Targeting gut microbiota for immunotherapy of diseases.

With advances in next-generation sequencing technology, there is growing evidence that the gut microbiome plays a key role in the host's innate and adaptive immune system. Gut microbes and their metabolites directly or indirectly regulate host immune cells. Crucially, dysregulation of the gut microbiota is often associated with many immune system diseases. In turn, microbes modulate disease immunotherapy. Data from preclinical to clinical studies suggest that the gut microbiota may influence the effectiveness of tumor immunotherapy, particularly immune checkpoint inhibitors (ICIs). In addition, the most critical issue now is a COVID-19 vaccine that generates strong and durable immunity. A growing number of clinical studies confirm the potential of gut microbes to enhance the efficacy of COVID-19 vaccines. However, it is still unclear how gut bacteria interact with immune cells and what treatments are based on gut microbes. Here, we outline recent advances in the effects and mechanisms of the gut microbiota and its metabolites (tryptophan metabolites, bile acids, short-chain fatty acids, and inosine) on different immune cells (dendritic cells, CD4+T cells, and macrophages). It also highlights innovative intervention strategies and clinical trials of microbiota-based checkpoint blocking therapies for tumor immunity, and ongoing efforts to maintain the long-term immunogenicity of COVID-19 vaccines. Finally, the challenges to be overcome in this area are discussed. These provide an important basis for further research and clinical translation of gut microbiota.

Peroxiredoxin II exerts neuroprotective effects by inhibiting endoplasmic reticulum stress and oxidative stress-induced neuronal pyroptosis.

BACKGROUND: Intracerebral hemorrhage (ICH) is a critical neurological condition with few treatment options, where secondary immune responses and specific cell death forms, like pyroptosis, worsen brain damage. Pyroptosis involves gasdermin-mediated membrane pores, increasing inflammation and neural harm, with the NLRP3/Caspase-1/GSDMD pathway being central to this process. Peroxiredoxin II (Prx II), recognized for its mitochondrial protection and reactive oxygen species (ROS) scavenging abilities, appears as a promising neuronal pyroptosis modulator. However, its exact role and action mechanisms need clearer definition. This research aims to explore Prx II impact on neuronal pyroptosis and elucidate its mechanisms, especially regarding endoplasmic reticulum (ER) stress and oxidative stress-induced neuronal damage modulation. METHODS AND RESULTS: Utilizing MTT assays, Microscopy, Hoechst/PI staining, Western blotting, and immunofluorescence, we found Prx II effectively reduces LPS/ATP-induced pyroptosis and neuroinflammation in HT22 hippocampal neuronal cells. Our results indicate Prx II's neuroprotective actions are mediated through PI3K/AKT activation and ER stress pathway inhibition, diminishing mitochondrial dysfunction and decreasing neuronal pyroptosis through the ROS/MAPK/NF-κB pathway. These findings highlight Prx II potential therapeutic value in improving intracerebral hemorrhage outcomes by lessening secondary brain injury via critical signaling pathway modulation involved in neuronal pyroptosis. CONCLUSIONS: Our study not only underlines Prx II importance in neuroprotection but also opens new therapeutic intervention avenues in intracerebral hemorrhage, stressing the complex interplay between redox regulation, ER stress, and mitochondrial dynamics in neuroinflammation and cell death management.

Blood microbial signatures associated with mortality in patients with sepsis: A pilot study.

Sepsis is a life-threatening illness caused by the dysregulated host response to infection. Nevertheless, our current knowledge of the microbial landscape in the blood of septic patients is still limited. Next-generation sequencing (NGS) is a sensitive method to quantitatively characterize microbiomes at various sites of the human body. In this study, we analyzed the blood microbial DNA of 22 adult patients with sepsis and 3 healthy subjects. The presence of non-human DNA was identified in both healthy and septic subjects. Septic patients had a markedly altered microbial DNA profile compared to healthy subjects over α- and ß-diversity. Unexpectedly, the patients could be further divided into two subgroups (C1 and C2) based on ß-diversity analysis. C1 patients showed much higher bacteria, viruses, fungi, and archaea abundance, and a higher level of α-diversity (Chao1, Observed and Shannon index) than both C2 patients and healthy subjects. The most striking difference was seen in the case of Streptomyces violaceusniger, Phenylobacterium sp. HYN0004, Caulobacter flavus, Streptomyces sp. 11-1-2, and Phenylobacterium zucineum, the abundance of which was the highest in the C1 group. Notably, C1 patients had a significantly poorer outcome than C2 patients. Moreover, by analyzing the patterns of microbe-microbe interactions in healthy and septic subjects, we revealed that C1 and C2 patients exhibited distinct co-occurrence and co-exclusion relationships. Together, our study uncovered two distinct microbial signatures in the blood of septic patients. Compositional and ecological analysis of blood microbial DNA may thus be useful in predicting mortality of septic patients.

