The gut-kidney axis is critical in acute kidney injury (AKI) pathophysiology, but its specific characteristics in intensive care unit (ICU) patients remain unclear. This study aimed to investigate compositional and functional alterations of gut microbiota in AKI patients. Patients were divided into AKI and non_AKI groups. Rectal swabs were collected within 24 h of ICU admission. 16SrDNA sequencing was performed to assess taxonomic composition. Alpha diversity, beta diversity, and Linear discriminant effect size analysis (LEfSe) analyses were conducted. Redundancy analysis (RDA) examined relationships between microbial communities and environmental factors. PICRUSt2 inferred metabolic functional differences. Average causal mediation effect (ACME) analysis explored relationships among dysbiosis, metabolic function, and clinical factors. A total of 193 individuals comprising 142 AKI and 51 non_AKI were enrolled in the study. Compared to non_AKI patients, the AKI group exhibited significantly higher gut microbiota species richness as measured by the ace index (p < 0.05), indicating an increase in moderately abundant species potentially including opportunistic pathogens. However, no significant differences were observed in chao1 index (another measure of richness), nor in the shannon and simpson indices (measures of overall diversity and evenness), suggesting that while certain bacterial populations expanded, the fundamental structure and balance of the gut ecosystem remained preserved. Significant differences in overall community composition (beta diversity, p < 0.05) were observed between groups. LEfSe identified AKI-associated dysbiosis characterized by proliferation of opportunistic pathogens (e.g., s__Staphylococcus haemolyticus, s__Ruminococcus bromii, and g__Veillonella) and extraintestinal bacterial intrusion (e.g., s__Sneathia amrii, s__Atopobium vaginae). RDA showed that serum creatinine (SCr, r² = 0.079, p = 0.006) and blood urea nitrogen (BUN, r² = 0.066, p = 0.007) were the only clinical factors significantly impacting microbial community structure. PICRUSt2 revealed significant functional alterations between groups, with multiple metabolic pathways (including URSIN-PWY, PWY-5420, PWY-5415, PWY-7854, PWY-5367, TYRFUMCAT-PWY, PWY-5181, PWY-7480, and PWY-5430) showing differential abundance. Exploratory mediation analysis constructed a potential association network linking gut microbiota dysbiosis, altered metabolic pathways, and SCr levels. AKI patients exhibited gut microbiota dysbiosis characterized by opportunistic pathogen proliferation and extraintestinal bacterial intrusion. These alterations were observed in association with disease severity and could potentially relate to SCr levels, possibly via modulation of specific metabolic pathways. This research was based on the analysis of hospital-acquired infection surveillance data and was not registered in a clinical trial registry.

The gut microbiota is profoundly disrupted during critical illness, yet the bacteriophage component has received almost no systematic study. Bacteriophages actively shape bacterial community composition through lytic and lysogenic interactions, but whether gut phage diversity tracks organ dysfunction severity in critically ill patients—and whether any such relationship is reproducible—is unknown. We analysed shotgun metagenomes from two independent ICU cohorts: a discovery cohort of 196 medical ICU patients (BioProject PRJNA1134172 Chicago Cohort, US) and an external exploratory replication cohort of 22 ARDS patients from a geographically distinct centre Qingdao cohort, China. A catalogue of 1,815 non-redundant viral operational taxonomic units (vOTUs) was constructed using geNomad and CheckV and clustered at 95

OBJECTIVE:To investigate the association between acute kidney injury (AKI) and the gut microbiota by integrating 16S sequencing analysis with mendelian randomization (MR). METHODS:1) MR analysis: The genome-wide association study (GWAS) dataset for AKI from the FinnGen consortium and the GWAS dataset for gut microbiota composition from the Dutch Microbiome Project were selected to screen single nucleotide polymorphism (SNP) associated with AKI as instrumental variable (IV) for genetic variation, using AKI as the exposure factor. Potential causal associations between AKI and gut microbiota were analyzed using a two-sample, one-way MR analysis with the primary analysis method of inverse variance weighted (IVW). Heterogeneity analysis was performed using the Cochran Q test. Potential pleiotropy was assessed using the MR-Egger intercept test. Sensitivity analysis was performed using the leave-one-out test. 2) Clinical cohort study: Consecutive patients admitted to the intensive care unit (ICU) of Qingdao Municipal Hospital between December 2024 and March 2025 were prospectively enrolled. Patients were classified into the AKI group or the non-AKI group based on the occurrence of AKI during their ICU stay, according to the diagnostic criteria from Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines (2012). Baseline clinical data were collected within 48 hours of ICU admission, including gender, age, height, weight, body mass index (BMI), major comorbidities, vital signs, serum creatinine (SCr), blood routine, C-reactive protein (CRP), interleukin-6 (IL-6), etc. Anal swabs were collected from patients within 48 hours of ICU admission for 16S rDNA high-throughput sequencing. Significant difference analysis and linear discriminant analysis effect size (LEfSe) were performed to characterize the gut microbiota profile in AKI patients and to further validate the findings from the MR analysis. RESULTS:1) MR analysis results: Using the GWAS summary statistics for gut microbiota and AKI, the MR analysis revealed that the genetic liability to AKI was associated with decreased abundance in six gut microbial taxa and increased abundance in one taxon. IVW analysis showed that at the genus level, genetic susceptibility to AKI was associated with lower abundance of Collinsella (β=-0.144, P=0.029), Lachnospiraceaenoname (β=-0.131, P=0.040), Roseburia (β=-0.126, P=0.047), and Parasutterella (β=-0.198, P=0.023). At the species level, AKI genetic susceptibility was linked to reduced abundance of Parasutterellaexcrementihominis (β=-0.197, P=0.024) and Roseburia unclassified (β=-0.280, P=0.012), while being associated with increased abundance of Bacteroidesintestinalis (β=0.358, P=0.013). Cochran Q test showed no heterogeneity, MR-Egger intercept test revealed no pleiotropy, and leave-one-out analysis verified the robustness of the results. 2) Clinical cohort study results: A total of 129 patients were initially enrolled. After excluding 25 patients with incomplete clinical data and 10 whose samples failed to generate sufficient 16S rDNA gene amplification for sequencing, 94 patients were included in the final analysis comprising 72 cases in the AKI group and 22 cases in the non-AKI group. Apart from higher SCr levels in the AKI group than those in the non-AKI group, no statistically significant differences were observed in other baseline clinical characteristics between the two groups. 16S rDNA high-throughput sequencing yielded 6 868 647 high-quality reads, which were clustered into 13 025 amplicon sequence variant (ASV). Significant difference analysis at the species level showed that, compared with the non-AKI group, patients in the AKI group had a relative enrichment of Streptococcus anginosus and Novosphingobium sp. B0.09-8. Conversely, the relative abundances of uncultured Prevotellasp., Alistipesshahii, uncultured Coprococcussp., Collinsellatanakaei, Streptococcus equinus, Alistipesindistinctus, Klebsiellasp. GRB36, and uncultured Oscillospirasp. were significantly lower in the AKI group. LEfSe analysis identified Veillonella unclassified, Ligilactobacillus unclassified, Collinsellatanakaei, Atopobium unclassified, and Streptococcus anginosus as potential biomarkers for the AKI group, whereas Alistipesshahii, uncultured Prevotella sp., and Agathobacter unclassified were more characteristic of the patients in the non-AKI group. CONCLUSIONS:The MR analysis suggests that the occurrence of AKI exerts an influence on the gut microbiota profile, characterized by a reduction in the abundance of the genus Collinsella. Findings from the real-world study further indicate significant differences in gut microbiota composition between patients with and without AKI. Overall, the gut microbiota of AKI patients is characterized by an enrichment of pro-inflammatory bacteria and a depletion of commensal symbionts. The genus Collinsellamay may serve as a potential biomarker for AKI.

