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Abstract Background Thyroid cancer is a common thyroid malignancy. The majority of thyroid lesion needs intraoperative frozen pathology diagnosis, which provides important information for precision operation. As digital whole slide images (WSIs) develop, deep learning methods for histopathological classification of the thyroid gland (paraffin sections) have achieved outstanding results. Our current study is to clarify whether deep learning assists pathology diagnosis for intraoperative frozen thyroid lesions or not. Methods We propose an artificial intelligence-assisted diagnostic system for frozen thyroid lesions that applies prior knowledge in tandem with a dichotomous judgment of whether the lesion is cancerous or not and a quadratic judgment of the type of cancerous lesion to categorize the frozen thyroid lesions into five categories: papillary thyroid carcinoma, medullary thyroid carcinoma, anaplastic thyroid carcinoma, follicular thyroid tumor, and non-cancerous lesion. We obtained 4409 frozen digital pathology sections (WSI) of thyroid from the First Affiliated Hospital of Sun Yat-sen University (SYSUFH) to train and test the model, and the performance was validated by a six-fold cross validation, 101 papillary microcarcinoma sections of thyroid were used to validate the system’s sensitivity, and 1388 WSIs of thyroid were used for the evaluation of the external dataset. The deep learning models were compared in terms of several metrics such as accuracy, F1 score, recall, precision and AUC (Area Under Curve). Results We developed the first deep learning-based frozen thyroid diagnostic classifier for histopathological WSI classification of papillary carcinoma, medullary carcinoma, follicular tumor, anaplastic carcinoma, and non-carcinoma lesion. On test slides, the system had an accuracy of 0.9459, a precision of 0.9475, and an AUC of 0.9955. In the papillary carcinoma test slides, the system was able to accurately predict even lesions as small as 2 mm in diameter. Tested with the acceleration component, the cut processing can be performed in 346.12 s and the visual inference prediction results can be obtained in 98.61 s, thus meeting the time requirements for intraoperative diagnosis. Our study employs a deep learning approach for high-precision classification of intraoperative frozen thyroid lesion distribution in the clinical setting, which has potential clinical implications for assisting pathologists and precision surgery of thyroid lesions.

IntroductionInsomnia Disorder (ID) has become the second most prevalent mental disorder, with significant negative effects on daytime cognitive functions. Previous studies suggested that mindfulness-based music listening (MBML) can effectively improve conflict control and attentional processing in healthy adults. However, the behavioral and neurophysiological characteristics of MBML in young adults with ID remain unclear.MethodsTo explore the behavioral and neurophysiological characteristics of MBML in regulating negative emotions among young Chinese adults with ID, 60 young adults with ID were asked to complete an emotion-word Stroop task under three mood states while recording event-related potentials (ERPs).ResultsTask and questionnaire results showed that (1) negative emotion induced by the negative simulated video significantly suppressed the attentional processing of emotional faces and words in the conflict control task among young people with ID, (2) MBML reduced cognitive and physical arousal levels, enhanced positive mood, and improved attentional control abilities in young adults with ID. The ERP results showed that a greater N3 effect and the smaller P3 and late positive component (LPC) effects reflected that MBML effectively regulated negative emotions induced by the negative simulated video and attentional processing abilities for conflict control in young adults with ID.DiscussionMaintaining mindfulness while listening to music may enhance positive emotional experiences and improve cognitive ability, and exhibit larger N3 effects and smaller P3 and LPC effects in the electrophysiology mechanism, with a reduction in the hyperarousal level in young adults with insomnia disorders.

Summary: The metastatic cancer of cervical lymph nodes presents complex shapes and poses significant challenges for doctors in determining its origin. We established a deep learning framework to predict the status of lymph nodes in patients with cervical lymphadenopathy (CLA) by hematoxylin and eosin (H&E) stained slides. This retrospective study utilized 1,036 cervical lymph node biopsy specimens at the First Affiliated Hospital of Sun Yat-Sen University (FAHSYSU). A multiple-instance learning algorithm designed for key region identification was applied, and cross-validation experiments were conducted in the dataset. Additionally, the model distinguished between primary lymphoma and metastatic cancer with high prediction accuracy. We also validated our model and other models on an external dataset. Our model showed better generalization and achieved the best results on both internal and external datasets. This algorithm offers an approach for evaluating cervical lymph node status before surgery, significantly aiding physicians in preoperative diagnosis and treatment planning.

