Category: Statistics

Am J Med Genet B Neuropsychiatr Genet. 2026 May 27. doi: 10.1002/ajmg.b.70024. Online ahead of print.

ABSTRACT

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most prevalent late-onset neurodegenerative diseases worldwide. Both are influenced in part by genetic factors and are currently incurable. Tobacco and alcohol, the two most common substances used among the general adult population, are potential AD/PD risk factors and are also heritable. Although important progress has been made, most existing research on the genetics of AD and PD has been carried out in individuals of European genetic ancestry. Investigations in a broad range of groups are crucial to understand disease mechanisms. Given the current availability of ancestry-specific tobacco and alcohol use as well as AD and PD genome-wide association study summary statistics, we performed global and local genetic correlation analyses using East Asian datasets. Genes within the correlated genetic regions were subsequently used to identify potentially enriched biological pathways between substance use and neurodegenerative diseases. We identified a global genetic correlation between smoking cessation and PD, which we confirmed in complementary European genetic ancestry data. Gene set enrichment analyses highlighted potentially shared genetic mechanisms between breast cancer and AD, which warrants further exploration. This work aims to promote further analyses across genetic ancestry groups.

PMID:42200344 | DOI:10.1002/ajmg.b.70024

J Phys Chem Lett. 2026 May 27. doi: 10.1021/acs.jpclett.6c00398. Online ahead of print.

ABSTRACT

We present a multitask machine-learning strategy for improving the prediction of molecular dipole moments by simultaneously training on quantum dipole magnitudes and inexpensive Mulliken atomic charges. With dipole magnitudes as the primary target and assuming only scalar dipole values are available without vector components, we examine whether incorporating lower-quality labels that do not quantitatively reproduce the target property can still enhance model accuracy. Mulliken charges were chosen intentionally as an auxiliary task since they lack quantitative accuracy yet encode qualitative physical information about charge distribution. Our results show that including Mulliken charges with a small weight in the loss function yields up to a 30% improvement in the dipole prediction accuracy. This multitask approach enables the model to learn a more physically grounded representation of charge distributions, thereby improving both the accuracy and the consistency of dipole magnitude predictions. These findings highlight that even auxiliary data of limited quantitative reliability can provide valuable qualitative physical insights, ultimately strengthening the predictive power of machine-learning models for molecular properties.

PMID:42200332 | DOI:10.1021/acs.jpclett.6c00398

J Dent Res. 2026 May 27:220345261442125. doi: 10.1177/00220345261442125. Online ahead of print.

ABSTRACT

Preadhesion mineralization and in situ nano-deposition improving dentin bonding durability are currently explained by divergent paradigms: the former is attributed to collagen strengthening and protease fossilization, while the latter is known for the release of interface-confined water. This study challenges this dichotomy by hypothesizing that preadhesion mineralization fundamentally acts as a dehydration strategy. Two bonding strategies were formulated: a polyacrylic acid-stabilized amorphous calcium fluoride (PAA-ACF) preadhesion mineralization and in situ ACF nano-deposition. Cryo-transmission electron microscopy (TEM) revealed collagen binding by ACF nanoparticles within 30 s, whereas scanning electron microscopy, X-ray diffraction, and TEM showed that PAA‑ACF-mediated intrafibrillar mineralization on etched dentin began within 30 min and reached completion by 3 h. The PAA-ACF 3-h mineralization group showed approximately twice the surface roughness and elastic modulus of the phosphoric acid (PA) and ACF 30-s deposition groups, as measured by atomic force microscopy, whereas its gelatinase activity (assessed by zymography) was substantially lower, only about one-fifth and one-third of the levels in the PA and ACF 30-s groups, respectively. Fourier transform infrared spectroscopy, water absorption, and thermogravimetric analysis confirmed that both strategies effectively released the interface-confined water. Notably, both the nano-deposition and mineralization groups displayed similarly low proteolytic activity in resin-dentin interfaces. After 30,000 thermal cycles, the micro-tensile bond strength of the 3-h group was statistically comparable to that of the ACF 30-s group and exceeded that of conventional PA wet-bonding. Pearson correlation analyses revealed that bonding strength correlated not with mechanical properties or protease activity of preadhered dentin but with the extent of dehydration, which facilitated infiltration of the hydrophobic adhesive monomer (Bis-GMA), as validated by Nile red tracing and micro-Raman analysis. In summary, both strategies enhance adhesive infiltration by releasing the interface-confined water, forming a defect-low hybrid layer. This finding unifies the understanding of dentin bond durability improvement under a common dehydration-based mechanism.

