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Background Minimal change disease (MCD) is a common pathological type of nephrotic syndrome. Relapses of MCD present a significant challenge for patients. This study aims to develop a predictive model for evaluating the probability of relapse in patients with MCD.Methods This study enrolled 152 patients with biopsy-confirmed MCD, all of whom received exclusive glucocorticoid treatment at the First Affiliated Hospital of Zhejiang University in Hangzhou, China, between October 2012 and April 2021. The Cox regression analysis was utilized to identify the risk factors associated with the relapse in MCD, and a nomogram was constructed to predict the probability of relapse.Results The results demonstrated that serum immunoglobulin E (IgE) levels > 936 IU/mL, age ≤ 30 years old, estimated glomerular filtration rate (eGFR) 12.3 mmol/L, and time to remission were independent risk factors associated with relapses in patients with MCD. A nomogram was established and achieved a concordance index of 0.726 (95% CI = 0.659–0.793). The receiver operating characteristic curves demonstrated areas under the curve of 0.771, 0.853, and 0.811 for the prediction of relapse at 1-, 2-, and 3-year intervals after achieving remission in MCD patients respectively. These findings along with the calibration curves indicated the good discrimination and calibration performance of the nomogram in this cohort.Conclusion: The established nomogram provides a valuable tool for the identification of patients with MCD who are at risk of relapse, which may facilitate prompt treatment for these patients.

Abstract In representation learning domain, the mainstream methods for model ensemble include “implicit” ensemble approaches, such as using techniques like dropout, and “explicit” ensemble methods, such as voting or weighted averaging based on multiple model outputs. Compared to implicit ensemble techniques, explicit ensemble methods allow for more flexibility in combining models with different structures to obtain different perspectives on representations. However, the representations obtained from different models do not guarantee a linear relationship, and simply linearly combining multiple model outputs may result in a degraded performance. Meanwhile, employing non‐linear fusion mechanisms such as distillation and meta‐learning can be uninterpretable and time‐consuming. To this end, we propose the hypothesis of linear fusion based on the output representations of deep learning models, and design a interpretable linear fusion method based on this hypothesis. This method applies a transform layer to map the output representations of different models to the same classification center. Experimental results demonstrate that compared to directly averaging the representations, our method achieves better performance. Additionally, our method retains the convenience of direct averaging while offering improved performance in terms of time and computational efficiency compared to non‐linear fusion. Furthermore, we test the applicability of our method in both computer vision and natural language processing representation tasks using supervised and semi‐supervised approaches.

Abstract Exosomes, nanosized vesicles, play a vital role in breast cancer (BC) occurrence, development, and drug resistance. Hence, we proceeded to study the potential prognostic value of exosome-related genes and their relationship to the immune microenvironment in BC. 121 exosome-related genes were provided by the ExoBCD database, and 7 final genes were selected to construct the prognostic signature. Besides, the expression levels of the 7 exosome-related genes were validated by the experiment in BC cell lines. Based on the signature, BC patients from the training and validation cohorts were separated into low- and high-risk groups. Subsequently, the R clusterProfiler package was applied to identify the distinct enrichment pathways between high-risk groups and low-risk groups. The relevance of the tumor immune microenvironment and exosome-related gene risk score were analyzed in BC. Eventually, the different expression levels of immune checkpoint-related genes were compared between the two risk groups. Based on the risk model, the low-risk groups were identified with a higher survival rate both in the training and validation cohorts. A better overall survival was revealed in patients with higher scores evaluated by the estimation of stromal and immune cells in malignant tumor tissues using expression (ESTIMATE) algorithm. Subsequently, BC patients with lower risk scores were indicated by higher expression levels of some immune checkpoint-related genes and immune cell infiltration. Exosomes are closely associated with the prognosis and immune cell infiltration of BC. These findings may contribute to improving immunotherapy and provide a new vision for BC treatment strategies.

BackgroundTo explore the mechanism of OIP5-AS1/CD147/TRPM7 axis to gastric cancer (GC) metastasis.MethodsBioinformatic analysis was performed to pick up the candidate genes associated with regulation GC metastasis. Using GC cell lines, AGS and MKN-45 as research objects, identify the effect of candidate genes on GC metastasis, judge cell proliferation status by MTT assay and cell clone number, and detect cell migration by Transwell and Wound-healing assay. The molecular mechanism of CD147/OIP5/TRPM7 axis regulating GC metastasis was further explored by RNA sequencing. The key signaling pathways were subsequently verified by flow cytometry and WB.ResultsBioinformatic analysis suggested OIP5-AS1/CD147/TRPM7 axis may be involving in GC metastasis. The RNA interference experiment proved that after gene interference, the proliferation ability of GC cells decreased significantly (P

