Search

Leprosy is a chronic infectious disease that mainly affects the skin and peripheral nerves, it can also invade deeper tissues and organs, including mucous membranes, lymph nodes, testes, eyes, and internal organs. Severe cases can result in deformities and disabilities. We encountered the case of a 39-year-old male with unexplained fever, headache and rash. The patient’s lesions were taken for histopathological examination and slit skin smear analysis. Further, the patient was detected of Mycobacterium leprae (M.leprae) nucleic acid sequences in the cerebrospinal fluid (CSF) and plasma, and M.leprae gene targets in the skin lesion tissue and blood. The patient was eventually diagnosed with multibacillary leprosy and type II leprosy reaction. These results suggest the possibility of bacteremia in patients with leprosy to some extent, and observation implies the potential invasion of CSF by M.leprae or its genetic material.

Lithium in coal, as a new type of associated mineral resource, has considerable potential for exploration. Exploration of high-lithium coal seams is essential for developing and using the associated lithium resources. To explore the distribution of lithium resources in the early stages of development in coal seams, the relationship between coal seam logging data and lithium content was analyzed by taking Guojiadi Coal Mine (China) as example. By analyzing the correlation between the different logging curves and the lithium content in coal and combining the K-means algorithm to identify the logging characteristics of different lithium-containing coal seams, we finally obtained the logging identification characteristics of high-lithium coal seams. The results reveal differences in the logging curves of coal seams with different lithium contents. The natural gamma and lateral resistivity of high-lithium coal seams are approximately 80 API and 100 Ω.M, respectively. Our study shows that the early identification of high-lithium coal seams can be evaluated from a logging perspective. We propose a preliminary identification method of high-lithium coal seam based on logging curve parameters by clustering analysis of borehole logging data to achieve accurate prediction.

IntroductionMycoplasma pneumoniae (MP) is the major cause of respiratory infections that threaten the health of children and adolescents worldwide. Therefore, an early, simple, and accurate detection approach for MP is critical to prevent outbreaks of MP-induced community-acquired pneumonia.MethodsHere, we explored a simple and accurate method for MP identification that combines loop-mediated isothermal amplification (LAMP) with the CRISPR/Cas12b assay in a one-pot reaction.ResultsIn the current study, the whole reaction was completed within 1 h at a constant temperature of 57°C. The limit of detection of this assay was 33.7 copies per reaction. The specificity of the LAMP-CRISPR/Cas12b method was 100%, without any cross-reactivity with other pathogens. Overall, 272 clinical samples were used to evaluate the clinical performance of LAMP-CRISPR/Cas12b. Compared with the gold standard results from real-time PCR, the present method provided a sensitivity of 88.11% (126/143), specificity of 100% (129/129), and consistency of 93.75% (255/272).DiscussionTaken together, our preliminary results illustrate that the LAMP-CRISPR/Cas12b method is a simple and reliable tool for MP diagnosis that can be performed in resource-limited regions.

Existing feeder block division methods fail to consider the complementary characteristics and uncertainty between power sources and loads, which result in excessive feeder blocks, low inter-block balance, and significant disparity in net load peak-valley difference. To address these issues, a medium-voltage feeder block division method that considers the uncertainty and complementary characteristics of sources and loads is proposed. Firstly, based on the probability density characteristics of sources and loads, an uncertainty model of DG output and load demand is established. Secondly, considering the constraints of block maximum load rate and feeder non-crossing, a feeder block division model is established. Additionally, a set of center circles is defined, and based on this, an improved K-means clustering algorithm is proposed. The initial clustering centers based on the center circles is set, and the clustering centers based on the arcs of the center circles corrected. And the weighted distances between power sources and clustering centers are calculated. An algorithm flow for improved K-means clustering feeder block division is designed accordingly. Finally, the case studies show that the result of block division is improved.

Tumors present a formidable health risk with limited curability and high mortality; existing treatments face challenges in addressing the unique tumor microenvironment (hypoxia, low pH, and high permeability), necessitating the development of new therapeutic approaches. Under certain circumstances, certain bacteria, especially anaerobes or parthenogenetic anaerobes, accumulate and proliferate in the tumor environment. This phenomenon activates a series of responses in the body that ultimately produce anti-tumor effects. These bacteria can target and colonize the tumor microenvironment, promoting responses aimed at targeting and fighting tumor cells. Understanding and exploiting such interactions holds promise for innovative therapeutic strategies, potentially augmenting existing treatments and contributing to the development of more effective and targeted approaches to fighting tumors. This paper reviews the tumor-promoting mechanisms and anti-tumor effects of the digestive tract microbiome and describes bacterial therapeutic strategies for tumors, including natural and engineered anti-tumor strategies.

IntroductionSwine influenza viruses (SIVs) pose significant economic losses to the pig industry and are a burden on global public health systems. The increasing complexity of the distribution and evolution of different serotypes of influenza strains in swine herds escalates the potential for the emergence of novel pandemic viruses, so it is essential to develop new vaccines based on swine influenza.MethodsHere, we constructed a self-assembling ferritin nanoparticle vaccine based on the hemagglutinin (HA) extracellular domain of swine influenza A (H1N1) virus using insect baculovirus expression vector system (IBEVS), and after two immunizations, the immunogenicities and protective efficacies of the HA-Ferritin nanoparticle vaccine against the swine influenza virus H1N1 strain in mice and piglets were evaluated.ResultsOur results demonstrated that HA-Ferritin nanoparticle vaccine induced more efficient immunity than traditional swine influenza vaccines. Vaccination with the HA-Ferritin nanoparticle vaccine elicited robust hemagglutinin inhibition titers and antigen-specific IgG antibodies and increased cytokine levels in serum. MF59 adjuvant can significantly promote the humoral immunity of HA-Ferritin nanoparticle vaccine. Furthermore, challenge tests showed that HA-Ferritin nanoparticle vaccine conferred full protection against lethal challenge with H1N1 virus and significantly decreased the severity of virus-associated lung lesions after challenge in both BALB/c mice and piglets.ConclusionTaken together, these results indicate that the hemagglutinin extracellular-based ferritin nanoparticle vaccine may be a promising vaccine candidate against SIVs infection.

Proanthocyanidins (PAs) and anthocyanins are flavonoids that contribute to the quality and health benefits of grapes and wine. Salinity affects their biosynthesis, but the underlying mechanism is still unclear. We studied the effects of NaCl stress on PA and anthocyanin biosynthesis in grape suspension cells derived from berry skins of Vitis vinifera L. Cabernet Sauvignon using metabolite profiling and transcriptome analysis. We treated the cells with low (75 mM NaCl) and high (150 mM NaCl) salinity for 4 and 7 days. High salinity inhibited cell growth and enhanced PA and anthocyanin accumulation more than low salinity. The salinity-induced PAs and anthocyanins lacked C5’-hydroxylation modification, suggesting the biological significance of delphinidin- and epigallocatechin-derivatives in coping with stress. The genes up-regulated by salinity stress indicated that the anthocyanin pathway was more sensitive to salt concentration than the PA pathway, and WGCNA analysis revealed the coordination between flavonoid biosynthesis and cell wall metabolism under salinity stress. We identified transcription factors potentially involved in regulating NaCl dose- and time-dependent PA and anthocyanin accumulation, showing the dynamic remodeling of flavonoid regulation network under different salinity levels and durations. Our study provides new insights into regulator candidates for tailoring flavonoid composition and molecular indicators of salt stress in grape cells.

