ArchivePsycho-vaccine refers to a small dose of stress that can enhance psychological immunity, and it may be a life-event, experience, training, learning, etc., that enters the human brain and self processes, enhancing the cognitive function of the brain, with the characteristics of irritability, accumulation, and covertness, and so on. The world military powers, represented by the United States, have begun extensive researches on psycho-vaccine, such as psychological resilience enhancement, “super-soldier” plan, and other projects. In-depth researches have been conducted on the action pathways, vaccination, and promotion of psycho-vaccine in whole army. Our military still lacks systematic research on psycho-vaccine, vaccination and prevention and control. There still exist some problems in the current research of psycho-vaccine, including uncertain specificity, unclear threshold of natural stress vaccination, uncertain chain-relationship of psycho-virus—psycho-vaccine—psycho-antibody, and unclear effect of novel psycho-vaccination. Future researches on psycho-vaccine should be carried out in following 4 aspects: ①confirm the specificity of different types of psycho-vaccine; ②clarify the doses, types, and ways of natural stress vaccination; ③uncover the chain relationship of psycho-virus—psycho-vaccine—psycho-antibdy; ④develop novel psycho-vaccination.
To evaluate the resuscitation efficacy of novel lyophilized platelets (LP, thrombin-stimulated platelets) combined with lactated Ringer’s (LR) solution in rabbits with hemorrhagic shock and seawater immersion.
Fifty rabbits were randomly assigned to 5 groups (Groups A, B, C, D and E, n=10). After all rabbits were anesthetized with 3% pentobarbital sodium at a dose of 1 mL/kg, soft tissue injury was inflicted in the left lower limb. The blood loss from the soft tissue injury was quantified after gauze hemostasis. The right lower limb was subjected to femoral artery catheterization, followed by blood withdrawal equivalent to 26% of the total blood volume of the rabbit. The rabbits were then vertically immersed in 3% artificial seawater, with the water level reaching above the xiphoid process, and were retrieved in 15 min later. Resuscitation strategies were applied to the rabbits from different group: Group A (no resuscitation), Group B (resuscitation with LR solution), Group C (resuscitation with LR solution and fresh platelets), Group D (resuscitation with LR solution and LP), and Group E (resuscitation with LR solution and novel LP). Coagulation function test, routine blood test, blood gas analysis, and thromboelastography were conducted at baseline and at 1, 2 and 4 h after injury.
The LP and rabbit model of hemorrhagic shock and seawater immersion were successfully prepared. At 1 h after injury, the mean arterial pressure (MAP) of Groups C, D and E (infused with platelet preparations) was significantly higher than that of Group A (without resuscitation, P<0.05); the lactate (Lac) content of Group C was obviously lower than that of Groups A and B (P<0.05); the base excess (BE) and blood urea nitrogen (BUN) levels of Groups C, D and E were notably lower than those of Groups A and B (P<0.05); and the prothrombin time (PT) of Group A was significantly longer than that of before injury (P<0.05). At 2 h after injury, the MAP of Groups C and D was significantly higher than that of Groups A and B, and that of Group E was notably higher than that of Group A (P<0.05); the Lac content of Groups C and E was obviously lower than that of Groups A and B, while that of Group D was also lower than that of Group A (P<0.05); the BE and BUN levels of Groups C, D and E were remarkably lower than those of Groups A and B (P<0.05); the maximum amplitude (MA) value of Group C was higher than that of Group A, while the value of Groups A and D at this time was significantly lower than the corresponding value before injury (P<0.05); and the activated partial clotting time (APTT) of Groups A and D was statistically longer than the corresponding baseline time (P<0.05). At 4 h after injury, the MAP of Groups C, D, and E was higher than that of Groups A and B, and that of Group B was higher than that of Group A (P<0.05); the Lac and BUN levels of Groups C, D, and E were lower than those of Groups A and B (P<0.05); the BE level of Groups C and D were lower than those of Groups A and B (P<0.05); the MA value of Groups B, C, and E were higher than those of Group A (P<0.05), while the MA value and APTT value of Groups A and D were significantly lower than their corresponding baseline values (P<0.05).