Research on the influencing factors of Chinese agricultural brand competitiveness based on DEMATEL-ISM.

Agricultural products are pivotal to the national economy, and a comprehensive analysis of brand competitiveness significantly contributes to the support of agricultural structural adjustment and modernization. Focusing on the Yangtze River Delta region of China, this study develops an evaluation index system encompassing four dimensions: core brand competitiveness, brand management, market competitiveness, and innovation in branding. Utilizing a DEMATEL-ISM model, this research elucidates the intrinsic relationships among factors that influence brand competitiveness, resulting in a four-tier hierarchical model. The analysis delineates key factors at superficial, intermediate, and profound levels that influence brand competitiveness. Notably, regional production bases, along with innovations in brand technology and systems, emerge as profound influencers. Drawing on these findings, the study recommends strategies to enhance production foundations, accurately define development trajectories, spearhead technological innovation to foster collective reform efforts, and advocate for institutional advancements to bolster healthy brand growth.

PBPK-PD model for predicting morphine pharmacokinetics, CNS effects and naloxone antagonism in humans.

Morphine and morphine-6-glucuronide (M6G) produce central nervous system (CNS) effects by activating mu-opioid receptors, while naloxone is used mainly for the reversal of opioid overdose, specifically for the fatal complication of respiratory depression, but also for alleviating opioid-induced side effects. In this study we developed a physiologically-based pharmacokinetic-pharmacodynamic (PBPK-PD) model to simultaneously predict pharmacokinetics and CNS effects (miosis, respiratory depression and analgesia) of morphine as well as antagonistic effects of naloxone against morphine. The pharmacokinetic and pharmacodynamic parameters were obtained from in vitro data, in silico, or animals. Pharmacokinetic and pharmacodynamic simulations were conducted using 39 and 36 clinical reports, respectively. The pharmacokinetics of morphine and M6G following oral or intravenous administration were simulated, and the PBPK-PD model was validated using clinical observations. The Emax model correlated CNS effects with free concentrations of morphine and M6G in brain parenchyma. The predicted CNS effects were compared with observations. Most clinical observations fell within the 5th-95th percentiles of simulations based on 1000 virtual individuals. Most of the simulated area under the concentration-time curve or peak concentrations also fell within 0.5-2-fold of observations. The contribution of morphine to CNS effects following intravenous or oral administration was larger than that of M6G. Pharmacokinetics and antagonistic effects of naloxone on CNS effects were also successfully predicted using the developed PBPK-PD model. In conclusion, the pharmacokinetics and pharmacodynamics of morphine and M6G, antagonistic effects of naloxone against morphine-induced CNS effects may be successfully predicted using the developed PBPK-PD model based on the parameters derived from in vitro, in silico, or animal studies.

Characteristics and Geological Significance of Lacustrine Hydrothermal Sedimentary Rocks in the Yingejing Sag in Bayingebi Basin, Inner Mongolia, Northwestern China.

In order to promote site screening for high-level radioactive waste (HLW) disposal purposes, the characteristics of argillaceous rock (potential host rock) from the Yingejing Sag of the Bayingebi Basin, Northwest China have been well discussed. Results show that (1) Unlike argillaceous host rocks in foreign countries, the argillaceous rock mainly consists of analcite, dolomite, and albite; the contents of clay minerals are only about 10%. Five typical structures could be categorized, dominating by the massive structure. (2) Geochemical characteristics have the characteristics of abundance in deep source gas and liquid trace elements, a gentle right dip in the distribution pattern of rare-earth elements. (3) Petrological and geochemical characteristics determine the argillaceous rock as the genesis of lacustrine hydrothermal sedimentary rock. The hydrothermal sedimentary model also has been constructed, mainly controlled by tectonic activity of the Altyn Tagh fault from 100 to 120 Ma. The massive argillites with analcite and dolomite would lay the foundation for confirming the site for HLW disposal purposes in China.

