A Near-Infrared Retinomorphic Device with High Dimensionality Reservoir Expression.

Physical reservoir-based reservoir computing (RC) systems for intelligent perception have recently gained attention because they require fewer computing resources. However, the system remains limited in infrared (IR) machine vision, including materials and physical reservoir expression power. Inspired by biological visual perception systems, the study proposes a near-infrared (NIR) retinomorphic device that simultaneously perceives and encodes narrow IR spectral information (at ≈980 nm). The proposed device, featuring core-shell upconversion nanoparticle/poly (3-hexylthiophene) (P3HT) nanocomposite channels, enables the absorption and conversion of NIR into high-energy photons to excite more photo carriers in P3HT. The photon-electron-coupled dynamics under the synergy of photovoltaic and photogating effects influence the nonlinearity and high dimensionality of the RC system under narrow-band NIR irradiation. The device also exhibits multilevel data storage capability (≥8 levels), excellent stability (≥2000 s), and durability (≥100 cycles). The system accurately identifies NIR static and dynamic handwritten digit images, achieving recognition accuracies of 91.13% and 90.07%, respectively. Thus, the device tackles intricate computations like solving second-order nonlinear dynamic equations with minimal errors (normalized mean squared error of 1.06 × 10⁻3 during prediction).

Anlotinib reverses osimertinib resistance via inhibiting epithelial-to-mesenchymal transition and angiogenesis in non-small cell lung cancer.

In the present, we aimed to investigate the effect of anlotinib on the potential reversal of osimertinib resistance by inhibiting the formation of epithelial-to-mesenchymal transition (EMT) and angiogenesis. In a clinical case, anlotinib reversed osimertinib resistance in Non-small cell lung cancer (NSCLC). We performed an immunohistochemical experiment on tumor tissues from three non-small cell lung cancer patients exhibiting osimertinib resistance to analyze alterations in the expression levels of EMT markers and vascular endothelial growth factor A (VEGFA) before and after osimertinib resistance. The results revealed the downregulation of E-cadherin, coupled with the upregulation of vimentin and VEGFA in tumor tissues of patients exhibiting osimertinib resistance, compared with the expression in tissues of patients before taking osimertinib. Subsequently, we established osimertinib-resistant cell lines and found that the osimertinib-resistant cells acquired the EMT features. Then, we analyzed the synergistic effects of the combination therapy to verify whether anlotinib could reverse osimertinib resistance by inhibiting EMT. The expression levels of VEGFA and micro-vessels were analyzed in the combination group in vitro. Finally, we explored the reversal of osimertinib resistance in combination with anlotinib in vivo with 20 nude mice. The combined treatment of osimertinib and anlotinib effectively prevented the metastasis of resistant cells, which also inhibited tumor growth, exerted anti-tumor activity, and ultimately reversed osimertinib resistance in mice. The co-administration of osimertinib and anlotinib demonstrated their synergistic efficacy in inhibiting EMT and angiogenesis in three NSCLC patients, ultimately reversing osimertinib resistance.

Reduced muscle mass is an important part of Global Leadership Initiative on Malnutrition criteria in nutritional diagnosis of hepatocellular carcinoma.

BACKGROUND: The Global Leadership Initiative on Malnutrition criteria (GLIM) was established to build a global consensus on the diagnostic criteria for malnutrition. The study aimed to assess the prevalence of the malnutrition diagnosed by GLIM criteria for patients with hepatocellular carcinoma (HCC), and to determine the role of the reduced muscle mass defined by CT scans in the GLIM criteria. METHODS: This cohort research was conducted on adult cirrhotic patients with HCC. The risk of malnutrition was screened by Nutritional Risk Screening 2002 (NRS-2002), and malnutrition was diagnosed by GLIM criteria. The third lumbar vertebrae (L3-SMI) were used to represent the muscle mass in GLIM criteria. The variables associated with overall mortality were assessed by multivariate Cox regression analyses. RESULTS: The incidence of malnutrition diagnosed by GLIM criteria was 49.7% (179/360) in patients with HCC. If reduced muscle mass was not included in GLIM criteria, the prevalence of malnutrition was 31.7% (114/360). GLIM-defined malnutrition (HR = 1.979, 95%CI 1.019-3.841, P = 0.044) was independently associated with overall mortality in patients with HCC. However, the GLIM-defined malnutrition (without muscle mass) was not associated with overall mortality (HR = 0.863, 95%CI 0.399-1.867, P = 0.709). CONCLUSIONS: Skeletal muscle mass is an integral component of the GLIM criteria for patients with HCC. The malnutrition is common in patients with HCC, and malnourishment is associated with higher overall mortality. GLIM criteria are recommended to assess the nutritional status of hospitalized patients with HCC, which is recommended and can be used as the basis for nutritional interventions.

