Prediction of miRNAs and diseases association based on sparse autoencoder and MLP.

Introduction: MicroRNAs (miRNAs) are small and non-coding RNA molecules which have multiple important regulatory roles within cells. With the deepening research on miRNAs, more and more researches show that the abnormal expression of miRNAs is closely related to various diseases. The relationship between miRNAs and diseases is crucial for discovering the pathogenesis of diseases and exploring new treatment methods. Methods: Therefore, we propose a new sparse autoencoder and MLP method (SPALP) to predict the association between miRNAs and diseases. In this study, we adopt advanced deep learning technologies, including sparse autoencoder and multi-layer perceptron (MLP), to improve the accuracy of predicting miRNA-disease associations. Firstly, the SPALP model uses a sparse autoencoder to perform feature learning and extract the initial features of miRNAs and diseases separately, obtaining the latent features of miRNAs and diseases. Then, the latent features combine miRNAs functional similarity data with diseases semantic similarity data to construct comprehensive miRNAs-diseases datasets. Subsequently, the MLP model can predict the unknown association among miRNAs and diseases. Result: To verify the performance of our model, we set up several comparative experiments. The experimental results show that, compared with traditional methods and other deep learning prediction methods, our method has significantly improved the accuracy of predicting miRNAs-disease associations, with 94.61% accuracy and 0.9859 AUC value. Finally, we conducted case study of SPALP model. We predicted the top 30 miRNAs that might be related to Lupus Erythematosus, Ecute Myeloid Leukemia, Cardiovascular, Stroke, Diabetes Mellitus five elderly diseases and validated that 27, 29, 29, 30, and 30 of the top 30 are indeed associated. Discussion: The SPALP approach introduced in this study is adept at forecasting the links between miRNAs and diseases, addressing the complexities of analyzing extensive bioinformatics datasets and enriching the comprehension contribution to disease progression of miRNAs.

Fangchinoline inhibits mouse oocyte meiosis by disturbing MPF activity.

Fangchinoline (FA) is an alkaloid derived from the traditional Chinese medicine Fangji. Numerous studies have shown that FA has a toxic effect on various cancer cells, but little is known about its toxic effects on germ cells, especially oocytes. In this study, we investigated the effects of FA on mouse oocyte maturation and its potential mechanisms. Our results showed that FA did not affect meiosis resumption but inhibited the first polar body extrusion. This inhibition is not due to abnormalities at the organelle level, such as chromosomes and mitochondrial, which was proved by detection of DNA damage and reactive oxygen species Further studies revealed that FA arrested the oocyte at the metaphase I stage, and this arrest was not caused by abnormal kinetochore-microtubule attachment or spindle assembly checkpoint activation. Instead, FA inhibits the activity of anaphase-promoting complexes (APC/C), as evidenced by the inhibition of CCNB1 degeneration. The decreased activity of APC/C may be due to a reduction in CDC25B activity as indicated by the high phosphorylation level of CDC25B (Ser323). This may further enhance Maturation-Promoting Factor (MPF) activity, which plays a critical role in meiosis. In conclusion, our study suggests that the metaphase I arrest caused by FA may be due to abnormalities in MPF and APC/C activity.

Association between body mass index and lymph node metastasis among women with cervical cancer: a systematic review and network meta-analysis.

PURPOSE: Lymph node status is a determinant of survival in patients with early-stage cervical cancer. However, the relationship between obesity and lymph node status remains unclear. Therefore, this systematic review aims to evaluate the correlation between body mass index (BMI) and lymph node metastasis in cervical cancer. METHODS: Cohort studies through six databases were reviewed until December 2021. Odds ratios (ORs) for lymphatic metastasis were estimated using random-effects models and network meta-analysis. BMI groups for lymph node metastasis were ranked. Heterogeneities were assessed using I2. Subgroup analyses were performed to determine possible sources of heterogeneity. RESULTS: No significant difference was found between obese (BMI ≥ 25) and non-obese patients (BMI < 25) (OR = 1.01; 95% CI 0.69-1.47; P = 0.97). In subgroup analyses, obesity was associated with higher risk among the Americans and advanced-stage patients. The grouping analysis based on BMI and the rankogram values revealed that the '35 ≤ BMI' group had the highest risk of lymph node metastasis. CONCLUSION: Although there were no significant differences in lymph node metastasis between obese and non-obese cervical cancer patients in overall analysis, patients with BMI ≥ 35 were at significantly higher risk of lymph node metastasis.

