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Although the past few decades have seen rising incomes and increased government attention to rural development, many children in rural China still lack regular access to micronutrient-rich diets. Insufficient diets and poor knowledge of nutrition among the poor result in nutritional problems, including iron-deficiency anaemia, which adversely affect attention and learning of students in school. Little research has been conducted in China documenting the prevalence of nutritional problems among vulnerable populations, such as school-age children, in rural areas. The absence of programmes to combat anaemia among students might be interpreted as a sign that the Government does not recognize its severity. The goals of this paper were to measure the prevalence of anaemia among school-age children in poor regions of Qinghai and Ningxia, to identify individual-, household- and school-based factors that correlate with anaemia in this region, and to report on the correlation between the anaemic status and the physical, psychological and cognitive outcomes. The results of a cross-sectional survey are reported here. The survey involved over 4,000 fourth and fifth grade students from 76 randomly-selected elementary schools in 10 poor counties in rural Qinghai province and Ningxia Hui Autonomous Region, located in the northwest region of China. Data were collected using a structured questionnaire and standardized tests. Trained professional nurses administered haemoglobin (Hb) tests (using Hemocue finger prick kits) and measured heights and weights of children. The baseline data showed that the overall anaemia rate was 24.9%, using the World Health Organization's blood Hb cut-offs of 120 g/L for children aged 12 years and older and 115 g/L for children aged 11 years and under. Children who lived and ate at school had higher rates of anaemia, as did children whose parents worked in farms or were away from home. Children with parents who had lower levels of education were more likely to be anaemic. The anaemic status correlated with the adverse physical, cognitive and psychological outcomes among the students. Such findings are consistent with findings of other recent studies in poor, northwest areas of China and led to conclude that anaemia remains a serious health problem among children in parts of China. [ABSTRACT FROM AUTHOR]

Introduction: Combined with massive lung aeration loss resulting from acute respiratory distress syndrome, hepatopulmonary syndrome, a liver-induced vascular lung disorder characterized by diffuse or localized dilated pulmonary capillaries, may induce hypoxaemia and death in patients with end-stage liver disease. Methods: The case of such a patient presenting with both disorders and in whom an extracorporeal membrane oxygenation was used is described. Results: A 51-year-old man with a five-year history of alcoholic cirrhosis was admitted for acute respiratory failure, platypnoea and severe hypoxaemia requiring emergency tracheal intubation. Following mechanical ventilation, hypoxaemia remained refractory to positive end-expiratory pressure, 100% of inspired oxygen and inhaled nitric oxide. Two-dimensional contrast-enhanced (agitated saline) transthoracic echocardiography disclosed a massive right-to-left extracardiac shunt, without patent foramen ovale. Contrast computed tomography (CT) of the thorax using quantitative analysis and colour encoding system established the diagnosis of acute respiratory distress syndrome aggravated by hepatopulmonary syndrome. According to the severity of the respiratory condition, a veno-venous extracorporeal membrane oxygenation was implemented and the patient was listed for emergency liver transplantation. Orthotopic liver transplantation was performed at Day 13. At the end of the surgical procedure, the improvement in oxygenation allowed removal of extracorporeal membrane oxygenation (Day 5). The patient was discharged from hospital at Day 48. Three months after hospital discharge, the patient recovered a correct physical autonomy status without supplemental O2. Conclusions: In a cirrhotic patient, acute respiratory distress syndrome was aggravated by hepatopulmonary syndrome causing life-threatening hypoxaemia not controlled by standard supportive measures. The use of extracorporeal membrane oxygenation, by controlling gas exchange, allowed the performing of a successful liver transplantation and final recovery. [ABSTRACT FROM AUTHOR]

Background: An mHealth-based school health education platform (EduSaltS) was promoted in real-world China to reduce salt intake among children and their families. This progress evaluation explores its implementation process and influencing factors using mixed methods., Methods: The mixed-methods process evaluation employed the RE-AIM framework. Quantitative data were collected from a management website monitoring 54,435 third-grade students across two cities. Questionnaire surveys (n = 27,542) assessed pre- and post-education effectiveness. Mixed-effects models were used to control cluster effects. Qualitative interviews (23 individuals and 8 focus groups) identified program performance, facilitators, and barriers. Findings were triangulated using the RE-AIM framework., Results: The program achieved 100% participation among all the third-grade classes of the 208 invited primary schools, with a 97.7% registration rate among all the 54,435 families, indicating high "Reach." Qualitative interviews revealed positive engagement from children and parents through the "small hands leading big hands" strategy. The high completion rate of 84.9% for each health cloud lesson and the significant improvement in salt reduction knowledge and behaviors scores from 75.0 (95%CI: 74.7-75.3) to 80.9 (95%CI: 80.6-81.2) out of 100 demonstrated the "Effect" of EduSaltS. The program's "Adoption" and "Implementation" were supported by attractive materials, reduced workload via auto-delivered lessons/activities and performance evaluation, and high fidelity to recommended activities, with medians 3.0 (IQR: 2.0-8.0)/class and 9.0 (IQR: 5.0-14.0)/school. Stable course completion rates (79.4%-93.4%) over one year indicated promising "Maintenance." Apart from the facilitating features praised by the interviewees, government support was the basis for the scaling up of EduSaltS. Barriers included the lack of smartphone skills among some parents and competing priorities for schools. Unhealthy off-campus environments, such as excessive use of salt in pre-packaged and restaurant foods, also hindered salt reduction efforts. The program's scalability was evident through its integration into existing health education, engagement of local governments and adaptation across various mobile devices., Conclusions: The mHealth-based school health education program is scalable and effective for public salt reduction in China. Identified barriers and facilitators can inform future health program scale-ups. The program's successful implementation demonstrates its potential for broader application in public health initiatives aimed at reducing dietary salt intake., (© 2024. The Author(s).)

Diarrhea is a common issue in domestic yaks (Bos grunniens) that can occur with pasture alterations and significantly impacts growth performance. Previous research has examined the microbiota of diarrhetic yaks; however, the structural changes in gut bacterial community and microbial interactions in yaks with grassland alteration-induced diarrhea remain poorly understood. To explore variations in gut microbiota homeostasis among yaks suffering from diarrhea, fecal microbiota diversity and composition were analyzed using 16 S rRNA amplicon sequencing. Gut fecal microbiota diversity was lower in diarrhetic yaks than in non-diarrhetic yaks. Furthermore, the bacterial community composition (including that of Proteobacteria and Actinobacteria) in the feces of diarrhetic yaks displayed significant alterations. Co-occurrence network analysis further underscored the compromised intestinal flora stability in yaks with diarrhea relative to that in non-diarrhetic yaks. Interestingly, the abundance of beneficial bacteria, such as Lachnospiraceae_AC2044_group and Lachnospiraceae_NK4A136_group, were decreased in yaks with diarrhea, and the reductions were negatively correlated with the fecal water content. Collectively, these findings indicate that diminished microbial stability and increased abundance of certain bacteria in the gut may contribute to diarrhea occurrence in yaks., (© 2024. The Author(s).)

Background: COVID-19 can cause cardiac complications and the latter are associated with poor prognosis and increased mortality. SARS-CoV-2 variants differ in their infectivity and pathogenicity, but how they affect cardiomyocytes (CMs) is unclear., Methods: The effects of SARS-CoV-2 variants were investigated using human induced pluripotent stem cell-derived (hiPSC-) CMs in vitro and Golden Syrian hamsters in vivo., Results: Different variants exhibited distinct tropism, mechanism of viral entry and pathology in the heart. Omicron BA.2 most efficiently infected and injured CMs in vitro and in vivo, and induced expression changes consistent with increased cardiac dysfunction, compared to other variants tested. Bioinformatics and upstream regulator analyses identified transcription factors and network predicted to control the unique transcriptome of Omicron BA.2 infected CMs. Increased infectivity of Omicron BA.2 is attributed to its ability to infect via endocytosis, independently of TMPRSS2, which is absent in CMs., Conclusions: In this study, we reveal previously unknown differences in how different SARS-CoV-2 variants affect CMs. Omicron BA.2, which is generally thought to cause mild disease, can damage CMs in vitro and in vivo. Our study highlights the need for further investigations to define the pathogenesis of cardiac complications arising from different SARS-CoV-2 variants., (© 2024. The Author(s).)

Infection of piglets with Glaesserella parasuis (G. parasuis) induces host immunosuppression. However, the mechanism underlying the immunosuppression of piglets remains unclear. Activation of the PD-1/PD-L1 axis has been shown to trigger host immunosuppression. Baicalin possesses anti-inflammatory and immunomodulatory functions. However, whether baicalin inhibits PD-1/PD-L1 activation and thus alleviates host immunosuppression has not been investigated. In this study, the effect of baicalin on the attenuation of piglet immunosuppression induced by G. parasuis was evaluated. Seventy piglets were randomly divided into the control group, infection group, levamisole group, BMS-1 group, 25 mg/kg baicalin group, 50 mg/kg baicalin group and 100 mg/kg baicalin group. Following pretreatment with levamisole, BMS-1 or baicalin, the piglets were challenged with 1 × 10 8  CFU of G. parasuis. Our results showed that baicalin, levamisole and BMS-1 modified routine blood indicators and biochemical parameters; downregulated IL-1β, IL-10, IL-18, TNF-α and IFN-γ mRNA expression; and upregulated IL-2 and IL-8 mRNA expression in blood. Baicalin, levamisole and BMS-1 increased the proportions of CD3 + T cells, CD3 + CD4 + T cells, CD3 + CD8 + T cells and CD3 - CD21 + B cells in the splenocyte population, increased the proportions of CD3 + T cells, CD3 + CD4 + T cells and CD3 + CD8 + T cells in the blood, and inhibited PD-1/PD-L1 and TIM-3 activation. Baicalin, levamisole and BMS-1 reduced p-PI3K, p-Akt, and p-mTOR expression, the p-MEK1/2/MEK1/2 and p-ERK1/2/ERK1/2 ratios and increased RAS expression. Baicalin, levamisole and BMS-1 provided substantial protection against G. parasuis challenge and relieved tissue histopathological damage. Our findings might provide new strategies for controlling G. parasuis infection and other immunosuppressive diseases., (© 2024. The Author(s).)

