Cardiac resident macrophages: Spatiotemporal distribution, development, physiological functions, and their translational potential on cardiac diseases.

Cardiac resident macrophages (CRMs) are the main population of cardiac immune cells. The role of these cells in regeneration, functional remodeling, and repair after cardiac injury is always the focus of research. However, in recent years, their dynamic changes and contributions in physiological states have a significant attention. CRMs have specific phenotypes and functions in different cardiac chambers or locations of the heart and at different stages. They further show specific differentiation and development processes. The present review will summarize the new progress about the spatiotemporal distribution, potential developmental regulation, and their roles in cardiac development and aging as well as the translational potential of CRMs on cardiac diseases. Of course, the research tools for CRMs, their respective advantages and disadvantages, and key issues on CRMs will further be discussed.

Effects of 12-week gait retraining on plantar flexion torque, architecture, and behavior of the medial gastrocnemius in vivo.

Objective: This study aims to explore the effects of 12-week gait retraining (GR) on plantar flexion torque, architecture, and behavior of the medial gastrocnemius (MG) during maximal voluntary isometric contraction (MVIC). Methods: Thirty healthy male rearfoot strikers were randomly assigned to the GR group (n = 15) and the control (CON) group (n = 15). The GR group was instructed to wear minimalist shoes and run with a forefoot strike pattern for the 12-week GR (3 times per week), whereas the CON group wore their own running shoes and ran with their original foot strike pattern. Participants were required to share screenshots of running tracks each time to ensure training supervision. The architecture and behavior of MG, as well as ankle torque data, were collected before and after the intervention. The architecture of MG, including fascicle length (FL), pennation angle, and muscle thickness, was obtained by measuring muscle morphology at rest using an ultrasound device. Ankle torque data during plantar flexion MVIC were obtained using a dynamometer, from which peak torque and early rate of torque development (RTD50) were calculated. The fascicle behavior of MG was simultaneously captured using an ultrasound device to calculate fascicle shortening, fascicle rotation, and maximal fascicle shortening velocity (Vmax). Results: After 12-week GR, 1) the RTD50 increased significantly in the GR group (p = 0.038), 2) normalized FL increased significantly in the GR group (p = 0.003), and 3) Vmax increased significantly in the GR group (p = 0.018). Conclusion: Compared to running training, GR significantly enhanced the rapid strength development capacity and contraction velocity of the MG. This indicates the potential of GR as a strategy to improve muscle function and mechanical efficiency, particularly in enhancing the ability of MG to generate and transmit force as well as the rapid contraction capability. Further research is necessary to explore the effects of GR on MG behavior during running in vivo.

The efficacy and safety of short-course radiotherapy followed by sequential chemotherapy and Cadonilimab for locally advanced rectal cancer: a protocol of a phase II study.

BACKGROUND: For patients with locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT), namely, intensifying preoperative treatment through the integration of radiotherapy and systemic chemotherapy before surgery, was commonly recommended as the standard treatment. However, the risk of distant metastasis at 3 years remained higher than 20%, and the complete response (CR) rate was less than 30%. Several clinical trials had suggested a higher complete response rate when combining single-agent immunotherapy with short-course radiotherapy (SCRT). The CheckMate 142 study had shown encouraging outcomes of dual immunotherapy and seemingly comparable toxicity for CRC compared with single-agent immunotherapy in historical results. Therefore, dual immunotherapy might be more feasible in conjunction with the TNT paradigm of SCRT. We performed a phase II study to investigate whether the addition of a dual immune checkpoint inhibitor bispecific antibody, Cadonilimab, to SCRT combined with chemotherapy might further increase the clinical benefit and prognosis for LARC patients. METHODS: This single-arm, multicenter, prospective, phase II study included patients with pathologically confirmed cT3-T4N0 or cT2-4N + rectal adenocarcinoma with an ECOG performance score of 0 or 1. Bispecific antibody immunotherapy was added to SCRT combined with chemotherapy. Patients enrolled would be treated with SCRT (25 Gy in five fractions over 1 week) for the pelvic cavity, followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX and Cadonilimab. The primary endpoint was the CR rate, which was the ratio of the pathological CR rate plus the clinical CR rate. The secondary endpoints included local-regional control, distant metastasis, disease-free survival, overall survival, toxicity profile, quality of life and functional outcome of the rectum. To detect an increase in the complete remission rate from 21.8% to 40% with 80% power, 50 patients were needed. DISCUSSION: This study would provide evidence on the efficacy and safety of SCRT plus bispecific antibody immunotherapy combined with chemotherapy as neoadjuvant therapy for patients with LARC, which might be used as a candidate potential therapy in the future. TRIAL REGISTRATION: This phase II trial was prospectively registered at ClinicalTrials.gov, under the identifier NCT05794750.