Single-cell analyses reveal evolution mimicry during the specification of breast cancer subtype.

Background: The stem or progenitor antecedents confer developmental plasticity and unique cell identities to cancer cells via genetic and epigenetic programs. A comprehensive characterization and mapping of the cell-of-origin of breast cancer using novel technologies to unveil novel subtype-specific therapeutic targets is still absent. Methods: We integrated 195,144 high-quality cells from normal breast tissues and 406,501 high-quality cells from primary breast cancer samples to create a large-scale single-cell atlas of human normal and cancerous breasts. Potential heterogeneous origin of malignant cells was explored by contrasting cancer cells against reference normal epithelial cells. Multi-omics analyses and both in vitro and in vivo experiments were performed to screen and validate potential subtype-specific treatment targets. Novel biomarkers of identified immune and stromal cell subpopulations were validated by immunohistochemistry in our cohort. Results: Tumor stratification based on cancer cell-of-origin patterns correlated with clinical outcomes, genomic aberrations and diverse microenvironment constitutions. We found that the luminal progenitor (LP) subtype was robustly associated with poor prognosis, genomic instability and dysfunctional immune microenvironment. However, the LP subtype patients were sensitive to neoadjuvant chemotherapy (NAC), PARP inhibitors (PARPi) and immunotherapy. The LP subtype-specific target PLK1 was investigated by both in vitro and in vivo experiments. Besides, large-scale single-cell profiling of breast cancer inspired us to identify a range of clinically relevant immune and stromal cell subpopulations, including subsets of innate lymphoid cells (ILCs), macrophages and endothelial cells. Conclusion: The present single-cell study revealed the cellular repertoire and cell-of-origin patterns of breast cancer. Combining single-cell and bulk transcriptome data, we elucidated the evolution mimicry from normal to malignant subtypes and expounded the LP subtype with vital clinical implications. Novel immune and stromal cell subpopulations of breast cancer identified in our study could be potential therapeutic targets. Taken together, Our findings lay the foundation for the precise prognostic and therapeutic stratification of breast cancer.

A Case of Invasive Pulmonary Aspergillosis.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a deep fungal infection caused by invasion of Aspergillus mycelium into the lung parenchyma resulting in tissue destruction and necrosis, which occurs more often in im-munosuppressed populations. The severity of the disease and the rapid progression of the lung lesions puts pa¬tients at high risk of death and poor prognosis if the correct therapeutic intervention is not given as early as possible. METHODS: Here we report a case of IPA, which was initially diagnosed as community-acquired pneumonia in a local hospital. The symptoms did not improve after receiving anti-infective treatment. The patient was diagnosed with IPA after completing a chest CT examination and an electronic bronchoscopy, as well as pathogenetic examination of the bronchoalveolar lavage fluid and pathological examination of the left bronchial mass in the respiratory department of our hospital, which was finally diagnosed as IPA. After one week of administration of voriconazole for anti-fungal infection treatment, the patient's symptoms improved significantly, and a repeat chest CT suggested that the lung lesions were better than before. In order to raise clinicians' awareness of this disease, we also conducted a literature analysis. RESULTS: The final diagnosis of IPA was made by analyzing the patient's history, symptoms, signs, and relevant findings. CONCLUSIONS: When the patient's clinical symptoms and imaging manifestations are consistent with IPA, electronic bronchoscopy and pathogenetic and pathological examinations may be appropriately performed to clarify the na-ture of the lesion. More consideration should be given to the possibility of disease diagnosis to avoid misdiagnosis and underdiagnosis. Appropriate treatment should be given at an early stage.

A Case of IgG4 Related Lung Disease.