Indoxyl sulphate-TNFα axis mediates uremic encephalopathy in rodent acute kidney injury.

Acute kidney injury (AKI) is often accompanied by uremic encephalopathy resulting from accumulation of uremic toxins in brain possibly due to impaired blood-brain barrier (BBB) function. Anionic uremic toxins are substrates or inhibitors of organic anionic transporters (OATs). In this study we investigated the CNS behaviors and expression/function of BBB OAT3 in AKI rats and mice, which received intraperitoneal injection of cisplatin 8 and 20 mg/kg, respectively. We showed that cisplatin treatment significantly inhibited the expressions of OAT3, synaptophysin and microtubule-associated protein 2 (MAP2), impaired locomotor and exploration activities, and increased accumulation of uremic toxins in the brain of AKI rats and mice. In vitro studies showed that uremic toxins neither alter OAT3 expression in human cerebral microvascular endothelial cells, nor synaptophysin and MAP2 expressions in human neuroblastoma (SH-SY5Y) cells. In contrast, tumour necrosis factor alpha (TNFα) and the conditioned medium (CM) from RAW264.7 cells treated with indoxyl sulfate (IS) significantly impaired OAT3 expression. TNFα and CM from IS-treated BV-2 cells also inhibited synaptophysin and MAP2 expressions in SH-SY5Y cells. The alterations caused by TNFα and CMs in vitro, and by AKI and TNFα in vivo were abolished by infliximab, a monoclonal antibody designed to intercept and neutralize TNFα, suggesting that AKI impaired the expressions of OAT3, synaptophysin and MAP2 in the brain via IS-induced TNFα release from macrophages or microglia (termed as IS-TNFα axis). Treatment of mice with TNFα (0.5 mg·kg-1·d-1, i.p. for 3 days) significantly increased p-p65 expression and reduced the expressions of Nrf2 and HO-1. Inhibiting NF-κB pathway, silencing p65, or activating Nrf2 and HO-1 obviously attenuated TNFα-induced downregulation of OAT3, synaptophysin and MAP2 expressions. Significantly increased p-p65 and decreased Nrf2 and HO-1 protein levels were also detected in brain of AKI mice and rats. We conclude that AKI inhibits the expressions of OAT3, synaptophysin and MAP2 due to IS-induced TNFα release from macrophages or microglia. TNFα impairs the expressions of OAT3, synaptophysin and MAP2 partly via activating NF-κB pathway and inhibiting Nrf2-HO-1 pathway.

The role of TET2 in solid tumors and its therapeutic potential: a comprehensive review.

Indeed, tumors are a significant health concern worldwide, and understanding the underlying mechanisms of tumor development is crucial for effective prevention and treatment. Epigenetics, which refers to changes in gene expression that are not caused by alterations in the DNA sequence itself, plays a critical role in the entire process of tumor development. It goes without saying that the effect of methylation on tumors is a significant aspect of epigenetics. Among the methylation modifications, DNA methylation is an important part, which plays a regulatory role in tumor-related genes. Ten-eleven translocation 2 (TET2) is a highly influential protein involved in the modification of DNA methylation. Its primary role is associated with the suppression of tumor development, making it a significant player in cancer research. However, TET2 is frequently mentioned in hematological diseases, its role in solid tumors has received little attention. Studying the changes of TET2 in solid tumors and the regulatory mechanism will facilitate its investigation as a clinical target for targeted therapy and may also provide directions for clinical treatment of malignant tumors.

Investigating the influence of excavating a tunnel undercrossing an existing tunnel at zero distance.

In urban areas with limited underground space, the new tunnel construction introduces additional loads and displacements to existing tunnels, raising serious safety concerns. These concerns become particularly pronounced in the case of closely undercrossing excavation at zero-distance. The conventional elastic foundation beam model, which assumes constant reaction coefficients for the subgrade, fails to account for foundation loss. In this study, the existing tunnel is modeled as an Euler-Bernoulli beam supported by the Pasternak elastic foundation, and the foundation loss caused by zero-distance undercrossing excavations is considered. Furthermore, an analytical solution is proposed to evaluate the mechanical response in segments, by establishing governing differential equations and boundary conditions for the excavation and neutral zones, and underpinning loads are also considered. The analytical solution is validated in two case studies. Finally, a parametric analysis is performed to explore the influence of various parameters on the mechanical response of the existing tunnel.

