Atherosclerosis (AS), the primary pathological contributor to cardiovascular diseases (CVDs), has increasingly affected younger populations due to modern dietary habits and sedentary lifestyles. Current diagnostic modalities, including ultrasound, MRI, and CT, primarily identify advanced lesions and inadequately evaluate plaque vulnerability, thereby hindering early detection. Conventional treatments, which involve long-term medications associated with side effects such as hepatic injury and surgical interventions that carry risks of restenosis and hemorrhage, underscore the urgent need for non-invasive, cost-effective early diagnostic methods and targeted therapies. Gut microbiota metabolites are pivotal in AS pathogenesis, with trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs) serving as functionally opposing biomarkers. TMAO is produced when gut bacteria, specifically Firmicutes and Proteobacteria, metabolize dietary choline and carnitine into trimethylamine (TMA), which the liver subsequently converts to TMAO via flavin-containing monooxygenase 3 (FMO3); TMAO is then excreted in urine. Variability in TMAO levels is influenced by marine food consumption and FMO3 modulation, which can be affected by genetics, age, and diet. Mechanistically, TMAO exacerbates AS by disrupting cholesterol metabolism, inducing endothelial dysfunction through the elevation of reactive oxygen species (ROS) and pro-inflammatory cytokines such as IL-6, and reducing nitric oxide levels. Additionally, TMAO activates NF-κB and NLRP3 pathways while enhancing platelet reactivity. Clinically, elevated TMAO levels correlate with early AS and serve as predictors of mortality in patients with stable coronary artery disease (CAD) and acute coronary syndrome (ACS), as well as major adverse cardiovascular events (MACE) in stroke patients. Conversely, SCFAs—namely acetate, propionate, and butyrate—are produced by gut bacteria such as Akkermansia muciniphila and Faecalibacterium prausnitzii through the fermentation of dietary fiber. These metabolites exert anti-AS effects: acetate aids in maintaining metabolic homeostasis; propionate protects endothelial function and reduces plaque area; and butyrate fortifies intestinal barriers while suppressing inflammation. Furthermore, SCFAs cross-regulate bile acid metabolism, thereby influencing TMAO levels, and antagonize the pro-inflammatory and lipid-disrupting effects of TMAO. The use of TMAO and SCFAs as standalone biomarkers is constrained by limitations. TMAO lacks specificity, while SCFA levels fluctuate based on gut microbiota and dietary intake. Traditional AS risk assessment tools, which include clinical indicators, imaging techniques, and single biomarkers such as CRP, LDL-C, and ASCVD scores, overlook gut metabolism and demonstrate inadequate performance in younger populations. This review advocates for an “antagonistic-complementary” combined strategy: utilizing acetate and TMAO for early AS, propionate and TMAO for progressive AS, and butyrate and TMAO for advanced AS, addressing endothelial dysfunction, lipid deposition, and plaque stability/thrombosis risk, respectively. For clinical application, standardization of detection methods is crucial; liquid chromatography-mass spectrometry (LC-MS) is the gold standard, necessitating a unified sample pretreatment protocol, such as extraction with 1% formic acid in methanol. Additionally, dried blood spots (DBS) facilitate non-invasive testing, provided that dietary controls are implemented prior to detection, including a 12-hour fast and avoidance of high-choline and high-fiber foods. Existing challenges encompass the absence of standardized systems, limited large-scale validation, and ambiguous interactions with conditions such as hypertension. The authors’ team has previously established connections between gut metabolites and AS, including the reduction of TMAO as a preventive measure for AS, thereby reinforcing this proposed strategy. Future research should prioritize standardization, the development of machine learning-optimized models, validation of interventions, and the exploration of multi-omics-based “gut microbiota-metabolite-vascular” networks. In conclusion, the combined detection of TMAO and SCFAs offers a novel framework for AS risk assessment, facilitating early diagnosis and targeted interventions while enhancing the integration of gut metabolism into cardiovascular disease management.