Abstract Breast cancer (BC) is one of the most frequent malignancies among women worldwide. Accumulating evidence indicates that long non-coding RNA (lncRNA) may affect BC progression. Exosomes, a class of small membrane vesicles, have been reported to promote tumor progression through transporting proteins, mRNAs, lncRNAs and some other small molecules. However, the interaction between exosome-related lncRNAs and the microenvironment of malignancies is unclear. Hence, we proceeded to investigate the relationship between exosome-related lncRNAs and BC microenvironment. 121 exosome-associated genes were extracted from ExoBCD database. Then, the Pearson analysis was used to screened out the exosome-related lncRNAs. After that, 15 exosome-related differentially expressed lncRNAs were identified by the correlation with BC prognosis. According to the sum of the expression of these 15 lncRNAs, extracted from The Cancer Genome Atlas, and the regression coefficients, an exosome-related lncRNAs signature was developed by using Cox regression analysis. With the median risk score of the training set, the patients in training and validation sets were separated to low-risk group and high-risk group. Subsequently, the lncRNA–mRNA co-expression network was constructed. The distinct enrichment pathways were compared among the different risk groups by using the R package clusterProfiler. The ESTIMATE method and ssGESA database were adopted to study the ESTIMATE Score and immune cell infiltration. Eventually, the expression of immune checkpoint associated genes, microsatellite instable and the immunophenoscore were further analyzed between different risk groups. Different risk groups exhibited different prognosis, with lower survival rate in the high-risk group. The differentially expressed genes between the different risk groups were enriched in biological processes pathways as well as immune responses. BC patients in high-risk group were identified with lower scores of ESTIMATE scores. Subsequently, we noticed that the infiltrating levels of aDCs, B cells, CD8+ T cells, iDCs, DCs, Neutrophils, macrophages, NK cells, pDCs, Tfh, T helper cells, TIL and Tregs were obvious elevated with the decreased risk score in training and validation cohorts. And some immune signatures were significantly activated with the decreased risk score in both cohorts. Eventually, the exosome-associated lncRNAs risk model was demonstrated to accurately predict immunotherapy response in patients with BC. The results of our study suggest that exosome-related lncRNAs risk model has close relationship with prognosis and immune cells infiltration in BC patients. These findings could make a great contribution to improving BC immunotherapy.

Abstract Background Painless bloody nipple discharge is often classified as pathological due to its association with malignant lesions. However, it can also be a completely harmless condition. Rusty pipe syndrome is a rare cause of benign, self-limiting bloody nipple discharge during late pregnancy and early lactation. Given that rusty pipe syndrome is not described in conventional textbooks, we thought it would be appropriate to bring this benign disease to the notice of readers. Case presentation A 31-year-old G1P1 female delivered an infant with a birth weight of 3000 g via cesarean section at 39 weeks of gestation. The baby was admitted to the pediatric intensive care unit for a suspected oblique inguinal hernia. The mother had bilateral painless bloody nipple discharge when she started to express milk. A physical examination uncovered no signs of inflammation, engorgement, palpable mass, tenderness, cracks or ulcers. A breast ultrasound and cytological analysis revealed no signs of a neoplasm. Without any medical intervention, the color of the rusty milk changed from dark brown to light brown during hospitalization and finally resolved six days postpartum. Conclusion Rusty pipe syndrome is a self-limiting benign condition that should be considered in the differential diagnosis of bloody nipple discharge. Awareness of this rare disease by medical professionals would be extremely beneficial for avoiding unneeded examinations and discontinuity of exclusive breastfeeding.