Abstract Introduction The management of erythrodermic psoriasis (EP), a rare but severe type of psoriasis, is challenging, especially in patients with concomitant chronic hepatitis B (CHB). We previously demonstrated that oxymatrine treatment alleviated severe plaque psoriasis, but its therapeutic potential in treating EP remains unexplored. This study was to assess the efficacy and safety of oxymatrine for the treatment of EP, with attention to concomitant CHB. Methods In this investigator-initiated clinical trial, four consecutive patients with EP, including two (A and B) with concomitant CHB, were treated with intravenous administration of oxymatrine as monotherapy for 8 weeks, and scheduled to be followed up for a minimum of 24 weeks. The primary outcome was at least 75% improvement in the psoriasis area and severity index (PASI 75) at week 32. Secondary outcomes included the body surface area (BSA) score, dermatology life quality index (DLQI)], and safety. Results Patients A, B, and C achieved PASI 75 at treatment completion and week 32, demonstrating improvements of 77.4%, 97.2%, and 100% in PASI, respectively. Their BSA and DLQI were also improved significantly at week 32 and throughout follow-up of 37, 57, and 105 weeks, respectively. The viral loads in patients A and B with CHB decreased modestly. Patient D discontinued after follow-up for 19 weeks, and the primary outcome could not be analyzed. No adverse events were reported during treatment and follow-up. Conclusion Oxymatrine appears to be efficacious and safe for the treatment of patients with EP, including those with concomitant CHB. Trial Registration This study was registered at the Chinese Clinical Trial Registry ( www.chictr.org.cn ; Registration number ChiCTR-TRC-14004301).

Abstract Background Small RNAs are essential for germ cell development and fertilization. However, fundamental questions remain, such as the level of conservation in small RNA composition between species and whether small RNAs control transposable elements in mammalian oocytes. Results Here, we use high-throughput sequencing to profile small RNAs and poly(A)-bearing long RNAs in oocytes of 12 representative vertebrate species (including 11 mammals). The results show that miRNAs are generally expressed in the oocytes of each representative species (although at low levels), whereas endo-siRNAs are specific to mice. Notably, piRNAs are predominant in oocytes of all species (except mice) and vary widely in length. We find PIWIL3-associated piRNAs are widespread in mammals and generally lack 3′-2′-O-methylation. Additionally, sequence identity is low between homologous piRNAs in different species, even among those present in syntenic piRNA clusters. Despite the species-specific divergence, piRNAs retain the capacity to silence younger TE subfamilies in oocytes. Conclusions Collectively, our findings illustrate a high level of diversity in the small RNA populations of mammalian oocytes. Furthermore, we identify sequence features related to conserved roles of small RNAs in silencing TEs, providing a large-scale reference for future in-depth study of small RNA functions in oocytes.

Psoriasis is a global health concern, and biological therapies have proven to be highly effective in treating psoriatic patients in many countries. We performed a bibliometric analysis of current research on biological agents for the treatments of psoriasis, investigating research patterns and public interest in this area. We conducted a thorough review of articles on biological agents for psoriasis in the Web of Science Core Collection spanning from 2000 to 2022. Our study involved examining the distribution of these articles based on publication year, affiliations, countries, authors, and journals. To visualize this data effectively, we employed bibliometric tools like CiteSpace and the R package bibliometrix. Our analysis encompassed 8,047 publications. The number of papers published sharply increased from 2009, either reaching its peak in 2022 or not yet reaching it. The United States (n = 2,292), Kristian Reich (n = 166), and British Journal of Dermatology (n = 368) emerged as the top countries, author, and journal, respectively, in terms of publication productivity. The burst references predominantly focused on evaluating the safety and efficacy of biological treatments. The keyword citation network identified 11 clusters, with research themes revolving around “double blind”, “efficacy”, “therapy”, “safety”, and “psoriatic arthritis” were the research focuses. Additionally, potential future research areas such as “multicenter,” “drug survival,” and “severity” were emphasized.This study sheds light on the evolving research landscape and public interest in biological agents for psoriasis. The results suggest rapid expansion in this field, with the United States at the forefront. Enhanced international collaboration is recommended, and forthcoming research endeavors may concentrate on predicting treatment outcomes and adverse effects. Researching new biological agents, broadening the indications for biological agent treatment, and creating personalized treatment plans may pave the way for further research.