Were there any missing mediators between visual impairment and anxiety symptoms? Results from Chinese Longitudinal Healthy Longevity Survey.

Introduction: Visual impairment, encompassing low visual acuity and visual field loss, significantly impacts the older adult population worldwide, leading to increased disability and mortality risks. Recent studies suggest a strong association between visual impairment and anxiety, particularly among older adults. This study aims to explore the relationship between visual impairment and anxiety symptoms in older adult individuals in China, and to investigate potential mediating factors. Methods: Data for this study were derived from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS), including 11,702 participants aged 65 and older. Visual impairment was assessed through self-reported visual function, while anxiety symptoms were measured using the 7-item Generalized Anxiety Disorder scale (GAD-7). Additional assessments included sleep quality and duration, exercise status, and dietary diversity. Logistic regression models and mediation analysis were employed to explore associations and mediating effects. Results: The findings indicate that visual impairment is significantly associated with increased anxiety symptoms among the older adult (OR = 1.51, 95% CI: 1.32-1.72, p < 0.001). Mediation analysis revealed that sleep quality, dietary diversity score (DDS), and plant-based DDS significantly mediated the relationship between visual impairment and anxiety. In contrast, sleep duration, exercise, and animal-based DDS did not show significant mediating effects. Conclusion: Visual impairment is a crucial predictor of anxiety symptoms in the older adult. Improving sleep quality and promoting a diverse plant-based diet may mitigate anxiety symptoms in this population. Interventions targeting these areas could enhance the mental health and quality of life of older adult individuals with visual impairment.

Transgenerational response of germline histone acetyltransferases and deacetylases to nanoplastics at predicted environmental doses in Caenorhabditis elegans.

Nanoplastics could cause toxic effects on organism and their offsprings; however, how this transgenerational toxicity is formed remains largely unclear. We here examined potential involvement of germline histone acetylation regulation in modulating transgenerational toxicity of polyetyrene nanoparticle (PS-NP) in Caenorhabditis elegans. At parental generation (P0-G), PS-NP (1-100 µg/L) decreased expressions of germline cbp-1 and taf-1 encoding histone acetyltransferases, as well as germline expressions of sir-2.1 and hda-3 encoding histone deacetylase. Decrease in these 4 germline genes were also observed in the offspring of PS-NP (1-100 µg/L) exposed nematodes. Germline RNAi of cbp-1, taf-1, sir-2.1 and hda-3 resulted in more severe transgenerational PS-NP toxicity on locomotion and brood size. Meanwhile, in PS-NP exposed nematodes, germline RNAi of cbp-1, taf-1, sir-2.1 and hda-3 increased expression of genes encoding insulin, FGF, Wnt, and/or Notch ligands and expressions of their receptor genes in the offspring. Susceptibility to transgenerational PS-NP toxicity in cbp-1(RNAi), taf-1(RNAi), sir-2.1(RNAi), and hda-3 (RNAi) was inhibited by RNAi of these germline ligands genes. Moreover, histone deacetylase inhibition served as molecular initiating event (MIE) leading to transgenerational toxicity in epigenetic adverse outcome pathway (AOP) for nanoplastics. Our data provided evidence that germline histone acetylation regulation functioned as an important mechanism for transgenerational toxicity of nanoplastics at predicted environmental doses (PEDs) by affecting secreted ligands in organisms.