Atherosclerosis (AS), the primary pathological contributor to cardiovascular diseases (CVDs), has increasingly affected younger populations due to modern dietary habits and sedentary lifestyles. Current diagnostic modalities, including ultrasound, MRI, and CT, primarily identify advanced lesions and inadequately evaluate plaque vulnerability, thereby hindering early detection. Conventional treatments, which involve long-term medications associated with side effects such as hepatic injury and surgical interventions that carry risks of restenosis and hemorrhage, underscore the urgent need for non-invasive, cost-effective early diagnostic methods and targeted therapies. Gut microbiota metabolites are pivotal in AS pathogenesis, with trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs) serving as functionally opposing biomarkers. TMAO is produced when gut bacteria, specifically Firmicutes and Proteobacteria, metabolize dietary choline and carnitine into trimethylamine (TMA), which the liver subsequently converts to TMAO via flavin-containing monooxygenase 3 (FMO3); TMAO is then excreted in urine. Variability in TMAO levels is influenced by marine food consumption and FMO3 modulation, which can be affected by genetics, age, and diet. Mechanistically, TMAO exacerbates AS by disrupting cholesterol metabolism, inducing endothelial dysfunction through the elevation of reactive oxygen species (ROS) and pro-inflammatory cytokines such as IL-6, and reducing nitric oxide levels. Additionally, TMAO activates NF-κB and NLRP3 pathways while enhancing platelet reactivity. Clinically, elevated TMAO levels correlate with early AS and serve as predictors of mortality in patients with stable coronary artery disease (CAD) and acute coronary syndrome (ACS), as well as major adverse cardiovascular events (MACE) in stroke patients. Conversely, SCFAs—namely acetate, propionate, and butyrate—are produced by gut bacteria such as Akkermansia muciniphila and Faecalibacterium prausnitzii through the fermentation of dietary fiber. These metabolites exert anti-AS effects: acetate aids in maintaining metabolic homeostasis; propionate protects endothelial function and reduces plaque area; and butyrate fortifies intestinal barriers while suppressing inflammation. Furthermore, SCFAs cross-regulate bile acid metabolism, thereby influencing TMAO levels, and antagonize the pro-inflammatory and lipid-disrupting effects of TMAO. The use of TMAO and SCFAs as standalone biomarkers is constrained by limitations. TMAO lacks specificity, while SCFA levels fluctuate based on gut microbiota and dietary intake. Traditional AS risk assessment tools, which include clinical indicators, imaging techniques, and single biomarkers such as CRP, LDL-C, and ASCVD scores, overlook gut metabolism and demonstrate inadequate performance in younger populations. This review advocates for an “antagonistic-complementary” combined strategy: utilizing acetate and TMAO for early AS, propionate and TMAO for progressive AS, and butyrate and TMAO for advanced AS, addressing endothelial dysfunction, lipid deposition, and plaque stability/thrombosis risk, respectively. For clinical application, standardization of detection methods is crucial; liquid chromatography-mass spectrometry (LC-MS) is the gold standard, necessitating a unified sample pretreatment protocol, such as extraction with 1% formic acid in methanol. Additionally, dried blood spots (DBS) facilitate non-invasive testing, provided that dietary controls are implemented prior to detection, including a 12-hour fast and avoidance of high-choline and high-fiber foods. Existing challenges encompass the absence of standardized systems, limited large-scale validation, and ambiguous interactions with conditions such as hypertension. The authors’ team has previously established connections between gut metabolites and AS, including the reduction of TMAO as a preventive measure for AS, thereby reinforcing this proposed strategy. Future research should prioritize standardization, the development of machine learning-optimized models, validation of interventions, and the exploration of multi-omics-based “gut microbiota-metabolite-vascular” networks. In conclusion, the combined detection of TMAO and SCFAs offers a novel framework for AS risk assessment, facilitating early diagnosis and targeted interventions while enhancing the integration of gut metabolism into cardiovascular disease management.

Lung cancer remains one of the leading causes of cancer-related morbidity and mortality worldwide, and its treatment continues to face major challenges such as therapeutic resistance and tumor recurrence. Pyroptosis, a newly characterized form of programmed cell death, induces tumor cell death through gasdermin-mediated membrane pore formation and is accompanied by the release of inflammatory mediators, thereby playing complex roles in lung cancer initiation, progression, and modulation of the tumor microenvironment. Active components and herbal formulas derived from traditional Chinese medicine can modulate pyroptosis-related signaling pathways through multi-target mechanisms, showing potential advantages in inducing lung cancer cell death, inhibiting proliferation and migration, and reversing chemoresistance. This review systematically summarizes relevant studies from domestic and international sources, focusing on the molecular mechanisms of pyroptosis, its roles in lung cancer development and tumor microenvironment remodeling, and the current research progress on traditional Chinese medicine-based interventions targeting pyroptosis, with the aim of providing references for the prevention and treatment of lung cancer using traditional Chinese medicine.

