The dynamic shifts of IL-10-producing Th17 and IL-17-producing Treg in health and disease: a crosstalk between ancient "Yin-Yang" theory and modern immunology.

The changes in T regulatory cell (Treg) and T helper cell (Th) 17 ratios holds paramount importance in ensuring internal homeostasis and disease progression. Recently, novel subsets of Treg and Th17, namely IL-17-producing Treg and IL-10-producing Th17 have been identified. IL-17-producing Treg and IL-10-producing Th17 are widely considered as the intermediates during Treg/Th17 transformation. These "bi-functional" cells exhibit plasticity and have been demonstrated with important roles in multiple physiological functions and disease processes. Yin and Yang represent opposing aspects of phenomena according to the ancient Chinese philosophy "Yin-Yang" theory. Furthermore, Yin can transform into Yang, and vice versa, under specific conditions. This theory has been widely used to describe the contrasting functions of immune cells and molecules. Therefore, immune-activating populations (Th17, M1 macrophage, etc.) and immune overreaction (inflammation, autoimmunity) can be considered Yang, while immunosuppressive populations (Treg, M2 macrophage, etc.) and immunosuppression (tumor, immunodeficiency) can be considered Yin. However, another important connotation of "Yin-Yang" theory, the conversion between Yin and Yang, has been rarely documented in immune studies. The discovery of IL-17-producing Treg and IL-10-producing Th17 enriches the meaning of "Yin-Yang" theory and further promotes the relationship between ancient "Yin-Yang" theory and modern immunology. Besides, illustrating the functions of IL-17-producing Treg and IL-10-producing Th17 and mechanisms governing their differentiation provides valuable insights into the mechanisms underlying the dynamically changing statement of immune statement in health and diseases.

Analysis of percutaneous nephrostomy exchange intervals: insights from a retrospective Merative MarketScan analysis between 2009-2021.

BACKGROUND: Current practices in nephrostomy exchange are guided by institutional or societal expert-consensus rather than evidence-based recommendations. OBJECTIVE: To examine the temporal distribution of exchanges and assess whether the observed distributions align with institutional, or expert-recommended guidelines where routine exchanges would be expected to occur within 60-89 days. Non-routine exchanges would be expected to occur either after 60 days or after 89 days. METHODS: Data were collected from the Merative™ MarketScan Commercial Claims and Encounters Databases and included all patients who underwent a PCN exchange from 2009 to 2021. The dataset was queried using ICD-9/10 and CPT coding systems. Outpatient exchanges were classified as routine exchanges, whereas inpatient exchanges were classified as non-routine exchanges. Chi-Square Goodness-of-Fit tests were used to compare observed frequencies against expected distributions of routine exchanges within the 59-89 day window, and non-routine exchanges to occur after either 60 or after 89 days. RESULTS: There was a total of 19,689 exchanges: of those, 41% (n = 8,058) exchange encounters occurred within 29 days, 67% (n = 13,213) occurred within 59 days, and 81% (n = 15,899) occurred within 89 days. Routine exchanges accounted for 76% of total exchanges: of those routine exchanges, 39% (n = 5,863) of routine exchanges occurred within 29 days, 67% (n = 10,057) occurred within 59 days, and 82% (n = 12,256) occurred within 89 days. Non-routine exchanges account for 24% of all exchanges in the study cohort. Of all non-routine exchanges (n = 4,737), 46% (n = 2,035) of non-routine exchange encounters occurred within 29 days, 67% (n = 3,156) within 60 days, and 77% (n = 3,643) within 89 days. Chi-square tests indicated significant deviations from the expected distributions for both routine (p < 0.01) and non-routine (p < 0.01) exchanges. CONCLUSION: A significant proportion of routine exchanges occur outside a 60-89 day window, and with a majority of routine exchange observations occurring prior to 59 days. A significant proportion of non-routine exchanges occur prior to 60 days and prior to 89 days. CLINICAL IMPACT: Significant disparities between existing guidelines and clinical practice, underscoring the need for evidence-based guidelines to reduce complication rates, improve patient outcomes, and reduce the burden of cost on the healthcare system.

Vision of the future: large language models in ophthalmology.