Activated hedgehog and insulin ligands by decreased transcriptional factor DAF-16 mediate transgenerational nanoplastic toxicity in Caenorhabditis elegans.

In Caenorhabditis elegans, transcriptional factor DAF-16 in insulin signaling pathway played important role in regulating transgenerational nanoplastic toxicity. Activation of insulin signals mediated transgenerational toxicity of polystyrene nanoparticle (PS-NP) by inhibiting DAF-16. Among identified germline ligands, expression of wrt-3 encoding hedgehog ligand was increased by RNAi of daf-16 in PS-NP exposed C. elegans. In PS-NP exposed C. elegans, expressions of 4 other germline hedgehog ligand genes and 10 hedgehog receptor genes were increased by daf-16 RNAi. Among these candidate genes, expressions of hedgehog ligand genes (grl-15, grl-16, qua-1, and wrt-1) and hedgehog receptor genes (ptr-23, scp-1, ptd-2, and ncr-1) could be increased by PS-NP (1-100 µg/L), and their transgenerational expressions were observed after PS-NP exposure. RNAi of grl-15, grl-16, qua-1, wrt-1, ptr-23, scp-1, ptd-2, and ncr-1 caused resistance to transgenerational PS-NP toxicity. In nematodes exposed to PS-NPs, RNAi of wrt-3, grl-15, grl-16, qua-1, and wrt-1 at parental generation (P0-G) inhibited expressions of ptr-23, scp-1, ptd-2, and ncr-1 in their offspring. Moreover, we observed increased expressions of insulin peptides genes (ins-3, ins-39, and daf-28) in PS-NP exposed daf-16(RNAi) nematodes, suggesting formation of feedback loop. We raise the molecular basis for formation of toxicity on multiple generations after nanoplastic exposure at P0-G.

6-PPD quinone at environmentally relevant concentrations induced damage on longevity in C. elegans: Mechanistic insight from inhibition in mitochondrial UPR response.

6-PPD quinone (6-PPDQ) exists widely in water environment media, causing acute lethality to some aquatic species. Long-term exposure to 6-PPDQ reduced the lifespan of Caenorhabditis elegans. However, the molecular basis for mitochondrial control of 6-PPDQ toxicity remains largely unclear. Using HSP-6 as marker of mitochondrial unfolded protein response (mt UPR), we observed activation of mt UPR by 0.1 and 1 µg/L 6-PPDQ and inhibition in mt UPR by 10 µg/L 6-PPDQ. Additionally, increased atfs-1, ubl-5, and dve-1 expressions were caused by 0.1 and 1 µg/L 6-PPDQ and decreased expressions of these genes were induced by 10 µg/L 6-PPDQ. Neuronal and intestinal RNA interference (RNAi) of hsp-6 caused susceptibility to 6-PPDQ toxicity on longevity, and atfs-1, ubl-5, and dve-1 acted in neurons and intestine to modulate mt UPR and 6-PPDQ toxicity on longevity. Meanwhile, 6-PPDQ (1 and 10 µg/L) increased expressions of histone methyltransferase genes met-2 and set-6, and decreased expressions of histone demethylase genes jmjd-1.2 and jmjd-3.1. Neuronal RNAi of set-6 and intestinal RNAi of met-2 accelerated hsp-6, atfs-1, ubl-5, and dve-1 expressions and extended lifespan of 6-PPDQ exposed nematodes. In contrast, neuronal RNAi of jmjd-1.2 and jmjd-3.1 and intestinal RNAi of jmjd-1.2 suppressed these 4 gene expressions and reduced lifespan of 6-PPDQ exposed nematodes o. In nematodes, RNAi of hsp-6 could also enhance mitochondrial dysfunction and mitochondrial reactive oxygen species (ROS) induced by 6-PPDQ. Therefore, 6-PPDQ caused damage on longevity was associated with suppression in mt UPR, which was under regulation of certain histone methylation related signals.

Isolation of anti-tumor monoclonal antibodies targeting on MICA/B α3 domain by single B cell technology for colon cancer therapy.