ObjectiveRandom skin flaps have many applications in plastic and reconstructive surgeries. However, distal flap necrosis restricts wider clinical utility. Mitophagy, a vital form of autophagy for damaged mitochondria, is excessively activated in flap ischemia/reperfusion (I/R) injury, thus inducing cell death. Aldehyde dehydrogenase-2 (ALDH2), an allosteric tetrameric enzyme, plays an important role in regulating mitophagy. We explored whether ALDH2 activated by N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide (Alda-1) could reduce the risk of ischemic random skin flap necrosis, and the possible mechanism of action.MethodsModified McFarlane flap models were established in 36 male Sprague-Dawley rats assigned randomly to three groups: a low-dose Alda-1 group (10 mg/kg/day), a high-dose Alda-1 group (20 mg/kg/day) and a control group. The percentage surviving skin flap area, neutrophil density and microvessel density (MVD) were evaluated on day 7. Oxidative stress was quantitated by measuring the superoxide dismutase (SOD) and malondialdehyde (MDA) levels. Blood perfusion and skin flap angiogenesis were assessed via laser Doppler flow imaging and lead oxide-gelatin angiography, respectively. The expression levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α), vascular endothelial growth factor (VEGF), ALDH2, PTEN-induced kinase 1 (PINK1), and E3 ubiquitin ligase (Parkin) were immunohistochemically detected. Indicators of mitophagy such as Beclin-1, p62, and microtubule-associated protein light chain 3 (LC3) were evaluated by immunofluorescence.ResultsAlda-1 significantly enhanced the survival area of random skin flaps. The SOD activity increased and the MDA level decreased, suggesting that Alda-1 reduced oxidative stress. ALDH2 was upregulated, and mitophagy-related proteins (PINK1, Parkin, Beclin-1, p62, and LC3) were downregulated, indicating that ALDH2 inhibited mitophagy through the PINK1/Parkin signaling pathway. Treatment with Alda-1 reduced neutrophil infiltration and expressions of inflammatory cytokines. Alda-1 significantly upregulated VEGF expression, increased the MVD, promoted angiogenesis, and enhanced blood perfusion.ConclusionALDH2 activation can effectively enhance random skin flap viability via inhibiting PINK1/Parkin-dependent mitophagy. Moreover, enhancement of ALDH2 activity also exerts anti-inflammatory and angiogenic properties.

The parameters of the discrete element simulation model for rice field soils serve as valuable data references for investigating the dynamic characteristics of the walking wheel of high-speed precision seeding machinery in paddy fields. The research specifically targets clay loam soil from a paddy field in South China. Calibration of essential soil parameters was achieved using EDEM_2022 software (and subsequent versions) discrete element simulation software, employing the Edinburgh Elasto-Plastic Adhesion (EEPA) nonlinear elastic-plastic contact model. The tillage layer and plough sub-base layer underwent calibration through slump and uniaxial compression tests, respectively. Influential contact parameters affecting slump and axial pressure were identified through a Plackett–Burman test. The optimal contact parameter combinations for the discrete element model of the tillage layer and plough sub-base layer were determined via a quadratic rotational orthogonal test. The accuracy of the discrete element simulation model’s parameters for paddy field soils was further validated through a comparative analysis of the simulation test’s cone penetration and the field soil trench test. Results indicate that the Coefficient of Restitution, surface energy, Contact Plasticity Ratio, and Tensile Exp significantly influence slump (p < 0.05). Additionally, the Coefficient of Restitution, Contact Plasticity Ratio, coefficient of rolling friction, and Tangential Stiff Multiplier significantly impact axial pressure (p < 0.05). Optimal contact parameters for the plough layer were achieved with a particle recovery coefficient of 0.49, a surface energy of 18.52 J/m2, a plastic deformation ratio of 0.45, and a tensile strength of 3.74. For the plough subsoil layer, optimal contact parameters were a particle recovery coefficient of 0.47, a coefficient of interparticle kinetic friction of 0.32, a plastic deformation ratio of 0.49, and a tangential stiffness factor of 0.31. Results from the cone penetration test reveal no significant disparity in compactness between the actual experiment and the simulation test. The calibrated discrete element model’s contact parameters have been verified as accurate and reliable. The findings of this study offer valuable data references for understanding the dynamic characteristics of the walking wheel of the entire machinery in high-speed precision seeding in paddy fields.

Abstract Government hotline plays a significant role in meeting the demands of the people and resolving social conflicts in China. In this paper, we propose an automatic work‐order assignment method based on event extraction and external knowledge to address the problem of low efficiency with manual assignment for Chinese government hotline. Our proposed assignment method is composed of four parts: (1) Semantic encoding layer, which extracts semantic information from the work‐order text and obtains semantic representation vectors with contextual feature information. (2) Event extraction layer which extracts the local features and global features from the semantic representation vectors with the help of the CRF network to enhance event extraction effect. (3) External knowledge embedding layer, which integrates ‘rights and responsibilities lists’ with the historical information of the work‐order to assist assignment. (4) Assignment layer which completes work‐order assignment by combining two output vectors from event extraction layer and external knowledge embedding layer. Experimental results show our proposed method can achieve better assignment performance compared with several baseline methods.