PURPOSE OF REVIEW: Large language models (LLMs) are rapidly entering the landscape of medicine in areas from patient interaction to clinical decision-making. This review discusses the evolving role of LLMs in ophthalmology, focusing on their current applications and future potential in enhancing ophthalmic care. RECENT FINDINGS: LLMs in ophthalmology have demonstrated potential in improving patient communication and aiding preliminary diagnostics because of their ability to process complex language and generate human-like domain-specific interactions. However, some studies have shown potential for harm and there have been no prospective real-world studies evaluating the safety and efficacy of LLMs in practice. SUMMARY: While current applications are largely theoretical and require rigorous safety testing before implementation, LLMs exhibit promise in augmenting patient care quality and efficiency. Challenges such as data privacy and user acceptance must be overcome before LLMs can be fully integrated into clinical practice.

The newest Oxford Nanopore R10.4.1 full-length 16S rRNA sequencing enables the accurate resolution of species-level microbial community profiling.

The long-read amplicon provides a species-level solution for the community. With the improvement of nanopore flowcells, the accuracy of Oxford Nanopore Technologies (ONT) R10.4.1 has been substantially enhanced, with an average of approximately 99%. To evaluate its effectiveness on amplicons, three types of microbiomes were analyzed by 16S ribosomal RNA (hereinafter referred to as "16S") amplicon sequencing using Novaseq, Pacbio sequel II, and Nanopore PromethION platforms (R9.4.1 and R10.4.1) in the current study. We showed the error rate, recall, precision, and bias index in the mock sample. The error rate of ONT R10.4.1 was greatly reduced, with a better recall in the case of the synthetic community. Meanwhile, in different types of environmental samples, ONT R10.4.1 analysis resulted in a composition similar to Pacbio data. We found that classification tools and databases influence ONT data. Based on these results, we conclude that the ONT R10.4.1 16S amplicon can also be used for application in environmental samples. IMPORTANCE The long-read amplicon supplies the community with a species-level solution. Due to the high error rate of nanopore sequencing early on, it has not been frequently used in 16S studies. Oxford Nanopore Technologies (ONT) introduced the R10.4.1 flowcell with Q20+ reagent to achieve more than 99% accuracy as sequencing technology advanced. However, there has been no published study on the performance of commercial PromethION sequencers with R10.4.1 flowcells on 16S sequencing or on the impact of accuracy improvement on taxonomy (R9.4.1 to R10.4.1) using 16S ONT data. In this study, three types of microbiomes were investigated by 16S ribosomal RNA (rRNA) amplicon sequencing using Novaseq, Pacbio sequel II, and Nanopore PromethION platforms (R9.4.1 and R10.4.1). In the mock sample, we displayed the error rate, recall, precision, and bias index. We observed that the error rate in ONT R10.4.1 is significantly lower, especially when deletions are involved. First and foremost, R10.4.1 and Pacific Bioscience platforms reveal a similar microbiome in environmental samples. This study shows that the R10.4.1 full-length 16S rRNA sequences allow for species identification of environmental microbiota.

Climate factors and host chemical profiles jointly drives the bacterial community assembly in Mussaenda pubescens stems.

Endophytic bacteria residing within host plants can significantly impact on the host's growth, health, and overall relationship with its surrounding environment. However, the process that shape the community assembly of stem bacterial endophytes (SBEs) remains poorly understood. This study explored the community structure, co-occurrence patterns, and ecological processes of the SBEs inhabiting the shrub host, Mussaenda pubescens, across seven locations in southeastern China. We found that the absolute abundances, alpha diversity, and community composition of SBE communities exhibited notable differences among various host populations. Stem chemical characteristics were the most important factors influencing SBE community distribution, followed by geographic distance and climatic factors. The beta diversity decomposition analyses indicated that SBE community dissimilarities between sites were nearly equally driven by similarity, replacement diversity, and richness difference. The co-occurrence network analysis revealed that the keystone taxa were mostly observed in rare species, which may be essential for preserving the ecosystem's functions. Conditionally abundant taxa (CAT) showcased the highest closeness centrality, while exhibiting the lowest degree centrality and betweenness centrality as opposed to rare taxa. In addition, stochastic processes also played an important role in structuring SBE communities, with ecological drift being the dominant factor for both abundant and rare taxa. This study would deepen our understanding of the ecological dynamics and microbial interactions within plant endophytic microbiomes.

Stenting and Angioplasty in Neurothrombectomy: Matched Analysis of Rescue Intracranial Stenting Versus Failed Thrombectomy.

