Investigating the causal association between gut microbiota and type 2 diabetes: a meta-analysis and Mendelian randomization.

Background: Studies have shown that gut dysbiosis contributes to the pathophysiology of type 2 diabetes mellitus (T2DM). Identifying specific gut microbiota dysbiosis may provide insight into the pathogenesis of T2DM. Purpose: This study investigated the causal relationship between gut microbiota and T2DM using meta-analysis and Mendelian randomization (MR). Methods: In the first part, we searched for literature on gut microbiota and T2DM, and conducted a meta-analysis. We observed differences in glycosylated hemoglobin and fasting blood glucose levels in both groups. Second, we obtained GWAS data from genome-wide association study database 19 (GWAS). We used two-sample MR analysis to verify the forward and reverse causal associations between gut microbiota and T2DM. Additionally, we selected the European GWAS data from the European Bioinformatics Institute (EBI) as a validation set for external validation of the MR analysis. In the third part, we aimed to clarify which gut microbiota contribute to the degree of causal association between group disorders and T2DM through multivariate MR analysis and Bayesian model averaging (MR-BMA). Results: 1. According to the meta-analysis results, the glycated hemoglobin concentration in the gut probiotic intervention group was significantly lower than in the control group. Following treatment, fasting blood glucose levels in the intervention group were significantly lower than those in the control group. 2. The results of two samples MR analysis revealed that there were causal relationships between six gut microbiota and T2DM. Genus Haemophilus and order Pasteurellaceae were negatively correlated with T2DM. Genus Actinomycetes, class Melanobacteria and genus Lactobacillus were positively correlated. Reverse MR analysis demonstrated that T2DM and gut microbiota did not have any reverse causal relationship. The external validation data set showed a causal relationship between gut microbiota and T2DM. 3. Multivariate MR analysis and MR-BMA results showed that the independent genus Haemophilus collection had the largest PP. Conclusion: Our research results suggest that gut microbiota is closely related to T2DM pathogenesis. The results of further MR research and an analysis of the prediction model indicate that a variety of gut microbiota disorders, including genus Haemophilus, are causally related to the development of T2DM. The findings of this study may provide some insight into the diagnosis and treatment of T2DM. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO.

Exploring explainable AI features in the vocal biomarkers of lung disease.

This review delves into the burgeoning field of explainable artificial intelligence (XAI) in the detection and analysis of lung diseases through vocal biomarkers. Lung diseases, often elusive in their early stages, pose a significant public health challenge. Recent advancements in AI have ushered in innovative methods for early detection, yet the black-box nature of many AI models limits their clinical applicability. XAI emerges as a pivotal tool, enhancing transparency and interpretability in AI-driven diagnostics. This review synthesizes current research on the application of XAI in analyzing vocal biomarkers for lung diseases, highlighting how these techniques elucidate the connections between specific vocal features and lung pathology. We critically examine the methodologies employed, the types of lung diseases studied, and the performance of various XAI models. The potential for XAI to aid in early detection, monitor disease progression, and personalize treatment strategies in pulmonary medicine is emphasized. Furthermore, this review identifies current challenges, including data heterogeneity and model generalizability, and proposes future directions for research. By offering a comprehensive analysis of explainable AI features in the context of lung disease detection, this review aims to bridge the gap between advanced computational approaches and clinical practice, paving the way for more transparent, reliable, and effective diagnostic tools.

Lovastatin-Induced Mitochondrial Oxidative Stress Leads to the Release of mtDNA to Promote Apoptosis by Activating cGAS-STING Pathway in Human Colorectal Cancer Cells.