Effective symptom management can alleviate the physical and psychological distress experienced by patients with cancer, improve quality of life, and contribute to treatment adherence and improve clinical outcomes. However, most existing guidelines are developed for healthcare professionals, and patients and the public have limited access to standardized and comprehensible guidance on symptom management. To address this gap and to facilitate effective communication and shared decision-making, this study proposes the development of a patient version of the cancer symptom management guideline. The development process will adhere to the methodological framework recommended by the Guidelines International Network and the World Health Organization. The GRADE approach will be employed to assess the certainty of evidence and to formulate recommendations. In addition, the process will be informed by the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) instrument and the Reporting Items for Practice Guidelines in Healthcare-Public or Patient Versions of Guidelines (RIGHT-PVG). This protocol outlines the establishment of the guideline working group, the identification and prioritization of key questions, evidence retrieval and appraisal, and the formulation of recommendations, with the aim of ensuring methodological rigor and transparency in the development of the patient guideline and providing methodological reference for similar guideline initiatives.

This study reports a new species of Culicoides(Avaritia)isolated from Xunke County, Heilongjiang Province, China. The new species, Culicoides(Avaritia)dongshanensis Liu et Wang, sp. nov., was identified and illustrated based on female adults. Its diagnostic characteristics are as follows: eyes contiguous over a short distance, with short interfacetal hair, antennal ratio(AR)of 1.20, palpal ratio(PR)of 2.16, wing length of 0.83 mm, mandible with 15 teeth, one pale spot in base cell M1, one pale spot in cell M4, two pale spots in cell A, and two unequal spermathecae. Type specimens were deposited at the Center for Disease Control and Prevention of the Northern Theater Command.

BackgroundObstructive sleep apnea （OSA） represents a prevalent sleep disordered breathing condition characterized by complex pathophysiology. The arousal threshold （ArTH）， a core non-anatomical contributor to OSA pathogenesis， is intimately tied to the disease severity and clinical phenotypes. To date， research regarding factors associated with ArTH has yielded inconsistent findings， and ArTH profiles and disparities across populations with different genetic backgrounds are not fully elucidated. ObjectiveTo explore the differences of ArTH in OSA patients with different genetic backgrounds and analyze the key factors affecting ArTH， thereby providing evidence for understanding OSA pathophysiology and formulating targeted treatment regimens. MethodsA total of 285 patients who met the diagnostic criteria for OSA， as defined by the Multidisciplinary Diagnosis and Treatment Guidelines for Adult Obstructive Sleep Apnea， were retrospectively enrolled in this study. All participants underwent overnight polysomnography （PSG） at the Sleep Medicine Center of Inner Mongolia Mental Health Center from December 2022 to May 2024. Based on the study design， the cohort was stratified into two distinct genetic background subgroups （group A and group B）. Demographic and clinical characteristics， the Epworth Sleepiness Scale （ESS） score， and overnight PSG data were collected. The apnea hypopnea index （AHI）， the lowest pulse oxygen saturation （LSpO₂）， and fraction of hypopneas （F_Hypopneas） were utilized as surrogate indicators to estimate ArTH in OSA patients. The influencing factors of low ArTH were tested by binary Logistic regression analysis. ResultsAmong the 285 OSA patients， there were 227 cases （79.65%） in group A and 58 cases （20.35%） in group B. Comparisons between the two genetic background subgroups revealed no statistically significant differences in the proportion of low ArTH， ESS score， PSG parameters， and the three markers for low ArTH （AHI<30 events/h， LSpO₂>82.5%， F_Hypopneas>58.3%） （P>0.05）. Binary Logistic regression analysis identified sex （OR=2.421， 95% CI： 1.070–5.478）， BMI （OR=0.847， 95% CI： 0.770–0.932）， N1 sleep duration （OR=0.974， 95% CI： 0.963–0.985）， and hypertension （OR=0.348， 95% CI： 0.143–0.848） as independent factors associated with low ArTH in the total cohort. Stratified analysis by genetic backgrounds revealed that sex（OR=3.799， 95% CI： 1.389–10.392）， BMI（OR=0.819， 95% CI：0.723–0.929）， and N1 sleep duration（OR=0.973， 95% CI： 0.961–0.986） were independent factors of low ArTH in group A. In contrast， only N1 sleep duration （OR=0.951， 95% CI： 0.911–0.993） remained a significant factor in group B. ConclusionArthur may have conservative characteristics in patients with OSA with different genetic backgrounds， but the pathophysiological mechanism of OSA may have population heterogeneity. ［Funded by Inner Mongolia Autonomous Region Natural Science Fundation Project （number， 2024QN08050）； Intra-institutional Scientific Research Project of Inner Mongolia Mental Health Center （number， 2022QNWN0010）］