OBJECTIVE:To analyze the factors influencing the development of refeeding syndrome (RFS) in patients with sepsis and its impact on clinical prognosis. METHODS:A retrospective case-control study method was used to collect the clinical data of patients with sepsis admitted to the intensive care unit (ICU) of Qingdao Municipal Hospital from December 2018 to December 2023. The patients were divided into RFS and non-RFS groups according to whether RFS occurred, and the basic data, nutritional status and assessment scale, laboratory indicators, nutritional intake, medical history and prognosis were compared between the two groups. Binary multifactorial Logistic regression analysis was used to screen the influencing factors of the occurrence of RFS in patients with sepsis. RESULTS:A total of 544 patients with sepsis were finally enrolled, of whom 250 did not develop RFS and 294 developed RFS, with an incidence of 54.0%. Compared with the non-RFS group, the patients in the RFS group had lower body mass index (BMI), albumin, prealbumin, baseline electrolytes (serum phosphorus, serum potassium, and serum magnesium), creatinine-height index, and protein intake, and had higher nutritional risk screening 2002 (NRS2002) score, sequential organ failure assessment (SOFA) score, calorie intake, and the proportions of feedings during the 48 hours of ICU admission, history of diabetes and septic shock. Binary multifactorial Logistic regression analysis showed that BMI [odds ratio (OR) = 0.910, 95% confidence interval (95%CI) was 0.857-0.947, P < 0.001], SOFA score (OR = 1.166, 95%CI was 1.085-1.254, P < 0.001), albumin (OR = 0.946, 95%CI was 0.902-0.991, P = 0.019), baseline serum phosphorus (OR = 0.343, 95%CI was 0.171-0.689, P = 0.003), baseline serum potassium (OR = 0.531, 95%CI was 0.377-0.746, P < 0.001), creatinine-height index (OR = 0.891, 95%CI was 0.819-0.970, P = 0.008), caloric intake (OR = 1.108, 95%CI was 1.043-1.178, P = 0.001), protein intake (OR = 0.107, 95%CI was 0.044-0.260, P < 0.001), and feedings during the 48 hours of ICU admission (OR = 0.592, 95%CI was 0.359-0.977, P = 0.040) and septic shock (OR = 0.538, 95%CI was 0.300-0.963, P = 0.037) were independent influence factors on the occurrence of RFS in septic patients. Of the 544 patients, 267 died at 28 days, with a mortality of 49.1%. The 28-day mortality of patients in the RFS group was significantly higher than that in the non-RFS group [54.4% (160/294) vs. 42.8% (107/250); χ2 = 7.302, P = 0.007]. 544 patients had a length of ICU stay of 20 (17, 24) days. The patients in the RFS group had a significantly longer length of ICU stay than that in the non-RFS group [days: 20 (17, 25) vs. 19 (17, 23); Z = -2.312, P = 0.021]. CONCLUSIONS:The incidence of RFS in septic patients is high. Factors influencing the occurrence of RFS in septic patients include BMI, SOFA score, albumin, baseline serum phosphorus, baseline serum potassium, caloric intake, protein intake, feeding within 48 hours of ICU admission, and septic shock. RFS prolongs the length of ICU stay and increases the 28-day mortality in patients with sepsis.