Influenza A virus (IAV) non-structural protein 1 (NS1) is a virulence factor that allows the virus to replicate efficiently by suppressing host innate immune responses. Previously, we demonstrated that the serine (S) at position 42 of NS1 in H1N1 swine influenza virus (SIV) is a critical residue in interferon (IFN) resistance, thus facilitating viral infections. Here, by lncRNA-seq, a total of 153 differentially expressed lncRNAs were identified, and the lncRNA HCG4 was selected due to its significantly higher expression after infection with the NS1 S42P mutant virus. Overexpression of HCG4 enhanced IFN-β production and suppressed SIV infection, highlighting the potential antiviral activity of HCG4 against SIV. Further investigation suggested that HCG4 served as a positive feedback mediator for RIG-I signaling. It alleviated the inhibitory effect on RIG-I K63-linked ubiquitination by NS1 protein, thereby resulting in an increase in RIG-I-mediated IFN production. Taken together, our findings demonstrate that HCG4 modulates the innate immune response to SIV infection through K63-linked RIG-I ubiquitination, providing insights into the role of lncRNAs in controlling viral infections.

BackgroundRadiofrequency ablation (RFA) is the primary curative treatment for hepatocellular carcinoma (HCC) patients who are not eligible for surgery. However, the effects of RFA on the global tumor immune response remain unclear.MethodIn this study, we examined the phenotypic and functional changes in peripheral blood mononuclear cells (PBMCs) from recurrent HCC patients who had undergone two RFA treatments using mass cytometry and high-throughput mRNA assays. ResultsWe observed significant increase in monocytes and decrease in T cell subpopulations three days after the first RFA treatment and three days after the second RFA treatment. The down-regulation of GZMB, GZMH, GZMK, and CD8A, which are involved in the cytotoxic function of T cells, was observed following RFA. Furthermore, the population of CD8 effector and memory T cells (CD8 Teff and CD8 Tem) significantly decreased after RFA. The expression of CD5 and CD161 in various T cell subpopulations also showed significant reductions. Additionally, elevated secretion of VEGF was observed in monocytes, B cells, regulatory T cells (Tregs), and CD4 naive T cells. ConclusionIn recurrent HCC patients, serum components derived from radiofrequency therapy can enhance the antigen-presenting capacity of monocytes. However, they also inhibit the anti-cancer immune response by reducing the population of CD8 effector and memory T cells and suppressing the activation of T cells, as well as down-regulating the expression of CD161 and CD5 in various T cell subpopulations. These tumor-derived components also contribute to an immunosuppressive microenvironment by promoting the secretion of VEGF in monocytes, Tregs, B cells, and CD4 naive T cells.

ObjectivesThe present study analyzed the impact of the COVID-19 pandemic on the prevalence and incidence of new leprosy cases, as well as the diversity, distribution, and temporal transmission of Mycobacterium leprae strains at the county level in leprae-endemic provinces in Southwest China.MethodsA total of 219 new leprosy cases during two periods, 2018–2019 and 2020–2021, were compared. We genetically characterized 83 clinical isolates of M. leprae in Guizhou using variable number tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). The obtained genetic profiles and cluster consequences of M. leprae were compared between the two periods.ResultsThere was an 18.97% decrease in the number of counties and districts reporting cases. Considering the initial months (January–March) of virus emergence, the number of new cases in 2021 increased by 167% compared to 2020. The number of patients with a delay of >12 months before COVID-19 (63.56%) was significantly higher than that during COVID-19 (48.51%). Eighty-one clinical isolates (97.60%) were positive for all 17 VNTR types, whereas two (2.40%) clinical isolates were positive for 16 VNTR types. The (GTA)9, (TA)18, (TTC)21 and (TA)10 loci showed higher polymorphism than the other loci. The VNTR profile of these clinical isolates generated five clusters, among which the counties where the patients were located were adjacent or relatively close to each other. SNP typing revealed that all clinical isolates possessed the single SNP3K.ConclusionCOVID-19 may have a negative/imbalanced impact on the prevention and control measures of leprosy, which could be a considerable fact for official health departments. Isolates formed clusters among counties in Guizhou, indicating that the transmission chain remained during the epidemic and was less influenced by COVID-19 preventative policies.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide. Circadian disruptors, such as chronic jet lag (CJ), may be new risk factors for MAFLD development. However, the roles of CJ on MAFLD are insufficiently understood, with mechanisms remaining elusive. Studies suggest a link between gut microbiome dysbiosis and MAFLD, but most of the studies are mainly focused on gut bacteria, ignoring other components of gut microbes, such as gut fungi (mycobiome), and few studies have addressed the rhythm of the gut fungi. This study explored the effects of CJ on MAFLD and its related microbiotic and mycobiotic mechanisms in mice fed a high fat and high fructose diet (HFHFD). Forty-eight C57BL6J male mice were divided into four groups: mice on a normal diet exposed to a normal circadian cycle (ND-NC), mice on a normal diet subjected to CJ (ND-CJ), mice on a HFHFD exposed to a normal circadian cycle (HFHFD-NC), and mice on a HFHFD subjected to CJ (HFHFD-CJ). After 16 weeks, the composition and rhythm of microbiota and mycobiome in colon contents were compared among groups. The results showed that CJ exacerbated hepatic steatohepatitis in the HFHFD-fed mice. Compared with HFHFD-NC mice, HFHFD-CJ mice had increases in Aspergillus, Blumeria and lower abundances of Akkermansia, Lactococcus, Prevotella, Clostridium, Bifidobacterium, Wickerhamomyces, and Saccharomycopsis genera. The fungi-bacterial interaction network became more complex after HFHFD and/or CJ interventions. The study revealed that CJ altered the composition and structure of the gut bacteria and fungi, disrupted the rhythmic oscillation of the gut microbiota and mycobiome, affected interactions among the gut microbiome, and promoted the progression of MAFLD in HFHFD mice.

The fundamental role of any neuron within a network is to transform complex spatiotemporal synaptic input patterns into individual output spikes. These spikes, in turn, act as inputs for other neurons in the network. Neurons must execute this function across a diverse range of physiological conditions, often based on species-specific traits. Therefore, it is crucial to determine the extent to which findings can be extrapolated between species and, ultimately, to humans. In this study, we employed a multidisciplinary approach to pinpoint the factors accounting for the observed electrophysiological differences between mice and rats, the two species most used in experimental and computational research. After analyzing the morphological properties of their hippocampal CA1 pyramidal cells, we conducted a statistical comparison of rat and mouse electrophysiological features in response to somatic current injections. This analysis aimed to uncover the parameters underlying these distinctions. Using a well-established computational workflow, we created ten distinct single-cell computational models of mouse CA1 pyramidal neurons, ready to be used in a full-scale hippocampal circuit. By comparing their responses to a variety of somatic and synaptic inputs with those of rat models, we generated experimentally testable hypotheses regarding species-specific differences in ion channel distribution, kinetics, and the electrophysiological mechanisms underlying their distinct responses to synaptic inputs during the behaviorally relevant Gamma and Sharp-Wave rhythms.

Alcohol-associated liver disease (ALD) is a condition that develops due to prolonged and excessive alcohol consumption. It encompasses various stages of liver damage, including fatty liver, alcoholic hepatitis, and cirrhosis. Immune cells, particularly macrophages, of various types play a significant role in the onset and progression of the disease. Macrophages observed in the liver exhibit diverse differentiation forms, and perform a range of functions. Beyond M1 and M2 macrophages, human macrophages can polarize into distinct phenotypes in response to various stimuli. Recent advancements have improved our understanding of macrophage diversity and their role in the progression of ALD. This mini-review provides a concise overview of the latest findings on the role and differentiation of macrophages in ALD. Additionally, it discusses potential therapeutic targets associated with macrophages and explores potential therapeutic strategies.

