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.

The neurovascular unit (NVU) is the smallest structural unit that maintains the integrity of the blood-brain barrier (BBB), regulates cerebral physiological activities, and maintains the homeostasis of the brain's internal environment. It has become a hot topic in the study of brain physiology and pathological changes. NVU plays a crucial role in age-dependent central nervous system diseases such as cerebral white matter lesions, cognitive impairment, and cerebrovascular disease. Its dysfunction can lead to destruction of BBB integrity, with subsequent protein leakage, immune-inflammatory responses, and alterations in cerebral hemodynamics, all of which can trigger seizures or progression of neurodegenerative disorders. Conversely, seizures can also accelerate NVU dysfunction and promote brain aging. The review summarizes the role of dysfunctional constituent cells of the NVU in the pathogenesis of age-dependent epilepsy and the research progress in related molecular pathways, aiming to provide new perspectives for epilepsy treatment research.

Spinal cord injury (SCI) is a central nervous system disease with high morbidity and disability rates, bringing serious economic and psychological burdens to families and society worldwide. AMP-activated protein kinase (AMPK) is an important sensor in the energy metabolism process in living organisms, which plays a central role in maintaining energy balance. It is currently considered a key target for the prevention and treatment of multiple diseases. Studies have shown that AMPK signaling can regulate autophagy, neuroinflammation, oxidative stress, mitochondrial function and other processes after SCI, thus affecting the pathological process of SCI. This review summarizes the research progress on AMPK signaling pathway involved in the regulation of SCI, in order to provide new ideas for the treatment and drug development of SCI.

Heatstroke, especially in high-temperature and high-humidity environments, is a life-threatening acute heat-injury disease that seriously endangers human health. Timely and effective on-site treatment is crucial for patients' survival and prognosis. Early recognition, rapid assessment, and on-site cooling are the core of pre-hospital treatment of heatstroke. Currently, there is a lack of standardized application procedures for pre-hospital emergency care of heatstroke. Therefore, the "Expert Consensus on Pre-hospital Emergency Management of Heatstroke (2024 edition)" was initiated by the Expert Group on Heatstroke Prevention of the People's Liberation Army and developed in collaboration with experts from local pre-hospital emergency care, emergency departments, and intensive care units. This consensus focuses on heatstroke prevention, on-site and ambulance-based treatment, and early emergency room interventions, and puts forward 10 evidence-based recommendations, aiming to provide a reference for scientific and standardized pre-hospital emergency care of heatstroke.

Objective To explore the influencing factors of different types of small intestinal bacterial overgrowth (SIBO). Methods A total of 539 patients who were hospitalized in the Department of Gastroenterology, the Sixth Medical Center of PLA General Hospital from June 2021 to December 2021 and who underwent methane-hydrogen breath test were retrospectively selected. Based on breath test results, patients were divided into SIBO-negative group (n=300) and SIBO-positive group (n=239). The clinical data were compared between two groups. According to the specific values of breath test results, SIBO-positive patients were further divided into hydrogen-producing bacterial overgrowth (hydrogen-positive, n=103), intestinal methanogen overgrowth (methanogen-positive, n=80), and simultaneous methanogen and hydrogen-producing bacterial overgrowth (double positive, n=56) groups. Multivariate logistic regression analysis was employed to identify influencing factors of different SIBO types. Additionally, SIBO-positive patients were categorized by age into <45 years (n=23), 45-60 years (n=82), 60-75 years (n=124), and ≥75 years (n=10) to compare SIBO positivity rates across age groups. Results The patients in SIBO-positive and double positive groups were older and had a lower body mass index (BMI) than those in SIBO-negative group, with statistically significant differences (P<0.05). Compared with the patients in SIBO-negative group, those in hydrogen-positive group showed a higher proportion of history of coronary heart disease, those in methanogen-positive group were older, and higher proportion of statin use, with statistically significant differences (P<0.05). Multivariate logistic regression analysis revealed that, among different SIBO types, a history of coronary heart disease served as an independent risk factor for hydrogen-producing bacterial overgrowth (OR=2.728, 95%CI 1.271-5.857, P=0.010). For methanogen overgrowth, increasing age was identified as an independent risk factor (OR=1.040, 95%CI 1.009-1.063, P=0.010), while the application of statin played the role of an independent protective factor (OR=0.420, 95%CI 0.236-0.754, P=0.003). As for the simultaneous overgrowth of methane-producing and hydrogen-producing bacteria, increased BMI was found to be an independent protective factor (OR=0.870, 95%CI 0.786-0.964, P=0.008). In SIBO-positive group, it was found that for patients aged <45 years, both the methane-positive rate and the double-positive rate were significantly lower than the hydrogen positivity rate (P<0.05). Moreover, among patients aged 45-60 years, the double-positive rate was significantly lower than the hydrogen positivity rate (P<0.01). When it comes to the hydrogen-positive rate, it was significantly lower for patients aged 45-60 and 60-75 years compared with that of patients aged <45 years (P<0.05). In contrast, the methane-positive rate and the double-positive rate were significantly higher for patients aged 45-60 and 60-75 years than those of patients aged <45 years (P<0.01). Conclusion A history of coronary heart disease and increasing age are independent risk factors for intestinal hydrogen-producing bacterial overgrowth and methanogen overgrowth, respectively. The application of statins and increased BMI are independent protective factors for intestinal methanogen simultaneous overgrowth of methanogen and hydrogen-producing bacteria, respectively.