To elucidate the vibrational characteristics of power chassis in paddy fields, we examined the Yanmar VPG6G rice transplanter across diverse terrains, including paddy fields, dry land, and concrete roads. Vibrational acceleration measurements, taken in longitudinal, transverse, and vertical orientations at key chassis locations, revealed noteworthy findings. The Mizuta power chassis exhibited its lowest root-mean-square (RMS) vibrational acceleration on concrete, while the highest was observed on paddy fields. The acceleration power spectra predominantly peaked between 1~14 Hz, with peak values amplifying as speed increased. Additionally, pendant orientation frequencies exceeded those of longitudinal and lateral directions. Both front and rear wheels mirrored the vibrational accelerations of the rear axle, but dynamic load coefficients for the front wheels consistently surpassed the rear, particularly at elevated speeds. This research not only enhances our understanding of terrain-induced vibrations and the intricate dynamics between terrain and tires but also lays the groundwork for designing optimized vibration-damping solutions tailored to prevalent road conditions.

Abstract Background Thin endometrium is a primary cause of defective endometrial receptivity, resulting in infertility or recurrent miscarriage. Much effort has been devoted toward regenerating thin endometrium by stem cell-based therapies. The human placenta-derived mesenchymal stem cells (HP-MSCs) are emerging alternative sources of MSCs with various advantages. To maximize their retention inside the uterus, we loaded HP-MSCs with cross-linked hyaluronic acid hydrogel (HA hydrogel) to investigate their therapeutic efficacy and possible underlying mechanisms. Methods Ethanol was injected into the mice uterus to establish the endometrium-injured model. The retention time of HP-MSCs and HA hydrogel was detected by in vivo imaging, while the distribution of HP-MSCs was detected by immunofluorescence staining. Functional restoration of the uterus was assessed by testing embryo implantation rates. The endometrial morphological alteration was observed by H&E staining, Masson staining, and immunohistochemistry. In vitro studies were further conducted using EdU, transwell, tube formation, and western blot assays. Results Instilled HP-MSCs with HA hydrogel (HP-MSCs-HA) exhibited a prolonged retention time in mouse uteri than normal HP-MSCs. In vivo studies showed that the HP-MSCs-HA could significantly increase the gland number and endometrial thickness (P

Government hotline is closely related to people’s lives and plays an important role in solving social problems and maintaining social stability in China. However, the event text of the hotline is inconsistent in length and unclear in elements, so it is a challenge for the operator to manually complete the assignment tasks of hotline event. To address these problems, we propose a joint learning method for event text classification and event assignment for Chinese government hotline. Firstly, graph convolution network (GCN) and BERT are used to process the event text respectively to obtain the corresponding representation vector. Then, the obtained two representation vectors are fused by the dynamic fusion gate to get fusion vector and classified the fusion vector through the text classification. Secondly, we use multi-attention mechanism to process the GCN result vector, BERT result vector and the “sanding” vector to obtain attentive “event-sanding” representation vector and calculate the corresponding department probability distribution. Finally, the historical prior knowledge based reorder model is used to sort the results of the “event-sanding” matching module and output the optimal assignment department of government hotline event. Experimental results show that our method can achieve better performance compared with several baseline approaches. The ablation experiments also demonstrate the validity of each proposed module in our model.

Abstract The fatigue strength of a component is known to highly depend on its surface quality, and it is thus necessary to develop a reliable and appropriate mathematical model for fatigue strength assessment that consider the effect of surface roughness. In this paper, different underlying physical mechanisms of the roughness effect at different regions of specimens were studied by fatigue testing of 7N01 aluminum alloy. For a quantitative analysis of the surface roughness effect, a revised stress field intensity approach for a fatigue strength assessment of microsized notches was proposed as a theoretical support. In the new model, a new form of weight function was built to adapt the characteristics of microsized notches. In addition, the effect of the field radius was fundamentally weakened on solution of the stress field intensity and the difficulty of fatigue failure region definition in the traditional method was overcome correspondingly in the proposed model, which made the calculated field strength accurate and objective. Finally, to demonstrate the validity of the revised approach quantitatively, specimens with conventionally sized notches were subjected to stress field intensity calculations. The results showed that the revised approach has satisfactory accuracy compared with the other two traditional approaches from the perspective of quantitative analysis.