BackgroundIGHMBP2 is a crucial gene for the development and maintenance of the nervous system, especially in the survival of motor neurons. Mutations in this gene have been associated with spinal muscular atrophy with respiratory distress type 1 (SMARD1) and Charcot-Marie-Tooth disease type 2S (CMT2S).MethodsWe conducted a systematic literature search using the PubMed database to identify studies published up to April 1st, 2023, that investigated the association between IGHMBP2 mutations and SMARD1 or CMT2S. We compared the non-truncating mutations and truncating mutations of the IGHMBP2 gene and selected high-frequency mutations of the IGHMBP2 gene.ResultsWe identified 52 articles that investigated the association between IGHMBP2 mutations and SMARD1/CMT2S. We found 6 hotspot mutations of the IGHMBP2 gene. The truncating mutations in trans were all associated with SMARD1.ConclusionThis study provides evidence that the complete LOF mechanism of the IGHMBP2 gene defect may be an important cause of SMARD1.

Introduction: The work aims to establish and analyze the factors influencing the efficacy of Invisalign in molar distalization and tooth movement. Objectives of the study: 1) identify factors contributing to molar distalization and tooth movement; 2) analyze the effectiveness of Invisalign technology in molar distalization and tooth movement.Methods: The study was conducted in 2020–2022 in Baoding (PRC) based on Baoding’s first central hospital. Forty patients (mean age 28.5 ± 1.5 years, 18–35 years; 20 women and 20 men) participated in the study.Results: All patients had mild to moderate degrees of tooth crowding, with an angle class II malocclusion, as well as maxillary third molars. Before and after the therapy, the condition of the alveolar bone, soft tissues, and facial height were measured. Fixation of the anterior teeth was performed. Calculations of the distal molar movement were performed. For orthodontic procedures, the second M of the upper jaw were moved, and then the first molars were moved.Discussion: Distalization of the upper molars was found to be an effective movement, with an efficiency of about 83% when vertical rectangular attachments were used. The first molar was moved distally by 2.85 mm without significant tilt or movement in the vertical plane.

The field of English for Specific Purposes (ESP) has gained considerable attention, mainly due to the growing importance of English teaching and the need for preparing international professionals. The primary academic emphasis of this field is largely centered on the study of English for Academic Purposes (EAP). It has become increasingly important for China to provide EAP education to its vast population of college students, who represent a significant proportion of global tertiary-level English learners. By doing so, they can improve their academic literacy and participate more effectively in international academic communication. In 2016, China’s College English Test Examination Board issued the National College English Test Syllabus which emphasized the importance of academic English literacy in the test design. This syllabus was released during a contentious debate among Chinese academics about the role of EAP in college English teaching and testing. Despite this heated discussion, there are currently few studies that have analyzed the linguistic nature of academic English tests in a quantitative manner. This paper calculates the academic word coverage of the reading passages in two crucial English proficiency tests designed for college students in China, the College English Test (CET) and the Test of English for Academic Purposes (TEAP). It is found that the academic word coverage of CET is increasing from the year 2013 to 2021 and that the academic word coverage of TEAP is slightly higher than that of CET. In this sense, these English tests can meet the requirements for measuring Chinese college students’ academic literacy. It is also found that there is a positive correlation between academic word coverage and language difficulty as is indicated by Flesch–Kincaid Grade Level. These findings provide an empirical reference for the study of academic English tests in China, and other parts of the world, and contribute to EAP teaching and testing reform for the development of students’ academic literacy.

BackgroundChina has experienced one of the fastest increases in the incidence of acute lymphoid leukemia (ALL). The aim of this study was to assess the long-term trends of the incidence and mortality of ALL in mainland China between 1990 and 2019 and to project these trends through 2028.MethodsData on ALL were extracted from the Global Burden of Disease Study 2019; population data were extracted from World Population Prospects 2019. An age–period–cohort framework was used in the analysis.ResultsThe net drift for the incidence of ALL was 7.5% (95% confidence interval [CI]: 7.1%, 7.8%) per year in women and 7.1% (95% CI: 6.7%, 7.6%) in men, and local drift was found to be higher than 0 in every studied age group (p

BackgroundThe role of matrix metalloproteinase 9 (MMP-9) in the pathophysiology of chronic kidney disease (CKD), which is associated with a nearly two-fold greater risk for urinary calculi compared to people without CKD, has been demonstrated. The aim of the research is to evaluate the association between MMP-9-1562C>T polymorphism, MMP-9 serum levels and nephrolithiasis risk.MethodsA hospital-based case-control study involving 302 kidney stone patients and 408 controls without kidney stone from southern China was conducted. Sanger sequencing was used to genotype the MMP-9-1562C>T polymorphism. The serum MMP-9 was measured in 105 kidney stone patients and 77 controls by enzyme-linked immunosorbent assay.ResultsCompared to the control group, the CT genotype was more frequent in nephrolithiasis patients (adjusted OR = 1.60, 95% CI = 1.09–2.37: the risk of developing nephrolithiasis in individuals with CT genotype compared to CC genotype). Moreover, there was also a higher frequency of CT/TT genotypes among patients with nephrolithiasis (adjusted OR = 1.49, 95% CI = 1.02–2.19: the risk of developing nephrolithiasis in individuals with CT/TT genotypes compared to CC genotype). The risk remained for the subgroups of patients aged >53, smokers with pack-years of smoking >20, non-drinkers, non-diabetic patients, patients with hypertension, recurrent episodes and calcium oxalate stones (OR = 2.26, 95% CI = 1.31–3.91; OR = 5.47, 95% CI = 1.10–27.30; OR = 1.76, 95% CI = 1.14–2.72; OR = 1.54, 95% CI = 1.03–2.30; OR = 1.97, 95% CI = 1.01–3.82; OR = 1.67, 95% CI = 1.06–2.62; OR = 1.54, 95% CI = 1.02–2.32, respectively). Biochemical parameters did not differ between genotypes. Compared to controls (18.57 ± 5.80 ng/mL), nephrolithiasis patients had significantly higher serum MMP-9 levels (30.17 ± 6.78 ng/mL, p T were significantly higher than those with CC genotype (32.00 ± 6.33 vs. 29.13 ± 6.85 ng/mL, p = 0.037).ConclusionThe MMP-9-1562C>T polymorphism in association with its soluble protein increased the risk of kidney stone, thus suggesting it could be used as a susceptibility biomarker for nephrolithiasis. Further functional studies and larger studies that include environmental exposure data are needed to confirm the findings.

BackgroundPostoperative adjuvant transarterial chemoembolization (PA-TACE) has been increasing widely used to improve the prognosis of hepatocellular carcinoma (HCC) patients. However, clinical outcomes vary from patient to patient, which calls for individualized prognostic prediction and early management.MethodsA total of 274 HCC patients who underwent PA-TACE were enrolled in this study. The prediction performance of five machine learning models was compared and the prognostic variables of postoperative outcomes were identified.ResultsCompared with other machine learning models, the risk prediction model based on ensemble learning strategies, including Boosting, Bagging, and Stacking algorithms, presented better prediction performance for overall mortality and HCC recurrence. Moreover, the results showed that the Stacking algorithm had relatively low time consumption, good discriminative ability, and the best prediction performance. In addition, according to time-dependent ROC analysis, the ensemble learning strategies were found to perform well in predicting both OS and RFS for the patients. Our study also found that BCLC Stage, hsCRP/ALB and frequency of PA-TACE were relatively important variables in both overall mortality and recurrence, while MVI contributed more to the recurrence of the patients.ConclusionAmong the five machine learning models, the ensemble learning strategies, especially the Stacking algorithm, could better predict the prognosis of HCC patients following PA-TACE. Machine learning models could also help clinicians identify the important prognostic factors that are clinically useful in individualized patient monitoring and management.