Heterozygous mutations in factor H aggravate pathological damage in a stable IgA deposition model induced by Lactobacillus casei cell wall extract.

Introduction: Activation of complement through the alternative pathway (AP) has a key role in the pathogenesis of IgA nephropathy (IgAN). We previously showed, by intraperitoneal injection of Lactobacillus casei cell wall extract (LCWE), C57BL/6 mice develop mild kidney damage in association with glomerular IgA deposition. To further address complement activity in causing glomerular histological alterations as suggested in the pathogenesis of IgAN, here we used mice with factor H mutation (FHW/R) to render AP overactivation in conjunction with LCWE injection to stimulate intestinal production of IgA. Methods: Dose response to LCWE were examined between two groups of FHW/R mice. Wild type (FHW/W) mice stimulated with LCWE were used as model control. Results: The FHW/R mice primed with high dose LCWE showed elevated IgA and IgA-IgG complex levels in serum. In addition to 100% positive rate of IgA and C3, they display elevated biomarkers of kidney dysfunction, coincided with severe pathological lesions, resembling those of IgAN. As compared to wild type controls stimulated by the same high dose LCWE, these FHW/R mice exhibited stronger complement activation in the kidney and in circulation. Discussion: The new mouse model shares many disease features with IgAN. The severity of glomerular lesions and the decline of kidney functions are further aggravated through complement overactivation. The model may be a useful tool for preclinical evaluation of treatment response to complement-inhibitors.

POI-associated EIF4ENIF1 mutations exhibit impaired translation regulation abilities.

Various genetic variants have been found to be associated with the clinical onset of premature ovarian insufficiency (POI). However, when measured in vitro, the functional influence of the variants can be difficult to determine. By whole-exome sequencing (WES) of 93 patients with sporadic POI, we found a missense variant c.623G > A;p.R208H in the EIF4ENIF1 gene. In silico prediction of the variant using different algorithms suggested it might be a damaging variant. We compared the property of EIF4ENIF1 R208H and Q842P, a POI-related mutant that we reported previously, with wildtype (WT) protein using 293FT cells in vitro. Surprisingly, a change in subcellular distribution and granule forming ability (Q842P) and nuclear import capacity (R208H) was not observed, despite domain prediction evidences. Since EIF4ENIF1 was reported to inhibit translation, we employed T&T-seq, a translation-transcription dual-omics sequencing method, to profile gene expression upon overexpression of EIF4ENIF1 WT and mutants. EIF4ENIF1 WT overexpression group exhibited significantly (P < 0.0001) lower translation efficiency (TE) than empty vector or GFP overexpression control group. Surprisingly, EIF4ENIF1 Q842P overexpression failed to repress global translation, showing an overall TE significantly higher than WT group. Overexpression R208H significantly (P < 0.0001) lowered the overall TE, whereas exhibiting a reduced translation inhibitory effect on high-TE genes (TE > 2 in GFP control group). Several fertility-associated genes, such as AMH in Q842P group and SERPINE1 and THBS1 in R208H group, was translationally up-regulated in mutant groups versus WT control, suggesting a potential mechanism of mutated EIF4ENIF1 causing POI via impaired translation repression. It is further proposed that T&T-seq can be a sensitive evaluation tool for the measurement of functional alteration by variants in many other translational regulator genes, not only EIF4ENIF1, helping to eliminate misinterpretation of clinical significance of genetic variants.

Autosomal recessive primary microcephaly type 2 associated with a novel WDR62 splicing variant that disrupts the expression of the functional transcript.

