwent MMU examination. Multivariable regression analyses were performed to identify parameters associated with ischemic vascular events (IVE). These parameters were used to develop a scoring nomogram to assess the probability of IVE. We elaborated the diagnostic performance of the MMU nomogram using receiver operating characteristic (ROC) curves. Results From December 2018 to December 2019, 98 patients (75 men, mean age 67 ± 8 years) were included; 50 were symptomatic and 48 were asymptomatic. Multivariable regression analyses revealed that plaque surface morphology (PSM) (odds ratio [OR] 2.99, 95% confidence interval [CI] 1.26–7.12, P = 0.013), intraplaque neovascularization (IPN) grades (OR 3.23, 95% CI 1.77–5.89, PConclusions In patients with proximal ICA > 50%, PSM, IPN grades, and CSD were independent variables associated with IVE. The MMU nomogram provided favorable value to risk stratification of IVE. Future large-scale studies with long-term follow-up are needed to validate these findings.

Hepatocellular carcinoma (HCC) is a major cause of cancer‐related death worldwide, accounting for 90% of liver cancers. Effective systemic treatments for advanced stage HCC are limited. The recent clinical application of mutated neoantigens as immunotherapeutic targets in several human cancers demonstrated that boosting host T cell responses to these antigens may help control patient tumors. With increased enthusiasm for targeting mutated neoantigens as a strategy in cancer immunotherapy, many clinical trials were initiated to apply mutated neoantigens as targets for the therapy of HCC and other solid tumors. However, recent studies suggest that targeting mutated neoantigens for the immunotherapy of HCC and other solid tumors has pitfalls and may not achieve efficacy without strategic changes. Herein, we discuss the limits of using neoantigens as targets in HCC immunotherapy and suggest alternative strategies to overcome these limits. Importantly, similar limits and alternative strategies are likely applicable to other intermediate and low tumor mutation burden cancers.

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection is lacking, and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARS-CoV-2 infection is a critical determinant for patients’ outcomes. SARS-CoV-2 infection results in seroconversion and production of anti-SARS-CoV-2 antibodies. The antibodies may suppress viral replication through neutralization but might also participate in COVID-19 pathogenesis through a process termed antibody-dependent enhancement. Rapid progress has been made in the research of antibody response and therapy in COVID-19 patients, including characterization of the clinical features of antibody responses in different populations infected by SARS-CoV-2, treatment of COVID-19 patients with convalescent plasma and intravenous immunoglobin products, isolation and characterization of a large panel of monoclonal neutralizing antibodies and early clinical testing, as well as clinical results from several COVID-19 vaccine candidates. In this review, we summarize the recent progress and discuss the implications of these findings in vaccine development.

BACKGROUND: Leg length discrepancy (LLD) can cause abnormal posture, muscle and/or joint pains, which leads to walking difficulties. The common treatment is to use a shoe lift on the shorter leg side, but this has unsatisfying results. OBJECTIVE: Through research and development, we created 3D printing orthotic insoles for LLD patients and aimed to improve their symptoms. METHODS: 1. Research and development of 3D printing orthotic insole: (1) foot scan and data acquisition; (2) insole software modeling; (3) 3D printing insole using TPU materials, and (4) post-processing. 2. Clinical observation: we customized insoles for LLD patients and required them to wear them while walking. We conducted general inquiries and a functional evaluation before and after 12 weeks of wearing insoles. RESULTS: There are seven complete cases. The joint and lower back pains were alleviated. The stride frequency, stride and pace were improved in all seven cases. Patients’ overall health condition improved significantly. CONCLUSIONS: The 3D printing orthotic insoles are made with clear procedures and practical operability. By wearing insoles, patients’ muscle and/or joint pains were relieved and their gaits were improved.

No current in vitro tumor model replicates a tumor’s in vivo microenvironment. A culturing technique that better preserves a tumor’s pathophysiological conditions is needed for some important clinical applications, including personalized drug-sensitivity/resistance assays. In this study, we utilized autologous serum or body fluid to build a 3D scaffold and grow a patient’s tumor. We named this technique “3D-ACM” (autologous culture method). Forty-five clinical samples from biopsies, surgically removed tumor tissues and malignant body fluids were cultured with 3D-ACM. Traditional 3D-FBS (fetal bovine serum) cultures were performed side-by-side for comparison. The results were that cells cultured in 3D-ACM rebuilt tissue-like structures, and retained their immuno-phenotypes and cytokine productions. In contrast, the 3D-FBS method promoted mesenchymal cell proliferation. In preliminary chemo drug-sensitivity assays, significantly higher mortality was always associated with FBS-cultured cells. Accordingly, 3D-ACM appears to more reliably preserve a tumor’s biological characteristics, which might improve the accuracy of drug-testing for personalized cancer treatment.

Introduction Transcranial color-coded duplex sonography (TCCS) with and without ultrasound contrast agent has been used to diagnose cerebral venous thrombosis, however, no experience in the diagnosis of patients with cerebral venous thrombosis and with dural arteriovenous fistula (dAVF) by contrast-enhanced TCCS has been reported yet. Case report The authors reported a 49-year-old male patient with straight sinus (StS) thrombosis and dAVF. Plain TCCS and contrast-enhanced TCCS demonstrated the direct presentation of the selected feeder and drainage veins of the dAVFs, arterialized venous flow waveform, and an enlarged optic nerve sheath diameter, indicating an increased intracranial pressure, and a filling defect in the StS even after administration of an ultrasound contrast agent. After intravascular thrombolysis and blockage of 2 feeders of the dAVF, TCCS still showed retrograde flow direction in the left basal vein and significantly elevated flow velocity in the StS, reflecting a high venous pressure caused by a high volume of arteriovenous shunt and severe stenosis in the StS. The patient's clinical manifestation did not substantially improve until 3 stents were implanted in the StS, and TCCS unveiled that the stents were well filled with flow signal, and the flow velocity in the StS dramatically decreased. Conclusions TCCS could provide reliable data about the feeder and drainage veins of dAVF in our case. The extent of an increase in venous flow velocity may be closely associated with clinical manifestations, which may influence therapy. Moreover, TCCS possesses a unique advantage in terms of evaluating the patency of the stents compared with other neuroimaging techniques.