Statins are 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors widely used in the treatment of hyperlipidemia. The inhibition of HMG-CoA reductase in the mevalonate pathway leads to the suppression of cell proliferation and induction of apoptosis. The cyclic GMP-AMP synthase (cGAS) stimulator of the interferon genes (STING) signaling pathway has been suggested to not only facilitate inflammatory responses and the production of type I interferons (IFN), but also activate other cellular processes, such as apoptosis. It has not been studied, however, whether cGAS-STING activation is involved in the apoptosis induced by statin treatment in human colorectal cancer cells. In this study, we reported that lovastatin impaired mitochondrial function, including the depolarization of mitochondrial membrane potential, reduction of oxygen consumption, mitochondrial DNA (mtDNA) integrity, and mtDNA abundance in human colorectal cancer HCT116 cells. The mitochondrial dysfunction markedly induced ROS production in mitochondria, whereas the defect in mitochondria respiration or depletion of mitochondria eliminated reactive oxygen species (ROS) production. The ROS-induced oxidative DNA damage by lovastatin treatment was attenuated by mitochondrial-targeted antioxidant mitoquinone (mitoQ). Upon DNA damage, mtDNA was released into the cytosol and bound to DNA sensor cGAS, thus activating the cGAS-STING signaling pathway to trigger a type I interferon response. This effect was not activated by nuclear DNA (nuDNA) or mitochondrial RNA, as the depletion of mitochondria compromised this effect, but not the knockdown of retinoic acid-inducible gene-1/melanoma differentiation-associated protein 5 (RIG-I/MDA5) adaptor or mitochondrial antiviral signaling protein (MAVS). Moreover, lovastatin-induced apoptosis was partly dependent on the cGAS-STING signaling pathway in HCT116 cells as the knockdown of cGAS or STING expression rescued cell viability and mitigated apoptosis. Similarly, the knockdown of cGAS or STING also attenuated the antitumor effect of lovastatin in the HCT116 xenograft model in vivo. Our findings suggest that lovastatin-induced apoptosis is at least partly mediated through the cGAS-STING signaling pathway by triggering mtDNA accumulation in the cytosol in human colorectal cancer HCT116 cells.

A Critical Appraisal of the Congress of Neurological Surgeons Evidence-Based Guidelines on the Evaluation and Treatment of Patients With Thoracolumbar Spine Trauma.

Background and objective Thoracolumbar spine trauma (TST) is frequently associated with spinal cord injury and other soft tissue and bony injuries. The management of such injuries requires an evidence-based approach. This study used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument to assess the methodological quality of clinical guidelines for the management of TST published by the Congress of Neurological Surgeons (CNS). Methods All clinical guidelines on TST published by CNS until 2020 were assessed. Five appraisers from three international centers evaluated the quality of eligible clinical guidelines by using AGREE II. Mean AGREE II scores for each domain were determined. In higher-quality domains, the scores for individual items were analyzed. Results A total of 12 guidelines published by CNS on TST were assessed. Mean scores for all six domains were as follows: Scope and Purpose (75.2%), Stakeholder Involvement (45.4%), Rigor of Development (57.0%), Clarity of Presentation (58.7%), Applicability (16.9%), and Editorial Independence (64.1%). The mean score for the overall quality of all CNS guidelines was 52.9% [95% confidence interval (CI): 52.2-53.5%]. The overall agreement among appraisers was excellent [intra-class correlation coefficients (ICCs) for each guideline ranged from 0.903 to 0.963]. Conclusions CNS guidelines for the management of TST demonstrated acceptable quality across most domains; however, the domains of Applicability and Stakeholder Involvement could be further improved in future guideline updates. The assessors concluded that all guidelines could still be recommended for clinical practice with or without modifications.

Effect of immune checkpoint inhibitors at different treatment time periods on prognosis of patients with extensive-stage small-cell lung cancer.

BACKGROUND: The application of immune checkpoint inhibitors (ICIs) in treating patients with extensive-stage small-cell lung cancer (ES-SCLC) has brought us new hope, but the real-world outcome is relatively lacking. Our aim was to investigate the clinical use, efficacy, and survival benefit of ICIs in ES-SCLC from real-world data analysis. METHODS: A retrospective analysis of ES-SCLC patients was conducted between 2012 and 2022. Progression-free survival (PFS) and overall survival (OS) were assessed between groups to evaluate the value of ICIs at different lines of treatment. PFS1 was defined as the duration from initial therapy to disease progression or death. PFS2 was defined as the duration from the first disease progression to the second disease progression or death. RESULTS: One hundred and eighty patients with ES-SCLC were included. We performed landmark analysis, which showed that compared to the second-line and subsequent-lines ICIs-combined therapy group (2SL-ICIs) and non-ICIs group, the first-line ICIs-combined therapy group (1L-ICIs) prolonged OS and PFS1. There was a trend toward prolonged OS in the 2SL-ICIs group than in the non-ICIs group, but the significance threshold was not met (median OS 11.94 months vs. 11.10 months, P = 0.14). A longer PFS2 was present in the 2SL-ICIs group than in the non-ICIs group (median PFS2 4.13 months vs. 2.60 months, P < 0.001). CONCLUSION: First-line ICIs plus chemotherapy should be applied in clinical practice. If patients did not use ICIs plus chemotherapy in first-line therapy, the use of ICIs in the second line or subsequent lines of treatment could prolong PFS2.

Research Progress on the Geomechanical Properties of Block-in-Matrix Rocks.