BackgroundCervical cancer (CC) poses a global health challenge, with a particularly poor prognosis in cases of recurrence, metastasis, or advanced stages. A single biomarker is inadequate to predict CC prognosis or identify CC patients likely to benefit from immunotherapy, presumably owing to tumor complexity and heterogeneity.MethodsUsing advanced Olink proteomics, we analyzed 92 oncology-related proteins in plasma from CC patients receiving immunotherapy, based upon the comparison of protein expression levels of pre-therapy with those of therapy-Cycle 6 in the partial response (PR) group and progressive disease (PD) group, respectively.Results55 proteins were identified to exhibit differential expression trends across pre-therapy and post-therapy in both PR and PD groups. Enriched GO terms and KEGG pathways were associated with vital oncological and immunological processes. A logistic regression model, using 5 proteins (ITGB5, TGF-α, TLR3, WIF-1, and ERBB3) with highest AUC values, demonstrated good predictive performance for prognosis of CC patients undergoing immunotherapy and showed potential across different cancer types. The effectiveness of these proteins in prognosis prediction was further validated using TCGA-CESC datasets. A negative correlation and previously unidentified roles of WIF-1 in CC immunotherapy was also first determined.ConclusionOur findings reveal multi-biomarker profiles effectively predicting CC prognosis and identifying patients benefitting most from immunotherapy, especially for those with limited treatment options and traditionally poor prognosis, paving the way for personalized immunotherapeutic treatments and improved clinical strategies.

Abstract Background Actin-like 7 A (ACTL7A) is essential for acrosome formation, fertilization and early embryo development. ACTL7A variants cause acrosome detachment responsible for male infertility and early embryonic arrest. In this study, we aim to explore the additional functions of ACTL7A beyond the process of acrosome biogenesis and investigate the possible underlying mechanisms. Methods Nuclear morphology analysis was used to observe the sperm head shape of ACTL7A-mutated patients. Actl7a knock-out (KO) mouse model was generated. Immunofluorescence and transmission electron microscopy (TEM) were performed to analyze the structure of spermatids during spermiogenesis. Tandem mass tags labeling quantitative proteomics strategy was employed to explore the underlying molecular mechanisms. The expression levels of key proteins in the pathway were analyzed by western blotting. Intracytoplasmic sperm injection (ICSI)-artificial oocyte activation (AOA) technology was utilized to overcome fertilization failure in male mice with a complete knockout of Actl7a. Results The new phenotype of small head sperm associated with loss of ACTL7A in patients was discovered, and further confirmed in Actl7a-KO mice. Immunofluorescence and TEM analyses revealed that the deletion of ACTL7A damaged the formation of acrosome-acroplaxome-manchette complex, leading to abnormalities in the shaping of sperm heads. Moreover, a proteomic analysis of testes from WT and Actl7a-KO mice revealed that differentially expressed genes were notably enriched in PI3K/AKT/mTOR signaling pathway which is strongly associated with autophagy. Inhibition of autophagy via PI3K/AKT/mTOR signaling pathway activation leading to PDLIM1 accumulation might elucidate the hindered development of manchette in Actl7a-KO mice. Remarkably, AOA successfully overcame fertilization failure and allowed for the successful production of healthy offspring from the Actl7a complete knockout male mice. Conclusions Loss of ACTL7A causes small head sperm as a result of defective acrosome-acroplaxome-manchette complex via autophagy inhibition. ICSI-AOA is an effective technique to rescue male infertility resulting from ACTL7A deletion. These findings provide essential evidence for the diagnosis and treatment of patients suffering from infertility.