PMID:42200302 | DOI:10.1177/00220345261442125

Stroke. 2026 May 27. doi: 10.1161/STROKEAHA.125.053752. Online ahead of print.

ABSTRACT

BACKGROUND: Mobile stroke units (MSUs) aim to expedite acute stroke management when compared with conventional emergency medical services (EMS). Despite the growing body of evidence surrounding MSUs and acute ischemic stroke, experience with intracerebral hemorrhage (ICH) in MSUs has been lacking. We aimed to evaluate the impact of MSU transportation, compared with EMS, on times to diagnosis and goal-directed treatment in patients with ICH.

METHODS: Retrospective analysis of patients with acute ICH triaged by MSU or EMS from January 2018 to December 2022 was performed at 2 tertiary institutions, the Cleveland Clinic (OH) and Stony Brook University (NY). In the EMS cohort, only patients seen between 08:00 and 20:00, corresponding to the operating hours of MSU, were included. Primary outcomes included diagnosis by computed tomography, administration of antihypertensives, and time to goal systolic blood pressure (<160 mm Hg). Analyses included descriptive statistics and multivariable regression modeling of log-transformed time metrics, adjusting for important patient demographic and clinical characteristics.

RESULTS: Among 540 patients screened with ICH, after removing those with exclusion criteria, 218 MSU patients were compared with 192 EMS patients. Cohorts had similar baseline demographics, majority male (53.7% MSU versus 49.5% EMS), mean age 67±14 and 68±16, respectively. MSUs reduced time to diagnosis by 28% (β=0.72 [95% CI, 0.62-0.82]; P<0.001). Antihypertensives were administered to 78% of MSU patients, whereas not routinely given to EMS-transported patients until emergency department arrival. This facilitated a time reduction of 54% in the administration time of antihypertensive medications in MSU compared with EMS transported patients (β, 0.46 [95% CI, 0.36-0.59]; P<0.001). With 87% of MSU patients achieving blood pressure goal within 1 hour from last known well, compared with 60% in EMS (P<0.001).

CONCLUSIONS: MSUs provide faster diagnosis and medical treatment for patients with acute ICH than patients transported by conventional EMS.

PMID:42200292 | DOI:10.1161/STROKEAHA.125.053752

Stroke. 2026 May 27. doi: 10.1161/STROKEAHA.126.055253. Online ahead of print.

ABSTRACT

BACKGROUND: Intracranial aneurysm (IA) is a common neurovascular disorder; rupture causes aneurysmal subarachnoid hemorrhage with high mortality. Despite available interventions, effective preventative therapies are lacking. We aimed to identify novel genetic determinants of IA and aneurysmal subarachnoid hemorrhage to improve risk prediction and nominate hypothesis-generating therapeutic candidates for future evaluation.

METHODS: We conducted a multiancestry genome-wide association study and statistical fine-mapping study across European and East Asian cohorts and applied rigorous multiancestry and multitrait meta-analyses to identify IA-associated loci. Utilizing the Multi-Ancestry Sum of Single Effects model tool for fine mapping, we fine-mapped ancestry-specific and shared signals across loci. To derive a credible set of candidate genes, we integrated data from functional mapping and annotation, polygenic priority score, multivariate set-based association test (combined), transcriptome-wide association study, and summary data-based Mendelian randomization, focusing on genes identified by at least 4 methods. Machine learning algorithms developed diagnostic models, and a polygenic score model was evaluated using the UK Biobank data set.