Reprogramming fibroblast into human iBlastoids.

The study of early human embryogenesis has relied on the use of blastocysts donated to research or simple stem cell culture systems such as pluripotent and trophoblast stem cells, which have been seminal in shedding light on many key developmental processes. However, simple culture systems lack the necessary complexity to adequately model the spatiotemporal, cellular and molecular dynamics occurring during the early phases of embryonic development. As such, an in vitro model of the human blastocyst is advantageous in many aspects to decipher human embryogenesis. Here we describe a step-by-step protocol for the generation of induced blastoids (iBlastoids), an in vitro integrated model of the human blastocyst derived via somatic reprogramming. This protocol details the workflow for reprogramming of human dermal fibroblasts and subsequent generation of iBlastoids using the reprogramming intermediates, which together takes ~27 days (21 days for reprogramming and 6 days for iBlastoid generation). We also discuss several characterization/functional assays that can be used on the iBlastoids. We believe that a person trained in cell culture with ~1 year of experience with human somatic cell and reprogramming/cell differentiation assays would be able to perform this protocol. In short, the iBlastoids present an alternative tool as a model to the blastocyst to facilitate the scientific community in the exploration of early human development.

Tumor phylogeography reveals block-shaped spatial heterogeneity and the mode of evolution in Hepatocellular Carcinoma.

Solid tumors are complex ecosystems with heterogeneous 3D structures, but the spatial intra-tumor heterogeneity (sITH) at the macroscopic (i.e., whole tumor) level is under-explored. Using a phylogeographic approach, we sequence genomes and transcriptomes from 235 spatially informed sectors across 13 hepatocellular carcinomas (HCC), generating one of the largest datasets for studying sITH. We find that tumor heterogeneity in HCC segregates into spatially variegated blocks with large genotypic and phenotypic differences. By dissecting the transcriptomic heterogeneity, we discover that 30% of patients had a "spatially competing distribution" (SCD), where different spatial blocks have distinct transcriptomic subtypes co-existing within a tumor, capturing the critical transition period in disease progression. Interestingly, the tumor regions with more advanced transcriptomic subtypes (e.g., higher cell cycle) often take clonal dominance with a wider geographic range, rejecting neutral evolution for SCD patients. Extending the statistical tests for detecting natural selection to many non-SCD patients reveal varying levels of selective signal across different tumors, implying that many evolutionary forces including natural selection and geographic isolation can influence the overall pattern of sITH. Taken together, tumor phylogeography unravels a dynamic landscape of sITH, pinpointing important evolutionary and clinical consequences of spatial heterogeneity in cancer.

Introgression and disruption of migration routes have shaped the genetic integrity of wildebeest populations.

The blue wildebeest (Connochaetes taurinus) is a keystone species in savanna ecosystems from southern to eastern Africa, and is well known for its spectacular migrations and locally extreme abundance. In contrast, the black wildebeest (C. gnou) is endemic to southern Africa, barely escaped extinction in the 1900s and is feared to be in danger of genetic swamping from the blue wildebeest. Despite the ecological importance of the wildebeest, there is a lack of understanding of how its unique migratory ecology has affected its gene flow, genetic structure and phylogeography. Here, we analyze whole genomes from 121 blue and 22 black wildebeest across the genus' range. We find discrete genetic structure consistent with the morphologically defined subspecies. Unexpectedly, our analyses reveal no signs of recent interspecific admixture, but rather a late Pleistocene introgression of black wildebeest into the southern blue wildebeest populations. Finally, we find that migratory blue wildebeest populations exhibit a combination of long-range panmixia, higher genetic diversity and lower inbreeding levels compared to neighboring populations whose migration has recently been disrupted. These findings provide crucial insights into the evolutionary history of the wildebeest, and tangible genetic evidence for the negative effects of anthropogenic activities on highly migratory ungulates.

Reevaluating Adiponectin's impact on obesity hypertension: a Chinese case-control study.