For rabbits with hemorrhagic shock and seawater immersion, the novel LP combined with LR solution can significantly increase the MAP level, reduce Lac content, and sustainably maintain blood clot firmness and coagulation function.
To explore the expression profile of adenosine A1 receptor in the paraventricular thalamic nucleus (PVT) in wakefulness/sleep state and its role in regulating sleep.
Male C57BL/6J mice (6~12 weeks old, weighing 22~28 g) were randomly divided into ZT0, ZT6, ZT10, ZT12, and sleep deprivation and recover0y sleep groups (n=16 or n=4). RT-qPCR and fluorescence in situ hybridization were used to observe the changes of adenosine A1 receptor in PVT. Whole-cell patch-clamp recording was conducted to determine the effects of adenosine on the membrane potential and discharge frequency of PVT neurons. The experimental animals were divided into adenosine A1 receptor interference group (n=8) and interference control group (n=7). After RNA interference, electroencephalography (EEG) and electromyography (EMG) were applied simultaneously to observe the changes in wake and sleep time between the 2 groups during sleep deprivation for 6 h and sleep recovery for 4 h.
RT-qPCR and fluorescence in situ hybridization confirmed that the expression of adenosine A1 receptor in PVT was affected by wakefulness/sleep state, with the level in the ZT0 group (active stage) significantly higher than that in the ZT12 group (non-active stage, P<0.05). Whole-cell patch clamp recording indicated that adenosine exerted inhibitory effects on PVT neurons through 2 distinct response types (P<0.05), and the inhibition was in a diminishing trend with a decrease in the expression level of adenosine A1 receptor. After sleep deprivation, the expression level of adenosine A1 receptor showed significant intergroup differences: the level was significantly higher in the sleep deprivation group than the recovery sleep group (P<0.05), while that of the recovery sleep group was higher than that of the ZT6 group and that of the ZT10 group (P<0.05). After knocking down adenosine A1 receptor (shRNA-A1R) in the PVT, the wakefulness timing of the shRNA-A1R group was significantly increased, while the sleep timing was significantly decreased within 1 h after sleep recovery when compared with the interference control group (P<0.05).
The expression of adenosine A1 receptor in the PVT is dynamically regulated by sleep pressure, which was increasing as sleep pressure rises.
To investigate whether aberrant DNA methylation of ubiquinol-cytochrome C reductase core protein 1 (UQCRC1) is related to cognitive impairment caused by neonatal sevoflurane exposure.
A total of 94 SPF C57 mice of either sex, aged 6 d, and weighing 4~6 g, were randomly divided into 7 groups: control group (Con, n=6), sevoflurane-6 and -24 h exposure groups (Sev-6 and -24 h, n=6), control+DMSO group (Con+DMSO, n=19), control+5-aza-2'-deoxycytidine (5-AZA, methylation inhibitor) group (Con+5-AZA, n=19), sevoflurane+DMSO group (Sev+DMSO group, n=19), and sevoflurane+5-AZA group (Sev+5-AZA group, n=19). From 6 to 8 d after birth, the mice of the Sev-6 and -24 h exposure groups were exposed to 3% sevoflurane daily (with 97% oxygen, 2 L/min, 2 h per day), while those from the Con groups were given exposure of 100% oxygen (2 L/min, 2 h per day). For the mice of the 5-AZA and DMSO groups, 1 mg/kg of 5-AZA or an equal volume of DMSO was injected intraperitoneally 30 min before daily exposure. In 6 and 24 h after the last exposure to sevoflurane, 6 mice from the Con, Sev-6 h, and Sev-24 h groups were euthanized for biochemical analysis, and in 24 h post-exposure, 6 mice from the Con+DMSO, Con+5-AZA, Sev+DMSO, and Sev+5-AZA groups were randomly selected for biochemical analysis, while another 3 mice from above each group were also randomly selected for morphological analysis. The remaining 10 mice in these groups underwent behavioral testing (open field test, novel object test, and Y-maze test) at 30~33 d after birth to assess cognitive function, and were euthanized in 24 h after the final behavioral test. RT-qPCR and Western blotting were used to detect the hippocampal expression of UQCRC1, DNA methyltransferases (Dnmts), and methyl CpG binding protein 2 (Mecp2) at mRNA and protein levels, respectively. Immunofluorescence assay was employed to observe the distribution and expression of UQCRC1 in the hippocampus. Bisulfite sequencing PCR (BSP) was applied to measure the methylation in the UQCRC1 promoter region.