Identifying the invasive cancer area is a crucial step in the automated diagnosis of digital pathology slices of the breast. When examining the pathological sections of patients with invasive ductal carcinoma, several evaluations are required specifically for the invasive cancer area. However, currently there is little work that can effectively distinguish the invasive cancer area from the ductal carcinoma in situ in whole slide images. To address this issue, we propose a novel architecture named ResMTUnet that combines the strengths of vision transformer and CNN, and uses multi-task learning to achieve accurate invasive carcinoma recognition and segmentation in breast cancer. Furthermore, we introduce a multi-scale input model based on ResMTUnet with conditional random field, named MS-ResMTUNet, to perform segmentation on WSIs. Our systematic experimentation has shown that the proposed network outperforms other competitive methods and effectively segments invasive carcinoma regions in WSIs. This lays a solid foundation for subsequent analysis of breast pathological slides in the future. The code is available at: https://github.com/liuyiqing2018/MS-ResMTUNet

Abstract. Background:. Visual inputs are critical for locomotor navigation and sensorimotor integration in the elderly; however, the mechanism needs to be explored intensively. The present study assessed the gait pattern after cataract surgery to investigate the effects of visual restoration on locomotion. Methods:. The prospective study recruited 32 patients (70.1 ± 5.2 years) with bilateral age-related cataracts in the Department of Ophthalmology at Peking University Third Hospital from October 2016 to December 2019. The temporal-spatial gait parameters and kinematic parameters were measured by the Footscan system and inertial measurement units. Paired t-test was employed to compare data normally distributed and Wilcoxon rank-sum test for non-normally distributed. Results:. After visual restoration, the walking speed increased by 9.3% (1.19 ± 0.40 m/s vs. 1.09 ± 0.34 m/s, P=0.008) and exhibited an efficient gait pattern with significant decrease in gait cycle (1.02 ± 0.08 s vs. 1.04 ± 0.07 s, P=0.012), stance time (0.66 ± 0.06 s vs. 0.68 ± 0.06 s, P=0.045), and single support time (0.36 ± 0.03 s vs. 0.37 ± 0.02 s, P=0.011). High amplitude of joint motion was detected in the sagittal plane in the left hip (37.6° ± 5.3° vs. 35.5° ± 6.2°, P=0.014), left thigh (38.0° ± 5.2° vs. 36.4° ± 5.8°, P=0.026), left shank (71.9° ± 5.7° vs. 70.1° ± 5.6°, P=0.031), and right knee (59.1° ± 4.8° vs. 56.4° ± 4.8°, P=0.001). The motor symmetry of thigh improved from 8.35 ± 5.30% to 6.30 ± 4.73% (P=0.042). Conclusions:. The accelerated gait in response to visual restoration is characterized by decreased stance time and increased range of joint motion. Training programs for improving muscle strength of lower extremities might be helpful to facilitate the adaptation to these changes in gait.

Novel anti-HER2 antibody-drug conjugates trastuzumab deruxtecan (DS-8201a) showed its effect in previously-treated HER2-low metastatic breast cancer, suggesting a promising future in HER2-low breast cancer. We retrospectively reviewed the clinicopathological data of 325 patients with stage I–III HER2 negative breast cancer who received neoadjuvant chemotherapy in the First Affiliated Hospital of Sun Yat-sen University from January 2016 to June 2021. In general, 91 patients (28.0%) were HER2-zero, and 234 patients (72.0%) were HER2-low. The pathological complete response (pCR) rate of the entire cohort was 17.3%. The pCR rate was 16.7% in HER2-low group, and 18.9% in HER2-zero group, showing no significant difference. Patients with HER2-low tumors had significantly longer overall survival (OS) than patients with HER2-zero tumors. ER status was the affecting factor of OS in HER2-low patients in both univariate and multivariate analysis. In conclusion, evidence for HER2-low BC as a distinct entity is insufficient, and more efforts are needed to standardize the scoring of HER2-low breast cancer.

