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Genome-Wide Association Study and Fine Mapping Uncover Key Genetic Loci and Credible Genes of Intracranial Aneurysm and Aneurysmal Subarachnoid Hemorrhage

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

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Effect of adding dexmedetomidine to fascia iliaca compartment block on postoperative analgesia in patients undergoing femoral fractures surgery: A randomized double-blind clinical trial

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

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Study on independent influencing factors of compliance in patients with schizophrenia treated with paliperidone palmitate injection

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

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Predictive value of ultrasound-assessed thickening fraction of intercostal muscle combined with diaphragmatic function for weaning and extubation outcomes in neurocritically ill patients

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

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Mechanism of kynurenine 3-monooxygenase inhibitor GSK180 in alleviating trauma-induced sepsis-induced acute kidney injury in rats

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

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Association of acute kidney injury with gut microbiota: a study integrating Mendelian randomization and real-world clinical cohort

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

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Analysis of risk factors and management strategies of poor healing of inguinal incision after weaning of veno-arterial extracorporeal membrane oxygenation

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2026 Apr;38(4):317-324. doi: 10.3760/cma.j.cn121430-20251126-00564.

ABSTRACT

OBJECTIVE: To analyze the occurrence and clinical characteristics of poor inguinal incision healing after weaning in patients undergoing peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO), and to explore its risk factors and clinical management strategies.

METHODS: A retrospective case-control study was conducted to select VA-ECMO patients admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital) from February 2022 to February 2025 as the study objects. All patients were weaned from ECMO under open surgery and were divided into normal incision healing group and poor incision healing group according to the healing of the inguinal incision on the side of ECMO catheterization after weaning. The basic data, clinical parameters and laboratory indicators between the two groups were compared, and the risk factors of poor inguinal incision healing after weaning in patients undergoing VA-ECMO were analyzed by univariate and multivariate Logistic regression analyses.

RESULTS: Finally, 41 patients undergoing VA-ECMO were enrolled, including 23 males and 18 females. Among the 41 patients, 27 patients had normal inguinal incision healing, 14 patients had poor inguinal incision healing, and the incidence of poor incision healing was 34%. There were statistically significant differences between the two groups of patients in terms of ECMO catheterization location and ECMO catheterization protocol (both P<0.05). The patients in the poor incision healing group often completed ECMO intubation in the operating room, and most of them chose the unilateral semi-incision catheterization protocol. Compared with the normal incision healing group, the length of ICU stay, the duration of mechanical ventilation and the duration of continuous application of vasoactive drugs in the poor incision healing group were longer [length of ICU stay (days): 29.0 (21.0, 39.0) vs. 15.0 (10.0, 19.0), duration of mechanical ventilation (hours): 454.0 (170.0, 789.0) vs. 134.0 (45.0, 269.0), duration of continuous application of vasoactive drugs (days): 18.5 (6.5, 24.3) vs. 5.0 (2.0, 12.0), all P<0.05], 3-day accumulated fluid balance overload after ECMO weaning [mL: 616.5 (-249.3, 2 148.0) vs. -878.0 (-1 603.0, -387.0), P<0.05], suggesting that the poor healing of inguinal incision after VA-ECMO weaning was related to the above factors. The results of univariate Logistic regression analysis showed that unilateral semi-incision catheterization [odds ratio (OR)=21.000, 95% confidence interval (95%CI) was 2.868-153.754, P=0.003], length of ICU stay>10 days (OR=5.571, 95%CI was 1.042-29.790, P=0.045) and positive 3-day accumulated fluid balance after ECMO weaning (OR=16.133, 95%CI was 3.244-80.224, P=0.001) were the risk factors for poor inguinal incision healing after weaning in patients undergoing VA-ECMO. The variables with statistical significance in univariate Logistic regression analysis were incorporated into the binary multivariate Logistic regression model. The analysis results showed that unilateral semi-incision catheterization (OR=13.203, 95%CI was 1.295-134.632, P=0.029) and positive 3-day accumulated fluid balance after ECMO weaning (OR=14.178, 95%CI was 1.985-101.245, P=0.008) were independent risk factors for poor inguinal incision healing after weaning in patients undergoing VA-ECMO. Fourteen patients with poor healing of inguinal incisions presented with massive exudate from the incision (12 cases), delayed incision healing (7 cases), non-healing of the incision (7 cases), incision infection (4 cases), lymphatic leakage (4 cases), and incision dehiscence (3 cases). In addition to routine dressing change, 12 cases underwent negative pressure sealed drainage (VSD), 7 cases underwent reoperation for debridement, and 2 cases underwent flap repair. Four patients died in the ICU with unhealed incisions, 2 patients had unhealed incisions at the time of discharge referral, and the remaining patients’ groin incisions eventually healed.