BackgroundPyroptosis is a novel identified form of inflammatory cell death that is important in the development and progression of various diseases, including malignancies. However, the relationship between pyroptosis and triple-negative breast cancer (TNBC) is still unclear. Therefore, we started to investigate the potential prognostic value of pyroptosis-associated genes in TNBC.MethodsThirty-three genes associated with pyroptosis were extracted from previous publications, 30 of which were identified in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort. On the basis of the 30 pyroptosis-related genes, patients with TNBC were divided into three subtypes through unsupervised cluster analysis. The prognostic value of each pyroptosis-associated gene was assessed, and six genes were selected by univariate and LASSO Cox regression analysis to establish a multigene signature. According to the median value of risk score, patients with TNBC in the training and validation cohorts were separated to high- and low-risk sets. The enrichment analysis was conducted on the differentially expressed genes (DEGs) of the two risk sets using R clusterProfiler package. Moreover, the ESTIMATE score and immune cell infiltration were calculated by the ESTIMATE and CIBERSORT methods. After that, the correlation among pyroptosis-associated risk score and the expression of immune checkpoint-associated genes as well as anti-cancer drugs sensitivities were further analyzed.ResultsIn the training and validation cohorts, patients with TNBC in the high-risk set were found in a lower survival rate than those in the low-risk set. Combined with the clinical characteristics, the pyroptosis-related risk score was identified as an independent risk factor for the prognosis of patients with TNBC. The enrichment analysis indicated that the DEGs between the two risk groups were mainly enriched by immune responses and activities. In addition, patients with TNBC in the low-risk set were found to have a higher value of ESTIMATE score and a higher rate of immune cell infiltration. Finally, the expression levels of five genes [programmed cell death protein 1 (PD-1); cytotoxic t-lymphocyte antigen-4 (CTLA4); lymphocyte activation gene 3 (LAG3); T cell immunoreceptor with Ig and ITIM domains (TIGIT)] associated with immune checkpoint inhibitors were identified to be higher in the low-risk sets. The sensitivities of some anti-cancer drugs commonly used in breast cancer were found closely related to the pyroptosis-associated risk model.ConclusionThe pyproptosis-associated risk model plays a vital role in the tumor immunity of TNBC and can be applied to be a prognostic predictor of patients with TNBC. Our discovery will provide novel insight for TNBC immunotherapies.

Porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and porcine deltacoronavirus (PDCoV) belong to the category of swine enteric coronavirus that cause acute diarrhea in piglets, which has resulted in massive losses to the pig husbandry. Therefore, a sensitive and rapid detection method which can differentially detect these viruses that lead to mixed infections in clinical cases, is urgently needed. According to the conserved regions of the PEDV M gene, TGEV S gene, and PDCoV N gene, and the reference gene of porcine (β-Actin), we designed new specific primers and probes for the multiplex qPCR assay capable of simultaneously detecting three RNA viruses. This method, with a great specificity, did not cross-react with the common porcine virus. Moreover, the limit of detection of the method we developed could reach 10 copies/μL ,and the intra- and inter-group coefficients of variation of it below 3%. Applying this assay to detect 462 clinical samples which were collected in 2022–2023, indicated that the discrete positive rates of PEDV, TGEV, and PDCoV were 19.70%, 0.87%, and 10.17%, respectively. The mixed infection rates of PEDV/TGEV, PEDV/PDCoV, TGEV/PDCoV, and PEDV/TGEV/PDCoV were 3.25%, 23.16%, 0.22%, and 11.90%, respectively. All in all, the multiplex qPCR assay we developed as a tool for differential and rapid diagnosing can be put on the active prevention and control of PEDV, TGEV, and PDCoV, , which can create great value in the diagnosis of swine diarrhea diseases.

Soil moisture is an important variable affecting land surface and climate interactions. This study used cross-wavelet and wavelet coherence methods to analyze the relationship between soil moisture and climatic factors in the study area based on the soil moisture data sequence and corresponding meteorological data observed on the surface of the desert steppe in Inner Mongolia. The results showed that soil moisture had a relatively high- or low-value period for months or even years. Soil moisture was significantly different between different slope positions and soil layers. The fluctuation and mean of soil moisture decreased gradually with the deepening of soil depth. The relationship between soil moisture and meteorological factors varied with time scales. The influence of precipitation on soil moisture was significant at time scales of 1–6 months and 10–15 months, while air temperature and soil temperature showed stable and continuous periodic influence on soil moisture at the time scale of 10–15 months. Climate indexes for the Pacific region, Pacific Decadal Oscillation (PDO), and North Atlantic Oscillation index (NAO) were the main climatic factors controlling soil moisture in the Inner Mongolia desert steppe and strongly correlated with soil moisture primarily on time scales of 4–7 months and 10–15 months. Pacific Decadal Oscillation (PDO) and Indian Ocean basin-wide warming (IOBW) showed a strong lag effect on soil moisture.