Compared with the Con group, the mRNA and protein levels of UQCRC1 were down-regulated (P<0.05), and the mRNA level of Dnmts was up-regulated (P<0.05) in both the Sev-6 h and Sev-24 h exposure groups, while the methylation level in the UQCRC1 promoter region was enhanced in the Sev-24 h exposure group (P<0.05). Additionally, the Sev+5-AZA group had obviously increased mRNA and protein levels of UQCRC1 (P<0.05), and notable improvement in cognitive impairment (P<0.05) when compared with the Sev+DMSO group.
Hypermethylation of UQCRC1 promoter region and thus down-regulating its mRNA and protein expression might be the main mechanism by which repeated neonatal sevoflurane exposure induces cognitive impairment later in life.
To prepare tubeimoside Ⅲ nanoemulsion (TBMⅢ-NE) and evaluate its adjuvant effect in vaccines.
TBMⅢ-NE was prepared using low-energy emulsification. Dynamic light scattering was used to characterize the particle size and polydispersity index of the obtained TBMⅢ-NE, and transmission electron microscopy (TEM) was employed to observe the morphology. CCK-8 assay was utilized to determine the cytotoxicity of TBMⅢ-NE on bone marrow-derived dendritic cells (BMDCs). The in vitro safety of TBMⅢ-NE was evaluated using a hemolysis assay. The ability of TBMⅢ-NE to promote the phagocytosis of antigens by DC2.4 cells was observed using confocal laser microscopy. After co-incubation of TBMⅢ-NE with BMDCs, the expression levels of CD40, CD86, MHC-Ⅰ, and CCR7 on the surface of BMDCs were detected using flow cytometry, and the levels of cytokines in the supernatant of BMDCs were measured using enzyme-linked immunosorbent assay (ELISA). After female BALB/c mice were immunized with the SARS-CoV-2 antigen RBD in combination with TBMⅢ-NE, ELISA was conducted to determine the serum levels of specific IgG, IgG2a, and IgG1 antibodies. The number of specific IFN-γ-secreting cells in mouse splenocytes was detected using enzyme-linked immunospot (ELISpot) assay.
The prepared blank nanoemulsion (BNE) and TBMⅢ-NE were in a particle size of 25.46 and 25.89 nm, and a polydispersity index of 0.214 and 0.125, respectively. TEM displayed that TBMⅢ-NE was in uniform sphere and well dispersed. When the TBMⅢ-NE adjuvant was diluted by 400-fold, the survival rate of BMDCs was approximately 86%. Compared with free TBMⅢ, the hemolytic toxicity of TBMⅢ-NE was significantly reduced (P<0.01). TBMⅢ-NE promoted the phagocytosis of antigens by DC2.4 cells and significantly increased the expression of CCR7 on the surface of BMDCs (P<0.05), indicating its potential to promote more dendritic cells to effectively migrate to lymph nodes. TBMⅢ-NE also promoted the expression of IL-6 and IL-1β in the supernatant of BMDCs (P<0.05). When combined with RBD, TBMⅢ-NE significantly increased the levels of specific IgG, IgG2a, and IgG1 antibodies in mouse serum (P<0.01) and promoted the secretion of specific IFN-γ in splenocytes (P<0.01), indicating that TBMⅢ-NE could enhance specific cellular immune responses.
A stable and highly effective TBMⅢ-NE that can induce humoral and cellular immune responses is successfully prepared.
To investigate the role of transcription factor EB (TFEB) in endotoxin-tolerant macrophages.
The RAW264.7 cells were divided into blank group (DMEM medium), LPS 5 group (5 ng/mL LPS treatment for 4 h), LPS 100 group (100 ng/mL LPS treatment for 4 h), and tolerance group (5 ng/mL LPS for 12 h followed by 100 ng/mL LPS for 4 h). The releases of inflammatory factors TNF-α and IL-6 were measured using ELISA. Western blotting and immunofluorescence assay were used to evaluate the distribution of autophagy-related proteins LC3 and P62, as well as TFEB in the cytoplasm and nucleus. Lentiviral overexpression of TFEB or siRNA-mediated knockdown of TFEB were performed to observe the changes in autophagy levels and bacterial clearance ability in the tolerant cells.