IntroductionIn children, erythromelalgia is a rare chronic pain syndrome characterized by erythema, severe burning pain, and itching of affected feet. Unfortunately, there is no definitive therapy available currently.Case reportHere, we report a case of primary erythromelalgia and the treatment response in a 10-year-old boy, whose genetic findings for mutations in the SCN9A gene were positive and skin biopsy results were diagnosed as small fiber neuropathy, while he has suffered from excruciating burning pain, itching, erythema, and recurrent infections over the past 3 years. He did not respond well to conventional treatment, and the only way to receive minimal relief was to immerse his feet in ice water. After a successful trial of spinal cord stimulation (SCS), the implantable pulse generator (IPG) was successfully implanted without complications, and it proved partial response to therapy.ConclusionThere is no specific, efficient treatment for pediatric erythromelalgia currently, but this case demonstrates neuromodulation serves as part of the multimodal regimen to treat pediatric erythromelalgia.

ObjectivesCutaneous tuberculosis with various manifestations can be divided into several clinical types according to the host's immune status and infective route. However, the etiological factors of this disease remain unclear. The objective of this study is to investigate the pathogens associated with the occurrence and different types of cutaneous tuberculosis.Methods58 Mycobacterium tuberculosis strains isolated from cutaneous tuberculosis over the last 20 years were sequenced and analyzed for genomic characteristics including lineage distribution, drug-resistance mutations, and mutations potentially associated with different sites of infection.ResultsThe M. tuberculosis strains from four major types of cutaneous tuberculosis and pulmonary tuberculosis shared similar genotypes and genomic composition. The strains isolated from cutaneous tuberculosis had a lower rate of drug resistance. Phylogenic analysis showed cutaneous tuberculosis and pulmonary tuberculosis isolates scattered on the three. Several SNPs in metabolism related genes exhibited a strong correlation with different infection sites.ConclusionsThe different infection sites of TB may barely be affected by large genomic changes in M. tuberculosis isolates, but the significant difference in SNPs of drug resistance gene and metabolism-related genes still deserves more attention.

Seizures are life-threatening complications of neuropsychiatric systemic lupus erythematosus (NPSLE) and are often associated with poor outcomes. Cyclophosphamide immunotherapy is the mainstay of NPSLE treatment. We report the unique case of a patient with NPSLE who developed seizures soon after her first and second doses of low-dose cyclophosphamide. The exact pathophysiological mechanism underlying cyclophosphamide-induced seizures is not well understood. However, this unusual drug-associated side effect of cyclophosphamide is thought to be due to the drug’s unique pharmacology. Clinicians should be aware of this complication to make a correct diagnosis and adjust the immunosuppressive regimens very carefully.

Aquaporins (AQPs) are highly-selective transmembrane water transporters that are involved in the adaptation to environmental challenges. However, the structure, function, and evolution of AQPs in bivalves remain largely unknown. In this study, AQP gene family members were identified in nine bivalve species, and their abundance rangs from 7 to 15. Nine AQPs (MmAQPs) were identified in the genome of hard clam (Mercenaria mercenaria), which is a euryhaline bivalve that has evolved sophisticated osmoregulatory mechanisms and salinity adaptation. Structurally, all MmAQPs contain 6 or 12 transmembrane α-helices, a major intrinsic protein (MIP) domain, and 2 asparagine-proline-alanine (NPA) motifs. MmAQPs were classified into three subfamilies based on phylogenetic analysis: AQP1-like, AQP3-like, and AQP8-like. No AQP11-like subfamily member was identified in the genome of hard clam. Tandem duplication resulted in a lineage-specific expansion in AQP8-like subfamily in hard clams. MmAQP8 genes showed different expression sensitivity to different environmental stressors. The gene expression patterns of three MmAQP8 were similar under heat, hypoxia, and air exposure stress, but differed greatly under salinity stress, indicating that tandem duplication events may accelerate the functional divergence of AQP8 genes in hard clams. AQP3-like members may have undergone gene loss during evolution, resulting in weakened glycerol and urea penetration in hard clams. Three orthologs of MmAQPs were detected in the genomes of Cyclina sinensis and Archivesica marissinica through synteny analyses. Tissue expression profiles showed that MmAQP genes were highly expressed in the foot and hepatopancreas. Under environmental stress, the expression levels of most of the MmAQP genes changed significantly to maintain metabolic homeostasis. Several MmAQP genes were downregulated to reduce water permeability under salinity and air exposure stress. Several MmAQP genes were significantly upregulated to promote the transmembrane transport of ammonia and reactive oxygen species and activate anti-apoptotic responses to resist stress. This study provides a comprehensive understanding of the AQP gene family in hard clams, and lays a foundation for further studies to explore the functions of AQPs in bivalves.

Prestack reverse-time migration (RTM) is a popular imaging technique for complex geological conditions, since the amplitude attenuation and velocity dispersion are common in seismic recordings. To image attenuated seismic recordings accurately, a robust migration algorithm with a stable attenuation compensation approach should be considered. In the context of the Q-compensated RTM approach based on the decoupled fractional Laplacians (DFLs) viscoacoustic wave equation, amplitude compensation can be implemented by flipping the sign of the dissipation term. However, the non-physical magnification of image amplitude could lead to a well-known numerical instability problem. The explicit stabilization operator can rectify the amplitude attenuation and suppress the numerical instability. However, limited by the inconvenient mixed-domain operator, the average Q value rather than the real Q value is often used in the compensation operator, lowering the compensated accuracy of the migration image. To overcome this problem, we propose a novel explicit Q-compensation scheme. The main advantage of the proposed compensation operator is that its order is space-invariant, making it more suitable for handling complex heterogeneous attenuation media. Several two-dimensional (2D) and three-dimensional (3D) synthetic models are used to verify the superiority of the proposed approach in terms of amplitude fidelity and image resolution. Field data further demonstrates that our approach has potential applications and can greatly enhance the resolution of seismic images.

ObjectiveTrauma is China's fifth leading cause of death and ranked first among youths. Trauma databases have been well-established in many countries to announce the current state of trauma rescue, treatment and care. Nevertheless, China hasn't yet established a comparable database. This paper included two national-level databases in China to describe the current situation of trauma treatment and the epidemiological characteristics of trauma incidence, which sought to provide data support for decision-making, resource allocation, trauma prevention, trauma management, and other aspects.MethodsThis study used the diagnosis and treatment data from the Hospital Quality Monitoring System (HQMS) and the China Trauma Rescue and Treatment Association (CTRTA) in 2019. A descriptive analysis was conducted to explore the demographic characteristics, trauma causes, injury degrees of trauma patients, disease burden and mortality rates in the abstracted hospitalized cases.ResultsA total of 4,532,029 trauma patients were included, of which 4,436,653 were from HQMS and 95,376 from CTRTA respectively. The age group with the highest proportion is 50-54 years old (493,320 [11.12%] in HQMS and 12,025 [12.61%] in CTRTA). Fall was the most frequent cause of trauma hospitalization, accounting for 40.51% of all cases, followed by traffic injuries, accounting for 25.22%. However, for trauma patients aged between 20 and 24 years old, the most common cause of injury was traffic accidents (28.20%). Hospital expenses for trauma patients in 2019 exceeded 100.30 billion yuan, which increases significantly with age, and fall costs the most. The mortality rate of trauma inpatients was 0.77%, which gradually increased with age after 30-year-old, and was the highest in the age group above 85 (1.86%).ConclusionThis paper summarizes the demographic characteristics, trauma causes distribution, disease burden, mortality rate, and other relative data of inpatients in 2019, which can now be used as an up-to-date clinical evidence base for national healthcare prevention and management in China.