BACKGROUND:Acute kidney injury (AKI) is a clinically complex syndrome with a high incidence and mortality rate in the intensive care unit (ICU). Early identification of high-risk patients and timely intervention are crucial. OBJECTIVE:A local database was used to construct a model that predicts the incidence of AKI in ICU patients within 48 hours. MATERIALS AND METHODS:We conducted a study involving 9,628 critically ill patients at Zhejiang Provincial People's Hospital and divided the cohort into derivation and validation groups. We collected and analyzed demographic data, vital signs, laboratory tests, medications, clinical interventions, and other information for all patients, resulting in a total of 232 variables. Six different machine learning algorithms were employed to construct models, and the optimal model was selected and validated. RESULTS:A total of 2,441 patients were included, of whom 1,138 (46.62%) met the AKI criteria. A model was derived that included 16 variables such as albumin transfusion, fluid balance, diastolic blood pressure (DBP), partial pressure of oxygen (PO2), blood glucose (GLU), platelet (PLT), baseline serum creatinine (bSCr), serum sodium, age, epinephrine, proton pump inhibitor (PPI), intra-abdominal infection, anemia, diabetes, glycerin fructose, and nutritional pathway. The area under the receiver operating characteristic curve (AUC) was 0.822. Subgroup analysis revealed the impact of blood pressure fluctuations on AKI. Additionally, the study demonstrated a bidirectional effect of albumin and fluid balance on AKI. CONCLUSION:This model is highly accurate and may facilitate the early diagnosis of and interventions for AKI.

Objective:Neutrophil elastase (NE) plays an important role in the development of acute respiratory distress syndrome (ARDS). Sivelestat sodium, as a selective NE inhibitor, may improve the outcomes of patients with sepsis-induced ARDS in previous studies, but there is a lack of solid evidence. This trial aimed to evaluate the effect of sivelestat sodium on oxygenation in patients with sepsis-induced ARDS. Methods:We conducted a multicenter, double-blind, randomized, placebo-controlled trial enrolling patients diagnosed with sepsis-induced ARDS admitted within 48 hours of the advent of symptoms. Patients were randomized in a 1:1 fashion to sivelestat or placebo. Trial drugs were administered as a 24-hour continuous intravenous infusion, for a minimum duration of 5 days and a maximum duration of 14 days. The primary outcome was the proportion of PaO2/FiO2 ratio improvement on Day 5 after randomization, defined by a greater than 50% improvement in PaO2/FiO2 compared with that on ICU admission or PaO2/FiO2 reached over 300 mmHg on Day 5. Results:The study was stopped midway due to a potential between-group difference in mortality observed during the interim analysis. Overall, a total of 70 patients were randomized, of whom 34 were assigned to receive sivelestat sodium and 36 placebo. On day 5, 19/34 (55.9%) patients in the sivelestat group had PaO2/FiO2 ratio improvement compared with 7/36 (19.4%) patients in the placebo group (risk difference, 0.36; 95% CI, 0.14 to 0.56, p<0.001). The Kaplan-Meier curves showed a significantly improved 28-day survival rate in patients receiving sivelestat than those not (hazard ratio, 0.32; 95% CI, 0.11 to 0.95; p=0.041). Conclusion:In patients with sepsis-induced ARDS, sivelestat sodium could improve oxygenation within the first five days and may be associated with decreased 28-day mortality.

OBJECTIVE:To explore the effects and mechanisms of the C-X-C motif chemokine ligand 12/C-X-C motif chemokine receptor 4 (CXCL12/CXCR4) signaling axis on apoptosis and autophagy in SH-SY5Y neuronal cells subjected to oxygen-glucose deprivation/reperfusion (OGD/R) model in vitro. METHODS:SH-SY5Y cells were divided into the following groups: OGD/R group and non-OGD/R group, with the OGD/R group subjected to OGD/R modeling and the non-OGD/R group receiving no treatment. Cells were also divided into CXCL12+ and CXCL12- groups; the CXCL12+ group received 0.1 mg/L exogenous recombinant CXCL12 (rhCXCL12) at reoxygenation, while the CXCL12- group did not. Another set of cells was divided into CXCL12+AMD3100 and CXCL12 groups; the CXCL12+AMD3100 group was pretreated with 2.5 mg/L AMD3100, a CXCR4 inhibitor, for 2 hours before OGD/R and received both 2.5 mg/L AMD3100 and 0.1 mg/L rhCXCL12 at reoxygenation, whereas the CXCL12 group received rhCXCL12 only. Additionally, cells were divided into small interfering RNA CXCR4 (siCXCR4) and small interfering RNA negative control (siNC) groups; the siCXCR4 group underwent CXCR4 knockdown before OGD/R modeling and received 0.1 mg/L rhCXCL12 at reoxygenation, while the siNC group, transfected with a negative control, received the same treatment. Protein expression of autophagy-related 16 (ATG16), microtubule-associated protein 1 light chain 3 (LC3), aquaporin-3 (AQP3), and CXCR4 was detected by Western blotting. Apoptosis rate and CXCR4 expression were measured by flow cytometry. RESULTS:Compared with the non-OGD/R group, the OGD/R group showed a significantly increased apoptosis rate and markedly decreased protein expression levels of ATG16, LC3, AQP3, and CXCR4 (all P < 0.05). CXCR4 fluorescent expression was also significantly reduced, suggesting that OGD/R simultaneously affects neuronal apoptosis and autophagy while inhibiting CXCR4 and AQP3 expression in SH-SY5Y cells. Compared with the CXCL12- group, the CXCL12+ group exhibited no significant change in apoptosis rate but demonstrated significantly increased protein expression of ATG16, LC3, and AQP3 (ATG16/GAPDH: 1.21±0.10 vs. 1.00±0.00; LC3/β-actin: 1.22±0.10 vs. 1.00±0.00; AQP3/β-actin: 1.26±0.04 vs. 1.00±0.00; all P < 0.05). CXCR4 expression was also significantly enhanced (fluorescence intensity: 1.19±0.05 vs. 1.00±0.00, P < 0.05), indicating that CXCL12 may promote autophagy in OGD/R-injured SH-SY5Y cells via the CXCR4/AQP3 pathway. Compared with the CXCL12 group, the CXCL12+AMD3100 group showed no significant difference in apoptosis rate but significantly lower protein levels of ATG16 and LC3 (ATG16/GAPDH: 0.75±0.08 vs. 1.00±0.00; LC3/GAPDH: 0.86±0.07 vs. 1.00±0.00; both P < 0.05), suggesting that CXCL12 induces autophagy in OGD/R SH-SY5Y cells through CXCR4. Compared with the siNC group, the siCXCR4 group showed no significant change in apoptosis rate but significantly reduced protein expression of ATG16, LC3, AQP3, and CXCR4 (ATG16/GAPDH: 0.76±0.06 vs. 1.00±0.00; LC3/GAPDH: 0.79±0.11 vs. 1.00±0.00; AQP3/GAPDH: 0.81±0.05 vs. 1.00±0.00; CXCR4/GAPDH: 0.86±0.04 vs. 1.00±0.00; all P < 0.05), indicating that CXCR4 knockdown suppresses OGD/R-induced autophagy in SH-SY5Y cells likely via AQP3. CONCLUSIONS:The CXCL12/CXCR4 signaling axis can regulate OGD/R-induced autophagy in SH-SY5Y cells through AQP3 without affecting apoptosis, indicating a role for this pathway in neuronal autophagy during cerebral ischemia/reperfusion injury.