AimThis study aims to investigate the biological effects of polyunsaturated fatty acid (PUFA)-derived metabolites in seminal plasma on male fertility and to evaluate the potential of PUFA as a biomarker for normozoospermic male infertility.MethodsFrom September 2011 to April 2012, We collected semen samples from 564 men aged 18 to 50 years old (mean=32.28 years old)ch., residing in the Sandu County, Guizhou Province, China. The donors included 376 men with normozoospermia (fertile: n=267; infertile: n=109) and 188 men with oligoasthenozoospermia (fertile: n=121; infertile: n=67). The samples thus obtained were then analyzed by liquid chromatography-mass spectrometry (LC-MS) to detect the levels of PUFA-derived metabolites in April 2013. Data were analyzed from December 1, 2020, to May 15, 2022.ResultsOur analysis of propensity score-matched cohorts revealed that the concentrations of 9/26 and 7/26 metabolites differed significantly between fertile and infertile men with normozoospermia and oligoasthenozoospermia, respectively (FDR < 0.05). In men with normozoospermia, higher levels of 7(R)-MaR1 (HR: 0.4 (95% CI [0.24, 0.64]) and 11,12-DHET (0.36 (95% CI [0.21, 0.58]) were significantly associated with a decreased risk of infertility, while higher levels of 17(S)-HDHA (HR: 2.32 (95% CI [1.44, 3.79]), LXA5 (HR: 8.38 (95% CI [4.81, 15.24]), 15d-PGJ2 (HR: 1.71 (95% CI [1.06, 2.76]), and PGJ2 (HR: 2.28 (95% CI [1.42, 3.7]) correlated with an increased risk of infertility. Our ROC model using the differentially expressed metabolites showed the value of the area under the curve to be 0.744.ConclusionThe PUFA-derived metabolites 7(R)-MaR1, 11,12-DHET, 17(S)-HDHA, LXA5, and PGJ2 might be considered as potential diagnostic biomarkers of infertility in normozoospermic men.

Effectively reducing the inflammatory response after spinal cord injury (SCI) is a challenging clinical problem and the subject of active investigation. This study employed a porous scaffold-based three dimensional long-term culture technique to obtain human umbilical cord mesenchymal stem cell (hUC-MSC)-derived Small Extracellular Vesicles (sEVs) (three dimensional culture over time, the “4D-sEVs”). Moreover, the vesicle size, number, and inner protein concentrations of the MSC 4D-sEVs contained altered protein profiles compared with those derived from 2D culture conditions. A proteomics analysis suggested broad changes, especially significant upregulation of Epidermal Growth Factors Receptor (EGFR) and Insulin-like Growth Factor Binding Protein 2 (IGFBP2) in 4D-sEVs compared with 2D-sEVs. The endocytosis of 4D-sEVs allowed for the binding of EGFR and IGFBP2, leading to downstream STAT3 phosphorylation and IL-10 secretion and effective induction of macrophages/microglia polarization from the pro-inflammatory M1 to anti-inflammatory M2 phenotype, both in vitro and in the injured areas of rats with compressive/contusive SCI. The reduction in neuroinflammation after 4D-sEVs delivery to the injury site epicenter led to significant neuroprotection, as evidenced by the number of surviving spinal neurons. Therefore, applying this novel 4D culture-derived Small Extracellular Vesicles could effectively curb the inflammatory response and increase tissue repair after SCI.

Different bone bruise patterns observed using magnetic resonance imaging (MRI) after non-contact anterior cruciate ligament (ACL) rupture and lateral patellar dislocation may indicate different knee injury mechanisms. In this study, 77 ACL ruptures and 77 patellar dislocations in knee MR images taken from patients with bone bruises at our institution between August 2020 and March 2022 were selected and analyzed. In order to determine typical bone bruising patterns following by ACL rupture and patellar dislocation, sagittal- and transverse-plane images were used to determine bone bruise locations in the directions of medial-lateral and superior-inferior with MR images. The presence, intensity, and location of the bone bruises in specific areas of the femur and tibial after ACL rupture and patellar dislocation were recorded. Relative bone bruise patterns after ACL rupture and patellar dislocation were classified. The results showed that there were four kinds of bone bruise patterns (1-, 2-, 3-, and 4- bone bruises) after ACL rupture. The most common two patterns after ACL rupture were 3- bone bruises (including the lateral femoral condyle and both the lateral-medial tibial plateau, LF + BT; both the lateral-medial femoral condyle and the lateral tibial plateau, BF + LT; and the medial femoral condyle and both the medial and lateral tibial plateau, MF + BT) followed by 4- bone bruises (both the lateral-medial femoral condyle and the tibial plateau, BF + BT), 2- bone bruises (the lateral femoral condyle and tibial plateau, LF + LT; the medial femoral condyle and the lateral tibial plateau, MF + LT; the lateral femoral condyle and the medial tibial plateau, LF + MT; the medial femoral condyle and the tibial plateau, MF + MT; both the lateral-medial tibial plateau, 0 + BT), and 1- bone bruise (only the lateral tibial plateau, 0 + LT). There was only a 1- bone bruise (the latera femoral condyle and medial patella bone bruise) for patellar dislocation, and the most common pattern of patellar dislocation was in the inferior medial patella and the lateral anterior inferior femur. The results suggested that bone bruise patterns after ACL rupture and patellar dislocation are completely different. There were four kinds of bone bruise patterns after non-contact ACL rupture, while there was only one kind of bone bruise pattern after patellar dislocation in patients, which was in the inferior medial patella and lateral anterior inferior femur.