CONCLUSIONS: The incidence of poor healing of inguinal incisions after weaning from VA-ECMO is relatively high, mainly manifested as excessive exudate from the incision, delayed incision healing, non-healing of the incision, incision infection, lymphatic leakage, and incision dehiscence. Unilateral semi-incision catheterization and positive 3-day accumulated fluid balance after ECMO weaning are independent risk factors for poor inguinal incision healing in patients undergoing VA-ECMO. Early application of VSD is an effective solution for treating poor incision healing accompanied by a large amount of exudate.

PMID:42200240 | DOI:10.3760/cma.j.cn121430-20251126-00564

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Phenotypic characteristics and functional alterations of lipopolysaccharide-induced low-density neutrophil

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2026 Apr;38(4):309-316. doi: 10.3760/cma.j.cn121430-20250801-00417.

ABSTRACT

OBJECTIVE: To observe the generation of low-density neutrophil (LDN) induced by lipopolysaccharide (LPS) stimulation in vitro to simulate a septic environment, and to analyze their generation mechanism, phenotype, and functional characteristics.

METHODS: 1) Analysis of LDN proportion in septic patients: A case-control study was conducted. Peripheral blood samples were collected from 45 septic patients admitted to the intensive care unit (ICU) of Suzhou Municipal Hospital from June 2022 to January 2024, and from 32 age- and sex-matched healthy volunteers as the control group. The proportion of LDN in the peripheral blood mononuclear cell (PBMC) layer and among total neutrophils was analyzed. The expression of CD10, a marker of mature neutrophils, was detected by flow cytometry to analyze the proportion of immature LDN. 2) LPS-induced LDN generation and mechanism analysis: Neutrophils were isolated from the peripheral blood of healthy volunteers. They were stimulated with different concentrations of LPS (10, 100, 1 000 μg/L) for 4 hours. High-density neutrophil (HDN) and LDN were separated by Percoll density gradient centrifugation, and the proportion of LDN was calculated. Neutrophil extracellular trap (NET) levels in the culture supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Neutrophils from healthy volunteers were divided into HDN control, LDN control, LPS-stimulated HDN, and LPS-stimulated LDN groups. The LPS-stimulated groups were treated with LPS (1 000 μg/L) for 4 hours, while the control groups received an equal volume of culture medium. Morphological changes were observed under transmission electron microscope. Additionally, neutrophils from healthy volunteers were divided into control group (an equal volume of culture medium), LPS group (stimulated with 1 000 μg/L LPS for 4 hours), and phorbol 12-myristate 13-acetate (PMA) group (stimulated with 100 nmol/L PMA for 4 hours). NET formation was observed under scanning electron microscope. In another experiment, neutrophils from healthy volunteers were divided into LPS group (stimulated with 1 000 μg/L LPS for 4 hours) and GSK484 pretreatment group (pretreated with 50 nmol/L GSK484, a NET release inhibitor, for 30 minutes before LPS stimulation). LDN generation was detected by flow cytometry, and NET levels in the supernatant were detected by ELISA. 3) Phenotypic and functional analysis of neutrophils: Neutrophils from healthy volunteers were divided into the same four groups as described above (HDN control, LDN control, LPS-stimulated HDN, LPS-stimulated LDN groups). The expression of granulocyte maturation markers (CD66b, CD15, CD16), chemokine receptors (CXCR2, CXCR4), and cell activation markers (CD11b, CD62L) was detected by flow cytometry. Chemotactic function was assessed using an agarose chemotaxis model, and the chemotactic distance (CD), chemotactic cell ratio (CCR), and chemotactic index (CI) were analyzed.