BACKGROUND: Successful reperfusion is one of the strongest predictors of functional outcomes after mechanical thrombectomy (MT). Despite continuous advancements in MT technology and techniques, reperfusion failure still occurs in ≈15% to 30% of patients with large vessel occlusion strokes undergoing MT. We aim to evaluate the safety and efficacy of rescue intracranial stenting for large vessel occlusion stroke after failed MT. METHODS: The SAINT (Stenting and Angioplasty in Neurothrombectomy) Study is a retrospective analysis of prospectively collected data from 14 comprehensive stroke centers through January 2015 to December 2020. Patients were included if they had anterior circulation large vessel occlusion stroke due to intracranial internal carotid artery and middle cerebral artery-M1/M2 segments and failed MT. The cohort was divided into 2 groups: rescue intracranial stenting and failed recanalization (modified Thrombolysis in Cerebral Ischemia score 0-1). Propensity score matching was used to balance the 2 groups. The primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale at 90 days. Secondary outcomes included functional independence (90-day modified Rankin Scale score 0-2). Safety measures included symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: A total of 499 patients were included in the analysis. Compared with the failed reperfusion group, rescue intracranial stenting had a favorable shift in the overall modified Rankin Scale score distribution (acOR, 2.31 [95% CI, 1.61-3.32]; P<0.001), higher rates of functional independence (35.1% versus 7%; adjusted odds ratio [aOR], 6.33 [95% CI, 3.14-12.76]; P<0.001), and lower mortality (28% versus 46.5%; aOR, 0.55 [95% CI, 0.31-0.96]; P=0.04) at 90 days. Rates of symptomatic intracerebral hemorrhage were comparable across both groups (7.1% versus 10.2%; aOR, 0.99 [95% CI, 0.42-2.34]; P=0.98). The matched cohort analysis demonstrated similar results. Specifically, rescue intracranial stenting (n=107) had a favorable shift in the overall modified Rankin Scale score distribution (acOR, 3.74 [95% CI, 2.16-6.57]; P<0.001), higher rates of functional independence (34.6% versus 6.5%; aOR, 10.91 [95% CI, 4.11-28.92]; P<0.001), and lower mortality (29.9% versus 43%; aOR, 0.49 [95% CI, 0.25-0.94]; P=0.03) at 90 days with similar rates of symptomatic intracerebral hemorrhage (7.5% versus 11.2%; aOR, 0.87 [95% CI, 0.31-2.42]; P=0.79) compared with patients who failed to reperfuse (n=107). There was no heterogeneity of treatment effect across the prespecified subgroups for improvement in functional outcomes. CONCLUSIONS: Acute intracranial stenting appears to be a safe and effective rescue strategy in patients with large vessel occlusion stroke who failed MT. Randomized multicenter trials are warranted.

The Standardized Inclusive Numeric Academic Index: An Index to Measure Academic Productivity in Plastic Surgery.

PURPOSE: Academic productivity is a poorly defined metric that is commonly used to determine faculty career advancement. While various indices incorporate scholarly activity, no specific index assimilates the perceived importance of a variety of academic accomplishments a physician may make. Herein, the development and validation of an algorithm to generate an academic productivity score based on surveying physicians nationwide are described. METHODS: From 2016 to 2018, an online cross-sectional survey was distributed to faculty members at an academic institution and plastic surgeons from different academic levels nationwide. Respondents were presented with randomized, binary comparisons of 42 different achievements of an academic physician and asked to choose the more important achievement. Descriptive statistics of demographics and "win rates" of each achievement were reported and an algorithm for academic productivity scoring was designed. To validate the proposed index, 30 curricula vitae of academic surgeons were anonymized and ranked in order of increasing academic achievement by 6 volunteers. Interrater reliability was assessed by Krippendorff α (α ≥ 0.800). RESULTS: Survey respondents completed an average of 116 (SD, 97.6) comparisons each, generating a total of 14,736 ranked comparisons. Of the 42 variables, the highest win rates were attained by being the dean of a medical school (0.90) and editor of a medical journal (0.88). The lowest win rates were attained by industry spokesperson (0.1) and members of the local medical society (0.1). Initial validity evidence found the interrater reliability for the 6 rankers to have a Krippendorff α value of 0.843. The interrater reliability between the average rater ranking and the algorithm-generated ranking had a Krippendorff α value of 0.925. CONCLUSIONS: The present study demonstrates that the standardized inclusive numeric academic index may be used as a valid, comprehensive measure of academic productivity. Future studies should assess its application across different medical specialties.

