Latest ArticlesThe inflammatory status in patients with chronic kidney disease (CKD) is closely associated with cardiovascular events, infections, and other complications, and is a powerful indicator for prognosis assessment. The core view of the "gut-kidney axis" theory reveals the relationship among inflammatory state, microbiota dysbiosis, and deterioration of renal function. The microbiota alters the microenvironment through structural changes and metabolites with different properties, subsequently leading to microbiota translocation, inducing inflammatory lesions, and damaging the kidneys. Recent studies have proposed that targeted microbiota intervention strategies such as probiotics, prebiotics, and synbiotics can modulate the microbiota structure, regulate the microenvironment, relieve renal inflammation, and affect the progression of renal disease, representing a potentially promising research direction in the future. This review discusses the characteristics of how intestinal microbiota influence the inflammatory status in CKD, focusing on the research progress of targeted microbiota intervention, aiming to discuss the effectiveness and scientific basis of these strategies, providing a foundation for the treatment of CKD and the expansion of targeted microbiota research, as well as offering references for the clinical application of probiotics, prebiotics, and synbiotics.
Objective To investigate the effect of miR-185-5p-mediated targeted negative regulation of transmembrane 9 superfamily member 1 (TM9SF1) on proliferation, migration and autophagy in lung adenocarcinoma cells. Methods The expression of miR-185-5p in lung adenocarcinoma tissues was analyzed using dataset GSE51853 downloaded from the Gene Expression Omnibus (GEO) database. Potential target proteins of miR-185-5p were predicted using online databases (miRTargetLink, miRTarbase, and DIANA-microT-CD), and autophagy-related proteins were obtained from HADb. The intersected results from these four databases was identified, and survival curves of vascular endothelial growth factor A (VEGFA) and TM9SF1 within the overlapping candidates were analyzed using the StarBase database. TM9SF1 3'UTR wild-type (WT) or TM9SF1 3'UTR mutant (MUT) reporter plasmids were separately co-transfected with miR-185-5p control plasmid (CON) or miR-185-5p overexpression plasmid (over-miR-185-5p) into HEK-293T cells. A dual-luciferase reporter gene assay was employed to assess the binding interaction between miR-185-5p and TM9SF1 and quantify the subsequent luciferase activity. Western blotting was used to assess TM9SF1 protein expression levels in A549 cells transfected with over-miR-185-5p. A549 cells were divided into three groups: (1) CON+NC group, co-transfected with miR-185-5p control plasmid and TM9SF1 control plasmid; (2) over-miR-185-5p+NC group, co-transfected with over-miR-185-5p and TM9SF1 control plasmid; (3) over-miR-185-5p+over-TM9SF1 group, co-transfected with both miR-185-5p and TM9SF1 overexpression plasmids. EdU cell proliferation assay, wound healing assay, and Transwell migration assay were performed to validate the effects of miR-185-5p targeted binding to TM9SF1 on proliferation and migration capacities in lung adenocarcinoma. Changes in autophagic flux and mitochondrial membrane potential (MMP) of lung adenocarcinoma cells were detected using stubRFP-sensGFP-LC3 lentivirus and JC-1 assays, respectively. Results In the GSE51853 dataset, miR-185-5p expression level was significantly lower in lung adenocarcinoma tissues compared with normal lung tissues (P<0.01). qRT-PCR analysis revealed that miR-185-5p expression was downregulated in lung adenocarcinoma cell lines NCI-H1299 and A549 compared with normal lung epithelial cells BEAS-2B (P<0.01). Bioinformatics predictions using miRTargetLink, miRTarbase, DIANA-microT-CD, and HADb databases indicated that miR-185-5p could target and regulate the autophagy-related protein TM9SF1. Dual-luciferase reporter assays and Western blotting demonstrated that miR-185-5p directly bound to the 3'UTR region of TM9SF1 mRNA, and overexpression of miR-185-5p significantly reduced the expression of target protein TM9SF1 (P<0.05). EdU cell proliferation, wound healing, and Transwell migration assays demonstrated that miR-185-5p overexpression inhibited proliferation and migration capacities of lung adenocarcinoma cells, whereas TM9SF1 overexpression could attenuate this inhibition effect (P<0.05). Results of stubRFP-sensGFP-LC3 for autophagic flux analysis demonstrated that overexpression of miR-185-5p enhanced autophagic flux in A549 cells, whereas co-overexpression of miR-185-5p and TM9SF1 suppressed autophagic flux. JC-1 assays showed a decreased MMP level in A549 cells after miR-185-5p overexpression, with higher MMP level observed when miR-185-5p and TM9SF1 were co-overexpressed. Conclusion miR-185-5p may suppress proliferation, migration, and autophagy capacities in lung adenocarcinoma cells by targeting TM9SF1 through negative regulation.