As a vital developmental event, metamorphosis controls the population dynamics of most marine invertebrates and affects the breeding of economic shellfish. Rapana venosa is an economically important species in China, but artificial aquaculture has hampered its metamorphosis process. Previous studies have found that juvenile oysters can effectively induce the metamorphosis of R. venosa, but the specific induction mechanism is not clear. Here, we investigated the mechanism underlying the response of R. venosa to juvenile oysters through the RNA-seq analysis. In this study, the gene set responses to metamorphosis cues (juvenile oysters) in R. venosa were identified, and GO and KEGG enrichment analyses were further performed on these gene sets. The results showed that the expression of the prototype of the class of immediate early genes, the transcription factor AP-1, was rapidly and significantly increased, and the molecular chaperone of NOS, HSP90, exhibited lower expression in the M12 group than in the control group. In contrast, the expression of inhibitors of apoptosis (IAPs) was significantly increased upon exposure to juvenile oysters. Additionally, the Wnt signaling pathway and MAPK signaling pathway were enriched in the trend analysis. These pathways may also play critical regulatory roles in the response to juvenile oysters. Taken together, the results show that competent larvae rapidly respond to the inducing effects of oysters via some immediate early genes, such as the transcription factor AP-1, which may further regulate downstream pathways such as the MAPK signaling pathway to cause subsequent changes, including a decrease in HSP90 and an increase in IAPs. These changes together may regulate the metamorphosis of R. venosa. This study provides further evidence that juvenile oysters are the metamorphosis cues of R. venosa, which may enhance our understanding of the metamorphosis mechanism in this marine invertebrate.

Background: Our aim was to determine the potential pharmacological mechanisms of the Guizhi decoction (GZD) in the treatment of osteoarthritis (OA) through an integrated approach of network pharmacological analyses, RNA sequencing (RNA-seq), and experimental validation.Methods: The quality control and identification of bioactive compounds of the GZD were carried out by using ultra-performance liquid chromatography (UPLC), and their OA-related genes were identified through overlapping traditional Chinese medicine systems pharmacology database (TCMSP), DrugBank and SEA Search Server databases, and GeneCards. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were implemented after constructing the component–target network. RNA-seq was used to screen differentially expressed genes (DEGs) under intervention conditions with and without the GZD in vitro. The crossover signaling pathways between RNA-seq and network pharmacology were then analyzed. Accordingly, protein–protein interaction (PPI) networks, GO, and KEGG analysis were performed using the Cytoscape, STRING, or DAVID database. The OA rat model was established to further verify the pharmacological effects in vivo. Hematoxylin–eosin (H&E) and safranin O/fast green (S-O) staining were used to grade the histopathological features of the cartilage. We verified the mRNA and protein expressions of the key targets related to the TNF signaling pathways in vivo and in vitro by qPCR, Western blotting (WB), and immunofluorescence assay. In addition, we also detected inflammatory cytokines in the rat serum by Luminex liquid suspension chip, which included tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β).Results: Eighteen compounds and 373 targets of the GZD were identified. A total of 2,356 OA-related genes were obtained from the GeneCards database. A total of three hub active ingredients of quercetin, kaempferol, and beta-sitosterol were determined, while 166 target genes associated with OA were finally overlapped. The RNA-seq analysis revealed 1,426 DEGs. In the KEGG intersection between network pharmacology and RNA-seq analysis, the closest screening relevant to GZD treatment was the TNF signaling pathway, of which TNF, IL-6, and IL-1β were classified as hub genes. In consistent, H&E and S-O staining of the rat model showed that GZD could attenuate cartilage degradation. When compared with the OA group in vivo and in vitro, the mRNA levels of TNF-α, IL-1β, IL-6, matrix metalloproteinase 3 (MMP3), and matrix metalloproteinase 9 (MMP9) were all downregulated in the GZD group (all p < 0.05). The expression levels of anabolic proteins (Col2α1 and SOX9) were all higher in the GZD group than in the OA group (p < 0.05), while the expression levels of the catabolic proteins (MMP9 and COX-2) and TNF-α in the GZD group were significantly lower than those in the OA group (p < 0.05). In addition, the expression levels of TNF, IL-6, and IL-1β were upregulated in the OA group, while the GZD group prevented such aberrations (p < 0.01).Conclusion: The present study reveals that the mechanism of the GZD against OA may be related to the regulation of the TNF signaling pathway and inhibition of inflammatory response.

Three-dimensional (3D) elastic reverse-time migration (ERTM) can image the subsurface 3D seismic structures, and it is an important tool for the Earth’s interior imaging. A common simulation kernel used in 3D ERTM is the current staggered-grid finite-difference (SGFD) method of the first-order elastic wave equation. However, the mere second-order accuracy in time of the current SGFD method can bring non-negligible time dispersion, which reduces the simulation accuracy and further leads to the distortion of the imaging results. This paper proposes a vector-based 3D ERTM using the high-order accuracy SGFD method in time to obtain high-accuracy images. This approach is a new high-resolution ERTM workflow that improves the imaging accuracy of conventional ERTM from numerical simulation. The proposed ERTM workflow is established on a quasi-stress–velocity wave equation and its vector wavefield decomposition form. Advanced SGFD schemes and their corresponding coefficients with fourth-order temporal accuracy solve the quasi-linear wave equation system. The normalized dot product imaging condition produces high-quality images using high-accuracy vector wavefields solved using the SGFD method. Through the numerical examples, we test the simulation efficiency and analyze how temporal accuracy in numerical simulations affects migration imaging quality. We include that the proposed method obtains highly accurate images.

ObjectivesNational data on the admission rate, distribution, in-hospital mortality, and economic burden of traumatic fractures in China is unclear. We aimed to conduct a cross-sectional population-based study to determine such above data at the national level in China.MethodsA national administrative database was used to review all traumatic fracture hospitalizations in China during 2020, from which a total of 2,025,169 inpatients with traumatic fractures was retrieved. Admission rates and in-hospital mortality rates stratified by age, sex, and region were calculated. The causes of traumatic fracture and economic burden were described.ResultsThe admission rate of traumatic fractures of all China population in 2020 was 1.437‰. The admission rate increased with age and varied with genders and causes of injuries. Falls are the leading cause of traumatic fracture hospitalization, followed by road traffic injuries. The most common diagnoses were femoral neck fractures, with a number of 138,377. The in-hospital mortality was 1.209‰. Road traffic injuries led to the highest in-hospital mortality. The median length of stay was 10 days, with the median hospitalization cost of ¥20,900 (about $3,056).ConclusionTraumatic fractures are concerning conditions with a high admission rate and in-hospital mortality in China, which are mainly caused by falls and road traffic injuries. The government should implement more public health policies to enhance the health of the elderly and improve transportation safety to prevent traumatic fractures.

Liver hepatocellular carcinoma (LIHC) is one of the most common liver malignancies with high mortality and morbidity. Thus, it is crucial to identify potential biomarker that is capable of accurately predicting the prognosis and therapeutic response of LIHC. Kinesin family member 5A (KIF5A) is a microtubule-based motor protein involved in the transport of macromolecules such as organelle proteins in cells. Recent studies have illustrated that the high expression of KIF5A was related to poor prognosis of solid tumors, including bladder cancer, prostate cancer, and breast cancer. However, little is currently known concerning the clinical significance of KIF5A expression in LIHC. Herein, by adopting multi-omics bioinformatics analysis, we comprehensively uncovered the potential function and the predictive value of KIF5A in stratifying clinical features among patients with LIHC, for which a high KIF5A level predicted an unfavorable clinical outcome. Results from KIF5A-related network and enrichment analyses illustrated that KIF5A might involve in microtubule-based process, antigen processing and presentation of exogenous peptide antigen via MHC class II. Furthermore, immune infiltration and immune function analyses revealed upregulated KIF5A could predict a unique tumor microenvironment with more CD8+T cells and a higher level of anti-tumor immune response. Evidence provided by immunohistochemistry staining (IHC) further validated our findings at the protein level. Taken together, KIF5A might serve as a novel prognostic biomarker for predicting immunotherapy response and could be a potential target for anti-cancer strategies for LIHC.