Background: Autosomal recessive primary microcephaly (MCPH) is a rare neurodevelopmental disorder characterized primarily by congenital microcephaly and intellectual disability but without extra-central nervous system malformations. This investigation aimed to elucidate the genetic underpinnings of microcephaly in a patient from a Chinese consanguineous family. Methods: A comprehensive clinical assessment, including brain magnetic resonance imaging (MRI), electroencephalogram (EEG), and genetic analyses, was conducted to evaluate the patient's condition. Whole-exome sequencing (WES) was employed to identify the causative gene, followed by Sanger sequencing, to confirm the mutation and its segregation within the family. Reverse transcript polymerase chain reaction (RT-PCR) was utilized to detect changes in splicing. Western blot was employed to reveal the difference of protein expression level between the wild-type and mutant WDR62 in vitro. Results: The patient exhibited classic MCPH symptoms, including microcephaly, recurrent epilepsy, delayed psychomotor development, and intellectual disability. Additionally, asymmetrical limb length was noted as a prominent feature. MRI findings indicated reduced brain volume with cortical malformations, while EEG demonstrated heightened sharp wave activity. A molecular analysis uncovered a novel homozygous variant c.4154-6 C > G in the WDR62 intron, and a functional analysis confirmed the pathogenicity of this mutation, resulting in the formation of an abnormal transcript with premature termination codons. Conclusion: This study enhances our understanding of the genetic heterogeneity associated with MCPH and highlights the pivotal role of genetic testing in the diagnosing and managing of rare neurodevelopmental disorders. Furthermore, it highlights the potential of emerging genetic therapies in treating conditions such as MCPH2.

A Time-Local Weighted Transformation Recognition Framework for Steady State Visual Evoked Potentials Based Brain-Computer Interfaces.

Canonical correlation analysis (CCA), Multivariate synchronization index (MSI), and their extended methods have been widely used for target recognition in Brain-computer interfaces (BCIs) based on Steady State Visual Evoked Potentials (SSVEP), and covariance calculation is an important process for these algorithms. Some studies have proved that embedding time-local information into the covariance can optimize the recognition effect of the above algorithms. However, the optimization effect can only be observed from the recognition results and the improvement principle of time-local information cannot be explained. Therefore, we propose a time-local weighted transformation (TT) recognition framework that directly embeds the time-local information into the electroencephalography signal through weighted transformation. The influence mechanism of time-local information on the SSVEP signal can then be observed in the frequency domain. Low-frequency noise is suppressed on the premise of sacrificing part of the SSVEP fundamental frequency energy, the harmonic energy of SSVEP is enhanced at the cost of introducing a small amount of high-frequency noise. The experimental results show that the TT recognition framework can significantly improve the recognition ability of the algorithms and the separability of extracted features. Its enhancement effect is significantly better than the traditional time-local covariance extraction method, which has enormous application potential.

Tanshinone IIA acts as a regulator of lipogenesis to overcome osimertinib acquired resistance in lung cancer.

Osimertinib is a novel epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), acting as the first-line medicine for advanced EGFR-mutated NSCLC. Recently, the acquired resistance to osimertinib brings great challenges to the advanced treatment. Therefore, it is in urgent need to find effective strategy to overcome osimertinib acquired resistance. Here, we demonstrated that SREBP pathway-driven lipogenesis was a key mediator to promote osimertinib acquired resistance, and firstly found Tanshinone IIA (Tan IIA), a natural pharmacologically active constituent isolated from Salvia miltiorrhiza, could overcome osimertinib-acquired resistance in vitro and in vivo via inhibiting SREBP pathway-mediated lipid lipogenesis by using LC-MS based cellular lipidomics analysis, quantitative real-time PCR (qRT-PCR) analysis, western blotting analysis, flow cytometry, small interfering RNAs transfection, and membrane fluidity assay et al. The results showed that SREBP1/2-driven lipogenesis was highly activated in osimertinib acquired resistant NSCLC cells, while knockdown or inhibition of SREBP1/2 could restore the sensitivity of NSCLC to osimertinib via altered the proportion of saturated phospholipids and unsaturated phospholipids in osimertinib acquired-resistant cells. Furthermore, Tanshinone IIA (Tan IIA) could reverse the acquired resistance to osimertinib in lung cancer. Mechanically, Tan IIA inhibited SREBP signaling mediated lipogenesis, changed the profiles of saturated phospholipids and unsaturated phospholipids, and thus promoted osimertinib acquired resistant cancer cells to be attacked by oxidative stress-induced damage and reduce the cell membrane fluidity. The reversal effect of Tan IIA on osimertinib acquired resistant NSCLC cells was also confirmed in vivo, which is helpful for the development of strategies to reverse osimertinib acquired resistance.