Glaesserella parasuis (G. parasuis) induces vascular damage and systemic inflammation. However, the mechanism by which it causes vascular damage is currently unclear. Baicalin has important anti-inflammatory, antibacterial and immunomodulatory functions. In this study, we explored the ability of baicalin and probenecid to protect against G. parasuis challenge in a piglet model. Sixty piglets were randomly divided into a control group; an infection group; a probenecid group; and 25 mg/kg, 50 mg/kg and 100 mg/kg baicalin groups. The probenecid group and the 25 mg/kg, 50 mg/kg and 100 mg/kg baicalin groups were injected intramuscularly with 20 mg/kg body weight (BW) probenecid and 25 mg/kg BW, 50 mg/kg BW and 100 mg/kg BW baicalin, respectively. All piglets except those from the control group were injected intraperitoneally with 1 × 10 8  CFU of G. parasuis. The control group was injected intraperitoneally with TSB. The results showed baicalin and probenecid protected piglets against G. parasuis challenge, improved body weight and decreased temperature changes in piglets. Baicalin and probenecid attenuated IL-1β, IL-10, IL-18, TNF-α and IFN-γ mRNA levels in the blood for 48 h, inhibited the production of the nucleosides ATP, ADP, AMP and UMP from 24 to 72 h, reduced Panx-1/P2Y6/P2X7 expression, weakened NF-kB, AP-1, NLRP3/Caspase-1 and ROCK/MLCK/MLC signalling activation, and upregulated VE-cadherin expression in the blood vessels of piglets challenged with G. parasuis. Baicalin and probenecid alleviated pathological tissue damage in piglets induced by G. parasuis. Our results might provide a promising strategy to control and treat G. parasuis infection in the clinical setting., (© 2024. The Author(s).)

Background: The oral administration of drugs for treating ulcerative colitis (UC) is hindered by several factors, including inadequate gastrointestinal stability, insufficient accumulation in colonic lesions, and uncontrolled drug release., Methods: A multiple sensitive nano-delivery system comprising β-cyclodextrin (CD) and 4-(hydroxymethyl)phenylboronic acid (PAPE) with enzyme/reactive oxygen species (ROS) sensitivity was developed to load celastrol (Cel) as a comprehensive treatment for UC., Results: Owing to the positive charge in the site of inflamed colonic mucosa, the negatively charged nanomedicine (Cel/NPs) could efficiently accumulate. Expectedly, Cel/NPs showed excellent localization ability to colon in vitro and in vivo tests. The elevated concentration of ROS and intestinal enzymes in the colon microenvironment quickly break the CD, resulting in Cel release partially to rebalance microbiota and recover the intestinal barrier. The accompanying cellular internalization of residual Cel/NPs, along with the high concentration of cellular ROS to trigger Cel burst release, could decrease the expression of inflammatory cytokines, inhibit colonic cell apoptosis, promote the macrophage polarization, scavenge ROS, and regulate the TLR4/NF-κB signaling pathway, which certified that Cel/NPs possessed a notably anti-UC therapy outcome., Conclusions: We provide a promising strategy for addressing UC symptoms via an enzyme/ROS-sensitive oral platform capable of releasing drugs on demand., (© 2024. The Author(s).)

Background: Norovirus gastroenteritis outbreaks were common in schools and kindergartens and were more related to faculty knowledge, attitude, and practice level. Gastroenteritis outbreaks caused by norovirus in educational institutions were the prominent cause of Public Health Emergency Events in China. This study aimed to explore the transformation in the contribution of KAP items related to outbreak prevention before and after intervention and the impact of demography factors on the intervention., Methods: This study sampled 1095 kindergarten and 1028 school staff in Shenzhen, China. We created a questionnaire consisting of 35 items in 4 parts, and each item was rated on a scale of 1-5 according to the accuracy. Univariate analysis of non-parametric tests and binary logistic regression were used to estimate the score difference on demographic characteristics, each item and KAP. The odds ratios (OR) with 95% confidence and intervals (CI) for the association between statistical indicators were mainly used to explain the effects before and after intervention., Results: Overall, 98.72% and 74.9% of the kindergarten and school participants were female, and all respondents had the highest scores difference of practice. Following intervention, univariate analysis indicated that primary school and female respondents achieved higher knowledge scores. Staff age beyond 35 (OR = 0.56, CI:0.34-0.92; OR = 0.67, CI:0.50-0.90) and with more than ten years of service (OR = 0.58, CI:0.36-0.91; OR = 0.38, CI:0.17-0.84) demonstrated a significantly lower post-intervention score for attitude and practice in both kindergartens and schools. The staff members exhibited a general lack of familiarity with the transmission of aerosols and the seasonal patterns of NoVs diarrhea pandemics. Item analysis revealed that kindergarten staff aged 26 and above demonstrated superior performance in terms of the efficacy of medical alcohol for inactivation (OR = 1.93, CI:1.13-3.31) and management strategies for unexplained vomiting among students (OR = 1.97, CI:1.21-3.18). Private school personnel displayed more significant improvement in their practices following educational interventions. School administrators' negative attitudes were primarily evident in their perspectives on morning inspections (OR = 0.11, CI:0.05-0.84)., Conclusions: The potential negative impact of faculty age on NoVs-related knowledge can be mitigated by the positive attitudes fostered through seniority. Furthermore, it is imperative to urgently address the lack of knowledge among administrators, and the identification and treatment of vomiting symptoms should be emphasized as crucial aspects of school prevention strategies. Therefore, education authorities should implement comprehensive public health interventions in the future., (© 2024. The Author(s).)

Objective: Using the preoperative pan-immune-inflammation value (PIV) and the monocyte to high-density lipoprotein ratio (MHR) to reflect inflammation, immunity, and cholesterol metabolism, we aim to develop and visualize a novel nomogram model for predicting the survival outcomes in patients with colorectal cancer (CRC)., Methods: A total of 172 patients with CRC who underwent radical resection were retrospectively analyzed. Survival analysis was conducted after patients were grouped according to the optimal cut-off values of PIV and MHR. Univariate and multivariate analyses were performed using Cox proportional hazards regression to screen the independent prognostic factors. Based on these factors, a nomogram was constructed and validated., Results: The PIV was significantly associated with tumor location (P < 0.001), tumor maximum diameter (P = 0.008), and T stage (P = 0.019). The MHR was closely related to gender (P = 0.016), tumor maximum diameter (P = 0.002), and T stage (P = 0.038). Multivariate analysis results showed that PIV (Hazard Ratio (HR) = 2.476, 95% Confidence Interval (CI) = 1.410-4.348, P = 0.002), MHR (HR = 3.803, 95%CI = 1.609-8.989, P = 0.002), CEA (HR = 1.977, 95%CI = 1.121-3.485, P = 0.019), and TNM stage (HR = 1.759, 95%CI = 1.010-3.063, P = 0.046) were independent prognostic indicators for overall survival (OS). A nomogram incorporating these variables was developed, demonstrating robust predictive accuracy for OS. The area under the curve (AUC) values of the predictive model for 1-, 2-, and 3- year are 0.791,0.768,0.811, respectively. The calibration curves for the probability of survival at 1-, 2-, and 3- year presented a high degree of credibility. Furthermore, Decision curve analysis (DCA) for the probability of survival at 1-, 2-, and 3- year demonstrate the significant clinical utility in predicting survival outcomes., Conclusion: Preoperative PIV and MHR are independent risk factors for CRC prognosis. The novel developed nomogram demonstrates a robust predictive ability, offering substantial utility in facilitating the clinical decision-making process., (© 2024. The Author(s).)

Background: Dynamical mathematical models defined by a system of differential equations are typically not easily accessible to non-experts. However, forecasts based on these types of models can help gain insights into the mechanisms driving the process and may outcompete simpler phenomenological growth models. Here we introduce a friendly toolbox, SpatialWavePredict, to characterize and forecast the spatial wave sub-epidemic model, which captures diverse wave dynamics by aggregating multiple asynchronous growth processes and has outperformed simpler phenomenological growth models in short-term forecasts of various infectious diseases outbreaks including SARS, Ebola, and the early waves of the COVID-19 pandemic in the US., Results: This tutorial-based primer introduces and illustrates a user-friendly MATLAB toolbox for fitting and forecasting time-series trajectories using an ensemble spatial wave sub-epidemic model based on ordinary differential equations. Scientists, policymakers, and students can use the toolbox to conduct real-time short-term forecasts. The five-parameter epidemic wave model in the toolbox aggregates linked overlapping sub-epidemics and captures a rich spectrum of epidemic wave dynamics, including oscillatory wave behavior and plateaus. An ensemble strategy aims to improve forecasting performance by combining the resulting top-ranked models. The toolbox provides a tutorial for forecasting time-series trajectories, including the full uncertainty distribution derived through parametric bootstrapping, which is needed to construct prediction intervals and evaluate their accuracy. Functions are available to assess forecasting performance, estimation methods, error structures in the data, and forecasting horizons. The toolbox also includes functions to quantify forecasting performance using metrics that evaluate point and distributional forecasts, including the weighted interval score., Conclusions: We have developed the first comprehensive toolbox to characterize and forecast time-series data using an ensemble spatial wave sub-epidemic wave model. As an epidemic situation or contagion occurs, the tools presented in this tutorial can facilitate policymakers to guide the implementation of containment strategies and assess the impact of control interventions. We demonstrate the functionality of the toolbox with examples, including a tutorial video, and is illustrated using daily data on the COVID-19 pandemic in the USA., (© 2024. The Author(s).)

Drought is one of the natural stresses that greatly impact plants. Castor bean (Ricinus communis L.) is an oil crop with high economic value. Drought is one of the factors limiting castor bean growth. The drought resistance mechanisms of castor bean have become a research focus. In this study, we used castor germinating embryos as experimental materials, and screened genes related to drought resistance through physiological measurements, proteomics and metabolomics joint analysis; castor drought-related genes were subjected to transient silencing expression analysis in castor leaves to validate their drought-resistant functions, and heterologous overexpression and backward complementary expression in Arabidopsis thaliana, and analysed the mechanism of the genes' response to the participation of Arabidopsis thaliana in drought-resistance.Three drought tolerance-related genes, RcECP 63, RcDDX 31 and RcA/HD1, were obtained by screening and analysis, and transient silencing of expression in castor leaves further verified that these three genes corresponded to drought stress, and heterologous overexpression and back-complementary expression of the three genes in Arabidopsis thaliana revealed that the function of these three genes in drought stress response.In this study, three drought tolerance related genes, RcECP 63, RcDDX 31 and RcA/HD1, were screened and analysed for gene function, which were found to be responsive to drought stress and to function in drought stress, laying the foundation for the study of drought tolerance mechanism in castor bean., (© 2024. The Author(s).)