The cells in the tolerance group had significantly lower contents of TNF-α and IL-6, as well as reduced bacterial clearance ability (P<0.01), down-regulated LC3 expression while up-regulated P62 level, and decreased expression of TFEB in both the cytoplasm and nucleus (P<0.01) when compared with the cells of the LPS 100 group. Overexpression of TFEB significantly increased LC3 level, reduced P62 level, and enhanced bacterial clearance ability in the endotoxin-tolerant cells (P<0.01). In contrast, siRNA-mediated knockdown of TFEB had no significant impacts on LC3 and P62 expression levels or bacterial clearance ability.
Overexpression of TFEB can restore the autophagy of endotoxin-tolerant cells and enhance their bacterial clearance capacity, thereby alleviating the immunosuppressive state of sepsis. These findings suggest that TFEB holds promise as a potential therapeutic target for the prevention and treatment of sepsis.
To explore the role of X chromosome encoded epigenetic regulator UTX in NK cell-mediated anti-tumor activity.
Male Ncr1-iCre mice were crossed with female UTXfl/fl mice to generate F1 Ncr1-iCre+UTXfl/- male mice, which were further crossed with female UTXfl/fl mice to obtain male Ncr1-iCre-UTXfl/-control mice (M-Con) and NK-specific deletion of UTX male mice Ncr1-iCre+UTXfl/- (M-KO), as well as female Ncr1-iCre-UTXfl/fl control mice (F-Con) and UTX-deficient female mice Ncr1-iCre+UTXfl/fl (F-KO). UTX-deficient mice were injected with melanoma cell line B16F10 via tail vein to observe pulmonary metastatic tumor nodules. Moreover, flow cytometry was applied to detect the proportion and quantity of pulmonary NK cells (CD3-CD19-NK1.1+), maturation makers KLRG1 and CD11b, activation receptors NKG2D and CD69, and effector molecules, including perforin, granzyme B, CD107a, and IFN-γ. Then pulmonary NK cells were sorted and co-cultured with B16F10 cells, and the apoptosis of the melanoma cells was measured with flow cytometry.
Compared with the M-Con mice, the M-KOmice presented less number of pulmonary tumor nodules (P<0.05), increased proportion and quantity of NK cells in the tumor microenvironment (P<0.01), though no obvious changes in the ratio of NK maturation makers KLRG1 to CD11b, enhanced expression level of cytotoxic molecule perforin (P<0.01), but no changes in the expression of effector molecule granzyme B, degranulation marker CD107a and cytokine IFN-γ in NK cells. Co-culture of NK cells and B16F10 cells promoted the apoptosis of tumor cells (P<0.05). Compared with the F-Con mice, the F-KO mice had no statistical difference in the number of pulmonary tumor nodules, but larger proportion and number of NK cells (P<0.05), decreased ratio of KLRG1 to CD11b (P<0.01), elevated level of perforin but decreased levels of granzyme B, CD107a and IFN-γ in NK cells (P<0.01). The co-culture of NK cells and B16F10 cells reduced the apoptosis of tumor cells in F-KOfemale mice (P<0.05).
NK-specific deletion of UTX regulates pulmonary metastasis of melanoma in a sex-dependent manner.
To investigate the molecular mechanism by which receptor activator of nuclear factor-κB ligand (RANKL) regulates autophagy and osteoclast differentiation through the ROS-HIF-1α signaling axis.
Mouse monocytic/macrophage RAW264.7 cells were randomly divided into control group, RANKL group, and 3 combined intervention groups, that is, RANKL+CQ group (intervention with autophagy inhibitor, CQ), RANKL+FG-4592 group (intervention with HIF-1α stabilizer, FG-4592), and RANKL+NAC group (intervention with ROS scavenger, NAC). The number of mature multinucleated osteoclasts was quantitatively detected with tartrate-resistant acid phosphatase (TRAP) staining; the protein levels of HIF-1α and LC3 were detected by Western blotting and the mRNA levels of osteoclast differentiation-related genes (TRAP, Cath K and MMP-9) were analyzed by qRT-PCR; autophagy flux and activity were observed by adenovirus mRFP-GFP-LC3 labeling system combined with confocal laser microscopy; and the production of intracellular reactive oxygen species (ROS) was measured by DCFH-DA probe.