Objective To investigate the improvement effects of homogeneous fecal microbiota transplantation (FMT) on chemotherapy-induced diarrhea (CID) in mice. Methods Fifteen C57BL/6N mice were divided into control group, CID model group and CID+FMT group according to the random number distribution and remainder grouping method, with 5 mice per group. Control group received no intervention, and their feces were used to prepare fecal bacteria suspension. CID model group was injected intraperitoneally with fluorouracil (65 mg/kg) for 5 consecutive days to construct the CID mouse model, followed by gavage with 0.1 ml of saline on alternate days. CID+FMT group was given 0.1 ml fecal bacteria suspension gavage on alternate days for one week, followed by intraperitoneal injection of fluorouracil (65 mg/kg) for 5 consecutive days to construct the CID mouse model, with the experiment ending on the 14th day. During the experiment, the mice's food intake and body weight were recorded. At the end of the experiment, the mice were euthanized with deep carbon dioxide anesthesia, and the mice colonic specimens from cecum to anus were collected for hematoxylin and eosin (HE) staining and histopathological examination. Fecal samples were collected for 16S rRNA gene sequencing. Shannon index, Simpson index and Chao1 algorithm were used to analyze the α-diversity species of the intestinal flora in each group of mice. Similarity analysis (Anosim) was used to perform non-parametric on the inter-group differences of intestinal flora among the mice. Linear discriminate analysis size effect (LEfSe) and nonmetric multidimensional scaling (NMDS) were employed to analyze the intestinal dominant flora and the similarity classification relationships in each group of mice. Results The colonic specimen's length from cecum to anus in CID model group was significantly shorter than that in control group (P<0.05), while there was no significant difference between CID+FMT group and CID model group (P>0.05). The weight of mice in CID model group decreased by 42.04%, while control group mice gained 10.24%, with a significant difference between the two groups (P<0.05). The weight of mice in CID+FMT group decreased by 8.12%, which was significantly improved compared to CID model group (P<0.05). HE staining results revealed the intestinal mucosal structure in CID model group was severely damaged, with atrophy and deformation, accompanied by inflammatory cell infiltration, and the pathological score was higher than that of control group (P<0.05). Compared with CID model group, the intestinal mucosal integrity and crypt cells in the CID+FMT group were improved, with less damage, and the pathological score was lower than that of CID model group, but the difference was not statistically significant (P>0.05). The α-diversity analysis showed that there were significant differences in the Shannon, Simpson and Chao1 indices among the three groups (P<0.05). ANOSIM and NMDS analysis revealed that the intestinal flora in CID+FMT group was closer to the normal intestinal flora compared to CID model group. LEfSe analysis showed that the intestinal flora in CID model group was enriched in famliy_Bacteroidaceae, and the intestinal flora in CID+FMT group was similar to that of control group, with an enrichenment of familiy_Enterobacteriaceae. Conclusion Homogeneous FMT can improve the abundance of intestinal flora in CID mice, making it more similar to normal intestinal flora, thereby protecting intestinal mucosa, reducing damage and alleviating the severity of CID.

Graves' ophthalmopathy (GO) is a specific autoimmune disease occurring in orbital tissues and is closely related to hyperthyroidism caused by Graves' disease (GD). Its disabling and disfiguring features significantly impact the quality of life of patients. The exact mechanism of GO still remains to be fully elucidated. In recent years, gene sequencing and medical microbiology studies have shown that changes in the gut microbiota may play a role in the development and progression of GO, with gut dysbiosis altering immune system regulatory signals and causing immune damage to organs. Clarifying the correlation between gut microbiota and GO helps to understand the disease's pathogenic mechanism and provides a theoretical basis for the diagnosis and treatment of GO. This review summarizes the impact of gut microbiota dysbiosis in the pathogenesis of GO and promising therapeutic approaches, including research progress in aspects such as gut microbiota experiments, case studies, pathogenesis, and treatment strategies.