Background: The study aimed to assess the impact of parotid lymph nodes (LNs) on the prognosis of patients with cutaneous squamous cell carcinomas of the head and neck (HNcSCC), and to develop an alternative LN assessment method to enhance locoregional control (LRC) and overall survival (OS) stratification., Methods: We retrospectively enrolled patients with surgically treated HNcSCC. Primary outcome variables were LRC and OS. The influence of parotid LNs and different LN assessment methods on prognosis was analyzed using Cox models, and comparisons were made using the C-index, Akaike Information Criterion, and Bayesian Information Criterion., Results: A total of 126 patients were included. Both intraparotid and periparotid LN statuses significantly linked with prognosis. The presence of extranodal extension (ENE) in cervical LNs, rather than parotid LNs, was predictive of decreased LRC and OS. In the Cox analysis, only N3 of the AJCC N classification, when compared to N0, showed reduced LRC and OS. In comparison to N0P1, only N0P3/N1P1 and N2P2/N2P3 of the O'Brien staging system tended to predict poorer LRC, with no subgroup emerging as an independent predictor for OS. The proposed LN assessment method, based on the number of metastatic LNs and ENE status in cervical LNs, demonstrated superior performance in terms of C-index, Akaike Information Criterion, and Bayesian Information Criterion compared to other systems., Conclusion: Parotid LNs were significant determinants of prognosis in metastatic HNcSCC. The novel LN assessment method proposed (1-2 vs. 3-4 vs. 5 + or ENE) displayed similar survival stratification to the AJCC N and O'Brien staging systems., (© 2024. The Author(s).)

Background: In 2020, the Lancet Commission identified 12 risk factors as priorities for prevention of dementia, and other studies identified APOE e4/e4 genotype and family history of Alzheimer's disease strongly associated with dementia outcomes; however, it is unclear how robust these relationships are across dementia subtypes and analytic scenarios. Specification curve analysis (SCA) is a new tool to probe how plausible analytical scenarios influence outcomes., Methods: We evaluated the heterogeneity of odds ratios for 12 risk factors reported from the Lancet 2020 report and two additional strong associated non-modifiable factors (APOE e4/e4 genotype and family history of Alzheimer's disease) with dementia outcomes across 450,707 UK Biobank participants using SCA with 5357 specifications across dementia subtypes (outcomes) and analytic models (e.g., standard demographic covariates such as age or sex and/or 14 correlated risk factors)., Results: SCA revealed variable dementia risks by subtype and age, with associations for TBI and APOE e4/e4 robust to model specification; in contrast, diabetes showed fluctuating links with dementia subtypes. We found that unattributed dementia participants had similar risk factor profiles to participants with defined subtypes., Conclusions: We observed heterogeneity in the risk of dementia, and estimates of risk were influenced by the inclusion of a combination of other modifiable risk factors; non-modifiable demographic factors had a minimal role in analytic heterogeneity. Future studies should report multiple plausible analytic scenarios to test the robustness of their association. Considering these combinations of risk factors could be advantageous for the clinical development and evaluation of novel screening models for different types of dementia., (© 2024. The Author(s).)

Background: The filamentous temperature-sensitive H protease (ftsH) gene family belongs to the ATP-dependent zinc metalloproteins, and ftsH genes play critical roles in plant chloroplast development and photosynthesis., Results: In this study, we performed genome-wide identification and a systematic analysis of soybean ftsH genes. A total of 18 GmftsH genes were identified. The subcellular localization was predicted to be mainly in cell membranes and chloroplasts, and the gene structures, conserved motifs, evolutionary relationships, and expression patterns were comprehensively analyzed. Phylogenetic analysis of the ftsH gene family from soybean and various other species revealed six distinct clades, all of which showed a close relationship to Arabidopsis thaliana. The members of the GmftsH gene family were distributed on 13 soybean chromosomes, with intron numbers ranging from 3 to 15, 13 pairs of repetitive segment. The covariance between these genes and related genes in different species of Oryza sativa, Zea mays, and Arabidopsis thaliana was further investigated. The transcript expression data revealed that the genes of this family showed different expression patterns in three parts, the root, stem, and leaf, and most of the genes were highly expressed in the leaves of the soybean plants. Fluorescence-based real-time quantitative PCR (qRT-PCR) showed that the expression level of GmftsH genes varied under different stress treatments. Specifically, the genes within this family exhibited various induction levels in response to stress conditions of 4℃, 20% PEG-6000, and 100 mmol/L NaCl. These findings suggest that the GmftsH gene family may play a crucial role in the abiotic stress response in soybeans. It was also found that the GmftsH7 gene was localized on the cell membrane, and its expression was significantly upregulated under 4 ℃ treatment. In summary, by conducting a genome-wide analysis of the GmftsH gene family, a strong theoretical basis is established for future studies on the functionality of GmftsH genes., Conclusions: This research can potentially serve as a guide for enhancing the stress tolerance characteristics of soybean., (© 2024. The Author(s).)

Background: Emergence of antibiotic resistance in bacteria is an important threat to global health. Antibiotic resistance genes (ARGs) are some of the key components to define bacterial resistance and their spread in different environments. Identification of ARGs, particularly from high-throughput sequencing data of the specimens, is the state-of-the-art method for comprehensively monitoring their spread and evolution. Current computational methods to identify ARGs mainly rely on alignment-based sequence similarities with known ARGs. Such approaches are limited by choice of reference databases and may potentially miss novel ARGs. The similarity thresholds are usually simple and could not accommodate variations across different gene families and regions. It is also difficult to scale up when sequence data are increasing., Results: In this study, we developed ARGNet, a deep neural network that incorporates an unsupervised learning autoencoder model to identify ARGs and a multiclass classification convolutional neural network to classify ARGs that do not depend on sequence alignment. This approach enables a more efficient discovery of both known and novel ARGs. ARGNet accepts both amino acid and nucleotide sequences of variable lengths, from partial (30-50 aa; 100-150 nt) sequences to full-length protein or genes, allowing its application in both target sequencing and metagenomic sequencing. Our performance evaluation showed that ARGNet outperformed other deep learning models including DeepARG and HMD-ARG in most of the application scenarios especially quasi-negative test and the analysis of prediction consistency with phylogenetic tree. ARGNet has a reduced inference runtime by up to 57% relative to DeepARG., Conclusions: ARGNet is flexible, efficient, and accurate at predicting a broad range of ARGs from the sequencing data. ARGNet is freely available at https://github.com/id-bioinfo/ARGNet , with an online service provided at https://ARGNet.hku.hk . Video Abstract., (© 2024. The Author(s).)

Background: Few studies have focused on functional impairment in depressed patients during symptomatic remission. The exact relationship between cognitive performance and functional outcomes of patients with Major depressive disorder (MDD) remains unclear., Methods: Participants diagnosed with MDD were included and interviewed at both baseline and follow-up. Cognitive function was assessed during acute episodes using the Cambridge Neuropsychological Test Automated Battery (CANTAB), which targeted attention (Rapid Visual Processing - RVP), visual memory (Pattern Recognition Memory - PRM), and executive function (Intra-Extra Dimensional Set Shift - IED). The 17-item Hamilton Depression Scale (HAMD) was used for symptom assessment. Participants were divided into two groups based on their SDSS (Social Disability Screening Schedule) scores, and the differences between their demographic information, HAMD scores, and baseline CANTAB test results were compared. Logistic regression analysis was used to identify cognitive predictors of social function during symptomatic remission., Results: According to the SDSS score at follow-up, 103 patients were divided into the normal social function group (n = 81,78.6%) and the poor social function group (n = 22, 21.4%) during clinical remission. Participants with poorer social function performed worse in the visual memory (PRM) and executive function tests (IED) at the baseline. Logistic regression analysis suggested that performance on the PRM (95%CI = 0.31-0.93, p = 0.030) and IED (95%CI = 1.01-1.13, p = 0.014) tests, instead of less severe symptoms, significantly contributed to functional outcomes., Conclusion: Better performance in visual memory and executive function during acute episodes may predict better social functional outcomes in individuals with MDD. A potential early intervention to improve social function in individuals with MDD could include the treatments for executive function and visual memory., (© 2024. The Author(s).)

Background: Oral leukoplakia (OLK) is a prevalent precancerous lesion with limited non-pharmacological treatment options. Surgery and various lasers are the mainstay of treatment; however, their relative efficacy and optimal choice remain unclear. This first network meta-analysis compared the effects of different lasers and surgical excision on post-treatment recurrence and comfort in OLK patients., Methods: We searched four databases for relevant randomized controlled trials (RCTs) up to April 2023. The primary outcome was post-treatment recurrence, and secondary outcomes included intraoperative hemorrhage and postoperative pain scores. The Cochrane Risk of Bias tool was used to assess the study quality. Meta-analysis and network meta-analysis were employed to determine efficacy and identify the optimal intervention., Results: A total of 11 RCTs including 917 patients and 1138 lesions were included. Er,Cr:YSGG laser treatment showed significantly lower recurrence rates compared to CO 2 laser (OR: 0.04; 95% CI: 0.01-0.18), CO 2 laser with margin extension (OR: 0.06; 95% CI: 0.01-0.60), Er:YAG laser (OR: 0.10; 95% CI: 0.03-0.37), electrocautery (OR: 0.03; 95% CI: 0.00-0.18), and standard care (OR: 0.08; 95% CI: 0.02-0.33). Er,Cr:YSGG laser also ranked the best for reducing recurrence, followed by standard care and CO 2 laser combined with photodynamic therapy (PDT). Er:YAG and Er:Cr:YSGG lasers minimized bleeding and pain, respectively. None of the interventions caused severe adverse effects., Conclusion: For non-homogeneous OLK, Er:YAG, Er:Cr:YSGG, and CO 2 laser combined with PDT offer promising alternatives to surgical excision, potentially reducing recurrence and improving patient comfort. Further high-quality RCTs are necessary to confirm these findings and determine the optimal laser-PDT combination for OLK treatment., (© 2024. The Author(s).)

Glaesserella parasuis, an important respiratory bacterial pathogen, causes Glässer's disease in piglets, with potential immunosuppression. We established a piglet infection model and explored the immunosuppression mechanism to improve our understanding of the host immune response to G. parasuis. Twenty piglets were randomly divided into two groups (n = 10). The infection group was intraperitoneally challenged with 2 × 10 8 CFU of G. parasuis in 2 mL TSB. The control group was intraperitoneally injected with equivalent TSB. After 72 h, the piglets were sacrificed, and spleen tissue was collected. PD-1/PD-L1 expression was determined. The splenocytes were isolated to detect CD3 + T, CD3 + CD4 + T, CD3 + CD8 + T and CD3 - CD21 + cell differentiation. Via data-independent acquisition (DIA), we compared the proteomics of healthy and infected spleen tissues. Glaesserella parasuis modified CD3 + T, CD3 + CD4 + T, CD3 + CD8 + T and CD3 - CD21 + cell differentiation and PD-1/PD-L1 expression in the spleen. The infection group had 596 proteins with significant differences in expression, of which 301 were significantly upregulated and 295 downregulated. Differentially expressed proteins (DEPs) were mainly related to immune responses. This is the first study on PD-1/PD-L1 expression in the spleen associated with immunosuppression in a piglet model to explore the protein changes related to immune responses via DIA., (© 2024. The Author(s).)