Compared with the control group, the RANKL group obtained significantly increased number of TRAP-positive multinucleated osteoclasts (P<0.05), up-regulated mRNA levels of osteoclast differentiation-related genes, activated autophagy pathway, as evidenced by the increased LC3-Ⅱ/LC3-Ⅰ ratio (P<0.05) and number of autophagic lysosomes (P<0.05), elevated intracellular ROS generation (P<0.05), and down-regulated HIF-1α protein level (P<0.05). NAC intervention significantly inhibited intracellular ROS accumulation (P<0.05), reversed the lowered expression of HIF-1α protein (P<0.05), decreased the LC3-Ⅱ/LC3-Ⅰ ratio (P<0.05) and autophagy flux and activity (P<0.05), and reduced expression levels of osteoclast differentiation-related genes and the number of mature osteoclasts (P<0.05). In the RANKL+FG-4592 group, HIF-1α protein level was significantly increased (P<0.05), autophagy activation was inhibited [with decreased LC3-Ⅱ/LC3-Ⅰ ratio (P<0.05) and autophagy flux and activity (P<0.05)], and the expression of osteoclast differentiation-related genes and number of mature osteoclasts were decreased (P<0.05) when compared with the RANKL group. While CQ treatment resulted in inhibited autophagy flux and activity (P<0.05), declined expression levels of osteoclast differentiation-related genes, and reduced number of mature osteoclasts (P<0.05).
RANKL activates autophagy through ROS-mediated down-regulation of HIF-1α, and thereby promotes osteoclast differentiation.
To analyze the correlation of cholecystectomy and changes in intestinal microbiota composition and function by observing functional characteristics of differential microbial communities.
A cross-sectional study was conducted on the patients (PC group, n=73) undergoing cholecystectomy in our hospital from 2020 to 2021. Another 56 healthy age- and gender-matched individuals (HC group) without a history of cholecystectomy were subjected and served as the control group. Fecal specimens were collected from the 2 groups. 16S rRNA sequencing analysis was performed to examine the changes in composition and function of intestinal microbiota.
There were no statistical differences between the 2 groups in baseline indicators, such as gender, age, BMI, smoking and drinking history, blood pressure, heart rate, and comorbidities, but significant difference was observed in total bilirubin (TBIL) between them (P<0.01). Alpha diversity analysis showed no significant difference in Chao1, Shannon, and Simpson indices between the 2 groups. Beta diversity analysis using the Bray-Curtis distance algorithm revealed a significant difference between the 2 groups at the class and genus levels (P<0.05). The analysis of microbiota relative abundance using LEFSE showed that Enterobacteriaceae, Lactobacillales, Citrobacter, Megasphaera, Lactobacillus, Enterococcus, Akkermansia, Streptococcus, Klebsiella, and Ruminococcus_gnavus were up-regulated in the PC group, and Lachnospiraceae, Sutterellaceae, Lachnospirales, Lachnospira, and Sutterella were down-regulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional prediction analysis indicated that significant differences were seen between the 2 groups in metabolic pathways, including ascorbic acid (vitamin C) metabolism and aldonic acid metabolism (P<0.05), tricarboxylic acid cycle (TCA cycle) (P<0.05), glutathione metabolism (P<0.05), glutamic acid metabolism (P<0.05), secondary bile acid metabolism (P<0.05), and pentose phosphate pathway (P<0.01).
Cholecystectomy is closely associated with the structural alterations in the composition of intestinal microbiota. Variations in microbiota composition and function may induce perturbations in TCA cycle and glutathione metabolism, glutamate metabolism, secondary bile acid metabolism, and pentose phosphate pathways.
To investigate the diversity and composition of gut fungi microbiota in patients with polycystic kidney disease (PKD) and its correlation with clinical indicators.