The differences in geomechanical properties and the uncertainty in the spatial distribution of Bimrock pose significant challenges to the construction and disaster prediction of geotechnical engineering. To clarify the geomechanical characteristics of Bimrock, this paper summarizes the basic concepts and classification methods of Bimrock at home and abroad. It discusses the methods and characteristics of determining the geometric features of Bimrock blocks and explores the influencing factors and laws of failure modes and strength under different stress states of Bimrock. The study finds that the failure mode of Bimrock is mainly influenced by factors such as block proportion, degree of welding between blocks and matrix, strength ratio between blocks and matrix, and geometric properties of blocks. Among these factors, block proportion is the most significant, and the degree of welding is a controlling factor. However, due to the complexity of Bimrock structures, there is a lack of applicable methods and mechanical models for the evaluation of geomechanical characteristics of Bimrock in engineering practice. This article also explores the influence and research methods of the geological characteristics of Bimrock in slope and tunnel engineering and, finally, provides prospects for the future research trends relating to Bimrock.

Microwave coagulation for liver metastases.

BACKGROUND: Liver metastases (i.e. secondary hepatic malignancies) are significantly more common than primary liver cancer. Long-term survival after radical surgical treatment is approximately 50%. For people in whom resection for cure is not feasible, other treatments must be considered. One treatment option is microwave coagulation utilising electromagnetic waves. It involves placing an electrode into a lesion under ultrasound or computed tomography guidance. OBJECTIVES: To evaluate the beneficial and harmful effects of microwave coagulation versus no intervention, other ablation methods, or systemic treatments in people with liver metastases regardless of the location of the primary tumour. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest date of search was 14 April 2023. SELECTION CRITERIA: Randomised clinical trials assessing beneficial or harmful effects of microwave coagulation and its comparators in people with liver metastases, irrespective of the location of the primary tumour. We included trials no matter the outcomes reported. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodological procedures. Our primary outcomes were: all-cause mortality at the last follow-up and time to mortality; health-related quality of life (HRQoL); and any adverse events or complications. Our secondary outcomes were: cancer mortality; disease-free survival; failure to clear liver metastases; recurrence of liver metastases; time to progression of liver metastases; and tumour response measures. We used risk ratios (RR) and hazard ratios (HR) with 95% confidence intervals (CI) to present the results. Two review authors independently extracted data and assessed the risk of bias using the Cochrane RoB 1 tool. We used GRADE methodology to assess the certainty of the evidence. MAIN RESULTS: Three randomised clinical trials fulfilled the inclusion criteria. The control interventions differed in the three trials; therefore, meta-analyses were not possible. The trials were at high risk of bias. The certainty of evidence of the assessed outcomes in the three comparisons was very low. Data on our prespecified outcomes were either missing or not reported. Microwave coagulation plus conventional transarterial chemoembolisation (TACE) versus conventional TACE alone One trial, conducted in China, randomised 50 participants (mean age 60 years, 76% males) with liver metastases from various primary sites. Authors reported that the follow-up period was at least one month. The trial reported adverse events or complications in the experimental group only and for tumour response measures. There were no dropouts in the trial. The trial did not report on any other outcomes. Microwave ablation versus conventional surgery One trial, conducted in Japan, randomised 40 participants (mean age 61 years, 53% males) with multiple liver metastases of colorectal cancer. Ten participants were excluded after randomisation (six from the experimental and four from the control group); thus, the trial analyses included 30 participants. Follow-up was three years. The reported number of deaths from all causes was 9/14 included participants in the microwave group versus 12/16 included participants in the conventional surgery group. The mean overall survival was 27 months in the microwave ablation and 25 months in the conventional surgery group. The three-year overall survival was 14% with microwave ablation and 23% with conventional surgery, resulting in an HR of 0.91 (95% CI 0.39 to 2.15). The reported frequency of adverse events or complications was comparable between the two groups, except for the required blood transfusion, which was more common in the conventional surgery group. There was no intervention-related mortality. Disease-free survival was 11.3 months in the microwave ablationgroup and 13.3 months in the conventional surgery group. The trial did not report on HRQoL. Microwave ablation versus radiofrequency ablation One trial, conducted in Germany, randomised 50 participants (mean age 62.8 years, 46% males) who were followed for 24 months. Two-year mortality showed an RR of 0.62 (95% CI 0.26 to 1.47). The trial reported that, by two years, 76.9% of participants in the microwave ablationgroup and 62.5% of participants in the radiofrequency ablation group survived (HR 0.63, 95% CI 0.23 to 1.73). The trial reported no deaths or major complications during the procedures in either group. There were two minor complications only in the radiofrequency ablation group (RR 0.19, 95% CI 0.01 to 3.67). The trial reported technical efficacy in 100% of procedures in both groups. Distant recurrence was reported for 10 participants in the microwave ablation group and nine participants in the radiofrequency ablation group (RR 1.03, 95% CI 0.50 to 2.08). No participant in the microwave ablation group demonstrated local progression at 12 months, while that occurred in two participants in the radiofrequency ablation group (RR 0.19, 95% CI 0.01 to 3.67). The trial did not report on HRQoL. One trial reported partial support by Medicor (MMS Medicor Medical Supplies GmbH, Kerpen, Germany) for statistical analysis. The remaining two trials did not provide information on funding. We identified four ongoing trials. AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effect of microwave ablation in addition to conventional TACE compared with conventional TACE alone on adverse events or complications. We do not know if microwave ablation compared with conventional surgery may have little to no effect on all-cause mortality. We do not know the effect of microwave ablation compared with radiofrequency ablation on all-cause mortality and adverse events or complications either. Data on all-cause mortality and time to mortality, HRQoL, adverse events or complications, cancer mortality, disease-free survival, failure to clear liver metastases, recurrence of liver metastases, time to progression of liver metastases, and tumour response measures were either insufficient or were lacking. In light of the current inconclusive evidence and the substantial gaps in data, the pursuit of additional good-quality, large randomised clinical trials is not only justified but also essential to elucidate the efficacy and comparative benefits of microwave ablation in relation to various interventions for liver metastases. The current version of the review, in comparison to the previous one, incorporates two new trials in two additional microwave ablation comparisons: 1. in addition to conventional TACE versus conventional TACE alone and 2. versus radiofrequency ablation.