Background Seizures are a common symptom in glioma patients, and they can cause brain dysfunction. However, the mechanism by which glioma-related epilepsy (GRE) causes alterations in brain networks remains elusive. Objective To investigate the potential pathogenic mechanism of GRE by analyzing the dynamic expression profiles of microRNA/ mRNA/ lncRNA in brain tissues of glioma patients. Methods Brain tissues of 16 patients with GRE and 9 patients with glioma without epilepsy (GNE) were collected. The total RNA was dephosphorylated, labeled, and hybridized to the Agilent Human miRNA Microarray, Release 19.0, 8 × 60 K. The cDNA was labeled and hybridized to the Agilent LncRNA + mRNA Human Gene Expression Microarray V3.0, 4 × 180 K. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. P-value 2 were considered the threshold of differential expression data. Data analyses were performed using R and Bioconductor. Results We found that 3 differentially expressed miRNAs (miR-10a-5p, miR-10b-5p, miR-629-3p), 6 differentially expressed lncRNAs (TTN-AS1, LINC00641, SNHG14, LINC00894, SNHG1, OIP5-AS1), and 49 differentially expressed mRNAs play a vitally critical role in developing GRE. The expression of GABARAPL1, GRAMD1B, and IQSEC3 were validated more than twofold higher in the GRE group than in the GNE group in the validation cohort. Pathways including ECM receptor interaction and long-term potentiation (LTP) may contribute to the disease’s progression. Meanwhile, We built a lncRNA-microRNA-Gene regulatory network with structural and functional significance. Conclusion These findings can offer a fresh perspective on GRE-induced brain network changes.

Recurrent implantation failure (RIF) associated with impaired endometrial receptivity and other factors. Disease-specific therapy has yet to be developed due to the lack of understanding of underlying mechanism(s). Herein we investigated the key factors of endometrial receptivity in RIF patients by transcriptomic sequencing. In vitro cellular model was used to delineate the molecular mechanism of key factors on proliferation, invasion and migration of trophoblast cells. SEMA4D was identified as the key factors of endometrial receptivity with significantly lower expression in the mid-secretory endometrium of RIF patients compared with those from normal fertile women. The binding of SEMA4D to its receptor Plexin-B1 on human trophoblast cells HTR-8/SVneo resulted in the activation of Met/PI3K/Akt signaling, which promotes trophoblast cell invasion and migration by enhancing MMP-2 expression. Moreover, the effect of SEMA4D on HTR-8/SVneo could be blocked by knocking down Met with specific siRNA or treating with LY294002. Collectively, our data indicate that decreased expression of SEMA4D in endometrium impair the process of trophoblast invasion and migration through Met/PI3K/Akt pathway, which provides insights into this essential physiological process in the development of RIF.

Rui-Qin Yang,1– 3 Min Chen,3,4 Qiang Zhang,5 Yi-Yang Gao,1– 3 Kang-Liang Lou,1– 3 Tong-Tong Lin,5 Wen-He Huang,1,2 Yun-Zhu Zeng,6 Yong-Qu Zhang,1– 3 Yong-Ying Dang,1– 3 Lei Ren,5,* Guo-Jun Zhang1,2,4,* 1Cancer Center & Department of Breast and Thyroid Surgery, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, People’s Republic of China; 2Key Laboratory for Endocrine-Related Cancer Precision Medicine of Xiamen, Xiang’an Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China; 3Clinical Central Research Core, Xiang’an Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China; 4Cancer Research Center, School of Medicine, Xiamen University, Xiamen, Fujian, People’s Republic of China; 5State Key Lab of Physical Chemistry of Solid Surface, College of Materials, Xiamen University, Xiamen, Fujian, People’s Republic of China; 6The Pathology department, Cancer Hospital, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guo-Jun Zhang, Tel +86-592-2889988, Fax +86-592-2889202, Email gjzhang@xah.xmu.edu.cnPurpose: Tumor-free surgical margin is crucial but challenging in breast-conserving surgery (BCS). Fluorescence imaging is a promising strategy for surgical navigation that can reliably assist the surgeon with visualization Of the tumor in real-time. Notably, finding an optimized fluorescent probe has been a challenging research topic. Herein, we developed a novel near-infrared (NIR) fluorescent probe based on tailored Hepatitis B Core virus-like protein (HBc VLP) and presented the preclinical imaging-guided surgery.Methods: The RGD-HBc160 VLP was synthesized by genetic engineering followed encapsulation of ICG via disassembly-reassembly. The applicability of the probe was tested for cell and tissue binding capacities through cell-based plate assays, xenograft mice model, and MMTV-PyVT mammary tumor transgenic mice. Subsequently, the efficacy of RGD-HBc160/ICG-guided surgery was evaluated in an infiltrative tumor-bearing mouse model. The protein-induced body’s immune response was further assessed.Results: The prepared RGD-HBc160/ICG showed outstanding integrin αvβ3 targeting ability in vitro and in vivo. After intravenous administration of probe, the fluorescence guidance facilitated more complete tumor resection and improved overall survival Of the infiltrative tumor-bearing mice. The probe also showed the excellent capability to differentiate between benign and malignant breast tissues in the mammary tumor transgenic mice. Interestingly, the ingenious tailoring of HBc VLP could not only endow its tumor-targeting ability towards integrin αvβ3 but also significantly reduce the humoral and cellular immune response.Conclusion: The RGD-HBc160/ICG holds promise as an effective tool to delineate tumor margin. These results have translational potential to achieve margin-negative resection and improve the stratification of patients for a potentially curative.Graphical Abstract: Keywords: breast Cancer, tumor margin, NIR fluorescence imaging, imaging-guided surgery, Hepatitis B core virus-like particles