BACKGROUND: Obesity and hypertension are major risk factors for cardiovascular diseases that affect millions of people worldwide. Both conditions are associated with chronic low-grade inflammation, which is mediated by adipokines such as adiponectin. Adiponectin is the most abundant adipokine that has a beneficial impact on metabolic and vascular biology, while high serum concentrations are associated with some syndromes. This "adiponectin paradox" still needs to be clarified in obesity-associated hypertension. The aim of this study was to investigate how adiponectin affects blood pressure, inflammation, and metabolic function in obesity hypertension using a Chinese adult case-control study. METHODS: A case-control study that had finished recruiting 153 subjects divided as four characteristic groups. Adiponectin serum levels were tested by ELISA in these subjects among these four characteristic Chinese adult physical examination groups. Waist circumference (WC), body mass index (BMI), systolic blood pressure (SB), diastolic blood pressure (DB), and other clinical laboratory data were collected. Analyzation of correlations between the research index and differences between groups was done by SPSS. RESULTS: Serum adiponectin levels in the| normal healthy group (NH group) were significantly higher than those in the newly diagnosed untreated just-obesity group (JO group), and negatively correlated with the visceral adiposity index. With multiple linear egression analysis, it was found that, for serum adiponectin, gender, serum albumin (ALB), alanine aminotransferase (ALT) and high-density lipoprotein cholesterol (HDLC) were the significant independent correlates, and for SB, age and HDLC were the significant independent correlates, and for DB, alkaline phosphatase (ALP) was the significant independent correlate. The other variables did not reach significance in the model. CONCLUSIONS: Our study reveals that adiponectin's role in obesity-hypertension is multifaceted and is influenced by the systemic metabolic homeostasis signaling axis. In obesity-related hypertension, compensatory effects, adiponectin resistance, and reduced adiponectin clearance from impaired kidneys and liver all contribute to the "adiponectin paradox".

Long term survival outcomes of surgery combined with hyperthermic intraperitoneal chemotherapy for perforated low-grade appendiceal mucinous neoplasms: A multicenter retrospective study.

BACKGROUND: Low-grade appendiceal mucinous neoplasms (LAMN) are very rare, accounting for approximately 0.2%-0.5% of gastrointestinal tumors. We conducted a multicenter retrospective study to explore the impact of different surgical procedures combined with HIPEC on the short-term outcomes and long-term survival of patients. METHODS: We retrospectively analyzed the clinicopathological data of 91 LAMN perforation patients from 9 teaching hospitals over a 10-year period, and divided them into HIPEC group and non-HIPEC group based on whether or not underwent HIPEC. RESULTS: Of the 91 patients with LAMN, 52 were in the HIPEC group and 39 in the non-HIPEC group. The Kaplan-Meier method predicted that 52 patients in the HIPEC group had 5- and 10-year overall survival rates of 82.7% and 76.9%, respectively, compared with predicted survival rates of 51.3% and 46.2% for the 39 patients in the non-HIPEC group, with a statistically significant difference between the two groups (χ2 = 10.622, p = 0.001; χ2 = 10.995, p = 0.001). Compared to the 5-year and 10-year relapse-free survival rates of 75.0% and 65.4% in the HIPEC group, respectively, the 5-year and 10-year relapse-free survival rates of 48.7% and 46.2% in the non-HIPEC group were significant different between the two outcomes (χ2 = 8.063, p = 0.005; χ2 = 6.775, p = 0.009). The incidence of postoperative electrolyte disturbances and hypoalbuminemia was significantly higher in the HIPEC group than in the non-HIPEC group (p = 0.023; p = 0.044). CONCLUSIONS: This study shows that surgery combined with HIPEC can significantly improve 5-year and 10-year overall survival rates and relapse-free survival rates of LAMN perforation patients, without affecting their short-term clinical outcomes.

Cuproptosis-Related Biomarkers and Characterization of Immune Infiltration in Sepsis.