Abstract Background Programmed Cell Death 2 Like (PDCD2L) correlates with cell proliferation, apoptosis and mouse embryonic development. However, the role of PDCD2L in human cancers is unclear. Methods Multiple bioinformatic methods, in vitro function experiments and validation were performed to clarify the oncogenic role of PDCD2L in human cancers. Results Our study found that PDCD2L was aberrantly expressed in multiple types of human cancers, and associated with clinical stage and molecular subtype. Furthermore, overexpression of PDCD2L predicted poor overall survival in adrenocortical carcinoma(ACC), kidney chromophobe(KICH), acute myeloid leukemia(LAML), brain lower grade glioma(LGG),liver hepatocellular carcinoma(LIHC), mesothelioma(MESO), uveal melanoma(UVM) and poor diseases free survival in ACC, bladder urothelial carcinoma(BLCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), kidney renal clear cell carcinoma(KIRC), kidney renal papillary cell carcinoma(KIRP), LGG, LIHC, and UVM. PDCD2L expression was negatively associated with cancer associated fibroblast in breast invasive carcinoma (BRCA), lung squamous cell carcinoma (LUSC), sarcoma (SARC), stomach adenocarcinoma (STAD) and testicular germ cell tumors (TGCT). Mechanically, we found that PDCD2L expression was associated with apoptosis, invasion and cell cycle by investigating single cell sequencing data. For further validation, PDCD2Lwas highly expressed in colorectal cancer (CRC) cell lines and tissue samples compared with the normal colon cell line and non-tumor adjacent colorectal mucosa tissues. PDCD2L knockdown induced the apoptosis and proliferation of CRC cells. Conclusions Our study shows that the oncogenic role of PDCD2L in various cancers and PDCD2L could be served as a biomarker of CRC.

Summary: Background: Determining the origin of bone metastatic cancer (OBMC) is of great significance to clinical therapeutics. It is challenging for pathologists to determine the OBMC with limited clinical information and bone biopsy. Methods: We designed a regional multiple-instance learning algorithm to predict the OBMC based on hematoxylin-eosin (H&E) staining slides alone. We collected 1041 cases from eight different hospitals and labeled 26,431 regions of interest to train the model. The performance of the model was assessed by ten-fold cross validation and external validation. Under the guidance of top3 predictions, we conducted an IHC test on 175 cases of unknown origins to compare the consistency of the results predicted by the model and indicated by the IHC markers. We also applied the model to identify whether there was tumor or not in a region, as well as distinguishing squamous cell carcinoma, adenocarcinoma, and neuroendocrine tumor. Findings: In the within-cohort, our model achieved a top1-accuracy of 91.35% and a top3-accuracy of 97.75%. In the external cohort, our model displayed a good generalizability with a top3-accuracy of 97.44%. The top1 consistency between the results of the model and the immunohistochemistry markers was 83.90% and the top3 consistency was 94.33%. The model obtained an accuracy of 98.98% to identify whether there was tumor or not and an accuracy of 93.85% to differentiate three types of cancers. Interpretation: Our model demonstrated good performance to predict the OBMC from routine histology and had great potential for assisting pathologists with determining the OBMC accurately. Funding: National Science Foundation of China (61875102 and 61975089), Natural Science Foundation of Guangdong province (2021A15-15012379 and 2022A1515 012550), Science and Technology Research Program of Shenzhen City (JCYJ20200109110606054 and WDZC20200821141349001), and Tsinghua University Spring Breeze Fund (2020Z99CFZ023).