Effect of large volume paracentesis performed just prior to transjugular intrahepatic portosystemic shunt on the anesthetic management during the procedure.

BACKGROUND AND AIMS: Patients often undergo paracentesis prior to a transjugular intrahepatic portosystemic shunt (TIPS) procedure to improve respiratory mechanics. However, the effect of large volume paracentesis (LVP) on intraoperative hemodynamics and anesthetic management when it is performed immediately before the TIPS procedure is not well documented. MATERIAL AND METHODS: This is a retrospective study in patients undergoing the TIPS procedure between 2004 and 2017. Patients were divided into two groups based on the volume of preoperative paracentesis, namely, small volume paracentesis (SVP), defined as paracentesis volume less than 5 L and LVP, defined as paracentesis volume of at least 5 L. Patients' demographics and perioperative information were collected through chart review. The Wilcoxon signed-rank test, student's t-test, and Fisher's exact test were used when appropriate. Uni- and multivariate linear regression analyses were used to determine the predictive value of paracentesis volume in relation to intraoperative hemodynamics and management of hypotension. RESULTS: Of 49 patients, 19 (39%) received LVP and the remainder received SVP. Baseline demographics were comparable between groups as were intraoperative hypotension and volume of infused crystalloid and colloid. However, vasopressor use (P = 0.02) and packed red blood cell transfusion (P = 0.01) were significantly higher in the large volume group. Paracentesis volume was an independent predictor of the phenylephrine dose (P = 0.0004), and of crystalloid (P = 0.05) and colloid (P = 0.009) volume administered after adjusting for age, sex, body mass index, alcohol use, hemoglobin, and model for end-stage liver disease score. CONCLUSION: The anesthetic management of patients who undergo LVP just prior to a TIPS procedure may require larger doses of vasopressors and colloids to prevent intraoperative hemodynamic instability during the TIPS placement but may be as well tolerated as SVP.

A dynamic attitude measurement system based on LINS.

A dynamic attitude measurement system (DAMS) is developed based on a laser inertial navigation system (LINS). Three factors of the dynamic attitude measurement error using LINS are analyzed: dynamic error, time synchronization and phase lag. An optimal coning errors compensation algorithm is used to reduce coning errors, and two-axis wobbling verification experiments are presented in the paper. The tests indicate that the attitude accuracy is improved 2-fold by the algorithm. In order to decrease coning errors further, the attitude updating frequency is improved from 200 Hz to 2000 Hz. At the same time, a novel finite impulse response (FIR) filter with three notches is designed to filter the dither frequency of the ring laser gyro (RLG). The comparison tests suggest that the new filter is five times more effective than the old one. The paper indicates that phase-frequency characteristics of FIR filter and first-order holder of navigation computer constitute the main sources of phase lag in LINS. A formula to calculate the LINS attitude phase lag is introduced in the paper. The expressions of dynamic attitude errors induced by phase lag are derived. The paper proposes a novel synchronization mechanism that is able to simultaneously solve the problems of dynamic test synchronization and phase compensation. A single-axis turntable and a laser interferometer are applied to verify the synchronization mechanism. The experiments results show that the theoretically calculated values of phase lag and attitude error induced by phase lag can both match perfectly with testing data. The block diagram of DAMS and physical photos are presented in the paper. The final experiments demonstrate that the real-time attitude measurement accuracy of DAMS can reach up to 20″ (1σ) and the synchronization error is less than 0.2 ms on the condition of three axes wobbling for 10 min.

Enhancing radiology training with GPT-4: Pilot analysis of automated feedback in trainee preliminary reports.