Histone methylation readers MRG1/2 interact with PIF4 to promote thermomorphogenesis in Arabidopsis.

Warm ambient conditions induce thermomorphogenesis and affect plant growth and development. However, the chromatin regulatory mechanisms involved in thermomorphogenesis remain largely obscure. In this study, we show that the histone methylation readers MORF-related gene 1 and 2 (MRG1/2) are required to promote hypocotyl elongation in response to warm ambient conditions. A transcriptome sequencing analysis indicates that MRG1/2 and phytochrome interacting factor 4 (PIF4) coactivate a number of thermoresponsive genes, including YUCCA8, which encodes a rate-limiting enzyme in the auxin biosynthesis pathway. Additionally, MRG2 physically interacts with PIF4 to bind to thermoresponsive genes and enhances the H4K5 acetylation of the chromatin of target genes in a PIF4-dependent manner. Furthermore, MRG2 competes with phyB for binding to PIF4 and stabilizes PIF4 in planta. Our study indicates that MRG1/2 activate thermoresponsive genes by inducing histone acetylation and stabilizing PIF4 in Arabidopsis.

All-Year High IAA and ABA Contents in Rhizome Buds May Contribute to Natural Four-Season Shooting in Woody Bamboo Cephalostachyum pingbianense.

To explore the regulation mechanism of endogenous phytohormones on rhizome bud germination in Cephalostachyum pingbianense, the contents of IAA, ABA, GA, and CTK in seven above- and under-ground bamboo structure components were determined using enzyme-linked immunosorbent assays (ELISA). The results showed that a higher content of IAA, GA, and CTK all year was found in above-ground components and dormant rhizome buds. Meanwhile, a higher ABA content in young shoots and a lower ABA content in the culm base and dormant rhizome buds were detected during the peak period of shooting. The amounts of emerging shoots and the grown bamboo culms were positively correlated with the content of IAA and the ratio of IAA/ABA and (IAA + CTK + GA)/ABA, while they were negatively correlated with the ratio of CTK/IAA in dormant rhizome buds. The all-year high contents of IAA (19-31 ng/g) and ABA (114-144 ng/g) in rhizome buds, as well as interactions among four hormones, may be the key physiological mechanisms to maintain rhizome bud germination throughout the year in C. pingbianense. As C. pingbianense is a special bamboo species of multi-season shoot sprouting, the above results may supplement scientific data for a comprehensive understanding of physiological mechanisms within the bamboo subfamily.

Damage of polyethylene microplastics on the intestine multilayer barrier, blood cell immune function and the repair effect of Leuconostoc mesenteroides DH in the large-scale loach (Paramisgurnus dabryanus).