Background Primary ciliary dyskinesia (PCD) represents a highly heterogenous disorder with extensive clinical and genetic patterns among populations of different geographic location and ethnic origin. However, data about Chinese patients are limited. We aimed to summarize the clinical and genetic spectrum of Chinese PCD patients based on all available literatures. Methods We searched Embase, Pubmed, Web of Science and Chinese databases including CNKI, SinoMed and Wanfang from 1981 to 2021, to identify articles reporting patients with PCD in China, which had included information about transmission electron microscopy and/or genetic testing. Results A total of 244 Chinese PCD patients in 52 articles were included. Of these patients, the mean age was 13.1 years, and 55 patients (22.5%) were diagnosed with PCD after 18 years old. Compared with patients diagnosed with PCD in childhood or infancy, patients diagnosed with PCD in adulthood had a higher prevalence of chronic wet cough, sinusitis, Pseudomonas aeruginosa (PA) isolation and radiological bronchiectasis as well as worse lung function. 25 PCD-related genes were identified in 142 patients, and DNAH5, DNAH11, CCDC39 and CCDC40 were the most frequently detected mutations. More than half of genetic variants were loss-of-function mutations, and the majority of these variants were seen only once. Correlations between PCD phenotype, genotype and ciliary ultrastructure were also evidenced. Conclusions Diagnostic delay and under-recognition of PCD remain a big issue in China, which contributes to progressive lung disease and PA infection indicating worse outcome. Specialist equipment and expertise are urgently required to facilitate the early diagnosis and treatment of PCD. Trial registry PROSPERO; No.: CRD42021257804; URL:www.crd.york.ac.uk/prospero/

To assess the influencing factors of transtemporal window quality and identify patients suitable for transcranial sonography (TCS) examination in two-dimensional imaging.In this cross-sectional study, TCS was performed in 161 consecutive patients through the temporal bone window (TBW) in the neurology or neurosurgery department. Each patient's sex, age, height, weight, and temporal bone thickness (TBT) were collected. After examination, the patients were divided into two groups: TBW success and TBW failure. The data were statistically compared between the two groups.Among the studied population, the total TBW success rate was 80.1% (95% confidence interval [CI]: 74-86). The TBW success rate was 91.4% (95% CI: 85-98) in males and 70.9% (95% CI: 61-81) in females (p = .001). Sex (p = .001), age (p = .002), height (p = .047), and TBT (p.001) showed significant differences between the TBW success and failure groups. In males, only TBT (p = .001) showed a significant difference; in females, age (p.001) and TBT (p = .003) showed a significant difference. The area under the receiver operating characteristic curve (AUC) of sex, age, and TBT and their combination was 0.686, 0.659, 0.842, and 0.922 (p.001), respectively. The AUC of the combination of parameters was significantly greater than that of age and sex alone (p = .007; p = .0002) but not greater than that of TBT (p = .090).The TBW success rate varied with sex, age, height, and TBT. Males, younger patients, taller patients, and patients with a thinner temporal bone tended to be more suitable for the examination by TCS.

So far, relatively few small molecules have been reported to promote tubulin degradation. Our previous studies have found that compound

We aimed to describe the evolution of flow pattern in the ophthalmic artery (OA) and supratrochlear artery (SA) by transcranial Doppler (TCD) ipsilateral to a severe proximal carotid artery stenosis before and after staged endovascular treatment (EVT).We insonated and recorded the flow patterns of OA and SA in 63 patients with ≥ 80% carotid artery stenosis before and after staged carotid angioplasty and stenting at 2-4 weeks apart. Based on the direction of OA and SA blood flow, we categorized patients into (1) reversed, (2) alternating, or (3) forward flow, groups. We evaluated the evolving sonographic flow patterns in OA and SA at the 3-time points and correlated them with the stenotic and flow velocity change.Despite the disconcordance between OA and SA, the evolution of flow direction were evoluted from reversed to alternating or from alternating to forward in both OA and SA. OA and SA's disagreement rate at three-time points was 19.1%, 49.2%, and 28.6%, respectively. After angioplasty alone, we detected an alternating flow in 21 (33.3%) and 46 (73.0%) patients in OA and SA, respectively. Alternating flow patterns in SA persisted in 20 patients (31.7%) after stenting. The post-angioplasty residual stenosis did not differ between the three flow pattern groups (p0.05).An alternating flow in OA or SA might mark the hemodynamic recovery after EVT. Insonation of SA may provide supporting evidence for hemodynamic change in patients with carotid artery stenosis undergoing EVT.