Copper oxide nanoparticles were successfully synthesized through a simple and ‘green’ route using starch as a capping and stabilizing agent under ultrasonic irradiation in alkaline medium. Unique reaction condition was prepared by ultrasonic irradiation, releasing the stored energy in the collapsed bubbles and heats the bubble contents that leads to Cu(II) reduction in the presence of starch. The obtained nanoparticle (CuO NPs@Starch) was characterized by advanced physical and chemical techniques like Transmission Electron Microscope (TEM), Fourier-transform infrared spectroscopy (FTIR), Uv–Vis spectroscopy, scanning electron microscopy (SEM), X-ray Diffraction (XRD) and energy-dispersive X-ray analysis (EDX). The properties of CuO NPs@Starch against gastric cancer (AGS and KATO III), pancreatic cancer (AsPC-1 and MIA PaCa-2), and colon cancer (HCT 116 and HCT-8) were evaluated. The viability of malignant cancer cell lines reduced dose-dependently in the presence of CuO NPs@Starch. After clinical study, CuO NPs@Starch can be utilized as an efficient drug in the treatment of gastric, pancreatic, and colon cancers in humans.

ObjectiveIntractable pain after peripheral nerve injury has become a major concern in the field of pain. Current evidence shows that routine medications or surgical treatment is associated with inconsistent results and different curative effects. Stable and effective treatment methods in clinical practice are also lacking. To date, there is no consensus on the pathophysiological mechanisms of pain. The present study investigates the potential regulatory role of regulatory T cells in the differentiation of macrophages on dorsal root ganglion (DRG) and explores the mechanism of nociceptive signals in the signal transfer station. The findings are expected to guide the prevention of various types of peripheral neuropathic pain.MethodsThirty-six male Sprague Dawley (SD) rats and 18 male Nude rats, of equal weight (250–300g), were used in this study. The rats were divided into 3 groups: SD rat sciatic nerve transection group (SNT group, n = 18), SD rat nerve transection experimental group (SNT/RAPA group, n = 18) and Nude rat nerve transection experimental group (SNT/NUDE group, n = 18). The behavior related to neuropathic pain of animals were comprehensively evaluated in all groups. Furthermore, we analyzed the degree of neuroma development, histology, gene, and protein expression, and compared their correlation with the ultrastructural changes of M1/M2 type differentiation of macrophages in DRG.ResultsSciatic nerve transection (SNT), induced the aggregation of several types of macrophages in lumbar DRG of SD rats leading to a higher ratio of M1/M2. Following the inhibition of the M1 type polarization of macrophages, axon outgrowth increased significantly. A significantly lower average autotomy score was reported in the SNT/NUDE group (*p < 0.05) and the SNT/RAPA group (@p < 0.05) as compared to that of the SNT group. The SNT/NUDE group showed no noticeable neuroma formation 30 days after the nerve transection. However, bulbous neuromas were observed in the nerve stumps of both the SNT control and SNT/RAPA groups. Immunofluorescence staining revealed a significant decrease in the proportion of M1/M2 macrophages in lumbar DRG of the SNT/NUDE group (**p < 0.001) and the SNT/RAPA group (@p < 0.05) compared to the SNT group. The expression of pain-related proteins was also decreased (@p < 0.05, *p < 0.05,**p < 0.001). Also, the expression of alpha-smooth muscle actin (α-SMA), neurofilament 200 (NF-200), and nerve growth factor low-affinity receptor p75 were significantly down-regulated in the nerve tissue (@p < 0.05, @@p < 0.001, **p < 0.001).ConclusionM1/M2 type differentiation of macrophages on DRG plays a significant role in the formation of traumatic painful neuroma after neurotomy. In combination with our previous study, the results of this study suggest that regulatory T cells reduce the ratio of M1/M2 macrophages and alleviate the pain of neuroma by regulating the polarization direction of macrophages on neuroma. These findings provide key insights into developing new strategies to manage painful neuroma.