A total of 44 PKD patients, 44 patients with non-polycystic chronic kidney disease (NPCKD) and 22 healthy controls (HC) admitted to our hospital from February 2023 to February 2024 were recruited. ITS1 DNA sequencing was applied to analyze the gut fungal composition. Bioinformatics analysis was used to compare the diversity and structural differences of fungi among the 3 groups. Pearson correlation analysis was performed to analyze the relationship between gut fungi and clinical indicators.
There were no significant differences in baseline characteristics (gender, age, body mass index, etc.) among the 3 groups, but statistical differences were seen in terms of serum indicators (such as serum creatinine, blood urea nitrogen, uric acid, estimated glomerular filtration rate, etc.) (P<0.01). Alpha diversity analysis showed no significant difference was seen between the PKD and HC groups, but the PKD group had significant differences to the NPCKD group (P<0.01). Beta diversity analysis revealed significant differences among the 3 groups and in pairwise comparisons (P=0.001). Fungi composition analysis found that the abundance of Candida was significantly higher in the PKD group than the other 2 groups (P<0.01), while the abundances of Aspergillus and Cladosporium were significantly lower in the PKD group than the HC group (P<0.05). Linear discriminant analysis (LEFSe) indicated that Candida was significantly enriched, while Aspergillus and Cladosporium were significantly reduced in the PKD group. Correlation analysis revealed that the abundance of Cladosporium was negatively correlated with cyst diameter and immunoglobulin light chain Kappa/Lambda ratio in the PKD group (P<0.05), while the abundance of Candida was positively correlated with liver/kidney cyst diameter (P<0.01).
PKD patients exhibit characteristic changes in gut fungi diversity and composition. The abundances of Cladosporium and Candida are closely associated with clinical indicators of PKD patients.
To investigate the predictive value of combined radiomic features derived from chest CT scans with clinical characteristics for epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer (NSCLC).
A multi-center case-control study was conducted on the clinical data and CT images of 1 070 NSCLC patients from the radiology departments of the 3 medical institutions between January 2013 and October 2023. The 719 NSCLC patients from the First Affiliated Hospital of Army Medical University were randomly divided into a training set and an internal validation set in a ratio of 7∶3; The 173 patients in the Eastern Theatre General Hospital and the 178 patients in Army Medical Centre of PLA were assigned into the external validation set 1 and 2, respectively. Least absolute shrinkage and selection operator (LASSO) regression was employed to identify the optimal radiomic features, which were subsequently used to construct a radiomics model. Univariate and multivariate logistic regression analyses were applied to identify clinical features associated with EGFR mutation, thereby developing a clinical model. The radiomic and clinical features were subsequently combined to develop a comprehensive model. All the 3 classification models were built using random forest (RF) machine learning. The area under curve (AUC), accuracy, sensitivity and specificity were utilized to evaluate the predictive performance of the models. Calibration curve was plotted to assess the goodness of fit of the comprehensive model, while decision curve analysis was performed to assess the clinical utility of the model.
The AUC value of the radiomics model was 0.762 4 (95%CI: 0.692 4~0.825 1), 0.745 4 (95%CI: 0.671 1~0.814 3), and 0.724 7 (95%CI: 0.639 7~0.801 6), respectively, in the internal validation set, external validation set 1, and external validation set 2; The AUC value of the clinical prediction model was 0.691 7 (95%CI: 0.627 9~0.757 6), 0.652 5 (95%CI: 0.576 7~0.729 1), and 0.779 2 (95%CI: 0.712 5~0.847 3), respectively in the above sets in turn; The comprehensive model constructed based on clinical features and radiomic features showed the best predictive efficacy, with an AUC value of 0.818 0 (95%CI: 0.757 7~0.874 3), 0.782 4 (95%CI: 0.703 1~0.848 2), and 0.796 6 (95%CI: 0.718 1~0.868 6), respectively in the above sets. Calibration curve analysis indicated that the comprehensive model had a good fit, while decision curve analysis revealed that the model provided a favorable net benefit.
Our comprehensive model constructed based on chest CT radiomic features and clinical characteristics shows superior predictive performance for EGFR gene mutations in NSCLC across multiple center datasets, which may be helpful for clinical decision-making for treatment strategies.
To compare the gut fungal composition between gout patients and healthy individuals through high-throughput sequencing of ribosomal DNA internal transcribed spacer 1 (ITS1).