Colon cancer (CC) is one of the most common gastrointestinal malignancies. Effectiveness of the existing therapies is limited. Immunotherapy is a promising complementary treatment approach for CC. Major histocompatibility complex class I-related protein A and B (MICA/B) are ligands for NK cells. Shedding of MICA/B from the surface of tumor cells by cleavage of MICA/B at the membrane proxial region in MICA/B α3 structural domain is one of immune evasion strategies leading to escape of cancer cells from immunosurveillance. In this study, we generated a panel of MICA/B monoclonal antibodies (mAbs) and identified one of mAbs, mAb RDM028, that had high binding affinity to MICA/B and recognized a site on MICA/B α3 structural domain that is critically important for cleavage of MICA/B. Our study has further demonstrated that RDM028 augmented the surface expression of MICA/B on HCT-116 human CC cells by inhibiting the MICA/B shedding resulting in the enhanced cyotoxicity of NK cells against HCT-116 human CC cells and mediated anti-tumor activity in nude mouse model of colon cancer. These results indicate that mAb RDM028 could be explored for developing as an effective immuno therapy against CC by targeting the MICA/B α3 domain to promot immunosurveillance mediated by MICA/B-NKG2D interaction.

GLIM-defined malnutrition in patients with acute abdomen associated with poor prognosis and increased economic burden: A cross-sectional study.

BACKGROUND: The Global Leadership Initiative on Malnutrition (GLIM) criteria have rapidly developed into a principal methodological framework for nutrition diagnosis. However, the applicability of the GLIM criteria in patients with acute abdomen has not been validated. METHODS: This is a cross-sectional study conducted on patients diagnosed with acute abdomen and admitted to a tertiary hospital in southwest China. Nutrition risk screening was conducted using the Nutrition Risk Screening 2002, and patients identified with nutrition risk were assessed for malnutrition based on the GLIM criteria. RESULTS: We enrolled a total of 440 patients with acute abdomen. The top three diagnoses of acute abdomen were intestinal obstruction (47.2%), acute appendicitis (23.1%), and digestive system perforation (8.8%). The prevalence of nutrition risk was 46.5%, with a malnutrition rate of 32.5% based on the GLIM. Patients with malnutrition according to the GLIM showed significantly higher rates of intensive care unit (ICU) admission (13.28% vs 7.07%; P = 0.003), increased hospitalization costs (median: 3315USD [interquartile range (IQR): 978-7852] vs 1641 [IQR: 816-3523] USD; P < 0.001), and longer length of hospital stay (LOS) (median: 8 [IQR: 5-13] vs 6 [IQR: 4-8] days; P < 0.001) compared with patients without malnutrition. Multivariate analysis indicated that GLIM-defined malnutrition was an independent predictor of hospitalization costs, and severe malnutrition was an independent predictor of ICU admission. CONCLUSION: GLIM criteria are applicable for diagnosing malnutrition in patients with acute abdomen. The prevalence of malnutrition was high in patients with acute abdomen. Malnutrition was associated with increased ICU admission and LOS, along with higher economic burden.

Racial and social-economic inequalities in systemic chemotherapy use among adult glioblastoma patients following surgery and radiotherapy.

Not all patients with glioblastoma multiforme (GBM) eligible for systemic chemotherapy after upfront surgery and radiotherapy finally receive it. The information on patients with GBM was retrieved from the surveillance, epidemiology, and end results database. Patients who underwent upfront surgery or biopsy and external beam radiotherapy between 2010 and 2019 were eligible for systemic chemotherapy. The available patient and tumor characteristics were assessed using multivariable logistic regression and chi-squared test. Out of the 16,682 patients eligible, 92.1% underwent systemic chemotherapy. The characteristics linked to the lowest systemic chemotherapy utilization included tumors of the brain stem/cerebellum (P = 0.01), former years of diagnosis (P = 0.001), ≥ 80 years of age (P < 0.001), Hispanic, Non-Hispanic Asian, Pacific Islander, or Black race (P < 0.001), non-partnered status (P < 0.001), and low median household income (P = 0.006). Primary tumor site, year of diagnosis, age, race, partnered status, and median household income correlated with the omission of systemic chemotherapy in GBM in adult patients.