RATIONALE AND OBJECTIVES: Radiology residents often receive limited feedback on preliminary reports issued during independent call. This study aimed to determine if Large Language Models (LLMs) can supplement traditional feedback by identifying missed diagnoses in radiology residents' preliminary reports. MATERIALS & METHODS: A randomly selected subset of 500 (250 train/250 validation) paired preliminary and final reports between 12/17/2022 and 5/22/2023 were extracted and de-identified from our institutional database. The prompts and report text were input into the GPT-4 language model via the GPT-4 API (gpt-4-0314 model version). Iterative prompt tuning was used on a subset of the training/validation sets to direct the model to identify important findings in the final report that were absent in preliminary reports. For testing, a subset of 10 reports with confirmed diagnostic errors were randomly selected. Fourteen residents with on-call experience assessed the LLM-generated discrepancies and completed a survey on their experience using a 5-point Likert scale. RESULTS: The model identified 24 unique missed diagnoses across 10 test reports with i% model prediction accuracy as rated by 14 residents. Five additional diagnoses were identified by users, resulting in a model sensitivity of 79.2 %. Post-evaluation surveys showed a mean satisfaction rating of 3.50 and perceived accuracy rating of 3.64 out of 5 for LLM-generated feedback. Most respondents (71.4 %) favored a combination of LLM-generated and traditional feedback. CONCLUSION: This pilot study on the use of LLM-generated feedback for radiology resident preliminary reports demonstrated notable accuracy in identifying missed diagnoses and was positively received, highlighting LLMs' potential role in supplementing conventional feedback methods.

Nanopore sequencing: flourishing in its teenage years.

Over the past decade, nanopore sequencing has experienced significant advancements and changes, transitioning from an initially emerging technology to a significant instrument in the field of genomic sequencing. However, as advancements in next-generation sequencing technology persist, nanopore sequencing also improves. This paper reviews the developments, applications, and outlook on nanopore sequencing technology. Currently, nanopore sequencing supports both DNA and RNA sequencing, making it widely applicable in areas such as telomere-to-telomere (T2T) genome assembly, direct RNA sequencing (DRS), and metagenomics. The openness and versatility of nanopore sequencing have established it as a preferred option for an increasing number of research teams, signaling a transformative influence on life science research. As nanopore sequencing technology advances, it provides a faster, more cost-effective approach with extended read lengths, demonstrating the significant potential for complex genome assembly, pathogen detection, environmental monitoring, and human disease research, offering a fresh perspective in sequencing technologies.

Immunosenescence: A new direction in anti-aging research.

The immune system is a major regulatory system of the body, that is composed of immune cells, immune organs, and related signaling factors. As an organism ages, observable age-related changes in the function of the immune system accumulate in a process described as 'immune aging. Research has shown that the impact of aging on immunity is detrimental, with various dysregulated responses that affect the function of immune cells at the cellular level. For example, increased aging has been shown to result in the abnormal chemotaxis of neutrophils and decreased phagocytosis of macrophages. Age-related diminished functionality of immune cell types has direct effects on host fitness, leading to poorer responses to vaccination, more inflammation and tissue damage, as well as autoimmune disorders and the inability to control infections. Similarly, age impacts the function of the immune system at the organ level, resulting in decreased hematopoietic function in the bone marrow, a gradual deficiency of catalase in the thymus, and thymic atrophy, resulting in reduced production of related immune cells such as B cells and T cells, further increasing the risk of autoimmune disorders in the elderly. As the immune function of the body weakens, aging cells and inflammatory factors cannot be cleared, resulting in a cycle of increased inflammation that accumulates over time. Cumulatively, the consequences of immune aging increase the likelihood of developing age-related diseases, such as Alzheimer's disease, atherosclerosis, and osteoporosis, among others. Therefore, targeting the age-related changes that occur within cells of the immune system might be an effective anti-aging strategy. In this article, we summarize the relevant literature on immune aging research, focusing on its impact on aging, in hopes of providing new directions for anti-aging research.

Towards inclusive biodesign and innovation: lowering barriers to entry in medical device development through large language model tools.

In the following narrative review, we discuss the potential role of large language models (LLMs) in medical device innovation, specifically examples using generative pretrained transformer-4. Throughout the biodesign process, LLMs can offer prompt-driven insights, aiding problem identification, knowledge assimilation and decision-making. Intellectual property analysis, regulatory assessment and market analysis emerge as key LLM applications. Through case examples, we underscore LLMs' transformative ability to democratise information access and expertise, facilitating inclusive innovation in medical devices as well as its effectiveness with providing real-time, individualised feedback for innovators of all experience levels. By mitigating entry barriers, LLMs accelerate transformative advancements, fostering collaboration among established and emerging stakeholders.