RESULTS: We identified 3 novel IA-associated loci and observed significant genetic correlations between IA and systemic phenotypes. We prioritized a credible set of 40 candidate genes, including GPX1 and NPC1 among the top-ranked candidates, and an expression-based K-nearest neighbor classifier achieved an area under the curve of 0.89 for case-control discrimination between IA cases and controls. We evaluated an IA polygenic score in the UK Biobank evaluation sample, which yielded an area under the curve of 0.83 (95% CI, 0.81-0.84); this performance reflects discrimination in this evaluation setting and warrants further validation in additional independent cohorts before clinical implementation. We observed nominal evidence of interaction between polygenic score and smoking (P=1.09×10^-2), suggesting an interplay between genetic susceptibility and a modifiable lifestyle factor. Computational drug repurposing nominated 32 drug classes, including JAK inhibitors and dopamine receptor antagonists, as hypothesis-generating candidates for future experimental evaluation.

CONCLUSIONS: These findings refine IA/aneurysmal subarachnoid hemorrhage-associated loci, prioritize credible candidate genes for functional follow-up, and provide hypothesis-generating translational leads that may inform future studies, pending validation in independent cohorts and experimental models.

PMID:42200286 | DOI:10.1161/STROKEAHA.126.055253

J Int Med Res. 2026 May;54(5):3000605261431479. doi: 10.1177/03000605261431479. Epub 2026 May 27.

ABSTRACT

BackgroundIn this study we investigated the effect of adding dexmedetomidine to fascia iliaca compartment block on postoperative analgesia in patients undergoing femoral fracture surgery.MethodsIn this double-blind randomized clinical trial study, 70 patients aged 20-75 years, classified as American Society of Anesthesiologists physical status I and II who were scheduled to undergo femoral fracture surgery under spinal anesthesia were included. Patients were divided into intervention and control groups using the block randomization method (35 patients in each group). In the intervention group, fascia iliaca block was performed using 20 cc of 0.25% bupivacaine with 0.5 cc of 50 μg dexmedetomidine (fascia iliaca compartment block + dexmedetomidine group), and in the control group, the block was performed using 20 cc of 0.25% bupivacaine alone (fascia iliaca block group). The outcomes, including the average time to achieve sensory block, analgesia duration, number of times rescue analgesia was needed, time to first rescue analgesia, and pain severity assessed using the visual analog scale within 24 h postoperatively, were measured and compared between the two groups.ResultsThe demographic data and time to reach sensory block were not significantly different between the two groups (p > 0.05). The mean analgesia duration in the fascia iliaca compartment block + dexmedetomidine group was significantly longer than that in the fascia iliaca block group (11.42 ± 1.65 vs. 9.26 ± 1.39 h; p = 0.001). An analgesic was prescribed for 11.4% and 31.4% of the patients 2-6 h postoperatively and for 54.3% and 77.1% at 6-12 h postoperatively in the fascia iliaca compartment block + dexmedetomidine and fascia iliaca block groups, respectively, representing a statistically significant difference between the two groups (p = 0.03). The visual analogue scale scores while in recovery, at 2 h postoperatively, and at 12-24 h postoperatively did not show a statistically significant difference between the two groups (p > 0.05); however, patients in the fascia iliaca compartment block group had significantly higher pain scores than those in the fascia iliaca compartment block + dexmedetomidine group at 2-6 h and 6-12 h postoperatively (p < 0.05).ConclusionAddition of dexmedetomidine to bupivacaine in the fascia iliaca block in femoral fracture surgeries reduces the severity of postoperative pain and need for analgesics and increases the analgesia duration.

PMID:42200281 | DOI:10.1177/03000605261431479

Riv Psichiatr. 2026 Mar-Apr;61(2):78-82. doi: 10.1708/4685.47000.