Fatigue has a tremendously adverse impact on pilot performance. This study aims to explore the Biceps Brachii (BB), Rectus Femoris (RF), Flexor Carpi Radialis (FCR), and Tibialis Anterior (TA) activities of fighter pilots in the early and late combat stages, and the target hitting time. A total of 13 volunteers were recruited to conduct simulated combats inside a real fighter cockpit. The surface Electromyography (sEMG) was collected from all volunteers in the initial and final 20s of flight, and the target hitting time during three simulated combats was recorded. The root mean square (RMS) values of right BB and TA were significantly higher than the left side values (p ​

Psoriasis is a recurrent chronic inflammatory skin disease. Unlike many of the latest psoriasis treatments that only confer limited curative effects and have certain side effects, oxymatrine effectively improves severe plaque psoriasis with mild adverse reactions. Here, we explored the genes and pathways underlying the effects of oxymatrine on psoriasis. Briefly, patients with severe plaque psoriasis were treated with oxymatrine and their lesioned skin samples were sequenced by full-length transcriptomics. Next, the differentially expressed genes (DEGs) in psoriatic lesions were identified and compared in oxymatrine-treated patients and healthy controls, their genes were functionally annotated, and protein–protein interaction network analysis and immunohistochemistry were performed. Both Psoriasis Area and Severity Index (PASI) and Body Surface Area (BSA) scores were recovered significantly from all 16 patients (all p < 0.001). The number of DEGs in patients before and after oxymatrine treatment was 4232, and 4105 DEGs were found between the psoriasis group (before oxymatrine treatment) and the normal control group [p < 0.01, |log2 fold change, (FC)| >1.5]. While most of the DEGs recovered significantly after oxymatrine treatment, only 650 DEGs were observed between the psoriasis group (after oxymatrine treatment) and the normal control group (p < 0.01, |log2FC|> 1.5). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that 64 pathways were significantly activated after oxymatrine treatment (p < 0.05). Only 12 pathways were statistically significant between after oxymatrine treatment and the normal control group (p < 0 .05). Among all the restored pathways, the improvement of the IL-17 signaling pathway was the most significant (p = 1.18E-06). Gene loci of oxymatrine action was assessed by protein interaction analysis on 205 DEGs that were co-expressed in 5 patients before and after oxymatrine treatment (p < 0.05, FC > 1.5). After oxymatrine treatment, the expression of two mitosis-related genes namely, cyclin dependent kinase 1 (CDK1) and cyclin B1 (CCNB1), that affect cell proliferation recovered significantly. In light of these results, we conclude that oxymatrine likely alters the abnormal expression of some genes and pathways in psoriasis patients. Multipathway and multitarget therapy can greatly ameliorate abnormalities in genes and pathways and effectively treat psoriasis. Importantly, among the DEGs, the proliferation-related genes, such as CDK1 and CCNB1, are likely important targets for treating psoriasis by oxymatrine. We believe that these findings may lead to a new treatment strategy for psoriasis.

This study aimed to establish a finite element model that vividly reflected the anterior cruciate ligament (ACL) geometry and investigated the ACL stress distribution under different loading conditions. The ACL’s three-dimensional finite element model was based on a human cadaveric knee. Simulations of three loading conditions (134 N anterior tibial load, 5 Nm external tibial torque, 5 Nm internal tibial torque) on the knee model were performed. Experiments were performed on a knee specimen using a robotic universal force/moment sensor testing system to validate the model. The simulation results of the established model were in good agreement with the experimental results. Under the anterior tibial load, the highest maximal principal stresses (14.884 MPa) were localized at the femoral insertion of the ACL. Under the external and internal tibial torque, the highest maximal principal stresses (0.815 MPa and 0.933 MPa, respectively) were mainly concentrated in the mid-substance of the ACL and near the tibial insertion site, respectively. Combining the location of maximum stress and the location of common clinical ACL rupture, the most dangerous load during ACL injury may be the anterior tibial load. ACL injuries were more frequently loaded by external tibial than internal tibial torque.