Background: Skin flap transplantation is a common wound repair method in orthopedic surgery, but skin flap necrosis remains problematic. Memantine, an excitatory amino acid receptor antagonist, is currently used in the treatment of moderate to severe Alzheimer's disease, due to its ability to promote angiogenesis and reduce oxidative stress. This study investigated the effect of memantine on the survival of random skin flaps in Sprague-Dawley (SD) rats. Materials and methods: Thirty six male SD rats were divided into control, high-dose (20 mg/kg per day), and low-dose (10 mg/kg per day) groups and underwent a McFarland flap procedure. Seven days later, the survival of the flap was evaluated, The microvascular density and neutrophil density were measured by hematoxylin and eosin staining. Lead angiography was used to detect angiogenesis, and laser Doppler was used to detect blood perfusion. Expression levels of vascular endothelial growth factor (VEGF), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, Toll-like receptor (TLR) 4, nuclear factor kappa B(NF-κB) and Mitogen-activated protein kinase（MAPK）were detected by immunohistochemistry. Oxidative stress was evaluated by measuring the levels of malondialdehyde (MDA) and superoxide dismutase (SOD). Results: Compared with the control group, the flap survival area of memantine group, especially the high-dose group, was larger, VEGF expression, microvascular density, angiogenesis, blood perfusion, and superoxide dismutase in the flap were higher in the Memantine-H group than in the Memantine-L and control groups (P

BackgroundAs a kind of small membrane vesicles, exosomes are secreted by most cell types from multivesicular endosomes, including tumor cells. The relationship between exosomes and immune response plays a vital role in the occurrence and development of tumors. Nevertheless, the interaction between exosomes and the microenvironment of tumors remains unclear. Therefore, we set out to study the influence of exosomes on the triple-negative breast cancer (TNBC) microenvironment.MethodOne hundred twenty-one exosome-related genes were downloaded from ExoBCD database, and IVL, CXCL13, and AP2S1 were final selected because of the association with TNBC prognosis. Based on the sum of the expression levels of these three genes, provided by The Cancer Genome Atlas (TCGA), and the regression coefficients, an exosome risk score model was established. With the median risk score value, the patients in the two databases were divided into high- and low-risk groups. R clusterProfiler package was employed to compare the different enrichment ways between the two groups. The ESTIMATE and CIBERSORT methods were employed to analyze ESTIMATE Score and immune cell infiltration. Finally, the correlation between the immune checkpoint-related gene expression levels and exosome-related risk was analyzed. The relationship between selected gene expression and drug sensitivity was also detected.ResultsDifferent risk groups exhibited distinct result of TNBC prognosis, with a higher survival rate in the low-risk group than in the high-risk group. The two groups were enriched by immune response and biological process pathways. A better overall survival (OS) was demonstrated in patients with high scores of immune and ESTIMATE rather than ones with low scores. Subsequently, we found that CD4+-activated memory T cells and M1 macrophages were both upregulated in the low-risk group, whereas M2 macrophages and activated mast cell were downregulated in the low-risk group in patients from the TCGA and GEO databases, respectively. Eventually, four genes previously proposed to be targets of immune checkpoint inhibitors were evaluated, resulting in the expression levels of CD274, CTLA4, LAG3, and TIM3 being higher in the low-risk group than high-risk group.ConclusionThe results of our study suggest that exosome-related risk model was related to the prognosis and ratio of immune cell infiltration in patients with TNBC. This discovery may make contributions to improve immunotherapy for TNBC.

The Lateolabrax maculatus is an important marine fish in China that can adapt to a wide range of water salinities. The gill is the main organ involved in fish osmoregulation and in this study, a cDNA library of the L. maculatus gill was constructed to understand gill function in Lateolabrax maculatus and it adaptation to salinity. A total raw data of 5.3G base pairs was obtained, followed removal of low-quality and linker DNA sequences and it yielded a total of 23,038,590 clean reads. After splicing and clustering, 31,976 unigenes were obtained. The average transcript length was 1327 bp and N50 was 2057 bp. In comparisons with other tissues analysis of the gill transcriptome revealed a high level of relative expression of apolipoprotein E, CD74, keratin, type I cytoskeleton 13, carbonic anhydrase, betaine-homocysteine S-methyltransferase, and aquaporin 3 (AQP3) genes. The L. maculatus aqp3 (Lm-aqp3) gene was specific for the gills Lm-aqp3 and this gene has a typical transmembrane structure of six alpha helices and a water channel domain. Phylogenetic analysis indicated that Lm-aqp3 clusters with the homologue genes from Labrus bergylta and Dicentrarchus labrax. Quantitative RT-PCR confirmed that Lm-aqp3 was highly abundant in the gills and low expressed in other tissues (stomach, liver, brain, spleen and testis). Analysis of Lm-aqp3 in freshwater aquaculture fish revealed that gene expression was significantly statistical higher than in seawater (20 ppt) fish, suggesting that Lm-aqp3 may play an important role in water metabolism and osmotic pressure regulation in L. maculatus. Keywords: Lateolabrax maculatus, Gill, Transcriptome, Aquaporin 3