BACKGROUND: Quantitative flow ratio (QFR) holds significant value in guiding drug-coated balloon (DCB) treatment and enhancing outcomes. However, the predictive capability of post-angioplasty QFR for long-term clinical events in patients with de novo lesions who receive DCB treatment remains uncertain. The aim of this study was to explore the potential significance of post-angioplasty QFR measurements in predicting clinical outcomes in patients underwent DCB treatment for de novo lesions. METHODS: Patients who underwent DCB-only intervention for de novo lesions were enrolled. QFR was conducted after DCB treatment. The patients were then categorized based on post-angioplasty QFR. The primary endpoint was major adverse cardiac events (MACE), encompassing all-cause death, cardiovascular death, nonfatal myocardial infarction, stroke, and target vessel revascularization. RESULTS: A total of 553 patients with 561 lesions were included. The median follow-up period was 505 days, during which 66 (11.8%) MACEs occurred. Based on post-procedural QFR grouping, there were 259 cases in the high QFR group (QFR > 0.93) and 302 cases in the low QFR group (QFR ≤ 0.93). Kaplan-Meier analysis revealed a significantly higher cumulative incidence of MACE in the low QFR group (log-rank P = 0.004). The multivariate Cox proportional hazards model demonstrated a significant inverse correlation between QFR and the occurrence of MACEs (HR = 0.522, 95%CI: 0.289-0.942, P = 0.031). Landmark analysis indicated that high QFR had a significant reducing effect on the cumulative incidence of MACEs within 1 year (log-rank P = 0.016) and 1-5 years (log-rank P = 0.026). CONCLUSIONS In patients who underwent DCB-only treatment for de novo lesions, higher post-procedural QFR values (> 0.93) were identified as an independent protective factor against adverse prognosis.

As a fundamental aspect of bone fracture treatment, fracture reduction plays a decisive role in restoring the structural integrity and function of bones. At present, fracture reduction techniques mostly rely on semi-automatic interaction methods or healthy-side bone templates for registration, which have many limitations in clinical practice. In order to enhance treatment efficiency and accuracy, an automatic fracture reduction algorithm is proposed. This algorithm utilizes the similarity of fracture cross-sections for registration, thereby reducing the workload of physicians and eliminating the need for a healthy-side bone template. Initially, the closed edge is identified and extracted by analyzing the differences in the fracture surface and the calorific value diagram of the roughness distribution. Next, the fracture section is determined by using the identified closed edge as a guideline for regional expansion and similarity matching. During the registration phase, the iterative closest point (ICP) algorithm is highly sensitive to distance. Therefore, the geometric features of point clouds are incorporated into the objective function of the registration algorithm to mitigate the influence of noise, and fracture section registration is implemented one by one. Finally, the algorithm is tested and compared on 180 simulated datasets and 16 publicly available datasets. The results show that the proposed algorithm significantly improves the registration accuracy, and the registration error of clinical bone fracture cases is controlled within 1.7 mm.
Algorithms ; Fractures, Bone/therapy* ; Humans