Selective loss of dopaminergic neurons in the substantia nigra (SN) is the main pathological feature of Parkinson's disease (PD), and nigral iron deposition is a key factor in the pathogenesis of PD. Excessive iron can lead to increased production of reactive oxygen species (ROS) in cells and cause cell damage. The abnormal synthesis and metabolism of cholesterol in the brain are closely related to the occurrence of central nervous system diseases, but the mechanisms remain unclear. This experiment investigates the effects and mechanisms of cholesterol and 24S-hydroxycholesterol (24S-OHC) on SH-SY5Y neurons and primary cultured ventral mesencephalon neurons. The viability of SH-SY5Y neurons and primary cultured ventral mesencephalon (VM) neurons was detected by cell counting kit-8 (CCK-8) assay. The intracellular ROS levels were detected by flow cytometry. The expressions of proteins related to ferroptosis, apoptosis, and necroptosis were detected by western blot. The mRNA expression of pro-inflammatory cytokines was detected by real-time PCR. In neurons treated with cholesterol or 24S-OHC, the protein expressions of iron regulatory protein 1 (IRP1), transferrin receptor 1 (TfR1), divalent metal transporter 1 (DMT1), and ferritin were increased, while the expression of ferroportin 1 (FPN1) was decreased, thus leading to increased intracellular iron levels. However, glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11; also called x-CT), ferroptosis suppressor protein 1 (FSP1), and malondialdehyde (MDA), the indicators of ferroptosis, showed no obvious alterations. Cholesterol induced the increased expressions of pro-inflammatory cytokines interleukin-1 beta (IL-1β) and IL-6 in neurons, and the Erk-NF-κB pathway changed accordingly. Moreover, the expressions of cleaved caspase-3, the ratio of Bax/Bcl-2, receptor-interacting protein kinase 1 (RIPK1), RIPK3, and phosphorylated mixed lineage kinase domain-like (p-MLKL) in neurons were also elevated by 24S-OHC treatment. Morphologically, we found nuclear membrane breakdown, chromatin condensation, organelle expansion, cytoplasmic vacuolization, and contents outflow in neurons, which were further signs of neuronal apoptosis and necroptosis. Additionally, co-treatment with deferoxamine (DFO) can partially reduce cleaved caspase-3 expression but cannot reduce p-MLKL expression. Our findings suggest that both cholesterol and 24S-OHC can raise the level of reactive oxygen species (ROS) and activate IRP1 to increase iron influx and decrease iron outflow in neurons. Despite the increase in iron content, ferroptosis is not observed. Cholesterol also increases the expressions of IL-1β and IL-6, which may be related to the Erk-NF-κB pathway, while 24S-OHC can cause both apoptosis and necroptosis. DFO can only partially reduce apoptosis but cannot prevent necroptosis in neurons.

Background: Hyaluronic acid (HA) filler treatment is a minimally-invasive alternative to surgery to volumize the cheeks. HAVOL (Restylane (R) Volyme) is a flexible HA filler suited to contouring and volumizing the midface. Methods: This randomized, evaluator-blinded, no-treatment controlled study evaluated effectiveness and safety of HA(VOL) for correction of midface volume deficit and midface contour deficiency in Chinese subjects. In total 111 subjects were randomized to HA(VOL) and 37 to no treatment (control). The primary endpoint was response, on the blinded evaluator-assessed Medicis Midface Volume Scale (MMVS), at 6 months after last injection for the treatment group and 6 months after randomization for controls, where response was defined as >= 1-point improvement from baseline on both sides of the face. Results: HA(VOL) was superior to no treatment at 6 months, meeting the primary objective: 76% versus 8% MMVS responders, a difference of 68% (CI: 55.7%-79.4%, p < 0.0001). These effects were sustained in 51% at 12 months after last injection. A majority (>= 96%) had improved aesthetic appearance of midface fullness at Month 1 (using the Global Aesthetic Improvement Scale [GAIS]), effects which remained in >= 80% up to 12 months. Volume change captured by 3D photography increased after 1 month to 3.6 mL (close to the total injected volume of 3.4 mL), and remained stable through 12 months. Over 97% reported satisfaction with results after treatment with HAVOL. Additionally, HAVOL was well tolerated, with no unanticipated related adverse events. Conclusions: This study showed that HAVOL is effective and well tolerated for midface treatment in a Chinese population.