Gastrointestinal stromal tumor (GIST) is the most prevalent mesenchymal tumor of the gastrointestinal tract, with imatinib serving as the first-line drug for metastatic GIST due to its good clinical efficacy. However, the majority of patients exhibit tumor progression within several years of drug therapy, primarily due to the high rate of drug resistance, which significantly impedes drug therapeutic outcome and patient prognosis. Traditional approaches to counteract resistance, including dosage increase and subsequent line therapy yielded suboptimal results. As a research hotspot, intestinal flora has been proven to be closely related to drug resistance of various tumors. In recent years, it has been observed that specific intestinal flora could serve as biomarkers for early GIST patient screening or as potential drug targets, and modulating the intestinal flora through interventions may delay or even reverse the progression of imatinib secondary drug resistance in GIST. This review delineates the drug resistance of GIST, correlations between intestinal flora and drug resistance of tumors, as well as the relationship between intestinal flora and drug resistance of GIST, aiming to provide novel perspectives and methodologies for clinical application.

Systemic lupus erythematosus (SLE) is a chronic diffuse connective tissue disease characterized by abnormal activation of the immune system, which attacks the body's tissues. It has a complex course and its pathological basis is vasculitis. In recent years, research on the relationship between SLE and the gut microbiota has increased significantly, but how to regulate the gut microbiota for the treatment of SLE remains unclear. Studies have found that the intestinal microbiota of SLE patients differs from that of healthy people in terms of Firmicutes, Bacteroidetes, Actinomycetes, and Proteobacteria, etc., and this has been verified in animal experiments. In this review, the changes of intestinal microbiota in SLE patients and their association with the pathogenesis and progression of the disease are systematically reviewed, aiming to provide new insights into the treatment of SLE.

Objective To analyze the epidemiological distribution, microbiological characteristics, drug-resistance status, and risk factors for mortality in adult intensive care unit (ICU) patients with Klebsiella pneumoniae infection. Methods This multi-center prospective cohort study included ICU patients with suspected infection from 67 hospitals across 16 Chinese provinces/municipalities between July 1, 2021 and December 31, 2022. Clinical data and microbiological results were collected, and patients were divided into survival and non-survival groups according to their survival status and drug-resistance situation. Risk factors for mortality and drug resistance in ICU patients with Klebsiella pneumonia infection were determined through univariate and multivariate logistic regression analyses. Results A total of 2964 ICU-infected patients were enrolled, with 12 175 microbial specimens submitted for testing. Among these, 487 specimens tested positive for Klebsiella pneumoniae. Ultimately, 314 patients with Klebsiella pneumoniae infection were identified, primarily from lung infections, with a drug-resistance rate of 78.3%. The in-hospital mortality rate of ICU patients infected with Klebsiella pneumoniae was 19.8%. Univariate and multivariate logistic regression analyses revealed that older age (P=0.027), high drug-resistance rate (P=0.028), and low clinical-effectiveness rate (P<0.001) were independent risk factors for mortality in ICU patients infected with Klebsiella pneumoniae. Drug-resistance analysis showed that, compared with non-resistant cases, ICU patients with drug-resistant Klebsiella pneumoniae infection had lower pathogen-clearance rates (P=0.003), clinical-effectiveness rates (P=0.004), and antibiotic-effectiveness rates (P<0.010), and higher mortality rates (P=0.006). Patients with Klebsiella pneumoniae abdominal infection (P=0.003) and urinary tract infection (P=0.007) had higher drug-resistance incidences. There were no statistically significant differences in clinical-effectiveness rate, Klebsiella pneumoniae clearance, drug-resistance incidence, mortality rate, or hospital-stay length between patients with lung infection and those with non-lung infection of Klebsiella pneumoniae (P>0.05). Compared with patients with non-bloodstream infection, patients with bloodstream infection of Klebsiella pneumoniae had lower clinical-effectiveness rates (P=0.027) and higher mortality rates (P=0.021). Conclusions Older age, high drug-resistance rate, and low clinical-effectiveness rate are independent risk factors for mortality in ICU patients infected with Klebsiella pneumoniae. ICU patients with bloodstream infection of Klebsiella pneumoniae may have lower clinical-effectiveness rates and higher mortality rates. ICU patients with abdominal and urinary tract infections caused by Klebsiella pneumoniae are more likely to develop drug resistance.