BACKGROUND: IgG4-related disease (IgG4-RD) is an immune-mediated systemic inflammatory fibrotic disease, which is a relatively rare and novel disease that can involve multiple organs or tissues, with variable clinical manifestations, and for which pulmonary involvement has been reported relatively infrequently. METHODS: Here we report a case of pulmonary infection that was initially suspected and received anti-inflammatory treatment, but the symptoms did not improve. CT examination indicated progression of the pulmonary lesion, and the nature of the lesion could not be determined by tracheoscopy and bronchoalveolar lavage. The diagnosis of IgG4 related lung disease (IgG4-RLD) was confirmed by percutaneous lung biopsy. A joint literature analysis was conducted to improve clinicians' understanding of this disease. RESULTS: The patient's history, symptoms, signs and relevant examination results were analyzed. The final diagnosis was IgG4-RLD. CONCLUSIONS: When the clinical symptoms and imaging manifestations of the patients are consistent with IgG4-RLD, pathological examination can be appropriately performed to clarify the nature of the lesions. More consideration should be given to the possibility of disease diagnosis to avoid misdiagnosis and underdiagnosis, and proper treatment should be given at an early stage.

Optical enhancement mode 2 improves the detection rate of gastric neoplastic lesion in high-risk populations: A multicenter randomized controlled clinical study.

OBJECTIVES: Detection of early neoplastic lesions is crucial for improving the survival rates of patients with gastric cancer. Optical enhancement mode 2 is a new image-enhanced endoscopic technique that offers bright images and can improve the visibility of neoplastic lesions. This study aimed to compare the detection of neoplastic lesions with optical enhancement mode 2 and white-light imaging (WLI) in a high-risk population. METHODS: In this prospective multicenter randomized controlled trial, patients were randomly assigned to optical enhancement mode 2 or WLI groups. Detection of suspicious neoplastic lesions during the examinations was recorded, and pathological diagnoses served as the gold standard. RESULTS: A total of 1211 and 1219 individuals were included in the optical enhancement mode 2 and WLI groups, respectively. The detection rate of neoplastic lesions was significantly higher in the optical enhancement mode 2 group (5.1% vs. 1.9%; risk ratio, 2.656 [95% confidence interval, 1.630-4.330]; p < 0.001). The detection rate of neoplastic lesions with an atrophic gastritis background was significantly higher in the optical enhancement mode 2 group (8.6% vs. 2.6%, p < 0.001). The optical enhancement mode 2 group also had a higher detection rate among endoscopists with different experiences. CONCLUSIONS: Optical enhancement mode 2 was more effective than WLI for detecting neoplastic lesions in the stomach, and can serve as a new method for screening early gastric cancer in clinical practice. CLINICAL REGISTRY: United States National Library of Medicine (https://www. CLINICALTRIALS: gov), ID: NCT040720521.

p27Kip1 and cytoplasmic pSer10p27 are promising biomarkers for predicting prognosis and chemotherapy response in ovarian cancer.

PURPOSE: The biological function of p27Kip1 largely depends on its subcellular localization and phosphorylation status. Different subcellular localizations and phosphorylation statuses of p27Kip1 may represent distinct clinical values, which are unclear in ovarian cancer. This study aimed to elucidate different subcellular localizations of p27Kip1 and pSer10p27 in predicting prognosis and chemotherapy response in ovarian cancer. METHODS: Meta-analyses were executed to evaluate the association of p27Kip1 and phosphorylated p27Kip1 with the prognosis of ovarian cancer patients. The expression levels and patterns of p27Kip1 and pSer10p27 were evaluated by immunohistochemistry. The correlations between different p27Kip1 states, clinicopathological features, and prognosis were analyzed. p27Kip1 and pSer10p27 expression levels in cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines were detected using WB. KEGG analysis and WB were performed to evaluate the pathways in which p27Kip1 was involved. RESULTS: Meta-analyses showed that p27Kip1 was associated with significantly better overall survival (OS) in ovarian cancer (HR=2.14; 95% CI [1.71-2.68]) and pSer10p27 was associated with significantly poor OS in mixed solid tumors (HR=2.56; 95% CI [1.76-3.73]). In our cohort of ovarian cancer patients, low total p27Kip1 remained independent risk factors of OS (HR=2.097; 95% CI [1.121-3.922], P=0.021) and PFS (HR=2.483; 95% CI [1.364-4.518], P=0.003), while low cytoplasmic pSer10p27 had independent protective effects in terms of OS (HR=0.472; 95% CI [0.248-0.898], P=0.022) and PFS (HR=0.488; 95% CI [0.261-0.910], P=0.024). Patients with low total p27Kip1/pSer10p27 and low nuclear p27Kip1 had worse chemotherapy responses, while patients with low cytoplasmic pSer10p27 expression had better chemotherapy responses. The protein levels of p27Kip1 and pSer10p27 were significantly reduced in the cisplatin-resistant cell lines SKOV3-cDDP and A2780-cDDP, and the level of p27Kip1/pSer10p27 was subjective to Akt activation. CONCLUSIONS: The present study demonstrates that p27Kip1 and cytoplasmic pSer10p27 are promising biomarkers for predicting prognosis and chemotherapy response in ovarian cancer.