At present, the effect of exogenous interleukin (IL) -17A in septic mice is still controversial. This study further explored the effect of exogenous IL-17A on multiple organ function and prognosis in septic mice. Mice model of sepsis was established by cecal ligation and puncture (CLP) method, and the mice were randomly divided into 8 groups according to different intervention measures: Sham+PBS, CLP+PBS, CLP+0.25μg IL-17A, CLP+0.5μg IL-17A, CLP+1μg IL-17A, CLP+2μg IL-17A, CLP+4μg IL-17A and CLP+Anti-IL-17A. Survival rates were monitored and recorded at 12-hour intervals, and the expression changes of blood routine, related inflammatory cytokines, liver and kidney function indexes of mice. Pathological injuries of lung, liver and kidney of mice in each group were detected by H&E staining, and the evaluation of bacterial translocation in vitro was performed by inoculation medium. The results showed that except for the sham-operated group, the 7-day survival rate of the mice in the CLP+1μg IL-17A group was the highest (75%). And exogenous administration of appropriate dose of IL-17A was beneficial to reduce alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and creatinine (Cre) in septic mice. The pathological damage of lung, liver and kidney tissue also can be alleviated, and the colony count of peripheral blood and spleen tissue of mice were also significantly decreased. From this, we concluded that exogenous administration of appropriate dose of IL-17A can improve the bacterial clearance ability of septic mice, and improve the multiple organ dysfunction and 7-day survival rate of the septic mice.

OBJECTIVE:To investigate the effect of prone position on the prognosis of patients with severe pneumonia in intensive care unit (ICU).METHODS:A retrospective cohort study was conducted. The patients with severe pneumonia admitted to the ICU of Qingdao Municipal Hospital from May 2022 to August 2023 were enrolled. The general information, etiology, underlying diseases, vital signs and laboratory indicators at ICU admission, clinical treatment and prognosis during ICU hospitalization were collected. The above clinical data of patients with different prognosis were compared. Multifactorial Logistic regression analysis was used to screen the related factors affecting survival during ICU in patients with severe pneumonia. The change in oxygenation index (PaO2/FiO2) of patients with severe pneumonia were observed at 1 hour before the first prone position, 1 hour after the first prone position, and 1 hour after the end of the first prone position. The effect of prone position on oxygenation in patients with severe pneumonia was analyzed. Spearman correlation analysis was used to investigate the correlation between the duration to first prone position and the change in the PaO2/FiO2 before and after prone position in patients with severe pneumonia.RESULTS:Finally, a total of 144 patients with severe pneumonia were enrolled, 45 survived and 99 died during ICU hospitalization, with a mortality of 68.8%. Compared with the survival group, the patients in the death group were older [years old: 81.00 (70.75, 86.00) vs. 71.00 (60.50, 81.50), P < 0.01], the proportion of pre-existing lung disease, heart rate (HR), respiratory rate (RR), blood lactic acid (Lac) and the ratio of continuous renal replacement therapy (CRRT) were higher [ratio of pre-existing lung disease: 23.2% (23/99) vs. 8.9% (4/45), HR (bpm): 99.61±22.47 vs. 91.49±18.76, RR (times/min): 22.50 (19.75, 29.25) vs. 20.00 (17.50, 24.50), Lac (mmol/L): 2.00 (1.55 , 3.25) vs. 1.60 (1.20, 1.95), CRRT ratio: 25.3% (25/99) vs. 6.7% (3/45), all P < 0.05], and the proportion of prone position was lower [41.4% (41/99) vs. 68.9% (31/45), P < 0.01]. Multifactorial Logistic regression analysis showed that age [odds ratio (OR) = 0.946, 95% confidence interval (95%CI) was 0.912-0.980, P = 0.002] and Lac (OR = 0.563, 95%CI was 0.340-0.930, P = 0.025) were negatively correlated with survival during ICU hospitalization in severe pneumonia patients, while prone position was positively correlated with survival (OR = 2.551, 95%CI was 1.067-6.095, P = 0.035), indicating that prone position was beneficial for improving ICU prognosis in severe pneumonia patients. The results of PaO2/FiO2 at different time points in prone position showed that PaO2/FiO2 at 1 hour of the first prone position in the patients with severe pneumonia was significantly higher than that at 1 hour before the first prone position [mmHg (1 mmHg ≈ 0.133 kPa): 146.69 (113.92, 257.25) vs. 111.75 (70.15, 212.20), P < 0.01], indicating that the prone position had a relevant effect on the improvement of oxygenation in patients. Spearman correlation analysis showed that the duration of the first prone position in patients with severe pneumonia was significantly and positively correlated with the improvement of oxygenation at 1 hour of the first prone position (r = 0.565, P < 0.001).CONCLUSIONS:The prone position is a therapeutic measure that can independently influence the prognosis of patients with severe pneumonia during ICU hospitalization. The prone position effectively improves oxygenation in patients with severe pneumonia and the first change in oxygenation in patients is related to the duration of the prone position.