Positive resection margin frequently exists in breast-conserving treatment (BCT) of early-stage breast cancer, and insufficient therapeutic efficacy is common during radiotherapy (RT) in advanced breast cancer patients. Moreover, a multimodal nanotherapy platform is urgently required for precision cancer medicine. Therefore, a biodegradable cyclic RGD pentapeptide/hollow virus-like gadolinium (Gd)-based indocyanine green (RHV-Gd@ICG) nanoprobe is developed to improve fluorescence image-guided surgery and breast cancer RT efficacy. RHV-Gd exhibits remarkably improved aqueous stability, tumor retention, and target specificity of ICG, and achieves outstanding magnetic resonance/second near-infrared (NIR-II) window multimodal imaging in vivo. The nanoprobe-based NIR-II fluorescence image guidance facilitates complete tumor resection, improves the overall mouse survival rate, and effectively discriminates between benign and malignant breast tissues in spontaneous breast cancer transgenic mice (area under the curve = 0.978; 95% confidence interval: 0.952, 1.0). Moreover, introducing the nanoprobe to tumors generated more reactive oxygen species under X-ray irradiation, improved RT sensitivity, and reduced mouse tumor progression. Notably, the nanoprobe is biodegradable in vivo and exhibits accelerated bodily clearance, which is expected to reduce the potential long-term inorganic nanoparticle toxicity. Overall, the nanoprobe provides a basis for developing precision breast cancer treatment strategies.

Preservation of a small population of cancer stem cells (CSCs) within a heterogeneous carcinoma serves as a paradigm to understand how select cells in a tissue maintain their undifferentiated status. In both embryogenesis and cancer, Snail has been correlated with stemness, but the molecular underpinning of this phenomenon remains largely ill-defined. In models of cutaneous squamous cell carcinoma (cSCC), we discovered a non-epithelial-mesenchymal transition function for the transcription factor Snail in maintaining the stemness of epidermal keratinocytes. Snail-expressing cells secrete the matricellular protein Mindin, which functions in an autocrine fashion to activate a Src-STAT3 pathway to reinforce their stem/progenitor phenotype. This pathway is activated by the engagement of Mindin with the leukocyte-specific integrin, CD11b (ITGAM), which is also unexpectedly expressed by epidermal keratinocytes. Interestingly, disruption of this signaling module in human cSCC attenuates tumorigenesis, suggesting that targeting Mindin would be a promising therapeutic approach to hinder cancer recurrence.

Polycystic ovary syndrome (PCOS) is a common endocrine-related cause of infertility in women and has an unknown etiology. Studies have shown that rhamnocitrin (Rha) exhibits positive effects on the reproductive system. This study investigated Rha’s antifibrotic effects on PCOS rats and revealed its underlying mechanisms. Female SD rats were randomized into 4 groups ( n = 8 , each); the control group received tea oil by intraperitoneal injection and 1% w / v CMC by oral gavage; the PCOS group received letrozole (1 mg/kg); the PCOS+Rha group received letrozole and Rha (5 mg/kg); the PCOS+Met group received letrozole and Met (265 mg/kg) for 21 days. At the study end, Rha treatment restored letrozole-induced alterations in the relative ovarian weights, body weight, and relative weights of uterine and visceral adipose tissues. Histological observation showed that Rha ameliorates ovarian structure and fibrosis in PCOS. Administration of Rha reduced letrozole-induced metabolic dysfunction by ameliorating the levels of TC, TG, and HDL-C in the PCOS rats. Rha treatment also modulated the serum levels of sex hormones, which decreased T, E2, and LH and increased FSH in PCOS rats. In addition, Rha treatment modulated insulin resistance and increased gene expression of antioxidant enzymes (Cat, Sod2, Gpx3, Mgst1, Prdx3, Gsta4, Gsr, and Sod1) in the ovaries of the PCOS rats. Finally, Rha treatment appeared to increase the activity of PPAR-γ and inhibit the TGF-β1/Smad pathway in the ovaries of the PCOS rats. Our findings suggest that Rha significantly ameliorated metabolic disturbances and ovarian fibrosis in the PCOS rats. Rha perhaps is an effective compound for preventing ovarian fibrosis in the future.

GDF15 has been recently recognized as a tumor-suppressive gene. However, the underlying mechanism by which GDF15 affects breast carcinogenesis is not well understood. Here, we showed that the inhibitory effect of GDF15 on cell proliferation was dependent on the nuclear localization of the protein. Dynamic translocation of GDF15 into the nucleus altered expression of a number of genes, including KISS-1, and resulted in inhibition of cell growth and invasive behavior. Using KISS-1 promoter-driven luciferase reporter and chromatin immunoprecipitation assays, we demonstrated that, in highly malignant breast cancer cells, GDF15 directly interacts with specific protein-1 (Sp1) at the Sp1-binding sites of the KISS-1 promoter, leading to upregulated KISS-1 expression. Our study indicates that nuclear GDF15 could serve as a transcriptional coactivator to mediate the expression of particular genes to reduce cell proliferation.