Revolutionizing aquatic eco-environmental monitoring: Utilizing the RPA-Cas-FQ detection platform for zooplankton.

The integration of recombinase polymerase amplification (RPA) with CRISPR/Cas technology has revolutionized molecular diagnostics and pathogen detection due to its unparalleled sensitivity and trans-cleavage ability. However, its potential in the ecological and environmental monitoring scenarios for aquatic ecosystems remains largely unexplored, particularly in accurate qualitative/quantitative detection, and its actual performance in handling complex real environmental samples. Using zooplankton as a model, we have successfully optimized the RPA-CRISPR/Cas12a fluorescence detection platform (RPA-Cas-FQ), providing several crucial "technical tips". Our findings indicate the sensitivity of CRISPR/Cas12a alone is 5 × 109 copies/reaction, which can be dramatically increased to 5 copies/reaction when combined with RPA. The optimized RPA-Cas-FQ enables reliable qualitative and semi-quantitative detection within 50 min, and exhibits a good linear relationship between fluorescence intensity and DNA concentration (R2 = 0.956-0.974***). Additionally, we developed a rapid and straightforward identification procedure for single zooplankton by incorporating heat-lysis and DNA-barcode techniques. We evaluated the platform's effectiveness using real environmental DNA (eDNA) samples from the Three Gorges Reservoir, confirming its practicality. The eDNA-RPA-Cas-FQ demonstrated strong consistency (Kappa = 0.43***) with eDNA-Metabarcoding in detecting species presence/absence in the reservoir. Furthermore, the two semi-quantitative eDNA quantification technologies showed a strong positive correlation (R2 = 0.58-0.87***). This platform also has the potential to monitor environmental pollutants by selecting appropriate indicator species. The novel insights and methodologies presented in this study represent a significant advancement in meeting the complex needs of aquatic ecosystem protection and monitoring.

A tempo-spatial controllable microfluidic shear-stress generator for in-vitro mimicking of the thrombus.

Pathological conditions linked to shear stress have been identified in hematological diseases, cardiovascular diseases, and cancer. These conditions often exhibit significantly elevated shear stress levels, surpassing 1000 dyn/cm2 in severely stenotic arteries. Heightened shear stress can induce mechanical harm to endothelial cells, potentially leading to bleeding and fatal consequences. However, current technology still grapples with limitations, including inadequate flexibility in simulating bodily shear stress environments, limited range of shear stress generation, and spatial and temporal adaptability. Consequently, a comprehensive understanding of the mechanisms underlying the impact of shear stress on physiological and pathological conditions, like thrombosis, remains inadequate. To address these limitations, this study presents a microfluidic-based shear stress generation chip as a proposed solution. The chip achieves a substantial 929-fold variation in shear stress solely by adjusting the degree of constriction in branch channels after PDMS fabrication. Experiments demonstrated that a rapid increase in shear stress up to 1000 dyn/cm2 significantly detached 88.2% cells from the substrate. Long-term exposure (24 h) to shear stress levels below 8.3 dyn/cm2 did not significantly impact cell growth. Furthermore, cells exposed to shear stress levels equal to or greater than 8.3 dyn/cm2 exhibited significant alterations in aspect ratio and orientation, following a normal distribution. This microfluidic chip provides a reliable tool for investigating cellular responses to the wide-ranging shear stress existing in both physiological and pathological flow conditions.

A brief overview of passive microvalves in microfluidics: Mechanism, manufacturing, and applications.

Microvalves play a crucial role in manipulating fluid states within a microfluidic system and are finding widespread applications in fields such as biology, medicine, and environmental preservation. Leveraging the characteristics and features of microvalves enables the realization of various complicated microfluidic functions. Continuous advancement in the manufacturing process contributes to more flexible control modes for passive microvalves. As a consequence, these valves are progressively shrinking in size while simultaneously improving in precision and stability. Although active microvalves have the benefits of low leakage, rapid response time, and wide adaptability range, the energy supply system limits the size and even their applicability in integration and miniaturization. In comparison, passive microvalves have the advantage of relying solely on the fluid flow or fluid driving pressure to control the open/close of fluid flow over active microvalves, in spite of having slightly reduced control accuracy. Their self-sustaining feature is highly consistent with the need for assembly and miniaturization in the point-of-care testing technology. Hence, these valves have attracted significant interest for research and application purposes. This review focuses on the recent literature on passive microvalves and details existing passive microvalves from three different aspects: operating principle, processing method, and applications. This work aims to increase the visibility of passive microvalves among researchers and enhance their comprehension by classifying them according to the aforementioned three aspects, facilitating the practical applications and further developments of passive microvalves. Additionally, this paper is expected to serve as a comprehensive and systematic reference for interdisciplinary researchers that intend to design related microfluidic systems.