ABSTRACT

INTRODUCTION: Patients with schizophrenia require long-term treatment, and poor medication compliance during therapy is a common issue. Poor compliance can lead to recurrent fluctuations in the patients’ disease course, exacerbate its progressive deterioration, severely impact patients’ social functioning and quality of life, and thus represents an increasingly serious public health problem. Long-acting injectable antipsychotics (LAIs) are generally considered one of the most effective treatments in psychiatry, which can reduce the substantial economic burden on patients and society, lowering readmission rates, improving patients’ quality of life, and decreasing healthcare costs. This study is a retrospective analysis based on follow-up data from patients with severe mental disorders.

OBJECTIVE: The study aims to explore the factors influencing medication compliance in schizophrenia patients treated with paliperidone palmitate injection, providing a basis for developing targeted compliance intervention strategies in clinical practice. The study included schizophrenia patients receiving paliperidone palmitate injection and systematically analyzed the impact of variables such as demographic characteristics, caregiver competence, social functioning, disease duration, and the presence of comorbid chronic conditions on medication compliance.

CONCLUSIONS: Medication compliance in patients with schizophrenia is influenced by the interaction of multiple factors. Among these, age ≥50 years is a core independent risk factor affecting medication compliance, while having a guardian with good caregiving ability serves as an independent protective factor. The impact of a disease duration ≥10 years on compliance approaches statistical significance (p=0.050). A comparison of social functioning across the dimensions of the SDSS revealed that differences in social functioning deficits between the two groups with different levels of medication compliance were only evident in the dimensions of social withdrawal and interest in and concern for the external environment. This suggests that deficits in these specific dimensions of social functioning are also important factors influencing medication compliance in patients.

PMID:42200256 | DOI:10.1708/4685.47000

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2026 Apr;38(4):371-379. doi: 10.3760/cma.j.cn121430-20250828-00462.

ABSTRACT

OBJECTIVE: To investigate the predictive value of ultrasound evaluation of intercostal muscle combined with diaphragmatic function for weaning and extubation outcomes in neurocritically ill patients.

METHODS: A retrospective case-control study was performed. Clinical data of patients receiving invasive mechanical ventilation via tracheal intubation admitted to the neurology intensive care unit (ICU) of The First Affiliated Hospital of Wannan Medical University (Yijishan Hospital of Wannan Medical University) from April 2023 to April 2025 were collected. Patients were divided into a weaning failure group and a weaning success group according to weaning and extubation outcomes. General baseline data, eye opening and motor reaction scores before extubation, air leakage volume of tracheal intubation cuff leak test, cough ability before extubation, routine blood test and blood biochemical indicators within 48 hours before extubation, and basic vital signs, respiratory mechanics parameters, arterial blood gas analysis results as well as intercostal muscle function indicators [intercostal muscle thickness at the end of inspiration (ICMTei), intercostal muscle thickness at the end of expiration (ICMTee), thickening fraction of intercostal muscle (TFic)] and diaphragmatic function indicators [diaphragmatic excursion (DE), diaphragmatic thickness at the end of inspiration (DTei), diaphragmatic thickness at the end of expiration (DTee), diaphragmatic thickening fraction (DTF)] assessed by ultrasound at the end of spontaneous breathing trial (SBT) were compared between the two groups. Meanwhile, the inpatient outcome indicators of patients were collected. Binary multivariate Logistic regression analysis was used to screen the influencing factors of weaning and extubation outcomes in neurocritically ill patients undergoing invasive mechanical ventilation via tracheal intubation. Receiver operator characteristic curve (ROC curve) was plotted to analyze the predictive value of the combination of TFic, DE and DTF for weaning and extubation outcomes in neurocritically ill patients undergoing invasive mechanical ventilation via tracheal intubation.