Gene therapy is likely to be the most promising way to tackle cancer, while defects in molecular strategies and delivery systems have led to an impasse in clinical application. Here, it is found that onco-miRNAs of the miR-515 and -449 families were upregulated in hepatocellular carcinoma (HCC), and the sponge targeting miR-515 family had a significant probability to suppress cancer cell proliferation. Then, we constructed non-toxic sponge-loaded magnetic nanodroplets containing 20% C6F14 (SLMNDs-20%) that are incorporated with fluorinated superparamagnetic iron oxide nanoparticles enhancing external magnetism-assisted targeting and enabling a direct visualization of SLMNDs-20% distribution in vivo via magnetic resonance imaging monitoring. SLMNDs-20% could be vaporized by programmable focused ultrasound (FUS) activation, achieving ∼45% in vitro sponge delivery efficiency and significantly enhancing in vivo sponge delivery without a clear apoptosis. Moreover, the sponge-1-carrying SLMNDs-20% could effectively suppress proliferation of xenograft HCC after FUS exposure because sponge-1-suppressing onco-miR-515 enhanced the expression of anti-oncogenes (P21, CD22, TIMP1, NFKB, and E-cadherin) in cancer cells. The current results indicated that ultrasonic cavitation-inducing sonoporation enhanced the intracellular delivery of sponge-1 using SLMNDs-20% after magnetic-assisted accumulation, which was a therapeutic approach to inhibit HCC progression.

Targeting enrichment of nanocarriers at tumor sites and effective drug release are critical in cancer treatment. Accordingly, we used fluorescent zeolitic imidazolate framework-8 nanoparticles loaded with doxorubicin (FZIF-8/DOX) as the core and a molecularly imprinted polymer (MIP) as the shell to synthesize tumor-sensitive biodegradable FZIF-8/DOX-MIP nanoparticles (FZIF-8/DOX-MIPs). The MIP prepared with the epitope of CD59 cell membrane glycoprotein as the template allowed FZIF-8/DOX-MIPs to be enriched to tumor sites by actively targeting recognition of MCF-7 cancer cells (CD59-positive). Moreover, using N,N'-diacrylylcystamine as the cross-linker and dimethylaminoethyl methacrylate as the main monomer, the MIP's framework will be broken under the stimulation of a tumor microenvironment (high-concentration glutathione and weakly acidic), so that the internal FZIF-8/DOX is exposed to a microacidic environment to release DOX through further degradation. More importantly, the ability of FZIF-8/DOX-MIPs in targeted fluorescence imaging and effective drug release has been validated both in vitro and in vivo. Compared to other cells and nanoparticles, FZIF-8/DOX-MIPs were more capable of being phagocytosed by MCF-7 cells and were more lethal to MCF-7 cells. In the comparative experiments carried out on tumor-bearing mice, FZIF-8/DOX-MIPs had the best inhibitory effect on the growth of MCF-7 tumors. Furthermore, the FZIF-8/DOX-MIPs can serve as a diagnostic agent because of the active targeting of MCF-7 cells and the stronger red fluorescence of the embedded carbon quantum dots. Because of the active targeting ability, good biocompatibility, tumor-sensitive biodegradability, and effective drug release performance, FZIF-8/DOX-MIPs can be widely used in tumor imaging and treatment.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumour in the oral and maxillofacial region. Numerous cancers share ten common traits (“hallmarks”) that govern the transformation of normal cells into cancer cells. Long non‐coding RNAs (lncRNAs) are important factors that contribute to tumorigenesis. However, very little is known about the cooperative relationships between lncRNAs and cancer hallmark‐associated genes in OSCC. Through integrative analysis of cancer hallmarks, somatic mutations, copy number variants (CNVs) and expression, some OSCC‐specific cancer hallmark‐associated genes and lncRNAs are identified. A computational framework to identify gene and lncRNA cooperative regulation pairs (GLCRPs) associated with different cancer hallmarks is developed based on the co‐expression and co‐occurrence of mutations. The distinct and common features of ten cancer hallmarks based on GLCRPs are characterized in OSCC. Cancer hallmark insensitivity to antigrowth signals and self‐sufficiency in growth signals are shared by most GLCRPs in OSCC. Some key GLCRPs participate in many cancer hallmarks in OSCC. Cancer hallmark‐associated GLCRP networks have complex patterns and specific functions in OSCC. Specially, some key GLCRPs are associated with the prognosis of OSCC patients. In summary, we generate a comprehensive landscape of cancer hallmark‐associated GLCRPs that can act as a starting point for future functional explorations, the identification of biomarkers and lncRNA‐based targeted therapy in OSCC.

Tumor-associated antigens (TAAs) have been tested in various clinical trials in cancer treatment but the patterns of specific T cell response to personalized TAA immunization remains to be fully understood. We report antigen-specific T cell responses in patients immunized with dendritic cell vaccines pulsed with personalized TAA panels. Tumor samples from patients were first analyzed to identify overexpressed TAAs. Autologous DCs were then transfected with pre-manufactured mRNAs encoding the full-length TAAs, overexpressed in the patients' tumors. Patients with glioblastoma multiforme (GBM) or advanced lung cancer received DC vaccines transfected with personalized TAA panels, in combination with low-dose cyclophosphamide, poly I:C, imiquimod and anti-PD-1 antibody. Antigen-specific T cell responses were measured. Safety and efficacy were evaluated. A total of ten patients were treated with DC vaccines transfected with personalized TAA panels containing 3-13 different TAAs. Among the seven patients tested for anti-TAA T cell responses, most of the TAAs induced antigen-specific CD4+ and/or CD8+ T cell responses, regardless of their expression levels in the tumor tissues. No Grade III/IV adverse events were observed among these patients. Furthermore, the treated patients were associated with favorable overall survival when compared to patients who received standard treatment in the same institution. Personalized TAA immunization-induced-specific CD4+ and CD8+ T cell responses without obvious autoimmune adverse events and was associated with favorable overall survival. These results support further studies on DC immunization with personalized TAA panels for combined immunotherapeutic regimens in solid tumor patients.Trial registration ClinicalTrials.gov, NCT02709616 (March, 2016), NCT02808364 (June 2016), NCT02808416 (June, 2016).