Background: Both genetic and environmental factors play crucial roles in the development of major depressive disorder (MDD) and suicide attempts (SA). However, the interaction between both items remains unknown. This study aims to explore the interactions between the genetic variants of the serotonin 2 A receptor (HTR2A) and the nitric oxide synthase 1 (NOS1) and environmental factors in patients who experience MDD and SA., Methods: A total of 334 patients with MDD and a history of SA (MDD-SA) were recruited alongside 518 patients with MDD with no history of SA (MDD-NSA), and 716 healthy controls (HC). The demographic data and clinical characteristics were collected. Sequenom mass spectrometry was used to detect eight tag-single nucleotide polymorphisms (tagSNPs) in HTR2A (rs1328683, rs17068986, and rs3125) and NOS1 (rs1123425, rs2682826, rs3741476, rs527590, and rs7959232). Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-environment interactions., Results: Four tagSNPs (rs17068986, rs3125, rs527590, and rs7959232) exhibited significant differences between the three groups. However, these differences were not significant between the MDD-SA and MDD-NSA groups after Bonferroni correction. A logistic regression analysis revealed that negative life events (OR = 1.495, 95%CI: 1.071-2.087, P = 0.018), self-guilt (OR = 2.263, 95%CI: 1.515-3.379, P < 0.001), and negative cognition (OR = 2.252, 95%CI: 1.264-4.013, P = 0.006) were all independently associated with SA in patients with MDD. Furthermore, GMDR analysis indicated a significant interaction between HTR2A rs3125 and negative life events. Negative life events in conjunction with the HTR2A rs3125 CG + GG genotype were associated with a higher SA risk in patients with MDD when compared to the absence of negative life events in conjunction with the CC genotype (OR = 2.547, 95% CI: 1.264-5.131, P = 0.009)., Conclusion: Several risk factors and a potential interaction between HTR2A rs3125 and negative life events were identified in patients with SA and MDD. The observed interaction likely modulates the risk of MDD and SA, shedding light on the pathogenesis of SA in patients with MDD., (© 2024. The Author(s).)

Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic condition in women of childbearing age and a major cause of anovulatory infertility. The pathophysiology of PCOS is complex. Recent studies have reported that apart from hyperandrogenism, insulin resistance, systemic chronic inflammation, and ovarian dysfunction, gut microbiota dysbiosis is also involved in PCOS development and may aggravate inflammation and metabolic dysfunction, forming a vicious cycle. As naturally occurring plant secondary metabolites, polyphenols have been demonstrated to have anticancer, antibacterial, vasodilator, and analgesic properties, mechanistically creating putative bioactive, low-molecular-weight metabolites in the human gut. Here, we summarize the role of gut microbiota dysbiosis in the development of PCOS and demonstrate the ability of different polyphenols - including anthocyanin, catechins, and resveratrol - to regulate gut microbes and alleviate chronic inflammation, thus providing new insights that may assist in the development of novel therapeutic strategies to treat women with PCOS., (© 2024. The Author(s).)

Background: The cardiometabolic index (CMI) is a new metric derived from the triglyceride-glucose index and body mass index and is considered a potential marker for cardiovascular risk assessment. This study aimed to examine the correlation between the CMI and the presence and severity of arteriosclerosis in patients with type 2 diabetes mellitus (T2DM)., Methods: This study involved 2243 patients with T2DM. The CMI was derived by dividing the triglyceride level (mmol/L) by the high-density lipoprotein level (mmol/L) and then multiplying the quotient by the waist-to-height ratio. Multivariate logistic regression was used to analyze the correlations between the CMI and BMI blood biomarkers, blood pressure, and brachial-ankle pulse wave velocity (baPWV)., Results: Patients were categorized into three groups based on their CMI: Group C1 (CMI < 0.775; n = 750), Group C2 (CMI: 0.775-1.355; n = 743), and Group C3 (CMI > 1.355; n = 750). Increased BMI, fasting glucose, insulin (at 120 min), total cholesterol (TC), and baPWV values were observed in Groups C2 and C3, with statistically significant trends (all trends P < 0.05). The CMI was positively correlated with systolic blood pressure (r = 0.74, P < 0.001). Multivariate analysis revealed that an increased CMI contributed to a greater risk for arteriosclerosis (OR = 1.87, 95%CI: 1.66-2.10, P < 0.001). Compared to the C1 group, the C2 group and C3 group had a greater risk of developing arteriosclerosis, with ORs of 4.55 (95%CI: 3.57-5.81, P<0.001) and 5.56 (95%CI: 4.32-7.17, P<0.001), respectively. The association was notably stronger in patients with a BMI below 21.62 kg/m² than in those with a BMI of 21.62 kg/m² or higher (OR = 4.53 vs. OR = 1.59)., Conclusions: These findings suggest that the CMI is a relevant and independent marker of arteriosclerosis in patients with T2DM and may be useful in the risk stratification and management of these patients., (© 2024. The Author(s).)

Background: Poor development of young children is a common issue in developing countries and it is well established that iron deficiency anemia is one of the risk factors. Research has shown that iron deficiency is a common micronutrient deficiency among children in rural China and can result in anemia. A previous paper using data from the same trial as those used in the current study, but conducted when sample children were younger, found that after 6 months of providing caregivers of children 6-11 months of age free access to iron-rich micronutrient powder (MNP) increased the hemoglobin concentrations (Hb) of their children. However, no effects were found 12 and 18 months after the intervention. The current study followed up the children four years after the start of the original intervention (when the children were 4-5 years old) and aims to assess the medium-term impacts of the MNP program on the nutritional status of the sample pre-school-aged children, including their levels of Hb, the prevalence of anemia, and the dietary diversity of the diets of the children., Methods: At baseline, this study sampled 1,802 children aged 6-11 months in rural Western China. The intervention lasted 18 months. In this medium-term follow-up study that successfully followed 81% (n = 1,464) of children (aged 49-65 months) from the original study population 4 years after the start of the intervention, we used both intention-to-treat (ITT) effect and average treatment on the treated effect (ATT) analyses to assess the medium-term impacts of the MNP distribution program on the nutritional status of sample children., Results: The ITT analysis shows that the MNP intervention decreased the prevalence of anemia of young children in the medium run by 8% (4 percentage points, p < 0.1). The ATT analysis shows that consuming 100 (out of 540) MNP sachets during the initial intervention led to a decrease in anemia of 4% (2 percentage points, p < 0.1). Among children with moderate anemia at baseline (Hb < 100 g/L), the intervention reduced the probability of anemia by 45% (9 percentage points, p < 0.1), and, for those families that complied by consuming 100 (out of 540) sachets, a 25% (5 percentage points, p < 0.05) reduction in the anemia rate was found. The MNP intervention also led to a persistent increase in dietary diversity among children that were moderately anemic at baseline. The results from the quantile treatment effect analysis demonstrated that children with lower Hb levels at baseline benefited relatively more from the MNP intervention., Conclusions: The findings of the current study reveal that the MNP intervention has medium-term effects on the nutritional status of children in rural China. The impacts of the MNP program were relatively higher for children that initially had more severe anemia levels. Hence, the implications of this study are that programs that aim to increase caregiver knowledge of nutrition and improve their feeding practices should be encouraged across rural China. Families, policymakers, and China's society overall need to continue to pay more attention to problems of childhood anemia in rural areas. This is particularly crucial for families with moderately anemic children at an early age as it can significantly contribute to improving the anemia status of children across rural areas of China., Trial Registration: ISRCTN44149146 (15/04/2013)., (© 2024. The Author(s).)

Background: The long-term sequelae of Coronavirus disease 2019 (COVID-19) in children are unclear. We investigated COVID-19 symptoms in school-aged children to determine their impact on patients and their families., Methods: This cross-sectional study, conducted on February 25-28, 2023, selected a representative kindergarten and 9-year school from Shenzhen, China. There were randomly two classes each for the 12 grades from kindergarten to junior high school. The school-aged children were aged 3-16 years. Literate parents completed an online questionnaire related to their children's COVID-19 symptoms since December 1, 2022. Descriptive statistics were computed as necessary. Univariate and multivariable linear regression analyses were performed, and variables with a p-value < 0.05 were considered to have a significant association with the subjective feeling scores for COVID-19 infection., Results: We included 936 school-aged children, with a COVID-19 infection rate of 68.5%. The prevalence of LC 28 (illness with symptoms lasting for 28 days) was 3.4%. During acute infection, the median number of the 641 children's symptoms was 3.0 (IQR: 1.0-5.0) and the median score of subjective feelings was 15.0 (IQR: 11.0-24.5). The top three symptoms were fever, cough/expectoration, and rhinobyon. Age of 13-16 years (adjusted beta: 3.60, 95% CI: 0.32-6.88) and comorbidities (adjusted beta: 3.47, 95% CI: 1.20-5.73) were independently associated with higher subjective feelings (p < 0.05). The top three characteristics associated with LC 28 were alopecia (33.3%, 5/15), cognitive dysfunction (29.2%, 7/24), and emotional problem (28.6%, 6/21)., Conclusions: Children with COVID-19 have a short duration of symptoms and milder symptoms, so they can self-medicate to minimize hospital crowding. Children with basic diseases require prompt attention. Although LC 28 is uncommon in children, mental and psychological problems after COVID-19 recovery should not be ignored., (© 2024. The Author(s).)

Background: Emerging evidence suggests that Rho GTPases play a crucial role in tumorigenesis and metastasis, but their involvement in the tumor microenvironment (TME) and prognosis of hepatocellular carcinoma (HCC) is not well understood., Methods: We aim to develop a tumor prognosis prediction system called the Rho GTPases-related gene score (RGPRG score) using Rho GTPase signaling genes and further bioinformatic analyses., Results: Our work found that HCC patients with a high RGPRG score had significantly worse survival and increased immunosuppressive cell fractions compared to those with a low RGPRG score. Single-cell cohort analysis revealed an immune-active TME in patients with a low RGPRG score, with strengthened communication from T/NK cells to other cells through MIF signaling networks. Targeting these alterations in TME, the patients with high RGPRG score have worse immunotherapeutic outcomes and decreased survival time in the immunotherapy cohort. Moreover, the RGPRG score was found to be correlated with survival in 27 other cancers. In vitro experiments confirmed that knockdown of the key Rho GTPase-signaling biomarker SFN significantly inhibited HCC cell proliferation, invasion, and migration., Conclusions: This study provides new insight into the TME features and clinical use of Rho GTPase gene pattern at the bulk-seq and single-cell level, which may contribute to guiding personalized treatment and improving clinical outcome in HCC., (© 2024. The Author(s).)