A Prediction Model for Prolonged Hospital Length of Stay (ProLOS) in Coronavirus Disease 2019 (COVID-19) Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the normalization of COVID-19 globally, it is crucial to construct a prediction model that enables clinicians to identify patients at risk for ProLOS based on demographics and serum inflammatory biomarkers. METHODS: The study included hospitalized patients with a confirmed diagnosis of COVID-19. These patients were randomly grouped into a training (80%) and a test (20%) cohort. The LASSO regression and ten-fold cross-validation method were applied to filter variables. The training cohort utilized multifactorial logistic regression analyses to identify the independent factors of ProLOS in COVID-19 patients. A 4-variable nomogram was created for clinical use. ROC curves were plotted, and the area under the curve (AUC) was calculated to evaluate the model's discrimination; calibration analysis was planned to assess the validity of the nomogram, and decision curve analysis (DCA) was used to evaluate the clinical usefulness of the model. RESULTS: The results showed that among 310 patients with COVID-19, 80 had extended hospitalization (80/310). Four independent risk factors for COVID-19 patients were identified: age, coexisting chronic respiratory diseases, white blood cell count (WBC), and serum albumin (ALB). A nomogram based on these variables was created. The AUC in the training cohort was 0.808 (95% CI: 0.75 - 0.8671), and the AUC in the test cohort was 0.815 (95% CI: 0.7031 - 0.9282). The model demonstrates good calibration and can be used with threshold probabilities ranging from 0% to 100% to obtain clinical net benefits. CONCLUSIONS: A predictive model has been created to accurately predict whether the hospitalization duration of COVID-19 patients will be prolonged. This model incorporates serum WBC, ALB levels, age, and the presence of chronic respiratory system diseases.

A Case of Organizing Pneumonia Resembling Lung Cancer.

BACKGROUND: Organizing pneumonia (OP) is a pathologic diagnosis with clinical and imaging manifestations that often resemble other diseases, such as infections and cancers, which can lead to delays in diagnosis and inappropriate management of the underlying disease. In this article, we present a case of organized pneumonia that resembles lung cancer. METHODS: We report a case of initial suspicion of pulmonary malignancy, treated with anti-inflammatory medication and then reviewed with CT suggesting no improvement, and finally confirmed to be OP by pathological biopsy taken via transbronchoscopy. A joint literature analysis was performed to raise clinicians' awareness of the diagnosis and treatment of OP. RESULTS: Initially, because of the atypical auxiliary findings, we thought that the disease turned out to be a lung tumor, which was eventually confirmed as OP by pathological diagnosis. CONCLUSIONS: The diagnosis and treatment of OP requires a combination of clinical information and radiological expertise, as well as biopsy to obtain histopathological evidence. That is, clinical-imaging-pathological tripartite cooperation and comprehensive analysis.

Transhepatic Bromelain and Acetylcysteine for Treatment of Posterior Gastric Pseudomyxoma Peritonei: A Case Report.