ObjectiveStudy the possible mechanism and delayed effect of tilapia skin collagen on skin aging for mice. Materials and MethodsKunming (KM) mice were randomly divided into the aging model group, the normal group, the positive control group (vitamin E) and the low, medium, high dose tilapia skin collagen groups (2.0, 4.0, 8.0 mg/g). The normal group was only injected with saline at the back and the neck. The other groups were injected subcutaneously with 5% D-galactose and ultraviolet light jointly to establish the aging model. After modeling, the positive control group was treated with a dose of 10% vitamin E once a day, and the low, medium, high dose tilapia skin collagen group was separately applied 2.0, 4.0, 8.0 mg/g of tilapia skin collagen for 40 days. The changes of skin tissue morphology, water content, hydroxyproline (Hyp) content, and superoxide dismutase (SOD) activity in mice were studied at the day 10, 20, 30, 40, 50. ResultsCompared with the normal group, the skin of mice in the aging model group was thinner, looser, and the skin moisture content, Hyp content, SOD activity were all decreased. For mice of the low, medium, high dose tilapia skin collagen group, the thickness of dermis increased, possessing close arrangement, and the moisture content, Hyp content, SOD activity were up-regulated significantly, which effectively alleviated the aging process of skin. The dose of tilapia skin collagen was directly proportional to the anti-aging effect. ConclusionsTilapia skin collagen has an obvious effect on improving skin aging.

OBJECTIVE:To explore the effect of interleukin-17A (IL-17A) on liver and kidney injury and prognosis in septic mice.METHODS:A total of 84 SPF male C57BL/6 mice were randomly divided into sham operation group (Sham group), cecal ligation and puncture (CLP) induced sepsis model group (CLP group), and IL-17A intervention group. IL-17A intervention group were then divided into five subgroups according to the dose of IL-17A (0.25, 0.5, 1, 2, 4 μg). Mice in the IL-17A intervention group were intraperitoneally injected with the corresponding dose of IL-17A 100 μL immediately after surgery. The other groups were intraperitoneally injected with 100 μL phosphate buffer solution (PBS). The survival rate of mice was observed at 7 days, and peripheral blood and liver, kidney and spleen tissues were collected. According to the 7-day survival, another 18 mice were randomly divided into Sham group, CLP group, and 1 μg IL-17A intervention group. Peripheral blood samples were collected at 12 hours and 24 hours after CLP, and the mice were sacrificed to obtain liver, kidney, and spleen tissues. The behavior and abdominal cavity of each group were observed. The levels of peripheral blood liver and kidney function indexes and inflammatory factors were detected. The histopathological changes of liver and kidney were observed under light microscope. The peripheral blood and spleen tissues were inoculated in the medium, the number of bacterial colonies was calculated, and the bacterial migration of each group was evaluated in vitro.RESULTS:Except for the Sham group, the 7-day survival rate of mice in the 1 μg IL-17A intervention group was the highest (75.0%), so this condition was selected as the intervention condition for the subsequent study. Compared with Sham group, the liver and kidney functions of CLP group were significantly damaged at each time point after operation. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and serum creatinine (SCr) reached the peak at 24 hours after operation, and the liver and kidney pathological scores reached the peak at 7 days after operation, the levels of inflammatory cytokines interleukin (IL-17A, IL-6, IL-10) reached the peak at 12 hours after operation, and tumor necrosis factor-α (TNF-α) reached the peak at 24 hours after operation. In addition, a large number of bacteria proliferated in the peripheral blood and spleen, which reached the peak on day 7. Compared with the CLP group, exogenous administration of 1 μg IL-17A significantly delayed the rising trend of each index in the early stage of sepsis [24-hour ALT (U/L): 166.95±5.20 vs. 271.30±6.11, 24-hour AST (U/L): 599.42±7.25 vs. 1 013.27±3.37, 24-hour BUN (mg/L): 815.4±26.3 vs. 1 191.2±39.4, 24-hour SCr (μmol/L): 29.34±0.87 vs. 60.75±3.83, 7-day liver pathological score: 2.50 (2.00, 3.00) vs. 9.00 (8.50, 9.00), 7-day kidney pathological score: 1.00 (1.00, 2.00) vs. 5.00 (4.50, 5.00), 12-hour IL-17A (ng/L): 105.21±0.31 vs. 111.28±1.37, 12-hour IL-6 (ng/L): 83.22±1.01 vs. 108.88±0.99, 12-hour IL-10 (ng/L): 731.54±3.04 vs. 790.25±2.54, 24-hour TNF-α (μg/L): 454.67±0.66 vs. 576.18±0.76, 7-day peripheral blood colony count (CFU/mL): 600 (400, 600) vs. 4 200 (4 200, 4 300), 7-day spleen tissue colony count (CFU/g): 4 600 (4 400, 4 600) vs. 23 400 (23 200, 23 500), all P < 0.05].CONCLUSIONS:Appropriate dose (1 μg) of exogenous IL-17A can reduce the lethal inflammatory response induced by CLP and improve the ability of bacterial clearance, thereby alleviating liver and kidney injury and improving the 7-day survival rate of septic mice.