Purpose: To compare the efficacy and safety of micropercutaneous nephrolithotomy (MPCNL) and flexible ureteroscopy (FURS) in the treatment of single upper ureteral calculi measuring 1 to 2 centimeters., Methods: This study is a retrospective analysis that combines a review of medical records with an outcomes management database. A total of 163 patients who underwent MPCNL and 137 patients who had FURS were identified between January 2017 and December 2021. Demographic data, operation time, hospitalization time, stone-free rate, and complication rate were collected and analyzed., Results: Preoperative general data of sex, age, BMI, serum creatinine, time of stone existence, stone hardness, stone diameter, preoperative hydronephrosis, and preoperative infection of the MPCNL group have no statistically significant difference with that of the FURS group. All MPCNL or FURS operations in both groups were successfully completed without any instances of reoperation or conversion to another surgical procedure. Patients who underwent MPCNL had a considerably reduced operation time (49.6 vs. 72.4 min; P<0.001), but a higher duration of hospitalization (9.1 vs. 3.9 days; P<0.001) compared to those who underwent FURS. The stone-free rate in the MPCNL group was superior to that of the FURS group, with a percentage of 90.8% compared to 71.5% (P<0.001). There was no statistically significant disparity in the rate of complications between the two groups (13.5% vs. 15.3%; P = 0.741)., Conclusion: Both MPCNL and FURS are viable and secure surgical choices for individuals with solitary upper ureteral calculi measuring 1 to 2 cm. The FURS procedure resulted in a shorter duration of hospitalization compared to MPCNL. However, it had a comparatively lower rate of successfully removing the stones and required a longer duration for the operation.There were no substantial disparities observed in the complication rate between the two groups.FURS is the preferable option for treating uncomplicated upper ureteral calculi, whereas MPCNL is the preferable option for treating complicated upper ureteral calculi.Prior to making treatment options, it is crucial to take into account the expertise of surgeons, the quality of the equipment, and the preferences of the patient., Trial Registration: No., (© 2024. The Author(s).)

Background: The complex etiology and pathogenesis underlying Chronic Non-Bacterial Prostatitis (CNP), coupled with the existence of a Blood Prostate Barrier (BPB), contribute to a lack of specificity and poor penetration of most drugs. Emodin (EMO), a potential natural compound for CNP treatment, exhibits commendable anti-inflammatory, anti-oxidant, and anti-fibrosis properties but suffers from the same problems as other drugs., Methods: By exploiting the recognition properties of lactoferrin (LF) receptors that target intestinal epithelial cells (NCM-460) and prostate epithelial cells (RWPE-1), a pathway is established for the transrectal absorption of EMO to effectively reach the prostate. Additionally, hyaluronic acid (HA) is employed, recognizing CD44 receptors which target macrophages within the inflamed prostate. This interaction facilitates the intraprostatic delivery of EMO, leading to its pronounced anti-inflammatory effects. A thermosensitive hydrogel (CS-Gel) prepared from chitosan (CS) and β-glycerophosphate disodium salt (β-GP) was used for rectal drug delivery with strong adhesion to achieve effective drug retention and sustained slow release. Thus, we developed a triple-targeted nanoparticle (NPs)/thermosensitive hydrogel (Gel) rectal drug delivery system. In this process, LF, with its positive charge, was utilized to load EMO through dialysis, producing LF@EMO-NPs. Subsequently, HA was employed to encapsulate EMO-loaded LF nanoparticles via electrostatic adsorption, yielding HA/LF@EMO-NPs. Finally, HA/LF@EMO-NPs lyophilized powder was added to CS-Gel (HA/LF@EMO-NPs Gel)., Results: Cellular assays indicated that NCM-460 and RWPE-1 cells showed high uptake of both LF@EMO-NPs and HA/LF@EMO-NPs, while Raw 264.7 cells exhibited substantial uptake of HA/LF@EMO-NPs. For LPS-induced Raw 264.7 cells, HA/LF@EMO-NPs can reduce the inflammatory responses by modulating TLR4/NF-κB signaling pathways. Tissue imaging corroborated the capacity of HA/LF-modified formulations to breach the BPB, accumulating within the gland's lumen. Animal experiments showed that rectal administration of HA/LF@EMO-NPs Gel significantly reduced inflammatory cytokine expression, oxidative stress levels and fibrosis in the CNP rats, in addition to exerting anti-inflammatory effects by inhibiting the NF-κB signaling pathway without obvious toxicity., Conclusion: This triple-targeted NPs/Gel rectal delivery system with slow-release anti-inflammatory, anti-oxidant, and anti-fibrosis properties shows great potential for the effective treatment of CNP., (© 2023. The Author(s).)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection has many neurological manifestations, and its effects on the nervous system are increasingly recognized. There has been no systematic analysis of electroencephalography (EEG) characteristics in children exhibiting neurological symptoms of Coronavirus disease 2019 (COVID-19). The primary aim of this study was to describe the EEG characteristics caused by COVID-19 infection in children who were showing neurological symptoms and to assess the relationship between COVID-19-related EEG changes and clinical features in these children., Method: This study included 125 pediatric patients infected with SARS-CoV2 and showing neurological symptoms, and their continuous EEG was recorded. In addition, the demographic and clinical characteristics of these patients were analyzed and the correlation between the two was investigated., Results: Abnormal EEG findings were detected in 31.20% (N = 39) of the patients. Abnormal discharges (43.59%) were the most common EEG abnormalities, followed by background abnormalities (41.03%). The proportion of patients diagnosed with febrile seizure was higher in the normal EEG group than in the abnormal EEG group (P = 0.002), while the opposite was true for epilepsy and encephalitis/encephalopathy (P = 0.016 and P = 0.003, respectively). The independent associated factors of abnormal EEG were age and total length of stay (P < 0.001 and P = 0.003, respectively). Non-specific EEG abnormalities were found in COVID-19-related encephalitis/encephalopathy., Conclusion: Our study corroborated that a small group of pediatric patients infected by COVID-19 and showing neurological symptoms may exhibit abnormal EEG. This study could help improve the understanding of clinical and EEG characteristics in children with COVID-19 and inform triage policies in other hospitals during the COVID-19 pandemic., (© 2024. The Author(s).)

Background: The ability of generating effective humoral immune responses to SARS-CoV-2 infection has not been clarified in lymphoma patients. The study aimed to investigate the antibody (Ab) production after SARS-Cov-2 infection and clarify the factors affecting the Ab generation in these patients., Patients & Methods: 80 lymphoma patients and 51 healthy controls were included in this prospective observational study. Clinical factors and treatment regimens affecting Ab positive rate (APR) and Ab levels were analyzed by univariate and multivariate methods., Results: The anti-SARS-CoV-2 IgG APR and Ab levels in lymphoma patients were significantly lower than those in healthy controls. Lymphoma patients with COVID-19 vaccination had significantly higher APR and Ab levels compared with those without vaccination. Additionally, the use of dexamethasone for COVID-19 treatment had a negative impact on Ab levels. For the impact of treatment regimens on the APR and Ab levels, the results showed that patients treated with ≥ 6 times CD20 monoclonal Ab (mAb) and patients treated with autologous hematopoietic stem cell transplantation (ASCT) prior to infection produced a statistically lower APR and Ab levels compared with those treated with 1-5 times CD20 mAb and those treated without ASCT, respectively. Furthermore, multiple regression analysis indicated that the number of anti-CD20 treatment was an independent predictor for both APR and Ab levels., Conclusions: Humoral immune response to SARS-CoV-2 infection was impaired in lymphoma patients partly due to anti-CD20 and ASCT treatment. COVID-19 vaccination may be more needed for these patients., (© 2024. The Author(s).)

Background: Acyl-CoA-binding domain-containing 3 (ACBD3) is a multifunctional protein, that plays essential roles in cellular signaling and membrane domain organization. Although the precise roles of ACBD3 in various cancers remain unclear. Thus, we aimed to determine the diverse roles of ACBD3 in pan-cancers., Methods: Relevant clinical and RNA-sequencing data for normal tissues and 33 tumors from The Cancer Genome Atlas (TCGA) database, the Human Protein Atlas, and other databases were applied to investigate ACBD3 expression in various cancers. ACBD3-binding and ACBD3-related target genes were obtained from the STRING and GEPIA2 databases. The possible functions of ACBD3-binding genes were explored using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We also applied the diagnostic value and survival prognosis analysis of ACBD3 in pan-cancers using R language. The mutational features of ACBD3 in various TCGA cancers were obtained from the cBioPortal database., Results: When compared with normal tissues, ACBD3 expression was statistically upregulated in eleven cancers and downregulated in three cancers. ACBD3 expression was remarkably different among various pathological stages of tumors, immune and molecular subtypes of cancers, cancer phosphorylation levels, and immune cell infiltration. The survival of four tumors was correlated with the expression level of ACBD3, including pancreatic adenocarcinoma, adrenocortical carcinoma, sarcoma, and glioma. The high accuracy in diagnosing multiple tumors and its correlation with prognosis indicated that ACBD3 may be a potential biomarker of pan-cancers., Conclusion: According to our pan-cancer analysis, ACBD3 may serve as a remarkable prognostic and diagnostic biomarker of pan-cancers as well as contribute to tumor development. ACBD3 may also provide new directions for cancer treatment targets in the future., (© 2023. The Author(s).)

Background: Influenza viruses, especially Influenza A virus and Influenza B virus, are respiratory pathogens and can cause seasonal epidemics and pandemics. Severe influenza viruses infection induces strong host-defense response and excessive inflammatory response, resulting in acute lung damage, multiple organ failure and high mortality. Isoquercitrin is a Chinese medicine monomer, which was reported to have multiple biological activities, including antiviral activity against HSV, IAV, SARS-CoV-2 and so on. Aims of this study were to assess the in vitro anti-IAV and anti-IBV activity, evaluate the in vivo protective efficacy against lethal infection of the influenza virus and searched for the more optimal method of drug administration of isoquercitrin., Methods: In vitro infection model (MDCK and A549 cells) and mouse lethal infection model of Influenza A virus and Influenza B virus were used to evaluate the antiviral activity of isoquercitrin., Results: Isoquercitrin could significantly suppress the replication in vitro and in vivo and reduced the mortality of mouse lethal infection models. Compared with virus infection group, isoquercitrin mitigated lung and multiple organ damage. Moreover, isoquercitrin blocked hyperproduction of cytokines induced by virus infection via inactivating NF-κB signaling. Among these routes of isoquercitrin administration, intramuscular injection is a better drug delivery method., Conclusion: Isoquercitrin is a potential Chinese medicine monomer Against Influenza A Virus and Influenza B Virus infection., (© 2023. The Author(s).)