Polygalasaponin F ameliorates middle cerebral artery occlusion-induced focal ischemia / reperfusion injury in rats through inhibiting TXNIP/NLRP3 signaling pathway.

BACKGROUND: Polygalasaponin F (PGSF), an oleanane triterpenoid saponin extracted from Polygala japonica, has been demonstrated with neuroprotective effect. However, the therapeutic effects and mechanisms of PGSF on focal ischemia remain unknown; METHODS: In this study, male Sprague Dawley (SD) rats aged 6-8 weeks were initially selected to establish a rat model of middle cerebral artery occlusion (MCAO) to evaluate the therapeutic effect of PGSF intervention and to investigate the impact of PGSF on the thioredoxin-interacting protein/NOD-, LRR-, and pyrin domain-containing protein 3 (TXNIP/NLRP3) inflammatory pathway. Secondly, brain neuron cells were isolated, and the cells received oxygen-glucose deprivation/reoxygenation (OGD/R) culture to establish the cell injury model in vitro. The mechanism of PGSF on the TXNIP/NLRP3 pathway was further validated; RESULTS: Our results showed that PGSF treatment reduced neurological scores, brain tissue water content and infarct volume and ameliorated the pathological changes in cerebral cortex in MCAO-induced focal ischemia rats. The TNF-α, IL-1ß and IL-6 levels decreased in MCAO-induced focal ischemia rats after PGSF treatment. Moreover, PGSF down-regulated the protein expressions of TXNIP, NLRP3, ASC, cleaved caspase-1, IL-1ß, and IL-18 in MCAO-induced focal ischemia rats. Meanwhile, PGSF treatment inhibited apoptosis, and reduced the levels of ROS, inflammatory cytokine and TXNIP/NLRP3 pathway-related proteins (TXNIP, NLRP3, ASC, cleaved caspase-1, IL-1ß, and IL-18) in OGD/R-induced neuronal injury cells. Finally, PGSF treatment also disrupted the interaction between NLRP3 and TXNIP in vitro; CONCLUSIONS: Our study demonstrated the therapeutic effects of PGSF on MCAO-induced focal ischemia rats. Moreover, the neuroprotective mechanism of PGSF on focal ischemia was associated with the inhibition of TXNIP/NLRP3 signaling pathway.

Jianpi Gushen Huayu decoction ameliorated diabetic nephropathy through modulating metabolites in kidney, and inhibiting TLR4/NF-κB/NLRP3 and JNK/P38 pathways.

BACKGROUND: Jianpi Gushen Huayu Decoction (JPGS) has been used to clinically treat diabetic nephropathy (DN) for many years. However, the protective mechanism of JPGS in treating DN remains unclear. AIM: To evaluate the therapeutic effects and the possible mechanism of JPGS on DN. METHODS: We first evaluated the therapeutic potential of JPGS on a DN mouse model. We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics. Furthermore, we examined the effects of JPGS on c-Jun N-terminal kinase (JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3). RESULTS: The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress. Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice. A total of 51 differential metabolites were screened. Pathway analysis results indicated that nine pathways significantly changed between the control and model groups, while six pathways significantly altered between the model and JPGS groups. Pathways related to cysteine and methionine metabolism; alanine, tryptophan metabolism; aspartate and glutamate metabolism; and riboflavin metabolism were identified as the key pathways through which JPGS affects DN. Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors. CONCLUSION: JPGS could markedly treat mice with streptozotocin (STZ)-induced DN, which is possibly related to the regulation of several metabolic pathways found in kidneys. Furthermore, JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathway-mediated apoptosis in DN mice.

Impact of drainage catheter material, size, and anti-dislodgement mechanism on percutaneous nephrostomy exchange intervals: a systematic review protocol.