Gout patients and healthy volunteers who visited our hospital from January 2023 to December 2024 were enrolled in this study. Then based on established medical guidelines, the gout patients were categorized into 3 groups: Group H (asymptomatic hyperuricemia, n=14), Group G (acute gouty arthritis, n=14), and Group I (intercritical period of gouty arthritis, n=15), and the healthy individuals were assigned into Group N (n=9). Fecal samples were collected from all the participants to undergo ITS1 sequencing analysis. The differences in diversity and composition of gut mycobiome, and FunGuild-derived fungal functions and nutritional status were compared among the 4 groups, and the correlation between the gut mycobiome and clinical indicators was analyzed.
There were no significant differences in baseline features such as gender, age, glomerular filtration rate (GFR), and levels of serum creatinine (SCr) and serum urea among Group N and other gout groups, but obvious differences were observed in body mass index (BMI), erythrocyte sedimentation rate, and levels of C-reactive protein (CRP), serum uric acid (SUA), and IL-1β and IL-6 (P<0.05). In terms of gut fungal diversity, ITS1 analysis showed there were no statistical differences in α-diversity or the principal coordinate analysis (PCoA) of β-diversity among the groups. However, as gout progressed, significant changes were observed in β-diversity indices, indicating a shift in the gut fungal community composition with disease advancement (P<0.05). The phyla Ascomycota, Basidiomycota, and Mucoromycotina were the dominant fungal phyla in all groups. Compared with the other 3 gout groups, the abundance of Pichia was significantly increased in Group N (P<0.05), that of Saccharomyces was in Group H (P<0.05), and that of Starmerella was in Group G (P<0.05). Correlation analysis between the gut mycobiome and clinical indices indicated that the relative abundance of Starmerella was significantly positively correlated with IL-1β (P<0.01) and IL-6 (P<0.05).The relative abundance of Pichia was significantly positively correlated with IL-1β and IL-6 levels (P<0.05), and negatively correlated with serum urea level (P<0.05), and the relative abundance of Saccharomyces was negatively correlated with IL-1β and IL-6 levels (P<0.05).
There exist significant alterations in both the diversity and composition of gut fungi among patients with gout at various stages. Notably, the fluctuations in the relative abundance of Starmerella, Pichia and Saccharomyces appear to correlate with key clinical indicators.
To explore the value of preoperative ultrasound examination in the prediction of restenosis of arteriovenous fistula (AVF) after percutaneous transluminal angioplasty (PTA) in hemodialysis patients.
A case-control trial was conducted on 225 hemodialysis patients who undergoing PTA due to AVF in our hospital January 2023 to May 2024. After 3 months of follow-up, they were divided into a patency group (n=204) and a restenosis group (n=21) according to the occurrence of postoperative restenosis. The preoperative clinical data and ultrasound parameters were compared between the groups. Binary logistic regression analysis was used to identify the independent factors for AVF restenosis after PTA. Receiver operating characteristic (ROC) curve was drawn to evaluate the value of preoperative stenosis length in the prediction of the restenosis after PTA.
There were significant differences in preoperative internal diameter at the site of stenosis, stenosis length, stenosis number, intimal thickness, and brachial artery flow between the 2 groups (P<0.05). Preoperative stenosis length (OR=1.856, 95%CI: 1.350~2.552, P<0.001) was an independent factor of AVF restenosis in hemodialysis patients after PTA. ROC curve analysis showed that the area under the curve of preoperative stenosis length in predicting restenosis after PTA was 0.868 (95%CI: 0.784~0.953, P<0.001), with a sensibility and specificity of 85.7% and 80.4%, respectively.
Preoperative stenosis length may be an independent factor for AVF restenosis after PTA in hemodialysis patients.
To develop a new biological age model based on the National Health and Nutrition Examination Survey (NHANES) database and evaluate its predictive performance for mortality outcomes.