Nanoplastic at environmentally relevant concentrations induces toxicity across multiple generations associated with inhibition in germline G protein-coupled receptor CED-1 in Caenorhabditis elegans.

Nanoplastics at environmentally relevant concentrations (ERCs) could cause transgenerational toxicity on organisms. Caenorhabditis elegans is an important model for the study of transgenerational toxicology of pollutants. Nevertheless, the underlying mechanisms for the control of transgenerational nanoplastic toxicity by germline signals remain largely unclear. In C. elegans, exposure to 1-100 µg/L polystyrene nanoparticle (PS-NP) decreased expression of germline ced-1 encoding a G protein-coupled receptor at parental generation (P0-G). After PS-NP exposure at P0-G, transgenerational decrease in germline ced-1 expression could be detected. Meanwhile, the susceptibility to transgenerational PS-NP toxicity was observed in ced-1(RNAi) animals. After PS-NP exposure at P0-G, germline RNAi of ced-1 increased expressions of met-2 and set-6 encoding histone methylation transferases. The susceptibility of ced-1(RNAi) to transgenerational PS-NP toxicity could be inhibited by RNAi of met-2 and set-6. Moreover, in PS-NP exposed met-2(RNAi) and set-6(RNAi) nematodes, expressions of ins-39, wrt-3, and/or efn-3 encoding secreted ligands were decreased. Therefore, our results demonstrated that inhibition in germline CED-1 mediated the toxicity induction of nanoplastics at ERCs across multiple generations in nematodes.

Trends and hotspots in gastrointestinal neoplasms risk assessment: A bibliometric analysis from 1984 to 2022.

BACKGROUND: Gastrointestinal neoplasm (GN) significantly impact the global cancer burden and mortality, necessitating early detection and treatment. Understanding the evolution and current state of research in this field is vital. AIM: To conducts a comprehensive bibliometric analysis of publications from 1984 to 2022 to elucidate the trends and hotspots in the GN risk assessment research, focusing on key contributors, institutions, and thematic evolution. METHODS: This study conducted a bibliometric analysis of data from the Web of Science Core Collection database using the "bibliometrix" R package, VOSviewer, and CiteSpace. The analysis focused on the distribution of publications, contributions by institutions and countries, and trends in keywords. The methods included data synthesis, network analysis, and visualization of international collaboration networks. RESULTS: This analysis of 1371 articles on GN risk assessment revealed a notable evolution in terms of research focus and collaboration. It highlights the United States' critical role in advancing this field, with significant contributions from institutions such as Brigham and Women's Hospital and the National Cancer Institute. The last five years, substantial advancements have been made, representing nearly 45% of the examined literature. Publication rates have dramatically increased, from 20 articles in 2002 to 112 in 2022, reflecting intensified research efforts. This study underscores a growing trend toward interdisciplinary and international collaboration, with the Journal of Clinical Oncology standing out as a key publication outlet. This shift toward more comprehensive and collaborative research methods marks a significant step in addressing GN risks. CONCLUSION: This study underscores advancements in GN risk assessment through genetic analyses and machine learning and reveals significant geographical disparities in research emphasis. This calls for enhanced global collaboration and integration of artificial intelligence to improve cancer prevention and treatment accuracy, ultimately enhancing worldwide patient care.

Research on intelligent forecasts of flight actions based on the implemented bi-LSTM.

Rapid identification of flight actions by utilizing flight data is more realistic so the quality of flight training can be objectively assessed. The bidirectional long short-term memory (bi-LSTM) algorithm is implemented to forecast the flight actions of aircraft. The dataset containing the flight actions is structured by collecting tagged flight data when real flight training is exercised. However, the dataset needs to be preprocessed and annotated with expert rules. One of the deep learning (DL) methods, called the bi-LSTM algorithm, is implemented to train and test, and the pivotal parameters of the algorithm are optimized. Finally, the constructed model is applied to forecast the flight actions of aircraft. The training's accuracy and loss rates are computed. The duration is kept between 1 through 3 h per session. Thus, the development of training the model is continued until an accuracy rate above 85% is achieved. The word-run inference time is kept under 2 s. Finally, the proposed algorithm's specific characteristics, which are short training time and high recognition accuracy, are achieved when complex rules and large sample sizes exist.

Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury.

ABSTRACT: The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury. Regulation of shifting microglia polarization from M1 (neurotoxic and proinflammatory type) to M2 (neuroprotective and anti-inflammatory type) after spinal cord injury appears to be crucial. Tryptanthrin possesses an anti-inflammatory biological function. However, its roles and the underlying molecular mechanisms in spinal cord injury remain unknown. In this study, we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro. Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway. Additionally, we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury, inhibited neuronal loss, and promoted tissue repair and functional recovery in a mouse model of spinal cord injury. Finally, using a conditional co-culture system, we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis. Taken together, these results suggest that by targeting the cGAS/STING/NF-κB axis, tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

Geniposide alleviates heart failure with preserved ejection fraction in mice by regulating cardiac oxidative stress via MMP2/SIRT1/GSK3ß pathway.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome with cardiac dysfunction, fluid retention and reduced exercise tolerance as the main manifestations. Current treatment of HFpEF is using combined medications of related comorbidities, there is an urgent need for a modest drug to treat HFpEF. Geniposide (GE), an iridoid glycoside extracted from Gardenia Jasminoides, has shown significant efficacy in the treatment of cardiovascular, digestive and central nervous system disorders. In this study we investigated the therapeutic effects of GE on HFpEF experimental models in vivo and in vitro. HFpEF was induced in mice by feeding with HFD and L-NAME (0.5 g/L) in drinking water for 8 weeks, meanwhile the mice were treated with GE (25, 50 mg/kg) every other day. Cardiac echocardiography and exhaustive exercise were performed, blood pressure was measured at the end of treatment, and heart tissue specimens were collected after the mice were euthanized. We showed that GE administration significantly ameliorated cardiac oxidative stress, inflammation, apoptosis, fibrosis and metabolic disturbances in the hearts of HFpEF mice. We demonstrated that GE promoted the transcriptional activation of Nrf2 by targeting MMP2 to affect upstream SIRT1 and downstream GSK3ß, which in turn alleviated the oxidative stress in the hearts of HFpEF mice. In H9c2 cells and HL-1 cells, we showed that treatment with GE (1 µM) significantly alleviated H2O2-induced oxidative stress through the MMP2/SIRT1/GSK3ß pathway. In summary, GE regulates cardiac oxidative stress via MMP2/SIRT1/GSK3ß pathway and reduces cardiac inflammation, apoptosis, fibrosis and metabolic disorders as well as cardiac dysfunction in HFpEF. GE exerts anti-oxidative stress properties by binding to MMP2, inhibiting ROS generation in HFpEF through the SIRT1/Nrf2 signaling pathway. In addition, GE can also affect the inhibition of the downstream MMP2 target GSK3ß, thereby suppressing the inflammatory and apoptotic responses in HFpEF. Taken together, GE alleviates oxidative stress/apoptosis/fibrosis and metabolic disorders as well as HFpEF through the MMP2/SIRT1/GSK3ß signaling pathway.

Prognostic significance of the novel immunonutritional marker of cholesterol-to-lymphocyte ratio in patients with non-metastatic breast cancer.