IntroductionUbiquitylation that mediated by ubiquitin ligases plays multiple roles not only in proteasome-mediated protein degradation but also in various cellular process including DNA repair, signal transduction and endocytosis. RING finger (RNF) proteins form the majority of these ubiquitin ligases. Recent studies have demonstrated the important roles of RNF finger proteins in tumorigenesis and tumor progression. Benzo[a]pyrene (BaP) is one of the most common environmental carcinogens causing lung cancer. The molecular mechanism of Bap carcinogenesis remains elusive. Considering the critical roles of RNF proteins in tumorigenesis and tumor progression, we speculate on whether Bap regulates RNF proteins resulting in carcinogenesis.MethodsWe used GEO analysis to identify the potential RING finger protein family member that contributes to Bap-induced NSCLC. We next used RT-qPCR, Western blot and ChIP assay to investigate the potential mechanism of Bap inhibits RNF182. BGS analyses were used to analyze the methylation level of RNF182.ResultsHere we reported that the carcinogen Bap suppresses the expression of ring finger protein 182 (RNF182) in non-small cell lung cancer (NSCLC) cells, which is mediated by abnormal hypermethylation in an AhR independent way and transcriptional regulation in an AhR dependent way. Furthermore, RNF182 exhibits low expression and hypermethylation in tumor tissues. RNF182 also significantly suppresses cell proliferation and induces cell cycle arrest in NSCLC cell lines.ConclusionThese results demonstrated that Bap inhibits RNF182 expression to promote lung cancer tumorigenesis through activating AhR and promoting abnormal methylation.

Abstract: In recent years, hydrogen is rapidly developing because it is environmentally friendly and sustainable. In this case, hydrogen energy storage systems (HESSs) can be widely used in the distribution network. The application of hybrid electric-hydrogen energy storage systems can solve the adverse effects caused by renewable energy access to the distribution network. In order to ensure the rationality and effectiveness of energy storage systems (ESSs) configuration, economic indicators of battery energy storage systems (BESSs) and hydrogen energy storage systems, power loss, and voltage fluctuation are chosen as the fitness function in this paper. Meanwhile, multi-objective particle swarm optimization (MOPSO) is used to solve Pareto non-dominated set of energy storage systems’ optimal configuration scheme, in which the technique for order preference by similarity to ideal solution (TOPSIS) based on information entropy weight (IEW) is used select the optimal solution in Pareto non-dominated solution set. Based on the extended IEEE-33 system and IEEE-69 system, the rationality of energy storage systems configuration scheme under 20% and 35% renewable energy penetration rate is analyzed. The simulation results show that the power loss can be reduced by 7.9%–22.8% and the voltage fluctuation can be reduced by 40.0%–71% when the renewable energy penetration rate is 20% and 35% respectively in IEEE-33 and 69 nodes systems. Therefore, it can be concluded that the locations and capacities of energy storage systems obtained by multi-objective particle swarm optimization can improve the distribution network stability and economy after accessing renewable generation.

BackgroundPrevious studies suggested that tumor size was an independent risk factor of prognosis for hepatocellular carcinoma (HCC). However, the general prognostic analysis did not consider the interaction between variables. The purpose of this study was to investigate whether the effect of tumor size on the prognosis of isolated HCC without vascular invasion varies according to covariates.MethodsPatients were selected from the Surveillance, Epidemiology, and End Results (SEER) database to investigate whether there was an interaction between age and tumor size on the prognosis. Then the trend test and the value of per 1 SD of tumor size were calculated. In addition, the data of Zhejiang Provincial People's Hospital meeting the requirements were selected to verify the obtained conclusions.ResultsMultivariable Cox regression analysis of the database cohort showed that age, gender, tumor size, pathological grade and marital status were independent risk factors for prognosis. Interaction test showed that there was an interaction between age and tumor size (P for interaction 65 years old. This result was confirmed by trend analysis (P for trend 65 years. Therefore, when analyzing the relationship between tumor size and prognosis, stratified analysis should be performed according to age.

BackgroundPeriventricular leukomalacia (PVL) is an essential cause of cerebral palsy in preterm infants, and cystic PVL (cPVL) is the most severe form of the disease. The pathogenesis of cPVL is complex, and immune imbalances and inflammatory responses may play an essential role in it.ObjectiveThis study aimed to investigate the correlation between peripheral blood lymphocyte subsets, especially γδT cells with the pathogenesis of cPVL in preterm infants.MethodsPeripheral blood from preterm infants with GA < 32 weeks and BW < 1,500 g was used in this study and was collected at 34 weeks corrected gestational age and within 24 h after the diagnosis with cranial MRI or cranial ultrasound. The infants were divided into cPVL groups and control groups. Flow cytometry was used to detect peripheral blood γδT, CD3+, CD4+, CD8+, and the proportion of total lymphocytes. Multiplex cell assays were used to detect the concentration of extracellular serum cytokines IL-6, IL-2, IL-8, IL-17A, IL-10, IL-1RA, eotaxin (CCL11), MCP-1 (CCL2), CXCL1, G-CSF, and IFNγ. A follow-up visit was carried out when the patient was 3 years old.ResultsAfter correcting for confounding factors, the proportion of peripheral blood γδT in the cPVL group was significantly lower than that in the control group (β: 0.216; 95% CI: 0.058–0.800, P < 0.022). Peripheral blood γδT (AUC: 0.722, P=0.006) and multivariate binary regression model (AUC: 0.865, P < 0.000) have good diagnostic values for cPVL. Peripheral blood γδT has some predictive power for neurodevelopmental outcomes in preterm infants (AUC: 0.743, P = 0.002).ConclusionIt seems that peripheral blood γδT cells are inversely correlated with cPVL, which is not only a risk factor for cPVL disease but also neurodevelopmental outcomes in preterm infants. However, the causality of cPVL and various lymphocytes is unclear and needs further study.

In most cancers, forkhead box N3 (FOXN3) acts as a transcriptional inhibitor to suppress tumor proliferation, but in pancreatic cancer, the opposite effect is observed. To confirm and investigate this phenomenon, FOXN3 expression in various carcinomas was determined using GEPIA2 and was found to be highly expressed in pancreatic cancer. Kaplan-Meier plotter was then used for survival analysis, revealing that high FOXN3 expression in pancreatic cancer might be associated with a poor prognosis. Similarly, clinical samples collected for immunohistochemical staining and survival analysis showed consistent results. The RNA-seq data of pancreatic cancer patients from the TCGA were then downloaded, and the differential expression gene set was obtained using R for gene set enrichment analysis (GSEA). The intersection of the above gene sets and FOXN3-related genes was defined as related differentially expressed gene sets (DEGs), and enrichment analysis was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, we analyzed the relationship between FOXN3 and immune infiltration in pancreatic cancer. Collectively, our findings reveal that FOXN3 is involved in the occurrence and progression of pancreatic cancer and may be useful as a prognostic tool in pancreatic cancer immunotherapy.

Colon cancer undergoes a traditional pathway from colon polyps to colon cancer. It is of great significance to investigate the key molecules involved in carcinogenesis from polyps to malignancies. Circular RNAs (circRNAs) are stably expressed in human body fluids such as plasma. Here, we demonstrated a differential expression pattern of plasma circRNAs in healthy individuals, colon polyp patients and colon cancer patients using circRNA Arraystar microarray. We explored that circRNA HADHA (circHADHA) was upregulated in plasma from polyp patients, whereas it was downregulated in plasma from colon cancer patients. Overexpression of circHADHA promoted autophagy in colon epithelial cells. Moreover, in colon cancer cells, overexpression of circHADHA promoted autophagy, whereas it inhibited cell proliferation and colony formation. CircHADHA increased the expression of ATG13 via miR-361 in both colon epithelial and cancer cells. ATG13 knockdown reduced autophagy even in the presence of circHADHA in colon cancer cells. Furthermore, the growth of circHADHA-overexpressing colon cancer cell-derived xenograft tumors was significantly decreased compared with control tumors in nude mice. In conclusion, circHADHA was differentially expressed in the plasma of healthy individuals, colon polyp patients and colon cancer patients. CircHADHA promoted autophagy by regulating ATG13 via miR-361 in both colon epithelial and cancer cells. CircHADHA suppressed tumor growth by inducing cell autophagy in colon cancer cells. CircHADHA potentially serves as a biomarker for screening of precursor colon cancer and a therapeutic target for colon cancer treatment.