This article describes a novel surgical technique for successful repair of intractable corneoscleral necrosis caused by severe ocular burns. In this prospective case series, 19 eyes of 15 consecutive patients with sectional scleral necrosis and persistent corneal epithelial defects were treated with tenonplasty and amniotic membrane transplantation. The main outcome measure was the stability of the ocular surface after reepithelialization and repair of defects. All patients underwent successful combined surgery involving tenonplasty and amniotic membrane transplantation, in which the conjunctival and corneal surfaces were reconstructed. The interval from injury to surgery was 37.4 ± 24.5 days (3–91 days), and the ocular surfaces became stabilized in 82.2 ± 35.4 days (26–156 days, median 87 days). At the final visit, all cases presented with corneal opacity and neovascularization to various degrees. The best-corrected visual acuity decreased from 2.83 ± 1.02 LogMAR preoperatively to 2.87 ± 1.31 LogMAR postoperatively. The results imply that tenonplasty combined with amniotic membrane transplantation could provide vascular supply to the ischemic sclera, repair defects in the conjunctiva, and promote corneal reepithelialization, thus facilitating ocular surface stabilization after burns.

The aim of this study was to investigate the relationship between morphologic characteristics of the calcifications detected by ultrasound in thyroid nodules and thyroid carcinoma. Morphologic characteristics of the calcifications on pre-operative ultrasound examinations of thyroids were compared with post-operative pathologic diagnoses in 543 patients undergoing thyroid surgery. Calcifications were divided into microcalcifications (≤2 mm) and macrocalcifications (>2 mm), and the latter were divided into eggshell calcifications in a row, eggshell discontinuous calcifications, irregular calcifications and multilayer-like calcifications, labeled types I-V. We found that thyroid microcalcifications and partial macrocalcifications, such as eggshell discontinuous calcifications, and multilayer-like calcifications were associated with thyroid carcinoma. In conclusion, microcalcifications were more commonly found in malignant thyroid nodules, particularly in papillary thyroid carcinoma. Eggshell discontinuous macrocalcifications and multilayer-like macrocalcifications also occurred mainly in malignant nodules.

Vaginitis is a gynecological disease affecting the health of millions of women all over the world. The traditional diagnosis of vaginitis is based on manual microscopy, which is time-consuming and tedious. The deep learning method offers a fast and reliable solution for an automatic early diagnosis of vaginitis. However, deep neural networks require massive well-annotated data. Manual annotation of microscopic images is highly cost extensive because it not only is a time-consuming process but also needs highly trained people (doctors, pathologists, or technicians). Most existing active learning approaches are not applicable in microscopic images due to the nature of complex backgrounds and numerous formed elements. To address the problem of high cost of labeling microscopic images, we present a data-efficient framework for the identification of vaginitis based on transfer learning and active learning strategies. The proposed informative sample selection strategy selected the minimal training subset, and then the pretrained convolutional neural network (CNN) was fine-tuned on the selected subset. The experiment results show that the proposed pipeline can save 37.5% annotation cost while maintaining competitive performance. The proposed promising novel framework can significantly save the annotation cost and has the potential of extending widely to other microscopic imaging applications, such as blood microscopic image analysis.

Histological analysis of carotid atherosclerotic plaque tissue specimens is a widely used method for studying the diagnosis of ischemic heart disease and stroke. Understanding the physiological and pathological mechanisms of carotid atherosclerotic plaque is of great significance for the effective prevention and treatment of plaque formation and rupture. In this work, we adapted a self-attention generative adversarial model to virtually stain label-free human carotid atherosclerotic plaque tissue sections into corresponding HE stained sections. The self-attention mechanism and multi-layer structure are introduced into the residual steps of the generator and in the discriminator. Our method achieved the best performance (SSIM, PSNR, and LPIPS of 0.53, 20.29, and 0.30, respectively) in comparison with other state-of-the-art methods.Clinical Relevance - The proposed approach allows for the virtual staining of unlabeled human carotid plaque tissue images. It identifies the histopathological features of atherosclerotic plaques in the same tissue sample which could facilitate the development of personalized prevention and other interventional treatments for carotid atherosclerosis.

BackgroundThyroid cancer is the most common malignancy of the endocrine system worldwide. Papillary thyroid cancer (PTC) is the most common pathologic type. The preoperative diagnosis of PTC and central lymph node metastasis (CLNM) or metastatic tendency is of great clinical significance to the diagnosis, treatment and prognosis of these patients. This study was conducted to investigate the correlation between ultrasound features and central CLNM of PTC.MethodsThis study retrospectively analyzed patients who underwent PTC surgery and central lymph node dissection in the Department of Surgery, Beijing Tiantan Hospital, from January 2019 to February 2020. According to the inclusion and exclusion criteria, data from 136 patients were ultimately included, and the clinical and ultrasonic data of the patients were analyzed by multivariate regression to evaluate the correlation among grayscale ultrasound (US), superb microvascular imaging (SMI) and contrast-enhanced ultrasound (CEUS) features of thyroid nodules and CLNM of PTCs.ResultsThe multivariate analysis showed that tumor size, multifocality, microcalcification characteristics, SMI vascularization, and CEUS evaluation of contact with the adjacent capsule were correlated with PTC metastasis (P=0.008, P=0.001, P=0.028, P=0.041, and P< 0.001, respectively). Comparisons of the area under the ROC curves revealed that the area under the ROC curve of the degree of nodular invasion into the thyroid capsule was the largest (AUC: 0.754). The sensitivity and specificity for evaluating CLNM of PTC were 67.7% and 83.1%, respectively.ConclusionsUltrasound characteristics of the following features are associated with a high risk of lymph node metastasis in PTCs: maximum diameter of nodules ≥1 cm, multifocality, ≥5 microcalcifications, abundant blood flow of SMI in nodules and nodule contact with the thyroid capsule ≥25% under CEUS. Ultrasound has clinical value in the preoperative evaluation of CLNM of PTCs.