BACKGROUND: Although there is a strong correlation between the novel cholesterol-to-lymphocyte ratio (CLR) and tumor survival, its prognostic significance in breast cancer (BC) is unknown. After analyzing the relationship between CLR and the overall survival (OS) of patients with BC, we created a predictive model. METHODS: Following retrospective enrollment, 1316 patients with BC were randomized into two cohorts: validation (n = 392) and training (n = 924). Distinct factors within the training dataset were identified for OS by univariate and multivariate Cox analyses; two-tailed P-value < 0.05 were considered to indicate statistical significance. On this premise, we developed novel signals for survival prediction and utilized the calibration curve, receiver operating characteristic curves, and concordance index (C-index) to validate their efficacy across both datasets. RESULTS: Patients with BC were categorized into two categories with differing prognoses based on the CLR score [hazard ratio = 0.492; 95% confidence interval (CI): 0.286-0.846, P = 0.009]. A prediction nomogram was created based on multivariate analysis, which showed that N stage, postoperative pathological categorization, and CLR score were all independently correlated with OS. In the training [C-index = 0.831 (95% CI: 0.788-0.874)] and validation [C-index = 0.775 (95% CI: 0.694-0.856)] cohorts, the nomogram demonstrated favorable performance in predicting OS. In both the training and validation cohorts, it outperformed the traditional staging system [C-index = 0.702 (95% CI: 0.623-0.782)] and [C-index = 0.709 (95% CI: 0.570-0.847)]. The accurate prediction by the signature was further demonstrated by the time-dependent receiver operating characteristic curves. CONCLUSIONS: The novel immunonutritional marker CLR could function as a simplified, cost-effective, easily accessible, non-invasive, and readily promotive prognostic indicator for patients with early-stage BC and demonstrates superior predictive power than the traditional staging system.

Hormone receptor expression in low-grade adenosquamous carcinoma of the breast progressing to high-grade metaplastic carcinoma: A case report.

RATIONALE: Breast low-grade adenosquamous carcinoma is an uncommon cancer that has been neglected in genetic and pathophysiological research. Consequently, medical practitioners face challenges in the effective diagnosis and treatment of this condition. PATIENT CONCERNS: We present the case of a 57-year-old Asian female patient who presented with bilateral breast masses on physical examination. Ultrasound and an MRI revealed a highly suspicious malignant mass in her right breast that was completely removed surgically. DIAGNOSES: After pathological analysis, the diagnosis was low-grade adenosquamous carcinoma with local high-grade transformation, and some of the tumor components were estrogen receptor positive. INTERVENTIONS: The patient underwent appropriate postoperative chemotherapy and achieved a favorable outcome. OUTCOMES: During the follow-up period after surgical resection, the patient did not experience any local recurrence or distant metastasis. LESSONS: Owing to the rare combination of estrogen receptor positivity and high-grade progression, this patient also required adjuvant chemotherapy. This enhances the essential foundation for diagnosing and treating this rare disease, and facilitates the implementation of treatment plans.

Efficacy of tacrolimus monotherapy in primary membranous nephropathy.

Objective: The aim of this study was to observe the remission of primary membranous nephropathy (PMN) and evaluate the efficacy of tacrolimus (TAC) monotherapy for PMN in comparison with TAC combined with a low-dose glucocorticoid (GC) protocol (TAC + GC). Methods: This was tested in a prospective monocentric observational trial of 70 patients with PMN, of whom 34 received TAC (0.05-0.075 mg/kg/day) or 36 received TAC (0.05-0.075 mg/kg/day) and GC (0.3-0.5 mg/kg/day of prednisone). Results: At 3, 6, 9, and 12 months of treatment, the effective rates in the TAC group and the TAC + GC group were similar (P > 0.05). The urinary protein quantification was reduced in patients under both therapeutic protocols, and the differences in the proteinuria quantification at 3, 6, 9, and 12 months of treatment were not statistically significant between the two groups (P > 0.05). The overall incidence of adverse reactions in the TAC group was lower than that in the TAC + GC group (23.5% < 36.1%), and the difference was statistically significant (P < 0.05). Conclusion: TAC monotherapy for PMN could effectively reduce urinary protein quantification and increase serum albumin levels. Compared with TAC + GC, TAC monotherapy for PMN had no difference in efficacy and fewer incidences of adverse reactions.

Longitudinal changes in sarcopenia was associated with survival among cirrhotic patients.