BACKGROUND/AIM: Pseudomyxoma peritonei (PMP) is a rare condition characterized by diffuse spread of mucinous tumors within the peritoneal cavity. Traditional treatment modalities, such as cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are challenging in cases of recurrent disease, owing to anatomical complexities and increasing morbidity and mortality risk. BromAc® has emerged as a novel, targeted therapy for PMP with evidence for intra-tumoral administration to break down mucin deposits. CASE REPORT: We present a 70-year-old female with confirmed diagnosis of symptomatic appendiceal PMP situated behind the stomach, refractory to prior CRS and HIPEC. Transhepatic intra-tumor injection of BromAc® was performed, guided by imaging, with catheter placement into the posterior gastric mucinous tumor. The procedure was well-tolerated, and post-treatment imaging revealed a significant 40% reduction in tumor burden. The patient had fever on cycle days two and three, which self-resolved and septic screen performed was negative. Following BromAc® administration, the patient demonstrated improvement in symptoms and quality of life. CONCLUSION: This case highlights the potential efficacy and safety of transhepatic administration of BromAc® for the treatment of recurrent PMP behind the stomach. The targeted delivery of BromAc® directly into a mucinous tumor via the transhepatic route offers a minimally invasive alternative for cases where traditional surgical interventions pose challenges. However, further research and clinical trials are warranted to validate the broader applicability of this novel approach, assess long-term outcomes, and optimize procedural parameters for enhanced therapeutic outcomes in PMP treatment.

Mated-Atom Nanozymes with Efficient Assisted NAD+ Replenishment for Skin Regeneration.

Excessive accumulation of reduced nicotinamide adenine dinucleotide (NADH) within biological organisms is closely associated with many diseases. It remains a challenge to efficiently convert superfluous and detrimental NADH to NAD+. NADH oxidase (NOX) is a crucial oxidoreductase that catalyzes the oxidation of NADH to NAD+. Herein, M1M2 (Mi=V/Mn/Fe/Co/Cu/Mo/Rh/Ru/Pd, i = 1 or 2) mated-atom nanozymes (MANs) are designed by mimicking natural enzymes with polymetallic active centers. Excitingly, RhCo MAN possesses excellent and sustainable NOX-like activity, with Km-NADH (16.11 µM) being lower than that of NOX-mimics reported so far. Thus, RhCo MAN can significantly promote the regeneration of NAD+ and regulate macrophage polarization toward the M2 phenotype through down-regulation of TLR4 expression, which may help to recover skin regeneration. However, RhRu MAN with peroxidase-like activity and RhMn MAN with superoxide dismutase-like activity exhibit little modulating effects on eczema. This work provides a new strategy to inhibit skin inflammation and promote skin regeneration.

Methods to increase the diagnostic efficiency of endoscopic ultrasound-guided fine-needle aspiration for solid pancreatic lesions: An updated review.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a means to procure adequate specimens for histological and cytologic analysis. The ideal EUS-FNA should be safe, accurate, and have a high sample adequacy rate and low adverse events rate. In recent years, many guidelines and trials on EUS-FNA have been published. The purpose of this article is to provide an update on the influence of some of the main factors on the diagnostic efficiency of EUS-FNA as well as a rare but serious complication known as needle tract seeding.

Nanobiotechnology augmented cancer stem cell guided management of cancer: liquid-biopsy, imaging, and treatment.

Cancer stem cells (CSCs) represent both a key driving force and therapeutic target of tumoral carcinogenesis, tumor evolution, progression, and recurrence. CSC-guided tumor diagnosis, treatment, and surveillance are strategically significant in improving cancer patients' overall survival. Due to the heterogeneity and plasticity of CSCs, high sensitivity, specificity, and outstanding targeting are demanded for CSC detection and targeting. Nanobiotechnologies, including biosensors, nano-probes, contrast enhancers, and drug delivery systems, share identical features required. Implementing these techniques may facilitate the overall performance of CSC detection and targeting. In this review, we focus on some of the most recent advances in how nanobiotechnologies leverage the characteristics of CSC to optimize cancer diagnosis and treatment in liquid biopsy, clinical imaging, and CSC-guided nano-treatment. Specifically, how nanobiotechnologies leverage the attributes of CSC to maximize the detection of circulating tumor DNA, circulating tumor cells, and exosomes, to improve positron emission computed tomography and magnetic resonance imaging, and to enhance the therapeutic effects of cytotoxic therapy, photodynamic therapy, immunotherapy therapy, and radioimmunotherapy are reviewed.

Gut microbiota and female health.