Background: The exact pathophysiology of TS is still elusive. Previous studies have identified default mode networks (DMN) abnormalities in patients with TS. However, these literatures investigated the neural activity during the tic suppression, not a true resting-state. Therefore, this study aimed to reveal the neural mechanism of Tourette's syndrome (TS) from the perspective of topological organization and functional connectivity within the DMN by electroencephalography (EEG) in resting-state., Methods: The study was conducted by analyzing the EEG data of TS patients with graph theory approaches. Thirty children with TS and thirty healthy controls (HCs) were recruited, and all subjects underwent resting-state EEG data acquisition. Functional connectivity within the DMN was calculated, and network properties were measured., Results: A significantly lower connectivity in the neural activity of the TS patients in the β band was found between the bilateral posterior cingulate cortex/retrosplenial cortex (t = -3.02, p < 0.05). Compared to HCs, the TS patients' local topological properties (degree centrality) in the left temporal lobe in the γ band were changed, while the global topological properties (global efficiency and local efficiency) in DMN exhibited no significant differences. It was also demonstrated that the degree centrality of the left temporal lobe in the γ band was positively related to the Yale Global Tic Severity Scale scores (r = 0.369, p = 0.045)., Conclusions: The functional connectivity and topological properties of the DMN of TS patients were disrupted, and abnormal DMN topological property alterations might affect the severity of tic in TS patients. The abnormal topological properties of the DMN in TS patients may be due to abnormal functional connectivity alterations. The findings provide novel insight into the neural mechanism of TS patients., (© 2023. The Author(s).)

Background: An immunosuppressive tumor microenvironment in ovarian cancer facilitates tumor progression and resistance to immunotherapy. The function of MYB Proto-Oncogene Like 2 (MYBL2) in the tumor microenvironment remains largely unexplored., Methods: A syngeneic intraovarian mouse model, flow cytometry analysis, and immunohistochemistry were used to explore the biological function of MYBL2 in tumor progression and immune escape. Molecular and biochemical strategies-namely RNA-sequencing, western blotting, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay, multiplex immunofluorescence, chromatic immunoprecipitation assay (CHIP) and luciferase assay-were used to reveal the mechanisms of MYBL2 in the OVC microenvironment., Results: We found tumor derived MYBL2 indicated poor prognosis and selectively correlated with tumor associated macrophages (TAMs) in ovarian cancer. Mechanically, C-C motif chemokine ligand 2 (CCL2) transcriptionally activated by MYBL2 induced TAMs recruitment and M2-like polarization in vitro. Using a syngeneic intraovarian mouse model, we identified MYBL2 promoted tumor malignancyand increased tumor-infiltrating immunosuppressive macrophages. Cyclin-dependent kinase 2 (CDK2) was a known upstream kinase to phosphorylate MYBL2 and promote its transcriptional function. The upstream inhibitor of CDK2, CVT-313, reprogrammed the tumor microenvironment and reduced anti-PD-1 resistance., Conclusions: The MYBL2/CCL2 axis contributing to TAMs recruitment and M2-like polarization is crucial to immune evasion and anti-PD-1 resistance in ovarian cancer, which is a potential target to enhance the efficacy of immunotherapy., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Femoral neck fractures are associated with substantial morbidity and mortality for older adults. Total hip arthroplasty (THA) and hemiarthroplasty (HA) are widely used in elderly patients with displaced femoral neck fractures (DFNF), but there is still controversy refering to the optimal chose for the management of DFNF in active elderly patients., Methods: This is a retrospective cohort study that incorporates medical record review with an outcomes management database. 73 patients who underwent HA and 66 patients who underwent THA were identified from January 2015 to December 2017. Data of age, gender, BMI, comorbidity status, operation time, blood loss, hospitalization time, in-hospital complication were collected and analyzed. Clinical follow-up and radiographic examinations were performed at approximately five years, and hip complications, Harris Hip Score (HHS) and EuroQol-5 Dimensions (EQ-5D) were assessed., Results: Preoperative general data of sex, age, BMI and charlson comorbidity score of THA group(n=55) has no statistically significant difference with that of HA group. Patients treated by THA had significantly longer operation time (105.5 vs 76.7 minutes; P < 0.001), more blood loss (524.1 vs 350.1 ml; P < 0.001) and longer hospitalization time (15.8 vs 13.8 days; P < 0.001). There was no significant differences between two groups in complications (32.7% vs 25.8%, P=0.432). No patients died during the hospitalization. After five years, only 33 patients in the THA group and 34 patents in the HA group were still alive, and the fraction surviving were not statistically significant between two groups (60.0% vs 54.8%, P> 0.05). The differences in hip function in favor of THA appeared to increase after the five-year follow-up, and the difference was significant in terms of the total Harris hip score (81.3 vs 73.1, P < 0.001) as well as in the dimensions of pain (38.9 vs 35.9, P=0.033), function (33.7 vs 29.2, P=0.001), absence of deformity (4.0 vs 3.9, P=0.023) and range of motion (4.6 vs 4.2, P=0.008). There was no significant differences between groups in hip dislocation rate (6.1% vs 0.0%, P=0.239). The erosion rate of hip joint in the THA group was significantly lower than that of the HA group (0.0% vs 26.5%, P=0.002). The health-related quality of life, according to EQ-5D index score, was found to be higher (0.69 vs 0.63, P= 0.001) in the THA group than the HA group after five years., Conclusion: THA may be a preferred management option for active elderly patients over 75 years. The more extensive surgery of THA is not associated with higher in-hospital complication rate or mortality rate. These patients can benefit from THA in terms of hip function and quality of life., Trial Registration: No., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: We aimed to identify the relationship between the genomic characteristics and clinical outcomes of oligo-metastatic breast cancer., Methods: Oligo-metastatic breast cancer diagnosed by pathology from January 2001 and August 2019 were reviewed and we matched the poly-metastatic patients based on the clinicopathological features of patients included. Clinicopathological values and data of genomic alterations were collected. Oligo-recurrence (oligo-R) was defined as a situation where disease progression occurred in less than 5 anatomical sites and other anatomic areas still suppressed by the ongoing therapy., Results: A total of 26 breast cancer patients were enrolled in our study, including 14 patients with strict oligo-metastatic disease (oligo-R > 6 months) and 12 with simultaneous poly-metastatic disease. PIK3CA, TP53 and ERBB2 were the most common shared alterations identified in patients included. Based on the median time of oligo-R, we divided the patients with oligo-metastasis into longer oligo-R group (oligo-R > 31.04 months) and shorter oligo-R group (oligo-R ≤ 31.04 months). The analysis of PIK3CA mutation sites showed that H1047R mutation was closely associated with oligo-metastasis, rather than poly-metastasis. H1047R mutation also predicted a better prognosis (oligo-R > 31.04 months) in oligo-metastatic breast cancer. In addition, HER2 positive was more likely to be related to a good outcome in patients with oligo-metastasis., Conclusions: Through the genetic analysis of samples from oligo-metastasis, we found the prognostic values of PIK3CA H1047R and HER2 in oligo- and poly-metastasis. We improved the stratification of prognosis and provided new insights for biological behaviors of oligo-metastatic breast cancer., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Recent studies have suggested a potential link between systemic inflammatory regulators and primary ovarian insufficiency (POI); however, a causal relationship between them remains unclear. In this study, we explored the causal link between systemic inflammatory regulators and POI risk using a bidirectional, two-sample Mendelian randomization (MR) strategy., Results: This approach utilized the most extensive genome-wide association study involving 41 systemic inflammatory regulators in a sample of 8,293 Finnish individuals and POI data from the FinnGen consortium (254 cases vs. 118,228 controls). The inverse variance weighting approach served as a primary MR method, and four additional MR techniques (Maximum Likelihood, MR-Egger, Weighted Median, and constrained maximum likelihood and model averaging Bayesian information criterion ) were applied to support and validate results. Cochran's Q statistics were used to assess the heterogeneity of instrumental variables, whereas the MR-Egger and MR Pleiotropy Residual Sum and Outlier tests detected horizontal pleiotropy. The MR Steiger test evaluated the strength of a causal association. Our findings suggest that lower levels of vascular endothelial growth factor (odds ratio [OR] = 0.73, 95% confidence interval [CI]: 0.54-0.99, P = 0.046) and interleukin-10 (OR = 0.54, 95% CI: 0.33-0.85, P = 0.021) are associated with an increased risk of POI. Reverse MR analysis revealed no significant effect of POI on the expression of these 41 systemic inflammatory regulators. No notable heterogeneity or horizontal pleiotropy was observed in the instrumental variables., Conclusions: This study revealed a causal association between 41 systemic inflammatory regulators and POI, demonstrating that decreased levels of VEGF and IL-10 are linked to an elevated risk of POI. Further investigations are necessary to assess the potential of these biomarkers as early predictors, preventive strategies, and therapeutic targets for POI., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Aims: Dissecting complex interactions among transcription factors (TFs), microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are central for understanding heart development and function. Although computational approaches and platforms have been described to infer relationships among regulatory factors and genes, current approaches do not adequately account for how highly diverse, interacting regulators that include noncoding RNAs (ncRNAs) control cardiac gene expression dynamics over time., Methods: To overcome this limitation, we devised an integrated framework, cardiac gene regulatory modeling (CGRM) that integrates LogicTRN and regulatory component analysis bioinformatics modeling platforms to infer complex regulatory mechanisms. We then used CGRM to identify and compare the TF-ncRNA gene regulatory networks that govern early- and late-stage cardiomyocytes (CMs) generated by in vitro differentiation of human pluripotent stem cells (hPSC) and ventricular and atrial CMs isolated during in vivo human cardiac development., Results: Comparisons of in vitro versus in vivo derived CMs revealed conserved regulatory networks among TFs and ncRNAs in early cells that significantly diverged in late staged cells. We report that cardiac genes ("heart targets") expressed in early-stage hPSC-CMs are primarily regulated by MESP1, miR-1, miR-23, lncRNAs NEAT1 and MALAT1, while GATA6, HAND2, miR-200c, NEAT1 and MALAT1 are critical for late hPSC-CMs. The inferred TF-miRNA-lncRNA networks regulating heart development and contraction were similar among early-stage CMs, among individual hPSC-CM datasets and between in vitro and in vivo samples. However, genes related to apoptosis, cell cycle and proliferation, and transmembrane transport showed a high degree of divergence between in vitro and in vivo derived late-stage CMs. Overall, late-, but not early-stage CMs diverged greatly in the expression of "heart target" transcripts and their regulatory mechanisms., Conclusions: In conclusion, we find that hPSC-CMs are regulated in a cell autonomous manner during early development that diverges significantly as a function of time when compared to in vivo derived CMs. These findings demonstrate the feasibility of using CGRM to reveal dynamic and complex transcriptional and posttranscriptional regulatory interactions that underlie cell directed versus environment-dependent CM development. These results with in vitro versus in vivo derived CMs thus establish this approach for detailed analyses of heart disease and for the analysis of cell regulatory systems in other biomedical fields., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Ulcerative colitis (UC) faces some barriers in oral therapy, such as how to safely deliver drugs to the colon and accumulate in the colon lesions. Hence, we report an advanced yeast particles system loaded with supramolecular nanoparticles with ROS scavenger (curcumin) to treat UC by reducing oxidative stress state and inflammatory response and accelerating the reprogramming of macrophages. In this study, the dual-sensitive materials are bonded on β-cyclodextrin (β-CD), the D-mannose (Man) is modified to adamantane (ADA), and then loaded with curcumin (CUR), to form a functional supramolecular nano-delivery system (Man-CUR NPs) through the host-guest interaction. To improve gastrointestinal stability and colonic accumulation of Man-CUR NPs, yeast cell wall microparticles (YPs) encapsulated Man-CUR NPs to form Man-CUR NYPs via electrostatic adsorption and vacuum extrusion technologies. As expected, the YPs showed the strong stability in complex gastrointestinal environment. In addition, the Man modified supramolecular nanoparticles demonstrated excellent targeting ability to macrophages in the in vitro cellular uptake study and the pH/ROS sensitive effect of Man-CUR NPs was confirmed by the pH/ROS-dual stimulation evaluation. They also enhanced lipopolysaccharide (LPS)-induced inflammatory model in macrophages through downregulation of pro-inflammatory factors, upregulation of anti-inflammatory factors, M2 macrophage polarization, and scavenging the excess ROS. Notably, in DSS-induced mice colitis model, Man-CUR NYPs can reduce the inflammatory responses by modulating TLR4/NF-κB signaling pathways, alleviate oxidative stress by Nrf2/HO-1 signaling pathway, promote macrophages reprogramming and improve the favorable recovery of the damaged colonic tissue. Taken together, this study not only provides strategy for "supramolecular curcumin nanoparticles with pH/ROS sensitive and multistage therapeutic effects" in "advanced yeast particles", but also provided strong theoretical support multi-effect therapy for UC., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: With the continuous advances in third-generation sequencing technology and the increasing affordability of next-generation sequencing technology, sequencing data from different sequencing technology platforms is becoming more common. While numerous benchmarking studies have been conducted to compare variant-calling performance across different platforms and approaches, little attention has been paid to the potential of leveraging the strengths of different platforms to optimize overall performance, especially integrating Oxford Nanopore and Illumina sequencing data., Results: We investigated the impact of multi-platform data on the performance of variant calling through carefully designed experiments with a deep learning-based variant caller named Clair3-MP (Multi-Platform). Through our research, we not only demonstrated the capability of ONT-Illumina data for improved variant calling, but also identified the optimal scenarios for utilizing ONT-Illumina data. In addition, we revealed that the improvement in variant calling using ONT-Illumina data comes from an improvement in difficult genomic regions, such as the large low-complexity regions and segmental and collapse duplication regions. Moreover, Clair3-MP can incorporate reference genome stratification information to achieve a small but measurable improvement in variant calling. Clair3-MP is accessible as an open-source project at: https://github.com/HKU-BAL/Clair3-MP ., Conclusions: These insights have important implications for researchers and practitioners alike, providing valuable guidance for improving the reliability and efficiency of genomic analysis in diverse applications., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Papillary thyroid carcinoma (PTC) is one of the most common thyroid carcinomas. The gross extrathyroidal extension and extensive metastases of PTC lead to high rates of recurrence and poor clinical outcomes. However, the mechanisms underlying PTC development are poorly understood. In this study, using single-cell RNA sequencing, the transcriptome profiles of two PTC patients were addressed, including PTC1 with low malignancy and good prognosis and PTC2 with high malignancy and poor prognosis. We found that epithelial subcluster Epi02 was the most associated with the malignant development of PTC cells, with which the fold change of Chitinase 3-like 1 (CHI3L1) is on the top of the differentially expressed genes between PTC1 and PTC2 (P < 0.001). However CHI3L1 is rarely investigated in PTC as far. We then studied its role in PTC with a series of experiments. Firstly, qRT-PCR analysis of 14 PTC patients showed that the expression of CHI3L1 was positively correlated with malignancy. In addition, overexpression or silencing of CHI3L1 in TPC-1 cells, a PTC cell line, cultured in vitro showed that the proliferation, invasion, and metastasis of the cells were promoted or alleviated by CHI3L1. Further, immunohistochemistry analysis of 110 PTC cases revealed a significant relationship between CHI3L1 protein expression and PTC progression, especially the T (P < 0.001), N (P < 0.001), M stages (P = 0.007) and gross ETE (P < 0.001). Together, our results prove that CHI3L1 is a positive regulator of malignant development of PTC, and it promotes proliferation, invasion, and metastasis of PTC cells. Our study improves understanding of the molecular mechanisms underlying the progression of PTC and provides new insights for the clinical diagnosis and treatment of PTC., (© 2023. The Author(s).)