RESULTS: A total of 233 neurocritically ill patients undergoing invasive mechanical ventilation via tracheal intubation were initially enrolled. After excluding 40 patients aged<18 years or ≥80 years, 55 patients with treatment abandonment or voluntary discharge, 11 patients with unclear ultrasound images, 5 patients undergoing tracheotomy before extubation and 11 patients with incomplete clinical data, 111 patients were finally included in the analysis, including 32 cases in the weaning failure group and 79 cases in the weaning success group. Univariate analysis showed that there were statistically significant differences in Glasgow Coma Scale (GCS) score at admission, eye opening and motor action scores before extubation, air leakage volume of tracheal intubation cuff leak test, cough ability before extubation, rapid shallow breathing index (RSBI) at the end of SBT (all P<0.05). At the end of SBT, TFic in the weaning failure group was higher than that in the weaning success group [15.76% (13.12%, 21.24%) vs. 10.00% (8.33%, 13.33%), P<0.05], while DE and DTF were lower than those in the weaning success group [DE (cm): 1.10 (1.05, 1.20) vs. 1.36 (1.25, 1.45), DTF: 18.75% (16.85%, 24.75%) vs. 27.27% (22.73%, 31.58%), both P<0.05]. Multivariate Logistic regression analysis showed that elevated TFic [odds ratio (OR)=0.731, 95% confidence interval (95%CI) was 0.583-0.917, P=0.007], elevated DE (OR=4.494, 95%CI was 1.663-12.146, P=0.003) and elevated DTF (OR=1.381, 95%CI was 1.078-1.770, P=0.011) were independent influencing factors for successful weaning and extubation in neurocritically ill patients undergoing invasive mechanical ventilation via tracheal intubation. ROC curve analysis showed that TFic, DE and DTF alone had certain predictive value for successful weaning in neurocritically ill patients undergoing invasive mechanical ventilation via tracheal intubation, and the combined application of the three indicators achieved the highest predictive value, with an area under the ROC curve (AUC) of 0.972 (95%CI was 0.948-0.997, P<0.001), a sensitivity of 88.6% and a specificity of 96.9%. Analysis of hospital outcome indicators showed that length of ICU stay, total length of hospital stay and total mechanical ventilation duration in the weaning failure group were longer than those in the weaning success group [length of ICU stay (days): 31.00 (18.25, 49.25) vs. 20.00 (8.00, 32.00), total length of hospital stay (days): 34.50 (22.00, 50.00) vs. 25.00 (16.00, 37.00), total mechanical ventilation duration (days): 18.50 (12.00, 30.25) vs. 8.00 (3.00, 10.00), all P<0.05].

CONCLUSIONS: Ultrasound assessment of TFic combined with DE and DTF has high application value in predicting successful weaning and extubation in neurocritically ill patients.

PMID:42200247 | DOI:10.3760/cma.j.cn121430-20250828-00462

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2026 Apr;38(4):353-361. doi: 10.3760/cma.j.cn121430-20251011-00502.

ABSTRACT

OBJECTIVE: To investigate the protective effect of kynurenine 3-monooxygenase (KMO) inhibitor GSK180 against trauma-induced sepsis (TIS)-induced acute kidney injury (AKI) and to explore its underlying mechanism.

METHODS: Male SPF healthy Sprague-Dawley (SD) rats were randomly divided into groups using a random number table. (1) A normal control group, a sham-operated (Sham) group, and TIS groups at 12, 24, and 48 hours were established, and 6 surviving rats were finally retained in each group for statistical analysis. The normal control group received no treatment. The Sham group was subjected only to laparotomy exploration and gentle cecal palpation followed by abdominal closure, and 40 mL/kg normal saline was injected subcutaneously for fluid resuscitation after surgery until the rats recovered voluntary movement. TIS groups were treated with combined injury to establish the TIS-induced AKI model, and postoperative management was identical to that of the Sham group. Samples were collected at each time point to detect inflammatory indicators such as white blood cell count (WBC), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP), as well as serum creatinine (SCr) and blood urea nitrogen (BUN) to evaluate inflammatory response and renal injury. Based on the severity of renal injury, renal tissues of the corresponding groups were harvested for proteomic analysis to screen candidate target proteins for related mechanistic intervention experiments. (2) In the KMO inhibitor intervention experiment, rats were randomly divided into the Sham group, TIS group, and KMO inhibitor intervention group, with 6 surviving rats retained in each group for statistical analysis. Procedures in the Sham and TIS groups were the same as described above; the KMO inhibitor intervention group was intraperitoneally injected with the KMO inhibitor GSK180 (10 mg/kg) at 2 hours after model establishment, while the Sham and TIS groups were intraperitoneally injected with an equal volume of normal saline. The above inflammatory and renal function indicators were detected at 24 hours after surgery. Periodic acid-Schiff (PAS) staining was used to observe histopathological changes of renal tissues. Terminal-deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) staining was adopted to observe cell apoptosis in renal tissues. Mitochondrial ultrastructure changes were examined by transmission electron microscopy. Mitochondrial reactive oxygen species (ROS) and membrane potential were detected by flow cytometry. Western blotting was performed to determine the expression of KMO, mitochondrial dynamics-related proteins [dynamin-related protein 1 (DRP1) and its phosphorylated form at Ser616 (p-DRP1 Ser616), mitofusin 2 (MFN2), optic atrophy protein 1 (OPA1)], and the apoptosis-inducing protein Bcl-2-associated X protein (BAX).