Background: Percutaneous nephrostomy (PCN) is a commonly performed procedure by interventional radiology and urology to treat urinary obstruction. In this procedure, a catheter is percutaneously placed into the renal pelvis for urinary diversion or hemorrhagic cystitis. Material type, catheter size, and catheter shape (anti-dislodgement feature) ultimately contribute to the inherent traits of longevity in drainage catheter device. Reviewing the relative strengths or weaknesses of products in the existing clinical market may help clinicians critically appraise the devices they use with evidence-based findings from this review. Furthermore, a deeper understanding of the relative strengths and weaknesses of existing devices may help inform the next generation of drainage catheter devices to prolong the interval between exchanges without detriment to patient safety. Methods: The following electronic databases will be queried: PubMed, Web of Science, Cochrane from their inception to January 2023 to identify randomized controlled trials (RCTs) and cohort studies to investigate the differences that our interventions of catheter material, size, and dislodgement mechanism will have on the exchange interval (standard of care 90 days vs. 60 days vs. 45 days vs. 30 days). The primary outcomes will be the drainage catheter exchange frequency. Ethics and dissemination: We aim to share our findings through high-impact peer reviewed journals. As drainage catheters and minimally invasive interventional radiology procedures become more popular, it is important for healthcare providers taking case of these populations to understand which variables might optimize patient care and minimize emergent exchanges. Data will be made available to readers. Registration: PROSPERO ( CRD42023432788, 16 June 2023).

Rosa laevigata Michx. Polysaccharide Ameliorates Diabetic Nephropathy in Mice through Inhibiting Ferroptosis and PI3K/AKT Pathway-Mediated Apoptosis and Modulating Tryptophan Metabolism.

Diabetic nephropathy (DN) is a metabolic disease wherein chronic hyperglycemia triggers various renal cell dysfunctions, eventually leading to progressive kidney failure. Rosa laevigata Michx. is a traditional Chinese herbal medicine. Many studies have confirmed its antioxidative, anti-inflammatory, and renoprotective effects. However, the effects and mechanisms of Rosa laevigata Michx. polysaccharide (RLP) in DN remain unclear. In this study, a DN mouse model was established to investigate the therapeutic effect of RLP on DN mice. Then, nontargeted metabolomics was used to analyze the potential mechanism of RLP in the treatment of DN. Finally, the effects of RLP on ferroptosis and the PI3K/AKT pathway were investigated. The results demonstrated that RLP effectively alleviated renal injury and reduced inflammation and oxidative stress in the kidney. In addition, nontargeted metabolomic analysis indicated that RLP could modulate riboflavin metabolism and tryptophan metabolism in DN mice. Notably, ferroptosis and PI3K/AKT pathway-mediated apoptosis in the kidney were also ameliorated following RLP treatment. In conclusion, this study confirmed that RLP had a significant therapeutic effect on DN mice. Furthermore, RLP treatment modulated tryptophan metabolism and inhibited ferroptosis and PI3K/AKT pathway-mediated apoptosis in the kidney.

Aqueous extract of Polygala japonica Houtt. ameliorated nonalcoholic steatohepatitis in mice through restoring the gut microbiota disorders and affecting the metabolites in feces and liver.

BACKGROUND: Polygala japonica Houtt. (PJ) has been demonstrated with several biological potentials such as lipid-lowering and anti-inflammatory effects. However, the effects and mechanisms of PJ on nonalcoholic steatohepatitis (NASH) remain unclear. PURPOSE: The aim of this study was to evaluate the effects of PJ on NASH and illustrate the mechanism based on modulating gut microbiota and host metabolism. MATERIALS AND METHODS: NASH mouse model was induced using methionine and choline deficient (MCD) diet and orally treated with PJ. The therapeutic, anti-inflammatory, and anti-oxidative effects of PJ on mice with NASH were firstly assessed. Then, the gut microbiota of mice was analyzed using 16S rRNA sequencing to assess the changes. Finally, the effects of PJ on the metabolites in liver and feces were explored by untargeted metabolomics. RESULTS: The results indicated that PJ could improve hepatic steatosis, liver injury, inflammatory response, and oxidative stress in NASH mice. PJ treatment also affected the diversity of gut microbiota and changed the relative abundances of Faecalibaculum. Lactobacillus, Muribaculaceae, Dubosiella, Akkermansia, Lachnospiraceae_NK4A136_group, and Turicibacter in NASH mice. In addition, PJ treatment modulated 59 metabolites both in liver and feces. Metabolites involved in histidine, and tryptophan metabolism pathways were identified as the key metabolites according to the correlation analysis between differential gut microbiota and metabolites. CONCLUSION: Our study demonstrated the therapeutic, anti-inflammatory and anti-oxidative potentials of PJ on NASH. The mechanisms of PJ treatment were related to the improvement of gut microbiota dysbiosis and the regulation of histidine and tryptophan metabolism.