Polyethylene microplastics (PE-MPs) has become a global concern due to their widespread distribution and hazardous properties in aquatic habitats. In this study, the accumulation effect of PE-MPs in the intestine of large-scale loach (Paramisgurnus dabryanus) was explored by adding different concentrations of PE-MPs to the water, the destination of PE-MPs after breaking the intestinal barrier and the effects caused. The collected data showed that PE-MPs accumulation for 21d altered the histomorphology and antioxidant enzyme activity of the intestine, induced dysbiosis of the intestinal flora. 10 mg/L of PE-MPs induced a significant increase in the transcript levels of intestinal immunity factors in loach after 21d of exposure. Moreover, the levels of diamine oxidase (DAO) and d-lactic acid (D-Lac) in the gut and serum of loach were significantly increased after exposure to PE-MPs at all concentrations (1, 5, 10 mg/L). Subsequently, the presence of PE-MPs was detected in the blood, suggesting that the disruption of the intestinal multilayer barrier allowed PE-MPs to spill into the circulation. The accumulation of PE-MPs (1,5,10 mg/L) in the blood led to massive apoptosis and necrosis of blood cells and activated phagocytosis in response to PE-MPs invasion. To alleviate the damage, this study further exposure the effect of probiotics on PE-MPs treated loach by adding Leuconostoc mesenteroides DH (109 CFU/g) to the feed. The results showed that DH significantly increased the intestinal index and reduced the levels of DAO and D-Lac. To investigate the reason, we followed the PE-MPs in the intestine and blood of the loach and found that the number of PE-MPs particles was significantly reduced in the probiotic group, while the PE-MPs content in the feces was elevated. Thus, we concluded that DH reducing the accumulation of PE-MPs in the intestinal by increases fecal PE-MPs, which in turn mitigates the damage to the intestinal barrier caused by PE-MPs, and reduces the amount of PE-MPs in the blood. This work offers a robust analysis to understand the mechanisms of damage to the intestinal barrier by MPs and the fate of MPs after escaping the intestinal barrier and provide a new perspective on the application of probiotics in mitigating PE-MPs toxicity.

Novel Pathogenic Mutation of P209L in TRPC6 Gene Causes Adult Focal Segmental Glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a leading kidney disease, clinically associated with proteinuria and progressive renal failure. The occurrence of this disease is partly related to gene mutations. We describe a single affected family member who presented with FSGS. We used high-throughput sequencing, sanger sequencing to identify the pathogenic mutations, and a systems genetics analysis in the BXD mice was conducted to explore the genetic regulatory mechanisms of pathogenic genes in the development of FSGS. We identified high urinary protein (++++) and creatinine levels (149 µmol/L) in a 29-year-old male diagnosed with a 5-year history of grade 2 hypertension. Histopathology of the kidney biopsy showed stromal hyperplasia at the glomerular segmental sclerosis and endothelial cell vacuolation degeneration. Whole-exome sequencing followed by Sanger sequencing revealed a heterozygous missense mutation (c.643C > T) in exon 2 of TRPC6, leading to the substitution of arginine with tryptophan at position 215 (p.Arg215Trp). Systems genetics analysis of the 53 BXD mice kidney transcriptomes identified Pygm as the upstream regulator of Trpc6. Those two genes are jointly involved in the regulation of FSGS mainly via Wnt and Hippo signaling pathways. We present a novel variant in the TRPC6 gene that causes FSGS. Moreover, our data suggested TRPC6 works with PYGM, as well as Wnt and Hippo signaling pathways to regulate renal function, which could guide future clinical prevention and targeted treatment for FSGS outcomes.

Resistant starch and the gut microbiome: Exploring beneficial interactions and dietary impacts.

The intricate relationship between resistant starch (RS) and the gut microbiome presents a dynamic frontier in nutrition science. This review synthesizes current understandings of how RS, an indigestible form of starch found naturally in certain foods and also enhanced through various modification methods, interacts with the gut microbiome. We particularly focus on how RS fermentation in the colon contributes to the production of beneficial volatile fatty acids (VFAs) such as butyrate, acetate, and propionate. These VFAs have been recognized for their vital roles in maintaining gut barrier integrity, modulating inflammation, and potentially influencing systemic health. Additionally, we discuss the dietary implications of consuming foods rich in RS, both in terms of gut health and broader metabolic outcomes. By consolidating these insights, we emphasize the significance of RS in the context of dietary strategies aimed at harnessing the gut microbiome's potential to impact human health.

CD163 as a Potential Biomarker-associated Immune Inflammation in Diabetes Mellitus: A Systematic Review and Bioinformatics Analysis.