After excluding pregnant women and those with incomplete clinical data, a total of 8 234 participants aged 20~79 years from NHANES 2007-2010 were included and assigned into a testing set, and another 17 522 non-pregnant participants (17~79 years old) subjected from NHANESⅢ were enrolled and served as a training set to construct the new biological age (new Bioage) model. Multiple linear regression was used to construct models for new Bioage and age-adjusted biological age (new-agefixed Bioage), and other types of biological ages were calculated. Pearson correlation analysis was performed to assess the correlation between biological age and chronological age. Based on new-agefixed Bioage, biological age acceleration was calculated, and then according to the results, the participants were divided into accelerated biological aging group (biological age acceleration ≥0, n=3 884) and decelerated biological aging group (biological age acceleration <0, n=4 350). Weighted data comparisons were conducted using the survey package in R, and Cox regression analysis was used to assess the impact of biological age acceleration on the mortality of the participants. Receiver operating characteristic (ROC) curve was plotted to determine the effect of new-agefixed Bioage and biological age acceleration on the area under the curve (AUC) for the mortality.
The new-agefixed Bioage model, composed of 9 variables, had the highest AUC value (AUC=0.889 2, P<0.001) in predicting mortality outcomes and showed high correlation with chronological age and other biological ages. The decelerated biological aging group had significantly larger proportions of males, whites, education level of high school or higher, middle to high household income, married (or with a partner), engaging in physical activity, having private insurance, and cancer (P<0.05), lower BMI, slower biological age acceleration level, and less proportions of smokers, hypertension, diabetes, cardiovascular disease, and chronic obstructive pulmonary disease when compared with the accelerated biological aging group (P<0.05). Cox regression analysis indicated that, compared to the decelerated biological aging group, the accelerated biological aging group had a significantly increased risk of mortality in Model3 [adjust for age group, gender, race, BMI, education level, household income, married (or with a partner), smoking status, heavy alcohol consumption, insurance status, physical activity, hypertension, diabetes, cardiovascular disease, chronic obstructive pulmonary disease, and cancer](HR=1.62, 95% CI: 1.28-2.06, P<0.001). ROC curve analysis revealed that new-agefixed Bioage significantly increased the AUC values (AUC=0.781, P<0.001; AUC=0.731, P<0.001) for middle-aged and elderly populations, while biological age acceleration significantly improved the AUC values (AUC=0.756, P<0.001) for the middle-aged population.
The new-agefixed Bioage model demonstrates high correlation with chronological age and other biological ages, and has good predictive performance for mortality outcomes, particularly in middle-aged and elderly populations.
To revise the Inventory of Alienation Toward Parents (IAP) and test its reliability and validity in a military population in order to provide a scientific tool for assessing the level and grade of parent-child alienation among military personnel.
Whole-cluster stratified random sampling was used to subject 8 641 service members from 8 Army units. Then all participants were surveyed with 18-item adolescent IAP, Beck Depression Inventory-Ⅱ, and Generalized Anxiety Disorder-7. SPSS 27.0 and AMOS 26.0 were used to perform item analysis, exploratory factor analysis (EFA), and confirmatory factor analysis (CFA) to assess reliability and validity. Subsequently, our revised 16-item version of IAP was employed to develop means, percentiles, cut-off scores, and category norms.
①Items 3 and 12 were deleted in item analysis. ②EFA extracted the original communication and emotional distance factors; CFA indicated that the two-factor model had good fitness, with the mother-child alienation scale: χ2/df=4.248, comparative fit index (CFI)=0.962, Tucker-Lewis index (TLI)= 0.929, root mean square error of approximation(RMSEA)= 0.028, standardized root mean squared residual (SRMR)=0.023; while the father-child alienation scale: χ2/df=5.41, CFI=0.939, TLI=0.901, RMSEA=0.032, SRMR=0.044. ③The internal consistency reliability of the total IAP was good (0.744~0.888). ④The total IAP score and scores of the mother-child and father-child subscales were positively correlated with depression and anxiety (r=0.395~0.493, P<0.01). ⑤ The average total IAP score for military personnel was 17.27±4.21, and the scores of mother-child alienation and father-child alienation were 8.64±2.26 and 8.62±2.43, respectively. With percentiles of P75 and P90 as the cut-off points, the total IAP score can be stratified into 3 levels, that is, normal (≤16), moderate (17~19), and severe (≥20). Then, additional category norms were developed based on demographic characteristics.
Our revised 16-item military version of IAP shows good reliability and validity. A preliminary and representative norm is developed primarily, and can be used to assess the level and grade of military parental alienation.