Objectives Some studies have identified tumour-infiltrating lymphocytes (TILs) in H&E-stained sections of gastric cancer, but the prognostic and clinicopathological significance of this remains unclear. The objective of this study is to evaluate the associations between H&E-based TIL density and prognosis and clinicopathological characteristics of patients with gastric cancer.Design Systematic review and meta-analysis.Data sources Cochrane Library, PubMed and Embase databases were searched through 25 February 2020.Eligibility criteria Studies evaluating the correlations between TILs assessed by H&E-stained sections and prognosis and clinicopathological characteristics of gastric cancer were included.Data extraction and synthesis Relevant data were extracted and risks of bias were assessed independently by two reviewers. HR and relative risk (RR) with 95% CI were pooled by random-effect models to estimate the associations between TIL density and overall survival (OS) and clinicopathological characteristics, respectively.Results We enrolled nine studies including 2835 cases for the present meta-analysis. High TILs were associated with superior OS (HR=0.68, 95% CI 0.52 to 0.87, p=0.003) compared with low TILs. High TILs were significantly associated with lower depth of invasion (T3–T4 vs T1–T2) (RR=0.58, 95% CI 0.50 to 0.66, p

Breast cancer (BC) is the most common malignancy in female, but the role of androgen receptor (AR) in triple-negative breast cancer (TNBC) is still unclear. This study aimed to exam the performance of innovative biomarkers for AR positive TNBC in diagnosis and therapies. Four datasets (GSE42568, GSE45827, GSE54002 and GSE76124) were analyzed by bioinformatic methods and the differential expression genes (DEGs) between the AR positive TNBC tissues and normal tissues were firstly identified by limma package and Venn diagrams. Next, Gene Ontologies (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to explore the relationship between these DEGs. Then, the Protein-protein interaction (PPI) network was constructed. CytoHubba and bioinformatic approaches including Molecular Complex Detection (MCODE), Gene Expression Profiling Interactive Analysis (GEPIA), the Kaplan–Meier (KM) plotter and The Human Pro-tein Atlas (THPA) were used to identify the hub genes. Lastly, a miRNA-hub-gene regulatory axis was constructed by use of Target Scan database and ENCORI database. As a result, a total of 390 common DEGs were identified, including 250 up-regulated and 140 down-regulated. GO and KEGG enrichment analysis showed that the up-regulated DEGs were mostly enriched in the cell division, mitotic nuclear division, nucleosome, midbody, protein heterodimerization activity, cadherin binding involved in cell−cell adhesion, systemic lupus erythematosus and alcoholism, while the down-regulated DEGs were mainly enriched in carbohydrate metabolic process, extracellular space, extracellular region, zinc ion binding and microRNAs in cancer. Then, 13 hub genes (CCNB2, FOXM1, HMMR, MAD2L1, RRM2, TPX2, TYMS, CEP55, AURKA, CCNB1, CDK1, TOP2A, PBK) were selected. The survival analysis revealed that only CCNB1 was associated with significantly poor survival (P

Address is a structured description used to identify a specific place or point of interest, and it provides an effective way to locate people or objects. The standardization of Chinese place name and address occupies an important position in the construction of a smart city. Traditional address specification technology often adopts methods based on text similarity or rule bases, which cannot handle complex, missing, and redundant address information well. This paper transforms the task of address standardization into calculating the similarity of address pairs, and proposes a contrast learning address matching model based on the attention-Bi-LSTM-CNN network (ABLC). First of all, ABLC use the Trie syntax tree algorithm to extract Chinese address elements. Next, based on the basic idea of contrast learning, a hybrid neural network is applied to learn the semantic information in the address. Finally, Manhattan distance is calculated as the similarity of the two addresses. Experiments on the self-constructed dataset with data augmentation demonstrate that the proposed model has better stability and performance compared with other baselines.

BACKGROUND AND OBJECTIVE: Blood vessel invasion plays a very important role in the progression and metastasis of cancer. However, blood vessel invasion as a prognostic factor for survival in non-small cell lung cancer (NSCLC) remains controversial. The aim of this study is to explore the relationship between blood vessel invasion and outcome in patients with NSCLC using meta-analysis. METHODS: A meta-analysis of published studies was conducted to investigate the effects of blood vessel invasion on both relapse-free survival (RFS) and overall survival (OS) for patients with NSCLC. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to assess the strength of this association. RESULTS: A total of 16,535 patients from 52 eligible studies were included in the systematic review and meta-analysis. In total, blood vessel invasion was detected in 29.8% (median; range from 6.2% to 77.0%) of patients with NSCLC. The univariate and multivariate estimates for RFS were 3.28 (95% CI: 2.14-5.05; P