Objective To explore the relationship between C-reactive protein/albumin ratio (CAR) and the disease severity in patients with severe pneumonia, and its predictive value for 28-day mortality risk. Methods A retrospective analysis was conducted on 152 patients with severe pneumonia admitted to Fuyang People's Hospital from January 2020 to January 2022. They were divided into non-critical illness group (n=51), critical illness group (n=63), and extremely critical illness group (n=38) based on the disease severity. The clinical data such as age and gender of patients was collected, and Pearson correlation analysis was used to explore the correlation between CAR and the severity of illness [determined by Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score]. Multivariate logistic regression was employed to identify independent influencing factors of the severity of illness. According to the survival status of patients after 28 days of treatment, they were divided into survival group (n=107) and death group (n=45). CAR was categorized into quintiles (Q₁-Q₅), and multivariate logistic regression analysis was conducted to explore the correlation between CAR and 28-day mortality risk in severe pneumonia patients. A restricted cubic spline (RCS) model was used to analyze the dose-response relationship between CAR and mortality risk. The predictive value of CAR and related indicators for patient mortality risk was evaluated using the receiver operating characteristic curve (ROC). Results CAR was significantly positively correlated with the severity of the disease (APACHE Ⅱ score) (r=0.716, P<0.05). Neutrophil/lymphocyte ratio (NLR), blood lactate (Lac), and high CAR were independent risk factors for the disease severity in patients with severe pneumonia (P<0.05). After adjusting for confounding factors, the mortality risk increased with the increase of CAR (P<0.05). Subgroup analysis of the screened confounding factors revealed that the correlation between CAR and 28-day mortality risk in severe pneumonia patients remained stable across different APACHE Ⅱ scores, GCS scores, SOFA scores, white blood cell counts (WBC), neutrophils (NEU), red cell volume distribution width (RDW), procalcitonin (PCT), and Lac, with interactions observed between NLR and Lac subgroups (P<0.05). The RCS model indicated that there was no non-linear dose-response relationship between CAR and 28-day mortality risk in patients with severe pneumonia of different genders. ROC curve analysis showed that CAR, Lac, and NLR had good predictive value for 28-day mortality in severe pneumonia patients, with the combined predictive efficacy being significantly higher than that of individual indicators. Conclusion There is a close relationship between CAR and the progression and prognosis of severe pneumonia, making it a new approach to assessing the severity of illness and predicting mortality risk in patients.

Objective To explore the role and mechanism of silent information regulator 1 (SIRT1) in postoperative cognitive dysfunction (POCD) of aged mice following sevoflurane (SEV) anesthesia. Methods (1) Fifteen-month-old male C57BL/6 mice were randomly divided into control group (n=8) and SEV group (n=24), and SIRT1 expression in hippocampus of mice was assessed using Western blotting on the 1st, 3rd and 7th day after 2% SEV exposure. (2) Fifteen-month-old male C57BL/6 mice were randomly divided into AAV-GFP, AAV-SIRT1, SEV+AAV-GFP and SEV+AAV-SIRT1 groups (n=20). AAV-SIRT1 and control AAV-GFP vectors were transfected into the brain of mice respectively. Five days after the transfection, the corresponding groups of mice were exposed to 2% SEV for 5 h. Morris water maze test was used to evaluate the spatial memory of mice before and after SEV exposure, TUNEL staining was applied to assess hippocampal neurons apoptosis, and Western blotting was utilized to measure the expression levels of SIRT1, xCT and glutathione peroxidase 4 (GPX4). (3) Hippocampal neurons of mice were divided into control, AAV-SIRT1, Fer-1, SEV, SEV+AAV-SIRT1 and SEV+ferrostatin-1 (Fer-1) groups. Neurons in SEV, SEV+AAV-SIRT1 and SEV+Fer-1 groups were exposed to 5% SEV for 4 h. SEV+AAV-SIRT1 and SEV+Fer-1 groups were transfected with AAV-SIRT1 or treated with Fer-1 respectively prior to SEV exposure. Neuronal death was evaluated via propidium iodide (PI) staining. Malondialdehyde (MDA) level and iron content were determined using ELISA, reactive oxygen species (ROS) level was determined using fluorescence probes. Results (1) Western blotting revealed a significant reduction in SIRT1 protein expression levels in the hippocampus tissue of SEV group mice compared to control group (P<0.05). (2) Morris water maze test results showed that, compared with AAV-GFP group, the escape latency of mice in SEV+AAV-GFP and SEV+AAV-SIRT1 groups significantly prolonged (P<0.05), and the frequency of crossing the platform significantly decreased (P<0.05). Compared with SEV+AAV-GFP group, the escape latency of mice in SEV+AAV-SIRT1 group shortened (P<0.05), and the frequency of crossing the platform on the 7th day increased (P<0.05). TUNEL staining, Western blotting and immunohistochemistry indicated that the apoptosis of hippocampal neurons, Bax and cleaved-caspase-3 protein expression levels significantly increased in SEV+AAV-GFP and SEV+AAV-SIRT1 groups compared with those in AAV-GFP group, while the expression of Bcl-2, GPX4, and xCT protein expression levels significantly decreased (P<0.05 or P<0.01 or P<0.001). Compared with SEV+AAV-GFP group, SEV+AAV-SIRT1 group showed that apoptosis of hippocampal neurons, Bax and cleaved-caspase-3 protein expression levels significantly decreased (P<0.05), while Bcl-2, GPX4, and xCT protein expression levels significantly increased (P<0.05). (3) In vitro, PI staining and ELISA demonstrated significantly increased PI positive rate, MDA level and iron content in hippocampus neurons of SEV group compared to control group (P<0.01). Compared with SEV group, the positive rate of PI staining, MDA level, iron content and ROS level in hippocampus neurons of SEV+AAV-SIRT1 and SEV+Fer-1 groups significantly decreased (P<0.05). Conclusions SEV anesthesia leads to a decrease in SIRT1 expression in hippocampus and neurons of aged mice, and the upregulation of SIRT1 could alleviate SEV-induced neuronal death and ferroptosis.