Cellular strategies to induce immune tolerance after liver transplantation: Clinical perspectives.

Liver transplantation (LT) has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techniques and perioperative management. However, long-term side-effects of immunosuppressants, like infection, metabolic disorders and malignant tumor are gaining more attention. Immune tolerance is the status in which LT recipients no longer need to take any immunosuppressants, but the liver function and intrahepatic histology maintain normal. The approaches to achieve immune tolerance after transplantation include spontaneous, operational and induced tolerance. The first two means require no specific intervention but withdrawing immunosuppressant gradually during follow-up. No clinical factors or biomarkers so far could accurately predict who are suitable for immunosuppressant withdraw after transplantation. With the understanding to the underlying mechanisms of immune tolerance, many strategies have been developed to induce tolerance in LT recipients. Cellular strategy is one of the most promising methods for immune tolerance induction, including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory immune cells. The safety and efficacy of various cell products have been evaluated by prospective preclinical and clinical trials, while obstacles still exist before translating into clinical practice. Here, we will summarize the latest perspectives and concerns on the clinical application of cellular strategies in LT recipients.

MSLTE: multiple self-supervised learning tasks for enhancing EEG emotion recognition.

Objective. The instability of the EEG acquisition devices may lead to information loss in the channels or frequency bands of the collected EEG. This phenomenon may be ignored in available models, which leads to the overfitting and low generalization of the model.Approach. Multiple self-supervised learning tasks are introduced in the proposed model to enhance the generalization of EEG emotion recognition and reduce the overfitting problem to some extent. Firstly, channel masking and frequency masking are introduced to simulate the information loss in certain channels and frequency bands resulting from the instability of EEG, and two self-supervised learning-based feature reconstruction tasks combining masked graph autoencoders (GAE) are constructed to enhance the generalization of the shared encoder. Secondly, to take full advantage of the complementary information contained in these two self-supervised learning tasks to ensure the reliability of feature reconstruction, a weight sharing (WS) mechanism is introduced between the two graph decoders. Thirdly, an adaptive weight multi-task loss (AWML) strategy based on homoscedastic uncertainty is adopted to combine the supervised learning loss and the two self-supervised learning losses to enhance the performance further.Main results. Experimental results on SEED, SEED-V, and DEAP datasets demonstrate that: (i) Generally, the proposed model achieves higher averaged emotion classification accuracy than various baselines included in both subject-dependent and subject-independent scenarios. (ii) Each key module contributes to the performance enhancement of the proposed model. (iii) It achieves higher training efficiency, and significantly lower model size and computational complexity than the state-of-the-art (SOTA) multi-task-based model. (iv) The performances of the proposed model are less influenced by the key parameters.Significance. The introduction of the self-supervised learning task helps to enhance the generalization of the EEG emotion recognition model and eliminate overfitting to some extent, which can be modified to be applied in other EEG-based classification tasks.

Shared genetic factors and causal association between chronic hepatitis C infection and diffuse large B cell lymphoma.

BACKGROUND: Epidemiological research and systematic meta-analyses indicate a higher risk of B-cell lymphomas in patients with chronic hepatitis C virus (HCV) compared to non-infected individuals. However, the genetic links between HCV and these lymphomas remain under-researched. METHODS: Mendelian randomization analysis was employed to explore the association between chronic hepatitis C (CHC) and B-cell lymphomas as well as chronic lymphocytic leukemia (CLL). Approximate Bayes Factor (ABF) localization analysis was conducted to find shared genetic variants that might connect CHC with B-cell lymphomas and chronic lymphocytic leukemia (CLL). Furthermore, The Variant Effect Predictor (VEP) was utilized to annotate the functional effects of the identified genetic variants. RESULTS: Mendelian randomization revealed a significant association between CHC and increased diffuse large B cell lymphoma (DLBCL) risk (OR: 1.34; 95% CI: 1.01-1.78; P = 0.0397). Subsequent colocalization analysis pinpointed two noteworthy variants, rs17208853 (chr6:32408583) and rs482759 (chr6:32227240) between these two traits. The annotation of these variants through the VEP revealed their respective associations with the butyrophilin-like protein 2 (BTNL2) and notch receptor 4 (NOTCH4) genes, along with the long non-coding RNA (lncRNA) TSBP1-AS1. CONCLUSION: This research provides a refined genetic understanding of the CHC-DLBCL connection, opening avenues for targeted therapeutic research and intervention.