RESULTS: 1) Analysis results of LDN proportion in septic patients: The proportion of neutrophils in the PBMC layer (0.362±0.125), the proportion of LDN among total neutrophils (0.439±0.162), and the proportion of CD10 LDN (0.222±0.093) in septic patients were higher than those in healthy controls (0.040±0.013, 0.014±0.004, and 0.005±0.002, respectively, all P<0.05). 2) LPS-induced LDN generation and mechanism analysis results: Transmission electron microscope showed increased surface protrusions and intracellular vacuoles in both HDN and LDN after LPS stimulation, particularly in the LPS-stimulated LDN group. After LPS stimulation, both the proportion of LDN and NET levels in the supernatant increased in a concentration-dependent manner (all P<0.05). Scanning electron microscope revealed that LPS stimulation induced NET formation in neutrophils, but to a lesser extent than PMA stimulation. GSK484 intervention inhibited LPS-induced LDN generation and NET release, with statistically significant differences compared with the LPS group [LDN count (×105): 3.75±0.52 vs. 7.07±1.14, NET (A value): 0.96±0.14 vs. 1.36±0.27, both P<0.05]. 3) Results of phenotypic and functional analysis of neutrophils: Cell phenotype analysis revealed that compared with the control groups, after LPS stimulation, both HDN and LDN showed increased expression of CD66b and CD11b, and decreased expression of CD16, CXCR2, and CD62L. Compared with the LPS-stimulated HDN group, the LPS-stimulated LDN group exhibited higher expression of CD66b [mean fluorescence intensity (MFI): 16 424±2 074 vs. 9 470±1 201, P<0.05] and lower expression of CD16 (MFI: 3 647±1 458 vs. 7 815±1 143, P<0.05), while CD15 expression showed no significant change. Regarding cell chemokine receptors, compared with the LPS-stimulated HDN group, the LPS-stimulated LDN group showed decreased CXCR2 expression and increased CXCR4 expression. Regarding activation markers, compared with the LPS-stimulated HDN group, the LPS-stimulated LDN group showed increased CD11b expression (MFI: 11 684±2 131 vs. 7 782±373, P<0.05) and decreased CD62L expression [(59.75±7.42)% vs. (82.18±14.06)%, P<0.05]. Chemotaxis assays showed that after LPS stimulation, CD, CCR, and CI of HDN and LDN were all decreased, with more pronounced decreases in the LPS-stimulated LDN group than in the LPS-stimulated HDN group [CD (μm): 886.5±342.7 vs. 1 633.0±295.0, CCR: (0.69±0.25)% vs. (2.44±1.40)%, CI: (9.63±8.94)% vs. (34.62±8.31)%, all P<0.05].

CONCLUSIONS: LPS induces LDN generation through a NET formation-dependent pathway. This LDN subpopulation displays a unique phenotype characterized by high expression of CD66b, CXCR4, CD11b and low expression of CD16, CXCR2, CD62L, accompanied by chemotactic dysfunction.

PMID:42200239 | DOI:10.3760/cma.j.cn121430-20250801-00417

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Nevin Manimala Statistics

Trends in risk factors associated with the increasing labor induction rate: A nationwide register study in Finland 2005-2023

Acta Obstet Gynecol Scand. 2026 May 27. doi: 10.1111/aogs.70267. Online ahead of print.

ABSTRACT

INTRODUCTION: Induction of labor (IOL) rates have been increasing in high-income countries. Although IOL aims to reduce maternal and neonatal morbidity, the benefits for many common indications remain uncertain. Because IOL may also have disadvantages and place a burden on the health-care system, it is important to clarify the factors underlying the rising national IOL rates.