Background: This study explores the latest epidemiological characteristics of posterior malleolus fracture and compares the epidemiological differences of posterior malleolus fracture in different periods, regions, and adult age groups., Methods: Clinical information of inpatients with posterior malleolus fracture in Shanghai Tongji Hospital and Karamay Central Hospital from January 2014 to February 2022 was reviewed and collected. The imaging data of patients were acquired using the Picture Archiving and Communication Systems. A statistical analysis was performed as to gender, current age, year of admission, injury mechanism, fracture type, and posterior malleolus fracture classification. Moreover, a comparative analysis was conducted on the injury mechanisms and morphological differences of posterior malleolus fracture at different periods, regions, and age groups., Results: A total of 472 patients (210 patients from Shanghai Tongji Hospital and 262 patients from Karamay Central Hospital) with posterior malleolus fracture and an average age of 48.7 ± 15.6 were included in this study. The peak of posterior malleolus fracture occurs in the age group of 50-59. The injury mechanisms mainly involve low-energy fall and sprain (411 cases, 87.1%), followed by traffic accidents (52 cases, 11.0%), and fall injury from height (9 cases, 1.9%). With aging, the number of fall and sprain cases increases and reaches the peak at the age of 50-59, followed by progressive decline. Traffic accidents presents a relatively flat small peak in the age group of 40-59. The number of cases according to different fracture types shows the following ascending order: trimalleolar fracture-supination external rotation (335 cases, 71.0%) > bimalleolar fracture (60 cases, 12.7%) > trimalleolar fracture-pronation extorsion (43 cases, 9.1%) > posterior malleolus + tibial shaft fracture (19 cases, 4.0%) > simple posterior malleolus fracture (15 cases, 3.2%). The numbers of cases corresponding to the Haraguchi I Type, II Type, and III Type of posterior malleolus fractures were 369 (78.2%), 49 (10.4%), and 54 (11.4%), respectively. The Tongji IIA Type represented the highest number of cases (249 cases, 52.8%), followed by the IIB Type (120 cases, 25.4%), I Type (54 cases, 11.4%), IIIB Type (36 cases, 7.6%), and IIIA type (13 cases, 2.8%). The trimalleolar fracture-supination external rotation, Haraguchi I Type and Tongji IIA Type of posterior malleolus fractures all presented an obvious peak of incidence in the age group of 50-59. However, no obvious statistical difference was observed in the injury mechanism, Haraguchi classification, and Tongji classification of posterior malleolus fractures among different years and regions in recent years (P > 0.05)., Conclusions: The injury mechanism of posterior malleolus fracture mainly involves low-energy fall and sprain cases. The trimalleolar fracture-supination external rotation, Haraguchi I type and Tongji IIA type of posterior malleolus fracture are predilection fracture types, and all present an obvious incidence peak in the age group of 50-59. Elderly patients have high risks of falling and their bones are more fragile, conditions which are potential risk factors of posterior malleolus fracture. Early positive control has important significance. This study provides references for relevant basic and clinical studies of posterior malleolus fracture., (© 2023. The Author(s).)

Background: Induction at 38-40 weeks of gestation has been broadly suggested for women with gestational diabetes mellitus (GDM), yet its benefits and risks remain unclear. This study aimed to systematically review and meta-analyze existing evidence on the effect of induction at term gestation among women with GDM., Methods: We searched MEDLINE, EMBASE, Cochrane Libraries, and Web of Science from inception to June 2021. We included randomized controlled trials (RCTs) and observational studies comparing induction with expectant management among GDM term pregnancies. Primary outcomes included caesarean section (CS) and macrosomia. All screening and extraction were conducted independently and in duplicates. Meta-analyses with random-effects models were conducted to generate the pooled odds ratios (ORs) and 95% confidence intervals (CIs) using the Mantel-Haenszel method. Methodological quality was assessed independently by two reviewers using the Cochrane Risk of Bias Tool for RCTs and the Newcastle-Ottawa Scale for observational studies., Results: Of the 4,791 citations, 11 studies were included (3 RCTs and 8 observational studies). Compared to expectant management, GDM women with induction had a significantly lower odds for macrosomia (RCTs 0.49 [0.30-0.81]); observational studies 0.64 [0.54-0.77]), but not for CS (RCTs 0.95 [0.64-1.43]); observational studies 1.03 [0.79-1.34]). Induction was associated with a lower odds of severe perineal lacerations in observational studies (0.59 [0.39-0.88]). No significant difference was observed for other maternal or neonatal morbidities, or perinatal mortality between groups., Conclusions: For GDM women, induction may reduce the risk of macrosomia and severe perineal lacerations compared to expectant management. Further rigorous studies with large sample sizes are warranted to better inform clinical implications., (© 2023. The Author(s).)

Objective: To construct a survival prediction model for patients with TNM stage III hepatocellular carcinoma (HCC) to guide the clinical diagnosis and treatment of HCC patients and improve prognosis., Methods: Based on data from patients with stage III (AJCC 7th TNM stage) recorded by the American Institute of Cancer Research from 2010 to 2013, risk factors affecting the prognosis were screened by Cox univariate and multivariate regression, line plots was constructed, and the credibility of the model was verified by Boostrap method. ROC operating curves, calibration curves and DCA clinical decision curves were used to evaluate the model, and Kaplan-Meier was used for survival analysis was used to evaluate the efficacy of the model. External survival data from patients newly diagnosed with stage III hepatocellular carcinoma during 2014-2015 were used to validate and fit the model and to optimize the model., Results: Age > 75 years vs.18-53 years [HR = 1.502; 95%CI(1.134-1.990)], stage IIIC vs. Stage IIIA [HR = 1.930; 95%CI(1.509-2.470)], lobotomy vs. non-surgery [HR = 0.295; 95%CI(0.228-0.383)], radiotherapy vs. non-radiotherapy [HR = 0.481; 95%CI(0.373-0.619)], chemotherapy vs. Non-chemotherapy [HR = 0.443; 95%CI(0.381-0.515)], positive serum AFP before treatment vs. negative [HR = 1.667; 95%CI(1.356-2.049)], the above indicators are independent prognostic factors for patients with stage III hepatocellular carcinoma, and the P values for the above results were less than 0.05. A joint prediction model was constructed based on age, TNM stage, whether and how to operate, whether to receive radiotherapy, whether to receive chemotherapy, pre-treatment serum AFP status and liver fibrosis score. The consistency index of the improved prognosis model was 0.725., Conclusions: The traditional TNM staging has limitations for clinical diagnosis and treatment, while the Nomogram model modified by TNM staging has good predictive efficacy and clinical significance., (© 2023. The Author(s).)