Therapeutic potential of natural flavonoids in pulmonary arterial hypertension: A review.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a fatal disease caused by pulmonary vascular remodeling, with a high incidence and mortality. At present, many clinical drugs for treating PAH mainly exert effects by relaxing the pulmonary artery, with limited therapeutic effects, so the search for viable therapeutic agents continues uninterrupted. In recent years, natural flavonoids have shown promising potential in the treatment of cardiovascular diseases. It is necessary to comprehensively elucidate the potential of natural flavonoids to combat PAH. PURPOSE: To evaluate the potential of natural flavonoids to hinder or slow down the occurrence and development of PAH, and to identify promising drug discovery candidates. METHODS: Literature was collected from PubMed, Science Direct, Web of science, CNKI databases and Google scholar. The search terms used included "pulmonary arterial hypertension", "pulmonary hypertension", "natural products", "natural flavonoids", "traditional chinese medicine", etc., and several combinations of these keywords. RESULTS: The resources, structural characteristics, mechanisms, potential and prospect strategies of natural flavonoids for treating PAH were summarized. Natural flavonoids offer different solutions as possible treatments for PAH. These mechanisms may involve various pathways and molecular targets related to the pathogenesis of PAH, such as inflammation, oxidative stress, vascular remodeling, genetic, ion channels, cell proliferation and autophagy. In addition, prospect strategies of natural flavonoids for anti-PAH including structural modification and nanomaterial delivery systems have been explored. This review suggests that the potential of natural flavonoids as alternative therapeutic agents in the prevention and treatment of PAH holds promise for future research and clinical applications. CONCLUSION: Despite displaying the enormous potential of flavonoids in PAH, some limitations need to be further explored. Firstly, using advanced drug discovery tools, including computer-aided design and high-throughput screening, to further investigate the safety, biological activity, and precise mechanism of action of flavonoids. Secondly, exploring the structural modifications of these compounds is expected to optimize their efficacy. Lastly, it is necessary to conduct well controlled clinical trials and a comprehensive evaluation of potential side effects to determine their effectiveness and safety.

Research Progress on Biological Evidence Identification in Fire Scenes.

Biological evidence is relatively common evidence in criminal cases, and it has strong probative power because it carries DNA information for individual identification. At the scene of fire-related cases, the complex thermal environment, the escape of trapped people, the firefighting and rescue operations, and the deliberate destruction of criminal suspects will all affect the biological evidence in the fire scene. Scholars at home and abroad have explored and studied the effectiveness of biological evidence identification in fire scenes, and found that the blood stains, semen stains, bones, etc. are the main biological evidence which can be easily recovered with DNA in fire scenes. In order to analyze the research status and development trend of biological evidence in fire scenes, this paper systematically sorts out the relevant research, mainly including the soot removal technology, appearance method of typical biological evidence, and possibility of identifying other biological evidence. This paper also prospects the next step of research direction, in order to provide reference for the identification of biological evidence and improve the value of biological evidence in fire scenes.

Treatment outcome, toxicity, and quality of life of patients with bronchus-associated lymphoid tissue lymphoma.

The disease failure patterns and optimal treatment of bronchus-associated lymphoid tissue (BALT) lymphoma are unknown. This retrospective study involved 71 patients with primary BALT lymphoma who had received radiotherapy (RT), surgery, immunochemotherapy (IC), or observation. The median follow-up time was 66 months. The 5-year overall survival and lymphoma-specific survival were 91.2% and 96.1%, respectively, and were not significantly different among treatments. The 5-year cumulative incidence of overall failure for RT, surgery, IC, and observation was 0%, 9.7% (p = .160), 30.8% (p = .017), and 31.3% (p = .039). There was no grade ≥3 toxicity in RT group according to the CTCAE 5.0 reporting system. Quality of life (QoL) was at similarly good levels among the treatment groups. BALT lymphoma had a favorable prognosis but persistent risk of relapse after IC or observation. Given the very low disease failure risk and good QoL, RT remains an effective initial treatment for BALT lymphoma.Key PointsBALT lymphoma has a favorable prognosis but a persistent progression and relapse risk.Radiotherapy is associated with lower failure of disease progression and relapse, low toxicity and good quality of life.