MATERIAL AND METHODS: This descriptive study included all singleton births in cephalic presentation delivered at 37+0 gestational weeks or later between January 1, 2005, and December 31, 2023, in Finland. Data from the Finnish Medical Birth Register were used to examine temporal trends in maternal characteristics, gestational age at delivery, pregnancy complications, and other pregnancy-related problems across three periods: 2005-2010, 2011-2016, and 2017-2023. Induced deliveries were analyzed separately. Risk ratios with 95% confidence intervals were calculated to describe changes over time, and odds ratios with 95% confidence intervals were estimated to assess associations between IOL and risk factors. Logistic regression models were adjusted for maternal age, body mass index (BMI), and parity.

RESULTS: The study sample included 880 478 births. The IOL rate doubled from 18% to 36%. In the IOL group, the most prevalent and increasingly common factors were maternal age ≥35 years, BMI ≥30 kg/m2, and gestational diabetes. Prelabor rupture of membranes, fear of childbirth, and other pregnancy-related problems-despite their lower overall proportions-showed the steepest increases. Similar but less pronounced trends were seen in the total study cohort. The odds of IOL remained stable across the study periods for maternal age ≥35 years, BMI ≥30 kg/m2, gestational diabetes, prelabor rupture of membranes, fear of childbirth, and other pregnancy-related problems; and all associations remained statistically significant after adjustment. The proportion of post-term pregnancy decreased significantly in both the total study cohort and the IOL group. In the IOL group, gestational age at birth shifted from post-term to late- and full term.

CONCLUSIONS: The main contributors to the increasing IOL rate were the increased prevalence of advanced maternal age, obesity, and gestational diabetes. The increases in the prevalence of other IOL indications were less extensive.

PMID:42200222 | DOI:10.1111/aogs.70267

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Nevin Manimala Statistics

Public Perception of Fluoride: An Infodemiological Analysis of YouTube Videos and Comments

JDR Clin Trans Res. 2026 May 27:23800844261446256. doi: 10.1177/23800844261446256. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to analyze the public’s perception of fluoride by investigating the most-viewed YouTube videos and their associated comments addressing fluoride in dental/public health contexts.

METHODS: Metadata and comments of YouTube videos were retrieved using the YouTube Data application programming interface (YouTube Data API) via Python. The top 100 most-viewed YouTube videos related to fluoride and their comments were analyzed. Sentiment analysis, Latent Dirichlet Allocation (LDA) topic modeling, word co-occurrence analysis, and word frequency analysis were performed. Statistical analyses including Spearman’s correlation, Kruskal-Wallis tests, and Mann-Whitney U tests were conducted to assess potential associations.

RESULT: A total of 76 eligible videos and 88,126 comments were analyzed. Approximately half (45%) of the retrieved videos were uploaded in 2024 and 2025. The mean (±standard deviation) and median sentiment scores were 9.5 ± 15.9 and 5.4, respectively. Significant negative correlations were observed between sentiment scores and both video views (r = -0.247, P = 0.032) and the number of comments (r = -0.486, P < 0.001). Among professional uploaders, videos by dental hygienists had a higher sentiment score compared with those by dentists (17.5 vs. -0.5). Topic modeling revealed that the term “poison” appeared 6 times more frequently in negative comments than in positive comments, followed by “conspiracy” and “bad,” whereas “love,” “care,” and “safe” were predominant in positive comments.

CONCLUSION: Fluoride has emerged as a controversial societal topic. The terms “poison” and “conspiracy” reflect prominent public concerns. Dental hygienists play a critical role in disseminating online information on fluoride, highlighting the need for targeted strategies to mitigate public anxiety and promote the appropriate use of fluoride in dental care.Knowledge Transfer Statement:The present study provides insights into public health communication. First, empowering professionals and optimizing video formats (eg, tutorials, skills-based demonstration, and short dramas) could enhance the reach and acceptance of evidence-based fluoride advocacy. Second, policymakers should address societal and historical factors shaping public distrust, rather than relying solely on scientific dissemination. Finally, due to contagion of negative emotions, there is a need to monitor and alleviate negative sentiments.

PMID:42200218 | DOI:10.1177/23800844261446256