Preeclampsia (PE) is a severe hypertensive disorder during pregnancy that seriously affects the health of pregnant women and fetuses. Currently, the treatment is merely symptomatic, with unsatisfactory efficacy and often resulting in an increased incidence of therapeutic preterm birth. An increasing number of studies on PE suggest that the "unitary" theory is no longer adequate to elucidate its pathogenesis. PE is regarded as a syndrome influenced by multiple factors, featuring a complex pathogenesis and the potential to affect multiple organs and systems. This review summarizes the latest advancements in the classification, etiology, pathogenesis, and research models (including animal and in vitro models) of PE, aiming to provide references for subsequent research and offer assistance in clinical prevention, screening, and treatment.

Objective To investigate the protective effects of secretomes released by three-dimensional cultured mesenchymal stem cells (MSCs) on neurons subjected to seawater immersion (SW) and stretch injury (SI), and to provide new insights into neuronal repair following SW combined with traumatic brain injury (TBI). Methods MSCs were cultured using the hanging drop method, and the conditioned medium (CM) containing MSCs secretomes was collected. A cellular model combining SW with SI was established using mouse hippocampal neuronal cells (HT22 cells). HT22 cells were randomly assigned to five groups: control, SI, SI+SW, SI+CM, and SI+SW+CM groups. Cell viability was assessed using the CCK-8 assay, apoptosis rate was measured by flow cytometry, cell migration ability was evaluated by scratch assay, and the expression levels of apoptosis-related proteins Bcl-2 and Bcl-2-associated protein (Bax), and ferroptosis-related proteins long-chain acyl-CoA synthetase 4 (ACSL4) and cyclooxygenase-2 (COX-2) were detected by Western blotting. Results Immersion in 15% seawater for 12 h significantly decreased HT22 cell viability (P<0.05). The CCK-8 assay indicated that cell viability in both the SI and SI+SW groups was significantly lower than that in control group after 12 h of treatment (P<0.05). Treatment with CM containing MSCs secretomes significantly increased cell viability in SI+CM group compared to SI group (P<0.0001), and in SI+SW+CM group compared to SI+SW group (P<0.001). Flow cytometry results revealed that the apoptosis rate in SI and SI+SW groups was significantly higher than that in control group (P<0.05 or P<0.001), while in SI+CM group was lower than that in SI group (P<0.05), and in SI+SW+CM group was lower than that in SI+SW group (P<0.05). Western blotting showed that compared to control group, SI and SI+SW groups exhibited reduced Bcl-2 expression level (P<0.01 or P<0.0001) and increased expression levels of Bax, ACSL4, and COX-2 (P<0.01 or P<0.0001). Compared to SI group, the SI+CM group displayed increased Bcl-2 expression level (P<0.05) and decreased expression levels of Bax, ACSL4, and COX-2 (P<0.05). Compared to SI+SW group, SI+SW+CM group exhibited increased Bcl-2 expression level (P<0.01) and decreased expression levels of Bax, ACSL4, and COX-2 (P<0.01 or P<0.001). Scratch assay results demonstrated that at both 12 h and 24 h, the cell migration rate in SI and SI+SW groups was significantly lower than that in control group (P<0.01 or P<0.0001), while the migration rate in SI+CM group was significantly higher than that in SI group (P<0.0001 or P<0.01), and the migration rate in SI+SW+CM group was significantly higher than that in SI+SW group (P<0.0001). Conclusion Secretomes derived from MSCs cultured using the hanging drop method can alleviate neuronal damage caused by SW and TBI, potentially offering a therapeutic approach for SW combined with TBI.