Introduction: Sepsis is a worldwide epidemic, with high morbidity and mortality. Cuproptosis is a form of cell death that is associated with a wide range of diseases. This study aimed to explore genes associated with cuproptosis in sepsis, construct predictive models and screen for potential targets. Methods: The LASSO algorithm and SVM-RFE model has been analysed the expression of cuproptosis-related genes in sepsis and immune infiltration characteristics and identified the marker genes under a diagnostic model. Gene-drug networks, mRNA-miRNA networks and PPI networks were constructed to screen for potential biological targets. The expression of marker genes was validated based on the GSE57065 dataset. Consensus clustering method was used to classify sepsis samples. Results: We found 381 genes associated with the development of sepsis and discovered significantly differentially expressed cuproptosis-related genes of 16 cell types in sepsis and immune infiltration with CD8/CD4 T cells being lower. NFE2L2, NLRP3, SLC31A1, DLD, DLAT, PDHB, MTF1, CDKN2A and DLST were identified as marker genes by the LASSO algorithm and the SVM-RFE model. AUC > 0.9 was constructed for PDHB and MTF1 alone respectively. The validation group data for PDHB (P=0.00099) and MTF1 (P=7.2e-14) were statistically significant. Consistent clustering analysis confirmed two subtypes. The C1 subtype may be more relevant to cellular metabolism and the C2 subtype has some relevance to immune molecules.The results of animal experiments showed that the gene expression was consistent with the bioinformatics analysis. Discussion: Our study systematically explored the relationship between sepsis and cuproptosis and constructed a diagnostic model. And, several cuproptosis-related genes may interfere with the progression of sepsis through immune cell infiltration.

In Situ-Derived N-Doped ZnO from ZIF-8 for Enhanced Ethanol Sensing in ZnO/MEMS Devices.

Microelectromechanical systems (MEMS) gas sensors have numerous advantages such as compact size, low power consumption, ease of integration, etc., while encountering challenges in sensitivity and high resistance because of their low sintering temperature. This work utilizes the in situ growth of Zeolitic Imidazolate Framework-8 (ZIF-8) followed by its conversion to N-doped ZnO. The results obtained from scanning electron microscopy (SEM) and transmission electron microscopy (TEM) indicate that the in situ derivation of ZIF-8 facilitates the adhesion of ZnO particles, forming an island-like structure and significantly reducing the interfaces between these particles. Furthermore, powder X-ray diffraction (XRD) analysis, elemental mapping, and X-ray photoelectron spectroscopy (XPS) analysis confirm the conversion of ZIF-8 to ZnO, the successful incorporation of N atoms into the ZnO lattice, and the creation of more oxygen vacancies. The ZIF-8-derived N-doped ZnO/MEMS sensor (ZIF (3)-ZnO/MEMS) exhibits remarkable gas sensitivity for ethanol detection. At an operating temperature of 290 °C, it delivers a substantial response value of 80 towards 25 ppm ethanol, a 13-fold enhancement compared with pristine ZnO/MEMS sensors. The sensor also exhibits an ultra-low theoretical detection limit of 11.5 ppb to ethanol, showcasing its excellent selectivity. The enhanced performance is attributed to the incorporation of N-doped ZnO, which generates abundant oxygen vacancies on the sensor's surface, leading to enhanced interaction with ethanol molecules. Additionally, a substantial two-order-of-magnitude decrease in the resistance of the gas-sensitive film is observed. Overall, this study provides valuable insights into the design and fabrication strategies applicable to high-performance MEMS gas sensors in a broader range of gas sensing.

A comparison of cardiovascular disease, cancer, mortality, and Graves' ophthalmopathy following treatment for hyperthyroidism: A Bayesian network meta-analysis.

OBJECTIVES: This network meta-analysis aimed to evaluate the association of anti-thyroid drugs (ATD), radioactive iodine (RAI), and thyroidectomy with subsequent outcomes in patients with newly-diagnosed hyperthyroidism. METHODS: The Ovid Medline, Ovid Embase, and Cochrane Library databases were searched for observational studies and randomized controlled trials. Included studies were published on or before 1st May 2022 involving at least two of the treatments among ATD, RAI, and thyroidectomy for hyperthyroidism. Pairwise comparisons and Bayesian network meta-analysis were used to estimate hazard ratios (HRs) and their credible interval (CrI) of outcomes, including cardiovascular disease (CVD), cancer, overall mortality, and Graves' ophthalmopathy (GO). RESULTS: A total of 22 cohort studies with 131,297 hyperthyroidism patients were included. Thyroidectomy was associated with lower risks of mortality and GO than ATD (HR = 0.54, 95% CrI: 0.31, 0.96; HR = 0.31, 95% CrI: 0.12, 0.64) and RAI (HR = 0.62, 95% CrI: 0.41, 0.95; HR = 0.18, 95% CrI: 0.07, 0.35). RAI had a higher risk of GO (HR = 1.70, 95% CrI: 1.02, 2.99) than ATD treatment. CONCLUSIONS: This Bayesian network meta-analysis indicated that thyroidectomy was associated with lower risks of mortality and GO in newly-diagnosed hyperthyroid patients compared to ATD and RAI. Relative to ATD, RAI therapy increased the risk of GO.