ObjectiveThe purpose of this study was to analyze risk factors of residual dizziness (RD) after successful treatment for benign paroxysmal positional vertigo (BPPV) in middle-aged and older adults.Methods181 patients with BPPV, after successful canalith repositioning maneuver (CRM) treatment, were recruited. All patients were divided into the middle-aged group (aged 45–59 years, n = 101) and the older group (over 60 years, n = 80). The clinical characteristics were recorded, including age, gender, numbers of maneuvers, involved canal, affected side, RD, comorbidities, dizziness handicap inventory score, and generalized anxiety disorder's 7-item scale score.ResultsThe incidence of RD in the older group was significantly higher than that of the middle-aged group (p = 0.033). Multivariate logistic regression analysis shows that age (odds ratio = 1.042, p = 0.006), moderate to severe dizziness (odds ratio = 2.017, p = 0.034), and moderate to severe anxiety (odds ratio = 2.228, p = 0.017) were independently associated with RD in middle-aged and older adults.ConclusionOlder adults exhibited higher incidence of RD after successful treatment for BPPV. Age, moderate to severe dizziness, and moderate to severe anxiety were independent risk factors of RD in middle-aged and older adults.

Proanthocyanidins (PAs) derived from grape berries determine the astringency and bitterness of red wines. The two leucoanthocyanidin reductases (VviLAR1 and VviLAR2) are crucial for PA accumulation in grapevine. Our previous studies show that the promoter of VviLAR1 contains multiple proposed bHLH transcription factor binding sites, but the corresponding bHLH family regulators remain unknown. Here we identified and functionally characterized VvibHLH93 as a new bHLH transcription factor in PA pathway. Yeast one-hybrid and electrophoretic mobility shift assays showed that VvibHLH93 bound the E/G-box in VviLAR1 promoter. And VvibHLH93 gene was mainly expressed in grape flowers, tendrils, stems and berries at PA active stages. Overexpression of VvibHLH93 suppressed PA accumulation in grape callus, which was linked to the repression of the transcript levels of two VviLARs. The gene expression analysis in transgenic grape callus and the dual-luciferase assay in tobacco leaves together revealed that VvibHLH93 targeted a broad set of structural genes and transcription factors in flavonoid pathway. This research enriches the regulatory mechanism of the two VviLAR genes, and provides new insights into regulating PA content in grape berries.

BackgroundInflammation, immunity, and nutrition status play important roles in tumorigenesis, progression, and metastasis. This study aimed to evaluate the prognostic value of Inflammation-Immunity-Nutrition Score (IINS) for overall survival (OS) and progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC) undergoing radical surgery.MethodsA total of 204 HCC patients who met the criteria were included in this retrospective study: 144 in the prediction model and 60 in the validation model. IINS was constructed based on the sum of classification scores of preoperative high-sensitivity C-reactive protein (hsCRP), lymphocyte (LYM), and albumin (ALB). The associations between the IINS group and the clinicopathologic characteristics were analyzed using Pearson’s χ2 test or Fisher’s exact test. Multivariate Cox regression analysis was used to evaluate variables significant on univariate analysis. Kaplan-Meier survival curves were conducted to investigate the prognostic values of IINS, Alpha-fetoprotein (AFP) and IINS-AFP classification. The prognostic performances of all the potential prognostic factors were further compared by receiver operating characteristic (ROC) curve, and time-dependent ROC curve. The internal validation and external validation were used to ensure the credibility of this prediction model.ResultsThe patients were divided into low and high IINS groups according to the median of IINS. According to multivariate Cox regression analyses, the Barcelona Clinic Liver Cancer (BCLC) Stage (P=0.003), AFP (P=0.013), and IINS (P=0.028) were independent prognostic factors for OS, and BCLC Stage (P=0.009), microvascular invasion (P=0.030), and IINS (P=0.031) were independent prognostic factors for PFS. High IINS group were associated with significantly worse OS and PFS compared with low IINS group (P

Human cancer statistics report that respiratory related cancers such as lung, laryngeal, oral and nasopharyngeal cancers account for a large proportion of tumors, and tumor metastasis remains the major reason for patient death. The metastasis of tumor cells requires actin cytoskeleton remodeling, in which fascin-1 plays an important role. Fascin-1 can cross-link F-actin microfilaments into bundles and form finger-like cell protrusions. Some studies have shown that fascin-1 is overexpressed in human tumors and is associated with tumor growth, migration and invasion. The role of fascin-1 in respiratory related cancers is not very clear. The main purpose of this study was to provide an updated literature review on the role of fascin-1 in the pathogenesis, diagnosis and management of respiratory related cancers. These studies suggested that fascin-1 can serve as an emerging biomarker and potential therapeutic target, and has attracted widespread attention.

Refuse transfer station (RTS) leachate treatment call for efficient methods to increase nutrient recovery (NH4+−N and PO43−−P) and chemical oxygen demand (COD) removal. In this study, the effects of various operational factors (seeding dose, pH, initial NH4+-N concentration, and reaction time) on biochar-seeded struvite precipitation were investigated at laboratory and pilot scales. Mealworm frass biochar (MFB) and corn stover biochar (CSB) were used as seeding materials to compare with traditional seed struvite. The maximum NH4+−N and PO43−−P recover efficiency of the MFB-seeded process reached 85.4 and 97.5%, higher than non-seeded (78.5 and 88.0%) and CSB-seeded (80.5 and 92.0%) processes and close to the struvite-seeded (84.5 and 95.1%) process. The MFB-seeded process also exhibited higher COD removal capacity (46.4%) compared to CSB-seeded (35.9%) and struvite-seeded (31.2%) processes and increased the average particle size of the struvite product from 33.7 to 70.2 μm for better sustained release. XRD, FT-IR, and SEM confirmed the orthorhombic crystal structure with organic matter attached to the struvite product. A pilot-scale test was further carried out in a custom-designed stirred tank reactor (20 L). In the pilot-scale test, the MFB-seeded process still spectacularly recovered 77.9% of NH4+−N and 96.1% of PO43−−P with 42.1% COD removal, which was slightly lower than the laboratory test due to insufficient and uniform agitation. On the whole, MFB-seeded struvite precipitation is considered to be a promising pretreatment method for rural RTS leachate.

Variations of the hepatic artery are very common, but they greatly increase the difficulty of surgery and the risk of complications in perihepatic surgeries such as liver transplantation, liver segmentectomy, and gastroduodenal surgery. Thus, it is important to precisely define the type of hepatic artery variant before surgery. However, there are often rare variants that cannot be defined with existing classifications. For example, the type of hepatic artery variant in the current case could not be classified with conventional classifications, and no such variation has been reported to date, involving two accessory left hepatic arteries from the common hepatic and left inferior phrenic arteries, respectively. Based on the existing 3DCT technology and the CRL classification method, which is applicable to the most common hepatic artery variants, we reviewed many rare variant types and proposed a new classification method (ex-CRL classification) for hepatic artery variations that do not fit the classic scope. The ex-CRL classification can accurately classify the vast majority of rare cases in the literature, greatly compensates for the limitations of current hepatic artery classifications, improves the generalization and understanding of rare cases, and reduces surgical complications.