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.

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 diagnostic value of 4 novel inflammatory markers related to routine blood tests, namely neutrophil-to-lymphocyte ratio (NLR), red blood cell distribution width (RDW), hemoglobin-to-RDW ratio (HRR) and systemic immune-inflammation index (SII), in elderly patients with chronic cardiovascular disease (CVD) complicated with frailty. Methods Retrospectively analyze 110 patients with chronic stable CVD who were hospitalized in the cadre ward of cardiovascular medicine at the Air Force Characteristic Medical Center from January 2022 to June 2023. According to the assessment results of the Fried scale, they were divided into three groups: non-frailty group (Fried score=0, n=30), the pre-frailty group (Fried score 1 or 2, n=40) and frailty group (Fried score ≥3, n=40). The differences in general information, the impairment rate of daily living activities, miniature nutritional assessment-short form (MNA-SF) scores, mini-mental state examination (MMSE) scores, and the indicators such as NLR, RDW, HRR, and SII among the three groups were compared. Spearman rank correlation was used to analyze the correlation between NLR, RDW, HRR, SII and frailty scores as well as each frailty indicator. Multivariate logistic regression analysis was performed to identify the independent risk factors for frailty in elderly patients with chronic CVD, and the receiver operating characteristic (ROC) curve was used to assess the clinical diagnostic value of NLR and HRR in elderly patients with chronic CVD complicated with frailty. Results Compared with non-frailty group and pre-frailty group, patients in frailty group were older, with higher impaired rates of daily living activities, NLR, RDW, and SII, and lower MNA-SF scores, MMSE scores, and HRR, and differences were statistically significant (P<0.05). Spearman rank correlation analysis showed that the frailty score was positively correlated with NLR (r_s=0.354, P<0.001), and RDW (r_s=0.448, P<0.001), negatively correlated with HRR (r_s=-0.232, P=0.024), and had no significant correlation with SII (r_s=0.144,P=0.167). Further analysis of the correlation between the above novel inflammatory markers and the 5 components of frailty showed that NLR was positively correlated with fatigue (r_s=0.228, P=0.017), slowed walking speed (r_s=0.299, P<0.001), and low physical function(r_s=0.319, P<0.001); RDW was positively correlated with decreased grip strength (r_s=0.321, P<0.001), slowed walking speed (r_s=0.422,P<0.001), and low physical function (r_s=0.246, P=0.001); and HRR was negatively correlated with slowed walking speed (r_s=-0.230, P=0.025), and low physical function (r_s=-0.299, P=0.003). Multivariate logistic regression analysis showed that MNA-SF score (OR=0.577, 95%CI 0.342-0.973) was an independent protective factor for pre-frailty in elderly patients with chronic CVD (P<0.05); NLR (OR=7.866, 95%CI 1.101-56.185) was an independent risk factor for frailty, while HRR (OR=0.344, 95%CI 0.120-0.983) and MNA-SF score (OR=0.292, 95%CI 0.146-0.580) were independent protective factors for frailty in elderly CVD patients (P<0.05). The area under the ROC curve of NLR and HRR for diagnosing frailty in elderly patients with chronic CVD were 0.778 and 0.749, respectively. Conclusion NLR and HRR have high clinical diagnostic value for frailty in elderly patients with chronic CVD, and are expected to become effective inflammatory markers for screening elderly patients with chronic CVD complicated with frailty.