Effectiveness of prophylactic antibacterial drugs for patients with liver cirrhosis and upper gastrointestinal bleeding: a systematic review and meta-analysis.

Background: Prophylactic antibacterial drugs are used for patients with liver cirrhosis and upper gastrointestinal bleeding, and independent studies have concluded that they can decrease the rate of infection, mortality, and rebleeding in these diseases. However, no comprehensive assessment of this effect has been reported in recent years and available data pertaining to the prognostic implications of diverse categories of antibiotic prophylaxis in individuals afflicted with cirrhosis are notably limited. The objective of this article is to assess the clinical effectiveness of prophylactic antibacterial drugs for patients with liver cirrhosis and upper gastrointestinal bleeding. Methods: Relevant randomized controlled studies and cohort studies which examined the value of prophylactic antibacterial drugs for patients with liver cirrhosis and upper gastrointestinal bleeding were retrieved via Cochrane Library, EMBASE, MedLine, and Web of Science. The search period was from database inception until 30 April 2023. Summing up the relevant data, the dichotomous variable was statistically analysed using the relative risk (RR) value and its 95% confidence interval (CI) and the continuous variable using the mean difference (MD) value and its 95% CI. All analyses were performed using Revman 5.4 software. The study has been registered on the PROSPERO website under registration number CRD42022343352. Results: Twenty-six studies (18 RCTs and 8 cohort studies, including 13,670 participants) were included to evaluate the effect of antibacterial prophylaxis versus no antibacterial prophylaxis or placebo. Prophylactic antibiotics reduced mortality rates (RR 0.66, 95% CI 0.51-0.83), infection rates (RR 0.41, 95% CI 0.35-0.49), rebleeding rates (RR 0.42, 95% CI 0.31-0.56), and length of hospital stay (MD -5.29, 95% CI -7.53, -3.04). Subgroup analysis revealed that the prophylactic administration of quinolone antimicrobials demonstrated the most favorable efficacy, followed by cephalosporins. Both interventions were effective in averting infections frequently observed in patients with liver cirrhosis and upper gastrointestinal bleeding. Conclusion: Based on our investigation, the prophylactic antibacterial drugs confers noteworthy advantages in patients afflicted by liver cirrhosis with upper gastrointestinal bleeding. It has been associated with reductions in mortality, infection incidence, rebleeding occurrences, and the duration of hospitalization. Among prophylactic antibacterial options, quinolones emerged as the foremost choice, with cephalosporins ranking closely thereafter. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022343352, identifier CRD42022343352.

Prognostic value of different radiation-related cell death genes in patients with lung adenocarcinoma.

BACKGROUND AND AIMS: Radiotherapy is widely applied for lung adenocarcinoma (LUAD), while individualized differences led to different outcomes. This study aimed to establish a multi-gene risk scoring model to predict the benefits of LUAD patients from radiotherapy, based on different types of cell death respectively. RESULTS: Other than autophagy, pyroptosis, ferroptosis and Immunogenic cell death (ICD), the LUAD prognostic model based on apoptosis had the best performance, and the area under curves (AUCs) of the receiver operating curve (ROC) for 1-, 3-, and 5-year OS were 0.700,0.736,0.723,respectively. Such genes were involved as SLC7A5, EXO1, ABAT, NLRP1 and GAR1. Then patients were divided into high and low risk groups by the median apoptosis-LUAD risk score. For patients in the high-risk group, i.e., the radiotherapy-tolerant group, we screened adjuvant chemotherapy and found that besides the conventional first-line chemotherapy regimen, drugs such as Fludarabine, Pevonedistat, and Podophyllotoxin Bromide may also have potential therapeutic value. CONCLUSION: The multi-gene risk scoring model based on apoptosis might predict the radiotherapy benefits of LUAD patients and for those radioresistant patients classified by the model we also provided effective adjuvant chemicals, which would be used to guide clinical treatment.