The gut microbiota is recognized as an endocrine organ with the capacity to influence distant organs and associated biological pathways. Recent advancements underscore the critical role of gut microbial homeostasis in female health; with dysbiosis potentially leading to diseases among women such as polycystic ovarian syndrome, endometriosis, breast cancer, cervical cancer, and ovarian cancer etc. Despite this, there has been limited discussion on the underlying mechanisms. This editorial explores the three potential mechanisms through which gut microbiota dysbiosis may impact the development of diseases among women, namely, the immune system, the gut microbiota-estrogen axis, and the metabolite pathway. We focused on approaches for treating diseases in women by addressing gut microbiota imbalances through probiotics, prebiotics supplementation, and fecal microbiota transplantation (FMT). Future studies should focus on determining the molecular mechanisms underlying associations between dysbiosis of gut microbiota and female diseases to realize precision medicine, with FMT emerging as a promising intervention.

Mechanically treated Mn2O3 triggers peracetic acid activation for superior non-radical oxidation of micropollutants: Identification of reactive complexes.

This study used a simple mechanical ball milling strategy to significantly improve the ability of Mn2O3 to activate peracetic acid (PAA) for sustainable and efficient degradation of organic micropollutant (like bisphenol A, BPA). BPA was successfully removed and detoxified via PAA activation by the bm-Mn2O3 within 30 min under neutral environment, with the BPA degradation kinetic rate improved by 3.4 times. Satisfactory BPA removal efficiency can still be achieved over a wide pH range, in actual water and after reuse of bm-Mn2O3 for four cycles. The change in hydrophilicity of Mn2O3 after ball milling evidently elevated the affinity of Mn2O3 for binding to PAA, while the reduction in particle size exposed more active sites contributing partially to catalytic oxidation. Further analysis revealed that BPA oxidation in the ball mill-treated Mn2O3 (bm-Mn2O3)/PAA process mainly depends on the bm-Mn2O3-PAA complex (i.e., Mn(III)-OO(O)CCH3) mediated non-radical pathway rather than R-O• and Mn(IV). Especially, the existence of the Mn(III)-PAA complex was definitely verified by in situ Raman spectroscopy and in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). Simultaneously, density functional theory calculations determined that PAA adsorbs readily on manganese sites thereby favoring the formation of Mn(III)-OO(O)CCH3 complexes. This study advances an in-depth understanding of the underlying mechanisms involved in the manganese oxide-catalyzed activation of PAA for superior non-radical oxidation of micropollutants.

Role of albumin-bilirubin score in non-malignant liver disease.

The albumin-bilirubin (ALBI) score, which was proposed to assess the prognosis of patients with hepatocellular carcinoma, has gradually been extended to other liver diseases in recent years, including primary biliary cholangitis, liver cirrhosis, hepatitis, liver transplantation, and liver injury. The ALBI score is often compared with classical scores such as the Child-Pugh and model for end-stage liver disease scores or other noninvasive prediction models. It is widely employed because of its immunity to subjective evaluation indicators and ease of obtaining detection indicators. An increasing number of studies have confirmed that it is highly accurate for assessing the prognosis of patients with chronic liver disease; additionally, it has demonstrated good predictive performance for outcomes beyond survival in patients with liver diseases, such as decompensation events. This article presents a review of the application of ALBI scores in various non-malignant liver diseases.

In Vivo Toxicology of Metabolizable Atomically Precise Au25 Clusters at Ultrahigh Doses.

Ultrasmall Au25(MPA)18 clusters show great potential in biocatalysts and bioimaging due to their well-defined, tunable structure and properties. Hence, in vivo pharmacokinetics and toxicity of Au nanoclusters (Au NCs) are very important for clinical translation, especially at high dosages. Herein, the in vivo hematological, tissue, and neurological effects following exposure to Au NCs (300 and 500 mg kg-1) were investigated, in which the concentration is 10 times higher than in therapeutic use. The biochemical and hematological parameters of the injected Au NCs were within normal limits, even at the ultrahigh level of 500 mg kg-1. Meanwhile, no histopathological changes were observed in the Au NC group, and immunofluorescence staining showed no obvious lesions in the major organs. Furthermore, real-time near-infrared-II (NIR-II) imaging showed that most of the Au25(MPA)18 and Au24Zn1(MPA)18 can be metabolized via the kidney. The results demonstrated that Au NCs exhibit good biosafety by evaluating the manifestation of toxic effects on major organs at ultrahigh doses, providing reliable data for their application in biomedicine.