Objective To investigate the predictive value of temperature gradients on the mortality of sepsis patients and their correlation with fluid input. Methods By means of a prospective observational method, 154 patients with sepsis or septic shock admitted to the Department of Critical Care Medicine at Nanfang Hospital, Southern Medical University from November 2019 to November 2021 were included as research subjects. They were divided into a survivor group (n=118) and a non-survivor group (n=36) according to whether they survived within 28 days. The core-to-toe temperature gradient (CTTG) and toe-to-room temperature gradient (TRTG) were monitored and calculated immediately upon admission to the intensive care unit (ICU) and 6 hours after admission. Receiver operating characteristic (ROC) curve was used to explore the predictive value of temperature gradients on mortality, and multivariate Cox regression analysis was performed to explore the risk factors of 28-day mortality in sepsis patients. The results were verified through survival analysis. Correlation analysis and multivariate analysis of variance were used to explore the correlation between temperature gradients and fluid input, as well as noradrenaline doses. Results Among the 154 patients, 118 survived within 28 days (survivor group), and 36 died (non-survivor group). ROC curve and multivariate Cox regression analysis showed that a toe-to-room temperature gradient of ≤5.35 ℃ within 6 hours after admission was a risk factor for 28-day mortality. Compared with patients with a high toe-to-room temperature gradient (>5.35 ℃), patients with a low toe-to-room temperature gradient (≤5.35 ℃) had a 2.74-fold increase in the risk of 28-day mortality (P=0.004, 95%CI 1.54, 9.12). The CTTG and TRTG upon admission to the ICU and 6 hours after admission were not significantly associated with fluid input or noradrenaline doses (P>0.05). Conclusions A toe-to-room temperature gradient of less than or equal to 5.35 ℃ within 6 hours after ICU admission is a risk factor for 28-day mortality in sepsis patients. The improvement of temperature gradients at different time points is not associated with fluid input.
Alzheimer's disease (AD), a major cause of dementia, is a common neurodegenerative disease, beginning with memory loss and difficulties with thinking, language and problem-solving skills. Intensification of population aging and the increasing incidence of AD have imposed a heavy burden on healthcare systems. Currently, the main pathological explanation remains the excessive accumulation of β‑amyloid plaques, formation of neurofibrillary tangles and neuronal loss, but the true etiology and pathogenesis of AD remain unknown. The advances of research in AD, with respect to genetics, pathophysiological mechanism, imaging diagnosis and laboratory diagnosis, are reviewed in this article, aiming to provide references for relevant research and potential clinical applications.
Good endometrial receptivity is an essential factor for embryo implantation, and gene expression in endometrial tissue during the window of implantation (WOI) is closely related to receptivity. Transcriptome sequencing technology enables the identification of gene expression profiles of endometrium during different menstrual phases, as well as microRNAs and long-chain non-coding RNA sequences involved in regulating gene expression. Combining this technology with bioinformatics analysis provides a better understanding of specific gene expression during the receptive period and offers technical support for studying its regulatory mechanism. Moreover, gene expression profiles of the endometrium during different menstrual phases hold significant clinical application value for accurately assessing endometrium receptivity in infertility patients and those with repeated implantation failure, thereby guiding individualized embryo transfer strategies. This review summarizes the progress of transcriptome sequencing in evaluating human endometrial receptivity and discusses future research directions. This review aims to understand the complex molecular mechanisms of endometrial receptivity formation and regulation from the transcriptional level, in order to improve the implantation rate of embryos in assisted reproductive technology and reduce the abortion rate.