RESULTS: (1) Compared with the normal control group, significant inflammatory response and renal function injury were observed in TIS groups at all-time points, and peaked at the 24 hours, indicating the most severe renal injury at this time point. Proteomic analysis showed that KMO expression was upregulated in renal tissues of the TIS 24-hour group compared with the normal control group, which was thus selected as the target for subsequent intervention. (2) The KMO inhibitor intervention experiment showed that compared with the Sham group, the rats in the TIS group exhibited systemic inflammatory response and renal dysfunction. Pathological observations revealed aggravated renal damage, increased cell apoptosis, and ultrastructural damage. The level of intracellular ROS was elevated, mitochondrial membrane potential was decreased, and mitochondrial dynamics were imbalanced. Compared with the TIS group, KMO inhibition could improve both systemic inflammatory response and renal function, the levels of WBC, TNF-α, IL-6, CRP, SCr, and BUN were decreased [WBC (×10⁹/L): 9.87±2.74 vs. 25.10±3.55, TNF-α (ng/L): 213.61±81.47 vs. 820.59±105.13, IL-6 (ng/L): 986.98±105.54 vs. 2 376.28±211.80, CRP (ng/L): 1 149.55±405.60 vs. 3 355.76±439.79, SCr (μmol/L): 57.67±12.36 vs. 129.67±10.52, BUN (mmol/L): 11.63±2.60 vs. 21.53±4.31, all P<0.05], alleviated histopathological changes in the kidney, ameliorated mitochondrial ultrastructural damage in renal cells, reduced mitochondrial ROS levels and stabilized membrane potential, and both cell apoptosis and mitochondrial dynamics balance had been improved, the phosphorylation level of DRP1 Ser616 and BAX expression were both decreased [p-DRP1 Ser616 protein (p-DRP1 Ser616/DRP1): 0.88±0.15 vs. 1.63±0.13, BAX protein (BAX/GAPDH): 1.24±0.13 vs. 2.40±0.26, both P<0.05], accompanied by upregulated expression of MFN2 and OPA1 [MFN2 protein (MFN2/GAPDH): 1.09±0.08 vs. 0.64±0.03, OPA1 protein (OPA1/GAPDH): 1.13±0.07 vs. 0.74±0.14, both P<0.05].

CONCLUSIONS: KMO is upregulated in TIS-induced AKI and serves as a key factor mediating renal injury. The KMO inhibitor GSK180 exerts renal protective effects by inhibiting DRP1-mediated mitochondrial fission, promoting MFN2/OPA1-dependent mitochondrial fusion, improving mitochondrial function, and alleviating inflammation, oxidative stress and cell apoptosis.

PMID:42200245 | DOI:10.3760/cma.j.cn121430-20251011-00502

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2026 Apr;38(4):337-345. doi: 10.3760/cma.j.cn121430-20250903-00472.

ABSTRACT

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.

PMID:42200243 | DOI:10.3760/cma.j.cn121430-20250903-00472