Integrated 16S rRNA Sequencing and Untargeted Metabolomics Analysis to Reveal the Protective Mechanisms of Polygonatum sibiricum Polysaccharide on Type 2 Diabetes Mellitus Model Rats.

BACKGROUND: Polygonatum sibiricum polysaccharide (PSP) can improve insulin resistance and inhibit oxidative stress. However, the detailed anti-diabetic mechanism of PSP is still poorly defined. METHODS: In this study, the anti-diabetic, anti-inflammatory and anti-oxidative effects of PSP were evaluated on a type 2 diabetes mellitus (T2DM) rat model. Furthermore, we investigated the changes in gut microbiota and serum metabolites in T2DM rats after PSP treatment through 16S rRNA sequencing and untargeted metabolomics analyses. RESULTS: Our results showed that PSP exhibited significant anti-diabetic, anti-inflammatory and anti-oxidative effects on T2DM model rats. In addition, 16S rRNA sequencing showed that PSP treatment decreased the Firmicutes/ Bacteroidetes ratio in the gut. At the genus level, PSP treatment increased the relative abundances of Blautia, Adlercreutzia, Akkermansia and Parabacteroides while decreasing Prevotella, Megamonas funiformis and Escherichia. Untargeted metabolomics analysis revealed that PSP treatment could affect 20 metabolites, including hexanoylglycine, (±)5(6)-DiHET, ecgonine, L-cysteine-S-sulfate, epitestosterone, (±)12(13)-DiHOME, glutathione, L-ornithine, Dmannose 6-phosphate, L-fucose, L-tryptophan, L-kynurenine, serotonin, melatonin, 3-hydroxyanthranilic acid, xylitol, UDP-D-glucuronate, hydroxyproline, 4-guanidinobutyric acid, D-proline in T2DM model rats, these metabolites are associated with arginine and proline metabolism, tryptophan metabolism, amino sugar and nucleotide sugar metabolism, pentose and glucuronate interconversions, glutathione metabolism, arginine biosynthesis, ascorbate and aldarate metabolism pathways. Spearman correlation analysis results showed that the modulatory effects of PSP on the arginine and proline metabolism, tryptophan metabolism, and glutathione metabolism pathways were related to the regulation of Prevotella, Megamonas funiformis, Escherichia, Blautia and Adlercreutzia. CONCLUSION: Our research revealed the therapeutic, anti-inflammatory and anti-oxidative effects of PSP on T2DM. The mechanisms of PSP on T2DM are associated with improving the dysbiosis of gut microbiota and regulating arginine and proline metabolism, tryptophan metabolism, and glutathione metabolism in serum.

Integrated 16S rRNA sequencing and nontargeted metabolomics analysis to reveal the mechanisms of Yu-Ye Tang on type 2 diabetes mellitus rats.

Introduction: Yu-Ye Tang (YYT) is a classical formula widely used in treatment of type 2 diabetes mellitus (T2DM). However, the specific mechanism of YYT in treating T2DM is not clear. Methods: The aim of this study was to investigate the therapeutic effect of YYT on T2DM by establishing a rat model of T2DM. The mechanism of action of YYT was also explored through investigating gut microbiota and serum metabolites. Results: The results indicated YYT had significant therapeutic effects on T2DM. Moreover, YYT could increase the abundance of Lactobacillus, Candidatus_Saccharimonas, UCG-005, Bacteroides and Blautia while decrease the abundance of and Allobaculum and Desulfovibrio in gut microbiota of T2DM rats. Nontargeted metabolomics analysis showed YYT treatment could regulate arachidonic acid metabolism, alanine, aspartate and glutamate metabolism, arginine and proline metabolism, glycerophospholipid metabolism, pentose and glucuronate interconversions, phenylalanine metabolism, steroid hormone biosynthesis, terpenoid backbone biosynthesis, tryptophan metabolism, and tyrosine metabolism in T2DM rats. Discussion: In conclusion, our research showed that YYT has a wide range of therapeutic effects on T2DM rats, including antioxidative and anti-inflammatory effects. Furthermore, YYT corrected the altered gut microbiota and serum metabolites in T2DM rats. This study suggests that YYT may have a therapeutic impact on T2DM by regulating gut microbiota and modulating tryptophan and glycerophospholipid metabolism, which are potential key pathways in treating T2DM.