BACKGROUND: Several studies have identified CD163 as a potential mediator of diabetes mellitus through an immune-inflammation. Further study is necessary to identify its specific mechanism. OBJECTIVES: In this study, we aimed to investigate CD163 as a potential biomarker associated with immune inflammation in diabetes mellitus through a systematic review and bioinformatics analysis. METHODS: We searched PubMed, Web of Science, the Cochrane Library, and Embase databases with a time limit of September 2, 2022. Furthermore, we conducted a systematic search and review based on PRISMA guidelines. Additionally, diabetic gene expression microarray datasets GSE29221, GSE30528, GSE30529, and GSE20966 were downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo) for bioinformatics analysis. The PROSPERO number for this study is CRD420222347160. RESULTS: Following the inclusion and exclusion criteria, seven articles included 1607 patients, comprising 912 diabetic patients and 695 non-diabetic patients. This systematic review found significantly higher levels of CD163 in diabetic patients compared to non-diabetic patients. People with diabetes had higher levels of CRP expression compared to the control group. Similarly, two of the three papers that used TNF- α as an outcome indicator showed higher expression levels in diabetic patients. Furthermore, IL-6 expression levels were higher in diabetic patients than in the control group. A total of 62 samples were analyzed by bioinformatics (33 case controls and 29 experimental groups), and 85 differential genes were identified containing CD163. According to the immune cell correlation analysis, CD163 was associated with macrophage M2, γδ T lymphocytes, macrophage M1, and other immune cells. Furthermore, to evaluate the diagnostic performance of CD163, we validated it using the GSE20966 dataset. In the validation set, CD163 showed high diagnostic accuracy. CONCLUSION: This study suggests CD163 participates in the inflammatory immune response associated with diabetes mellitus and its complications by involving several immune cells. Furthermore, the results suggest CD163 may be a potential biomarker reflecting immune inflammation in diabetic mellitus.

The impact of superselective adrenal artery embolization on renal function in patients with primary aldosteronism: a prospective cohort study.

Superselective adrenal artery embolization (SAAE) is an effective treatment for patients with primary aldosteronism (PA). However, the impact of SAAE on renal function in the PA population remains uncertain. We investigated the estimated glomerular filtration rate (eGFR) and age, sex, body mass index, and diabetes-specific percentiles of eGFR residuals in 182 PA patients treated with SAAE in a prospective cohort from Nanchang SAAE in treating PA registry study. Data suggest that SAAE caused a significant decrease in eGFR from 91.9 ± 26.1 to 88.7 ± 24.1 ml/min/1.73 m2 (p < 0.05) after a median follow-up of 8 months in PA patients. Patients experienced a significant decrease in eGFR from 110.6 ± 18.9 to 103.8 ± 18.2 ml/min/1.73 m2 (p < 0.001) and a very slight increase from 71.1 ± 14.8 to 71.8 ± 17.8 ml/min/1.73 m2 (p = 0.770) with baseline eGFR ≥90 and <90 ml/min/1.73 m2, respectively. Patients with high eGFR residuals (glomerular hyperfiltration) experienced a significant decrease in their eGFR levels from 123.1 ± 22.6 to 105.0 ± 18.6 ml/min/1.73 m2 (p < 0.001). In contrast, there was no significant impact of SAAE on the eGFR of patients with normal or low eGFR residuals. The very early eGFR changes (24 h after SAAE) best predicted the effect of SAAE on eGFR changes after median of eight months in PA patients. On the whole, SAAE seems to have a beneficial impact on renal function in patients with PA, the results of which vary depending on the patient's baseline eGFR and glomerular hyperfiltration status.

Effect of Sequence of Radiotherapy Combined With Immunotherapy on the Incidence of Pneumonitis in Patients With Lung Cancer: A Systematic Review and Network Meta-Analysis.

BACKGROUND: With the widespread application of immune checkpoint inhibitor (ICI) combined with radiotherapy (RT) for the treatment of lung cancer, increasing attention has been paid to treatment-related pneumonitis. The effect of the treatment sequence on the incidence of pneumonitis remains unclear. METHODS: We searched databases including PubMed, Embase, and ClinicalTrials.gov, meeting abstracts, and reference lists of relevant review articles for literature published on radio- and immunotherapy in lung cancer. Stata software (version 16.0) was used for meta-analysis. Data on the incidence of any grade and ≥ grade 3 pneumonitis was pooled using the random effects model. Bayesian network meta-analysis was used for arm-based pairwise comparisons. Subgroup analyses were performed to identify the potential influencing factors. RESULTS: Thirty-eight studies met our inclusion criteria. The network meta-analysis showed no significant difference between the incidence of pneumonitis in concurrent ICI with RT (concurrent arm) and RT followed by ICI (RT-first arm) (odds ratio [OR]: 0.71, 95% confidence interval [CI]: 0.10-4.81). In the meta-analysis of single group rates, RT following ICI (ICI-first arm) exhibited higher incidence of any grade pneumonitis compared with concurrent- and RT-first arms, with 0.321 (95% CI: 0.260-0.386) for programmed cell death protein 1 (PD-1) inhibitors from clinical trials, and 0.480 (95% CI: 0.363-0.598) for PD-1 inhibitors from real-world retrospective data, respectively. CONCLUSION: No significant difference in the incidence of any grade and grade ≥ 3 pneumonitis was found between RT-first and concurrent arms. The ICI-first arm exhibited a higher incidence of pneumonitis, which needs to be further confirmed by follow-up studies.