Obesity-related kidney disease is now recognized as a global health issue, with a substantial number of patients developing progressive renal failure and end-stage renal disease. Interestingly, recent studies indicate light pollution is a novel environmental risk factor for chronic kidney disease. However, the impact of light pollution on obesity-related kidney disease remains largely unknown, with its underlying mechanism insufficiently explained. Renal hypoxia induced factor 1α (HIF1α) is critical in the development of glomerulosclerosis and renal fibrosis. The present study explored effects of constant light exposure on high fat diet (HFD) -induced renal injury and its association with HIF1α signal pathway. Thirty-two male Sprague Dawley rats were divided into four groups according to diet (HFD or normal chow diet) and light cycles (light/dark or constant light). After 16 weeks treatment, rats were sacrificed and pathophysiological assessments were performed. In normal chow fed rats, constant light exposure led to glucose abnormalities and dyslipidemia. In HFD fed rats, constant light exposure exacerbated obesity, glucose abnormalities, insulin resistance, dyslipidemia, renal functional decline, proteinuria, glomerulomegaly, renal inflammation and fibrosis. And, constant light exposure caused an increase in HIF1α and a decrease in prolyl hydroxylase domain 1 (PHD1) and PHD2 expression in kidneys of HFD-fed rats. Then, we demonstrated that BMAL1 bound directly to the promoters of PHD1 in mouse podocyte clone 5 cell line (MPC5) by ChIP assays. In conclusion, chronic constant light exposure aggravates HFD-induced renal injuries in rats, and it is associated with activation of HIF1α signal pathway.

Fibrates, which are agonists of peroxisome proliferator-activated receptor alpha, have received increasing attention in the treatment of primary biliary cholangitis. Reduced alkaline phosphatase levels and improved clinical outcomes were observed in patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid (UDCA) monotherapy4 when treated with bezafibrate or fenofibrate combined with UDCA. In contrast to obeticholic acid, which exacerbates pruritus in patients, fibrates have been shown to relieve pruritus. Clinical trial outcomes show potential for the treatment of primary biliary cholangitis by targeting peroxisome proliferator-activated receptors. It is currently agreed that primary biliary cholangitis is an autoimmune-mediated cholestatic liver disease, and peroxisome proliferator-activated receptor is a nuclear receptor that regulates the functions of multiple immune cells, thus playing an important role in regulating innate and adaptive immunity. Therefore, this review focuses on the immune disorder of primary biliary cholangitis and summarizes the regulation of hepatic immunity when peroxisome proliferator-activated receptors are targeted for treating primary biliary cholangitis.

Suppressor of cytokine signaling 1 (SOCS-1) is implicated in both virus infection and carcinogenesis. This study investigated the role of HCV infection on SOCS-1 in normal and HCV-infected tissues and revealed a possible mechanism underlying HCV-induced hepatocellular carcinoma (HCC) genesis. In total, 10 HCV-HCC tissues, seven adjacent tissues, seven distal tissues, and 16 normal liver tissues were collected. SOCS-1 expression in tissue sections was detected by immunohistochemistry. After viral load was quantified, the correlation between SOCS-1 expression and viral load was analyzed in different tissues. Then, HCV replicon model was used to detect a relationship between HCV and SOCS-1. Subsequently, methylation-specific PCR (MSP) was applied to show the methylation status of SOCS-1 genes in normal tissues and HCV-replicating cell lines. A correlation between gene methylation, SOCS-1 expression, and HCV was analyzed. The lowest expression of SOCS-1 was observed in HCV-HCC tissues. Tissues with a higher HCV viral load showed lower SOCS-1 expression (p = 0.0282). Consistently, SOCS-1 mRNA and protein were lower in HCV-replicating cell lines than in uninfected ones. Furthermore, gene methylation was found in all examined tissues but higher in HCC tissues, and it is positively correlated with HCV viral load (r2 = 0.7309, p < 0.0001). HCV infection would upregulate methylation of the SOCS-1 gene in HCV-replicating cell lines. The downregulation of SOCS-1 in normal and HCV-replicating cell lines may result from HCV infection through epigenetic regulation, in which gene methylation in the CpG island of SOCS-1 promoters upon HCV infection suppresses its expression.

Cochlear nerve deficiency (CND) is often associated with variable outcomes of cochlear implantation (CI). We assessed previous investigations aiming to identify the main factors that determine CI outcomes, which would enable us to develop predictive models. Seventy patients with CND and normal cochlea who underwent CI surgery were retrospectively examined. First, using a data-driven approach, we collected demographic information, radiographic measurements, audiological findings, and audition and speech assessments. Next, CI outcomes were evaluated based on the scores obtained after 2 years of CI from the Categories of Auditory Performance index, Speech Intelligibility Rating, Infant/Toddler Meaningful Auditory Integration Scale or Meaningful Auditory Integration Scale, and Meaningful Use of Speech Scale. Then, we measured and averaged the audiological and radiographic characteristics of the patients to form feature vectors, adopting a multivariate feature selection method, called stability selection, to select the features that were consistent within a certain range of model parameters. Stability selection analysis identified two out of six characteristics, namely the vestibulocochlear nerve (VCN) area and the number of nerve bundles, which played an important role in predicting the hearing and speech rehabilitation results of CND patients. Finally, we used a parameter-optimized support vector machine (SVM) as a classifier to study the postoperative hearing and speech rehabilitation of the patients. For hearing rehabilitation, the accuracy rate was 71% for both the SVM classification and the area under the curve (AUC), whereas for speech rehabilitation, the accuracy rate for SVM classification and AUC was 93% and 94%, respectively. Our results identified that a greater number of nerve bundles and a larger VCN area were associated with better CI outcomes. The number of nerve bundles and VCN area can predict CI outcomes in patients with CND. These findings can help surgeons in selecting the side for CI and provide reasonable expectations for the outcomes of CI surgery.

Neonicotinoids (NEOs) are the most widely used insecticides in the world and pose a serious threat to aquatic ecosystems. The combined use of free-floating aquatic plants and associated microorganisms has a tremendous potential for remediating water contaminated by pesticides. The aim of this study was to determine whether plant growth-promoting bacteria (PGPB) could enhance the phytoremediation efficiency of duckweed (Lemna aequinoctialis) in NEO-contaminated water. A total of 18 different bacteria were isolated from pesticide-stressed agricultural soil. One of the isolates, Pseudomonas monteilii FC02, exhibited an excellent ability to promote duckweed growth and was selected for the NEO removal experiment. The influence of strain FC02 inoculation on the accumulation of three typical NEOs (dinotefuran, thiacloprid, and imidaclothiz) in plant tissues, the removal efficiency in water, and plant growth parameters were evaluated during the 14-day experimental period. The results showed that strain FC02 inoculation significantly (p

ObjectiveThis study aimed to evaluate potential predictors for recovery time in pregnant patients with moderate to severe ovarian hyperstimulation syndrome (OHSS).MethodsA total of 424 pregnant patients with moderate to severe OHSS who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) were retrospectively identified. The clinical features and laboratory findings within 24 h after admission were collected. Treatment for OHSS was carried out according to standard procedures, including fluid replacement therapy, human albumin, aspirin, low-molecular-weight heparin, and paracentesis, when necessary. Patients were discharged from the hospital when the tmorning hematocrit was

In recent years, an increasing number of online social value co-creation activities are conducted by companies in their marketing campaigns. A question is that whether these activities that take social responsibilities could help enterprises improve marketing performance. Drawing from social interaction theory, this study explores the causal effect of online social value co-creation on consumer purchase intention through three experiments. The results show that social value co-creation can stimulate consumer purchase intention. Moreover, consumer-company identification plays a mediating role in linking social value co-creation to purchase intention. In addition, compared to low social norms, high social norms are more likely to weaken the influence of social value co-creation on consumers' buying intention. The study provides both theoretical and practical implications to research area. Limitation and future research directions are also discussed.