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 investigate the comparative neuroprotective effects of human umbilical cord mesenchymal stem cells (hUC-MSCs-Exos) administered via different routes on hypoxic ischemic brain damage (HIBD) in neonatal mice. Methods Healthy one-week-old SPF-grade BALB/c mice were randomly divided into 4 groups: sham operation group (n=6), model group (n=6), exosome group 1 (n=8), exosome group 2 (n=8). HIBD was induced using the Rice-Vannucci method. Exosome group 1 and Exosome group 2 were intraperitoneal injection/intranasal drip of phosphate buffer (PBS) 100 μl containing 10 μl exosomes within 24 h after successful modeling, respectively. Sham operation and model groups were intraperitoneal injection of PBS 100 μl. On the 7th day after the intervention, neuromotor function was assessed using the horizontal grid test and pole climbing test. On the 2nd day after the evaluation, all mice were killed and their brains were removed by decapitation. HE staining was used to observe the pathological injury of brain tissue, toluidine blue staining was used to observe the survival of neurons in cerebral cortex, and TUNEL staining was used to observe the apoptosis of cerebral cortex cells. Results Compared with sham operation group, model group, exosome group 1 and exosome group 2 exhibited increased hind limb drops in horizontal grid test and climbing scores (P<0.05). No significant difference was found in model group, exosome group 1 and exosome group 2 in these measures (P<0.05). Significant pathology was observed in model group, exosome group 1 and exosome group 2 compared to sham operation group (P<0.05), with significantly reduced damage in exosome group 1 and exosome group 2 compared to model group (P<0.05). Compared with sham operation group, Nissl body count was lower in model group and exosome group 1 and exosome group 2, with a higher count in exosome group 2 compared to exosome group 1 (P<0.05). Compared with sham operation group, apoptotic cells were higher in model group and exosome group 1 and exosome group 2, with a significant reduction in exosome group 1 and exosome group 2 compared to model group, and the lowest in exosome group 2 (P<0.05). Conclusions hUC-MSCs-Exos can improve the neuronal motor function, promote neuron repair and inhibit apoptosis in HIBD mice. Intranasal administration of hUC-MSCs-Exos is more effective than intraperitoneal administration for reducing neuronal apoptosis in HIBP neonatal mice, offering a convenient and rapid method suitable for clinical application.

Objective To explore the pathogenic mechanisms of Legionella pneumophila (L. pneumophila) infection inhibiting the fusion of endosome-lysosome fusion in mouse macrophages. Methods Twelve C57 mice were randomly divided into control group and L. pneumophila infection group (n=6 each). After anesthesia, an equal volume of physiological saline or L. pneumophila solution was administered nasally. Body weight changes were monitored for 3 consecutive days, and the lungs were extracted to assess injury. Hematoxylin and eosin (HE) staining and immunohistochemical staining were performed to observe the pathological characteristics of lung tissue in both groups. Transcriptome sequencing was utilized to analyze differentially expressed genes (DEGs) and associated signaling pathways in lung tissues. Mouse bone marrow macrophages (BMDMs) were isolated and co-cultured with L. pneumophila, with infection status confirmed by immunofluorescence staining. Transcriptome sequencing was employed to analyze DEGs and enriched related signaling pathways before and after infection. Core genes involved in the post-infection signaling pathway were identified, and the consistency of their mRNA expression levels in vivo and in vitro was verified using RT-qPCR. The expression of relevant proteins was detected by Western Blotting, and bacterial proliferation assays were conducted to evaluate the intracellular replication of L. pneumophila. Results Compared with control group, the body weight of mice in L. pneumophila infection group significantly decreased (P<0.001) on the second and third day post-infection. Edema and red hepatoid degeneration were observed in both left and right lung tissues, with lesion areas spreading from the hilum to the lung periphery. HE staining revealed increased inflammatory cell infiltration in the alveolar spaces, thickening of alveolar septa and increased fibrin exudation in L. pneumophila infection group. Immunohistochemistry results showed a significant increase in myeloperoxidase (MPO) activity in the lung tissue infected mice (P<0.001). Transcriptome sequencing identified 2550 DEGs, with 1444 up-regulated genes and 1106 down-regulated genes. KEGG enrichment analysis indicated that these DEGs were mainly involved in pathways related to tumor necrosis factor, rheumatoid arthritis, Rap1, PI3K-Ak, and phagosome pathways. Immunofluorescence results showed in vitro proliferation of L. pneumophila within mouse BMDMs. Transcriptome sequencing identified 2550 DEGs, including 1677 up-regulated genes and 873 down-regulated genes. KEGG enrichment analysis showed that enrichment in pathway related to transcription dysregulation in cancer, PI3K-Akt and phagosome pathways. Thirteen core genes, including tubulin β1 (Tubb1), were identified from the overlap between mouse lung tissue and BMDMs. RT-qPCR results demonstrated a significant decrease in Tubb1 expression in both lung tissue and BMDMs infected with L. pneumophila (P<0.001). Western Blotting results revealed significant decreases in Rab7, Tubb1, and LAMP2 protein expression (P<0.05), and increases in iNOS and MPO expression (P<0.05). Intracellular proliferation experiments indicated that L. pneumophila gradually increased within BMDMs over time. Conclusion The potential mechanism of L. pneumophila infection in mouse macrophages involves the down-regulation of Rab7/Tubb1/LAMP2 which inhibits the endosome-lysosome fusion.