Dazhu Hongjingtian Injection for Ischemic Stroke: Protocol for a Prospective, Multicenter Observational Study.

BACKGROUND: Although results from in vitro studies and small randomized controlled trials have shown positive effects of Dazhu hongjingtian injection (DZHJTI) on acute ischemic stroke (AIS), their generalizability to routine clinical practice remains to be established. OBJECTIVE: The primary aim of this study is to evaluate the effectiveness of DZHJTI treatment for AIS with regard to changes in the stroke-related neurological deficit from baseline to outpatient follow-up, mortality, subsequent vascular events, disability, and traditional Chinese medicine syndrome in real-world clinical settings. By monitoring for adverse events or significant changes in vital signs and laboratory parameters, we also aim to assess the safety of DZHJTI. METHODS: This prospective, multicenter cohort study plans to enroll 2000 patients with AIS within 14 days of symptom onset from 30 hospitals across China. Eligible patients will be followed up for 6 months after initiating medication treatments. The primary outcome will be the change in the National Institute of Health Stroke Scale score from baseline to outpatient follow-up. The secondary outcomes include overall mortality, stroke recurrence, new-onset major vascular events, global disability, and improvement of traditional Chinese medicine syndrome in 6 months. Adverse events or clinically significant changes in vital signs and laboratory parameters, regardless of the severity, will be recorded during the trial to assess the safety of DZHJTI. An augmented inverse propensity weighted estimator will be used to reduce variability and improve accuracy in average treatment effects estimation. RESULTS: The clinical trial registration was approved in October 2022, and the recruitment and enrollment of participants started in November 2022. The study's outcomes are expected to be published in 2025 in reputable, peer-reviewed health-related research journals. CONCLUSIONS: This real-world cohort study is the first to assess the effectiveness and safety of DZHJTI in treating AIS. It may provide additional clinical evidence, including the duration of response, long-term drug effectiveness, and subgroup efficacy data. The study results will be valuable for clinicians and patients seeking optimal treatment for AIS and could lead to better use of DZHJTI and improved patient outcomes. TRIAL REGISTRATION: ITMCTR ITMCTR2022000005; http://tinyurl.com/554ns8m5. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52447.

Postoperative Metachronous Metastasis of Bladder Cancer to Penis: A Case Report.

BACKGROUND: Penile metastases are extremely rare events, originating primarily from primary pelvic tumours of the prostate, bladder, and gastrointestinal tract. The underlying mechanism of bladder cancer metastasis to the penis remains unclear. Metastasis to the penis is usually considered a late manifestation of systemic spread. Therefore, the prognosis of patients with penile metastasis remains poor and their survival period is short. Therefore, reporting this rare case will help to better understand the characteristics, diagnosis, and treatment processes of the disease, with the aim of improving the accuracy and efficiency of diagnosis and treatment. CASE DESCRIPTION: A 65-year-old male received transurethral resection of a bladder tumor. One year later, he underwent radical cystectomy because of the recurrence and progression of bladder cancer. Postoperative pathology demonstrated that the stage of bladder cancer was T3N0M0. One year later, he discovered a penile mass that gradually grew and became hard, accompanied by urinary retention, but without other clinical symptoms. The patient underwent a complete penectomy. Histopathology and immunohistochemistry results demonstrated the tumour's origin as a bladder urothelial carcinoma. The patient received systemic chemotherapy after surgery, but died 7 months later. CONCLUSIONS: Although penile metastasis of bladder cancer typically indicates an advanced stage of the malignant tumour and poor prognosis, we recommend that male patients with a history of bladder cancer should undergo a regular clinical examination of the penis to rapidly detect the disease and receive early treatment. In this case, despite treatment measures such as systemic chemotherapy and penectomy, the patient's prognosis remained poor.