Background: Sarcopenia is common in patients with liver cirrhosis and is an independent predictor of multiple clinical outcomes. Most studies to date have used a static assessment of sarcopenia. However, there is very limited data evaluating the temporal course of muscle area in cirrhosis. To bridge this gap in clinical studies, we performed a longitudinal analysis to evaluate the impact of changes in sarcopenia for cirrhotic patients. Methods: Adult patients with clinically diagnosed liver cirrhosis who underwent at least 2 abdominal computed tomography (CT) scans in the hospital were enrolled. The interval between the two abdominal scans was 6 ± 1 months. Patients were categorized into persistent non-sarcopenia, new-onset sarcopenia, sarcopenia to non-sarcopenia, and persistent sarcopenia based on changes in sarcopenia. Kaplan-Meier method and Log-rank tests were used to separately compare unadjusted survival curves by different statuses of sarcopenia. Cox regression analysis was performed to assess the associations between different states of sarcopenia and overall mortality. The association between persistent non-sarcopenia and new-onset sarcopenia was analyzed by multivariate logistic regression analysis. Results: A total of 307 patients were included for analysis. At the second assessment, 10.10% (31/307) patients were new-onset sarcopenia, 27.69% (85/307) with persistent sarcopenia status, while 13.03% (40/307) patients with sarcopenia developed non-sarcopenia and 49.19% (151/307) with persistent non-sarcopenia status. The overall survival rate was significantly lower in the persistent sarcopenia and new-onset sarcopenia than in the non-sarcopenia group and sarcopenia to non-sarcopenia group (p < 0.001). Persistent sarcopenia (HR 5.799, 95%CI 1.563-21.521, p = 0.009) and new onset sarcopenia (HR 5.205, 95%CI 1.482-18.282, p = 0.010) were identified as poor prognostic factors for cirrhotic patients. The etiology of cirrhosis and the initial skeletal muscle mass were independent risk factors for new-onset sarcopenia. Conclusion: Sarcopenia is a dynamically changing process in patients with cirrhosis. Persistent and new-onset sarcopenia were independently and robustly associated with overall survival.

ALKBH5 promotes non-small cell lung cancer progression and susceptibility to anti-PD-L1 therapy by modulating interactions between tumor and macrophages.

BACKGROUND: Understanding the mechanisms that mediate the interaction between tumor and immune cells may provide therapeutic benefit to patients with cancer. The N6-methyladenosine (m6A) demethylase, ALKBH5 (alkB homolog 5), is overexpressed in non-small cell lung cancer. However, its role in the tumor microenvironment is unknown. METHODS: Datasets and tissue samples were used to determine the relationship between ALKBH5 expression and immunotherapy efficacy. Bioinformatic analysis, colorimetric assay to determine m6A RNA methylation, dual luciferase reporter assay, RNA/m6A-modified RNA immunoprecipitation, RNA stability assay, and RNA sequencing were used to investigate the regulatory mechanism of ALKBH5 in non-small cell lung cancer. In vitro and in vivo assays were performed to determine the contribution of ALKBH5 to the development of non-small cell lung cancer. RESULTS: ALKBH5 was upregulated in primary non-small cell lung cancer tissues. ALKBH5 was positively correlated with programmed death-ligand 1 expression and macrophage infiltration and was associated with immunotherapy response. JAK2 was identified as a target of ALKBH5-mediated m6A modification, which activates the JAK2/p-STAT3 pathway to promote non-small cell lung cancer progression. ALKBH5 was found to recruit programmed death-ligand 1-positive tumor-associated macrophages and promote M2 macrophage polarization by inducing the secretion of CCL2 and CXCL10. ALKBH5 and tumor-associated macrophage-secreted IL-6 showed a synergistic effect to activate the JAK2/p-STAT3 pathway in cancer cells. CONCLUSIONS: ALKBH5 promotes non-small cell lung cancer progression by regulating cancer and tumor-associated macrophage behavior through the JAK2/p-STAT3 pathway and the expression of CCL2 and CXCL10, respectively. These findings suggest that targeting ALKBH5 is a promising strategy of enhancing the anti-tumor immune response in patients with NSCLC and that identifying ALKBH5 status could facilitate prediction of clinical response to anti-PD-L1 immunotherapy.