OBJECTIVE: To investigate the effect and mechanism of Shuangshi Tonglin Capsules (SSTL) in the treatment of prostate fibrosis (PF). METHODS: Human prostate stromal cells (WPMY-1) were used for in vitro experiments to establish PF cell models induced with estradiol (E₂). The cell proliferation, migration and clonogenic capacity were determined by cell counting kit-8, scratch assay, and crystal violet staining, respectively. Sprague-Dawley rats were used for in vivo experiments. The changes in histomorphology and organ index of rat prostate by SSTL were determined. Pathologic changes and collagen deposition changes in rat prostate were observed by haematoxylin and eosin (HE) and Masson staining. Enzyme-linked immunosorbent assay kits were used to determine changes in rat PF markers fibroblast growth factor-23 (FGF-23), E₂ and prostate specific antigen (PSA). Mechanistically, changes in oxidative stress indicators by SSTL were determined in WPMY-1 cells and PF rats. Then the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and transforming growth factor-β1 (TGF-β1)/Smad pathway-related proteins as well as Nrf2 and TGF-β1 mRNA were further detected by Western blot or quantitative real-time polymerase chain reaction both in vivo and in vitro. RESULTS: In the efficacy study, SSTL significantly reduced the proliferation, migration, and clonogenic ability of cells, improved the morphology of the glandular tissue, significantly reduced the prostate index, reduced glandular fibrous tissue and collagen deposition, and resulted in a significant decrease in the levels of FGF-23, E₂ and PSA (P<0.01 or P<0.05). In the mechanistic study, SSTL ameliorated oxidative stress by significantly increasing superoxide dismutase and glutathione peroxidase levels and decreasing malondialdehyde level in WPMY-1 cells and rats (P<0.01 or P<0.05). SSTL significantly elevated the expressions of Nrf2, HO-1, NAD(P)H quinone oxidoreductase 1 (NQO-1), and Smad7 proteins in both cells and rats, and significantly decreased the expressions of TGF-β1, collagen I, α-smooth muscle actin and Smad4 proteins (P<0.01 or P<0.05). SSTL also elevated the content of Nrf2 mRNA and decreased the content of TGF-β1 mRNA in cells and rats (P<0.01 or P<0.05). The Nrf2 inhibitor ML385 was added in in vitro experiments to further validate the pathway relevance. CONCLUSION SSTL was effective in improving PF in vivo and in vitro, and its mechanism of action may function through the Nrf2/TGF-β1 signaling pathway.
Male ; NF-E2-Related Factor 2/metabolism* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Signal Transduction/drug effects* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Humans ; Fibrosis ; Prostate/drug effects* ; Cell Proliferation/drug effects* ; Capsules ; Cell Movement/drug effects* ; Oxidative Stress/drug effects* ; Rats

OBJECTIVES: Transcervical resection of adhesions (TCRA) under hysteroscopy is the mainstay treatment for intrauterine adhesions (IUA), but its effectiveness varies depending on the surgical approach. This study aims to investigate the impact of different surgical techniques on endometrial repair and pregnancy outcomes in patients with secondary infertility and moderate-to-severe IUA. METHODS: A retrospective analysis was conducted on 225 patients who underwent TCRA followed by in vitro fertilization and embryo transfer between January 2021 and December 2022. Patients were grouped based on the surgical method: A cold knife group (n=127) and an electrosurgical group (n=98). Adhesions were separated using either cold knife or electrosurgical instruments. Postoperative visualization of uterine angle and tubal ostia, endometrial restoration, vascular endothelial growth factor (VEGF) expression in adhesion tissues, and clinical pregnancy outcomes were compared. Univariate and multivariate Logistic regression analyses were performed to identify factors influencing pregnancy outcomes. A LightGBM model was constructed to predict pregnancy outcomes. RESULTS: Compared with the electrosurgical group, patients in the cold knife group had significantly greater postoperative endometrial thickness [(8.86±0.53) mm vs (8.10±0.87) mm, P<0.05], higher live birth rates (64.57% vs 30.61%, P<0.05), and lower VEGF expression (1.31±0.09 vs 1.53±0.16, P<0.05). Logistic regression analyses identified age, number of visible tubal ostia postoperatively, and surgical method as significant factors affecting pregnancy outcomes (P<0.05). The LightGBM model based on surgical method had an area under the curve (AUC) of 0.882 (0.838-0.926), with internal validation AUC of 0.817 (0.790-0.840). CONCLUSIONS Cold knife surgery promotes faster recovery of the endometrial microenvironment and earlier improvement of fertility in patients with secondary infertility and IUA Surgical method is a key factor influencing pregnancy outcomes, and the LightGBM model based on surgical approach shows good predictive performance for pregnancy outcomes in patients with moderate-to-severe IUA.
Humans ; Female ; Pregnancy ; Tissue Adhesions/surgery* ; Retrospective Studies ; Adult ; Pregnancy Outcome ; Uterine Diseases/surgery* ; Hysteroscopy/methods* ; Infertility, Female/etiology* ; Electrosurgery/methods* ; Fertilization in Vitro ; Endometrium/surgery* ; Embryo Transfer ; Vascular Endothelial Growth Factor A/metabolism*