Background: The COVID-19 pandemic continues to impact global health and China requires a 14-day quarantine for individuals on flights with positive COVID-19 cases. This quarantine can impact mental well-being, including sleep. This study aims to examine the impact of psychosocial and behavioral factors on insomnia among individuals undergoing quarantine in hotels., Methods: This study was a cross-sectional survey carried out in Guangzhou, China. The data was gathered through online questionnaires distributed to international passengers who arrived in Guangzhou on flights and were required to undergo a 14-day quarantine in hotels arranged by the local government. The questionnaires were sent to the participants through the government health hotline "12,320.", Results: Of the 1003 passengers who were quarantined, 6.7% reported significant anxiety and 25.0% had varying degrees of insomnia. Anxiety was positively associated with insomnia (β = 0.92, P < 0.001), while collectivism (β = -0.07, P = 0.036), indoor exercise (β = -0.50, P < 0.001), and the perceived people orientation of the public health service (β = -0.20, P = 0.001) were negatively associated with insomnia. The study also identified moderating effects, such that a higher sense of collectivism, a greater frequency of indoor exercise, and a higher perception of the people-oriented of the public health service were associated with a lower impact of anxiety on insomnia. These moderating effects were also observed in participants with varying degrees of insomnia., Conclusions: This study reveals that a proportion of people undergoing entry quarantine experience insomnia and confirms how psychosocial and behavioral factors can alleviate insomnia in this population., (© 2023. The Author(s).)

Background: First-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as erlotinib, have been shown to target tumors with L858R (exon 21) and exon 19 deletions, resulting in significant clinical benefits. However, acquired resistance often occurs due to EGFR mutations. Therefore, novel therapeutic strategies for treatment of patients with EGFR-positive tumors are needed. Berberine (BBR) is an active alkaloid extracted from pharmaceutical plants such as Coptis chinensis. Berberine has been shown to significantly inhibit EGFR activity and mediate anticancer effects in multiple preclinical studies. We investigated whether combining BBR with erlotinib could augment erlotinib-induced cell growth inhibition of EGFR-positive cells in a mouse xenograft model., Methods: We examined the antitumor activities and potential mechanisms of erlotinib in combination with berberine in vitro and in vivo using the MTT assay, immunoblotting, flow cytometry, and tumor xenograft models., Results: In vitro studies with A431 cells showed that synergistic cell growth inhibition by the combination of BBR and erlotinib was associated with significantly greater inhibition of pEGFR and pAKT, and inhibition of cyclin D and Bcl-2 expression compared to that observed in response to BBR or erlotinib alone. The efficacy of the combination treatment was also investigated in nude mice. Consistent with the in vitro results, BBR plus erlotinib significantly reduced tumor growth., Conclusion: Our data supported use of BBR in combination with erlotinib as a novel strategy for treatment of patients with EGFR positive tumors., (© 2023. The Author(s).)

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes non-symptomatic infection, mild influenza-like symptoms to pneumonia, severe acute respiratory distress syndrome, and even death, reflecting different clinical symptoms of viral infection. However, the mechanism of its pathogenicity remains unclear. Host-specific traits have a breakthrough significance for studying the pathogenicity of SARS-CoV-2. We previously reported SARS-CoV-2/BMA8, a mouse-adapted strain, was lethal to aged BALB/c mice but not to aged C57BL/6N mice. Here, we further investigate the differences in pathogenicity of BMA8 strain against wild-type aged C57BL/6N and BALB/c mice., Methods: Whole blood and tissues were collected from mice before and after BMA8 strain infection. Viral replication and infectivity were assessed by detection of viral RNA copies and viral titers; the degree of inflammation in mice was tested by whole blood cell count, ELISA and RT-qPCR assays; the pathogenicity of SARS-CoV-2/BMA8 in mice was measured by Histopathology and Immunohistochemistry; and the immune level of mice was evaluated by flow cytometry to detect the number of CD8 + T cells., Results: Our results suggest that SARS-CoV-2/BMA8 strain caused lower pathogenicity and inflammation level in C57BL/6N mice than in BALB/c mice. Interestingly, BALB/c mice whose MHC class I haplotype is H-2K d showed more severe pathogenicity after infection with BMA8 strain, while blockade of H-2K b in C57BL/6N mice was also able to cause this phenomenon. Furthermore, H-2K b inhibition increased the expression of cytokines/chemokines and accelerated the decrease of CD8 + T cells caused by SARS-CoV-2/BMA8 infection., Conclusions: Taken together, our work shows that host MHC molecules play a crucial role in the pathogenicity differences of SARS-CoV-2/BMA8 infection. This provides a more profound insight into the pathogenesis of SARS-CoV-2, and contributes enlightenment and guidance for controlling the virus spread., (© 2023. The Author(s).)

Background: RNA-sequencing (RNA-seq) has been widely used to study the dynamic expression patterns of transcribed genes, which can lead to new biological insights. However, processing and analyzing these huge amounts of histological data remains a great challenge for wet labs and field researchers who lack bioinformatics experience and computational resources., Results: We present BarleyExpDB, an easy-to-operate, free, and web-accessible database that integrates transcriptional profiles of barley at different growth and developmental stages, tissues, and stress conditions, as well as differential expression of mutants and populations to build a platform for barley expression and visualization. The expression of a gene of interest can be easily queried by searching by known gene ID or sequence similarity. Expression data can be displayed as a heat map, along with functional descriptions as well as Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Proteins Families Database, and Simple Modular Architecture Research Tool annotations., Conclusions: BarleyExpDB will serve as a valuable resource for the barley research community to leverage the vast publicly available RNA-seq datasets for functional genomics research and crop molecular breeding., (© 2023. The Author(s).)

Background: Despite progress in developing wound care strategies, there is currently no treatment that promotes the self-tissue repair capabilities. H 2 has been shown to effectively protect cells and tissues from oxidative and inflammatory damage. While comprehensive effects and how H 2 functions in wound healing remains unknown, especially for the link between H 2 and extracellular matrix (ECM) deposition and epidermal stem cells (EpSCs) activation., Methods: Here, we established a cutaneous aseptic wound model and applied a high concentration of H 2 (66% H 2 ) in a treatment chamber. Molecular mechanisms and the effects of healing were evaluated by gene functional enrichment analysis, digital spatial profiler analysis, blood perfusion/oxygen detection assay, in vitro tube formation assay, enzyme-linked immunosorbent assay, immunofluorescent staining, non-targeted metabonomic analysis, flow cytometry, transmission electron microscope, and live-cell imaging., Results: We revealed that a high concentration of H 2 (66% H 2 ) greatly increased the healing rate (3 times higher than the control group) on day 11 post-wounding. The effect was not dependent on O 2 or anti-reactive oxygen species functions. Histological and cellular experiments proved the fast re-epithelialization in the H 2 group. ECM components early (3 days post-wounding) deposition were found in the H 2 group of the proximal wound, especially for the dermal col-I, epidermal col-III, and dermis-epidermis-junction col-XVII. H 2 accelerated early autologous EpSCs proliferation (1-2 days in advance) and then differentiation into myoepithelial cells. These epidermal myoepithelial cells could further contribute to ECM deposition. Other beneficial outcomes include sustained moist healing, greater vascularization, less T-helper-1 and T-helper-17 cell-related systemic inflammation, and better tissue remodelling., Conclusion: We have discovered a novel pattern of wound healing induced by molecular hydrogen treatment. This is the first time to reveal the direct link between H 2 and ECM deposition and EpSCs activation. These H 2 -induced multiple advantages in healing may be related to the enhancement of cell viability in various cells and the maintenance of mitochondrial functions at a basic level in the biological processes of life., (© 2023. The Author(s).)

Background: Bone is one of the most frequent sites for breast cancer metastasis. Breast cancer bone metastasis (BCBM) leads to skeletal morbidities including pain, fractures, and spinal compression, all of which severely impact quality of life. Immunotherapy is a promising therapy for patients with advanced cancer, but whether it may provide benefit to metastatic bone cancer is currently unknown. Thus, a better understanding of the immune landscape of bone-disseminated breast cancers may reveal new therapeutic strategies. In this study, we use histopathological analysis to investigate changes within the immune microenvironment of primary breast cancer and paired BCBM., Methods: Sixty-three patients with BCBM, including 31 with paired primary and bone metastatic lesions, were included in our study. The percentage of stroma and stromal tumor-infiltrating lymphocytes (TILs) was evaluated by histopathological analysis. The quantification of stromal TILs (CD4 + and CD8 +), macrophages (CD68 + and HLA-DR +), programmed cell death protein 1 (PD-1), and programmed cell death protein ligand 1 (PD-L1) was evaluated through immunohistochemical (IHC) staining. Statistical analysis was performed with paired t test, Wilcoxon test, spearman correlation test, and univariate and multivariate cox regression., Results: Median survival after BCBM pathological diagnosis was 20.5 months (range: 3-95 months). Of the immune parameters measured, none correlated with survival after bone metastasis was diagnosed. Compared to the primary site, bone metastases exhibited more tumor stroma (mean: 58.5% vs 28.87%, p < 0.001) and less TILs (mean: 8.45% vs 14.03%, p = 0.042), as determined by H&E analysis. The quantification of primary vs metastatic tissue area with CD4 + (23.95/mm 2 vs 51.69/mm 2 , p = 0.027 and with CD8 + (18.15/mm 2 vs 58.95/mm 2 , p = 0.004) TILs similarly followed this trend and was reduced in number for bone metastases. The number of CD68 + and HLA-DR + macrophages showed no significant difference between primary sites and bone metastases. PD-1 expression was present in 68.25% of the bone metastasis, while PD-L1 expression was only present in 7.94% of the bone metastasis., Conclusions: Our findings suggest that compared to the primary breast cancer site, bone metastases harbor a less active immune microenvironment. Despite this relatively dampened immune landscape, expression of PD-1 and PD-L1 in the bone metastasis indicates a potential benefit from immune checkpoint inhibitors for some BCBM cases., (© 2023. The Author(s).)