Objective To compare the disease burden and evolving trends of major malignant tumors in China and globally from 1990 to 2021, and conduct predictive analysis, so as to provide a reference for formulating prevention and treatment policies for malignant tumor in China. Methods Based on the Global Burden of Disease Database 2021 (GBD 2021), descriptive research methods were used to analyze the incidence and mortality of major malignant tumors in China and globally, as well as the changes in their rankings. The Joinpoint log-linear model was applied to analyze trends in age-standardized incidence rates (ASIR) and age-standardized mortality rates (ASMR) of malignant tumors in China and globally from 1990-2021. A Bayesian age-period-cohort (BAPC) model was constructed using R 4.4.0 to predict the incidence trends of malignant tumor in China and globally from 2022 to 2035. Results In 2021, there were 17.2294 million new cases of malignant tumors (excluding non-melanoma skin cancer) and 9.7763 million deaths globally, with an ASIR of 201.06/100,000 and ASMR of 115.11/100,000. In China, 4.5375 million new cases and 2.7964 million deaths were reported, with ASIR and ASMR of 221.30/100,000 and 136.36/100,000, respectively. Lung cancer ranked first in both incidence and mortality of malignant tumors in China and globally. Female breast cancer had the second-highest ASIR in China. The number of incident cases and deaths from digestive system malignancies included in this study accounted for 42.0% of the total incident cases and 46.8% of the total deaths from all cancers in China, respectively. From 1990 to 2021, the average annual percentage change (AAPC) for overall ASIR of malignant tumors in China was 0.30, while ASMR declined (AAPC: -0.97). Globally, ASIR decreased slightly (AAPC: -0.10), and ASMR declined (AAPC: -0.78). The BAPC model predicted that by 2035, China's ASIR of malignant tumors may rise to 252.44/100,000, whereas the global ASIR is expected to decrease to 183.05/100,000. Conclusions China has achieved some success in cancer prevention and treatment, but still faces a heavy disease burden, with ASIR and ASMR exceeding global averages and ASIR persistently increasing. Cancer prevention and control work such as health education should be strengthened. Precise prevention and control measures should be taken for key cancer types, and preventive interventions should be focused on the elderly population.
Objective To investigate the effects of a 100 mT static magnetic field (SMF) on emotional behavior and brain damage-related molecules in mice. Methods Fifty-eight C57BL/6N mice were randomly divided into control group (n=25) and observation group (n=33). Mice in observation group were exposed to a 100 mT SMF for 0.5 h/d over 14 consecutive days, while mice in control group underwent pseudo-exposure. On the 7 and 14 days of exposure, anxiety-like behavior was assessed using open field and elevated plus maze tests. Cerebral blood flow was monitored using laser speckle imaging, and the levels of tumor necrosis factor-α(TNF-α), interleukin (IL)-1β, IL-4, central nervous system specific protein β (S100β), neuron-specific enolase (NSE), and brain-derived neurotrophic factor (BDNF) were measured by radioimmunoassay. BDNF expression in the brain was detected by immunofluorescence. Results On the 7 and 14 days of SMF exposure, the open field and elevated plus maze tests showed no statistically significant differences between observation and control groups in the frequencies, durations, and distance entering the central area of the open field and the open arm of the elevated plus maze (P>0.05). Laser speckle imaging revealed no significant difference in cerebral cortical perfusion compared with pre-exposure period (P>0.05). The results of radioimmunoassay showed that compared with control group, on the 7 d of SMF exposure, the serum IL-1β, NSE and S100β levels were significantly increased (P<0.05), the serum BDNF level was significantly decreased (P<0.05), and the IL-1β and TNF-α contents in brain tissues were significantly increased in observation group (P<0.01). On the 14 d of SMF exposure, serum IL-1β, TNF‑α, NSE, and S100β levels were significantly increased (P<0.05, P<0.0001), and the brain IL-1β and TNF‑α levels were significantly increased (P<0.01) in observation group. No statistically significant differences were found in anti-inflammatory cytokine IL-4 level of serum and brain tissue or BDNF content of brain tissue between the two groups (P>0.05). Conclusion Continuous exposure to a 100 mT SMF for 14 d at 0.5 h/d induces neuroinflammation and brain damage in mice, without inducing anxiety-like behavior.