Expression of overall survival-EMT-immune cell infiltration genes predict the prognosis of glioma.

This study investigates the crucial role of immune- and epithelial-mesenchymal transition (EMT)-associated genes and non-coding RNAs in glioma development and diagnosis, given the challenging 5-year survival rates associated with this prevalent CNS malignant tumor. Clinical and RNA data from glioma patients were meticulously gathered from CGGA databases, and EMT-related genes were sourced from dbEMT2.0, while immune-related genes were obtained from MSigDB. Employing consensus clustering, novel molecular subgroups were identified. Subsequent analyses, including ESTIMATE, TIMER, and MCP counter, provided insights into the tumor microenvironment (TIME) and immune status. Functional studies, embracing GO, KEGG, GSVA, and GSEA analyses, unraveled the underlying mechanisms governing these molecular subgroups. Utilizing the LASSO algorithm and multivariate Cox regression, a prognostic risk model was crafted. The study unveiled two distinct molecular subgroups with significantly disparate survival outcomes. A more favorable prognosis was linked to low immune scores, high tumor purity, and an abundance of immune infiltrating cells with differential expression of non-coding RNAs, including miRNAs. Functional analyses illuminated enrichment of immune- and EMT-associated pathways in differentially expressed genes and non-coding RNAs between these subgroups. GSVA and GSEA analyses hinted at abnormal EMT status potentially contributing to glioma-associated immune disorders. The risk model, centered on OS-EMT-ICI genes, exhibited promise in accurately predicting survival in glioma. Additionally, a nomogram integrating the risk model with clinical characteristics demonstrated notable accuracy in prognostic predictions for glioma patients. In conclusion, OS-EMT-ICI gene and non-coding RNA expression emerges as a valuable indicator intricately linked to immune microenvironment dysregulation, offering a robust tool for precise prognosis prediction in glioma patients within the OBMRC framework.

Disparities in mortality risk after diagnosis of hematological malignancies in 185 countries: A global data analysis.

This study was to report proxy measures for mortality risk in patients with hematological malignancies across 185 countries globally and explore its association with their socioeconomic status and treatment. The incidence, mortality, and 5-year prevalence data were extracted from the GLOBOCAN database. The data regarding the human development index (HDI), gross national income (GNI), vulnerability index, and concordance with cancer Essential Medicines List (EML) were obtained from open-source reports. The ratio of mortality to 5-year-prevalence (MPR) and that of mortality to incidence (MIR) were calculated and age-standardized using Segi's world standard population. Finally, the possible associations were assessed using Pearson correlation analyses. In 2020, the global incidence, mortality, and 5-year prevalence of HMs were 1,278,362, 711,840, and 3,616,685, respectively. Global age-standardized MPR and MIR were 0.15 and 0.44, respectively; they varied significantly among 6 regions, 185 countries, 4 HM types, and 4 HDI groups worldwide. Older populations always had higher ratios. The correlation of MPRs and MIRs with HDI, GNI, and concordance with cancer EML was negative, whereas it was positive with the vulnerability index (lower was better). Increasing access to cancer drugs in resource-limited regions with a focus on vulnerable children may aid in reducing HM-related mortality risk.

Case Report: Itraconazole Oral Solution Continuous Therapy for Infantile Tinea Capitis.

Tinea capitis is a common fungal infection caused by dermatophytes in children, but it is rare in infants. Although oral itraconazole has been widely used to treat tinea capitis, its use in infants is limited due to its low prevalence in this age group. A previous study reported the effectiveness of itraconazole continuous therapy in treating infantile tinea capitis caused by Microsporum canis. However, this approach has not been extended to tinea capitis caused by other fungi. In this study, we present four cases of infantile tinea capitis treated with continuous itraconazole oral solution therapy (5 mg/kg/day). Two patients were infected with M. canis, one patient with Nannizzia gypsea, and another with Trichophyton tonsurans. This study assesses the efficacy and safety of itraconazole oral solution continuous therapy, expanding our understanding by demonstrating its effectiveness for infantile tinea capitis caused by T. tonsurans and N. gypsea.