OBJECTIVE:To analyze the risk factors related to the prognosis of patients with sepsis in intensive care unit (ICU), construct a nomogram model, and verify its predictive efficacy. METHODS:A retrospective cohort study was conducted using data from Medical Information Mart for Intensive Care-IV 0.4 [MIMIC-IV (version 2.0)]. The information of 6 500 patients with sepsis who meet the diagnostic criteria of Sepsis-3 were collected, including demography characteristics, complications, laboratory indicators within 24 hours after ICU admission, and final outcome. Using a simple random sampling method, the patients were divided into a training set and a validation set at a ratio of 7 : 3. The restricted cubic spline (RCS) was used to explore whether there was a linear relationship between each variable and the prognosis, and the nonlinear variables were truncated into categorical variables. All variables were screened by LASSO regression and included in multivariate Cox regression analysis to analyze the death risk factors in ICU patients with sepsis, and construct a nomograph. The consistency index, calibration curve and receiver operator characteristic curve (ROC curve) were used to evaluate the prediction efficiency of nomogram model. The decision curve analysis (DCA) was used to validate the clinical value of the model and its impact on actual decision-making. RESULTS:Among 6 500 patients with sepsis, 4 551 were in the training set and 1 949 were in the validation set. The 28-day, 90-day and 1-year mortality in the training set were 27.73% (1 262/4 551), 34.76% (1 582/4 551), and 42.98% (1 956/4 551), respectively, those in the validation set were 27.24% (531/1 949), 33.91% (661/1 949), and 42.23% (823/1 949), respectively. Both in training set and the validation set, compared with the final survival patients, the death patients were older, and had higher sequential organ failure assessment (SOFA) score and simplified acute physiology score II (SAPS II), more comorbidities, less urine output, and more use of vasoactive drugs, kidney replacement therapy, and mechanical ventilation. By RCS analysis, the variables with potential nonlinear correlation with the prognosis risk of septic patients were transformed into categorical variable. The variables screened by LASSO regression were enrolled in the multivariate Cox regression model. The results showed that age [hazard ratio (HR) = 1.021, 95% confidence interval (95%CI) was 1.018-1.024], SOFA score (HR = 1.020, 95%CI was 1.000-1.040), SAPS II score > 44 (HR = 1.480, 95%CI was 1.340-1.634), mean arterial pressure (MAP) ≤ 75 mmHg (1 mmHg ≈ 0.133 kPa; HR = 1.120, 95%CI was 1.026-1.222), respiratory rate (RR; HR = 1.044, 95%CI was 1.034-1.055), cerebrovascular disease (HR = 1.620, 95%CI was 1.443-1.818), malignant tumor (HR = 1.604, 95%CI was 1.447-1.778), severe liver disease (HR = 1.330, 95%CI was 1.157-1.530), use of vasoactive drugs within 24 hours (HR = 1.213, 95%CI was 1.101-1.336), arterial partial pressure of oxygen (PaO2; HR = 0.999, 95%CI was 0.998-1.000), blood lactic acid (Lac; HR = 1.066, 95%CI was 1.053-1.079), blood urea nitrogen (BUN) > 8.9 mmol/L (HR = 1.257, 95%CI was 1.144-1.381), total bilirubin (TBil; HR = 1.023, 95%CI was 1.015-1.031), and prothrombin time (PT) > 14.5 s (HR = 1.232, 95%CI was 1.127-1.347) were associated with the death of ICU patients with sepsis (all P < 0.05). Based on the above factors, a nomogram model was constructed, and the model validation results showed that the consistency index was 0.730. The calibration curve showed a good consistency between the predicted results of the nomogram model and observed results in the training and validation sets. ROC curve analysis showed that the area under the ROC curve (AUC) predicted by the nomogram model in the training set and the validation set for 28-day, 90-day and 1-year death risk was 0.771 (95%CI was 0.756-0.786) and 0.761 (95%CI was 0.738-0.784), 0.777 (95%CI was 0.763-0.791) and 0.765 (95%CI was 0.744-0.787), 0.677 (95%CI was 0.648-0.707) and 0.685 (95%CI was 0.641-0.728), respectively. DCA analysis showed that the nomogram model had significant net benefits in predicting 28-day, 90-day, and 1-year death risk, verifying the clinical value of the model and its good impact on actual decision-making. CONCLUSIONS:The death risk factors related to ICU patients with sepsis include age, SOFA score, SAPS II score > 44, MAP ≤ 75 mmHg, RR, cerebrovascular disease, malignant tumors, severe liver disease, use of vasoactive drugs within 24 hours, PaO2, Lac, BUN, TBil, PT > 14.5 s. The nomogram model constructed based on this can predict the death risk of ICU patients with sepsis.

消化道异物在临床中很常见，其中鱼骨误服最为常见。大部分患者根据病史及症状即可确诊，少有发生肠外并发症的报道。本例患者入院时无明确的异物误服史，整个发病过程中未出现弥漫性腹膜炎等并发症，但同时出现了肝脓肿及胆囊穿孔两种罕见的肠外并发症，现给予报道。

Objective: Study the repair effect of tilapia collagen on acute wounds, and the effect on the expression level of related genes and its metabolic direction in the repair process.Materials and methods: After the full-thickness skin defect model was constructed in standard deviation rats, the wound healing effect was observed and evaluated by means of characterization, histology, and immunohistochemistry. RT-PCR, fluorescence tracer, frozen section and other techniques were used to observe the effect of fish collagen on the expression of related genes and its metabolic direction in the process of wound repair.Results: After implantation, there was no immune rejection reaction, fish collagen fused with new collagen fibers in the early stage of wound repair, and was gradually degraded and replaced by new collagen in the later stage. It has excellent performance in inducing vascular growth, promoting collagen deposition and maturation, and re-epithelialization. The results of fluorescent tracer showed that fish collagen was decomposed, and the decomposition products were involved in the wound repair process and remained at the wound site as a part of the new tissue. RT-PCR results showed that, without affecting collagen deposition, the expression level of collagen-related genes was down-regulated due to the implantation of fish collagen.Conclusion: Fish collagen has good biocompatibility and wound repair ability. It is decomposed and utilized in the process of wound repair to form new tissues.