Tumor segmentation is a fundamental task in histopathological image analysis. Creating accurate pixel-wise annotations for such segmentation tasks in a fully-supervised training framework requires significant effort. To reduce the burden of manual annotation, we propose a novel weakly supervised segmentation framework based on sparse patch annotation, i.e., only small portions of patches in an image are labeled as ‘tumor’ or ‘normal’. The framework consists of a patch-wise segmentation model called PSeger, and an innovative semi-supervised algorithm. PSeger has two branches for patch classification and image classification, respectively. This two-branch structure enables the model to learn more general features and thus reduce the risk of overfitting when learning sparsely annotated data. We incorporate the idea of consistency learning and self-training into the semi-supervised training strategy to take advantage of the unlabeled images. Trained on the BCSS dataset with only 25% of the images labeled (five patches for each labeled image), our proposed method achieved competitive performance compared to the fully supervised pixel-wise segmentation models. Experiments demonstrate that the proposed solution has the potential to reduce the burden of labeling histopathological images.

The heel-to-toe drop of running shoes is a key parameter influencing lower extremity kinematics during running. Previous studies testing running shoes with lower or larger drops generally used minimalist or maximalist shoes, where the factors outside of the drop may lead to the observed changes in running biomechanics. Therefore, our aim was to compare the strike patterns, impact force, and lower extremity biomechanics when running in shoes that varied only in their drops. Eighteen habitual rearfoot strikers performed trials wearing running shoes with four drop conditions: 15 mm, 10 mm, 5 mm, and without a drop. Three-dimensional (3D) tracks of the reflective markers and impact force were synchronously collected using a video graphic acquisition system and two force plates. The biomechanical parameters were compared among the four drop conditions using one-way ANOVA of repeated measures. A greater foot inclination angle (p = 0.001, ηp2 = 0.36) at initial contact and a lower vertical loading rate (p = 0.002, ηp2 = 0.32) during the standing phase were found when running in shoes with large drops compared with running in shoes without a drop. Running in shoes with large drops, as opposed to without, significantly increased the peak knee extension moment (p = 0.002, ηp2 = 0.27), but decreased the peak ankle eversion moment (p = 0.001, ηp2 = 0.35). These findings suggest that the heel-to-toe drop of running shoes significantly influences the running pattern and the loading on lower extremity joints. Running shoes with large drops may be disadvantageous for runners with knee weakness and advantageous for runners with ankle weakness.

Background: Cervical cancer (CC) poses a global health challenge, with a particularly poor prognosis in cases of recurrence, metastasis, or advanced stages. A single biomarker is inadequate to predict CC prognosis or identify CC patients likely to benefit from immunotherapy, presumably owing to tumor complexity and heterogeneity. Methods: Using advanced Olink proteomics, we analyzed 92 oncology-related proteins in plasma from CC patients receiving immunotherapy, based upon the comparison of protein expression levels of pre-therapy with those of therapy-Cycle 6 in the partial response (PR) group and progressive disease (PD) group, respectively. Results: 55 proteins were identified to exhibit differential expression trends across pre-therapy and post-therapy in both PR and PD groups. Enriched GO terms and KEGG pathways were associated with vital oncological and immunological processes. A logistic regression model, using 5 proteins (ITGB5, TGF-α, TLR3, WIF-1, and ERBB3) with highest AUC values, demonstrated good predictive performance for prognosis of CC patients undergoing immunotherapy and showed potential across different cancer types. The effectiveness of these proteins in prognosis prediction was further validated using TCGA-CESC datasets. A negative correlation and previously unidentified roles of WIF-1 in CC immunotherapy was also first determined. Conclusion: Our findings reveal multi-biomarker profiles effectively predicting CC prognosis and identifying patients benefitting most from immunotherapy, especially for those with limited treatment options and traditionally poor prognosis, paving the way for personalized immunotherapeutic treatments and improved clinical strategies. [ABSTRACT FROM AUTHOR]