Neoadjuvant chemoimmunotherapy for locally advanced esophageal squamous cell carcinoma: Data from literature review and a real-world analysis.

BACKGROUND: Neoadjuvant chemoimmunotherapy (NCIT) for locally advanced esophageal squamous cell carcinoma (ESCC) is supported by increasing data, but the sample size is limited, and the findings are not completely consistent. We conducted a real-world study and a meta-analysis to evaluate the efficacy and safety of NCIT in locally advanced ESCC. METHODS: We retrospectively assessed the outcomes of patients with locally advanced ESCC who completed NICT and subsequent esophagectomy at our hospital between January 2019 and December 2022, including pathological complete response (pCR) rate, major pathological response (MPR) rate, 1-, 2-, and 3-year overall survival (OS) rates, disease control rate (DCR), objective response rate (ORR), 1-year recurrence rate, R0 resection rate and adverse events. Moreover, a meta-analysis of 27 published literatures was also conducted for comparison. RESULTS: In the analysis, 128 patients were studied, with 25% achieving pCR, 46.1% MPR, and 99.2% R0 resection. The 1-, 2-, and 3-year OS rates were 91.41% (95% CI: 85.15%-95.63%), 75.00% (95% CI: 66.58%-82.23%) and 64.84% (95% CI: 55.91%-73.07%).ORR and DCR were 31.2% (95% CI: 23.31-39.99) and 64.1% (95% CI: 55.15%-72.38%), and the 1-year recurrence rate was 26.7% (95% CI: 22.5%-38.1%). Treatment-related events occurred in 96.1% but were acceptable. In a meta-analysis of 27 studies with 1734 patients, pooled rates for pCR, MPR, ORR, DCR, and R0 resection were 29%, 52%, 71%, 97%, and 98%, respectively, with a 1-year recurrence rate of 12%. CONCLUSION: NCIT is safe and provides potential survival benefits for patients with locally advanced ESCC. However, randomized phase 3 trial data is still needed.

Duodenal-jejunal bypass improves hypothalamic oxidative stress and inflammation in diabetic rats via glucagon-like peptide 1-mediated Nrf2/HO-1 signaling.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is often accompanied by impaired glucose utilization in the brain, leading to oxidative stress, neuronal cell injury and infla-mmation. Previous studies have shown that duodenal jejunal bypass (DJB) surgery significantly improves brain glucose metabolism in T2DM rats, the role and the metabolism of DJB in improving brain oxidative stress and inflammation condition in T2DM rats remain unclear. AIM: To investigate the role and metabolism of DJB in improving hypothalamic oxidative stress and inflammation condition in T2DM rats. METHODS: A T2DM rat model was induced via a high-glucose and high-fat diet, combined with a low-dose streptozotocin injection. T2DM rats were divided into DJB operation and Sham operation groups. DJB surgical intervention was carried out on T2DM rats. The differential expression of hypothalamic proteins was analyzed using quantitative proteomics analysis. Proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of T2DM rats were analyzed by flow cytometry, quantitative real-time PCR, Western blotting, and immunofluorescence. RESULTS: Quantitative proteomics analysis showed significant differences in proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of rats with T2DM-DJB after DJB surgery, compared to the T2DM-Sham groups of rats. Oxidative stress-related proteins (glucagon-like peptide 1 receptor, Nrf2, and HO-1) were significantly increased (P < 0.05) in the hypothalamus of rats with T2DM after DJB surgery. DJB surgery significantly reduced (P < 0.05) hypothalamic inflammation in T2DM rats by inhibiting the activation of NF-κB and decreasing the expression of interleukin (IL)-1ß and IL-6. DJB surgery significantly reduced (P < 0.05) the expression of factors related to neuronal injury (glial fibrillary acidic protein and Caspase-3) in the hypothalamus of T2DM rats and upregulated (P < 0.05) the expression of neuroprotective factors (C-fos, Ki67, Bcl-2, and BDNF), thereby reducing hypothalamic injury in T2DM rats. CONCLUSION: DJB surgery improve oxidative stress and inflammation in the hypothalamus of T2DM rats and reduce neuronal cell injury by activating the glucagon-like peptide 1 receptor-mediated Nrf2/HO-1 signaling pathway.