CT imaging is often used to confirm COVID-19, playing a crucial role in the diagnosis and assessment due to its high sensitivity. The purpose of this study is to investigate results of quantitative CT analysis for CT patterns in SARS-CoV-2 infected patients, and how these relate to viral load and pathophysiological states. We recruited patients who had confirmed SARS-CoV-2 infection and undergone chest CT within 24 hours of confirmation. By quantitative CT analysis, and collecting clinical data, we explored correlations between those variables. Our research included 253 patients, after screening by exclusion criteria, 171 patients were included in final cohort. The incidence of SARS-CoV-2 associated pneumonia was 74.3%. The ROC test results showed AUCs for leukomonocyte count, and virus genes were 0.703, 0.562, 0.567, and 0.582, respectively. GGO pattern in CT was correlated PaO /FiO ratio. Multiple linear regression results indicated GGO was associated with PaO /FiO . Meanwhile, the consolidation was correlated with PaCO level. Additionally, consolidation was also associated with neutrophil–lymphocyte ratio. Conclusion: Lymphocyte count may be a potential marker for predicting SARS-CoV-2 pneumonia, independent of virus load. Additionally, GGO is correlated with hypoxia, while consolidation is associated with PaCO levels and inflammation, which may affect aeration in the lungs.

Background To construct and validate a risk assessment model for acute kidney injury (AKI) in patients with acute pancreatitis (AP) in the intensive care unit (ICU). Methods A total of 963 patients diagnosed with acute pancreatitis (AP) from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database was included. These patients were randomly divided into training set (N = 674) and validation set (N = 289) at a ratio of 7:3. Clinical characteristics were utilized to establish a nomogram for the prediction of AKI during ICU stay. These variables were selected by the least absolute shrinkage and selection operation (LASSO) regression and included in multivariate logistic regression analysis. Variables with P-values less than 0.05 were included in the final model. A nomogram was constructed based on the final model. The predicted accuracy of the nomogram was assessed by calculating the receiver operating characteristic curve (ROC) and the area under the curve (AUC). Moreover, calibration curves and Hosmer-Lemeshow goodness-of-fit test (HL test) were performed to evaluate model performance. Decision curve analysis (DCA) evaluated the clinical net benefit of the model. Results A multivariable model that included 6 variables: weight, SOFA score, white blood cell count, albumin, chronic heart failure, and sepsis. The C-index of the nomogram was 0.82, and the area under the receiver operating characteristic curve (AUC) of the training set and validation set were 0.82 (95% confidence interval:0.79–0.86) and 0.76 (95% confidence interval: 0.70–0.82), respectively. Calibration plots showed good consistency between predicted and observed outcomes in both the training and validation sets. DCA confirmed the clinical value of the model and its good impact on actual decision-making. Conclusion We identified risk factors associated with the development of AKI in patients with AP. A risk prediction model for AKI in ICU patients with AP was constructed, and improving the treatment strategy of relevant factors in the model can reduce the risk of AKI in AP patients.

IntroductionChemokine-like factor (CKLF)-like MARVEL transmembrane domain containing 6 (CMTM6) is a protein localized to the cell membrane and is known for its ability to co-localize with PD-L1 on the plasma membrane, prevent PD-L1 degradation, and maintain PD-L1 expression on the cell membrane. CMTM6 is highly expressed and plays an important role in various tumors such as oral squamous cell carcinoma (OSCC) and colorectal cancer (CRC), however, its role in Glioblastoma multiforme (GBM) is unclear.MethodsIn this paper, to investigate the role of CMTM6 in GBM, we analyzed the expression of CMTM6 in GBM, the interaction with CMTM6 and the associated genes by bioinformatics. Importantly, we analyzed the expression of CMTM6 in GBM in relation to tumor-infiltrating lymphocytes (TILs), immunoinhibitors, immunostimulators, chemokines and chemokine receptors. We further analyzed the function of CMTM6 and performed in vitro experiments to verify it. Finally, the sensitivity of CMTM6 to drugs was also analyzed and the relationship between CMTM6 and the anticancer drug Piperlonguminine (PL) was verified in vitro.ResultsThe results showed that CMTM6 was highly expressed in GBM and correlated with multiple genes. Furthermore, CMTM6 is closely related to the immune microenvironment and inflammatory response in GBM. Bioinformatic analysis of CMTM6 correlated with the function of GBM, and our experiments demonstrated that CMTM6 significantly promoted the migration of GBM cells and epithelial-mesenchymal transition (EMT), but had no significant effect on other functions. Interestingly, we found that in GBM, PL promotes the expression of CMTM6.DiscussionIn this paper, we have performed a detailed analysis and validation of the role of CMTM6 in GBM using bioinformatics analysis and in vitro experiments to demonstrate that CMTM6 may be a potential target for glioma therapy.

Background:Condyloma cuminata (CA) is a sexually transmitted disease caused by human papillomavirus (HPV) infection, which is prone to recurrence and difficult to cure in the short term. CD207 is a C-type lectin receptor that is specifically expressed on the surface of Langerhans cells (LCs) and is considered as an LC-specific immunohistochemical marker. The main purpose of this study is to explore the correlation between the expression of CD207 in CA skin lesions and the duration of CA disease course and frequency of recurrence, in order to provide new prognostic markers for CA to clinicians.Materials and Methods:A total of 40 male patients with CA and their skin lesions were collected, as well as 40 healthy male penile tissue samples. The skin lesions of CA were clinically and histologically confirmed by acetic acid test. The expression of CD207 in epidermal tissues was detected using immunohistochemistry. The difference in the number of CD207 positive cells between CA skin lesions and healthy skin controls was compared, and the association between the number of CD207 positive cells in CA skin lesions and the duration of disease course and the frequency of recurrence was determined through Spearman correlation analysis.Conclusion:In CA skin lesions, CD207 positive cells were found to have morphological abnormalities and the number of cells was significantly reduced compared to healthy skin, suggesting that there may be antigen presentation dysfunction in CA skin lesions, which may be the reason for the prolonged and unresolved condition of the disease. The fewer CD207 positive cells in CA skin lesions, the longer the disease course and the more frequent the recurrence, therefore, the expression level of CD207 can be used as a new prognostic marker for predicting the outcome of CA.