OBJECTIVE Vigabatrin (VGB) is the first-line treatment for infantile spasms (IS). Previous studies have shown that VGB exposure may cause vigabatrin-associated brain abnormalities on magnetic resonance imaging (MRI) (VABAM). Based on previous studies, this study aimed to go further to explore the possible risk factors and the incidence of VABAM. In addition, diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI) were compared to explore whether DWI should be used as a routine examination sequence when MRI is performed in children receiving VGB. METHODS Children with IS receiving VGB were selected as the study subjects. Whether VABAM occurred or not was categorized as the VABAM group and the non-VABAM group, respectively. Their general clinical data and medication exposure were collected. The possible risk factors of VABAM and different MRI sequences were compared and statistically analyzed. RESULTS A total of 77 children with IS were enrolled in the study, of which 25 (32.5%) developed VABAM. Twenty-three of the 25 VABAM cases have a peak dosage of VGB between 50 and 150 mg/kg/day. The earliest observation time of VABAM was 30 days. Regression analysis of relevant risk factors showed that the peak dosage of VGB was the risk factor for VABAM. Comparison between different MRI sequences showed that DWI is more sensitive than T2WI to the evaluation of VABAM. SIGNIFICANCE In our study, the occurrence of VABAM was 32.5%, indicating a higher incidence than in most previous reports. In addition, we once again verified that the peak dosage of VGB was the risk factor of VABAM. Caution should be exercised that our data also suggest that VABAM may occur even using the conventional dosage of VGB (ie, 50-150 mg/kg/day). Therefore, even when using the conventional dosage of VGB, regular MRI examination should be required. Furthermore, DWI sequence should be used as a routine examination sequence when MRI is performed in children with IS who are receiving VGB.

This study aimed to explore antithrombotic strategy and its relationship with outcomes in patients with atrial fibrillation (AF) at high risk for stroke and chronic coronary syndrome (CCS) in real-world clinical practice. Patients with AF at high risk for stroke complicated with CCS from China Atrial Fibrillation Registry (CAFR) were enrolled. The patients were divided into non-antithrombotic (Non-AT) group, oral anticoagulants (OAC) group, antiplatelet therapy (APT) group (aspirin or clopidogrel), and dual antiplatelet therapy (DAPT) group (aspirin + clopidogrel) according to their antithrombotic strategies at baseline. The patients with OAC + single antiplatelet drug (14 cases) and OAC + dual antiplatelet therapy (7 cases) were excluded for the small sample size. The primary effectiveness outcome was the composite outcome of coronary events, thromboembolism, and all-cause mortality. The primary safety outcome was major bleeding events. From 2011 to 2018, 25,512 patients were included in the CARF study, 769 patients with AF at high risk for stroke and CCS were enrolled in this study. After a follow-up of 47.4 ± 25.3 months, the incidences of primary effectiveness outcome were 44.6%, 25.7%, 43.6%, and 29.1% in the four groups, respectively (P

Objective This study aimed to describe our experience of managing cesarean scar pregnancy (CSP) and outcomes depending on ultrasound imaging features. Methods A retrospective, cohort observational study was performed on 31 consecutive patients with CSP at 6 to 9 weeks of gestation from April 2015 to January 2021. All patients were evaluated for the residual myometrial thickness (RMT), growth direction of the gestational sac (GS), blood flow, and chorionic parenchyma using ultrasonography. Patients underwent curettage or methotrexate (MTX) combined with curettage in CSP depending on the age of the GS. Blood loss of >500 mL with curettage was considered major bleeding. Results Twenty-five (80.6%) patients had successful treatment, and six (19.4%) patients had major bleeding. The incidence of major bleeding was significantly higher in patients with >7 weeks of gestation, types II and III CSP, mixed and exogenous types of the growth direction of the GS, an RMT Conclusions The exogenous and mixed types of the GS, an RMT

To evaluate whether sirolimus treatment could relieve the later burden of new-onset seizures in patients with tuberous sclerosis complex (TSC) prior to epilepsy.A real-world matched case-control study was nested in another registry cohort study. Infants with TSC (12 months old) without seizures whose parents agreed on sirolimus treatment for other symptoms were eligible for inclusion to the early sirolimus (ES) group. These patients were enrolled from 2015 to 2018. Controls in the late sirolimus (LS) group were matched from the registry cohort database for 2015-2018. Age and genotype were used as the initial stratifying criteria and other symptoms as the greedy matching criteria at a matching ratio of 1:4. None of the preventive drugs were introduced before seizure onset or before 2 years of age in the LS group. Both groups were followed up until June 2020. The primary objective was a comparison of the characteristics of the first seizure between the two groups. The secondary objective was the assessment of the final seizure status at the endpoint.There were 42 and 168 patients with TSC in the ES and LS groups, respectively. Early sirolimus treatment significantly reduced the seizure onset, especially in the patients aged6 months. The mean onset-age was significantly delayed by sirolimus treatment (11.34±7.93 months vs. 6.94±6.03 months, P0.001). The subtype of seizures that benefited the most was spastic (onset) seizures (all were infantile spasms) [5/42 (11.90%) vs. 73/168 (43.45%), P0.001]; these seizures were either eliminated or alleviated. The sirolimus treatment addition prior to seizures was more effective than its addition after seizures in reducing drug-resistant epilepsy [10/42 (23.81%) vs. 70/147 (47.62%), P=0.004].Early sirolimus treatment for TSC effectively modified the disease by preventing infantile spasms, delaying seizure onset, and relieving its severity. The anti-epileptogenic effect of sirolimus may be time- and dose-dependent.