Persistent inflammation, immuno-suppression and catabolism syndrome (PICS) occurs at the later stage of sepsis, characterized by T cell dysfunction with severe poor outcome. Recent studies found that T cell function be largely affected by its metabolic status. In sepsis, a variety of signaling molecules, including the nutrients, could trigger T cell to undergo metabolic reprogramming that from oxidative phosphorylation to aerobic glycolysis via phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinases (Akt)-mammalian target of rapamycin (mTOR) pathway, leading to severe alterations of its immune phenotype. Glucagon-like peptide-1 (GLP-1) is a kind of incretin hormone that could regulate nutrients and energy metabolism in the body. It can reduce blood glucose level, suppress the immune and inflammatory responses. Plasma GLP-1 levels were rapidly elevated in sepsis and correlated closely with the outcome in critical care. GLP-1 receptor (GLP-1R) agonist could block the glycolysis of T cells, reduce glucose transporter type 1 mRNA expression, and inhibit T cell proliferation. Therefore, the elevated GLP-1 level may represent the metabolic switch toward "aerobic glycolysis", reflecting the pathological status of PICS. Here, the review elucidates the regulation of GLP-1 on the immune function and metabolic reprogramming of T cells and provides strategies for the prevention and treatment of T cell immune dysfunction in sepsis via GLP-1 receptor.
Non-functioning pituitary adenomas (NFPAs) are relatively common. Apart from hyperprolactinemia caused by pituitary compression, they typically lack overt hormonal hypersecretion and usually present with clinical symptoms due to mass effects. Previously considered a uniform entity, NFPAs are actually a highly heterogeneous group of tumors, including aggressive subtypes like silent corticotroph adenomas (SCA) and null cell adenomas. The 2022 WHO new classification of pituitary tumors employs transcription factors [e.g., pituitary-specific transcription factor 1 (PIT-1), T-box transcription factor 19 (TBX19, also known as TPIT), steroidogenic factor 1 (SF-1)] for detailed categorization, allowing precise subclassification of NFPAs into multiple subtypes derived from distinct cell lineages, including silent gonadotroph adenomas, SCA, and plurihormonal PIT-1-positive adenomas. This helps identify highly invasive subtypes with high recurrence risk, guiding clinical diagnosis and treatment, prognostic assessment, and individualized management. The new classification also provides a theoretical basis for targeted therapies of NFPAs (e.g., somatostatin analogs and temozolomide). This review comprehensively discusses the latest pathological classification of NFPAs and its clinical implications, aiming to enhance understanding of this disease and offer valuable insights for precise diagnosis, treatment, and prognostic assessment.
Objective To investigate the risk factors associated with recurrence of high-grade non-functioning pituitary neuroendocrine tumors (NF-PitNETs) following total resection. Methods A retrospective study was conducted on the clinical data of 252 patients with high-grade NF-PitNETs who underwent surgical treatment at the Department of Neurosurgery, Beijing Tiantan Hospital from January 2012 to December 2023, and met the inclusion criteria. High-grade NF-PitNETs included Knosp 3A, 3B, and 4-grade subtypes. Kaplan-Meier curves and Log-rank tests were employed to compare the progression-free survival (PFS) of Knosp 3A, 3B, and 4-grade patients. Cox regression analysis was applied to identify the risk factors associated with the recurrence of high-grade NF-PitNETs. Receiver operating characteristic (ROC) curve was used to calculate the area under the curve (AUC) of each recurrence-related factor to evaluate the diagnostic efficiency. Results Survival analysis revealed that there were significant differences in PFS among Knosp 3A, 3B, and 4-grade patients (P<0.001). The PFS of Knosp 3A was significantly better than that of grade 3B and 4-grade (P<0.05), while there was no significant difference between Knosp 3B and 4-grade (P=0.118). After integrating the three groups into Knosp 3A group and 3B-4 group, there were significant differences in PFS and some clinical features between the two groups (P<0.05). Cox regression analysis indicated that age <55 years old (HR=2.883, 95%CI 1.253-6.634; P=0.013), T2 heterogeneous signal (HR=1.842, 95%CI 1.061-3.197; P=0.030), Knosp 3B-4 (HR=2.190, 95%CI 1.069-4.488; P=0.032), and Ki-67 ≥3% (HR=2.266, 95%CI 1.265-4.061; P=0.006) were risk factors related to tumor recurrence. ROC curve analysis showed that the AUCs of the above-mentioned risk factors were 0.682, 0.706, 0.709 and 0.750, respectively, and the AUC of the multi-factor combined model (age+T2 signal+Knosp grade+Ki-67) was 0.838, which was significantly larger than that of each single risk factor (P<0.05). Conclusion High-grade NF-PitNETs patients with age <55 years old, T2 heterogeneous signal, Knosp 3B-4 and Ki-67≥3% have a higher recurrence risk. The combined application of multiple risk factors can improve the predictive value of recurrence.