Serum ferritin level is an effective prognostic factor for lung cancer immunotherapy.

Immunotherapy of lung cancer has achieved promising clinical results. However, it is urgent to develop predictive biomarkers for effective immunotherapy. While ferroptosis plays a critical role in immunotherapy efficacy, ferritin is an important regulatory factor. We, therefore, hypothesize that basal serum ferritin levels before immunotherapy and their corresponding changes during immunotherapy can be useful predictors of immunotherapy response in patients with lung cancer. We measured serum ferritin levels in 107 patients with lung cancer before and during immune checkpoint blockade treatments and studied the correlation between ferritin levels, response rate, and survival. Moreover, the correlation between basal ferritin and PD-L1 expression, tumor stages and pathological types was also analyzed. Patients with lower basal serum ferritin levels before immunotherapy had longer progression-free survival (PFS) (median 7 vs 4 months, P = .023) and higher disease control rate (DCR) (X2 = 4.837, P = .028), those with downregulated serum ferritin levels during immunotherapy correlated with longer PFS (median 9.5 vs 4 months, P < .001) and higher DCR (X2 = 6.475, P = .011). However, the "integrated factor", which was calculated as the combination of lower basal serum ferritin levels before immunotherapy and downregulated serum ferritin levels during immunotherapy, correlated with prolonged PFS (P < .001). Multivariate analyses revealed that the basal serum ferritin levels before immunotherapy and the corresponding changes during immunotherapy were both strong independent prognostic factors (hazard ratio (HR) = 1.60, P = .041; HR = 2.65, P = .001). These findings suggest that serum ferritin levels can be used as a prognostic biomarker for lung cancer in predicting immunotherapy efficacy.

Harnessing the power of clinical decision support systems: challenges and opportunities.

Clinical decision support systems (CDSSs) are increasingly integrated into healthcare settings to improve patient outcomes, reduce medical errors and enhance clinical efficiency by providing clinicians with evidence-based recommendations at the point of care. However, the adoption and optimisation of these systems remain a challenge. This review aims to provide an overview of the current state of CDSS, discussing their development, implementation, benefits, limitations and future directions. We also explore the potential for enhancing their effectiveness and provide an outlook for future developments in this field. There are several challenges in CDSS implementation, including data privacy concerns, system integration and clinician acceptance. While CDSS have demonstrated significant potential, their adoption and optimisation remain a challenge.

Can Ultrasound-Guided Continuous Paravertebral Block Reduce the Incidence of Chronic Postsurgical Pain in Patients with Thoracoscopic Lung Cancer Surgery? A Randomized Controlled Trial.

Background: Thoracoscopic lung cancer surgery is accompanied by severe pain. Both continuous paravertebral block (CPVB) and continuous wound infiltration (CWI) are widely used for perioperative analgesia in thoracoscopic surgery. However, the effects of these different methods on chronic postsurgical pain (CPSP) are still unknown. Patients and Methods. This prospective randomized controlled trial assessed the eligibility of 113 patients. Ninety-seven patients who met the inclusion criteria were randomly divided into a CPVB group and a CWI group, and 80 patients were analyzed in the final study. The primary outcome measures were the incidence and intensity of chronic postsurgical pain (CPSP) at 3, 6, and 9 months after surgery. The secondary outcome measures were the numerical rating scale (NRS) score of rest and activity at 12, 18, and 24 hours and on the 2nd, 3rd, and 7th days postoperatively; the Barthel Activities of Daily Living (ADL) score of activity levels on the 1st, 2nd, 3rd, and 7th days postoperatively; and the long-term quality of the life score at 3, 6, and 9 months postoperatively. Results: The incidence of chronic postsurgical pain in the CWI group was significantly higher than that in the CPVB group at 3, 6, and 9 months after surgery (all P < 0.05). The intensity of chronic postsurgical pain was significantly decreased in the CPVB group at 3, 6, and 9 months after surgery (P < 0.05). NRS-R and NRS-A scores were significantly decreased in the CPVB group within the first week after thoracoscopic surgery (P < 0.001). ADL scores were increased in the CPVB group within 3 days postoperatively. However, there were no differences in the ADL score on the 7th postoperative day or the long-term quality of the life score at 3, 6, and 9 months postoperatively. Conclusion: Continuous ultrasound-guided paravertebral block reduced the intensity of acute pain within 7 days postoperatively and reduced the incidence of chronic pain at 3, 6, and 9 months after surgery, but there was no significant advantage in long-term quality of life. This trial is registered with ChiCTR2000038505.