As we all know, inhibiting the activity of dihydrofolate reductase (DHFR) has always been an effective strategy for folate antimetabolites to treat tumors. In the past, it mainly relied on chemical drugs. Here, we propose a new strategy, (3-propanecarboxyl)triphenylphosphonium bromide (CTPB)-modified molecularly imprinted polymer nanomedicine (MIP-CTPB). MIP-CTPB prepared by imprinting the active center of DHFR can specifically bind to the active center to block the catalytic activity of DHFR, thereby inhibiting the synthesis of DNA and ultimately inhibiting the tumor growth. The modification of CTPB allows the nanomedicine to be targeted and enriched in mitochondria, where DHFR is abundant. The confocal laser imaging results show that MIP-CTPB can target mitochondria. Cytotoxicity experiments show that MIP-CTPB inhibits HeLa cell proliferation by 42.2%. In vivo experiments show that the tumor volume of the MIP-CTPB-treated group is only one-sixth of that of the untreated group. The fluorescent and paramagnetic properties of the nanomedicine enable targeted fluorescence imaging of mitochondria and T2-weighted magnetic resonance imaging of tumors. This research not only opens up a new direction for the application of molecular imprinting, but also provides a new idea for tumor antimetabolic therapy guided by targeted mitochondrial imaging.

The morbidity and mortality of cardiovascular diseases are increasing annually, which is one of the primary causes of human death. Recent studies have shown that epoxyeicosatrienoic acids (EETs), endogenous metabolites of arachidonic acid (AA) via CYP450 epoxygenase, possess a spectrum of protective properties in cardiovascular system. EETs not only alleviate cardiac remodeling and injury in different pathological models, but also improve subsequent hemodynamic disturbances and cardiac dysfunction. Meanwhile, various studies have demonstrated that EETs, as endothelial-derived hyperpolarizing factors, regulate vascular tone by activating various ion channels on endothelium and smooth muscle, which in turn can lower blood pressure, improve coronary blood flow and regulate pulmonary artery pressure. In addition, EETs are protective in endothelium, including inhibiting inflammation and adhesion of endothelial cells, attenuating platelet aggregation, promoting fibrinolysis and revascularization. EETs can also prevent aortic remodeling, including attenuating atherosclerosis, adventitial remodeling, and aortic calcification. Therefore, it is clinically important to study the physiological and pathophysiological effects of EETs in the cardiovascular system to further elucidate the mechanisms, as well as provide new strategy for the prevention and treatment of cardiovascular diseases. This review summarizes the endogenous cardioprotective effects and mechanisms of EETs in order to provide a new insight for research in this field.

To explore the application value of next generation sequencing (NGS) in preimplantation genetic diagnosis of α/β complex thalassemia couple.The coding regions of α-globin genes (HBA1, HBA2) and β-globin gene (HBB) were selected as the target regions. The high-density and closely linked single nucleotide polymorphism (SNP) sites were selected as the genetic linkage markers in the upstream and downstream 2M regions of the gene. After NGS, the effective SNP sites were selected to construct the haplotype of the couple, and the risk chromosome of the mutation carried by the couple was determined. The NGS technology was used to sequence the variations of HBA1, HBA2 and HBB directly and construct haplotype linkage analysis for preimplantation genetic diagnosis.Direct sequencing and haplotype linkage analysis of HBA1, HBA2 and HBB showed that two of the six blastocysts were α/β complex thalassemia, one was β-thalassemia heterozygote, two were α-thalassemias heterozygotes, and one was intermediate α-thalassemia. A well-developed embryo underwent preimplantation genetic diagnosis was implanted into the mother's uterus, and a healthy infant was born at term.Preimplantation genetic diagnosis can be carried out by NGS technology in α/β complex thalassemia couples, and abortion caused by aneuploid embryo selection can be avoided.采用二代测序对α/β复合型地中海贫血夫妇进行胚胎植入前遗传学诊断.探讨二代测序在α/β复合型地中海贫血夫妇胚胎植入前遗传学诊断的应用价值。.选择α-珠蛋白基因（HBA1、HBA2）和β-珠蛋白基因（HBB）编码区为目标区域，在基因上下游2M区域内选择高密度紧密连锁的单核苷酸多态位点作为遗传连锁标记，二代测序后选择有效单核苷酸多态位点构建夫妇单体型，确定夫妇携带致病基因的风险染色体。采用二代测序技术对胚胎HBA1、HBA2和HBB直接测序和构建单体型连锁分析进行植入前遗传学诊断。.胚胎HBA1、HBA2和HBB直接测序和构建单体型连锁分析结果显示，活检的6个囊胚中2个为α/β复合型地中海贫血，1个为β地中海贫血杂合携带，2个为α地中海贫血杂合携带，1个为中间型α地中海贫血。选择发育良好且植入前遗传学诊断结果提示可以移植的胚胎植入母体子宫后，足月分娩一健康婴儿。.采用二代测序技术可对α/β复合型地中海贫血夫妇进行胚胎植入前遗传学诊断，同时可以避免选择非整倍体胚胎而导致的流产问题。.